Effect of isoproterenol on regional myocardial segment work, O2 consumption, and oxygen balance

We tested the hypothesis that positive inotropic stimulation by isoproterenol alters the relationship between regional segment work and regional myocardial oxygen consumption. Regional parameters were compared with external cardiac work and global LV oxygen consumption. In anesthetized open-chest dogs, regional myocardial segment length (ultrasonic dimension crystals) and force development (miniature force transducer) were measured. The integrated multiples of myocardial shortening by corresponding force during an averaged beat expressed segment work (area under the systolic portion of the length-force loop). External cardiac work was calculated from aortic blood pressure and cardiac output. Global and regional myocardial MVO2 were evaluated at baseline and during intravenous infusion of isoproterenol (0.5 and 1.0 micrograms/kg per min). Regional coronary blood flow was measured with radioactive microspheres, and microspectrophotometry of frozen myocardial biopsies was used to evaluate O2 saturation in small arteries and veins. These parameters were used to calculate regional MVO2. Arterial and coronary sinus O2 saturation was used to calculate global LV O2 consumption. Regional myocardial O2 balance was estimated by measurement of NADH redox level using surface fluorometry. It was found that 0.5 micrograms/kg per min isoproterenol increased regional segment work/minute from 4650 +/- 495 to 6750 +/- 750 mm.g/min. Corresponding regional oxygen consumption was disproportionately increased from 5.43 +/- 0.61 to 15.24 +/- 1.37 ml/min per 100 g. External cardiac work was found to decrease from 728 +/- 13 to 562 +/- 25 mmHg.1/min (due to decreased aortic blood pressure), whereas global myocardial O2 consumption increased. Regional myocardial O2 extraction and NADH fluorescence were elevated, indicating impaired tissue oxygenation. Regional MVO2 was increased by 153 +/- 56%, but regional work by only 45.3 +/- 33% (P < 0.05). These results indicate that regional contraction efficiency was markedly reduced by isoproterenol.