Reperfusion injury in ischemic myocardium: protective effects of ruthenium red and of nitroprusside.
Coronary reperfusion following myocardial ischemia may result in further damage to injured myocytes, as judged by their ultrastructural appearance. Ruthenium red is an inorganic dye with calcium flux-inhibiting properties which protects ischemic myocardium against reperfusion damage, as judged by biochemical indices of mitochondrial function. In this study, we produced myocardial ischemia in pigs by means of reversible coronary artery occlusion. The pigs were infused with either ruthenium red or nitroprusside (an after-load reducing agent with no known calcium flux-inhibiting properties) prior to and during coronary reperfusion. During reperfusion, both ruthenium red and nitroprusside produced similar lowering of mean arterial pressure, while mean arterial pressure rose in pigs not receiving these drugs. Myocardial samples from the ischemic reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and glycogen depletion were graded independently on a three-point scale by two investigators. For each of the organelles studied, ischemic damage was significantly less for treated animals than for controls. This protective effect was similar for both ruthenium red-treated animals and nitroprusside-treated animals. These results suggest that the protective effects of ruthenium red treatment are attributable to its afterload reducing properties rather than to inhibition of transmembrane calcium flux in cardiac fibers.
Carry
M M
MM
Division of Medicine, John L. McClellan Memorial Veterans Hospital, Little Rock, Arkansas.
Mrak
R E
RE
Murphy
M L
ML
Peng
C F
CF
Straub
K D
KD
Fody
E P
EP
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003327:Coronary Disease / Q000150:complications* / Q000473:pathology; D006321:Heart / Q000187:drug effects; D008854:Microscopy, Electron; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009599:Nitroprusside / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D013552:Swine
D012430:Ruthenium Red; D009599:Nitroprusside; D002118:Calcium