Anti-ischemic effects of inotropic agents in experimental right ventricular 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.
Department of Anesthesiology, University Hospital of Aachen, Aachen, Germany. mhein@ukaachen.de
M
M
Hein
A B
AB
Roehl
J H
JH
Baumert
K
K
Scherer
P
P
Steendijk
R
R
Rossaint
D000818:Animals; D001784:Blood Gas Analysis; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004280:Dobutamine / Q000627:therapeutic use; D005260:Female; D006352:Heart Ventricles; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006835:Hydrazones / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood; D020105:Milrinone / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000150:complications*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000209:etiology*; D009205:Myocarditis / Q000097:blood / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009211:Myoglobin / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D011724:Pyridazines / Q000627:therapeutic use; D000077464:Simendan; D013552:Swine; D020107:Troponin T / Q000097:blood
D002316:Cardiotonic Agents; D006835:Hydrazones; D018836:Inflammation Mediators; D009211:Myoglobin; D011724:Pyridazines; D020107:Troponin T; D000077464:Simendan; D004280:Dobutamine; D020105:Milrinone