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BACKGROUND Recent studies have shown the potential of PDE-5 inhibition on acute and chronic heart failure. Nevertheless it remained unclear, how far load-reducing properties and direct effects on myocardial contractility are responsible for these observations. In the present study, we investigated the effects of vardenafil on myocardial contractility and vascular function in a dose-response study. METHODS We performed left ventricular pressure-volume analysis in young adult rats by using a Millar microtip conductance catheter. Pressure-volume loops were recorded before and after intravenous injection of vardenafil (3, 10, 30, 100, 300 μg/kg, n = 6/group). RESULTS Treatment with vardenafil resulted in a significant (p < 0.05) increase in the load-independent cardiac contractility parameters reaching its maximum at the dose of 100μg/kg (ESPVR: 2.15 ± 0.15 vs. 3.29 ± 0.26 mm Hg/μL; PRSW: 93.28 ± 4.04 vs. 134.90 ± 6.27 mm Hg; peak positive dP/dt/EDV: 38.73 ± 7.97 vs. 53.02 ± 3.74 mm Hg·s-1·µL-1; before versus after 100 μg/kg vardenafil). Results of the in vitro organ-bath experiments showed an augmented vasorelaxation of precontracted aortic rings after vardenafil treatment. CONCLUSION Our data supports the hypothesis that the usage of vardenafil as "inodilators" could have beneficial effects in heart failure patients.

Introduction: Cardiac transplantation is the most effective treatment of end-stage heart failure. Brain dead (BD) donors are currently the only reliable source for cardiac grafts. However, hemodynamic instability and cardiac dysfunction have been demonstrated in BD donors and this could therefore also affect posttransplant graft function. Hypothesis: Based upon the protective effect of Prolyl-Hydroxylase (PHD)-Hypoxia Inducible Factor (HIF)-1 pathway against ischemia/reperfusion injury (IRI), we tested the hypothesis that treatment of BD donor rats with the non-selective PHD inhibitor dimethyloxalylglycine (DMOG) results in a better graft heart condition in recipients after heterotopic transplantation. Methods: Lewis rats were injected with one shot DMOG (30 mg/kg i.v.) (n = 7) or equal volume of physiological saline (n = 7) and maintained BD for 5h by a subdurally placed and inflated balloon catheter. Controls were sham-operated (n = 11). Then, hearts were explanted, stored in cold preservation solution, heterotopically transplanted and after 1.5h reperfusion left-ventricular (LV) graft function was evaluated in vivo. Myocardial histological and molecular biological analyses were performed. Results: BD was associated with decreased LV function. DMOG treatment of BD animals resulted in better load-independent contractility and end-diastolic stiffness parameters (ESPVR E´max (mmHg/µl): BD+DMOG: 3.7 ± 0.6 vs BD: 3.1 ± 0.5; EDPVR (mmHg/µl): BD+DMOG: 0.13 ± 0.03 vs BD: 0.31 ± 0.06 p

BACKGROUND: Many donor organs come from youths involved in alcohol-related accidental death. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion while acute ethanol intoxication is associated with myocardial functional and morphological changes. The aims of this work were 1) to evaluate in rats the time-course cardiac effects of acute ethanol-exposure and 2) to explore how its abuse by donors might affect recipients in cardiac pump function after transplantation. METHODS: Rats received saline or ethanol (3.45 g/kg, ip). We evaluated both the mechanical and electrical aspects of cardiac function 1 h, 6 h or 24 h after injection. Plasma cardiac troponin-T and glucose-levels were measured and histological examination of the myocardium was performed. In addition, heart transplantation was performed, in which donors received ethanol 6 h or 24 h prior to explantation. Graft function was measured 1 h or 24 h after transplantation. Myocardial TBARS-concentration was measured; mRNA and protein expression was assessed by quantitative real-time PCR and Western blot, respectively. RESULTS: Ethanol administration resulted in decreased load-dependent (-34 ± 9%) and load-independent (-33 ± 12%) contractility parameters, LV end-diastolic pressure and elevated blood glucose levels at 1 h, which were reversed to the level of controls after 6 h and 24 h. In contrast to systolic dysfunction, active relaxation and passive stiffness are slowly recovered or sustained during 24 h. Moreover, troponin-T-levels were increased at 1 h, 6 h and 24 h after ethanol injection. ST-segment elevation (+47 ± 10%), elongated QT-interval (+38 ± 4%), enlarged cardiomyocyte, DNA-strand breaks, increased both mRNA and protein levels of superoxide dismutase-1, glutathione peroxydase-4, cytochrome-c-oxidase and metalloproteinase-9 were observed 24 h following ethanol-exposure. After heart transplantation, decreased myocardial contractility and relaxation, oxidative stress and altered protein expression were observed. CONCLUSIONS: These results demonstrate acute alcohol abuse increases the susceptibility of donor hearts to ischemia/reperfusion in a rat heart transplant model even though the global contractile function recovers 6 h after ethanol-administration.

/2.3% vs. DCD 64.1 /3.1%, p 0.61). Extension of the circulatory arrest time to 30 minutes still allowed for resuscitation and transplantation of the heart. Conclusions: Our findings suggest that the DCD heart can support the circulation after transplantation. Function was comparable to the transplanted BSD heart. Contrary to previous concerns over impairment of RV function in the DCD heart, load-independent assessment of RV function revealed good contractility before and after transplantation. Utilization of DCD hearts for human cardiac transplantation may allow for expansion of the donor pool.

Objective: Serine-protease inhibitors such as aprotinin reduce perioperative blood loss and may improve post pump cardiac performance due to their anti-inflammatory properties. After the „aprotinin era“, we investigated the efficacy of the novel synthetic serine-protease inhibitor CU2010 on blood loss and reperfusion injuryin a canine model. Methods: 36 dogs were divided into six groups: control, aprotinin (Hammersmith scheme), and CU2010 (0.5, 0.83, 1.25 and 1.66mg/kg). All animals underwent 90-minute cardiopulmonary bypass with 60 minutes of hypothermic cardioplegic arrest. Endpoints were blood loss during the first two hours after protamin, recovery of myocardial contractility (slope of the end-systolic pressure volume relationship, Ees), coronary blood flow and vascular reactivity. Results: CU2010 dose-dependently reduced blood loss comparble to aprotinin (Figure 1, *p

Aims: The non-specific serine-protease inhibitor aprotinin is used to reduce perioperative blood loss after cardiopulmonary bypass. Because of allergic and infectious risk and clinical side effets substitutes of aprotinin would be highly preferable. We investigated the efficacy of the novel synthetic serine-protease inhibitors CU2010 and CU2020 on blood loss in a canine model. Methods: 37 dogs were divided into five groups: control (n=5), aprotinin (n=8; Hammersmith scheme), CU2010 I. (n=8, 1,6mg/kg Hammersmith scheme) CU2010 II. (n=8, 1,6mg/kg continuous infusion) and CU2020 (n=8, 4,98mg/kg, Hammersmith scheme). All animals underwent 90-minute cardiopulmonary bypass. Endpoints were blood loss during the first two hours after application of protamin (T100-T220), activated clotting time (ACT), partial thromboplastin time (PTT), normalized prothrombin time (Quick). Results: CU2010 and CU2020 significantly reduced blood loss comparable to aprotinin (Fig. 1, *p