[Cyclosporine A prevents ischemia-reperfusion induced myocardial dysfunction in the isolated heart of the rat].
Cyclosporin A (CyA) has been shown to prevent mitochondrial injury following ischemia-reperfusion injury. Therefore, the present study was designed to investigate the effect of CyA on ischemia-reperfusion injury in the isolated rat heart preparation. Hearts from Sprague-Dawley rats were perfused in the Langerdorffmode at constant pressure (80 cm H2O) and paced (270 beats/min). After equilibration, hearts were treated with CyA (10(-5) mol/l) (n = 8) or its vehicle, cremophor (Cr) (n = 8) for 10 minutes before exposure to 30 minutes of global ischemia and 60 minutes of reperfusion. Hemodynamic variable vascular reactivity, and oxygen consumption (MVO2) were tested at baseline and at selected points during reperfusion Hemodynamic variables were significantly improved in the CyA group. The maximal mean percentage of preservation for left ventricular developed pressure (PDVG) was -14.9 +/- 10.7% and +31.5 +/- 23.6% respectively for Cr and CyA group (p<0.05) The maximal mean percentage of preservation for dp/dt was -11.7 +/- 11.4% and +28.3 +/- 29.9% respectively for Cr and CyA group (p < 0.05): the compliance, -dP/dt was also preserved, maximal mean preservation was -25.9 +/- 9.2% and +53.1 + 30.1% respectively in Cr and CyA group (p < 0.01). Oxygen debt was decreased at 30 minutes of reperfusion in the CyA-treated hearts: 0.06 x 10(-2) +/- 0.23 x 10(-2) cc/min/g compared to Cr-treated hearts: 0.61 x 10(-2) +/- 0.37 x 10(-2) cc/min/g (p = 0.05). The coronary endothelial dependent and independent responses were similarly decreased in both groups during reperfusion. Thus, in the isolated rat heart preparation, CyA preserves myocardial function (hemodynamic variables) and oxygen consumption without affecting the coronary vascular function during ischemia-reperfusion injury.
Mathieu
P
P
Service de Chirurgie, Institut de Cardiologie de Montréal, Québec, Canada.
Bendavid
Y
Y
Buluran
J
J
Cartier
R
R
D000818:Animals; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D016572:Cyclosporine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D006439:Hemodynamics; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008954:Models, Biological; D010101:Oxygen Consumption; D011379:Prognosis; D051381:Rats; D015427:Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology; D018754:Ventricular Dysfunction / Q000209:etiology / Q000517:prevention & control*
D007166:Immunosuppressive Agents; D016572:Cyclosporine