Transgenic A1 adenosine receptor overexpression markedly improves myocardial energy state during ischemia-reperfusion.
A1 adenosine (A1AR) activation may reduce ischemia-reperfusion injury. Metabolic and functional responses to 30 min global normothermic ischemia and 20 min reperfusion were compared in wild-type and transgenic mouse hearts with approximately 100-fold overexpression of coupled cardiac A1ARs. 31P-NMR spectroscopy revealed that ATP was better preserved in transgenic v wild-type hearts: 53 +/- 11% of preischemic ATP remained after ischemia in transgenic hearts v only 4 +/- 4% in wild-type hearts. However, recovery of ATP after reperfusion was similar in transgenic (46 +/- 5%) and wild-type hearts (37 +/- 12%). Reductions in phosphocreatine (PCr) and cytosolic pH during ischemia were similar in both groups. However, recovery of PCR on reperfusion was higher in transgenic (67 +/- 8%) v wild-type hearts (36 +/- 8%), and recovery of pH was greater in transgenic (pH = 7.11 +/- 0.05) v wild-type hearts (pH = 6.90 +/- 0.02). Bioenergetic state ([ATP]/[ADP].[Pi]) was higher in transgenic v wild-type hearts during ischemia-reperfusion. Time to ischemic contracture was prolonged in transgenic (13.6 +/- 0.8 min) v wild-type hearts (10.4 +/- 0.3 min). Degree of contracture was lower and recovery of function in reperfusion higher in transgenic v wild-type hearts. In conclusion, A1AR overexpression reduces ATP loss and improves bioenergetic state during severe ischemic insult and reperfusion. These changes may contribute to improved functional tolerance.
Headrick
J P
JP
Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Gauthier
N S
NS
Berr
S S
SS
Morrison
R R
RR
Matherne
G P
GP
D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000235:genetics*
D018047:Receptors, Purinergic P1