Effect of Inosine on Ventricular Regional Perfusion and Infarct Size after Coronary Occlusion

Abstract

In 16 dogs inosine was infused at 0.5 mmol/min i.v. for 5 min beginning 15 min after coronary occlusion. Tracer microspheres were used to estimate flow in subepicardium and subendocardium of nonischemic, central ischemic, and borderline ischemic muscle. Estimates of flow before occlusion, 5 min after occlusion, during inosine infusion, 30 min after infusion and 60 min after infusion were obtained. Coronary occlusion reduced flow in the central ischemic regions by 75-95%. The reduction in flow was greatest in subendocardium. In the borderline regions subendocardial flow was reduced by 30% while subepicardial flow was unaffected. The major effects of inosine were seen in nonischemic and borderline ischemic regions. Flow in borderline subendocardium returned to its pre-occlusion value, and flow in nonischemic myocardium increased by approximately 60-80%. However, only in the ischemic regions was the increase in flow sustained for the entire 60 min. In 20 dogs infarct size was determined using nitro blue tetrazolium stain. In 10 controls infarct size was 20.1%, while in 10 inosine-treated dogs infarct size was 15.2% of left ventricular weight (p < 0.01). Thus, following coronary occlusion inosine infusion was associated with an increase in perfusion of ischemic myocardium and a reduction in infarct size.

Inosine Inhibits Inflammatory Cytokine Production by a Posttranscriptional Mechanism and Protects Against Endotoxin-Induced Shock

“…For example, it prevents glial cell death during glucose deprivation (36,37), decreases the release of intracellular enzymes from hypoxic lymphocytes (38), improves renal function during ischemia (39,40), and removes the harmful effects of total hepatic ischemia (41). Inosine administration has also been shown to improve myocardial function during acute left ventricular failure (42,43) and decrease infarct size after coronary occlusion (44,45). Despite the accumulating evidence of inosine's protective effects, there is little information on the mode(s) of action of this metabolite in inflammatory/ischemic processes.…”

Inosine: a protective agent in an organ culture model of myocardial ischemia.

“…As mentioned in the introduction, exogenous inosine has been shown to increase myocardial blood flow and to salvage 25% of ischemic myocardium during canine coronary artery occlusion (Devous et al, 1979). This quantitation of myocardial salvage was determined by staining with nitro blue tetrazolium.…”

“…For example, Devous and Jones (1979) demonstrated a 25% reduction in canine myocardial infarct size when 2.5 mM inosine was administered 15 minutes after initiation of a 5-hour occlusion of the left anterior descending coronary artery. In these experiments, inosine was also found to increase myocardial perfusion, especially in borderline ischemic myocardium.…”

The influence of inosine on the size of myocardial ischaemia and myocardial metabolism in the pig*

“…Although the estimation of myocardial extraction ratio of substrates should be interpreted with caution in view of concomitant increase in myocardial blood flow induced by inosine (Devous & Jones, 1979), the results of these determinations allow the conclusion that myocardial metabolism is likely to be unaffected by inosine infusion. This most likely results from the fact that the area of ischaemic myocardium was relatively small.…”