Summary
When cardiac muscle becomes hypoxic or ischaemic the cells become oedematous and the fine ultrastructure of the mitochondria is altered. Developed tension declines and resting tension increases. The cellular stores of ATP and CP are depleted and the mitochondria exhibit an altered respiration, characterized by a reduced state III respiration and a lowered respiratory control index. The calcium accumulating activity of the mitochondria is enhanced. During reperfusion the calcium content of the mitochondria increases and total tissue calcium rises. Using these changes in function as indices of the severity of the damage caused by hypoxia, ischaemia, and reperfusion we have investigated whether pretreatment with the slow channel Ca2+ antagonists verapamil and nifedipine provides protection.
Adult male New Zealand White rabbits were injected twice daily with either saline, verapamil, or nifedipine for 2–3 days before starting the experiments. The drugs were given subcutaneously or intraperitoneally and the last injection was given 2 h before killing the animals. The hearts were isolated, Langendorff perfused and then made ischaemic. Ischaemia was induced by occluding the coronary perfusion line. If hypoxic conditions were required they were established by substituting 95% N2 and 5% CO2 for 95% O2 + 5% CO2 in the gas mixture.
Pretreatment with either verapamil or nifedipine protected the mitochondria against the ischaemic- and hypoxic-induced changes in mitochondrial function. This pretreatment also prevented the mitochondria from accumulating excessive amounts of calcium; it resulted in the preservation of the fine ultrastructure of the myocardium and in the maintenance of its high energy phosphate (ATP and CP) reserves: a similar protective effect was observed when the drugs were added directly to the coronary perfusion circuit.
These investigations were supported by grants from The Wellcome Foundation and the Medical Research Council
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© 1980 Springer-Verlag Berlin-Heidelberg
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Nayler, W.G., Ferrari, F., Slade, A. (1980). Cardioprotective Actions of Calcium-Antagonists in Myocardial Anoxia and Ischaemia. In: Fleckenstein, A., Roskamm, H. (eds) Calcium-Antagonismus. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-67595-9_13
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DOI: https://doi.org/10.1007/978-3-642-67595-9_13
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