Augmentation of myocardial digoxin concentration in hemorrhagic shock.
The effect of the shock state on myocardial digoxin uptake and plasma digoxin levels was examined in unanesthetized dogs following hemorrhage. Five minutes after intravenous administration of tritiated digoxin the myocardial digoxin content in animals with shock was greater than in normal animals in both left ventricle (LV) (165 plus or minus 15 (SD) ng/g vs 130 plus or minus 26 ng/g, P smaller than 0.02 and right ventricle (RV) (142 plus or minus 13 ng/g vs 111 plus or minus 22 ng/g. P smaller than 0.02) as was the plasma digoxin concentration (61.6 plus or minus 11.8 ng/ml vs 44.3 plus or minus 4.6 ng/ml, P smaller than 0.02). After one hour, in another group of dogs, the difference in myocardial concentration of digoxin between test and normal groups was even greater (LV: 213 plus or minus 26 ng/g vs 133 plus or minus 13 ng/g, P smaller than 0.001; RV: 171 plus or minus 9 ng/g vs 111 plus or minus 8 ng/g. P smaller than 0.001) despite lower plasma digoxin concentration in the test group (12.9 plus or minus 2.9 ng/ml vs 17.3 plus or minus 2.5 ng/ml, P smaller than 0.05). Diminished peripheral blood flow, peripheral digoxin delivery and uptake were probably responsible for the early difference in plasma digoxin levels. Resultant greater plasma concentrations of digoxin presented to the myocardium in the early phase, coupled with relative preservation of myocardial blood flow, may explain the greater myocardial uptake in animals with shock although myocardial mechanical factors may also be implicated. Augmented uptake of digoxin by the myocardium in canine hemorrhagic shock may be relevant to the altered susceptibility to glycoside action in clinical shock syndromes.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D004077:Digoxin / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006454:Hemoglobins / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010313:Partial Pressure; D011188:Potassium / Q000097:blood; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000378:metabolism*; D013997:Time Factors
D006454:Hemoglobins; D002245:Carbon Dioxide; D004077:Digoxin; D011188:Potassium