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Stunning and myocardial contractile autoregulation studied on the isolated isovolumic blood‐perfused dog heart
Authors:P. J. F. Tucci,O. Sant'Ana,R. J. Nogueira,N. Murad,A. C. Lopes,A. Sa  udo,C. A. Peres
Affiliation:P. J. F. Tucci,O. Sant'Ana,R. J. Nogueira,N. Murad,A. C. Lopes,A. Sañudo,C. A. Peres
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 instantaneous increase in developed pressure (Δ1DP) followed by a continuous slow performance increase (Δ2DP) in C and S. Δ1DP (C: 35 ± 2.2 mmHg; S: 27 ± 2.1 mmHg; P = 0.002) and Δ2DP (C: 20 ± 1.6 mmHg; S: 14 ± 1.3 mmHg; P = 0.002) decreased proportionally, while Δ21DP (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 Δ1DP can be understood as a decline of the myofilaments calcium responsiveness, the main pathophysiological effect of stunning. The reason for the weakening of Δ2DP, 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, Δ2DP 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.
Keywords:Bowditch effect  Frank–  Starling mechanism  heterometric autoregulation  homeometric autoregulation  ischaemia/reperfusion  length‐dependent activation  stunned myocardium
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