RELATIVE ROLES OF INTRACELLULAR CA2+ AND PH IN SHAPING MYOCARDIAL CONTRACTILE RESPONSE TO ACUTE RESPIRATORY ALKALOSIS

During acute respiratory alkalosis, myocardial contractility initially increases but then declines toward control levels. To elucidate the m echanism of this response, two parallel strategies were adopted: isovo lumic left ventricular developed pressure (DP) and intracellular pH (p H(i)) were measured in isolated ferret hearts using P-31-nuclear magne tic resonance spectroscopy, and isometric developed tension (DT) and i ntracellular Ca2+ concentration ([Ca2+]i) were measured in ferret papi llary muscles using microinjected fura 2 salt. When hypocapnia was ind uced by sudden introduction of perfusate equilibrated with 2% CO2 (fro m 5% CO2 in control), DP increased to a maximum of 120 +/- 3% (SE; n = 7) of control within 40 s. Afterward, DP decreased toward control lev els, reaching a new steady state in 2-3 min. In contrast, pH(i) increa sed from control (7.11 +/- 0.01) only after 30 s of hypocapnia and rea ched a peak of 7.25 +/- 0.02 between 80 and 100 s. Thus pH(i) lagged b ehind contractility. In contrast to pH(i), [Ca2+]i changed in parallel with DT: when DT reached a maximum (251 +/- 63% of control; n = 5) du ring hypocapnia, the amplitude of [Ca2+]i transients also peaked (190 +/- 22% of control; n = 5). A simulation of contractile force based on our measurements of pH(i) and [Ca2+]i, along with published Ca2+-tens ion relations, described adequately the changes in developed force dur ing hypocapnia. These results indicate that the biphasic changes in [C a2+]i, coupled with an out-of-phase change in pH(i), underlie the biph asic response of myocardial contractility to hypocapnia.