Heterometric regulation and calcium sensitivity of the infarcted rat heart
Mill, J.G.; Stefanon, I.; Leite, C.M.; Vassallo, D.V.
Brazilian Journal of Medical and Biological Research 24(4): 429-436
1991
ISSN/ISBN: 0100-879X PMID: 1840426 Document Number: 370193
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 length, 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 Langerdorff 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+ concentration (0.8, 1.25 and 2.5 mM). In control hearts submitted to a DP of 5 mmHg, the ISP increased from 36 .+-. 3 to 63 .+-. 4 and to 74 .+-. 4 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 19 .+-. 2 to 26 .+-. 2 and to 27 .+-. 3 mmHg. The decompressed response to Ca2+ was not modified by increasing DP up to 25 mmHg, the greatest DP tested. At this DP, ISP increased from 75 .+-. 4 to 103 .+-. 5 and to 114 .+-. 5 mmHg in control hearts and from 45 .+-. 2 to 54 .+-. 3 and to 55 .+-. 4 mmHg in infarcted 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 desensitization to extracellular Ca2+ of infarcted hearts cannot be reduced by increasing preload levels. However, ther depressed mechanical response may be partially compensated for by an improvement of the length-dependent contractile response of the hypertrophied muscle surviving infarction.