Decrease in internal H+ and positive inotropic effect of heptaminol hydrochloride: a 31P n.m.r. spectroscopy study in rat isolated heart.
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 degrees 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. 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.
Berthiau
F
F
Laboratoire de Biophysique Cellulaire, Faculté de Médecine, Tours, France.
Garnier
D
D
Argibay
J A
JA
Seguin
F
F
Pourrias
B
B
Grivet
J P
JP
Le Pape
A
A
D000471:Alkalosis / Q000378:metabolism; D000605:Amino Alcohols / Q000494:pharmacology*; D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology; D006321:Heart / Q000187:drug effects*; D006535:Heptaminol / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007474:Ion Exchange; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical
D000605:Amino Alcohols; D006535:Heptaminol; D012964:Sodium; D011188:Potassium