Intracellular acidosis and contractility in the normal and ischemic heart as examined by 31P NMR

William E. Jacobus, Ira H. Pores, Scott K. Lucas, Myron L. Weisfeldt, John T. Flaherty

Research output: Contribution to journalArticle

Abstract

31P was used to investigate correlations between intracellular pH (pHi) and myocardial contractility in the normal and ischemic isolated, perfused isovolumic rabbit heart. Intracellular pH was calculated from the chemical shift of Pi in hearts perfused with phosphate-free buffer. Normal intracellular pH was 7.22 ± 0.02 (n = 15). To calibrate the relationship between pHi and left ventricular developed pressure (LVDP), respiratory acidosis was induced by mixing 65% O2: 30% N2: 5% CO2 with 65% O2: 35% CO2 using Krebs buffer containing 24 mm HCO3-. The results show that a 0.22 pH unit acidification correlates with a 50% reduction in LVDP. The correlation between pHi and LVDP was also studied in two models of ischemia: total global ischemia and steady state partial ischemia (50% reduction of LVDP). In both ischemic conditions, a 50% lowering in LVDP correlated with only a 0.09 pH unit acidification. Thus, while intracellular acidosis may account for 40 to 50% of the depression of LVDP oberved during the early phases of ischemia, other factor must also play a role. Mass spectrometry was used to examine the potential regulatory role of tissue oxygen (PmO2). The model of steady-state partial ischemia was employed. Changes in LVDP and MVO2 correlated quite closely with reductions in coronary flow. However, up to a 50% reduction in flow, pHi remained near normal, and tissue PmO2 was normal or slightly elevated. These latter results suggest that an efficient autoregulatory mechanism controls both function and MVO2 in close parallel to changes in flow. As a result, the metabolic supply/demand balance is maintained. However, beyond a 50% reduction in flow, this mechanism fails and metabolic indicies of ischemia are expressed.

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume14
Issue numberSUPPL. 3
DOIs
StatePublished - Sep 1982

Keywords

  • Acidosis
  • Intracellular pH
  • Ischemia
  • Mass spectrometry
  • Myocardial contractility
  • P NMR
  • Perfused hearts
  • Respiratory acidosis
  • Wall tension

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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