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Am J Physiol Heart Circ Physiol (October 9, 2003). doi:10.1152/ajpheart.00022.2003
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Submitted on January 13, 2003
Accepted on September 22, 2003

Responses of Chronically Hypoxic Rat Hearts to Ischemia: KATP-Channel Blockade Does Not Abolish Increased Right Ventricular Tolerance to Ischemia

Joerg Forkel1, Xiaochao Chen2, Susanne Wandinger1, Florian Keser1, Alexey Duschin2, Uwe Schwanke2, Stilla Frede3, Parwis Massoudy1, Rainer Schulz2, Heinz Jakob1, and Gerd Heusch2*

1 Division of Cardiothoracic Surgery, University of Essen, Essen, Germany
2 Institute of Pathophysiology, University of Essen, Essen, Germany
3 Institute of Physiology, University of Essen, Essen, Germany

* To whom correspondence should be addressed. E-mail: gerd.heusch{at}uni-essen.de.

Chronic hypoxia may precondition the myocardium and protect from ischemia/reperfusion damage. We therefore examined the recovery of left and right ventricular function after ischemia and reperfusion (15min each) in isolated bloodperfused working hearts from normoxic (Norm) and hypoxic (Hypo, 14 days 10.5% O2) adult rats. In addition, the mRNA expression of hypoxia inducible factor (HIF)-1{alpha} and the protein expression of endothelial NOS (eNOS) were measured. Postischemic left ventricular function recovered to 66±6% and 67±5% of baseline in Norm and Hypo, respectively. In contrast, postischemic right ventricular function was 93±2% of baseline in Hypo vs. 67±3% in Norm (p<0.05). Improved postischemic right ventricular function in Hypo (93±2% and 96±2% of baseline) was observed with 95% O2 or 21% O2 in the perfusate, and it was not attenuated by glibenclamide (5µmol/L,10µmol/L) (86±4% and 106±6% recovery). HIF-1{alpha} mRNA and eNOS protein expression were increased in both left and right hypoxic ventricles. In cnclusion, postischemic right, but not left ventricular function was improved by preceding chronic hypoxia. KATP-channels are not responsible for the increased right ventricular tolerance to ischemia following chronic hypoxia of adult rat hearts.




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