Influence of intracellular acidosis on contractile function in the working rat heart

F. M H Jeffrey, C. R. Malloy, G. K. Radda

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Abstract

The decrease in myocardial contractility during ischemia, hypoxia, and extracellular acidosis has been attributed to intracellular acidosis. Previous studies of the relationship between pH and contractile state have utilized respiratory or metabolic acidosis to alter intracellular pH. We developed a model in the working perfused rat heart to study the effects of intracellular acidosis with normal external pH and otpimal O2 delivery. Intracellular pH and high-energy phosphates were monitored by 31P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH4Cl (extracellular pH, 7.4). The subsequent washout of NH3 from the cytosol generated a slight acidosis (from intracellular pH 7.0 to 6.8) which was associated with little change in the determinants of O2 consumption (rate-pressure product) and O2 delivery (coronary flow). Acidosis induced a substantial decrease in aortic flow and stroke volume which was associated with little change in peak systolic pressure. Results were qualitatively similar at different external [Ca2+] (1.75, 2.5, 3.15 mM) and preload (12 or 21 cmH2O) but were most prominent at the lowest external [Ca2+] and left atrial pressure. In contrast to this model of isolated intracellular acidosis, hearts subject to a respiratory (extracellular plus intracellular) acidosis showed a marked reduction in pressure development. It was concluded that 1) for the same intracellular acidosis the influence on tension development was more pronounced with a combined extra- and intracellular acidosis than with an isolated intracellular achidosis, and 2) stroke volume at constant preload was impaired by intracellular acidosis even though changes in developed pressure were minimal. These observations suggest that isolated intracellular acidosis has adverse effects on diastolic compliance and/or relaxation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume253
Issue number6
StatePublished - 1987

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Acidosis
Pressure
Stroke Volume
Respiratory Acidosis
Atrial Pressure
Cytosol
Compliance
Magnetic Resonance Spectroscopy
Ischemia
Phosphates
Blood Pressure

ASJC Scopus subject areas

  • Physiology

Cite this

Influence of intracellular acidosis on contractile function in the working rat heart. / Jeffrey, F. M H; Malloy, C. R.; Radda, G. K.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 253, No. 6, 1987.

Research output: Contribution to journalArticle

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