Supersensitivity mismatch of adenosine in the transplanted human heart: chrono- and dromotropy versus inotropy

Supersensitive negative chronotropic and dromotropic effects have been described for adenosine after human heart transplantation. The present study investigated a potential antiadrenergic negative inotropic effect of adenosine in heart transplant recipients compared to normal subjects. Sinus cycle length, PR interval, blood pressure, and inotropic response in vivo were compared in seven orthotopic heart transplant recipients and seven healthy volunteers (controls). Fractional shortening, velocity of circumferential fiber shortening, and systolic pressure/dimension ratio were calculated using M-mode echocardiography. Baseline ventricular contractility was normal in both groups. Although adenosine induced a significant exaggeration of the negative chronotropic and dromotropic effect in the transplant group, the positive inotropic effect of 20 ng/kg x min isoproterenol (FS 53.2 +/- 8.8 vs 51.0 +/- 4.6%, P/D 5.8 +/- 1.9 vs 6.0 +/- 0.8 mm Hg/mm, Vcf 0.21 +/- 0.04 vs 0.20 +/- 0.02%/ms for heart recipients vs controls) was not reduced by the additional administration of 150 micrograms/kg adenosine (FS 52.2 +/- 8.6 vs 51.7 +/- 5.6%, P/D 5.5 +/- 1.5 vs 5.4 +/- 0.8 mm Hg/mm, Vcf 0.24 +/- 0.07 vs 0.21 +/- 0.02%/ms for transplant recipients vs controls). In contrast to a chronotropic and dromotropic supersensitivity, adenosine does not attenuate the catecholamine-induced increase in contractility in the human ventricle in vivo after heart transplantation.