Dalynn T. Badenhop, East Carolina School of' Medicine
The patient with orthotopic heart transplant (OHT) presents as a very challenging patient for exercise rehabilitation primarily because of his new cardiac physiology and hemodynamics and his immunosuppressive status. The immunosuppressive drug regimen that patients with OHT must follow is responsible for numerous comorbidities in this population. In many cases patients with OHT, because of their lifelong need to maintain their immunosuppressive status, are trading the medical management of one chronic disea se for another. Cyclosporine causes hypertension in most patients with OHT.
Prednisone therapy produces the following side effects: 1) sodium and fluid retention, 2) loss of muscle mass, 3) glucose intolerance/ diabetes mellitus, 4) osteoporosis, 5) fat redistribution from extremities to torso, 6) gastric irritation, 7) increased appetite, 8) increased susceptibility to opportunistic infections, 9) predisposition to peptic ulcers, and 10) increased potassium excretion. The triple drug immunosuppressive regimen of patients with OHT manifests some of the traditional risk factors for coronary artery disease such as elevated blood lipids and hypertension. These patients are also susceptible to plaque deposition because of chronic injury to the heart and blood vessels caused by repeated episodes of rejection. A complication of immunosupp ressive therapy includes an increased tendency to develop lymphoproliferative malignancies. All of these side effects are counterproductive to the goals and objectives of exercise rehabilitation after cardiac transplantation.
At rest, the ability of a patient with OHT to maintain homeostasis[ a constant or steady state of the body] is not greatly affected. The lower resting stroke volume and left ventricular ejection fraction of a patient with OHT is compensated for by a higher resting heart rate to effect a similar cardiac output at rest compared with age-matched controls. Although individual studies have reported higher than normal resting blood pressures in this population as a whole, reports have indicated resting blood pres sures in the normal range. This may be due to advances in treating the hypertension associated with the administration of cyclosporine.
Peripheral factors contribute to impaired physical performance in patients with congestive heart failure (CHF). Published data support the fact that peripheral physiology remains impaired in patients with OHT for a prolonged period of time after heart tran splantation. Skeletal muscle biopsies 6 wk after orthotopic cardiac transplantation are grossly abnormal and include intracellular lipid and glycogen accumulations, increased pinocytosis [increases fluid in cells], and markedly thickened capillary basemen t membranes. Skeletal muscle contractile function remains unaltered for 6 wk after transplantation. Peripheral factors, including high arterial lactates, still predominate in patients who are 15 months post-transplant. The vascular system becomes intrinsi c a lly stiff in response to the long-term, low-flow state of CHF. Peripheral vasodilator capacity remains impaired for as long as 4 months after heart transplantation. Improvements in cardiac function act indirectly and slowly to improve peripheral vascul ar function. No intervention, other than increasing physical activity after transplantation, has been shown to improve impaired peripheral physiology in these patients.
Although the hearts of patients with orthotopic heart transplant respond in such a way that individuals remain remarkably asymptomatic, some transplanted hearts exhibit impaired diastolic filling owing to altered ventricular compliance or relaxation. This restrictive physiology is associated with elevated left ventricular filling pressures and abnormal right heart hemodynamics that may pose a functional limitation early post-transplantation. There is evidence that over time there is a normalization of rest and exercise central hemodynamics in response to exercise after cardiac transplantation, including significant decreases in ventricular filling pressures, pulmonary artery pressures, and pulmonary vascular resistance..
The denervated heart, subsequent to transplantation, offers a unique model of cardiovascular exercise physiology. In the innervated heart, neural regulation plays an instrumental role in the body's response to exercise. The transplanted heart loses its neu ral regulator but retains its humoral [blood chemicals] regulator. As a result, the transplanted heart's response to exercise is altered. Cardiac denervation results in a loss of autonomic modulation of cardiac output. Humoral regulation of cardiac output becomes the primary physiologic mechanism for responding to increasing physical demands. Because this mechanism is secondary in normal cardiac physiology, the response to exercise in the patient with OHT tends to be delayed and blunted as compared to norm a l subjects.
Two studies have reviewed the possibility of increased sensitivity over time of the denervated transplanted human heart to catecholamines, but this does not seem to be the case. Changes in cardiac and systemic physiology and hemodynamics over time in patie nts with OHT is an important consideration in applying exercise as a therapeutic intervention.
Peak cardiorespiratory and cardiovascular responses to exercise in patients with OHT are blunted in comparison to normal age-matched control subjects. Peak heart rate and systolic blood pressure values are 80% of those achieved by normal subjects. Because of higher resting heart rates and lower peak heart rates, heart rate range (defined as the difference between resting heart rate and peak heart rate) is the cardiorespiratory parameter most affected by cardiac transplantation. Normal heart rate ranges are from 90 to 100 bpm, whereas heart rate ranges in patients with OHT are only 40-50 bpm or approximately 50% of normal. Physical work capacity in patients with OHT is similarly significantly reduced to 46% of that achieved in normal subjects (96 W vs 208 w). Peak metabolic equivalent (MET)[amt. of oxygen per kilogram of body weight per minute w/body at rest] levels achieved during graded exercise testing of patients with OHT (5.6 METs) approximate only 60% of that achieved by age-matched controls (9.3 METs).
Ventilatory data indicate an earlier onset of anaerobiosis [shortness of breath] in patients with OHT vs normal subjects.
The hemodynamic mechanisms by which patients with OHT augment cardiac output during exercise are atypical. The transplanted, chronically denervated, non rejecting left ventricle demonstrates normal contractility and contractile reserve. The denervated hear t contributes to the exercise response by different mechanisms compared with a normally innervated heart. The rate of rise in cardiac output and peak cardiac output is lower in patients with a transplant because of lower maximal heart rates. Peak exercise values for cardiac outputs and cardiac indices in patients with OHT are only 45 and 78% of those in age-matched controls. The ability of the denervated heart to perform anything more than mild exercise is critically dependent on the release of catecholami n es into the blood stream to augment cardiac output by increasing heart rate and increasing contractility. Sympathetic response to peak exercise is actually increased in patients late after transplant. The heart rate response to exercise in patients with OH
T is appropriate for the levels of circulating catecholamines. There is a distinct reduction in the exercise capacity of the patient with OHT who is taking a betablocker medication. Soon after surgery, patients with OHT achieve peak values on graded exerci se testing that are slightly lower in comparison with patients who undergo coronary artery bypass graft (CABG) surgery. Peak heart rates are similar but recovery heart rates decline faster in patients after CABG. Maximal oxygen consumption and oxygen puls e values in patients with a transplant are 87% of those in patients after CABG.
Exercise training has been shown to be useful and effective in improving exercise tolerance and aerobic capacity in patients with OHT. This improvement in exercise capacity is associated with pulmonary as well as cardiovascular changes. These types of bene fits are not seen in patients with OHT who undergo usual and customary care post-transplantation. Most peak values measured in patients with OHT after exercise training do not match the responses of subjects who are healthy. Peak heart rate and systolic b lood pressure improve to 87 and 86% of normal, respectively. Values for ventilation at peak exercise after exercise training in patients with OHT approach 100% of those achieved in age-matched controls. Patients with OHT consistently exhibit a 20-30% incr e a se in the oxygen uptake level at which their ventilatory threshold occurs as a result of exercise training. Heart rate range remains significantly lower in patients with heart transplant post-exercise training, achieving values which are 54% of those i n the normal population. Peak MET levels improve somewhat from 5.6 to 6.4 METs, or from 60 to 69% of levels achieved in age matched controls. The most significant improvement occurs in physical work capacity. As a result of exercise training, patients with O HT are capable of performing a peak workload which is 74% of that performed by normal subjects. Three factors contribute to lower peak values on initial graded exercise testing in patients with OHT: 1) decreased muscle mass as a result of prolonged preo per ative physical inactivity, 2) lower peak heart rates, and 3) lower peak blood pressures.
A significant increase in oxygen uptake in response to exercise training is consistent across all studies and is always paralleled by a significant increase in peak heart rate. Three mechanisms have been proposed to account for this increase in peak heart rate with exercise training: 1 ) exercise training in patients with OHT results in elevated norepinephrine and epinephrine concentrations at peak exercise which products higher heart rates which may, in part; 2) exercise training in patients with OHT resul ts in significant increases in lean tissue, specifically leg skeletal muscle hypertrophy, which contributes to increased muscular endurance and peak exercise heart rates; and 3) the phenomenon of early acceleration of the heart rate after orthostasis and r apid deceleration after exercise in recipients of a transplant implies a local cardiac mechanism rather than a response to circulating catecholamines contributing to higher peak heart rates after orthotopic heart transplantation.
Changes in cardiac and systemic physiology and hemodynamics over time in patients with OHT are an important consideration in utilizing exercise as a therapeutic intervention. There is evidence for a time-dependent normalization of rest and exercise central hemodynamics in patients with OHT, including a more typical heart rate response to exercise and recovery heart rate after exercise. Patients with OHT exhibit 510% increases in peak exercise heart rates and systolic blood pressures from early to late post- transplantation. The changes indicate that the improvement in exercise capacity post-transplantation is associated with pulmonary as well as cardiovascular changes. Peripheral abnormalities associated with congestive heart failure, such as the pattern of b lood lactate accumulation, persist in patients with OHT as late as 12-15 months post-transplantation despite adequate oxygen transport. From early to late post-transplantation, patients with OHT increase their average maximum MET level from approximately 5.0 to 6.0 METs. These improved physiological capacities allow the patient with OHT to improve their physical work capacity on the average of 37% from early to late post-transplantation. The general trend for cardiac and systemic changes over time is for m o re significant changes to occur from early transplant (less than 6 months post-transplant) to mid-transplant (6-12 months post-transplant), vs from mid-transplant to late transplant (greater than 12 months post-transplant).
Cardiopulmonary exercise testing serves an important role in the prognosis and optimal timing of cardiac transplantation in patients with severe heart failure who are ambulatory. This is a particularly important consideration because of the limited availab ility of donor hearts. Patients with greater functional impairment have more cardiac events and life-threatening arrhythmias and should be considered for earlier transplantation. The ability of a patient to increase their exercise tolerance while on aggre ssive medical therapy indicates a restored compensation and better prognosis. These patients should be offered the option of being taken off the cardiac transplant list in order to maximize their own survival (before and after transplant) and that of more c ompromised patients. Cardiac transplantation improves ejection fraction, but comparable improvement in exercise capacity is not always achieved.
Evaluation of graft function by exercise testing after orthotopic cardiac transplantation is essential in assessing the progress of a patient with OHT and in providing the patient with appropriate activity guidelines. Because of the significant cardiovascu lar adaptations that occur during the first year post-transplantation, serial testing at 3,6, and 12 months post-discharge is recommended. Exercise electrocardiograms are not useful in patients with OHT for the detection of ischemia. Utilization of treadm ill test prediction equations to estimate the functional capacity of a patient with OHT in METs and to establish exercise training, recreational or vocational activities will over predict the "true" functional capacity of a patient with OHT as much as 46% . To avoid the risk of infection, all equipment associated with cardiopulmonary exercise testing and training should be sterilized. Reduced exercise tolerance in patients with OHT may be due to the use of graded exercise testing protocols that do not allow time for an appropriate increase in HR and oxygen consumption at each workload. The graded exercise test protocol should include an effective warm-up stage to permit circulating catecholamines to be effective. Treadmill tests performed on patients with OH T shou ld use exercise protocols of 3-5 min stages with one MET increments per stage to allow time for the denervated heart to respond to the increased workload. Electrocardiographic and blood pressure response to exercise should be monitored in conjunctio n with utilization of a rating of perceived exertion (RPE) scale.
Attention should be paid to the following physiological parameters when performing graded exercise tests or prescribing exercise for patients with OHT: 1) resting sinus tachycardia, 2) elevated blood pressure, 3) early onset of anaerobiosis due to a limite d aerobic capacity, 4) delayed heart rate and stroke volume response, 5) diminished maximal capacity due to a reduced cardiac output, 6) absence of anginal symptoms due to denervation, 7) most recent cardiac biopsy scores because rejection can negatively effect performance, 8) two separate P waves may be seen on the electrocardiogram (ECG), 9) reduced peak heart rate, and 10) delayed recovery of heart rate.
Exercise training may be prescribed for the patient who is pre transplant as part of a comprehensive management plan including diet, drug therapy, and frequent follow-up. Selected patients may benefit from exercise training, but a thorough evaluation of ca rdiopulmonary function and current medications must be performed before considering exercise training as an adjunct to routine therapy in this patient population.
When patients with OHT are stable after surgery, they are at low to intermediate risk for complications as a result of exercise training.
Exercise training is a useful and important therapeutic intervention for improving exercise tolerance and maximizing psychosocial outcomes in patients who have undergone heart transplantation (21). Outpatient exercise training programs in patients with OHT begun as early as 8-12 wk post-transplantation, or as late as 7 months post-transplantation, show significant improvements in overall functional capacity. Duration's of exercise training in patients with OHT ranging from as short as 10 wk to as long as 16 months are effective in producing improved exercise tolerance. Frequencies ranging from three to five times per week are an effective conditioning stimulus in this patient population. Duration of each individual training session can range from 30 to 48 mi n and can include both continuous and interval types of training bouts. Modalities for exercise training patients with OHT include walking, walk-jogging, cycling, cycle ergometry, rowing ergometry, arm ergometry, stair-stepping, treadmill walking, and cal isthenics.
Blood pressure should be carefully monitored at rest and during the exercise session since hypertension is a common side effect of cyclosporine. Abnormal exercise blood pressure responses may help identify right-sided heart failure that may be an indicatio n of rejection. Longer periods of warm-up and cool-down are indicated because the physiological responses to exercise and recovery take longer. As is true with all patients with cardiac problems, there should be a gradual increase in time, intensity and f requency of exercise based on the patient's response to individual bouts of exercise.
Because patients with OHT risk infection, staff, other patients, and family members who have active infections should not come into contact with a patient with OHT. Exercise personnel should be aware of the side effects of the immunosuppressive drug regime n that patients with OHT must follow.
Finally, knowledge of the most recent cardiac biopsy score is important since rejection will result in decreased exercise tolerance and possibly complex ventricular arrhythmias on their exercise ECG. Periodic ECG monitoring during exercise therapy is recom mended. Exercise training should be discontinued during periods of severe graft rejection, maintained at current levels without further progression during times of moderate rejection, and slowly progressed during periods of mild rejection.
The significant improvement in the long-term survival of patients with OHT has caused a flurry of activity in the cardiac transplant arena in the last 10 yr. Despite improved survival rates, many patients with a cardiac transplant have been excluded from c ardiac rehabilitation programs because of the manifestation of other chronic diseases as a result of maintaining their immunosuppressive state and potential limitations to exercise. The unique cardiac physiology and hemodynamics and immunosuppressive stat us of a patient with OHT are important parameters to monitor in their rehabilitation. Cardiac denervation results in a loss of autonomic control of cardiac output in response to exercise. Humoral regulation of cardiac output becomes the primary physiologi c a l mechanism for responding, to increasing physical demands. As a result, the response to exercise in patients with OHT tends to be delayed and blunted. Peak values for cardiorespiratory and cardiovascular responses to exercise in patients with OHT rang e from 50 to 80% of peak values obtained in normal age matched control subjects.
In some patients, reduced ventricular compliance may be responsible for a reduction in their physical work capacity. Peripheral physiology remains impaired in patients with OHT for a prolonged period of time after heart transplantation. Increasing physical activity improves impaired peripheral physiology in patients with OHT. Exercise training is a significant therapeutic intervention in their successful clinical course.
Exercise training is effective in improving exercise tolerance in patients with OHT. The most significant improvement occurs in physical work capacity. A significant increase in peak heart rate is always associated with this increase in physical work capac ity. The specific mechanisms for this increased heart rate with training have not been elucidated. There is a time-dependent normalization of rest and exercise hemodynamics in patients with OHT. Significant changes occur in systemic and cardiac physiology from early post-transplantation to mid-posttransplantation. The process of normalizing systemic and cardiac physiology and hemodynamics after cardiac transplantation is accelerated and maximized by the therapeutic intervention of exercise training.
Cardiopulmonary exercise testing is important in evaluating patients with CHF prior to cardiac transplantation and in evaluating graft function after transplantation.
Graded exercise testing protocols, including effective warm-up, cool-down, and smaller MET increments, should be used. In addition, close attention should be paid to physiological parameters and responses unique to the patient with OHT. Exercise training m ay be utilized in selected patients who are awaiting OHT to prevent further deconditioning. Duration, frequency, and modalities of exercise training, similar to those used in other populations of patients with cardiac problems, have been found to be effec tive in patients with OHT. A MET level at or slightly below the ventilatory threshold, or an RPE of 12-14, is used to establish an initial level of exercise intensity in patients with OHT. Exercise personnel should be aware of the side effects of the immu n osuppressive drug regimen of a patient with OHT and the patient's most recent cardiac biopsy score indicating any graf t rejection.
Medicine and Science in Sports and Exercise, July 1995 pp.975-84
Contributed by Lisa Haas. Exercise Technologist, Gloucester, VA Abridged by D. Marshall, Upbeat,
If someone gives you a copy of the new transplant based mystery, Harvest by Tess Gerritsen, you probably ought to use it as a doorstop. It's pretty bad stuff about people being murdered for their organs, and Russians, and bloody surgical operations in vivi d detail. As the reviewer says, "the climax is too drawn out and the final revelations will surprise only readers who move their lips." Pocket, $22 (352p) ISBN 0-671 55301-1
From England, regular UpBeat reader, Tx Len Ironmonger, reports that his transplant center, Harefield Hospital, began it's program in 1980 and is the largest in the world. As of 6/28/96 they had performed the following transplants: 1301 heart; 409 heart lu ng; 4 heart/lung/liver; 3 heart/kidney; 210 single lung; 57 double lung; 22 bilateral single lung for a total of 2006 transplants, including 285 children aged 16 years and under. There are well over 100 patients who are going strong after more than 10 yea rs and one of the originals done in 1980 is still doing well after 16 years. Len does add that the donor supply has been declining and that the signed donor card system doesn't seem to do the job in England either. They have recently started National Regi s t er, but it has been slow to grow. Apparently the Rotary Club has taken it on as a project and are trying to get 7 million names into the Register within the next year.
The astute reader may wonder why the sentence regarding giving heart transplant recipients a slow start during treadmill tests was underlined in the lead article. I did that in the hopes that someone in authority pushing the buttons lot our treadmill stres s tests might see it, and take it to heart as they say. I've said every year, we ought to be allowed a 5 minute warm-up before any testing begins just to get the catecholamines flowing. Instead it's jump on the treadmill, and off we go into the oblivion o f shortness of breath, not because we're really stressed out, but merely because once our heart gets behind the pace it can never catch up. The best solution, I've found, is to tell them you need a bathroom as close to the time for your stress test as you c an estimate. Then go out and walk briskly up and down the halls for 5 minutes. Trouble is all too often you come back all "chemed up" only to find the test start is delayed by the Doc being called to the phone and you're aced out.
The Heartman, Tx Cliff Steer of San Jose, lugged both his transplanted heart and kidney to Europe this summer. While there he managed to pick up CMV with pneumonia in Spain. He had to be flown home on an emergency basis. Says Cliff, "They said it was CMV, but I think it was Franko's revenge."
Tx Gloria Sanders of West Linn, OR is having to consider a kidney transplant "after 7 plus years of cyclosporine." She would like to hear from others who have had the same disappointing experience. Her address is 1344 Troon Dr.., 97068. She also reports th at in the seven years she's had no mosquito bites, but that somehow yellow jackets don't seem to hold the same respect for "cyclorepel."
The "Organ Donors are heroes in the Making" word puzzle T-shirts are still available for $10 each from Steve Brosnihan, Fly By Knight Designs, P.O. Box 111, Bristol, R102809 - 401-253-5909. XXL is $11.50.
Palo Alto, heart/lung Tx Penny Toni, reports: "I made a lovely flea collar for my dog by threading cyclo. capsules on fishline. She ran around the house rubbing her neck on the ground, rear end in the air. Looked lovely Didn't work. Dog has fleas, floor do esn't."
Another organization we should have mentioned previously is Transplant Awareness, Inc. of Arlington, VA. This is a nonprofit group run by volunteers who have had transplants. Heart Tx Claude Brady of the DC TRIO support group is the President. This group o ffers a variety of T-shirts, pins, and even license plate frames, all promoting organ donation. All profits from these sales are used to promote transplantation awareness. Send for a free brochure to: Transplant Awareness, Inc., P.O. Box 7634, Arlington, VA 22207.
By Susan Milius - UPI Science Writer
WASHINGTON, July 18 (UPI 7/18/ 96) -- Transplanting parts of pigs, baboons or other animals into people is worth trying despite the risks of spreading some animal plague to humans, a new report said.
However, the chance of loosing a new disease among people, as well as questions of ethics, means these transplants need careful monitoring, said the first report on the topic from the Institute of Medicine, part of the independent National Academy of Scien ces.
"With safeguards and special regulation, the benefits outweigh the risks," said Dr.. Norman Levinsky, chairman of the department of medicine at Boston University Medical Center and chair of the report committee.
Western doctors have not yet gotten animal-to-human transplants to work, although Levinsky said a clinical trial of pig-to-person therapy for diabetes is underway in Europe.
After early failures, researchers in the United States and many European countries have concentrated on test-tube or animal research, trying only a rare experiment with human recipients. An attempt to put baboon bone marrow into San Francisco AIDS patient Jeff Getty last year -- the baboon cells do not seem to have survived -- was a rare clinical experiment.
In spite of Western caution, the report said, "several countries, including Russian, China, and some Eastern European nations, have forged ahead." Based on "anecdotal reports, hundreds of (mixed-species) transplants have been performed in these countries f or the treatment of diabetes, using pancreatic tissue from pigs, cows and rabbits," said the new report. Just how successful they have been is not yet clear.
Two big needs have been driving the research for animal-to-human transplants, Levinsky told United Press International. There are nowhere near enough whole organs to go around, and about half the people on waiting lists will die without finding a transplan t. In 1993, the United Network for Organ Sharing reported, 33,000 people were searching for organs but only 7,600 people donated.
"After passage of (the National Organ Transplant Act), the solution to the organ shortage was first thought to reside with increased public education," said the new report. However, those hopes have died as increased efforts failed to bring in more organs. Only about 40 percent of the people who might supply organs do so.
The other potential benefit of animal-to-people transplants involves not whole organs, but cells or bits of tissue. The number of people these procedures might benefit dwarfs the list of whole-organ recipients. "Not to be too grandiose, there are hundreds of thousands, or millions of people" who might someday use cell or tissue transplants, Levinsky said.
Animal experiments hint that doctors might someday free people with diabetes from a lifetime of insulin injection. Instead of prescribing shots, surgeons could implant islet cells from a pig's pancreas for a permanent internal source of insulin.
Levinsky also said early experiments looked promising for transplanting animal nerve tissue into people suffering the neural deterioration of Parkinson's disease. In theory, the animal tissue would give off dopamine, the vital brain chemical that dwindles away in Parkinson's patients.
This bright future, if it arrives, brings with it the risk of some virus, bacteria or other organism hitchhiking on the animal transplant, establishing itself in the patient's body and then spreading to family members, caregivers and possibly the general p ublic.
Diseases clearly do jump the species barrier, said the report. The AIDS virus, originally from monkeys, may be the most famous example, and researchers suspect that the Ebola virus normally resides in a non-human species.
The report also pointed out the Marburg virus, a cousin to Ebola, entered Germany in 1967 in a shipment of vervet monkeys and made 31 people sick, killing 23 percent of them. In 1976, a shepherd in Pakistan caught Crimean Congo hemorrhagic fever, a disease of domestic animals. Doctors misdiagnosed the problem as a peptic ulcer and performed a medical procedure that ended up spreading the disease to 17 people, killing 24 percent.
The risk is real, but scientists have no way to estimate how great the risk is, the report concluded. "We believe it's a rare occurrence, but there's no way to tell," said virologist Stephen S. Morse from Rockefeller University in New York, another member of the report committee.
He suggested that a similar situation might be the long use of insulin from pigs or cattle before the development of artificial insulin. No new diseases have been traced to that practice.
The report recommends a variety of screening and monitoring procedures to reduce risks or at least to catch problems early. For example, the report committee suggested that anyone receiving an animal transplant agree to lifelong monitoring for diseases.
However, "there's no completely safe position short of saying, 'don't do it,'" Morse said.
Whether the potential benefits justify the risks boil to an individual value judgment, he concluded. "This is an issue on which people who are well-informed -with good intentions --can disagree."
ORLANDO, Fla., (UPI 8/29/96) Grapefruit juice and prescription drugs don't mix, researchers warned Thursday. A substance in grapefruit juice, but not in orange juice, can make the body absorb too much or too little of common drugs, said researchers at the national meeting of the American Chemical Society in Orlando, Fla. However, the effect has potential benefits-if researchers can harness them.
The amount of calcium channel blockers, drugs used to treat heart patients, can triple in the blood stream leading to a greater than expected dip in blood pressure if someone washes down the pills with grapefruit juice, said Barbara Ameer, a pharmacology c onsultant in Princeton, N.J.
Other drugs that can react with grapefruit juice include estrogen- type hormones, used to ease menopause, and the popular antihistamine called terfenadine, or Seldane, prescribed for allergy sufferers.
Ameer and colleagues reported that researchers were even able to see a difference in electrocardiograms between patients that did, and did not, drink grapefruit juice when taking Seldane. Heart rhythm abnormalities were no longer detectable when people sep arated their pills and grapefruit juice by more than two hours.
Seldane's makers, however, said they have been unable to pin down a grapefruit interaction although they have received anecdotal reports. "There is no causal link based on available data," said Charles Rouse, spokesman for Hoechst Marion Rousel in Kansas C ity, Missouri. "There may have been other risk factors. We're not sure it's clinically significant."
Gay Yee from the University of Florida's College of Pharmacy in Gainesville, has proposed a way to take advantage of the grapefruit effect. Organ transplant patients who take cyclosporine to keep their bodies from rejecting the transplanted tissue often ta ke other drugs to enhance absorption. Part of the motive for reducing the dosage needed for cyclosporine is cost, since insurance companies often do not cover the drug, leaving patients to pay between $5,000 and $10,000 a year for the rest of their lives.
The anti fungal drug ketoconazole can reduce the need for cyclosporine by 80 percent, "but we'd much rather have them take something natural, like grapefruit juice, if we can achieve the same effect," Yee said.
In a study of 14 people, Yee and colleagues have been able to use grapefruit juice to enhance the concentrations of cyclosporine by an average of 40 percent. Yee said, "We're continuing the study to determine the optimal dose of grapefruit juice."
By Lidia Wasowicz - UPI Science Writer
PALO ALTO, Calif.,(UPI 7/29/96) In an extraordinary set of circumstances, a dying teenager received two hearts within 24 hours, doctors said Monday.
John Sterling Still-Luster, 17, of Anderson --just outside of Redding in Northern California -- was reported in critical but stable condition at the Lucile Salter Packard Children's Hospital at Stanford where he underwent a heart-lung transplant Saturday a fternoon after the first donor heart he received Friday evening began to fail.
The youth, who had been awaiting an available new heart for seven months, was rushed to the intensive care unit last week as his condition worsened, hospital spokeswoman Andrea Brant told United Press International.
"He was having heart failure and was being monitored at the Stanford hospital," Brant said.
"Friday afternoon, they got word they had a donor heart and he'd get it Friday evening. The operation was scheduled for 8 p.m. (PDT)."
But almost immediately following the transplant performed by a team of surgeons headed by Dr.. Darrel Wilson, problems developed with the new heart.
"He had a graft that was failing for unknown reasons," Brant said.
Considering the tremendous shortages of available donor organs, it was nothing less than an incredible stroke of luck that just as the new heart began to fail a heart-lung combination became available for transplant.
"These were very unusual circumstances as far as the timing goes," Wilson said. "The patient's lungs had suffered some damage over the long haul from the diseased heart so the surgeons decided to use both organs," Brant said.
The second surgery was performed Saturday afternoon by the same team, again headed by Dr.. Wilson.
"The patient is on medication to support his new heart and blood pressure and is on a ventilator, which is standard procedure for this kind of transplant," Brant said.
"It is too early for a prognosis, but John is improving."
His parents and brother were by his side as he was recovering.
By Matt Truell - Associated Press Writer
TOPEKA, Kan. (AP 8/31/96) -- A hospital has agreed to pay a $265,000 settlement to former patients in its heart transplant program, which shut down amid reports that it accepted patients when it was performing no transplants and rejecting almost every hear t offered.
The University of Kansas Medical Center will pay $11,000 each to 15 patients or their families who were kept waiting on the transplant list from May 1994 to March 1995. Only one heart was accepted for transplant during that time.
"I am stunned that these violations occurred in a program involving patients with severe, life-threatening medical conditions," Attorney General Carla Stovall said Thursday in announcing the settlement.
Overall, 36 patients were billed $500,000 and not told of problems in the program, a state audit found. The program was shut down in April 1995.
Five of the patients have died, but the deaths were not blamed on the program.
Medical center officials denied deceiving any patients, and said they agreed to the settlement only to resolve the issue. The problems were first reported by The Kansas City Star in May 1995.
The state audit, covering February 1994 to April 1995, found that of 66 donor hearts offered, 41 were rejected for medical reasons and 23 for nonmedical reasons -including a lack of staff to perform the transplants and care for patients after surgery.
Two hearts were accepted for transplants, one in February 1994 and one more than a year later, in March 1995.
The hospital lied by telling patients they had been added to the program's waiting list when they had not, the investigation found. Some also were given false information about the reason donor hearts were rejected.
Charles Rentfro of Kansas City, who was on the transplant list, said he was satisfied with the settlement. He is awaiting a transplant at St. Luke's Hospital in Kansas City, Mo.
NEW YORK, (Reuter 9/6/96) - A murder defendant who got a controversial taxpayer-financed $400,000 heart transplant then fled to the Dominican Republic to avoid prosecution was sentenced to 25 years in prison, the government said on Sunday.
The case against Bartolome Moya, the purported leader of a brutal New York City drug ring, drew national attention because it raised ethical questions about whether criminals facing life imprisonment should receive hard-to-obtain organs and whether taxpaye rs' should pay for such expensive transplants.
Federal prosecutors said that Moya was sentenced Wednesday after previously pleading guilty to participating in the violent drug ring, including his involvement in murders.
The bizarre case began in 1993 when Moya and others in his group were indicted by federal grand jury in Manhattan on charges of committing at least a dozen murders and numerous kidnappings, bombing and other violent crimes between July 1988 and July 1991.
U.S. District Judge Thomas Griesa dismissed the case against Moya because he suffered from chronic heart disease and was likely to die. The case was dismissed without prejudice, meaning that prosecutors could refile charges.
Moya was allowed to spend his last days with his family in Philadelphia, where he enrolled in a heart transplant program at Temple University, concealing information about the criminal charges he faced. The chief cardiologist at Temple later said that Moya met medical criteria as a candidate for the operation and that his background would not have been considered in any case.
The 1994 transplant was financed by Pennsylvania Medicaid funds. When federal prosecutors learned about the successful operation they obtained a new indictment against Moya. He was rearrested and returned to prison. When the judge learned that Moya would d ie without necessary daily medication and needed regular care by his Philadelphia doctors, he released him to home custody.
Although Moya complied for several months, in July 1994 he fled to the Dominican Republic. He was arrested there in October 1994 and returned to New York to face pending charges.
In sentencing Moya, Griesa denied the defendant's application for a reduced sentence based on medical complications related to his heart transplant.
By Kerri Selland
PITTSBURGH, (Reuter 8/22/96) - Six years after receiving a heart transplant, Robert Smith woke one morning last year with bumps the size of small eggs on his right leg.
"I knew they weren't normal," the 64 year-old resident of Nesquehoning, Pennsylvania, said. After his doctor ran tests, Smith was sent to Pittsburgh, where he received an experimental treatment for tumors in transplant patients.
Eight days later, the malignant tumors disappeared. A year later, they have not returned. "There were no side effects," Smith said on Thursday via telephone from his home. "I felt line."
Organ transplant patients who develop malignant tumors -- a condition called post-transplant lymphoproliferative disease (PTLD) -- may benefit from a treatment being researched at the University of Pittsburgh Medical Center, according to Dr.. Michael Nales nik, one of the researchers.
The new treatment showed promise in a study that began last year and involved seven patients including Smith, Nalesnik said.
"We have a lot of work to do, research is ongoing," Nalesnik said. "But it appears promising. We'd like to expand it and use it on more patients."
In the study, cells were removed from the immune systems of patients who developed malignant tumors after an organ transplant. Tumors can develop after an organ transplant because of a resulting weakness in the immune system.
The cells were then mixed with Interleukin-2, a natural hormone that stimulated the cells to become lymphokine-activated killer cells (LAK cells.) The LAK cells, which kill tumor cells while sparing normal ones and are used in other forms of cancer therapy , were infused back into the patients' bloodstreams.
Nalesnik said tumors disappeared in four of the patients and have not recurred. The medical center plans to use the treatment on at least 20 more patients.
According to the medical center, about 2 percent of transplant patients develop PTLD. Tumors can develop months or even years after a transplant.
Nalesnik said only a small percentage of tumors respond to traditional treatments. which include temporarily reducing them or eliminating drugs patients took to suppress their immune systems and prevent organ rejection.
Nalesnik plans to present the study's results next week in Spain at a meeting of the International Congress of the Transplantation Society.
Other researchers said the treatment was encouraging. '"I would love to see more people treated this way," said Dr.. Israel Penn, a transplant researcher at the University of Cincinnati Medical Center. "It could be a significant advancement in the manageme nt of these patients."
By Bob Mims - Associated Press Writer
SALT LAKE CITY (AP 8/28/96)-- A year ago, a liver transplant snatched Larry Hagman from death's door -- but not before the actor put one foot into what he has become convinced was the hereafter.
A 15-hour, $350,000 operation saved his life. But it was his "spiritual" experience that revitalized it, says the television star best known as the villainous Texas oil man J.R. Ewing on "Dallas."
"1 was able to look over the edge. I got a little glimpse into what was the next step," says Hagman, in town to preside over the medals ceremonies at the U.S. Transplant Games at the University of Utah.
The 64-year-old grandfather of five and self-described former heavy drinker was suffering from advanced cirrhosis and cancer of the liver when he underwent surgery at Los Angeles' Cedars-Sinai Medical Center on Aug. 23, 1995. Sometime during the operation, or in the hours of recovery -- he's not sure which -- Hagman believes he brushed up against death.
"I didn't see a light some people see, but I had a wonderful feeling of bliss and warmth," says the son of Broadway star Mary Martin.
Hagman says it turned out he got two gifts when he underwent the surgeon's scalpel: a healthy liver and the inspiration to make the most of his new lease on life.
The past year has been a busy one, as he has tried to make each moment count. His summer has included hunting and fishing expeditions and a five-day stint on his Harley motorcycle in the Colorado 500. He's traveled extensively, too, angling in Oregon, visi ting Europe twice and Texas a half-dozen times.
Since the transplant, Hagman had a cameo role in Oliver Stone's "Nixon," and most recently starred in the TV pilot "Orleans." He will portray the patriarch of a powerful Southern family in that mid-season replacement series.
But it is off the screen where Hagman tries to repay some of the enormous debt he feels he owes. He has become a zealot for the organ donor cause, both in public and private.
In addition to being national spokesman for the National Kidney Foundation's transplant games, he volunteers at St. Vincent's Hospital in Los Angeles, consoling frightened patients.
"I counsel, encourage, meet them when they come in for their operations, and after," he says. "I try to offer some solace, like 'Don' t be afraid, it will be a little uncomfortable for a brief time, but you'll be OK.'"
While recovery from his own transplant has gone smoothly with no rejection episodes, Hagman still has his health hurdles. He remains a diabetic and, despite four years of sobriety, the specter of alcoholism is never far away.
"I was never a violent drunk or had blackouts, things like that," he says. "But I stayed a little (inebriated) all day long .... Toward the end, it got down to pure vodka with a little juice."
A month ago, the old Hagman visited him in the night. The actor saw himself standing as an island in the swirl of a Hollywood party. Then came the horror.
"I looked down and I had an empty champagne glass in my hand," he says, anger slipping briefly into his voice. "1 thought, 'What the (expletive) are you doing?!'
"I woke up, and I WANTED to wake up, too."
Hagman was placed on Cedars-Sinai's transplant waiting list on July 19, 1995, after doctors discovered a tumor on his liver. He received his replacement organ about six weeks later.
He is convinced it was just luck, not celebrity, that surgeons found a match for him in time.
"You just go on the list as a number. I would hate to believe otherwise. It wouldn't be fair," he says. "There are 46,000 people waiting around for livers (and other organs). And there' s so many livers kickin' around, if people would just sign those donor cards and make sure your loved ones agree to that."
Hagman practices what he's been preaching. His California driver's license lists him as an organ donor. "They can have whatever they want," he says with a laugh, then adds: "Except for the liver. They don't do that twice."
By Casey Combs - Associated Press Writer
PITTSBURGH (AP 8/27/96) -- Transplanted livers from female donors are more likely to fail than male livers, according to the largest study ever on the risks of liver transplants. Surgeons remain baffled as to why.
"I personally could not believe it was true. I really thought (at first) it was some kind of statistical problem," said Dr.. lgnazio Marino, associate surgery professor at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute, the world 's leading liver transplant center.
"We think it probably has to do with some hormonal factor in the life of a female .... But this is just a guess," Marino said.
Marino and Dr.. Howard Doyle, a specialist in clinical statistics, studied 2,376 liver transplants performed in Pittsburgh from November 1987 to December 1993.
About 31 percent of the transplants failed, with the patient dying or getting another liver.
A liver transplanted from a female donor to a male patient failed in 45 percent of the cases, yet a liver from a male donor to a male patient failed 28 percent of the time.
Female patients also fared better with livers from male donors. Livers from female donors failed in 36 percent of the cases, but male livers failed in only 22 percent of female patients.
The younger the female donor, the more likely her liver will work in another person, the research showed.
Dr.. Michael Abecassis, director of liver transplants at Northwestern Memorial Hospital in Chicago, speculated that livers from older women have slightly more fatty tissue in them, and fattier livers fail more often.
"The bottom line is: Nobody knows," Abecassis said.
Smaller studies had indicated, and most surgeons suspect from experience, that livers from women fail more often, but this is the first research based on more than a couple of hundred transplants to support those suspicions, Abecassis said.
The data allows researchers to determine which transplants are most likely to succeed by considering age, sex, patient health and other factors, doctors said.
In 1994, the most recant year statistics are available, nearly 4,000 people were waiting for livers, 46 percent of them women, the network said.