Glucose Tolerance and Left Ventricular Pressure-Volume Relationships in Frequently Used Mouse Strains

We investigated glucose tolerance and left ventricular contractile performance in 4 frequently used mouse strains (Swiss, C57BL/6J, DBA2, and BalbC) at 24 weeks. Glucose tolerance was tested by measuring blood glucose levels in time after intraperitoneal glucose injection (2 mg/g body weight). Left ventricular contractility was assessed by pressure-conductance analysis. Peak glucose levels and glucose area under the curve were higher (all P < .05) in C57BL/6J (418 ± 65 mg/dL and 813 ± 100 mg·h/dL) versus Swiss (237 ± 66 mg/dL and 470 ± 126 mg·h/dL), DBA2 (113 ± 20 mg/dL and 304 ± 49 mg·h/dL, P < .01), and BalbC mice (174 ± 55 mg/dL and 416 ± 70 mg·h/dL). Cardiac output was higher (all P < .05) in Swiss (14038 ± 4530 μL/min) versus C57BL/6J (10405 ± 2683 μL/min), DBA2 (10438 ± 3251 μL/min), and BalbC mice (8466 ± 3013 μL/min). Load-independent left ventricular contractility assessed as recruitable stroke work (PRSW) was comparable in all strains. In conclusion, glucose tolerance and load-dependent left ventricular performance parameters were different between 4 mice background strains, but PRSW was comparable

Diabetes mellitus and the metabolic syndrome do not abolish, but might reduce, the cardioprotective effect of ischemic postconditioning

ObjectiveIschemic preconditioning fails to protect the diabetic heart against lethal reperfusion injury. Because the pathways of ischemic pre- and postconditioning partially overlap, we evaluated the cardioprotective effect of ischemic postconditioning in mouse models of type 2 diabetes (ObOb) and the metabolic syndrome (DKO).MethodsMice (C57BL/6J, ObOb, and DKO; aged 24 weeks; n = 24, n = 28, and n = 18, respectively) underwent reperfusion after 30 minutes of coronary occlusion with or without ischemic postconditioning (3 cycles of 10 seconds reperfusion–reocclusion). Left ventricular contractility and infarct size were assessed 60 minutes later with pressure conductance analysis and 2,3,5-triphenyl-tetrazolium chloride staining, respectively. In a second cohort (C57BL/6J and DKO; aged 12 weeks; n = 31 and n = 24, respectively) cardiac cine magnetic resonance imaging was performed after 1 and 10 weeks, followed by pressure conductance analysis and Sirius red staining.ResultsIn the C57BL6/J mice, the infarct size was lower (40%, P < 10−5) and the load independent preload recruitable stroke work was greater after ischemic postconditioning (P < .05). In the ObOb and DKO mice, ischemic postconditioning reduced the infarct size by 24% (P < 10−5). In the C57BL/6J mice, the ejection fraction was greater and the myocardial mass was lower 10 weeks after ischemic postconditioning (P < .05). Tagging grid deformation was increased after ischemic postconditioning in both infarcted and remote areas. After ischemic postconditioning, the survival and ejection fraction were greater in the DKO mice (67% vs 17% and 44% ± 11% vs 59% ± 2%, P < .05 for both), and the collagen content was lower for both C57BL/6J and DKO mice (P < .05 for both).ConclusionsThe cardioprotective effect of ischemic postconditioning was sustained in C57BL/6J mice after 10 weeks and protected against adverse left ventricular remodeling. In mouse models of type 2 diabetes, protection against lethal reperfusion injury is present, leading to increased survival after ischemia and reperfusion

Increased Cardiac Myocyte PDE5 Levels in Human and Murine Pressure Overload Hypertrophy Contribute to Adverse LV Remodeling

Background: The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC). Methodology/Principal Findings: In patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5-TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dtmax and dP/dtmin with prolonged tau (P<0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro. Conclusions/Significance: Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target

POSTCONDITIONEREN VAN HET HART IN DIABETES EN HET METABOOL SYNDROOM Een multimodale evaluatie en de therapeutische implicaties van het postconditioneren van myocardweefsel in diabetes mellitus type II en het metabool syndroom

As the prevalence of the MS rises rapidly and the components of the MS increase the overall cardiovascular risk synergistically, interest for this syndrome is growing rapidly. The MS leads to very specific cardiomyocyte changes, and as the natural course of the MS is detrimental, it necessitates a tailored approach with correction of the individual risk factors and prevention of the hypertrophic and inflammatory stimuli. Although IPreC fails to protect the diabetic heart against ischemic events, we have shown that IPostC is still beneficial at short and long term, both improving functional outcome and infarct size. New pharmacological insights should enable us to reactivate endogenous cardioprotective pathways in this high risk population and to apply it in cardiovascular interventions.status: publishe

PRT tissue treatment efficacy: comparative study in rat implantation model

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How to Operate on Inoperable Patients: Minimally Invasive Direct Coronary Artery Bypass

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Routine thymectomy in congenital cardiac surgery changes adaptive immunity without clinical relevance

The actual importance of the thymus in both children and adults is largely unclear. In congenital cardiac surgery, a partial or total thymectomy is frequently performed to improve access to the heart and great vessels. We performed a literature search to evaluate the effect on the adaptive immune system of the removal of thymus tissue in patients with congenital heart disease. A PubMed search according to Dunning's standard provided 149 articles, of which 13 addressed our search question. Each study has been tabulated with author, cases, controls, follow-up, methods, results and limitations. A first group of articles repeatedly showed the effect on the T-cell compartment, including the impact on subgroups of this compartment. More recent studies, usually with a longer follow-up, confirm that the earlier changes in T-cell population appear to be permanent. Only one author found a normalization of T-cell population five years after thymectomy. In contrast to these clear changes in T-cell population, there is currently no clear clinical relevance. A literature search on thymectomy in congenital cardiac surgery revealed clear changes in T-cell-related immunity; however, there is a lack of clinical relevance. Further investigation of the adaptive immune system is required to explain this discrepancy.status: publishe

A collaborative environment is beneficial for reducing the learning curve in Robotic Assisted Minimally Invasive Direct Coronary Artery Bypass

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