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J Mol Cell Cardiol. 1997 Jan;29(1):175-82.

Adenosine preconditioning of human myocardium is dependent upon the ATP-sensitive K+ channel.

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  • 1University of Colorado Health Sciences Center, Department of Surgery, Denver 80262, USA.

Abstract

Evidence supports the involvement of adenosine receptor stimulation and activation of K(ATP) channels in ischemic preconditioning of human myocardium. It is unknown, however, whether protection mediated by adenosine receptors is dependent upon the K(ATP) channel in the human heart. The purpose of this study was to determine whether adenosine-mediated protection against a simulated ischemia-reperfusion injury in human myocardium is dependent upon K(ATP) channels. Isolated human right atrial trabeculae were placed in tissue baths at 37 degrees C, oxygenated with a modified Tyrode solution, and field stimulated at 1 Hz. Trabeculae were subjected to 45 min of normothermic simulated ischemia (hypoxic, substrate-free buffer with pacing at 3 Hz.) and 60 min of reperfusion (I/R trabeculae). Trabeculae were preconditioned with simulated ischemia (IPC trabeculae) or adenosine receptor stimulation (adenosine, 125 micromol/l) for 5 min (ADO trabeculae) prior to simulated ischemic-reperfusion injury. Inhibition of the K(ATP) channel with glibenclamide (10 micromol/l) was combined with adenosine pretreatment (ADO+GLI trabeculae) or alone (GLI trabeculae) prior to simulated ischemic-reperfusion injury. Developed force (DF) at end reperfusion (mean+/-S.E.) was compared to baseline developed force, and tissue creatine kinase (CK) activity at end reperfusion was measured. I/R trabeculae showed 27+/-2% of baseline DF, whereas IPC trabeculae or ADO trabeculae showed 50+/-4% and 43+/-3% of baseline DF, respectively. ADO+GLI trabeculae showed 25+/-2% and GLI trabeculae showed 23+/-4% of baseline DF. Tissue CK activity was enhanced in the IPC and ADO trabeculae (433+/-63 U/g wet myocardium, and 415+/-28 U/g wet myocardium, respectively). I/R trabeculae had 196+/-26 U/g wet myocardium and ADO+GLI trabeculae had 277+/-38 U/g wet myocardium at end reperfusion. The results suggest that ischemic preconditioning and adenosine receptor stimulation confer functional protection against simulated ischemic-reperfusion, and adenosine mediated protection is eliminated by K(ATP) channel inhibition in human myocardium.

PMID:
9040032
[PubMed - indexed for MEDLINE]
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