The purpose of this study was twofold: 1) to investigate the feasibility and usefulness of cardiac microdialysis for the simultaneous estimation of regional cardiac interstitial fluid (ISF) adenosine (ADO) concentration and coronary blood flow (CBF); and 2) to determine the changes in the ISF levels of ADO and CBF during cardiac stimulation or regional myocardial ischemia. Cardiac microdialysis probes were implanted in the left ventricular myocardium of chloralose-urethan-anesthetized dogs and perfused with Krebs-Henseleit buffer. The concentration of ADO in the effluent dialysate was used as an index of intramyocardial ISF ADO concentration while local CBF was measured by H2 clearance via a platinum wire within the dialysis fiber. Dialysate ADO was elevated immediately after insertion of the microdialysis probe, declined rapidly in the first 20 min, stabilized by 60 min, and remained constant for 2 h. Based on the relationship in vitro and in vivo between microdialysis probe perfusion rate and dialysate ADO concentration, ISF ADO concentration within the left ventricular myocardium was estimated to be 0.9-1.3 microM. Dobutamine (10 micrograms.kg-1.min-1) infusion resulted in a 36% increase in CBF and a 2.5-fold increase in dialysate ADO (n = 9; P less than 0.05). Regional myocardial ischemia, induced by occlusion of the left anterior descending artery (LAD), caused a 13-fold increase in dialysate ADO in the LAD perfused myocardium (n = 9; P less than 0.05). These results are consistent with the ADO hypothesis and suggest that cardiac microdialysis provides a reliable technique for the sampling of regional intramyocardial ISF.

The prolonged ventricular dysfunction following brief periods of coronary artery occlusion that does not produce irreversible damage has been termed the "stunned" myocardium. Although ventricular function returns to preischemic values by 1 to 7 days after reperfusion is established, inotropic therapy may be necessary to enhance contractility in the stunned heart. The purpose of this study was to determine the effect of pyruvate on ventricular function in normal and stunned myocardium. Eight chloralose/urethane anesthetized dogs were instrumented with ultrasonic crystals to measure systolic wall thickening in the left anterior descending artery (LAD) and left circumflex artery perfused regions of the left ventricle. Pyruvate (1 ml/min of 150 mM sodium pyruvate, pH 7.4) was infused directly into the LAD prior to and 30 minutes after a 10 minute LAD occlusion. Prior to LAD occlusion, LAD pyruvate infusion increased systolic wall thickening in the LAD-perfused region from 16.2% +/- 4.3% to 23.4% +/- 5.1% (p less than 0.05). Thirty minutes after LAD occlusion, regional wall thickening was depressed (3.3% +/- 2.6%; p less than 0.05), which is indicative of stunned myocardium. Subsequent LAD pyruvate infusion increased wall thickening in the stunned myocardium to 12.7% +/- 2.5%. The improvement of regional ventricular function was maintained only during the pyruvate infusion, as function returned to prepyruvate levels within 20 minutes after cessation of pyruvate infusion. These data indicate that pyruvate exerts a positive inotropic effect in normal and stunned myocardium. If pyruvate, a key intermediate in energy-producing pathways, exerts its inotropic effect through an enhancement of the energy state of the heart, it may have advantages over traditional inotropic agents in the treatment of postischemic contractile dysfunction.

While ISF adenosine is increased during acute systemic hypoxia and is increased in relation to the oxygen supply:demand imbalance, consistent with a role of adenosine in hypoxic hyperaemia in the heart, adenosine is not necessary for the maintenance of a sustained increase in coronary blood flow during hypoxia.

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