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Bell–shaped concentration–response curve for myocardial stimulation by glucocorticoids

The isolated perfused rat heart was used to study the myocardial effects of glucocorticoid methylprednisolone sodium succinate (MPSS 0, 100, 500 and 1000 mg/1) in normoxic conditions. Various physiological variables including coronary flow rate (CFR), left ventricular developed pressure (LVDP), dP/dTmax, dP/dTmix, and heart rate (HR) were assessed. At the end of the perfusion period the hearts were freeze clamped and analyzed for tissue content of calcium and various metabolites. MPSS (500 mg/1) resulted in vasodilatation and inotropic stimulation. An increase was found in CFR (+17% 4), LVDP (+ 6% 1), dP/dTmax, (+13% 2), dP/dTmix, (+ 9% 3); (P < 0.05). Heart rate was depressed (– 14% 2, P < 0.05). MPSS (100 mg/1) had no effect on CFR or contractility. MPSS (1000 mg/1) resulted in a transient vasodilatation and a progressive myocardial depression. MPSS perfusion (100 and 500 mg/1) increased the adenine nucleotide pool and at all concentrations MPSS elevated the myocardial content of lactate. We conclude that in normoxic conditions there is a bell–shaped curve of myocardial inotropic stimulation by the glucocorticoid hormone, and also a stimulation of metabolism possibly by increased cellular supply of substrates.