Altered Distribution of Tritiated Digoxin in the Infarcted Canine Left Ventricle

In order to determine the distribution pattern of digoxin in infarcted and ischemic tissue, the early uptake of tritiated digoxin (3H-digoxin) in the acutely and chronically infarcted canine left ventricle (LV) was studied. Seven open-chest anesthetized dogs were given 3H-digoxin intravenously 1 hour following acute anterior-wall infarction produced by serial coronary arterial branch ligations. Central and peripheral zones of infarction, ischemic border zones, and nonischemic myocardium were demarcated by epicardial electrode mapping. Two hours after 3H-digoxin administration, animals were sacrificed and epicardial and endocardial samples from each zone were analyzed for 3H-digoxin uptake. Significantly lower digoxin concentrations (ng/g wet weight ± (SEM) were found in both endocardial (endo) and epicardial (epi) regions of the center (endo 27 ± 11; epi 58 ± 10) and periphery (endo 51 ± 13; epi 112 ± 13) of the infarct as compared to the border (endo 217 ± 21; epi 242 ± 15) and nonischemic (endo 256 ± 22; epi 220 ± 20) zones. Significant transmural gradients of the glycoside observed in infarct zones (endo/epi ratio 0.46) were the reverse of those found in nonischemic portions of the myocardium (endo/epi ratio 1.16). Four dogs with chronic infarcts showed 3H-digoxin uptake patterns similar to acutely infarcted animals. In four sham-operated dogs, 3H-digoxin uptake was homogeneous in all areas of the LV. This marked alteration of early 3H-digoxin uptake by the infarcted LV may predispose to electrical instability and the genesis of ectopic rhythm disturbances. The pattern of LV digoxin uptake appears to reflect, at least in part, regional blood flow to infarcted, ischemic, and nonischemic tissue.

[1]  T. Smith.  Contribution of Quantitative Assay Technics to the Understanding of the Clinical Pharmacology of Digitalis , 1972, Circulation.

[2]  D. Harrison,et al.  The relation between myocardial 3 H-digoxin concentration and its hemodynamic effects. , 1972, The American journal of cardiology.

[3]  J. Han.  The concepts of reentrant activity responsible for ectopic rhythms. , 1971, The American journal of cardiology.

[4]  S. Kaihara,et al.  Regional myocardial blood flow in the dog studied with radioactive microspheres. , 1971, Cardiovascular research.

[5]  W. Abelmann,et al.  Digitalis intoxication. , 1971, Lancet.

[6]  T. Akera,et al.  MEMBRANE ADENOSINE TRIPHOSPHATASE: THE EFFECT OF POTASSIUM ON THE FORMATION AND DISSOCIATION OF THE OUABAIN-ENZYME COMPLEX , 1971 .

[7]  L. Becker,et al.  Effect of Ischemia and Antianginal Drugs on the Distribution of Radioactive Microspheres in the Canine Left Ventricle , 1971, Circulation research.

[8]  J. Covell,et al.  Factors Influencing Infarct Size Following Experimental Coronary Artery Occlusions , 1971, Circulation.

[9]  J. C. Norman,et al.  Experimental myocardial infarction. VI. Efficacy and toxicity of digitalis in acute and healing phase in intact conscious dogs. , 1970, The Journal of clinical investigation.

[10]  J. C. Norman,et al.  Experimental myocardial infarction. I. Production of left ventricular failure by gradual coronary occlusion in intact conscious dogs. , 1970, Cardiovascular research.

[11]  J. Han,et al.  Mechanisms of ventricular arrhythmias associated with myocardial infarction. , 1969, The American journal of cardiology.

[12]  M. Noble,et al.  Total and Regional Coronary Blood Flow Measured by Radioactive Microspheres in Conscious and Anesthetized Dogs , 1969, Circulation research.

[13]  R. Whalen,et al.  Digitalis and experimental myocardial infarction. , 1969, American heart journal.

[14]  F. Marcus,et al.  Alteration of the body distribution of tritiated digoxin by acute hyperkalemia in the dog. , 1969, Journal of Pharmacology and Experimental Therapeutics.

[15]  D. Griggs,et al.  Effect of coronary constriction on myocardial distribution of iodoantipyrine-131-I. , 1968, The American journal of physiology.

[16]  R. Albers,et al.  Studies on the interaction of ouabain and other cardio-active steroids with sodium-potassium-activated adenosine triphosphatase. , 1968, Molecular pharmacology.

[17]  J. P. Manning,et al.  Cardiac alkaline and acid phosphatase activity and potassium concentration in dogs with acute myocardial infarction. , 1968, Cardiovascular research.

[18]  J. Doherty.  The Clinical Pharmacology of Digitalis Glycosides: A Review , 1968, The American journal of the medical sciences.

[19]  H. Matsui,et al.  Mechanism of cardiac glycoside inhibition of the (Na+-K+)-dependent ATPase from cardiac tissue. , 1968, Biochimica et biophysica acta.

[20]  W. Hood,et al.  Myocardial Infarction Following Coronary Ligation in Dogs: Hemodynamic Effects of Isoproterenol And Acetylstrophanthidin , 1967, Circulation research.

[21]  J. Doherty,et al.  Tissue concentration and turnover of tritiated digoxin in dogs. , 1966, The American journal of cardiology.

[22]  D. Singer,et al.  Effects of digitalis on electrical activity of cardiac fibers , 1964 .

[23]  R. Jennings,et al.  Electrolyte Alterations in Acute Myocardial Ischemic Injury , 1964, Circulation research.

[24]  G. Moe,et al.  Nonuniform Recovery of Excitability in Ventricular Muscle , 1964, Circulation research.

[25]  George A. Bray,et al.  A simple efficient liquid scintillator for counting aqueous solutions in a liquid scintillation counter , 1960 .

[26]  G. Moe,et al.  The Action of Several Cardiac Glycosides on Conduction Velocity and Ventricular Excitability in the Dog Heart , 1951, Circulation.

[27]  George W. Snedecor,et al.  Statistical methods applied to experiments in agriculture and biology. , 1946 .

[28]  W. Modell,et al.  EFFECT OF EXPERIMENTAL CARDIAC INFARCTION ON RESPONSE TO DIGITALIS , 1938 .