Ischemia reperfusion www.selleckchem.com/products/Calcitriol-(Rocaltrol).html injury is a multifaceted damage, comprising effects on cardiomyocytes function and death and endothelial function. Due to Inhibitors,Modulators,Libraries the lack of effect on coronary flow by lixisenatide, we assume a direct effect on cardiomyocyte function and survival. Sonne and co workers found that GLP 1 amide, which is the first breakdown fragment of GLP 1 amide but not a GLP 1 receptor agonist, did not reduce infarct size but however increased functional recovery of ischemia hearts. Based on these finding the authors proposed that be side the known GLP 1 receptor another hitherto unidenti fied receptor could be responsible for effects of GLP 1 like peptides in rat hearts. Only a limited numbers of pre clinical studies have in vestigated so far effects of GLP 1 peptides on long term consequences Inhibitors,Modulators,Libraries after myocardial ischemia and reperfusion.

Using liraglutide, Noyan Ashraf and coworkers demon Inhibitors,Modulators,Libraries strated cardioprotection after myocardial infarction in diabetic and non diabetic mice. Liu and coworkers treated rats two weeks after myocardial infarction with either GLP 1 or the exenatide analog AC3174 and noticed improved cardiac function and morphology. In contrast to those previous studies, we performed only a transient and not permanent Inhibitors,Modulators,Libraries ligation of the left coronary artery in our rat model in order to obtain re sults closer to the clinical situation in which almost all patients with myocardial infarction are reperfused. The transient ischemia reperfusion protocol resulted in only moderate changes of systolic function after a long term recovery period.

LVP and dpdtmax were Inhibitors,Modulators,Libraries slightly reduced in the ischemia reperfusion group versus sham treated animals. Ramipril but not lixisenatide normalized LVP but not dpdtmax. Major differences were observed for the active treatments regarding diastolic function, in par ticular on left ventricular end diastolic pressure and the relaxation time tau Weiss. These functional im provements occur despite lack of effect on increased car diac fibrosis assessed by specific morphological staining and gene expression analysis. In addition, heart weight did not significantly differ between the various groups rul ing out strong effects on hypertrophy of cardiomyocytes as potential mode of action. Moreover, we noticed no effects on plasma glucose and insulin by lixisenatide treat ment in this non diabetic model.

Hence, indirect effects on heart metabolism via glucose uptake may not suffi ciently explain the observed improvement in cardiac function. A broader gene expression pattern of www.selleckchem.com/products/wortmannin.html genes involved in rat cardiac remodeling delivered two major findings. First, the myocardial infarction is a major driver of gene expression changes and drug effects in the non infarct regions of infarcted hearts are rather moderate. Second, lixisenatide and the ACE inhibitor ramipril are similar in their reaction pattern, indicating activation of more common protective signaling pathways for both treat ments.