Alterations of myocardial amino acid metabolism in chronic ischemic heart disease.

Arteriovenous differences (A-V) of all naturally occurring amino acids, lactate, and oxygen were measured simultaneously with coronary sinus blood flow (CSBF) in 8 normal subjects and 11 patients with coronary artery disease at rest and during pacing stress. Mean values for CSBF and myocardial oxygen consumptions (MVO2) for the two groups were similar at rest and during pacing, although mean CSBF and MVO2 increased significantly in both groups in the paced as compared to the rest state. Alanine (ala) was the only amino acid released by the myocardium, while only glutamic acid(glu) demonstrated uptake. Mean A-V ala was negative at rest in the control and coronary disease groups (-4.8+/-3.8 vs. -22.0+/-3.0 nmol/ml, respectively), but was significantly more negative in the coronary group (P less than 0.001) and not statistically different than zero in the normals. A-V ala became significantly negative with pacing in the normals (-10.0+/-4.3 nmol/ml), remained unchanged in the coronary group (-23.0+/-2.9 nmol/ml), and was significantly more negative in the coronary group (P less than 0.05). Calculation of data on the basis of net ala flux ([A-V] X [CSBF X hematocrit]) yielded similar results as that obtained with A-V differences. A-V glu was significantly positive in normals (27.7 +/- 8.9 nmol/ml, P less than 0.01) and coronary patients (59.9 +/- 8.9 nmol/ml, P less than 0.01) at rest but significantly greater in the latter group (P less than 0.001). With pacing, A-V glu remained significantly greater than zero in coronary patients (35.3 +/- 6.3 nmol/ml) and decreased to zero in the normals (4.3 +/- 11.8 nmol/ml). Calculation of net glu flux (nmol/min) at rest yielded data similar to that based on A-V difference. With pacing, net glu flux in the coronary patients did not decrease due to the augmentation of CSBF. No relation between A-V glu or ala and CSBF, MVO2 or A-V lactate was noted. The data demonstrate that specific alterations of myocardial amino acid metabolism characterize patients with chronic ischemic heart disease.

Responses of coronary arteries of cardiac transplant patients to acetylcholine.

Accelerated coronary atherosclerosis is a major cause of graft failure after heart transplantation. Graft atherosclerosis is typically diffuse and difficult to detect even with coronary arteriography. Recently, acetylcholine was shown to dilate blood vessels by releasing a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). We have demonstrated paradoxical vasoconstriction induced by acetylcholine both early and late in the course of coronary atherosclerosis in patients, suggesting an association of endothelial dysfunction and atherosclerosis. In this report, we tested the hypothesis that coronary arteries of heart transplant patients can show endothelial dysfunction before or in the early stages of angiographically evident coronary atherosclerosis. Acetylcholine was infused into the left anterior descending artery of 13 heart transplant patients at 12 (n = 9) and 24 (n = 4) mo after transplantation. Vascular responses were evaluated by quantitative angiography. Among patients with angiographically smooth coronary arteries, relatively few (6/25) arterial segments had preserved vasodilator responses, while the majority failed to dilate (10/25) or paradoxically constricted (9/25). Angiographically irregular coronary arteries were present in three patients, in whom 8/10 segments showed marked paradoxical constriction and the remaining 2/10 failed to dilate. Only 1 of 13 patients retained appropriate dilation to acetylcholine in all segments. Nitroglycerin, which acts directly on vascular smooth muscle, dilated nearly all segments. No clinical features of the patients, including myocardial rejection appeared to correlate with the impaired functional response of vessels. Thus impaired response to acetylcholine is a common early finding in heart transplant patients and emphasizes the potential importance of endothelial dysfunction in the development of atherosclerosis.

Atherosclerosis influences the vasomotor response of epicardial coronary arteries to exercise.

We studied the vasomotion of epicardial coronary arteries during exercise and tested the hypotheses that abnormal vasoconstriction is related to the presence of atherosclerosis and may be related to endothelial dilator dysfunction. During cardiac catheterization quantitative coronary angiography was performed in 21 patients during supine bicycle exercise. 21 of 28 smooth, angiographically normal vessel segments dilated (14.0 +/- 1.8%) during exercise; four smooth segments did not change whereas only three constricted. In contrast, 15 of 16 vessel segments with irregularities constricted in response to exercise (17.0 +/- 0.1%) with only one segment dilating. All 10 stenotic segments constricted to exercise (23 +/- 4%). Six patients also received intracoronary acetylcholine before exercise to test endothelium-dependent dilator function. In five of six patients all nine vessel segments showed the same directional response to acetylcholine and exercise. Three irregular and two stenotic segments constricted with acetylcholine (51 +/- 21%) and exercise (9.0 +/- 0.6%). In contrast, four smooth segments dilated to acetylcholine (19 +/- 6%) and exercise (9 +/- 1%). Both exercise and acetylcholine generally dilated smooth but constricted irregular and stenosed coronary segments. It appears likely that atherosclerosis plays an important role in the abnormal vasomotion of diseased coronary arteries during exercise and the pattern of abnormality suggests impairment of vasodilator function.

Pericardial effusions after cardiac transplantation.

OBJECTIVES: The aim of this study was to determine the etiologic factors in the formation of significant pericardial effusion after orthotopic heart transplantation and to determine the association of pericardial effusion with survival. BACKGROUND: The formation of pericardial effusions has been well described after orthotopic heart transplantation, but the risk factors for development of effusions remain unclear. Rejection and cyclosporine have been cited as possible causes, but anatomic factors have not been studied. METHODS: We conducted a retrospective review of medical records and echocardiograms of 203 consecutive patients at one center, including ischemic time, incidence and severity of rejection, weight difference between donor and recipient and previous cardiac surgical history. Multivariate analysis was performed, and actuarial survival rate curves were calculated according to the Kaplan-Meier method. RESULTS: Eighteen (8.9%) of 203 transplant recipients developed moderate to large pericardial effusions. Forty-four percent of patients required pericardiocentesis, and 28% subsequently required pericardiectomy for management of the effusions. Multivariate analysis identified the presence of a positive weight difference between recipient and donor (recipient weight > donor weight) and the lack of previous median sternotomy as the most powerful predictors of effusion formation. No significant association was found with rejection. There was no difference in actuarial survival rate between patients with and without effusions. CONCLUSIONS: A positive mismatch in weight between recipient and donor and the absence of previous cardiac surgery are associated with the formation of significant pericardial effusions. Closer monitoring of these patients at risk may be warranted.

Cardiomyopathy of limb-girdle muscular dystrophy.

OBJECTIVES: This study sought to find an association between dilated cardiomyopathy and limb-girdle muscular dystrophy. BACKGROUND: Cardiomyopathy has been seen in various neuromuscular disorders, but it has not been recognized to be associated with limb-girdle muscular dystrophy. METHODS: We investigated three sisters with well documented limb-girdle dystrophy and congestive heart failure by the 3rd decade of life. All underwent noninvasive evaluation of left ventricular systolic function by both echocardiography and radionuclide scanning, and one also had cardiac catheterization. Deoxyribonucleic acid (DNA) linkage analysis was performed in these affected subjects and in the unaffected family members, and DNA was extracted from mononuclear cells with primer sequences for three chromosome 13q microsatellite markers. RESULTS: The parents had no evidence of clinical disease, but all three sisters had echocardiographic evidence of dilated cardiomyopathy. The sister with additional evidence of left ventricular dysfunction of cardiac catheterization had no coronary artery disease. The affected subjects had the same paternal allele for three potential markers of limb-girdle muscular dystrophy but different maternal alleles. The very small family size did not permit statistical confirmation or refutation of linkage for chromosome 13q markers. CONCLUSIONS: Demonstrable cardiomyopathy accompanying limb-girdle muscular dystrophy and its probable genetic associations require continued investigation by anticipating the cardiomyopathy in limb-girdle muscular dystrophy.

Clinical response to coronary artery reoperations.

Repeat coronary artery bypass operations were performed on 112 patients at a university hospital between 1971 and 1981. When compared with patients who did poorly after a first operation but did not have repeat surgery, patients undergoing repeat surgery tended to be younger, to have a higher smoking rate and to have fewer prior myocardial infarctions, fewer diseased vessels and fewer lesions in distal vessels. At least 1 graft was occluded in 83% of patients undergoing reoperation, and a mean of 1.7 grafts were placed at reoperation. The operative mortality rate was 4%, with a follow-up mortality rate of 6% at a mean of 3.8 years. After reoperation, patients initially showed improvement to a mean specific activity scale class of 1.6, compared with 2.4 before the first operation and 2.7 before the second operation. The principal correlate of a better long-term symptomatic response compared with that in the period before the first operation was a lower serum cholesterol level, whereas the principal correlate of a better symptomatic response compared with that in the period just before the reoperation was the left ventricular ejection fraction. As recurrent symptoms after a first coronary artery operation become more prevalent, consideration of the selection factors and prognostic correlates of reoperation will become increasingly important.

Serial assessment of left ventricular function and mass after orthotopic heart transplantation: a 4-year longitudinal study.

Long-term changes in left ventricular performance and geometry in the transplanted human heart have been incompletely described. Therefore, two-dimensional echocardiograms were performed on 22 recipients of an orthotopic heart transplant at 1 month (32 +/- 20 days), 1 year (11 +/- 3 months) and 4 years (54 +/- 9 months) after transplantation. All studies were performed at a time when the patient had no pathologic evidence of rejection. Ten healthy men served as a normal control group. Over 4 years of follow-up, mean systolic blood pressure in the study patients increased from 121 +/- 12 (p = NS vs. values in the control group) to 139 +/- 11 mm Hg (p less than 0.05 vs. both control values and values at 1 month); mean diastolic blood pressure increased from 72 +/- 7 (p = NS vs. normal values in the control group) to 93 +/- 8 mm Hg (p less than 0.05 vs. both control values and values at 1 month). Left ventricular end-systolic volume increased from 42 +/- 10 (p = NS vs. control values) to 51 +/- 14 ml (p less than 0.05 vs. both control values and values at 1 month) and end-diastolic volume increased from 103 +/- 28 (p = NS vs. control values) to 112 +/- 27 ml (p less than 0.05 vs. control values) over 4 years. Left ventricular mass and ejection fraction did not change significantly within the patient cohort and remained similar to that found in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Attenuation of coronary vascular resistance by selective alpha 1-adrenergic blockade in patients with coronary artery disease.

Alpha-adrenergic-mediated coronary vasoconstriction during stress such as cold pressor testing may contribute to myocardial ischemia by increasing coronary vascular resistance in patients with severe coronary artery disease. Nonselective alpha-receptor blockade with phentolamine abolishes both the peripheral and coronary vasoconstriction during cold pressor testing, but causes reflex tachycardia and increased inotropy. To determine the role of selective alpha 1-receptor blockade, the changes in coronary vascular resistance during cold pressor testing were measured in 18 patients with coronary artery disease before and after intravenous administration of 100 mg of trimazosin. Cold pressor testing was performed at a constant paced subanginal heart rate of 95 +/- 5 beats/min (+/- 1 SD). Before trimazosin, cold pressor testing increased mean arterial pressure by 9 +/- 4% (102 +/- 14 to 111 +/- 14 mm Hg, p less than 0.001) with no change in coronary sinus blood flow, but significantly increased coronary vascular resistance by 15 +/- 19% (1.02 +/- 0.46 to 1.15 +/- 0.57 units, p less than 0.05). Five minutes after trimazosin, cold pressor testing increased mean arterial pressure by 6 +/- 5% (p less than 0.001) with a marked attenuation of the increase in coronary vascular resistance (6 +/- 11%, p = NS), which was significantly less than before trimazosin (p less than 0.02). Trimazosin did not increase plasma norepinephrine concentration at rest, suggesting that in the dosage used trimazosin caused selective alpha 1-receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention by nifedipine of cold pressor-induced decrease in left ventricular ejection fraction.

To examine the effects of nifedipine on changes in ventricular function produced by cold, the cold pressor test was administered to eight patients with angiographically documented coronary artery disease. Radionuclide ventriculograms were obtained at baseline and during the cold pressor stimulus both before and after administration of nifedipine, 10 mg buccally; thus, four serial radionuclide ventriculograms were obtained per patient. The cold pressor stimulus did not produce any significant difference in the mean (+/- standard deviation) peak rate-pressure product during the control or nifedipine test (10,900 +/- 3,390 versus 10,600 +/- 3,700). However, the increase in systolic blood pressure (p = 0.05) and the peak systolic blood pressure achieved (p less than 0.001) were greater during the control (134 +/- 19 to 160 +/- 25 mm Hg) than during the nifedipine (125 +/- 18 to 145 +/- 21 mm Hg) cold pressor test. The mean global left ventricular ejection fraction decreased during the control cold pressor test from a baseline value of 0.60 +/- 0.08 to 0.52 +/- 0.08 (p = 0.004). After nifedipine, this variable did not change during the repeat cold pressor test (0.63 +/- 0.09) compared with the repeat baseline value (0.63 +/- 0.11). Therefore, the difference in left ventricular ejection fraction response during control versus nifedipine cold pressor testing was highly significant (p less than 0.0001). In patients with obstructive coronary artery disease, nifedipine abolished the decrease in left ventricular ejection fraction observed during the control cold pressor test and may be of value to protect patients from cold-induced left ventricular dysfunction. The mechanism may be a combination of coronary artery vasodilation and systolic unloading of the left ventricle.

Acetaminophen metabolism in subjects fed charcoal-broiled beef.

The effects of consumption of charcoal-broiled beef on the metabolism of acetaminophen by conjugation were determined in nine normal subjects. We had reported that beef prepared in this manner accelerates the oxidative metabolism of drugs, including the oxidation of phenacetin to N-acetyl-p-aminophenol (acetaminophen). In nine normal subjects, a control diet was followed by a charcoal-broiled beef diet, which was followed by the control diet. The charcoal-broiled beef had little or no effect on the plasma-level profile of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate, or on the urinary excretion of acetaminophen, acetaminophen glucuronide, acetaminophen sulfate, 3-methoxy-acetaminophen, or the cysteine and mercapturic acid conjugates of acetaminophen. Results indicate that the enzyme systems that conjugate acetaminophen in man are subject to little or no influence by charcoal-broiled beef. Therefore dietary factors that increase drug oxidations cannot be assumed to have a similar effect on drug conjugation.

Clinical utility and management impact of M-mode echocardiography.

To determine the clinical utility and management impact of M-mode echocardiography, 182 echocardiograms were analyzed at a university teaching hospital. The physicians who ordered the echocardiograms said that 12 percent provided crucial information that was not available from other tests and that 26 percent resulted in a change in patient management. According to two independent board-certified cardiologist-reviewers, 86 percent of echocardiograms were appropriately ordered, but only 15 echocardiograms (8 percent) were actually needed for a change to a new and appropriate management. According to the reviewers, the 77 Group I M-mode echocardiograms (those ordered to evaluate left ventricular function, left atrial size, potential cardiac sources of emboli, or the possibility of bacterial endocarditis, or those ordered in patients who, according to the ordering physician, had undergone or would undergo catheterization regardless of the results of echocardiography) were less likely than the 105 Group II M-mode echocardiograms (those ordered to evaluate possible mitral valve prolapse, hypertrophic cardiomyopathy, valvular function, or the pericardium) to be ordered appropriately, to provide helpful information, or to provide crucial results. Group I echocardiograms had reviewer-assessed appropriate management impact in only one case (1 percent) compared with a 13 percent rate of management impact for Group II M-mode echocardiograms (p less than 0.01). Although echocardiography can be accurate and valuable with yields similar to those of other noninvasive procedures, 77 (42 percent) of 182 M-mode echocardiograms in this hospital could be predicted at the time of ordering to be in a low-yield group.

Synthesis of N-hydroxyacetaminophen, a postulated toxic metabolite of acetaminophen, and its phenolic sulfate conjugate.

The synthesis of N-hydroxyacetaminophen (N-acetyl-N-hydroxy-p-aminophenol, 4), a postulated toxic metabolite of acetaminophen (N-acetyl-p-aminophenol, 3), and its phenolic sulfate conjugate (potassium N-acetyl-N-hydroxy-p-aminophenyl sulfate) (13) is described. Potassium p-nitrophenyl sulfate was reduced to the hydroxylamine, acetylated, and treated with sulfatase to yield N-hydroxyacetaminophen. The structures assigned are supported by the spectral data (IR, UV, MS, 1H NMR, and 13C NMR). N-Hydroxyacetaminophen was found to be moderately unstable at physiological pH and temperature, whereas it phenolic sulfate conjugate was stable.

Mechanism of decomposition of N-hydroxyacetaminophen, a postulated toxic metabolite of acetaminophen.

The decomposition of N-hydroxyacetaminophen (N-acetyl-N-hydroxy-p-aminophenol, 2), a postulated toxic metabolite of acetaminophen (N-acetyl-p-aminophenol, 1) in aqueous solution is quantitatively accounted for by the appearance of equimolar amounts of p-nitrosophenol and acetaminophen. The rate of decomposition depends on initial concentration and varies with pH. Antioxidants decrease the rate of decomposition and change the products. In the presence of cysteine, N-acetyl-3-(S-cysteine)-p-aminophenol, an in vivo metabolite of acetaminophen, is a product of decomposition.

The changing "natural history" of symptomatic coronary artery disease: basis versus bias.

In contrast to the 20 to 30% reduction in ischemic heart disease mortality that has been demonstrated by national mortality statistics and by several randomized controlled trials, an uncritical reading of recent "natural history" studies suggests far greater improvements in the survival of symptomatic coronary patients. Although the intrinsic accuracy of such natural history studies is not questioned, attempts to compare patients from different studies and different eras may greatly overestimate the true improvement in natural history because of at least 3 biases in the selection of cases from the spectrum of diseased patients. Because of lead-time bias, patients who are diagnosed earlier live longer regardless of whether interventions are efficacious. Because of referral bias, current patients may have symptoms or anatomy that place them at a different stage of severity than patients who were chosen for earlier studies. Because of incidence-prevalence bias, prevalence studies will be over-represented with survivors of previous incidence cohorts who have slower-progressing disease. We suggest that all natural history studies be carefully scrutinized for such biases before they are compared with each other.

Therapy of coronary vasoconstriction in patients with coronary artery disease.

Patients with obstructive coronary artery disease and stable, exertional angina respond to the alpha adrenergic stimulus of the cold pressor test with an inappropriate increase in coronary vascular resistance. The clinical significance of this abnormal response and its possible role in the pathogenesis of ischemic heart disease are discussed. Comparison of the anti-anginal agents currently in use of undergoing investigation suggests that the calcium antagonists may be the most effective therapy for coronary vasoconstriction. Nifedipine, 10 mg buccally, successfully prevented the increase in coronary vascular resistance during the cold pressor test in 10 of 10 patients, whereas the response in placebo-treated patients was unaltered. This dose of nifedipine was without effect on systemic hemodynamics or myocardial oxygen consumption, suggesting a selective antivasoconstrictor effect on the coronary vasculature.

Inappropriate coronary vasoconstriction in patients with coronary artery disease: a role for nifedipine?

Coronary arterial vasoconstriction, well recognized in Prinzmetal's variant angina, may participate in the pathogenesis of classic angina as well. Several recent studies in patients with obstructive coronary artery disease suggest that apparently spontaneous reductions in coronary blood flow can result in myocardial ischemia and even infarction. Evidence supporting the alpha adrenergic nervous system as a cause of such coronary vasoconstriction is reviewed, particularly the results of provocative testing with the cold pressor stimulus. Upon exposure of the skin to cold, patients with coronary artery disease demonstrate an inappropriate coronary vasoconstrictor response, often sufficient to produce angina. Normal patients, by contrast, show no change in coronary vascular resistance. In patients with a diseases coronary circulation, inappropriate vasoconstriction further restricts myocardial perfusion and appears to be little affected by beta adrenergic blocking agents or nitrates in the usual dosages. Nifedipine has proved effective in preventing coronary arterial spasm in patients with Prinzmetal's angina. Studies currently in progress suggest that it is also effective in blocking inappropriate coronary vasoconstriction in patients with typical angina. Nifedipine may thus be a useful addition to the treatment of ischemic heart disease.

Effects of prostacyclin on coronary hemodynamics at rest and in response to cold pressor testing in patients with angina pectoris.

To assess the effect of prostacyclin on the diseased coronary circulation basally and, in particular, on the coronary responses to the cold pressor test, a small dose of 4 ng/kg/min and a large dose of 8 to 10 ng/kg/min was infused in 11 patients with stable angina pectoris. Coronary blood flow was measured by coronary sinus thermodilution technique. The mean blood pressure decreased from 97 +/- 5 to 89 +/- 5 mm Hg during the low-dose infusion (p less than 0.005) and to 81 +/- 5 mm Hg during the high-dose infusion (p less than 0.001); the heart rate increased from 65 +/- 4 to 69 +/- 4 beats/min during the low-dose infusion (p less than 0.05) and to 78 +/- 5 beats/min during the high-dose infusion (p less than 0.001). Systemic vascular resistance decreased by 11 +/- 4% with small doses (p less than 0.05) and by 38 +/- 4% with large doses (p less than 0.001) of prostacyclin, and coronary vascular resistance decreased by 16 +/- 7% (p less than 0.05) with the small dose and by 29 +/- 6% (p less than 0.001) with the large dose of prostacyclin. Seven of 11 patients showed a baseline vasoconstrictor response to the cold pressor test (increase in coronary vascular resistance of 11 +/- 2%). This increase in coronary vascular resistance was not altered by either the small or the large dose of prostacyclin. Thus, prostacyclin causes marked coronary and systemic vasodilation, with no evidence of selective enhancement of the sensitivity of the diseased coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency of hypercholesterolemia after cardiac transplantation.

Cardiac transplant patients are prone to accelerated coronary atherosclerosis. The mechanism by which this process occurs is not yet known, although immunologically mediated arterial injury is thought to play a primary role in its pathogenesis. Despite immunosuppressive potency, patients treated with cyclosporin A remain at significant risk for the development of accelerated atherosclerosis. It is hypothesized that cyclosporin A's hepatotoxic effects might contribute to the atherosclerotic process by impairing low density lipoprotein hepatic clearance in transplant patients, which would be reflected in a more atherogenic lipoprotein profile. To test this hypothesis, serum cholesterol levels were analyzed after transplantation. Significant and progressive increases in total cholesterol and in the total-to-high density lipoprotein cholesterol ratio were found. This atherogenic lipoprotein profile may contribute to accelerated atherosclerosis in cardiac transplant patients treated with cyclosporin A.

Long-term survival of more than 2,000 patients after coronary artery bypass grafting.

Among 2,004 patients who underwent their first coronary artery bypass graft operation between January 1970 and December 1980 without concomitant valve replacement or aneurysmectomy, life-table survival was 89% at 5 years and 80% at 8 years after surgery. In a multivariate Cox model analysis, the independent correlates of long-term survival were emergent operation with cardiogenic shock (multivariate mortality rate ratio [RR] = 14.0), use of a postoperative intraaortic balloon pump (RR = 3.9), ejection fraction less than 50% (RR = 2.4), preoperative history of congestive heart failure (RR = 2.2), cardiopulmonary bypass time (RR = 1.4 for each 30-minute increment), uncorrected mitral regurgitation (RR = 1.5 for each increment of angiographic gradation), left main coronary artery narrowing (RR = 1.7) and diabetes (RR = 1.6). After controlling for these factors, age, sex and the percentage of narrowings that were bypassed were not independent correlates of long-term survival.

Lovastatin therapy for hypercholesterolemia in cardiac transplant recipients.

Hypercholesterolemia (type II hyperlipidemia) after cardiac transplantation is common and may play a role in the accelerated rate of coronary atherosclerosis seen following the procedure. However, conventional cholesterol-lowering drugs are either ineffective or contraindicated for use in transplant recipients. The presence of type II hyperlipidemia was identified in 11 cardiac transplant recipients during a mean follow-up period of 15 months (range 3 to 41) after transplantation. Lovastatin, at an initial dosage of 20 mg/day, was administered for a period of 1 year. The maximal dosage of lovastatin was 60 mg/day. All patients received maintenance dosages of immunosuppressive agents, including cyclosporine-A, prednisone and, in some instances, azathioprine. Lipid profiles, hepatic transaminases, serum creatinine, creatine kinase and cyclosporine-A serum trough levels were measured quarterly. Total cholesterol decreased by 27% (354 +/- 50 vs 258 +/- 36 mg/dl, p less than 0.01) after 3 months and remained stable thereafter. Similarly, low density lipoprotein cholesterol decreased by 34% (221 +/- 51 vs 146 +/- 40 mg/dl, p less than 0.01) after 3 months and remained constant. Triglycerides, high density lipoprotein, hepatic transaminases, creatinine, creatine kinase and trough cyclosporine-A levels remained stable during the 1-year follow-up period. Lovastatin was uniformly well tolerated in this study group. When given in modest dosages, lovastatin appears to be a safe, effective and well-tolerated therapy for hypercholesterolemia in cardiac transplant recipients.