Disparate effects of three types of extracellular acidosis on left ventricular function

Effects of acidosis on muscle contractile function have been studied extens ively. However, the relative effects of different types of extracellular ac idosis on left ventricular (LV) contractile function, especially the tempor al features of contraction, have not been investigated in a single model. W e constituted perfusion buffers of identical ionic composition, including C a2+ concentration ([Ca2+]), to mimic physiological control condition (pH 7. 40) and three types of acidosis with pH of 7.03: inorganic (IA), respirator y (RA), and lactic (LA). Isolated rabbit hearts (n = 9) were perfused with acidotic buffers chosen at random, each preceded by the control buffer. Und er steady-state conditions, instantaneous LV pressure (P-v) and volume (V-v ) were recorded for a range of V-v. The results were as follows. 1) LV pass ive (end-diastolic) elastance increased with IA and RA. However, this incre ase may not be a direct effect of acidosis; it can be explained on the basi s of myocardial turgor. 2) Although LV inotropic state (peak active P-v and elastance) was depressed by all three acidotic buffers, the magnitude of i notropic depression was significantly less for LA. 3) Temporal features of P-v were altered differently. Whereas IA and RA reduced time to peak P-v (t (max)) and hastened isovolumic relaxation at a common level of LV wall stre ss, LA significantly increased t(max) and retarded relaxation. These result s and a model-based interpretation suggest that cooperative feedback (i.e., force-activation interaction) plays an important role in acidosis-induced changes in LV contractile function. Furthermore, it is proposed that LA-ind uced responses comprise two components, one due to intracellular acidosis a nd the other due to pH-independent effects of lactate ions.