Short-term endothelin receptor blockade with tezosentan has both immediate and long-term beneficial effects in rats with myocardial infarction
Martine Clozel, MD*,*,
Changbin Qiu, MD, PhD* ,
Chang-Shen Qiu*,
Patrick Hess* and
Jean-Paul Clozel, MD*
* Actelion Ltd., Allschwil, Switzerland
Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai, China
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Figure 1 Effects of tezosentan on lung weights at 48 h after myocardial infarction (MI) or sham operation. Tezosentan (10 mg/kg, IV; MI + tezo) or vehicle (saline, 1 ml/kg, IV; MI + veh) was injected at 1 h and 24 h after MI. Sham-operated rats (Sham) received vehicle at the same time points. Lung weight was measured at 48 h after MI or sham operation. BW = body weight; **p < 0.01; ***p < 0.001.
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Figure 2 Light micrographs of the lungs at 48 h after myocardial infarction (MI) or sham operation. Tezosentan (10 mg/kg, IV; MI + tezo) or vehicle (saline, 1 ml/kg, IV; MI + veh) was injected at 1 h and 24 h after MI. Tezosentan largely prevented the lung damage (overt capillary dilation and eosin-like edematous materials) seen in the vehicle-treated MI rats (MI + veh). In sham-operated rats (Sham), no pulmonary capillary dilation or edema was observed at 48 h after operation. Hematoxillin eosin stain, x 100.
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Figure 3 Kaplan-Meier curves showing the effects of tezosentan on survival rate of rats after myocardial infarction (MI) or sham operation. Tezosentan (10 mg/kg, IV; MI + tezo) or vehicle (saline, 1 ml/kg, IV; MI + veh) was injected at 1 h and 24 h after MI. Sham-operated rats (Sham) received vehicle at the same time points.
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