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Heterometric regulation and calcium sensitivity of the infarcted rat heart
J G Mill1, I Stefanon, C M Leite
1Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, Brasil.
Insights
Following myocardial infarction, surviving heart muscle shows reduced calcium sensitivity. Increasing diastolic pressure does not improve this calcium desensitization in infarcted rat ventricles.
Area of Science:
- Cardiovascular Physiology
- Cardiac Pathophysiology
Background:
- Myocardial infarction (MI) leads to surviving hypertrophied myocardium.
- This post-MI myocardium exhibits reduced sensitivity to extracellular calcium (Ca2+).
- Calcium's inotropic effect is influenced by sarcomere length.
Purpose of the Study:
- To investigate if increasing diastolic pressure (DP) can modulate calcium desensitization in infarcted left ventricles (LV).
Main Methods:
- Rats underwent left coronary artery ligation (MI) or sham-operation.
- Hearts were isolated and perfused using the Langendorff technique 8-10 days post-procedure.
- Left ventricular isovolumic systolic pressure (ISP) was measured across varying diastolic pressures (0-25 mmHg) and extracellular Ca2+ concentrations (0.8, 1.25, 2.5 mM).
Main Results:
- Infarcted hearts showed significantly depressed responses to extracellular Ca2+ compared to control hearts at all tested pressures.
- Increasing diastolic pressure up to 25 mmHg did not alter the reduced Ca2+ responsiveness in the infarcted ventricles.
- Control hearts demonstrated a robust increase in ISP with rising Ca2+ and DP, unlike infarcted hearts.
Conclusions:
- The surviving myocardium post-MI is desensitized to extracellular Ca2+.
- Elevating diastolic pressure does not overcome the impaired calcium sensitivity in infarcted rat hearts.
- These findings highlight a persistent deficit in calcium handling following myocardial infarction.
Abstract:
1. 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). 2. 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). 3. 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 depressed 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.(ABSTRACT TRUNCATED AT 250 WORDS)