Long-Term Preservation of Ischemic Myocardium after Experimental Coronary Artery Occlusion

Abstract

A B S T R A C T The results of experiments with indirect methods have suggested that various interventions reduce infarct size after coronary artery occlusion. To determine and quantify directly both the shortand long-term effects of several interventions on myocardial salvage without relying on indirect methods, the left coronary artery was occluded in 880 rats; they were then given either no treatment or one of the following interventions: (a) hyaluronidase, an enzyme that hydrolyzes interstitial glycoproteins, 1,500 National Formulary (NF) U/kg i.v. 5 min and 24 h after occlusion; (b) cobra venom factor, a protein that depletes the third component of complement, 20 U/kg i.v. 5 min after occlusion; (c) a glucocorticoid: hydrocortisone, 50 mg/kg i.v. 5 min after occlusion; or the fivefold more potent methylprednisolone (MP): (i) 50 mg/kg i.v. 5 min after occlusion or (ii) 50 mg/kg i.v. 5 min after occlusion followed by 50 mg/kg i.m. 3, 6, and 24 h after occlusion; or (d) reserpine, an agent that depletes the heart of catecholamines, 0.5 mg/kg i.m. once on each of the 3 days before occlusion. The animals were sacrificed either 2 days after occlusion, i.e., at the time of peak necrosis, or after 3 wk, i.e., after the infarct was completely healed. The amount of preserved myocardium was then assessed by two independent techniques: planimetric measurement of serial histologic sections and creatine kinase activity of the whole left ventricle. The amount of normal myocardium preserved at 21 days postocclusion was significantly increased, by 22.3±7.8% (P < 0.025) after the administration of hyaluronidase, by 25.3 ±5.8% (P < 0.005) after cobra venom factor, by 14.5 ±6.9% (P < 0.05) after hydrocortisone, by 20.8±8.2% (P < 0.025) after the single dose of MP, by 20.9±3.9% (P < 0

Atrial natriuretic peptide in a rat model of cardiac failure. Atrial and ventricular mRNA, atrial content, plasma levels, and effect of volume loading.

“…Infarction was produced by left coronary arterial ligation as described previously14 and as modified by MacLean et al 15 In male Sprague-Dawley rats, the left coronary artery was ligated approximately 2 mm from its origin with a 6-0 suture. In the shamoperated rats, the suture was tied loosely so as not to obstruct coronary flow.…”

The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction.

“…This value is comparable to that reported by Weiblen et al '8 The time course of the infiltration of leukocytes into infarcted myocardium has been well characterized. In animal models of permanent coronary artery occlusion, leukocytes migrate to regions of myocardial injury within 24 hours, reaching a peak within [4][5] days. '9 However, Sommers and Jennings20 reported that reinstituting myocardial blood flow after temporary coronary artery occlusion accelerated the infiltration of inflammatory cells into injured myocardium.…”

“…Several agents are effective in reducing the extent of myocardial infarction resulting from experimentally induced acute myocardial ischemia in a variety of animal models.1 One such agent, ibuprofen, is a nonsteroidal antiinflammatory compound that has been reported to exert cardioprotective effects by significantly reducing the extent of irreversible myocardial injury to experimental ischemia in the dog,2'3 the cat,4 and the rat.5 Ibuprofen renders its cardioprotective effects administered orally,3 intravenously2 or intramuscularly. 5 Several independent investigators have demonstrated protective effects in a variety of experimental models of myocardial ischemia and infarction, but little is known about ibuprofen's mechanism of action. Apparently, the beneficial effects of ibuprofen do not derive from alteration of the balance of myocardial oxygen supply and demand in a favorable manner.…”

Neutrophil chemoattractants generated in two phases during reperfusion of ischemic myocardium in the rabbit. Evidence for a role for C5a and interleukin-8.

“…Clq and products of complement activation, e.g., C3b and CSb-9, have been detected in infarcted myocardium (11)(12)(13) and in the systemic circulation ( 14). Moreover, agents such as cobra venom factor or soluble complement receptor-i which deplete or inactivate complement have been shown to reduce infarct size in animal models (15,16). Activation of the complement system results in the liberation of several soluble products, amongst which is the cleavage product of the fifth component, CSa.…”