Compared effects of ruthenium red and cis [Ru(NH3)4Cl2]Cl on the isolated ischaemic-reperfused rat heart.
The sequence ischaemia-reperfusion is characterized by reperfusion damage. The calcium overload occurring at the beginning of reperfusion is one of the main mechanisms responsible for reperfusion damage. Ruthenium red, a blocker of the mitochondrial calcium uniport system, could prevent this damage by preserving the ATP synthesis in the mitochondria. We tested ruthenium red and another ruthenium compound, cis-tetrammine dichlororuthenium (III) chloride in our experimental model of ischaemic-reperfused rat hearts. After a 15 minute-stabilization period, the hearts were submitted to a 30 minute global ischaemia period and then reperfused for 45 minutes with the standard perfusion solution or with ruthenium red or cis-tetrammine dichlororuthenium (III) chloride at 1, 3 or 9 microM. Ruthenium red at 3 microM exerted a protective effect in our experimental conditions by showing a significant improvement of the contractility recovery at the end of reperfusion and a significant decrease of the malondialdehyde production, which reflects free radical production. The cis-tetrammine dichlororuthenium (III) chloride (containing 1 Ru ion per molecule) at 9 microM was slightly less efficient than ruthenium red at 3 microM (containing 3 Ru ions per molecule). The heart ruthenium binding was better for the ruthenium red than for the cis-tetrammine dichlororuthenium (III) chloride, suggesting a role of the ruthenium ion complexation in the crossing of the membrane, whereas the cardiac effect seemed to be linked to the ruthenium ion heart concentration, which was similar for the ruthenium red at 3 microM and for the cis-tetrammine dichlororuthenium (III) chloride at 9 microM. One can hope that ruthenium compounds would limit reperfusion damage and infarct size after ischaemia in in vivo models.
Leperre
A
A
Laboratoire de Pharmacologie, Faculté de Médecine, Reims, France.
Millart
H
H
Prévost
A
A
Trenque
T
T
Kantelip
J P
JP
Keppler
B K
BK
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002317:Cardiovascular Agents / Q000378:metabolism / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017975:Ruthenium Compounds / Q000494:pharmacology*; D012430:Ruthenium Red / Q000378:metabolism / Q000494:pharmacology*
D002317:Cardiovascular Agents; D005609:Free Radicals; D009124:Muscle Proteins; D017975:Ruthenium Compounds; D012430:Ruthenium Red; D008315:Malondialdehyde; D003402:Creatine Kinase; D002118:Calcium