Alter Infarct Size Research Articles

Effect of the Thromboxane Receptor Antagonist SQ 29,548 on Myocardial Infarct Size in Dogs

The effect of thromboxane A2/prostaglandin endoperoxide receptor blockade on infarct size following myocardial ischemia plus reperfusion was determined in dogs. In anesthetized dogs SQ 29,548 (0.2 mg/kg/h) caused a 1,000-fold shift in the dose flow-response curve of renal and mesenteric beds to U-46619, indicating potent receptor blockade. The vasoconstrictor response of the left circumflex coronary artery (LCX) to U-46619 was completely inhibited by SQ 29,548. Three additional groups of anesthetized dogs were subjected to LCX occlusion and 10 min later were given (a) SQ 29,548 (0.2 mg/kg loading dose + 0.2 mg/kg/h infusion intravenously, i.v., n = 7), a thromboxane A2/prostaglandin endoperoxide receptor antagonist; (b) vehicle (n = 7); and (c) SQ 28,585 (0.2 mg/kg loading dose + 0.2 mg/kg/h infusion i.v., n = 3), an inactive compound structurally related to SQ 29,548. After 90 min of occlusion, the LCX was reperfused for 5 h. The area at risk and infarct size were then determined. The cardiac area at risk was similar in size for all groups. Infarct size as a percentage of the total area at risk was large, 79 +/- 2% in vehicle controls, but this was markedly reduced to 45 +/- 8% with SQ 29,548 treatment. SQ 28,585 did not alter infarct size as compared with vehicle controls. Area at risk and infarct size were highly correlated (r = 0.95) in vehicle-treated animals. None of the drug treatments resulted in a significantly altered hemodynamic status. Thus, blockade of thromboxane A2/prostaglandin endoperoxide receptors during ischemia plus reperfusion resulted in a significant salvage of myocardial tissue and suggests a deleterious role for thromboxane A2 in ischemia.

Influence of sulfinpyrazone and naproxen on infarct size in the dog

To assess the potential role of platelet inhibitory agents in the treatment of myocardial infarction, the effect on infarct size of two platelet inhibitors, sulfinpyrazone and naproxen, was evaluated. In addition to platelet inhibition, sulfinpyrazone increases epicardial collateral flow and naproxen has lysosomal-stabilizing activity. Thirty-eight open chest dogs were given intravenously sulfinpyrazone (30 mg/kg, n = 11), naproxen (30 mg/kg, n = 14) or saline solution (n = 13) 10 minutes before and 3 and 6 hours after ligation of the mid left anterior descending coronary artery. Drug doses were sufficient to inhibit adenosine diphosphate-induced platelet aggregation. The dogs were killed 72 hours after occlusion. Myocardium at risk of infarction—that is, the area supplied by the occluded artery (anatomic risk area)—was identified by simultaneous perfusion of the aortic root with Evans blue and of the coronary artery distal to the occlusion with clear saline solution. Hearts were sliced horizontally and stained with triphenyl-tetrazolium-chloride. The infarcted area and anatomic risk area were measured with videoplanimetry. The percent of left ventricle infarcted was not significantly different among the control, sulfinpyrazone and naproxen groups (28 ± 2, 30 ± 1, 28 ± 2 percent, respectively) nor was percent of anatomic risk area infarcted significantly different (75 ± 3, 79 ± 3, 75 ± 3 percent, respectively). Thus, neither sulfinpyrazone nor naproxen in platelet inhibitory doses altered infarct size. These results indicate that neither inhibitory effects on platelet function and prostaglandin synthesis nor associated lysosomal-stabilizing properties identify agents with consistent infarct-sparing action.

Changes in myocardial oxygen consumption 45 minutes after experimental coronary occlusion do not alter infarct size.

The influence of myocardial oxygen consumption (MVO2) at the moment of coronary occlusion on the size of the ensuing infarct was investigated in two groups of anaesthetised dogs. In one group (n = 9) coronary occlusion was produced at a high MVO2, estimated to be 14.6 +/- 2.1 cm3 O2 X min-1 X 100g-1 which was changed midway during the occlusion period of 90 min to a low MVO2 estimated to be 6.7 +/- 1.6. In the second group (n = 9) the MVO2, was elevated after 45 min an estimate of 5.1 +/- 0.9 to one of 13.2 +/- 3.7 cm3 X min-1 X 100g-1. In this way the MVO2 averaged over the entire 90 min occlusion period was equal in both groups. Infarct size expressed as a percentage of perfusion area was 68 +/- 28% in group 1 and 32 +/- 30% in group 2 (P less than 0.025). The mass of the perfusion areas did not differ significantly between the groups. Haemodynamics changes were similar in both groups except for a higher rate in group 1 in the period with low MVO2 (109 vs 66 per min, P less than 0.001). Collateral flow was not different between the two groups 45 min after occlusion. It is concluded that the MOV2 at the moment of occlusion significantly influences infarct size. Drastic changes of MVO2 induced at 45 min (ie at half time of the occlusion period of 90 min) had no measurable effect on infarct size.

Small Animal Model for Myocardial Infarction

Myocardial infarctions were produced in rats by electrocauterization of the left anterior descending artery, and the extent of myocardial damage was measured by serial serum levels of creatine phosphokinase activity utilizing spectrophotometric analysis. All animals were also evaluated for myocardial damage by electrocardiographic wave alterations. A correlation between myocardial infarct size and serum creatine phosphokinase was demonstrated. Significant arrhythmias and death occurred only in experimental groups where myocardial infarction had been produced. This small animal model offers a quick, inexpensive, and simple method for screening therapeutic agents that alter infarct size.