Objectives: Recently, the mitochondrial adenosine triphosphate-sensitive potassium channel has been suggested to be the final common effector of myocardial preconditioning. The purpose of this study is to determine whether selective mitochondrial adenosine triphosphate-sensitive potassium channel activation alone can precondition human myocardium from an ischemia/reperfusion insult. Methods: Isolated human fight atrial trabeculae were placed in tissue baths, paced, and subjected to 30 minutes of normothermic hypoxia (ischemia) followed by 45 minutes of reoxygenation (reperfusion). Trabeculae were preconditioned with a selective mitochondrial adenosine triphosphate-sensitive potassium channel opener (diazoxide 30 μmol/L) or a nonselective purinergic agonist, adenosine (125 μmol/L), for 5 minutes (adenosine) followed by a 10-minute washout period. Developed force at end reperfusion (mean ± standard error) was compared with baseline, and tissue creatine kinase and adenosine triphosphate levels were measured after ischemia/reperfusion. Results: Trabeculae subjected to ischemia/reperfusion exhibited 30% ± 2% of baseline developed force, whereas trabeculae subjected to selective adenosine triphosphate-sensitive potassium channel opening (diazoxide) and nonselective purinergic agonist (adenosine) recovered to 55% ± 7% and 46% ± 3% of baseline developed force, respectively. Tissue creatine kinase activity was preserved in both the diazoxide- and adenosine-treated trabeculae (5.4 ± 12 and 5.4 ± 14 μmol/L per gram wet tissue) compared with ischemia/reperfusion (1.8 ± 0.2 U/mg wet tissue). Adenosine triphosphate levels at end reperfusion were also increased in the trabeculae treated with selective (diazoxide) and nonselective (adenosine) adenosine triphosphate-sensitive potassium channel opener (4.1 ± 0.01 and 4.4 ± 0.2 μmol/L per gram wet tissue) compared with trabeculae subjected to ischemia/reperfusion (1.5 ± 0.1 μmol/L per gram wet tissue). Conclusions: These results suggest that selective mitochondrial adenosine triphosphate-sensitive potassium channel activation preconditions human myocardium and the protection conferred is equal to that of adenosine preconditioning. Targeted openers of mitochondrial adenosine triphosphate-sensitive potassium channels promote constructive protection of myocellular energy levels, contractile function, and cellular viability in human myocardium after ischemia/reperfusion.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine