Diabetes mellitus (DM) is associated with characteristic structural and functional changes of the myocardium, termed diabetic cardiomyopathy. As a distinct entity independent of coronary atherosclerosis, diabetic cardiomyopathy is an increasingly recognized cause of heart failure. A detailed understanding of diabetic cardiac dysfunction, using relevant animal models, is required for the effective prevention and treatment of cardiovascular complications in diabetic patients. We investigated and compared cardiac performance in rat models of type 1 DM (streptozotocin induced) and type 2 DM (Zucker diabetic fatty rats) using a pressure-volume (P-V) conductance catheter system. Left ventricular (LV) systolic and diastolic function was evaluated in vivo at different preloads, including the slope of the end-systolic P-V relation (ESPVR) and end-diastolic P-V relationship (EDPVR), preload recruitable stroke work (PRSW), maximal slope of the systolic pressure increment (dP/dt(max)), and its relation to end-diastolic volume (dP/dt(max)-EDV) as well as the time constant of LV relaxation and maximal slope of the diastolic pressure decrement. Type 1 DM was associated with decreased LV systolic pressure, dP/dt(max), slope of ESPVR and dP/dt(max)-EDV, PRSW, ejection fraction, and cardiac and stroke work indexes, indicating marked systolic dysfunction. In type 2 DM rats, systolic indexes were altered only to a lower extent and the increase of LV stiffness was more pronounced, as indicated by the higher slopes of EDPVR. Our data suggest that DM is characterized by decreased systolic performance and delayed relaxation (mainly in type 1 DM), accompanied by increased diastolic stiffness of the heart (more remarkably in type 2 DM). Based on the sophisticated method of P-V analysis, different characteristics of type 1 and type 2 diabetic cardiac dysfunction can be demonstrated.

BackgroundA retrospective analysis was conducted of the early and long-term outcomes after surgery for infective endocarditis (IE).Material/MethodsWe included 360 patients with IE operated upon between 1993 and 2012. The primary endpoint was overall cumulative postoperative survival at 30 days. Secondary endpoints were early postoperative outcomes and complication rates. Factors associated with 30-day mortality were analyzed.ResultsMean age was 58.7±14.7 years and 26.9% (n=97) were female. The mean follow-up was 4.41±4.53 years. Postoperative survival was 81.7% at 30 days, 69.4% at 1 year, 63.3% at 5 years, and 63.3% at 10 years. Non-survivors were significantly older (p=0.014), with higher NYHA Class (p=0.002), had higher rates of preoperative diabetes mellitus (p=0.005), renal failure (p=0.001), and hepatic disease (p=0.002). Furthermore, non-survivors had higher baseline alanine aminotransferase (ALT, p=0.048), aspartate transaminase (AST, p=0.027), bilirubin (p=0.013), white cell count (WCC, p=0.034), and CRP (p=0.049). Factors associated with 30-day mortality were longer duration of surgery, CPB, and aortic cross-clamping times (p<0.001, p<0.001, and p=0.003, respectively), as well as higher RBC, FFP, and platelet transfusion requirements (p<0.001, p=0.005, and p<0.001, respectively). Multivariate logistic regression analysis revealed liver cirrhosis (OR 4.583, 95-CI: 1.096–19.170, p=0.037) and longer CPB time (OR 1.025, 95-CI 1.008–1.042, p=0.004) as independent predictors of 30-day mortality.ConclusionsSurgical treatment of IE shows satisfactory early, midterm, and long-term results. Multivariate logistic regression analysis revealed cirrhosis and longer CPB time as independent predictors of 30-day mortality.

Background and purpose:Patients with diabetes mellitus exhibit generalized endothelial and cardiac dysfunction with decreased nitric oxide production. Elevated intracellular cyclic guanosine monophosphate (cGMP) levels contribute to an effective cardioprotection in different pathophysiological conditions. In this study, we investigated whether chronic treatment with the phosphodiesterase-5 inhibitor vardenafil could improve diabetic cardiovascular dysfunction by up-regulating the nitric oxide-cGMP pathway in the vessel wall and myocardium. Experimental approach: Diabetes was induced in young rats by a single intraperitoneal injection of streptozotocin (60 mg·kg -1 ). In the treatment group, vardenafil (10 mg·kg -1 ·day -1 ) was given orally for 8 weeks. Diabetic control animals received vehicle for the same time. Left ventricular pressure-volume relations were measured by using a microtip Millar pressure-volume conductance catheter, and indexes of contractility, such as the slope of end-systolic pressure-volume relationship (Emax) and preload recruitable stroke work (PRSW), were calculated. In organ bath experiments for isometric tension with rings of isolated aortae, endothelium-dependent and independent vasorelaxation was investigated by using acetylcholine and sodium nitroprusside. Key results: When compared with the non-diabetic controls, diabetic rats showed increased myocardial and vascular transforming growth factor-b1 expression, impaired left ventricular contractility (impairment of Emax by 53%, PRSW by 40%; P < 0.05) and vascular dysfunction. Treatment with vardenafil resulted in higher cGMP levels, reduced transforming growth factor-b1 expression, significantly improved cardiac function (improvement of Emax by 95%, PRSW by 69%; P < 0.05) and greater vasorelaxation to acetylcholine and sodium nitroprusside in aortae from diabetic animals. Conclusions and implications:Our results demonstrate that impaired vascular cGMP signalling contributes to the development of diabetic vascular and cardiac dysfunction, which can be prevented by chronic phosphodiesterase-5 inhibition. (2009) British Journal of Pharmacology

ObjectivesGender specific differences receive increasing attention and are known to affect the outcome of cardiovascular diseases. We investigated possible risk-factors for gender-specific differences in ascending aortic aneurysm surgery.Methods548 consecutive patients (male: n = 390, age: 58.3±14.4 years; female: n = 158, age: 65.3±12.9 years) with aneurysms of the ascending aorta eligible for cardiac surgery were retrospectively analyzed.ResultsWomen were significantly older when operation was indicated (p<0.001) and presented with significantly more hypertension (p=0.04) and chronic obstructive pulmonary disease (COPD; p = 0.017), whereas men had significantly more previous cardiac operations (p = 0.016). Normalized aortic diameters (diameter / body surface area) were significantly larger in women (3.10±0.6 cm) vs. (2.75±0,5 cm, p≤0.001) in men, without differences in absolute values (5.74±1.04 cm vs. 5.86±1.34 cm). The aortic arch was significantly more involved in aneurysm formation in women (p = 0.04). Follow-up was available in 93% of the patients with a mean follow-up time of 3.9±3.9 (0-17.8) years. 30-day mortality was 3.5% in men (n=12) and 7.9% in women (n=11; p = 0.058). Univariate regression analysis shows gender specific risk factors for 30-day mortality in men to be age: p = 0.028; myocardial infarction: p = 0.0.24 and in women diameter of the ascending aorta: p=0.014; renal insufficiency: p=0.007. Long-term survival was significantly reduced in women (log-rank p = 0.0052).ConclusionsThe outcome after surgery for ascending aortic aneurysm is less favourable in women with significantly reduced long-term survival and a trend to increased 30-day mortality in this cohort. Larger normalized aortic diameters, higher incidence of involvement of the aortic arch and differences in comorbidities may contribute to gender differences. Women undergo surgery at higher age and more progressed state of aortic disease. Therefore, gender-specific guidelines for ascending replacement may be useful to improve outcome in women.

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