Background— Secreted factors from epicardial adipose tissue (EAT) have been implicated in the development of cardiomyocyte dysfunction. This study aimed to assess whether alterations in the secretory profile of EAT in patients with type 2 diabetes mellitus (DM2) affect contractile function and insulin action in cardiomyocytes. Methods and Results— Contractile function and insulin action were analyzed in primary adult rat cardiomyocytes incubated with conditioned media (CM) generated from explants of EAT biopsies obtained from patients without and with DM2. CM from subcutaneous and pericardial adipose tissue biopsies from the same patients served as the control. Cardiomyocytes treated with CM (EAT) from DM2 patients showed reductions in sarcomere shortening, cytosolic Ca 2+ fluxes, expression of sarcoplasmic endoplasmic reticulum ATPase 2a, and decreased insulin-mediated Akt-Ser473-phosphorylation as compared with CM from the other groups. Profiling of the CM showed that activin A, angiopoietin-2, and CD14 selectively accumulated in CM-EAT-DM2 versus CM-EAT in patients without DM2 and CM from the other fat depots. Accordingly, EAT biopsies from DM2 patients were characterized by clusters of CD14-positive monocytes. Furthermore, SMAD2-phosphorylation, a downstream target of activin A signaling, was elevated in cardiomyocytes treated with CM (EAT) from DM2 patients, and the detrimental effects of CM (EAT) from DM2 patients were partially abolished in cardiomyocytes pretreated with a neutralizing antibody against activin A. Finally, both recombinant activin A and angiopoietin-2 reduced cardiomyocyte contractile function, but only activin A reduced the expression of sarcoplasmic endoplasmic reticulum ATPase 2a. Conclusions— Collectively, our data implicate DM2-related alterations in the secretory profile of EAT in the pathogenesis of diabetes mellitus–related heart disease.

ContextAdipokines are linked to the development of cardiovascular dysfunction in type 2 diabetes (DM2). In DM2-patients, circulating levels of omentin-1, an adipokine preferentially expressed in epicardial adipose tissue, are decreased. This study investigated whether omentin-1 has a cardioprotective function.MethodsOmentin-1 levels in plasma and cardiac fat depots were determined in DM2-patients versus controls. Moreover, the relation between omentin-1 levels and cardiac function was examined in men with uncomplicated DM2. Finally, we determined whether omentin-1 could reverse the induction of cardiomyocyte dysfunction by conditioned media derived from epicardial adipose tissue from patients with DM2.ResultsOmentin-1 was highly expressed and secreted by epicardial adipose tissue, and reduced in DM2. Circulating omentin-1 levels were lower in DM2 versus controls, and positively correlated with the diastolic parameters early peak filling rate, early deceleration peak and early deceleration mean (all P<0.05). The improved diastolic function following pioglitazone treatment associated with increases in omentin-1 levels (P<0.05). In vitro, exposure of cardiomyocytes to conditioned media derived from epicardial adipose tissue from patients with DM2 induced contractile dysfunction and insulin resistance, which was prevented by the addition of recombinant omentin.ConclusionThese data identify omentin-1 as a cardioprotective adipokine, and indicate that decreases in omentin-1 levels could contribute to the induction of cardiovascular dysfunction in DM2.

Veno-arterial extracorporeal membrane oxygenation (ECMO) may be implanted using peripheral ECMO (pECMO) or central ECMO (cECMO) cannulation techniques. The aim of this study was to compare the outcome between these two cannulation techniques. A retrospective study was performed at Düsseldorf University Hospital from October 2009 through June 2011. Inclusion criteria were patients with veno-arterial ECMO support ≥24 h. Various pre-and postimplantation variables were investigated including postimplantation hemodynamic and ECMO parameters, oxygenation/ventilation parameters at 3, 6, 12, 24, 48, 72 h, as well as renal and liver function tests at first and third postoperative days following implantation. Outcome data of patients receiving pECMO were compared with those who received cECMO. The inclusion criteria were met by 37 patients (25 pECMO and 12 cECMO). There were no significant differences in baseline characteristics between these two groups except for younger age in pECMO patients (P = 0.005). All postimplantation variables were comparable between the two groups except for higher PO2 and lower PCO2 values at the 3rd hour postimplantation in patients with pECMO (P = 0.007 and 0.01, respectively). Eleven (44%) of the pECMO patients required re-exploration for bleeding versus 100% of patients with cECMO (P = 0.01). Ischemic leg complication was observed in four pECMO and three cECMO patients. Thirty-day mortality in patients with pECMO and cECMO was 60% versus 67%, respectively (P = 1.00). In this study, no particular oxygenation/ventilation, hemodymanic, or end-organ function advantage was observed with either cannulation technique. However, more bleeding and resternotomy complications were observed in cECMO patients.