Heterometric regulation and calcium sensitivity of the infarcted rat heart

RESUMO

The surviving hypertrophied muscle remaining after myocardial infarction in rats is less sensitive to extracellular Ca2+ than the normal myocardium. Since the inotropic effect of Ca2+ is modulated by sarcomere lenght, the present study was undertaken to determine if Ca2+ desensitization of infarcted left ventricles (LV) can be modulated by increasing the diastolic pressure (DP). Rats submitted to left coronary artery ligation (N+11) or sham-operation (N=9) were killed 8-10 days later and their hearts perfused by the Langendorff technique. A balloon was introduced into the LV cavity to measure the isovolumic systolic pressure (ISP) produced by DP changes (0 to 25 mmHg) at three Ca2+ concentrations (0.8, 1.25 and 2.5 mM). In control hearts submitted to a DP of mmHg, the ISP increased from 36ñ3 to 63ñ4 and to 74ñ4 mmHg as external Ca2+ was changed from 0.8 to 1.25 and to 2.5 mM, respectively. in contrast,in infarcted hearts submitted to the same DP and Ca2+ concentrations, the ISP increased from 19ñ2 to 26ñ2 and to 27ñ3 mmHg. The depressed response to Ca2+ was not modified by increasing DP up to 25 mmHg, the greatest DP tested. At this DP, ISP increased from 75ñ4 to 103ñ5 and 114ñ5 mmHg control hearts and from 45ñ2 to 54ñ3 and to 55ñ4 mmHg in infarted hearts. Ventricular function curve normalization in relation to a DP of 5 mmHg, indicated that the relative increases of ISP as a function of DP, produced by infarcted hearts, were higher than controls for DP higher than 10 mmHg. These results indicate that indicate that desensitization to extracellular Ca2+ of infarcted hearts cannot be reduced by increasing preload levels. However, the depressed mechanical response may be partially compensated for by an improvement of the length-dependent contractile response of the hypertrophied muscle surviving infarction