Effects of acidosis and ischemia on contractility and intracellular pH of rat heart.

Abstract

SUMMARY The effects of respiratory and metabolic acidosis on myocardial contractility and energy production have been investigated in the perfused rat heart. Respiratory acidosis, produced by increasing the Pco 2 , caused an 80% inhibition of pressure development at pH 6.7. When artificial buffers (plus HCI) were used in place of bicarbonate and CO 2 , only a 30% inhibition of pressure development was observed at pH 6.7. Respiratory acidosis produced a greater intracellular acidosis than artificial buffer acidosis at the same extracellular pH. We conclude that both intracellular and extracellular H + impair myocardial function but by separate mechanisms. Intracellular acidosis per se was shown to have little effect on the balance between energy production and energy utilization, and energy stores were relatively well maintained under these conditions. The contribution of intracellular acidosis to ischemic heart failure was examined using an ischemia model in which the coronary flow was decreased during diastole. Consequent restricted oxygen delivery produced a pattern of heterogeneous oxygenation. A fall in effluent pH was concomitant with the decline in myocardial performance, and the intracellular pH fell as the extracellular space became more acidotic. The data suggest that the fall of intracellular and extracellular pH were the principal determinants of the decline of pressure development in the tissue as a whole during the early stages of ischemia. We conclude that mechanical function is depressed in ischemia not only in anoxic regions of the heart but also in adjacent aerobic regions because of the pH change.ALTHOUGH it is well documented that decreased oxygen delivery and accumulation of metabolic end products are components of ischemia, the relative contribution of acidosis and hypoxia to ischemic heart failure has not been properly delineated. Myocardial performance is impaired by either anoxia, produced by equilibrating the perfusate with nitrogen instead of oxygen while maintaining the coronary flow, Previous experiments have demonstrated depression of myocardial contractility by acidosis, but the relative importance of intracellular and extracellular pH has not been unequivocally determined. Initially, it was suggested that extracellular pH was the principal determinant of cardiac work,"' 8 but more recently the importance of intracellular pH has been recognized."" 13 A role for intracellular pH was based on the assumption that there is a greater decline in intracellular pH during respiratory acidosis, produced by increasing the Pco 2 , than during metabolic acidosis, produced by decreasing the bicarbonate concentration. This difference is considered to be due to the high permeability of the sarcolemma to CO 2 and its relatively low permeability to protons or bicarbonate. Because metabolic acidosis causes a smaller negative inotropic effect than respiratory acidosis at the same extracellular pH, l3il4 it was concluded that intracellular pH is an important determinant of myocardial contractility. Howe...

Haemodynamic and metabolic effects in diabetic ketoacidosis in rats of treatment with sodium bicarbonate or a mixture of sodium bicarbonate and sodium carbonate

“…Indeed, the data of Steenbergen et al [13] suggests that the rise in phi seen in the present studies would, if taking place in the absence of other factors, have produced a significant positive inotropic effect. The cause of the relative hypotension in the alkalitreated groups remains to be conclusively demonstrated.…”

“…Specifically, this appears to be the case for the negative inotropic effect of systemic acidosis [13,14] and for the inhibition of hepatic gluconeogenesis from lactate [15,16]. It is therefore a testable hypothesis that therapies which correct intracellular acidosis are advantageous in haemodynamic and metabolic terms.…”

A novel antagonist, No. 7943, of the Na+/Ca2+ exchange current in guinea‐pig cardiac ventricular cells

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Left ventricular contractility is reduced by hypercapnic acidosis and thoracolumbar epidural anesthesia in rabbits

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