Oriented to Thoracic Transplant Recipients -- MAY 1997
The UPBEAT! Archive
Cardiac transplantation is now an accepted treatment for end-stage heart disease, relieving symptoms, increasing exercise tolerance, and improving survival. A number of studies have demonstrated that exercise training can further improve exercise capacity and quality of life. The atypical response of the denervated heart to exercise requires that training intensity be based on metabolic measurements and/or perceived exertion rather than heart rate, in order to ensure efficacy and safety.
With 3, 5, and l0-year survival rates of approximately 70, 60 and 40% , respectively, there is no longer any doubt that cardiac transplantation is the treatment of choice for selected patients suffering from end-stage congestive heart failure. By the same token, this high survival rate increases the pool of patients who are potential candidates for exercise rehabilitation.
The transplantation procedure improves both the length and the quality of life. However, it also commits the patient to lifelong rigorous medical follow-up protocol - one which can seriously strain vocational, family, interpersonal and social relationships. In addition to this, severe deconditioning frequently follows months of debilitating ill-health, and one can readily appreciate the need for formal post-surgical rehabilitation. This should include not only physical training, but also guidance in smoking cessation, a prudent diet, weight control, advice on the effects and side-effects of medication, and psychological and vocational counseling. This review deals with the exercise training component of rehabilitation, as well as some aspects of the pathophysiology of the transplanted heart.
Rarely have clinicians and basic scientists been presented with such fertile common ground as in the field of organ transplantation. Early studies established the atypical physiologic responses of the transplanted heart to a bout of physical effort.
Immediately after surgery, the function of the denervated heart is slightly impaired as a result of myocardial anoxia. Right- and left-sided chamber filling pressures are elevated. However, within days the myocardium recovers, pulmonary hypertension regresses, and intravascular pressures normalize. Thereafter, any significant return to these abnormalities is seen only after the onset of an episode of transplant rejection.
The resting heart rate is rapid, usually 15-25 beats per minute above that of age and sex-matched controls. This is due to the absence of vagal influence on the sino-atrial node. The rate does not alter in response to the Valsalva maneuver (forced effort of the breath against a closed throat), carotid sinus massage, or a change in body position from lying to standing. Apart from this relative tachycardia, resting ventricular performance is within normal limits. There is, however, some mild impairment of diastolic function during exercise.
Heart transplant patients compete regularly in the World Transplant Games, and some have taken part in long-distance runs. including the Boston Marathon. There is no doubt that such individuals can perform heavy bouts of exercise. However, the mechanism by which the denervated heart responds to physical effort is atypical. It beats at the high intrinsic rate of the sino-atrial node and lacks any direct neural influence, and therefore cannot respond to physical exertion by immediate acceleration. In the early stages of exercise it relies entirely on the Frank-Starling mechanism to increase stroke volume. With increasing effort, the heart rate, contractility, and ejection fraction increase in response to climbing levels of catecholamines. The tendency of the heart rate to continue to rise after the cessation of exercise, and its tardy return to resting levels in the recovery period, are due to the increased sensitivity of the myocardium to circulating catecholamines.
Peak work rate and peak oxygen intake are generally reported as being lower in heart transplant patients than in age-matched controls. This is probably due to a combination of central and peripheral limitations. Maximal heart rate is also lower than in normals, as is stroke volume, with the result that maximal cardiac output is reduced by approximately 25%. There is also evidence that impairment of pulmonary diffusing capacity may be partially responsible for the diminished peak oxygen intake.
Increasing attention is being focused on the role of abnormal skeletal muscle metabolism as a limiting factor in exercise tolerance following heart transplantation. A prolonged period of preoperative physical inactivity can lead to disuse atrophy, and this may be aggravated by the side-effect of immunosuppressant steroid therapy. Apart from this, however, there is now evidence that the preexisting heart failure state is associated with abnormalities in skeletal muscle metabolism, and that this may persist for some time after heart transplantation.
With regard to isometric exercise, the normal response is an increase in peripheral resistance, a rise in systolic and diastolic blood pressure. and an increase in heart rate. In the heart transplant patient, blood pressure reacts in an identical fashion; peripheral resistance increases. but there is no acceleration in heart rate.
Early experiments established that reinnervation could occur in the dog heart. Naturally, such an outcome in the human heart would be highly desirable, and a number of workers have addressed this issue over the years, only to arrive at the conclusion that the human transplanted heart remains denervated. Nevertheless, there have been occasional reports of anginal-type symptoms in individuals who have developed post-transplant coronary atherosclerosis, suggesting afferent reinnervation. As a result, various techniques have been employed to detect autonomic reinnervation, including analysis of heart rate variability, positron emission tomography (an x-ray technique), measurement of myocardial norepinephrine release, and immunohistochemical examination of myocardial tissue for evidence of neuron growth. From these, one can conclude that while there is evidence that some degree of autonomic reinnervation occurs in the transplanted heart over time, it appears to be inconsistent. A recent study, however, suggests that where it does take place, it may confer practical benefit in terms of improved exercise capacity.
McGregor has recently described the early postoperative rehabilitation measures practiced in the Mayo Clinic. With minor variations, their measures are similar to those followed in most units. After 24 - 48 hours of intensive care monitoring, patients commence the customary breathing, postural and mobilization exercises. These are carried out twice daily. Intensity of effort is monitored by heart rate (which should not exceed the resting rate by more than 30 beats per min.), and breathing frequency (which should not exceed 30 breaths per min.). Oxygen saturation should not fall below 90%. By the fifth day patients are walking in the ward, and they may then begin to use a cycle ergometer, pedaling at zero resistance for 3-5 min. at a perceived exertion of 12 - 14 on the Borg scale ('fairly light' to 'somewhat hard'). As performance improves, the duration of exercise and the power outputs on the ergometer are increased. Corridor walking is introduced, and by the time of discharge from hospital (usually about 3 weeks after surgery) a low-level incremental exercise test may be carried out on the cycle ergometer or the treadmill. This test allows for the prescription of a walking or stationary cycling program, which can then be carried out during the early (4-8 weeks) outpatient phase.
An exercise training program contains four components: the mode, or type of exercise; the intensity; the duration and the frequency of workouts. The most critical of these is intensity, which is determined from the preliminary exercise test, carried out either on a treadmill or a cycle ergometer. The protocol will vary with the laboratory, but in general calls for continuous progressive increments in work rate of one to two MET's (3.5-7.0 ml/kg/min.) until maximal effort is achieved, ideally within 10-14 min. A suitable treadmill protocol is that proposed by Savin. Alternatively, the Naughton or the modified Bruce can be used. A common incremental cycle ergometer protocol utilizes power outputs of 100 kpm/min. (17 watts) or, in the case of the more severely deconditioned individual, 50 kpm/min. (8 watts).
Whatever the protocol, it is customary to monitor the exercise ECG continuously, and at every successive work stage the Borg rating of perceived exertion (RPE) and the blood pressure. A further refinement is the collection and analysis of expired air to measure ventilation, oxygen consumption, and carbon dioxide production. This permits a physiological determination of maximal effort, as demonstrated by the achievement of an oxygen plateau, i.e. failure of oxygen intake to rise despite an increase in work rate. It also allows ventilatory measurement of the anaerobic threshold (known as the ventilatory threshold) the level of exertion at which there is a disproportionate rise in blood lactate - and exercise becomes increasingly anaerobic. The ventilatory threshold is usually attainable even by patients who are unable or unwilling to exert maximal effort. It is the preferred training intensity for cardiac patients and poorly conditioned subjects, and occurs at an oxygen intake of between 50 and 65% of VO2max in both normals and heart transplant patients. In the event that respiratory gas analysis is not carried out, maximal effort can be assumed from the subject's subjective rating of 19-20 on the Borg scale of perceived exertion ('very, very hard'), and the ventilatory threshold from a rating of 12- 14 ('somewhat hard').
Heart rate alone cannot be used to prescribe an intensity of exercise because of the atypical response to effort. The current recommendation is to identify the level of energy expenditure on the exercise test at which the ventilatory threshold occurs (measured directly or estimated from the RPF,), and express this in terms of walking pace, power output on the cycle ergometer, stair stepping cadence, for example.
The mode of training depends upon the experience and preference of the rehabilitation team, but should adhere to the accepted principle that cardiovascular fitness is achieved most consistently by dynamic activity involving large muscle groups. for example walking/jogging, cycling, swimming, circuit training. The Toronto program prescribes walking progressing to jogging. with stationary cycling or swimming either on a temporary or permanent basis for those who have problems ambulating.
Whatever the mode, the exercise session should be carried out between three to five times weekly, and the duration progressively increased from 15-60 min. Initially, patients will need supervision during exercise sessions, but eventually most will be able to train at home without risk, attending a supervised class only once a week. and later only once monthly.
The development of hypertension is always a potential problem in the management o1' heart transplant patients. While there is good evidence that this is a side-effect of immunosuppressant cyclosporine and/or steroid therapy, a recent report suggests that it might be due to chronically elevated levels of circulating norepinephrine. If this is so, then an exercise training program should help. since it has been shown to reduce catecholamine levels and have an anti-hypertensive effect. particularly in hyperadrenergic individuals. In any event, a resting systolic blood pressure greater than 200mmHg, or a diastolic pressure greater than 110mmHg, is a contraindication to exercise training, as is an exaggerated inotropic exercise response in which the systolic pressure exceeds 250mmHg or the diastolic pressure 120 mmHg.
It is reported that an accelerated form of coronary atherosclerosis develops in 50% of heart transplant patients by the fifth postoperative year. Unfortunately, one cannot rely on angina as a symptom of myocardial ischaemia. Furthermore, exercise-induced ST-segment depression is frequently absent. despite anglographic evidence of severe coronary vascular insufficiency. Whether this is due to the typical lower heart rate attained by transplant patients on exercise testing, or a difference in pathophysiology between transplant vasculopathy and native coronary atherosclerosis. remains unclear. There is always, of course, the possibility of exercise-induced ischaemia giving rise to arrhythmias. but the likelihood of this is reduced if the training intensity is kept at or just below the ventilatory threshold.
Acute episodes of graft rejection are an ever-present threat; they are most accurately detected by endomyocardial biopsy. Rejection may be accompanied by episodes of ventricular arrhythmias, particularly when there is a concurrent coronary artery disease. Again, maintaining the training level at the ventilatory threshold will ensure that the arrhythmia threshold is not reached. Obviously, major rejection episodes are a contraindication to training. Intercurrent infections due to immunosuppression, particularly cytomegalovirus infection, are another hazard. Despite this formidable list of potential problems. however, total abstinence from physical activity is seldom required. and even then only for relatively brief interludes.
Historically, cardiac exercise rehabilitation has its origins in the 1960s, with the care of the acute myocardial infarction survivor. Since then, the spectrum has broadened to include a variety of cardiac conditions. Heart transplantation patients were not considered until the early 1980s, and consequently the number of reports dealing with the effects of exercise training in these individuals has been limited.
The earliest report was from Squires and coworkers, who demonstrated that a training regimen could be both effective and safe. Since that time there have been nine reports: four from Europe and five from North America. Of these, eight have dealt with orthotopic transplant recipients, with only two devoted to patients who have undergone the far less common heterotopic procedure (in which the donor heart is implanted in the chest in parallel with the recipient heart).
There is general agreement that an aerobic-type training program can result in significant improvement in cardiopulmonary fitness. Peak oxygen intake is increased, and the onset of anaerobiasis is delayed; the latter is reflected in an increase in the absolute ventilatory threshold and a reduction in blood lactates at equivalent submaximal work rates. A decrease in resting and submaximal heart rates has also been reported, together with an increase in maximal rate pressure product, the extent of these changes depending to some degree on the intensity and duration of the training program. The shorter programs have all resulted in appreciable gains in cardiorespiratory fitness, but a reduction in resting heart rate (probably due to a reduction in resting plasma norepinephrine and/or a down-regulation of myocardial beta-receptor sensitivity) and an increase in lean body mass have only been noted after a longer training period, such as was reported by the Toronto program. There have been no reports of a training-induced change in cardiac dimensions or function. All programs used a training intensity corresponding to 12-14 on the Borg rating of perceived exertion scale, the ventilatory threshold, and/or 60 - 70% of peak oxygen intake.
It is claimed that much of the training effect is due to an increase in lean body mass, or an improved skeletal muscle metabolism. Recently, Braith et al have reported a correlation between leg strength and peak oxygen intake in heart transplant recipients, and this would argue for the inclusion of one or two weekly sessions of resistance training to supplement the aerobic regimen. In fact, Horber et al have demonstrated that renal transplant patients responded well to an isokinetic muscle training regimen, with an improvement in strength and cardiorespiratory fitness. To date, however, there have been no reports on the effectiveness of a heart transplantation exercise program which employs strength training alone.
The routine use of a comprehensive exercise rehabilitation program following cardiac transplantation is a safe and effective way to maximize the benefits of surgery. Published studies have shown that an exercise rehabilitation program can induce a good training effect, although complete restoration of physiological function may not be possible. However, the prescription of exercise must take into account the denervated heart's peculiar response to effort, and must rely on perceived exertion and metabolic measurements rather than on target heart rates for defining the intensity of training.
It is tempting to speculate as to whether a comprehensive rehabilitation program which includes not only exercise training (resistive as well as aerobic) but also dietary advice and weight control might favorably influence long-term post-transplantation hypertension and coronary atherosclerosis. Further studies are needed in this regard.
Journal of Cardiovascular Risk, April 1996, Vol. 3 No. 2, pp. 154-159
John Bray - New York Times
When demand far exceeds supply, does it make sense to generate more demand'? Perhaps, if you area commodities trader want to run up the price. But what if we are talking about the business of heart transplants, with its substantial public investment and nonnegotiable raw materials?
The number of people waiting for heart transplants far exceeds the number of those receiving them. Yet a new technology approved by the Federal Government will probably exacerbate the imbalance, add to of cost of transplants and intensify turmoil on the waiting line.
Devices that can keep people alive for months while they await donated organs are entering the health care mainstream. The products, called ventricular assist devices, mechanically help pump the heart.
Since October 1994, the Food and Drug Administration has approved three models by three manufacturers- Thermo Cardiosystems, Aviomed and Thoratec - for use as bridges to transplants. All had already been used experimentally for some years. In January 1996, the taxpayer-financed Medicare program for the elderly and disabled started paying for the use of the first design by Thermo Cardiosystems. Now, the Health Care Financing Administration, which runs Medicare, says it will cover the two other models, too.
So far, hundreds of patients have received these devices, which have done their job.
By using such a machine, a patient makes an impressive demonstration of his need for new heart, and can move up on the waiting lists for donor hearts. And hospitals that don't offer the machines risk losing patients to institutions that do, further fueling competition among transplant centers that may not be appropriate.
In a distribution system that is supposed to be driven by the patient's medical needs and time on the waiting list, Medicare has introduced a twist that seems to add special urgency to Medicare patients on these devices.
In its guidelines for the pumps use, the Health Care Financing Administration has specified that surgeons should make "every reasonable effort to transplant patients on such devices as soon as practicable."
An analyst with the Health Care Financing Administration told me last December that "we don't want 50 people on these devices, 40 of whom are not going to get an organ."
Medicare's payments vary for using these devices, depending on the circumstances of each case, the differences in hospitals' billing decisions and the payment scales of the region. In an example provided by the agency, Medicare would pay about $15,000 for a patient to be on such a device for one week at a Boston hospital.
Then there are the surgeon's fees associated with installing and removing the devices, about $3,000 total, the agency said.
A heart transplant is already expensive - usually about $100,000. Medicare spent nearly $45 million on 494 heart transplants in 1995; the total reflects only the costs associated with the procedure and immediate postoperative' care, not the continuing associated expenses like drugs. It costs $325 just to get on a waiting list.
The analyst with the Health Care Financing Administration told me that it almost didn't approve coverage for the devices. It gave its O.K. only after taking a second look and setting some ground rules requiring, for example, that the patient be approved and listed as a candidate by a Medicare heart transplant center.
The Health Care Financing Administration is betting that its guidelines will encourage the medical establishment to use the devices responsibly. The agency wants transplant centers to show some restraint, but the technology has spread quickly.
Heart transplant centers have popped up all over the country in recent years. The number of patients awaiting new hearts at all transplant centers has grown steadily, but the number of transplants has failed to keep pace. In 1994, the last year for which complete figures were ;available, 6,378 people were in line for transplants, while just 2340 received them, according to the United Network for Organ Sharing, the Federal contractor that tracks transplant data. In that year, 724 people died while on the waiting list.
Patients understandably grasp at the glimmer of hope these devices offer. But heart transplantation is not ready for greater demand, and taxpayers should not be asked to subsidize it, especially when Washington is talking about reining in Medicare spending.
John Bray is a writer and editor in Woodbury, Conn. He has written extensively on the science and business of medicine.
Contributed by Tx Jim Gleason, Collegeville, PA
To: The mailer of the unsealed envelope from Miami addressed to UpBeat w/o return address - please be advised it arrived, still unsealed and empty.
Apparently long term tenure on immunosuppressants tends to bring out a latent potato gene in the transplant body. It must be this gene that promotes the funny little growths all over the place, some a lot more serious than others. The regular visits to the dermatologist have become the basis for first name conversations about the Doc's kids in college we're paying for, as he waves his magic wand around the body freezing anything new sprouting. However, the recent polyp on the vocal cord got surgical attention at the insistence of my friendly Tx Physician, who took note of a newly acquired hoarseness of the patient's voice. Even though I thought I was doing an excellent "Cosby" he made the appointment with the ENT doctor for exam and then surgery to biopsy. The exam goes fine, but try and avoid the surgery. You've been through much worse, but not being permitted to talk for a week can get on your nerves, not to mention waiting for the results of the biopsy. I also have been told they put a clamp on your tongue and tie it to a cement block hanging off the side of the table - at least the tongue feels numb for quite a while afterwards.
Avid readers of UpBeat may remember several months ago the possibility of an Addison's attack was mentioned as a potential for those of us who are now addicted to prednisone and thus have no functioning adrenal system. Well, I'll be golly go to hell if I didn't have one of those things, but in the midst of the action, never recognized what it was.
Rather briefly, it occurred while the "Principle Caregiver" and patient were taking a cheapy off-season vacation in a rented condo at Cape Hatteras. We had both tried the same "local fish" at dinner - yellowfin tuna, fresh caught. Yeah right! By the time I had trekked up the 44 steps to the condo (everything at Hatteras is built high enough that global warming will have no effect complete with no elevators) I was wondering once again if the great TCAD had finally struck. Sitting to read the paper and catch my breath, I discovered my arms and shoulders ached. Deciding that feeling poorly deserved bed, in getting up I lost balance and nearly flattened the kitchen counter. With help I made it to the bed, when in trying to continue to read I noticed it was difficult because my vision seemed to be dissolving into random small spots. About then the diarrhea struck. Problem was my blood pressure had dropped so low I needed help to make the short journey to the bathroom. Now at this point we reached what has to be the epitome of "principal care giving" because as the caregiver was nearly dragging and carrying the patient to the required fixture, she also was stuck with the same requirement. Propping the patient up on the facility and hoping for the best, she made a dash to the other end of the apartment to the fortunate presence of a second bathroom. This relative condition of rotation existed for about an hour followed by the patient literally passing out in bed with a pulse and BP lower than the bait being lowered off the fishing pier next door. However, by 3 AM l awoke with a thirst that needed attention and finding I could again maneuver, I even awoke the caregiver and jubilantly warned her I was going to live to haunt her another day.
Later review of the situation on the Internet pointed clearly to scombroid food poisoning for both of us. Yet as the Tx physician pointed out the Principle Caregiver's adrenal system swung into action and limited the effects on her to just an intestinal disturbance. With no adrenal action in this corpus largeum, the blood vessels just opened up and the BP dropped to zero causing the other symptoms.
Now if you get into this situation the best place for you is an emergency room. (We couldn't figure out how an ambulance crew was ever going to get me down six flights of stairs - and figured when they heard the word transplant helicopters would start hovering.) Later, my Tx Doctor told me - and remember he didn't tell you anything. nor did I, UpBeat does not practice medicine - that the treatment over the phone would have been 20 mg. of prednisone, and in the hospital, under care, maybe even 100 mg. would have been given. (Remember the admonishment that if your body gets under stress you're going to need more prednisone so to be sure and tell the people treating you about your condition? Well food poisoning is stress.)
Tx Judy Holden of Santa Monica wrote of how appreciative she was to learn why it was that she had to get up so many times during the night that she just sleeps with her sneakers on. But she came back with yet another of the mystery questions that confronts tenured Tx recipients. As Judy says, "Why do I need a box of Kleenex every time I eat or drink anything. It doesn't matter if it's hot or cold, bland or spicy, my nose runs every time." Well mine does too, and has for my memory since Tx, so I thought my recent visit to the ear, nose and throat doctor would be just the time and place to finally get the answer.
"Say, Doctor," say I, "Several transplant recipients I know and I have wondered why it is that every time we eat our noses begin to run like faucets?" I could see he was a bit befuddled in thinking about the problem, so in an errant attempt to help him out I blurted, "Could it have something to do with the drugs?"
"Oh yeah, must be the drugs," was his immediate reply. So there you have it, another UpBeat exclusive.
Somewhat selfishly, but also in the common interest, it would be most interesting to learn of the most original, unusual, lavish, thoughtful, fun, or even serious ways heart and lung recipients have devised to celebrate their 10th anniversary of transplantation. We'll publish the most interesting in any and all areas. Please let us know what you did, or are contemplating doing.
NOTICE TO READERS: DUE TO SOME COMMITMENTS ON BEHALF OF THE UPBEAT STAFF (THERE ARE REALLY 2- 1 EAST AND I WEST COAST) THE JUNE ISSUE WILL BE A BIT DIFFERENT THAN ANYTHING IN THE PAST. WE HOPE YOU WILL ENJOY IT. REGULAR PUBLICATION WILL RESUME IN JULY.
By Linda Carroll, MSNBC
You may not be able to make a silk purse out of a sow's ear, but new research may lead to something much more useful. Many researchers predict that doctors will soon be able to make the sow's heart beat inside a human body while the animal's lungs do the breathing.
Through genetic engineering, scientists have created pigs with designer organs that can be transplanted into people organs that human bodies may not reject. Transplant specialists have turned to animal donors because of the growing shortage of human donor organs.
"Right now, there are 51,000 patients in the United States waiting for an organ transplant," says Dr. Hans Sollinger, a professor of surgery at the University of Wisconsin in Madison. "And unfortunately, at the current rate of organ donation, eight to 10 people are dying each day because they don't get an organ on time.
"There are only two ways out of the dilemma: cure the diseases that damage these organs or find a new source of donors." And, Sollinger says, science hasn't advanced to the stage where a cure will be found in the foreseeable future. That's where the pigs come in.
Pigs are the perfect choice for organ donors, experts say. "They're available in very large numbers," explains Jeffrey Platt, professor of experimental surgery, pediatrics and immunology at Duke University in Durham, N.C. "And pig organs are appropriate in size." Another advantage is their abundant litters, Platt says. When a particularly well engineered pig is developed, it will be able to reproduce its genes quickly. Beyond this, there isn't a pig protection lobby, like there is for primates, Platt says.
Researchers are already using pig livers temporarily connected to a human being outside the body to purify blood in people with sudden and potentially fatal liver failure. When people develop this kind of liver failure, their organs don't break down toxins in the blood. And this can result in damage to the brain which will send the patient into a coma, explains Dr. Andrew Klein, director of the comprehensive transplant center and chief of the transplant division at the Johns Hopkins University School of Medicine.
Several years ago, Klein and his colleagues brought a woman out of such a coma by hooking her up to a pig liver. After only four hours on the pig liver the woman woke up, Klein says. That pig liver gave doctors time to locate a human liver, and after a transplant the woman fully recovered. according to Klein.
Other researchers have transplanted fetal pig tissue into the brains of people with advanced Parkinson's Disease. Some of these patients who experienced great improvement in their symptoms have had pig tissue in their brains for more than two years.
The idea of transplanting animal organs called xenotransplants. after Xenos. the Greek word for strange isn't new. Sollinger says. The first xenotransplants were attempted at the turn of the century. "These organs were rejected in a very short time." he adds. "The problem is that when you cross the species barrier with the exception of the large apes man has antibodies against the donor animal's tissues. These antibodies immediately and aggressively attack the organ, resulting in rejection in a few minutes."
But now researchers at Duke University and a small New Jersey company called Nextran may have found a way around the cross-species rejection problem. Scientists have discovered that certain kinds of proteins called complement proteins circulate in the blood and act as scouts, seeking out and glomming onto foreign matter in the body. By attaching to the "invader." the complement proteins mark it for destruction by other parts of the immune system. Other proteins membrane cofactor protein (MCP) and decay accelerating factor (DAF). for example protect the body's own organs from destruction. They do this by blocking the complement protein from attaching to the organ. Using this research. Nextran has designed and genetically engineered pigs with organs that will produce the human protective proteins MCP and DAF.
So far, attempts to transplant animal organs including those from apes have failed. In one of the most publicized cases. 2-week-old Baby Fae was given a baboon heart to replace the defective organ she was born with. Three weeks after the transplant. the infant died, her new heart having been attacked and destroyed by her immune system.
And even though primate organs are closer to those of human beings, doctors these days say apes are a bad choice. This is partly because animal rights activists have deplored the use of primates for transplants and partly because apes aren't designed well for use as organ donors. Apes take a long time to mature, Platt explains. And perhaps more importantly, apes may carry viruses that can be easily transmitted to human beings. Most researchers today believe that HIV originated in monkeys and was eventually passed on to human beings.
But Platt is hopeful that genetically engineered pigs with organs that produce human protective proteins will lead to successful xenotransplants in the not-too-distant future. "This isn't science fiction," he says. "But I think it will probably be a few years before we begin to do xenotransplants on an experimental basis. And it will be some years more before anything could become routine practice."
Still, some scientists argue that the whole idea of animal transplants is fraught with peril. In Britain, the government called a moratorium on transplant research citing fears of an unknown virus spreading from the pigs to humans.
Although researchers like Platt agree that this is a possibility, they say it is unlikely. "I think it's hype mostly," Platt says. "Clearly there are viruses that can be transmitted from pigs to humans influenza is one example." But, Platt says, if there was a harmful virus it probably would already have been transmitted to the human population through people who work in meat packing plants and slaughter houses.
Even if the new genetically engineered pigs don't carry viruses, some heart transplant experts are pessimistic when it comes to predicting how long it will take to have routine pig-organ transplants. "The immune system has a way of detecting the smallest amount of foreign substance in the body," says Dr. James Southard, a professor of surgery at the University of Wisconsin at Madison. "My feeling is that we're not going to make much of a dent in the organ-shortage problem with xenotransplants.
"Of course, 50 years ago, I wouldn't have thought we'd go to the moon, either."
By Claudia Coates - Associated Press Writer
PITTSBURGH (AP 5/7/97) -- An experiment inspired by rebellious organ transplant patients who discarded their vital anti-rejection medicine suggests some can be weaned off the drugs, which are prescribed for life but often cause debilitating side effects.
The drugs, lauded when introduced a decade ago because they made previously risky transplants commonplace, nevertheless leave patients open to infection and cancer. Yet all recipients of donated organs have been required to take drugs the rest of their lives to keep their own immune systems from fighting the foreign tissue.
Over time, a few patients balked at the side effects and threw away their pills. Some fell ill and had to resume medication. But some thrived without it.
Now, researchers have weaned 25 children with transplanted livers off anti-rejection drugs for as long as 7 1/2 years. Six other children in the carefully selected group went back on their pills.
"None of them have died, and none of them have required a retransplant," said Dr. Jorge Reyes, director of liver transplantation at Children's Hospital in Pittsburgh, who heads the study.
Reyes plans to present his findings next week at a meeting in Chicago of the American Society of Transplant Physicians. The Mayo Clinic in Rochester, Minn., is conducting a similar study, he said.
Most transplant patients take either cyclosporin or FK506, also called tacrolimus, to suppress their immune systems. With their natural infection fighters hobbled, patients develop cancer so commonly that their form of it has a name: posttransplant lymphoproliferative disorder.
"Every year I get a child who comes in with it," Reyes said.
Cyclosporin can also cause high blood pressure, thickened gums, arrested growth, extra facial and body hair and a reddened, puffy face.
Some patients battling organ rejection also take steroids, which can weaken bones and cause severe acne, blindness and mood swings.
More than 24,000 liver transplants have been performed since 1988, but Reyes estimated fewer than 10 percent of the recipients would be good candidates to give up drugs.
He said additional studies focusing on other transplanted organs would be needed before researchers could speculate on a drug-free existence for non-liver recipients.
"We believe in principle that everybody could eventually come off," he said.
Reyes firmly cautioned that no transplant patient should cease anti-rejection medicine without a doctor's consent.
Dr. Alan Langnas, a liver-transplant surgeon at the University of Nebraska, said he, too, learned that some of his patients do well after halting their drugs while others do very badly.
"There's a high price to be paid if you choose the wrong patient," Langnas warned.
Reyes said liver patients were the only group appropriate for the study because doctors can monitor the liver's function and restore the medicine at the first sign of rejection.
A researcher would not suggest heart recipients, for example, give up drugs because the first sign of rejection could be a fatal heart attack. Some kidney recipients have given up drugs, but the risks are too strong for researchers to recommend it, Reyes said.
At the study's onset, all 31 children had had their new livers for at least five years and had gone at least two years without a rejection episode, Reyes said. Eighteen were taken off drugs abruptly because they had developed cancer or an infection. The 13 others were taken off gradually as researchers tested their liver function, at first every week then tapering off to l0-week intervals.
The patients who tapered off had fewer rejection episodes than the patients who were withdrawn abruptly, and the cancers and infections that afflicted the latter group disappeared when their immune systems were restored.
One boy in the study, Kevin Wilkens. 16, of Oak Harbor, Ohio, was 5 when he got a new liver at Children's. He took cyclosporin and prednisone, asteroid, but was taken off prednisone because of stomach cramps. Over the last few years. his dose o1' cyclosporin has been reduced to nothing.
He's taken no transplant medicine the last two months and says he feels fine.
"It sort of surprises me, too." said Kevin, who pumps gas part-time and plays second base on his high school baseball team. "I'm just like any other 16-year-old around, other than I got some scars on me."
Dr. Thomas Starzl, who pioneered liver transplants in 1967 at the University of Colorado and joined the University of Pittsburgh Medical Center in 1981, has a theory why some patients can discontinue antirejection drugs. In all organ recipients who survive a long time, doctors find cells from the grafted organ settled into the host body's skin, lymph nodes, heart and bone marrow, and cells from the host body in the new organ. Starzl and Reyes believe the exchange of cells promotes harmony.
"We haven't proved it yet, and we don't know," Reyes said.
Other researchers believe the determining factor in host-graft harmony is how well tissues match. Body tissue has a type, just as blood does.
Reyes said researchers might never have tried the experiment if not for those willful patients who threw their drugs away -- and lived.
"We come upon these things almost by accident," Reyes said.
One of the rebellious patients was Betty Baird, a Uniontown woman who received a new liver in 1980, flushed her pills down the toilet three years later and has been fine without them. The drugs had warped her emotional stability; one morning she "came to" just as she was placing a pillow over her wailing baby's face.
"I didn't even keep a few just in case," Ms. Baird said.
Ed. Note: The spelling of cyclosporine above is as/AP. A rumor that after reading this story the management of Novartis set up a chapter of Heaven's Gate is unfounded.
By Yuri Kageyama - Associated Press Writer
TOKYO (AP 4/24/97) -- A 27-year-old man in the Parliament balcony looked on, pleased, while lawmakers below passed a bill Thursday that would allow lifesaving organ transplants in Japan.
Hirofumi Kiuchi had to go to Los Angeles in 1993 to get his new heart. "I prayed for the American who died," he said. "And I vowed to take really good care of this heart."
Passage of the bill -- which still must clear the upper house -- came a week after an 8-year old Japanese girl died in Los Angeles, waiting for a heart transplant that never came. Her plight aroused a flood of sympathy at home.
But organ transplants long have been a volatile issue in Japan, where taboos remain about cutting into bodies and some fear doctors may be more intent on harvesting organs to perform a transplant than trying to save an elderly or disabled patient.
The only heart transplant in Japan was in 1968; it failed and the surgeon was accused of seeking frivolous fame.
The bill, which passed the lower house 320148, recognizes brain death as the definition for death. It also states that organs from brain-dead donors can be used for transplants. The upper house has yet to set a vote.
Current law defines death as when the patient's heart stops beating. At that point, organs rapidly deteriorate and become unsuitable for transplant.
So transplants in Japan mostly have been limited mostly to corneas and kidneys, and to a lesser degree liver sections, which are not as prone to rapid deterioration or can be taken from living donors.
No law bans transplants from brain-dead donors, but without legislation explicitly permitting them, surgeons have been afraid to perform them.
While lawmakers debated the bill, about 20 protesters outside the Parliament building, some in wheelchairs, demanded the bill be thrown out.
"It could spread to the idea that the handicapped, the elderly don't deserve to live," said protester Yoshiko Aoki.
Even if the bill passes the upper house and becomes law, doubts remain about whether there will be many organ donations. In Japan, only one of every 20 people on the waiting list for kidney transplants finds a donor. In the United States, the figure is one in three.
The bill requires a written statement of intent from the donor as well as consent from the donor's family. Children under 6 cannot be donors. Still, lawmaker Hiroshi Imai said he was optimistic.
"Public understanding is increasing," he said. "I talked it over with my family just two or three weeks ago, and I plan to become an organ donor."
By Salah Nasrawi - AP Writer
CAIRO, Egypt (AP 5/4/97)-- A leading Muslim scholar has decided to donate his organs after his death, prompting a debate in Egypt over the legality -- and desirability -- of organ transplants. The declaration by Mohammed Sayed Tantawi, the grand sheik of al-Azhar, has added credibility to the government's effort to legalize the practice, which is still banned in Egypt.
Donating organs after death is allowed in some of the strictest Muslim countries, such as Iran and Saudi Arabia. But many Muslim scholars oppose the idea, saying human bodies are sacred and should not be violated after death.
One of Egypt's leading clerics, Sheik Mohammed Mutwali Sharawi, even opposes transplants from living donors to someone else, a practice permitted in this predominantly Muslim country.
In a ruling published in Cairo newspapers Sunday, Tantawi provided support for organ donations, saying it was permissible in Islam under certain conditions. Among them: that the person had given permission or that the person's family authorizes it.
His ruling also included a more controversial provision: Doctors can take organs if the family is not available to authorize it. "Concerned authorities can permit that," he said.
Although not law, a ruling by the sheik of al-Azhar, one of the Muslim world's leading institutions of religious scholarship, carries weight among Egyptians and other Muslims.
Tantawi's decision last week to be an organ donor and his ruling were welcomed by state owned newspapers, which support the effort to legalize the practice and find badly needed organs for thousands of patients on waiting lists across the country.
"He is a leading example," said Ibrahim Sada, editor in chief of Akhbar AI-Youm. "He refuses to hold the stick in the middle, regardless of whether that will make some people angry or not."
Well-to-do Egyptians needing transplants travel abroad when a living donor is not available or when they are in need of a vital organ.
Egyptian doctors complain they are being barred from taking part in medical advances because of the ban and deprived of lucrative fees in performing such operations.
"It is a pity that Egypt, which was a pioneer of progress among the Muslim nations, is now facing attempts to drive it backward," Hamdi elSeyed, the head of the powerful Doctors Syndicate, told a meeting Thursday debating the issue.
Some doctors, however, have argued against lifting the ban.
"Transplant is wrong and we cannot exclude the religious argument because the constitution says that Egypt is an Islamic state," said Safawat Hassan Lutfi, an anesthesiologist.
On Sunday, the Egyptian parliament began discussions on a draft bill proposed by the government to permit such transplants. It could take days for the bill to reach the floor.
By Linda Ashton - Associated Press Writer
SEATTLE (AP 4/21/97) -- Hilde Kvant rushed to the United States when she got word her brother suffered a brain aneurysm while visiting this country. By the time she arrived from Norway, Bjorn Ove Grandurn was brain dead and on life support.
Rather than just making arrangements for a melancholy return to Norway, Mrs. Kvant and her husband lvar did something unusual -- they donated Grandum's organs to Americans.
"It's not unheard of to have foreign nationals become donors in the United States, but it's rare," said Joel Newman, a spokesman for the United Network for Organ Sharing in Richmond. Va.
The Kvants, weary and grieving, agreed to an airport interview with The Associated Press last Thursday before returning to their home in Bergen, Norway.
"We're doing this to get others to think about donation," Ivar Kvant said.
"We don't need to know who he's helping." Kvant said. "It's important to know his death isn't for nothing -- that people are helped with this donation."
By donating Grandum' s heart, heart valves, kidneys, lungs, pancreas and liver, the Kvants were able to help a half-dozen Puget Sound people and their families, said Tamila Timm, procurement coordinator at LifeCenter Northwest, the organ donation center for Washington, Alaska, northern Idaho and Montana.
There are a number of reasons why such donations are rare.
For one thing, few people die while on vacation. The age and health of the deceased and the manner of death also can rule out donation. In other cases, families may raise cultural or religious objections.
But a donation can have a memorable effect when made in another country.
The best-known example of international organ donation occurred in 1994 after bandits shot and killed a 7-year-old California boy, Nicholas Green, during his family's vacation in southern Italy.
Italians were stunned by his family's decision to donate his organs, an act that saved seven people in Italy and inspired a surge of organ donations in a country where the practice remains unusual.
Norway has no organ donation program. In Japan, transplants are virtually nonexistent.
The country does not legally recognize brain death. Death is considered to occur after a patient's heart stops beating, but at that point internal organs deteriorate quickly and become unsuitable for transplant.
Eight-year-old Miyuki Monobe of Tokyo came to UCLA Medical Center in California in search of a new heart. She died last week before a suitable donor organ could be found.
The United Network for Organ Sharing doesn't keep specific records on the number of international donations, Newman said. But even the number of domestic donations is small. Of the more than 2 million deaths in the United States each year, organs might be feasibly donated in only 15,000-20,000 cases. Of those candidates, organs from only 5,400 deceased Americans are donated to others.
Grandum, 32, was always busy, his sister said. He had worked day and night to save for his trip to the United States. An Oslo taxi driver, he had two children.
"He was very fond of traveling. He really enjoyed life," Mrs. Kvant said.
Grandum planned to drive from Seattle north to British Columbia to visit relatives. He never got out of town, collapsing in his hotel room April 13.
Grandum telephoned his sister from Harborview Medical Center to tell her what was happening. It was their last conversation. When she and her husband got to Seattle on April 15. machinery was keeping Grandum alive.
Although their native country had no donation program, the Kvants knew what it was like for those who wait for organs.
They endured an agonizing wait for a liver for Ivar's gravely ill 2-year-old niece in England. The toddler suffered a heart attack and subsequent brain damage while waiting for a donor organ.
As a result, the family had talked about organ donation before, and Mrs. Kvant knew they were making the right decision for her brother.
Still, she said, "It's hard to think about this when you just have lost someone.
By Evan Perez - Associated Press Writer MIAMI (AP 5/8/97) -- Barreling down a crowded highway in the back of a patrol car, Raimund Stillfried saw his yearlong wait for a kidney and pancreas transplant come down to a race against time and traffic without a minute to spare. The organs, which would give the man severely ill from diabetes a chance at a new life, were located earlier Tuesday. But Stillfried couldn't be found and the organs were due to go to the next patient on the list if Stillfried didn't arrive at the hospital before the seven-hour deadline expired.
"He was nervous," said Metro-Dade police Sgt. Ozzie Hernandez, who rushed Stillfried to Jackson Memorial Hospital at speeds topping 100 mph. The high-speed race across town capped a more than six-hour search for Stillfried.
Stillfried had come to Miami from his native Caracas, Venezuela, for a checkup and to find out where he stood on the organ transplant list at Jackson Memorial. The news wasn't good.
During a morning meeting, the 33-year-old father of three was told his wait would be at least a few months longer. Stillfried thought he might die before the organs were found.
Stillfried and his wife left to go shopping. Fifteen minutes later, the hospital called. using the pager that transplant patients are supposed to carry with them. Stillfried had forgotten his.
Relatives took to the roads, combing store parking lots and restaurants the couple frequented. Gonzalez called rental car companies, eventually finding the agency that had rented the white Mazda 626 to the couple.
A neighbor drove to stores and asked workers to page the Stillfrieds. She also called a radio station and asked them to broadcast an emergency message.
Police, who had been combing the area and stopping white Mazdas, finally caught up with the Stillfrieds at a discount wholesale store in Kendall, a suburb southwest of Miami.
They hustled them to the station, where officers tried in vain to get a helicopter.
Hernandez put Stillfried into a squad car and sped for the hospital across the city. usually about 45 minutes away. Luckily, traffic wasn't as heavy as expected. Stillfried arrived about four minutes before doctors would have given the organs to another patient.
Disclaimer: The material in this document has been collected by Don Marshall and friends. If any of the views and opinions expressed here are taken the wrong way, we can be nothing m ore than sorry. New ideas and materials are welcome all the time. As a policy, UpBeat is sent upon request to heart and heart/lung transplant recipients and other interested parties. Donations of $15 per year, or more, from Tx recipients, if not a burden, are vital. From all others t he donation is specifically requested. The date shown after the name on the address label indicates the last time a donation was received. Please make checks payable to Don Marshall, as we cannot afford to become nonprofit. Send materials, letters, or checks to:
P.O. Box 482
Mathews, VA 23109-0482