Vinten-Johansen J, Nakanishi K, Zhao Z Q, McGee D S, Tan P
Department of Cardiothoracic Surgery, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1096.
Circulation. 1993 Nov;88(5 Pt 2):II350-8.
Adenosine is a cardioprotective autacoid that exerts receptor-mediated protection from ischemia/reperfusion injury. In ischemically injured hearts, avoidance of ischemia/reperfusion injury with hypothermic chemical cardioplegia may be incomplete, and consequently, postischemic left ventricular (LV) function may be severely depressed and chamber stiffness increased. This study tested the hypothesis that the adenosine-regulating agent acadesine improves myocardial protection with hypothermic blood cardioplegia (BCP), resulting in better postischemic LV function and diastolic characteristics in hearts injured by 45 minutes of normothermic global ischemia.
Eighteen anesthetized (350 micrograms fentanyl citrate, 5 mg diazepam) dogs on total vented bypass were randomized to receive vehicle (n = 5), low-dose acadesine (LDA, 0.125 mg.kg-1.min-1, n = 6) or high-dose acadesine (HDA, 0.5 mg.kg-1.min-1, n = 7) continuously infused 30 minutes before global ischemia and discontinued 10 minutes after aortic cross-clamp removal. Hearts were protected with cold (4 degrees C) multidose (every 20 minutes) potassium BCP, which contained saline vehicle, 1 mg/L acadesine (LDA), or 4 mg/L acadesine (HDA) for a total of 1 hour of cardioplegic arrest. Postischemic LV function, assessed by the slope of the end-systolic pressure-volume (impedance catheter) relation, was depressed by 34 +/- 7% of baseline (5.6 +/- 1.0 versus 2.7 +/- 0.7 mm Hg/mL, P < .05) in vehicle. With LDA, there was variable improvement in postischemic function (5.1 +/- 1.3 versus 3.6 +/- 0.6 mm Hg/mL, P = .26 versus baseline). In contrast, there was complete postischemic functional recovery with HDA (5.9 +/- 0.6 versus 5.2 +/- 0.8 mm Hg/mL, P = .54). Postischemic chamber stiffness was preserved in both LDA and HDA.
We conclude that the higher dose of acadesine improves myocardial protection when used as a pretreatment and BCP adjuvant, resulting in better postischemic LV systolic function and diastolic characteristics.
