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Decreased left ventricular function, myocarditis, and coronary arteriolar medial thickening following monocrotaline administration in adult rats

Department of Pediatrics, McGill University and Division of Cardiology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada

Submitted 28 November 2005 ; accepted in final form 21 March 2007

Decreased right as well as left ventricular function can be associated with pulmonary hypertension (PH). Numerous investigations have examined cardiac function following induction of pulmonary hypertension with monocrotaline (MCT) assuming that MCT has no direct cardiac effect. We tested this assumption by examining left ventricular function and histology of isolated and perfused hearts from MCT-treated rats. Experiments were performed on 50 male Sprague-Dawley rats [348 ± 6 g (SD)]. Thirty-seven rats received MCT (50 mg/kg sc; MCT group) while the remainder did not (Control group). Three weeks later, pulmonary artery pressure was assessed echocardiographically in 20 MCT and 8 Control rats. The hearts were then excised and perfused in the constant pressure Langendorff mode to determine peak left ventricular pressure (LVP), the peak instantaneous rate of pressure increase (+dP/dt_max) and decrease (–dP/dt_max), as well as the rate pressure product (RPP). Histological sections were subsequently examined. Pulmonary artery pressure was higher in the MCT-treated group compared with the Control group [12.9 ± 6 vs. 51 ± 35.3 mmHg (P < 0.01)]. Left ventricular systolic function and diastolic relaxation were decreased in the MCT group compared with the Control group (+dP/dt_max 4,178 ± 388 vs. 2,801 ± 503 mmHg/s, LVP 115 ± 11 vs. 83 ± 14 mmHg, RPP 33,688 ± 1,910 vs. 23,541 ± 3,858 beats·min^–1·mmHg^–1, –dP/dt_max –3,036 ± 247 vs. –2,091 ± 389 mmHg/s; P < 0.0001). The impairment of cardiac function was associated with myocarditis and coronary arteriolar medial thickening. Similarly depressed ventricular function and inflammatory infiltration was seen in 12 rats 7 days after MCT administration. Our findings appear unrelated to the degree of PH and indicate a direct cardiotoxic effect of MCT.

cardiovascular physiology; pyrrolizidine alkaloids; cardiomyopathy; coronary vessels

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