Reduction in infarct size by the phospholipase inhibitor quinacrine in dogs with coronary artery occlusion.
It has been suggested that activation of tissue phospholipases may contribute to the development of ischemic cell injury. In the present study we sought to assess whether administration of the phospholipase inhibitor quinacrine would reduce the extent of myocardial necrosis after coronary artery occlusion. In open-chest, anesthetized dogs the left anterior descending coronary artery was ligated, and technetium-99-labeled albumin microspheres were injected into the left atrium to measure the area at risk. The animals were then randomly divided into a control group (n = 8) and a group receiving quinacrine (5 mg/kg intravenous bolus followed by a 40 micrograms/kg/min infusion for 6 hours; n = 9). The animals were killed 6 hours after occlusion, and the infarcted area was delineated by triphenyltetrazolium chloride staining. The extent of the risk region was similar in the two groups (32.3 +/- 2.1% of the left ventricle in control dogs and 34.2 +/- 3.4% in quinacrine-treated dogs). Infarct size was 86.4 +/- 8.8% of the risk region in control animals, whereas in treated dogs it averaged 62.3 +/- 6.4% of the risk region (p = 0.05). No differences were found in heart rate, arterial pressure, and rate-pressure product between the two groups. Thus administration of the phospholipase inhibitor quinacrine reduced the extent of myocardial necrosis in a model of fixed coronary artery occlusion. Preservation of membrane phospholipids, reduced formation of lipoxygenase metabolites, or both may mediate this phenomenon.
Chiariello
M
M
Department of Medicine, Second School of Medicine, University of Naples, Italy.
Ambrosio
G
G
Cappelli-Bigazzi
M
M
Perrone-Filardi
P
P
Tritto
I
I
Nevola
E
E
Golino
P
P
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D006439:Hemodynamics; D009203:Myocardial Infarction / Q000188:drug therapy / Q000517:prevention & control; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009336:Necrosis; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010743:Phospholipids / Q000032:analysis; D011796:Quinacrine / Q000627:therapeutic use*
D010743:Phospholipids; D010740:Phospholipases; D011796:Quinacrine