Inhibition of surgically induced ischemia/reperfusion injury by oxygen free radical scavengers.
Recent experimental work implicates oxygen free radicals as mediators of ischemia/reperfusion injury. A simple cardioplegic solution was designed to scavenge superoxide anion and hydroxyl free radical with superoxide dismutase (10 micrograms/ml), mannitol (325 mOsm/L), and KCl 25 mEq/L (FRS). Hemodynamic and subcellular functions were studied in seven in situ canine models of hypothermic global ischemia receiving FRS, compared to a group (n = 7) receiving hyperosmolar, hyperkalemic saline (HSK) and to a standard model of topical hypothermia (TH, n = 5). Following 60 minutes of ischemia (10 degrees to 15 degrees C), hearts were reperfused and rewarmed. After 45 minutes of reperfusion, left ventricular peak systolic pressure (LVPSP), developed pressure (LVDP), dP/dt max, -dP/dt max, compliance, and elastic stiffness constant (K) were improved in the FRS group and not significantly different from control. Sarcoplasmic reticulum (SR) calcium transport in the FRS group was significantly improved (control = 1.077 +/- 0.022, TH = 0.754 +/- 0.018, HSK = 0.725 +/- 0.05, and FRS = 0.966 +/- 0.05 mumol/mg-min). Calcium adenosine triphosphatase (ATPase) activity did not differ significantly from control at pH 7.0. In this model of hypothermic global ischemia and reperfusion, free radical scavengers provide significant protection of mechanical and subcellular function. These findings support the hypothesis that oxygen free radicals are important mediators of myocardial ischemia and reperfusion injury.
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002315:Cardiopulmonary Bypass; D004285:Dogs; D005260:Female; D005609:Free Radicals; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen; D011183:Postoperative Complications; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology
D005609:Free Radicals; D013482:Superoxide Dismutase; D010100:Oxygen; D002118:Calcium