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. 1989 Dec;98(4):1233–1240. doi: 10.1111/j.1476-5381.1989.tb12669.x

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

F Berthiau 1, D Garnier 1, J A Argibay 1, F Seguin 1, B Pourrias 1, J P Grivet 1, A Le Pape 1
PMCID: PMC1854797  PMID: 2611491

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 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Blanchard E. M., Solaro R. J. Inhibition of the activation and troponin calcium binding of dog cardiac myofibrils by acidic pH. Circ Res. 1984 Sep;55(3):382–391. doi: 10.1161/01.res.55.3.382. [DOI] [PubMed] [Google Scholar]
  2. CORABOEUF E., BOISTEL J. Etude à l'aide de microélectrodes intracellulaires de l'action d'un tonicardiaque: l'amino.6-methyl.2-heptanol.2 (2831 R.P) sur le tissu nodal du coeur de chien. C R Seances Soc Biol Fil. 1953 May;147(9-10):774–779. [PubMed] [Google Scholar]
  3. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  4. Chapman R. A. Control of cardiac contractility at the cellular level. Am J Physiol. 1983 Oct;245(4):H535–H552. doi: 10.1152/ajpheart.1983.245.4.H535. [DOI] [PubMed] [Google Scholar]
  5. Chesnais J. M., Coraboeuf E., Sauviat M. P., Vassas J. M. Sensitivity to H, Li and Mg ions of the slow inward sodium current in frog atrial fibres. J Mol Cell Cardiol. 1975 Sep;7(9):627–642. doi: 10.1016/0022-2828(75)90140-6. [DOI] [PubMed] [Google Scholar]
  6. Deitmer J. W., Ellis D. Interactions between the regulation of the intracellular pH and sodium activity of sheep cardiac Purkinje fibres. J Physiol. 1980 Jul;304:471–488. doi: 10.1113/jphysiol.1980.sp013337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fabiato A., Fabiato F. Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles. J Physiol. 1978 Mar;276:233–255. doi: 10.1113/jphysiol.1978.sp012231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fabiato A. Use of aequorin for the appraisal of the hypothesis of the release of calcium from the sarcoplasmic reticulum induced by a change of pH in skinned cardiac cells. Cell Calcium. 1985 Apr;6(1-2):95–108. doi: 10.1016/0143-4160(85)90037-5. [DOI] [PubMed] [Google Scholar]
  9. Frelin C., Vigne P., Barbry P., Lazdunski M. Interaction of guanidinium and guanidinium derivatives with the Na+/H+ exchange system. Eur J Biochem. 1986 Jan 15;154(2):241–245. doi: 10.1111/j.1432-1033.1986.tb09388.x. [DOI] [PubMed] [Google Scholar]
  10. Frelin C., Vigne P., Barbry P., Lazdunski M. Molecular properties of amiloride action and of its Na+ transporting targets. Kidney Int. 1987 Dec;32(6):785–793. doi: 10.1038/ki.1987.277. [DOI] [PubMed] [Google Scholar]
  11. Hoerter J. A., Lauer C., Vassort G., Guéron M. Sustained function of normoxic hearts depleted in ATP and phosphocreatine: a 31P-NMR study. Am J Physiol. 1988 Aug;255(2 Pt 1):C192–C201. doi: 10.1152/ajpcell.1988.255.2.C192. [DOI] [PubMed] [Google Scholar]
  12. Hoerter J. A., Miceli M. V., Renlund D. G., Jacobus W. E., Gerstenblith G., Lakatta E. G. A phosphorus-31 nuclear magnetic resonance study of the metabolic, contractile, and ionic consequences of induced calcium alterations in the isovolumic rat heart. Circ Res. 1986 Apr;58(4):539–551. doi: 10.1161/01.res.58.4.539. [DOI] [PubMed] [Google Scholar]
  13. Irisawa H., Sato R. Intra- and extracellular actions of proton on the calcium current of isolated guinea pig ventricular cells. Circ Res. 1986 Sep;59(3):348–355. doi: 10.1161/01.res.59.3.348. [DOI] [PubMed] [Google Scholar]
  14. Kohlhardt M., Haap K., Figulla H. R. Influence of low extracellular pH upon the Ca inward current and isometric contractile force in mammalian ventricular myocardium. Pflugers Arch. 1976 Oct 15;366(1):31–38. doi: 10.1007/BF02486557. [DOI] [PubMed] [Google Scholar]
  15. LOUBATIERES A. Propriétés cardiotoniques d'un amino-alcool aliphatique, l'amino.6-méthyl.2-heptanol.2 (2831 R.P). Arch Int Pharmacodyn Ther. 1951 Feb;85(3-4):333–356. [PubMed] [Google Scholar]
  16. Lavanchy N., Martin J., Rossi A. Caractérisation par la spectroscopie en RMN du 31P, de l'état du métabolisme énergétique cardiaque: comparaison avec les données biochimiques. J Physiol (Paris) 1985;80(3):196–201. [PubMed] [Google Scholar]
  17. Lazdunski M., Frelin C., Vigne P. The sodium/hydrogen exchange system in cardiac cells: its biochemical and pharmacological properties and its role in regulating internal concentrations of sodium and internal pH. J Mol Cell Cardiol. 1985 Nov;17(11):1029–1042. doi: 10.1016/s0022-2828(85)80119-x. [DOI] [PubMed] [Google Scholar]
  18. MUELLER P., SCHATZMANN H. J., WEIDMANN S. EFFETS DU CHLORHYDRATE D'HEPTAMINOL SUR LA CONTRACTION LE POTENTIEL D'ACTION ET LE TAUX DE POTASSIUM INTRACELLULAIRE DES FIBRES CARDIAQUES. C R Seances Soc Biol Fil. 1964;158:1850–1853. [PubMed] [Google Scholar]
  19. Moon R. B., Richards J. H. Determination of intracellular pH by 31P magnetic resonance. J Biol Chem. 1973 Oct 25;248(20):7276–7278. [PubMed] [Google Scholar]
  20. Orchard C. H. The role of the sarcoplasmic reticulum in the response of ferret and rat heart muscle to acidosis. J Physiol. 1987 Mar;384:431–449. doi: 10.1113/jphysiol.1987.sp016462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Philipson K. D., Bersohn M. M., Nishimoto A. Y. Effects of pH on Na+-Ca2+ exchange in canine cardiac sarcolemmal vesicles. Circ Res. 1982 Feb;50(2):287–293. doi: 10.1161/01.res.50.2.287. [DOI] [PubMed] [Google Scholar]
  22. Poole-Wilson P. A., Langer G. A. Effects of acidosis on mechanical function and Ca2+ exchange in rabbit myocardium. Am J Physiol. 1979 Apr;236(4):H525–H533. doi: 10.1152/ajpheart.1979.236.4.H525. [DOI] [PubMed] [Google Scholar]
  23. Pourrias B., Sergant M., Raynaud G. Effet hémodynamique systémique, pulmonaire et coronaire et action sur le métabolisme cardiaque du chlorhydrate d'heptaminol. Therapie. 1969 May-Jun;24(3):451–466. [PubMed] [Google Scholar]
  24. Steenbergen C., Deleeuw G., Rich T., Williamson J. R. Effects of acidosis and ischemia on contractility and intracellular pH of rat heart. Circ Res. 1977 Dec;41(6):849–858. doi: 10.1161/01.res.41.6.849. [DOI] [PubMed] [Google Scholar]
  25. Vassort G., Whittembury J., Mullins L. J. Increases in internal Ca2+ and decreases in internal H+ are induced by general anesthetics in squid axons. Biophys J. 1986 Jul;50(1):11–19. doi: 10.1016/S0006-3495(86)83434-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vogel S., Sperelakis N. Blockade of myocardial slow inward current at low pH. Am J Physiol. 1977 Sep;233(3):C99–103. doi: 10.1152/ajpcell.1977.233.3.C99. [DOI] [PubMed] [Google Scholar]
  27. Williamson J. R., Safer B., Rich T., Schaffer S., Kobayashi K. Effects of acidosis on myocardial contractility and metabolism. Acta Med Scand Suppl. 1976;587:95–112. doi: 10.1111/j.0954-6820.1976.tb05871.x. [DOI] [PubMed] [Google Scholar]

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