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 mechanism of this response, two parallel strategies were adopted: isovolumic left ventricular developed pressure (DP) and intracellular pH (pHi) were measured in isolated ferret hearts using 31P-nuclear magnetic resonance spectroscopy, and isometric developed tension (DT) and intracellular Ca2+ concentration ([Ca2+]i) were measured in ferret papillary muscles using microinjected fura 2 salt. When hypocapnia was induced by sudden introduction of perfusate equilibrated with 2% CO2 (from 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 levels, reaching a new steady state in 2-3 min. In contrast, pHi increased from control (7.11 +/- 0.01) only after 30 s of hypocapnia and reached a peak of 7.25 +/- 0.02 between 80 and 100 s. Thus pHi lagged behind contractility. In contrast to pHi, [Ca2+]i changed in parallel with DT: when DT reached a maximum (251 +/- 63% of control; n = 5) during 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 pHi and [Ca2+]i, along with published Ca(2+)-tension relations, described adequately the changes in developed force during hypocapnia. These results indicate that the biphasic changes in [Ca2+]i, coupled with an out-of-phase change in pHi, underlie the biphasic response of myocardial contractility to hypocapnia.