Inosine: a protective agent in an organ culture model of myocardial ischemia

Circ Res. 1982 Aug;51(2):181-8. doi: 10.1161/01.res.51.2.181.

Abstract

Fetal mouse hearts in organ culture provide a model of ischemic-like injury in which the myocardial protective effect of pharmacological agents can be studied independent of blood flow. To investigate the potential protective effect of a diffusable purine under ischemic-like conditions, we used 4 mM inosine in fetal mouse heart organ cultures deprived of oxygen and oxidizable substrates for 1-10 hours. We studied hearts (n = 258) immediately after simulated ischemia (early) and after a 20-hour recovery period (late), by utilizing three indices of myocardial viability. Thallium-201 accumulation is an early marker of myocardial viability during injury, whereas the percentage of lactic dehydrogenase release from hearts to culture medium and the percentage of irreversibly injured myocytes assessed by planimetry of midventricular histological sections are late markers, used after recovery from injury. At 10 hours of injury, thallium-201 accumulation was 38% greater in inosine-supplied hearts, 3.50 +/- 0.16 vs. 2.54 +/- 0.08 (counts/min per mg wet weight)/(counts/min per microliter medium) (mean +/- SEM) (P less than 0.001). After recovery from 10 hours of injury, lactic dehydrogenase release was 29% less in inosine-supplied hearts, 35 +/- 3% vs. 49 +/- 3% (P less than 0.001). After recovery from 8 hours of injury, the percentage of histologically irreversibly injured tissue was 23% less in inosine-supplied hearts, 60 +/- 7% vs. 78 +/- 3% (P less than 0.05). These data indicate that inosine has a protective effect on fetal mouse myocardium during simulated ischemia and suggest that inosine deserves further evaluation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Coronary Disease / drug therapy*
  • Coronary Disease / pathology
  • Coronary Disease / physiopathology
  • Female
  • Fetal Heart
  • Inosine / pharmacology*
  • L-Lactate Dehydrogenase / analysis
  • Mice
  • Models, Cardiovascular
  • Myocardium / pathology
  • Organ Culture Techniques
  • Radioisotopes
  • Thallium

Substances

  • Radioisotopes
  • Inosine
  • Thallium
  • L-Lactate Dehydrogenase