Intracellular pH and intrinsic H+ buffering capacity in normal and hypertrophied right ventricle of ferret heart

Abstract

To answer the questions: (a) What is the effect of hypertrophy on the intracellular pH (pHi) and buffering power of cardiac muscle, and (b) How does hypertrophy affect the ability of cardiac muscle to recover from intracellular acidosis induced by hypoxia.In nominally HCO3(-)-free, HEPES-buffered Tyrode solution (35 degrees C), pHi and the intrinsic buffering power (beta i, measured in the presence of amiloride) was investigated using pH-sensitive microelectrodes.beta i was similar in both preparations (25 mM/pH unit at pHi 7.04). beta i was inversely related to pHi but the relationship was not significantly modified by hypertrophy. In the absence of amiloride, the time constant of pHi recovery (tau r) on removal of NH+4, was similar in normal (4.0 +/- 0.2 min, n = 5) and in hypertrophied muscles (4.3 +/- 0.3 min, n = 4; n.s.). In both preparations, net acid extrusion (JH) was similarly increased at lower values of pHi. Lowering temperature from 35 degrees to 22 degrees caused an alkalinization (0.15 pH units) of pHi. At 22 degrees C the mean values of pHi, beta i, tau r and JH were similar in normal and in hypertrophied muscles. At both temperatures and in both groups of preparations, recovery of pHi following hypoxia is approximately exponential. The time constant of recovery of pHi following hypoxia (tau rh) at 22 degrees C was not significantly different in hypertrophied muscles (7.2 +/- 0.9 min, n = 8) compared to controls (10.6 +/- 1.8 min, n = 13). However, at 35 degrees C, there was a significant difference in the mean values of tau rh which was smaller for hypertrophied muscles (3.9 +/- 0.3 min, n = 7) than for normal (7.1 +/- 1.1 min, n = 4, P < 0.005). For pHi 6.8-7.0, net acid extrusion in hypertrophied preparations was increased by a factor of 4 compared to normal.The intracellular buffering capacity and the pHi regulating capacity via Na+/H+ exchange are not significantly modified by right ventricular hypertrophy in ferret heart. The faster pHi recovery from hypoxia-induced acidification can be interpreted in terms of the role of lactate efflux in pHi control. The possible role of energy compartmentalization, its influence on the Na+ gradient and thus on pHi control after hypoxia, is discussed.