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Circulation, Vol 90, 204-212, Copyright © 1994 by American Heart Association

ARTICLES

Myocardial blood flow at rest and during pharmacological vasodilation in cardiac transplants during and after successful treatment of rejection

SY Chan, J Kobashigawa, LW Stevenson, E Brownfield, RC Brunken and HR Schelbert
Department of Molecular and Medical Pharmacology, Ahmanson-UCLA Cardiomyopathy Center.

BACKGROUND: The relative intracoronary flow reserve has been found to be reduced during acute transplant rejection, but the effects of rejection on absolute flows at rest and during hyperemia have not been established previously. This has now become possible through noninvasive quantification of myocardial blood flow with positron emission tomography. METHODS AND RESULTS: Myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia was quantified in 10 transplant patients (group A) during an acute, biopsy-proven rejection episode and again after successful immunosuppressive treatment and in 6 transplant patients (group B) without prior rejection episode. In group A patients, MBF during rejection averaged 1.7 +/- 0.3 mL.min-1.g-1 at rest and 2.5 +/- 0.9 mL.min-1.g-1 during hyperemia; after recovery, MBF at rest had declined to 1.2 +/- 0.3 mL.-1.g-1 (P < .001) but had increased to 3.9 +/- 1.1 mL.-1.g-1 (P < .001) during hyperemia. Flows after recovery from rejection were similar to those in the group B patients (0.9 +/- 0.2 and 3.9 +/- 0.7 mL.min-1.g-1). Flow reserve in the group A patients was only 1.5 +/- 0.5 during rejection but improved to 3.4 +/- 0.9 at recovery (P < .001) and thus remained lower than in the control patients (4.5 +/- 0.7, P < .05). Minimal coronary resistance during dipyridamole vasodilation was elevated during rejection (40 +/- 11 mm Hg.mL-1.min-1.g-1); after recovery, it no longer differed from that in the group B patients (26 +/- 11 versus 22 +/- 4 mm Hg.mL-1.min-1.g-1). MBF during rejection was increased relative to cardiac work, as demonstrated by significantly higher ratios of blood flow to rate-pressure product than those at recovery and in the control patients. CONCLUSIONS: A decrease in hyperemic and an increase in resting myocardial blood flow, in excess to cardiac work, account for the previously reported reduction in coronary flow reserve. Because both alterations improve with antirejection treatment, they may reflect reversible alterations, presumably of endothelial function, local coagulation, and edema. The compromise in flow reserve and hyperemic flows may contribute to acute and chronic injury from rejection and thus provides a rationale for exercise restriction during rejection. The results further suggest a potential role for serial noninvasive flow measurements to guide immunosuppressive therapy.

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