Stunning and myocardial contractile autoregulation studied on the isolated isovolumic blood-perfused dog heart

Abstract

Aim: To study, for the first time, the effects of stunning on homeometric and heterometric autoregulation.Methods and results Ischaemia (15 min)/reperfusion (30 min) was induced in the isovolumic blood-perfused dog heart preparation. Heart rate elevations (n=9) from 60 to 200 beats min(-1), in steps of 20 beats min(-1), promoted the same inotropic stimulation in control (C) and stunning (S), indicating that ischaemia/reperfusion does not affect the changes in calcium kinetics elicited by the Bowditch effect. Sudden ventricular dilation (VD) (n=10) evoked an <LF>instantaneous increase in developed pressure (Delta(1)DP) followed by a continuous slow performance increase (Delta(2)DP) in C and S. Delta(1)DP (C: 35+/-2.2 mmHg; S: 27+/-2.1 mmHg; P=0.002) and Delta(2)DP (C: 20+/-1.6 mmHg; S: 14+/-1.3 mmHg; P=0.002) decreased proportionally, while Delta(2)/Delta(1)DP (C: 0.57+/-0.13; S: 0.58+/-0.14) and slow response time course (T/2) were unchanged (C: 55+/-6.6 s; S: 57+/-7.7 s) after ischaemia/reperfusion. the reduction of Delta(1)DP can be understood as a decline of the myofilaments calcium responsiveness, the main pathophysiological effect of stunning. the reason for the weakening of Delta(2)DP, due to intracellular calcium gain, was not determined but it was supposed that its complete manifestation could be restricted by cyclic adenosine monophosphate (cAMP) myocardial content reduction. As reported by others, Delta(2)DP depends on myocardial cAMP, and it has been shown that myocardial cAMP is decreased after ischaemia/reperfusion.Conclusions: Contractile depression due to stunning has no effect on the inotropic stimulation generated by the Bowditch phenomenon. Immediate and time-dependent enhancements of contraction evoked by sudden VD are proportionally reduced and the slow response time course is unaffected in the stunned myocardium.