Stabilization of left ventricular function with D-(-)-3-hydroxybutyrate after coronary occlusion in the intact dog

The D-(-) isomer or natural form of 3-hydroxybutyrate (D-(-)-3OHB) is a readily used energy substrate. Studies on anesthetized intact dogs in our laboratory have demonstrated that raising the arterial level of D-(-)-3OHB to 1 mM enhances the ketone uptake not only by the normal, but also by the acutely ischemic myocardium, though at a lower rate. Whether this moderate rise in arterial D-(-)-3OHB does modify the time course of left ventricular (LV) function during acute regional ischemia remains unsettled. In the present study, 13 anesthetized intact dogs with occluded left anterior descending (LAD) coronary artery (balloon catheter) were infused with D-(-)-3OHB as the L-(+)-arginine salt at a rate of 20 mumol/kg/min i.v. for 90 min, starting 40 min after the LAD occlusion. Arterial D-(-)-3OHB rose to 1.1 mM. Arterial pH was not modified. By comparison with the decline observed in 13 saline-treated ischemic dogs, the ketone treatment significantly stabilized the time course of LV peak positive dP/dt and output per minute. This effect was not attributable to the simultaneous infusion of arginine since it was not observed with equimolar infusions of this amino acid alone in eight additional ischemic dogs.