Reduction of myocardial infarction by postischemic administration of the calpain inhibitor A-705253 in comparison to the Na(+)/H(+) exchange inhibitor Cariporide (R) in isolated perfused rabbit hearts

The calpain inhibitor A-705253 and the Na(+)/H(+) exchange inhibitor Cariporide (R) were studied in isolated perfused rabbit hearts subjected to 60 min occlusion of the ramus interventricularis of the left coronary artery (below the origin of the first diagonal branch), followed by 120 min of reperfusion. The inhibitors were added to the perfusion fluid solely or in combination at the beginning of reperfusion. Hemodynamic monitoring and biochemical analysis of perfusion fluid from the coronary outflow were performed. Myocardial infarct size and area at risk (transiently not perfused myocardium) were determined from left ventricular slices after a special staining procedure with Evans blue and 2,3,5-triphenyltetrazolium chloride. The infarcted area (dead myocardium) was 72.7 +/- 4.0% of the area at risk in untreated controls, but was significantly smaller in the presence of the inhibitors. The largest effect was observed with 10(-6) M A-705253, which reduced the infarcted area to 49.2 +/- 4.1% of the area at risk, corresponding to a reduction of 33.6%. Cariporide (R) at 10(-6) M reduced the infarct size to the same extent. The combination of both inhibitors, however, did not further improve cardioprotection. No significant difference was observed between the experimental groups in coronary perfusion, left ventricular pressure, heart rate, or in the release of lactate dehydrogenase and creatine kinase from heart muscle

Effect of modified ultrafiltration on the inflammatory response in paediatric open-heart surgery:A prospective randomized study

Modified ultrafiltration (MUF) is often used in conjunction with paediatric cardiac surgery with cardiopulmonary bypass (CPB) and is thought to improve clinical outcome. It is unclear whether these improvements (if any) are due to the removal of inflammatory mediators. In this prospective study, 18 children aged 12-24 months undergoing uncomplicated cardiac surgery with methylprednisolone added in the pump prime were randomized to receive CPB with (n = 10) and without (n = 8) MUF. Cytokines (TNFalpha, IL-6, IL-1beta, IL-10, IL-1ra), complement split products (C3d, C4d) and coagulation system activation (F1 + 2, ATIII) were measured pre-, peri- and up to 48 h postoperatively. For clinical outcome, the alveolar-arterial oxygen (A-a) gradient, transfusion requirement, drain loss, mean blood pressure and requirement for inotropic support were registered up to 24 h postoperatively. Our results show an improvement in postoperative oxygenation as well as a tendency towards decreased drain loss and improved haemodynamics in the MUF group. There were no intergroup differences detectable for TNFalpha, IL-1beta, IL-1ra, complement and coagulation markers. We conclude that MUF in itself does not significantly influence TNFalpha, IL-1beta, IL-1ra and the complement and coagulation profiles in children undergoing cardiac surgery with CPB. Despite this, there was some evidence for improved clinical outcome. Our results do not support that MUF improves postoperative organ function by modulation of the measured markers of inflammation

Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper

Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps. © 2016 The Author