Adenosine Preconditioning of Human Myocardium is Dependent upon the ATP-sensitive K+Channel

• Published in: Journal of molecular and cellular cardiology 1997-01, Vol.29 (1), p.175-182
• Main Authors: Cleveland, Jr, Joseph C., Meldrum, Daniel R., Rowland, Robert T., Banerjee, Anirban, Harken, Alden H.
• Format: Article
• Language: English
• Subjects: Adenosine - pharmacology; Adenosine receptor stimulation; Adenosine Triphosphate - pharmacology; Analysis of Variance; Cardiovascular Agents - pharmacology; Computer Simulation; Creatine Kinase - metabolism; Glyburide - pharmacology; Human myocardium; Humans; In Vitro Techniques; Ischemic preconditioning; Ischemic Preconditioning, Myocardial; KATPchannels; Myocardial Reperfusion Injury - prevention & control; Potassium Channels - drug effects; Purinergic P1 Receptor Agonists
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1006/jmcc.1996.0262

Evidence supports the involvement of adenosine receptor stimulation and activation of KATPchannels in ischemic preconditioning of human myocardium. It is unknown, however, whether protection mediated by adenosine receptors is dependent upon the KATPchannel 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 KATPchannels. Isolated human right atrial trabeculae were placed in tissue baths at 37°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 μmol/l) for 5 min (ADO trabeculae) prior to simulated ischemic–reperfusion injury. Inhibition of the KATPchannel with glibenclamide (10 μmol/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 KATPchannel inhibition in human myocardium.