BACKGROUND: Right ventricular (RV) function is an important determinant of survival after myocardial infarction. The efficacy of reperfusion therapy might be increased by the cardioprotective action of inotropic agents, which are used for symptomatic therapy in situations with compromised hemodynamics. Therefore, we used a porcine model of RV ischemia and reperfusion (IR) injury to study the influence of milrinone, levosimendan and dobutamine on the extent and degree of myocardial injury. METHODS: IR injury was induced by temporary ligation of the distal right coronary artery for 90 min, followed by 120 min of reperfusion. Treatment was initiated 30 min after coronary artery occlusion. A bolus of milrinone (n=12; 50 microg/kg) and levosimendan (n=10; 24 microg/kg) was applied in different groups, followed by continuous infusion of the drugs at 0.5 and 0.2 microg/kg/min, respectively. The effects on myocardial injury and inflammation were compared with a control (n=12) and a dobutamine group (n=10), where treatment was started with an infusion of 5 microg/kg/min. RESULTS: Milrinone and levosimendan reduced the resulting infarct size with respect to the area at risk (41.7+/-10.2%, 45.7+/-8.1%) when compared with the control group (58.3+/-6.1%). In contrast, dobutamine had no effect (55.8+/-7.7%). All drugs reduced the number of neutrophils infiltrating into the different myocardial regions and the circulating levels of interleukin-6. Increased levels of tumor necrosis factor alpha during reperfusion were only abated by milrinone and levosimendan. CONCLUSIONS: Cardioprotective properties of milrinone and levosimendan were demonstrated for the first time in a clinically relevant model of RV infarction.
BACKGROUND: Right ventricular (RV) function is an important determinant of survival after myocardial infarction. The efficacy of reperfusion therapy might be increased by the cardioprotective action of inotropic agents, which are used for symptomatic therapy in situations with compromised hemodynamics. Therefore, we used a porcine model of RV ischemia and reperfusion (IR) injury to study the influence of milrinone, levosimendan and dobutamine on the extent and degree of myocardial injury. METHODS: IR injury was induced by temporary ligation of the distal right coronary artery for 90 min, followed by 120 min of reperfusion. Treatment was initiated 30 min after coronary artery occlusion. A bolus of milrinone (n=12; 50 microg/kg) and levosimendan (n=10; 24 microg/kg) was applied in different groups, followed by continuous infusion of the drugs at 0.5 and 0.2 microg/kg/min, respectively. The effects on myocardial injury and inflammation were compared with a control (n=12) and a dobutamine group (n=10), where treatment was started with an infusion of 5 microg/kg/min. RESULTS:Milrinone and levosimendan reduced the resulting infarct size with respect to the area at risk (41.7+/-10.2%, 45.7+/-8.1%) when compared with the control group (58.3+/-6.1%). In contrast, dobutamine had no effect (55.8+/-7.7%). All drugs reduced the number of neutrophils infiltrating into the different myocardial regions and the circulating levels of interleukin-6. Increased levels of tumor necrosis factor alpha during reperfusion were only abated by milrinone and levosimendan. CONCLUSIONS: Cardioprotective properties of milrinone and levosimendan were demonstrated for the first time in a clinically relevant model of RV infarction.
Authors: Kian-Keong Poh; Xin Xu; Mark Y Chan; Chi-Hang Lee; Edgar L Tay; Adrian F Low; Koo Hui Chan; Winnie Sia; Liang-Qiu Tang; Huay Cheem Tan; Charles Y Lui; Vincent Nguyen; Kenichi Fujise; Ming-He Huang Journal: Eur J Clin Pharmacol Date: 2014-01-25 Impact factor: 2.953
Authors: Anna B Roehl; Marc Hein; Philipp D Loetscher; Jan Rossaint; Joachim Weis; Rolf Rossaint; Mark Coburn Journal: BMC Neurol Date: 2010-10-21 Impact factor: 2.474
Authors: Anna B Roehl; Norbert Zoremba; Markus Kipp; Johannes Schiefer; Andreas Goetzenich; Christian Bleilevens; Nikolaus Kuehn-Velten; Rene Tolba; Rolf Rossaint; Marc Hein Journal: BMC Neurol Date: 2012-08-24 Impact factor: 2.474