Coronary vascular reactivity after heart transplantation in dogs: nitroglycerin-induced response

Coronary reactivity during rejection still remains an unresolved question. Evidence of residual coronary dilator reserve would lend support to the therapeutic approach of increasing myocardial blood flow during episodes of acute rejection. This hypothesis was tested in canine heart transplants. Fourteen orthotopic heart transplantations were performed and electronic implants were positioned for long-term hemodynamic studies. Of the 14 study dogs, nine were nonimmunosuppressed; five dogs with transplants received standard triple therapy (cyclosporine, azathioprine, and prednisone). Nitroglycerin challenge consisted of an intravenous bolus administration at a dose of 4 to 5 micrograms/kg. This pharmacologic challenge was performed 3 hours after surgery, 2 to 3 days after transplantation, and 24 hours or less before death for the nonimmunosuppressed group. Nitroglycerin always exerted its peripheral vasodilator effect: arterial pressure decreased by 20% and total peripheral resistance by 25% to 35%, which favors the observed increment in cardiac index. There were, however, significant differences in the cardiac effect of nitroglycerin: during acute rejection this effect was severely blunted (less than 10%). On the contrary, coronary blood flow always increased after nitroglycerin administration (40% in the postoperative period, 42% in immunosuppressed dogs, and 33% during acute rejection). These results indicate that nitroglycerin elicits its coronary vasodilator effect despite acute rejection episodes. The concept of a functional reversible vasoconstrictor component present during acute rejection gains support from this study and brings a challenging new avenue for therapeutic approaches.