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)