Protection against hypoxic injury in isolated-perfused rat heart by ruthenium red.
Changes in intracellular calcium content and energy production during the period of hypoxia appear to be necessary for the development of cellular injury. Ruthenium red, a hexavalent dye which inhibits the active uptake of calcium by mitochondria, might improve a cell's energy status thereby minimizing hypoxic injury. Rat heart tissue was perfused retrogradely with Krebs-Henseleit medium containing 2.5 mM calcium and 10 mM glucose. The infusion of 0.1, 1.0 or 1.24, but not 0.01 microM, ruthenium red throughout 60 min of hypoxia and 30 min of reoxygenation decreased, in a dose-dependent manner, the release of lactate dehydrogenase normally seen at reoxygenation. When the infusion of 1.24 microM ruthenium red was begun after 45 min of hypoxia, lactate dehydrogenase release at reoxygenation after 60 min of hypoxia was decreased, but to a lesser extent than when this agent was present throughout hypoxia. Ruthenium red, 1.24 microM, had no significant effects on coronary flow or function in oxygenated heart tissue. When present throughout hypoxia and reoxygenation, 1.24 microM ruthenium red prevented the decrease in coronary flow normally seen and allowed recovery of heart rate, +dP/dT, -dP/dT and work (defined as the product of developed pressure and heart rate) to normal levels. Significant functional protection was not evident at reoxygenation when ruthenium red was infused after 45 min of hypoxia or in the absence of glucose. Cardiac ATP, creatine phosphate and energy charge were decreased after 60 min of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin.
Y
Y
Park
D K
DK
Bowles
J P
JP
Kehrer
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012428:Ruthenium / Q000494:pharmacology*; D012430:Ruthenium Red / Q000494:pharmacology*
D012430:Ruthenium Red; D012428:Ruthenium; D007770:L-Lactate Dehydrogenase; D010100:Oxygen