TiProtec preserves endothelial function in a rat model.

Background: Coronary artery bypass surgery provides excellent patency rates; however, the early and/or late graft failure reduces the long-term benefit of myocardial revascularization. We investigated the effectiveness of generally used saline, Custodiol solutions and a new solution (TiProtec) at preserving endothelium after cold ischemia and warm reperfusion injury.

Materials And Methods: Aortic transplantations were performed in Lewis rats.

Effects of soluble guanylate cyclase activation on heart transplantation in a rat model.

Background: The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway is an important key mechanism to protect the heart from ischemia/reperfusion injury. However, this pathway is disrupted in several cardiovascular diseases as a result of decreased NO bioavailability and increased NO-insensitive forms of sGC. Cinaciguat preferentially activates these NO-insensitive, oxidized forms of sGC.

Endothelial dysfunction of bypass graft: direct comparison of in vitro and in vivo models of ischemia-reperfusion injury.

Background: Although, ischemia/reperfusion induced vascular dysfunction has been widely described, no comparative study of in vivo- and in vitro-models exist. In this study, we provide a direct comparison between models (A) ischemic storage and in-vitro reoxygenation (B) ischemic storage and in vitro reperfusion (C) ischemic storage and in-vivo reperfusion.

Methods And Results: Aortic arches from rats were stored for 2 hours in saline.

Graft preservation with heparinized blood/saline solution induces severe graft dysfunction.

Objectives: Vascular grafts are often stored in cold physiological saline/heparinized blood preservation solution. Until now, only in vitro studies investigated the effect of the aforementioned preservation solutions on endothelial function. The main goal of our study was to compare the storage effect of physiological saline and heparinized blood after short-time cold storage and warm reperfusion in a rat model of aortic transplantation.

Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction.

The pathophysiology of ischemic myocardial injury involves cellular events, reactive oxygen species, and an inflammatory reaction cascade. The zinc complex of acetylsalicylic acid (Zn(ASA)2) has been found to possess higher anti-inflammatory and lower ulcerogenic activities than acetylsalicylic acid (ASA). Herein, we studied the effects of both ASA and Zn(ASA)2 against acute myocardial ischemia.

An altered pattern of myocardial histopathological and molecular changes underlies the different characteristics of type-1 and type-2 diabetic cardiac dysfunction.

Increasing evidence suggests that both types of diabetes mellitus (DM) lead to cardiac structural and functional changes. In this study we investigated and compared functional characteristics and underlying subcellular pathological features in rat models of type-1 and type-2 diabetic cardiomyopathy. Type-1 DM was induced by streptozotocin.

Does imaging αvβ3 integrin expression with PET detect changes in angiogenesis during bevacizumab therapy?

Unlabelled: In recent years, there has been a growing interest in molecular imaging markers of tumor-induced angiogenesis. Several radiolabeled RGD (arginine, glycine, aspartate) peptides have been developed for PET imaging of αvβ3 integrins in the tumor vasculature, but there are only limited data on how angiogenesis inhibitors affect the tumor uptake of these peptides.

Methods: Changes in (68)Ga-NODAGA-c(RGDfK) peptide uptake were measured using PET during bevacizumab therapy of 2 αvβ3-negative squamous cell carcinoma cell lines (A-431 and FaDu) that induce αvβ3-positive neovasculature when transplanted into nude mice.

Vascular dysfunction induced by hypochlorite is improved by the selective phosphodiesterase-5-inhibitor vardenafil.

Reactive oxygen species, such as hypochlorite induce oxidative stress, which impairs nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signalling and leads to vascular dysfunction. It has been proposed, that elevated cGMP-levels may contribute to an effective cytoprotection against oxidative stress. We investigated the effects of vardenafil, a selective inhibitor of the cGMP-degrading phosphodiesterase-5 enzyme on vascular dysfunction induced by hypochlorite.

Q50, an iron-chelating and zinc-complexing agent, improves cardiac function in rat models of ischemia/reperfusion-induced myocardial injury.

Background: Reperfusion of ischemic myocardium may contribute to substantial cardiac tissue damage, but the addition of iron chelators, zinc or zinc complexes has been shown to prevent heart from reperfusion injury. We investigated the possible beneficial effects of an iron-chelating and zinc-complexing agent, Q50, in rat models of ischemia/reperfusion (I/R)-induced myocardial infarction and on global reversible myocardial I/R injury after heart transplantation.

Methods And Results: Rats underwent 45-min myocardial ischemia by left anterior descending coronary artery ligation followed by 24h reperfusion.

Prolyl-hydroxylase inhibition preserves endothelial cell function in a rat model of vascular ischemia reperfusion injury.

Storage protocols of vascular grafts need further improvement against ischemia-reperfusion (IR) injury. Hypoxia elicits a variety of complex cellular responses by altering the activity of many signaling pathways, such as the oxygen-dependent prolyl-hyroxylase domain-containing enzyme (PHD). Reduction of PHD activity during hypoxia leads to stabilization and accumulation of hypoxia inducible factor (HIF) 1α.

Acute ethanol exposure increases the susceptibility of the donor hearts to ischemia/reperfusion injury after transplantation in rats.

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.

Reendothelialization of human heart valve neoscaffolds using umbilical cord-derived endothelial cells.

Background: Heart valve tissue engineering represents a concept for improving the current methods of valvular heart disease therapy. The aim of this study was to develop tissue engineered heart valves combining human umbilical vein endothelial cells (HUVECs) and decellularized human heart valve matrices.

Methods And Results: Pulmonary (n=9) and aortic (n=6) human allografts were harvested from explanted hearts from heart transplant recipients and were decellularized using a detergent-based cell extraction method.

Nitric oxide- and heme-independent activation of soluble guanylate cyclase attenuates peroxynitrite-induced endothelial dysfunction in rat aorta.

Oxidative stress interferes with nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) signalling pathway through reduction of endogenous NO and formation of the strong intermediate oxidant peroxynitrite and leads to vascular dysfunction. We evaluated the effects of oral treatment with NO- and heme-independent sGC activator cinaciguat on peroxynitrite-induced vascular dysfunction in rat aorta. Sprague-Dawley rats were treated orally 2 times at an interval of 17 hours with vehicle or with cinaciguat (10 mg/kg).

Enhancement of myocardial and vascular function after phosphodiesterase-5 inhibition in a rat model.

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.

Hearts of surviving MLP-KO mice show transient changes of intracellular calcium handling.

The muscle Lim protein knock-out (MLP-KO) mouse model is extensively used for studying the pathophysiology of dilated cardiomyopathy. However, explanation is lacking for the observed long survival of the diseased mice which develop until adulthood despite the gene defect, which theoretically predestines them to early death due to heart failure. We hypothesized that adaptive changes of cardiac intracellular calcium (Ca(i)(2+)) handling might explain the phenomenon.

Pharmacological activation of soluble guanylate cyclase protects the heart against ischemic injury.

Background: The role of the nitric oxide/cGMP/cGMP-dependent protein kinase G pathway in myocardial protection and preconditioning has been the object of intensive investigations. The novel soluble guanylate cyclase activator cinaciguat has been reported to elevate intracellular [cGMP] and activate the nitric oxide/cGMP/cGMP-dependent protein kinase G pathway in vivo. We investigated the effects of cinaciguat on myocardial infarction induced by isoproterenol in rats.

Dose-dependent effects of a selective phosphodiesterase-5-inhibitor on endothelial dysfunction induced by peroxynitrite in rat aorta.

Reactive oxygen species, such as peroxynitrite, induce oxidative stress and DNA injury leading to endothelial dysfunction. It has been proposed, that elevated intracellular cyclic GMP (cGMP)-levels may contribute to an effective cytoprotection against nitro-oxidative stress. We investigated the dose-dependent effects of vardenafil, an inhibitor of phosphodiesterase-5, on endothelial dysfunction induced by peroxynitrite.

Comparative investigation of the left ventricular pressure-volume relationship in rat models of type 1 and type 2 diabetes mellitus.

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.

Effects of selective phosphodiesterase-5-inhibition on myocardial contractility and reperfusion injury after heart transplantation.

Recently, the infarct reducing and cardioprotective effects of phosphodiesterase-5-inhibitors were described. In this study, we investigated these effects on ischemia/reperfusion injury in a rat model of heart transplantation. Three groups were assigned for our study: a vardenafil preconditioning group, an ischemic control, and a nonischemic control.