title: Relative roles of intracellular Ca2+ and pH in shaping myocardial contractile response to acute respiratory alkalosis.
abstract: 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.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: H
authors.initials: H
authors.lastname: Kusuoka
authors.forename: P H
authors.initials: PH
authors.lastname: Backx
authors.forename: M
authors.initials: M
authors.lastname: Camilion de Hurtado
authors.forename: M
authors.initials: M
authors.lastname: Azan-Backx
authors.forename: E
authors.initials: E
authors.lastname: Marban
authors.forename: H E
authors.initials: HE
authors.lastname: Cingolani
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000472:Alkalosis, Respiratory / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002245:Carbon Dioxide / Q000494:pharmacology; D004734:Energy Metabolism; D005289:Ferrets; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D016277:Ventricular Function, Left
chemical_list: D010710:Phosphates; D010725:Phosphocreatine; D002245:Carbon Dioxide; D010758:Phosphorus; D001262:Atenolol; D000255:Adenosine Triphosphate; D002118:Calcium