title: Ischemic and anesthetic preconditioning reduces cytosolic [Ca2+] and improves Ca(2+) responses in intact hearts.
abstract: Ca(+) loading during reperfusion after myocardial ischemia is linked to reduced cardiac function. Like ischemic preconditioning (IPC), a volatile anesthetic given briefly before ischemia can reduce reperfusion injury. We determined whether IPC and sevoflurane preconditioning (SPC) before ischemia equivalently improve mechanical and metabolic function, reduce cytosolic Ca(2+) loading, and improve myocardial Ca(2+) responsiveness. Four groups of guinea pig isolated hearts were perfused: no ischemia, no treatment before 30-min global ischemia and 60-min reperfusion (control), IPC (two 2-min occlusions) before ischemia, and SPC (3.5 vol%, two 2-min exposures) before ischemia. Intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured at the left ventricular (LV) free wall with the fluorescent probe indo 1. Ca(2+) responsiveness was assessed by changing extracellular [Ca(2+)]. In control hearts, initial reperfusion increased diastolic [Ca(2+)] and diastolic LV pressure (LVP), and the maximal and minimal derivatives of LVP (dLVP/dt(max) and dLVP/dt(min), respectively), O(2) consumption, and cardiac efficiency (CE). Throughout reperfusion, IPC and SPC similarly reduced ischemic contracture, ventricular fibrillation, and enzyme release, attenuated rises in systolic and diastolic [Ca(2+)], improved contractile and relaxation indexes, O(2) consumption, and CE, and reduced infarct size. Diastolic [Ca(2+)] at 50% dLVP/dt(min) was right shifted by 32-53 +/- 8 nM after 30-min reperfusion for all groups. Phasic [Ca(2+)] at 50% dLVP/dt(max) was not altered in control but was left shifted by -235 +/- 40 nM [Ca(2+)] after IPC and by -135 +/- 20 nM [Ca(2+)] after SPC. Both SPC and IPC similarly reduce Ca(2+) loading, while augmenting contractile responsiveness to Ca(2+), improving postischemia cardiac function and attenuating permanent damage.
authors.affiliation: Anesthesiology Research Laboratories, Department of Anesthesiology, and Cardiovascular Research Center, The Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: J
authors.initials: J
authors.lastname: An
authors.forename: S G
authors.initials: SG
authors.lastname: Varadarajan
authors.forename: E
authors.initials: E
authors.lastname: Novalija
authors.forename: D F
authors.initials: DF
authors.lastname: Stowe
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D003971:Diastole; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial; D008738:Methyl Ethers / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D011312:Pressure; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D000077149:Sevoflurane; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D002118:Calcium