COMPARED EFFECTS OF RUTHENIUM RED AND CIS [RU(NH3)(4)CL-2]CL ON THE ISOLATED ISCHEMIC-REPERFUSED RAT-HEART

The sequence ischaemia-reperfusion is characterized by reperfusion dam age. The calcium overload occurring at the beginning of reperfusion is one of the main mechanisms responsible for reperfusion damage. Ruthen ium red, a blocker of the mitochondrial calcium uniport system, could prevent this damage by preserving the ATP synthesis in the mitochondri a. We tested ruthenium red and another ruthenium compound, cis-tetramm ine dichlororuthenium (III) chloride in our experimental model of isch aemic-reperfused rat hearts. After a 15 minute-stabilization period, t he hearts were submitted to a 30 minute global ischaemia period and th en reperfused for 45 minutes with the standard perfusion solution or w ith ruthenium red or cis-tetrammine dichlororuthenium (III) chloride a t 1, 3 or 9 mu M. Ruthenium red at 3 mu M exerted a protective effect in our experimental conditions by showing a significant improvement of the contractility recovery at the end of reperfusion and a significan t decrease of the malondialdehyde production, which reflects free radi cal production. The cis-tetrammine dichlororuthenium (III) chloride (c ontaining 1 Ru ion per molecule) at 9 mu M was slighty less efficient than ruthenium red at 3 mu M (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, wherea s the cardiac effect seemed to be linked to the ruthenium ion heart co ncentration, which was similar for the ruthenium red at 3 mu M and for the cis-tetrammine dichlororuthenium (III) chloride at 9 mu M. One ca n hope that ruthenium compounds would limit reperfusion damage and inf arct size after ischaemia in in vivo models.