Resuscitation of injured myocardium with adenosine and biventricular assist

Abstract

Recovery of energy metabolism and contractility in stunned myocardium requires several days, even when mechanical circulatory support is employed. This double-blind study was undertaken to determine if myocardial recovery could be accelerated by intracoronary infusion of adenosine during reperfusion. Ten mongrel dogs were subjected to 45 minutes of global normothermic ischemia while on biventricular support with centrifugal pumps. During initial reperfusion, 20 minutes later, and at hourly intervals for 4 hours, dogs received 100 mL/min of unaltered blood or blood enriched with adenosine (0.2 mmol/L) into the coronary arteries for 5 minutes. Circulatory support was discontinued after 4 hours or sooner if the first time derivative of left ventricular pressure exceeded 2,000 mm Hg/s. Animals that received adenosine were weaned sooner (72 ± 27 versus 216 ± 54 minutes) and had higher systolic pressure (110 ± 21 versus 57 ± 36 mm Hg), lower left ventricular end-diastolic pressure (23.8 ± 4.8 versus 34.0 ± 7.2 mm Hg), and higher first time derivative of left ventricular pressure (3,407 ± 812 versus 1,510 ± 1376 mm Hg/s) than controls at the completion of the experiment ( p < 0.05). Final myocardium adenosine triphosphate levels were higher in the adenosine group (20.0 ± 3.6 versus 14.2 ± 4.0 mgmol/g protein; p < 0.05). Determination of infusion and coronary sinus blood concentrations demonstrated a 90% uptake of adenosine. All adenosine animals survived, but 2 of 5 control animals died within 1 hour of weaning. Reperfusion with adenosine-enriched blood accelerated recovery of ischemic myocardium and should be considered for patients requiring mechanical circulatory support after a heart operation.