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Calcium preconditioning in human myocardium
B S Cain1, D R Meldrum, X Meng
1Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
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.