Oxygen transport during anemic hypoxia in pigs: effects of digoxin on metabolism.
We tested whether digoxin would limit tissue hypoxia during severe anemia by improving peripheral O2 distribution or decreasing O2 demands. Hematocrit (Hct) was reduced in eight control and eight digoxin-treated pigs from 27-28% to 17-18, 11-12, and 7-8%. Whole body and hindlimb blood flow, O2 transport, O2 extraction, and O2 consumption and serum catecholamines (epinephrine and norepinephrine) were determined at each Hct. Arterial and femoral venous lactate and O2 deficit were obtained to reflect tissue hypoxia. Cardiac output was significantly greater (P less than 0.05) with digoxin, as expected, but there were no differences in hindlimb blood flow. Also, whole body and hindlimb O2 extractions were equal in both groups for similar levels of O2 transport, suggesting that digoxin did not alter the relationship of O2 flow to metabolism in regional circulations. As whole body O2 consumption fell, controls accumulated more (P less than 0.05) O2 deficit and arterial lactate than the digoxin group. Furthermore, the slope demonstrating the linear increase of lactate with respect to O2 deficit was much steeper in controls (y = 1.11 + 0.06x) than in digoxin (y = 1.36 + 0.02x), suggesting that there were differences in the degree of tissue hypoxia for comparable O2 deficit. This may be attributed to the marked differences in catecholamine response: epinephrine was higher in controls at Hct of 7-8% and norepinephrine was higher at Hcts of 11-12 and 7-8%. Digoxin may have inhibited the release of catecholamine or reduced the stimulus for catecholamine secretion during anemia. We speculate that digoxin markedly improved the balance between peripheral O2 supply and demand during anemia by inhibiting catecholamine thermogenesis, thereby decreasing O2 demands. This may explain some of the salutary effects of glycosides in high-output cardiac failure with normal ventricular function.
Saltiel
A
A
Department of Pediatrics, Yale University, New Haven, Connecticut 06510.
Sanfilippo
D J
DJ
Hendler
R
R
Lister
G
G
D000740:Anemia / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004077:Digoxin / Q000494:pharmacology*; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D010100:Oxygen / Q000493:pharmacokinetics*; D010101:Oxygen Consumption / Q000187:drug effects; D013552:Swine
D002395:Catecholamines; D007773:Lactates; D019344:Lactic Acid; D004077:Digoxin; D010100:Oxygen