Proceedings: Changes of the oxygen consumption in the heart muscle cell related to the heart rate and contraction force.
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Biomedical subjects
Publications and source records attributed to M Siess.
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The efficiency of cardiac work measured in isolated guinea pig atria can be influenced by change of the heart rate or the stroke work due to electric stimulation or drug actions: An increased cardiac performance caused by enhanced heart rate needs considerably more oxygen than an increase of the total cardiac work to the same degree due solely to a positive inotropic action. Oxidation of long and short chain fatty acids lowers the efficiency of cardiac work connected with negative inotropic effects. An increase of the heart rate is followed by a shift to the oxidation of carbohydrates, at rest to the oxidation of FFA. Long chain fatty acids are not sufficient for the increased demand of energy in the cardiac muscle at high heart rates and are then poorly oxidized. The problems connected with the Ca++ binding of FFA in the cardiac cytoplasm after inhibition of their oxidation well be discussed.
In isolated electrically driven left and in spontaneously beating right guinea-pig atria, the calcium ionophore ionomycin produced a concentration-dependent positive inotropic and chronotropic effect with a threshold near 10(-7) mol/l and a pD2 of 6.31 +/- 0.09 and 5.94 +/- 0.07, respectively. At low [Ca2+]o (0.5 mmol/l), the positive inotropic effect of ionomycin (3 X 10(-6) mol/l) was strongly attenuated by ryanodine and nifedipine, and slightly attenuated by pindolol and mepyramine; atropine had no effect. The positive chronotropic effect of ionomycin was slightly reduced by cimetidine or pindolol, whereas atropine, nifedipine, and ryanodine showed no inhibitory activity. The oxygen consumption of resting left atria was significantly enhanced by addition of ionomycin. It is concluded that the action of ionomycin involves at least the following mechanisms: I) release of Ca2+ from sarcoplasmic reticulum, II) influx of Ca2+ from the extracellular space, and, having little significance, III) release of catecholamines and histamine from sympathetic nerve endings and tissue mast cells. However, additional mechanisms of action of ionomycin cannot be excluded.
The inotropic and chronotropic effects of the calcium ionophore A23187 (calimycin = CA) in isolated, superfused, electrically driven, auxotonically contracting left and spontaneously beating right guinea-pig atria were examined at different Ca2+ concentrations. 10(-6) to 10(-5) mol/l CA shows significantly positive inotropic and chronotropic effects. The inotropic effect of CA can be significantly diminished by relatively high concentrations of Ca2+ channel antagonists and relatively low concentrations of ryanodine. The positive chronotropic effect of CA can be reduced slightly, but significantly, by beta-adrenoceptor antagonists and histamine H2-receptor antagonists. From this we infer that the positive inotropic effect of CA is mainly due to the release of Ca2+ from cardiac sarcoplasmic reticulum, whereas catecholamine and histamine release appear to contribute to the positive chronotropic effect of the ionophore.