Ribose infusion accelerates thallium redistribution with early imaging compared with late 24-hour imaging without ribose.

To determine if early (4-h) thallium-201 imaging with ribose infusion would enhance detection of thallium redistribution better than late (24-h) imaging without ribose infusion, 15 patients with coronary artery disease underwent thallium stress tests by both methods within 2 weeks. All 15 patients had quantitative coronary angiography. After immediate postexercise planar imaging during the first of two exercise tests, patients were randomized to receive either intravenous ribose (3.3 mg/kg per min) or a control infusion of saline solution for 30 min. Images performed at 4 h for the ribose study were compared with those at 24 h for the saline control study. During the second test, exercise was carried to the same rate-pressure product and each patient received the opposite infusion. Four-hour postexercise images after ribose infusion identified 21 reversible defects not seen in the 24-h saline study. Three reversible defects were seen only in saline studies, but not with ribose at 4 h (p less than 0.01); 15 reversible defects were seen with both tests. When analyzed with respect to the 31 vascular territories supplied by a coronary artery with a greater than 50% stenosis, 8 territories had reversible defects present in the ribose but not the saline study and the saline study did not demonstrate reversible defects in territories that were seen in the ribose study (p less than 0.01). In 14 of these territories, reversible defects were seen with both tests. In 6 of 15 patients, additional vascular territories with reversible defects were identified after ribose infusion. It is concluded that ribose enhances the detection of thallium redistribution at 4 h compared with 24-h control images in patients with coronary artery disease and, therefore, substantially improves the identification of viable ischemic myocardium.

OKT3 monoclonal antibody given for ten versus fourteen days as immunosuppressive prophylaxis in heart transplantation.

We have previously reported that murine antihuman monoclonal antibody OKT3 (Orthoclone OKT3) given for 14 days after heart transplantation is effective as immunosuppressive prophylaxis. The optimal protocol for OKT3 prophylaxis in heart transplantation is unknown, particularly the duration of OKT3 therapy. We conducted a consecutively allocated overlapping 6-month study with 68 heart transplant patients, comparing 14-day OKT3 (n = 34) to 10-day OKT3 treatment (n = 34). Both protocols included OKT3 given beginning 24 to 48 hours after operation, cyclosporine beginning on postoperative day 3, low-dosage steroids and azathioprine to prevent antibody production to OKT3, and a steroid pulse plus randomization to plus or minus vincristine after stopping OKT3. Pretransplant characteristics including age, sex, cause of congestive heart failure, and absence of positive pretransplant crossmatch were similar between the two groups. Although the infection rate was not significantly different between the two groups and mortality (one patient in each group) did not differ, 14-day prophylaxis decreased the number of treated rejection episodes per patient for the 6-month study (1.59 +/- 0.18 versus 2.24 +/- 0.19, p = 0.016). A 14-day course of OKT3 also decreased the risk of rejection during the 6-month follow-up period (p less than 0.05). In addition to having a decreased number of rejection episodes, patients in the 14-day protocol were also more likely to be withdrawn from maintenance steroids (79% versus 53%, p = 0.02). In conclusion, a measurable dose response efficacy can be demonstrated for 14-day versus 10-day OKT3 prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypercholesterolemia after heart transplantation: amelioration by corticosteroid-free maintenance immunosuppression.

Most heart transplant recipients develop hypercholesterolemia, the cause of which is poorly understood. To test the hypothesis that corticosteroids contribute to the hypercholesterolemia, we reviewed 117 consecutive heart transplant recipients who survived more than 4 months, of whom 51 (44%) required and 66 (56%) did not require maintenance corticosteroids, chronic immunosuppression maintained with cyclosporine and azathioprine only. Fasting serum cholesterol levels were measured every 3 months and were found to be 21% to 26% lower during the first 18 months after heart transplantation in the group that did not require chronic corticosteroid administration (p less than 0.001). Beginning 3 months after transplantation, average serum cholesterol levels ranged from 199 +/- 8 mg/dl to 211 +/- 9 mg/dl in the corticosteroid-free group compared with 262 +/- 8 mg/dl to 272 +/- 8 mg/dl in patients requiring corticosteroid maintenance immunosuppression. Because serum cyclosporine levels did not differ between the groups, a contribution by cyclosporine to posttransplant hypercholesterolemia could not be substantiated. Although the hypercholesterolemia that occurs after heart transplantation is undoubtedly multifactorial, corticosteroid administration contributes importantly to its development.

Relationship between corticosteroid exposure and plasma lipid levels in heart transplant recipients.

PURPOSE: Accelerated coronary atherosclerosis is a major cause of heart graft failure two years and more after heart transplantation, yet its etiology remains undetermined. We conducted this study to determine the prevalence of coronary risk-associated lipid abnormalities, and the relationship between lipid levels and exposure to corticosteroids and cyclosporine, in heart transplant recipients. PATIENTS AND METHODS: The records of 92 consecutive heart transplant recipients from three different transplantation centers were reviewed. Patients from the three centers varied in age, in corticosteroid regimens, and in the proportion undergoing transplantation for ischemic cardiomyopathy. Although 11 patients were not receiving corticosteroids at the time of the study, all patients had received them immediately after transplantation. In addition to information pertaining to demographics, pretransplant medical history, rejection episodes, drug doses, renal function, and blood glucose levels, data on dietary intake and body weight were collected and plasma lipid levels were measured at the time of record review. RESULTS: A significant number, 48 (52 percent), of heart transplant recipients were above the sex- and age-adjusted 75th percentile, and 35 (38 percent) were above the 90th percentile for total cholesterol in comparison with a general reference population. Similar elevations were found in low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol levels. Bivariate analysis demonstrated cumulative prednisone exposure (r = 0.40, p = 0.0001) and cumulative cyclosporine exposure (r = 0.22, p = 0.04) but not diet or etiology of pretransplant heart disease to be significantly associated with age- or sex-adjusted total cholesterol percentiles. Low-density lipoprotein cholesterol percentiles were also correlated with cumulative prednisone (r = 0.37, p = 0.001) and cumulative cyclosporine exposure (r = 0.24, p = 0.02). Stepwise multiple linear regression analysis, however, demonstrated cumulative prednisone exposure to be the strongest predictor of both total and low-density lipoprotein cholesterol levels and percentiles (p = 0.0001), independent of cumulative cyclosporine exposure and other clinical variables. CONCLUSION: These data suggest that long-term corticosteroid exposure may result in an increased prevalence of unfavorable lipid profiles in heart transplant recipients.