Increase in experimental infarct size with digoxin in a canine model of myocardial ischemia-reperfusion injury.
In the present study, dogs were pretreated with intravenous digoxin, 0.0125 mg/kg/day, for 6 to 7 consecutive days to achieve clinically relevant serum concentrations; untreated animals were used as control subjects. After pretreatment, nine digoxin-pretreated dogs and nine control dogs were anesthetized and subjected to a 60-minute occlusion of the left circumflex coronary artery, followed by 6 hours of reperfusion. Anatomic myocardial infarct size, expressed as a percentage of the areas at risk of infarction and as a percentage of the total left ventricle were: 20.2 +/- 3.3% control vs 35.4 +/- 6.2% digoxin-pretreated (p less than 0.05) and 8.6 +/- 1.3% control vs 14.7 +/- 2.5% digoxin-pretreated (p less than 0.05), respectively (2.04 +/- 0.37 ng/ml serum digoxin). Regional myocardial blood flow in the nonischemic and ischemic zones tended to be lower in digoxin-pretreated than in control animals at baseline testing and were significantly reduced in the anterior subendocardial sites of digoxin-pretreated dogs during ischemia and reperfusion. These data suggest that an exacerbation or enhancement of myocardial ischemia-reperfusion injury may occur in the presence of clinically observable serum digoxin concentrations.
Lynch
J J
JJ
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109.
Simpson
P J
PJ
Gallagher
K P
KP
McClanahan
T B
TB
Lee
K A
KA
Lucchesi
B R
BR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D004285:Dogs; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D011188:Potassium / Q000097:blood; D012964:Sodium / Q000097:blood
D004077:Digoxin; D012964:Sodium; D011188:Potassium