Calcium preconditioning in human myocardium.
BACKGROUND
Ischemic stress and other protein kinase C (PKC)-linked receptor stimuli can induce rapid cardiac protection against ischemia-reperfusion injury. We and others have demonstrated that exogenous calcium (Ca2+) pretreatment confers PKC-mediated cardiac functional and infarct protection in animal models, but it remains unknown whether Ca2+ preconditioning confers similar postischemic functional protection in human myocardium, and, if so, whether the mechanism is mediated by PKC. We postulated that Ca2+ preconditioning confers ischemic tolerance to human myocardium by a PKC-dependent mechanism.


METHODS
Human atrial trabeculae were suspended in organ baths and paced at 1 Hz, and force development was recorded. After 90 minutes of equilibration, all trabeculae were subjected to ischemia (45 minutes) and reperfusion (120 minutes). Exogenous CaCl2 (3.0 mmol/L for 5 minutes) or vehicle (saline solution) was administered before simulated ischemia, with or without concurrent PKC inhibition (bisindolylmaleimide I, 150 nmol/L).


RESULTS
Ischemia-reperfusion resulted in decreased postischemic developed force, Ca2+ preconditioning protected human myocardium against ischemia-reperfusion injury (p < 0.05 versus control ischemia-reperfusion), and concurrent PKC inhibition abolished the salutary effect of Ca2+ preconditioning in human myocardium (p < 0.05 versus Ca2+ preconditioning).


CONCLUSIONS
Preconditioning with Ca2+ represents a potent means of accessing PKC-mediated protection of the human myocardium against ischemia-reperfusion injury.
Cain
B S
BS
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
Meldrum
D R
DR
Meng
X
X
Shames
B D
BD
Banerjee
A
A
Harken
A H
AH
D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000627:therapeutic use*; D002122:Calcium Chloride / Q000627:therapeutic use; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D012965:Sodium Chloride; D013997:Time Factors
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D012965:Sodium Chloride; D011493:Protein Kinase C; D002122:Calcium Chloride; C088060:bisindolylmaleimide; D002118:Calcium