Abstract
Myocardial infarct size has been measured after 1 hr of mechanical occlusion of the circumflex coronary artery and 5 hr of reperfusion in control dogs infused with saline, and in dogs infused with activated protein C (aPC) (1mg/kg/hr i.v.). Infusion of aPC during reperfusion produced a sustained doubling of activated partial thromboplastin time and no change in thrombin time at a final plasma parent drug concentration of 1.25 +/- 0.11 mug/ml. aPC infusion did not alter systolic arterial pressure, cardiac rate or the rate pressure product when compared to time-related alterations observed in control dogs. ST-segment deviation and the intensity and duration of cardiac arrhythmias associated with reperfusion of ischemic myocardium also were similar between groups. Resultant infarct sizes were 34.8 +/- 3.9 and 33.2 +/- 6.2% of the left ventricular mass placed at risk of necrosis in control and aPC-treated dogs. respectively. aPC infusion was associated with a small reduction in leukocytosis in response to myocardial ischemic injury, but did not alter the localization of leukocytes within ischemic and infarcted myocardium. In vitro concentrations of aPC (0.3, 1 and 3 mug/ml), comparable to the plasma concentration that inhibited blood coagulation in dogs, did not alter superoxide production or CD11b/CD18-mediated adhesion of chemotactic factor f-Met-Leu-Phe-stimulated neutrophils. Present data indicate that aPC lacks cardioprotectant activity at an infusion rate inhibiting coagulation. Apart from inhibition of thrombin generation, no evidence of an anti-inflammatory effect of aPC was observed.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|