Inhibition of accelerated coronary atherosclerosis with dehydroepiandrosterone in the heterotopic rabbit model of cardiac transplantation.

BACKGROUND: Accelerated coronary atherosclerosis has become a critical problem in cardiac transplantation. Although the pathogenesis of this disease is unknown, hypercholesterolemia has been shown to be a major risk factor. METHODS AND RESULTS: To study this problem, a hypercholesterolemic rabbit model of heterotopic cardiac transplantation was developed to study accelerated graft atherosclerosis. Based on suggestions in the literature, it was hypothesized that dehydroepiandrosterone (DHEA) may retard the progression of the disease. Using semiquantitative light microscopy, a predilection for the development of small vessel occlusive disease in the transplanted hearts was found. Chronic DHEA administration produced a 45% reduction in the number of significantly stenosed vessels in the transplanted hearts (p < 0.05) compared with controls and a 62% reduction in the nontransplanted hearts (p < 0.05), yielding an overall 50% reduction in the number of significantly stenosed vessels in both the transplanted and nontransplanted hearts. This reduction in luminal stenosis was observed in the absence of any significant alterations in lipid profiles. CONCLUSIONS: It is concluded that chronic DHEA administration in a hypercholesterolemic rabbit model of heterotopic cardiac transplantation significantly retards the progression of accelerated atherosclerosis in both the transplanted heart and in the native heart.

Revised technique of heterotopic heart transplantation in rabbits.

The technique of heterotopically transplanting a rabbit heart into the abdominal position of a recipient rabbit is discussed. Myocardial preservation, vascular anatomy of the recipient, and general anesthetic considerations are described, as are techniques to avoid anesthetic death, hemorrhage, and paraplegia. Application of these techniques to experimental models of accelerated coronary atherosclerosis and reperfusion injury are suggested.

Efficacy of recombinant-derived human superoxide dismutase on porcine left ventricular contractility after normothermic global myocardial ischemia and hypothermic cardioplegic arrest.

A porcine model of normothermic global ischemia (40 minutes) followed by systemic cooling to 25 degrees C with 4 degrees C crystalloid cardioplegic arrest (90 minutes) was used to assess the efficacy of recombinant-derived human superoxide dismutase (r-HSOD) on postreperfusion left ventricular function while on cardiopulmonary bypass. Isovolumic hemodynamic function was monitored, and adenine nucleotide pool was measured in myocardial biopsy specimens and coronary sinus effluent. The treatment group of pigs (n = 7) received 15 mg/kg r-HSOD immediately before warm reperfusion, both left ventricular peak systolic pressure and developed pressure were significantly better in the r-HSOD group of pigs (p less than 0.05 vs. placebo). This improvement persisted at 60 minutes of reperfusion (p less than 0.05 vs. placebo). Myocardial ATP and total adenine nucleotides did not differ, nor did adenine nucleotide catabolites in the coronary sinus effluent differ between treatment groups of pigs. The exception to this was the nucleotide catabolite inosine, which was significantly elevated in coronary sinus effluent of pigs treated with r-HSOD at 30 minutes of reperfusion (p less than 0.05 vs. placebo). In this model of global ischemia and reperfusion, a recombinant-derived human free-radical scavenger provides significant protection of systolic but not diastolic function. Values for myocardial ATP and total adenine nucleotide content suggest that the improvement in mechanical function during reperfusion is not due to enhanced preservation of myocardial bioenergetics.

Specific FSH suppression in male rat by porcine follicular fluid.

A variety of protocols using intact, castrated, and sham-castrated adult male rats was used to test the ability of porcine follicular fluid to selectively suppress serum follicle-stimulating hormone (FSH). A total dose of 500 microliters follicular fluid injected intraperitoneally will suppress FSH in the rat with testes within 5 h of injection. This is more than is necessary to suppress FSH in the intact or ovariectomized female. A total dose of 1 ml of follicular fluid is needed to suppress FSH reliably in the castrated male rat. Serum FSH is suppressed significantly beginning between 4 and 5.5 h after intraperitoneal injection of 1 ml of follicular fluid and 3 h after intravenous injection. The suppression continues until 10 h postinjection and is abated by 26 h postinjection. Serum luteinizing hormone (LH) is unaffected by follicular fluid in any protocol tested. It is concluded that 1) follicular fluid can suppress serum FSH in the male if large enough doses are given, 2) follicular fluid has no effect on serum LH, and 3) follicular fluid suppresses serum FSH levels in the male as well as previously tried testicular sources. These results suggest that the delay in demonstrating the existence of inhibin may be due to the use of males as both source and test subject.