Decrease in internal H + and positive inotropic effect of heptaminol hydrochloride: a 31P n.m.r. spectroscopy study in rat isolated heart

Abstract

1 The cardiotonic effect of heptaminol hydrochloride (Hept-a-myl, Delalande) was studied using ³¹P-nuclear magnetic resonance (n.m.r.) spectroscopy and left ventricular pressure (LVP) measurements in rat isolated hearts. The possibility of this effect being mediated by an intracellular realkalinisation was tested. 2 Isolated hearts were perfused at 10 ml min⁻¹ by the Langendorff method with Krebs-Henseleit solution at 37°C and stimulated at 5 Hz. Mechanical activity was measured as variations of left ventricular pressure (LVP). ³¹P-n.m.r. spectra were recorded every 2 min. Changes in cardiac adenosine triphosphate (ATP), phosphocreatine (PCr) and inorganic phosphate (Pi) were followed and intracellular pH (pHi) was estimated from the chemical shift of Pi. 3 The effects of heptaminol were tested in different conditions: normoxia, moderate ischaemia, severe ischaemia, and moderate ischaemia in the presence of amiloride or guanidinium chloride as inhibitors of the Na-H exchange. 4 In normoxia, heptaminol induced a cyclic increase of systolic LVP, associated with an increase in Pi. No significant effect on pHi was observed. In changing from normoxia to moderate ischaemia, PCr and systolic LVP decreased; a mild intracellular acidification (pHi 6.96) was obtained. Heptaminol induced a restoration of pHi and increased LVP. In severe ischaemia, the realkalinization effect and the restoration of LVP induced by heptaminol were no longer observed. During moderate ischaemia, Na-H exchange inhibitors decreased pHi and LVP. Heptaminol applied in the presence of these inhibitors was unable to restore pHi and LVP. 5 These results suggest that the positive inotropic effect of heptaminol during moderate ischaemia could be related to a restoration of internal pH, possibly mediated by a stimulation of the Na-H exchange.