Protective Effect of Adenosine in Feline Model of Acute Myocardial Ischemia-Reperfusion

ABSTRACT

BACKGROUND: Reestabilshment of blood flow is a standard therapeutic modality to salvage the myocardium at risk in an acute phase of myocardial infarction. However, there are significant evidences that reperfusion per se may injure the potentially viable myocardium, and a number of pharmacological agents were tried to reduce this reperfusion injury. Adenosine, an endogenous vasodilator, is suggested to reduce repergusion inury. To evaluate the myocardial protective effect of adenosine, magnetic resonance spectroscopy with superscript P was applied to feline model of acute myocardial ischemia-reperfusion, as well as pathological examination. METHODS: Effects of adenosine on the recovery of high energy phosphorous metabolites during 90 minutes of reperfusion period following 90 minutes of left anterior descending coronary artery ligation were assessed by31P spectroscopy in 27 cats(10 control group, 8 adenosine I group, 9 adenosine II group). In adenosine groups 0.2 mg/kg/min of adenosine was infused intravenously for 90 minutes from 30 miniutes before reperfusion in group I, and from just before reperfusion in group II. The experiments were performed on a 4.7 T/30 cm Biospec MRS/MRI system and the MR signals were obtained by using inner-diameter 1.5 cm-sized doubly tuned surface coil. The size of the spectral peaks was measured by area integration method. RESULTS: 1) Phosphocreatine(PCr) decreased rapidly with progression of ischemia, and recovered in reperfusion period in each group. PCr values in the reperfusion period were significantly higher in adenosine group than those in control group, although there was no difference between adenosine group I and II. 2) ATP decreased with progression of ischemia, and recovered in reperfusion period in each group. ATP values in the reperfusion period were significantly higher in adenosine groups than those in control group, byt there was no difference between adenosine group I and II. 3) pH decreased uniformly with progression of ischemia and recovered in reperfusion period, showing no difference between control and adenosine groups. 4) PCr/ATP ratio, representing the potential of oxidative phosphorylation, dereased with progression of ischemia and increased in reperfusion period. PCr/ATP ratio showed no difference between control, adenosine I and II groups. 5) Risk area/left ventricle ratio was not different in control and adenosine groups. Infarct size/risk area and infarct size/left ventricle ratios were smaller in adenosine II than those in control group. Howerver no significant diffence was noticed between adenosine I and control, and between adenosine I and II group. CONCLUSION: Intravenous infusion of adenosine showed the tendency of reducing the infarct size in the feline model of acute myocardial ischemia-reperfusion, and adenosine could improve significantly the recovery of high energy phosphate metabolites. This myocardial pretective effect of adenosine is considered to be present mainly in the reperfusion period.