Clinical data suggest a link between the activation of the renin-angiotensin system and cardiovascular ischemic events. Leukocyte accumulation in the vessel wall is a hallmark of early atherosclerosis and plaque progression. E-Selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) are adhesion molecules participating in mediating interactions between leukocytes and endothelial cells and have been found to be expressed in athero-sclerotic plaques. We investigated whether angiotensin II, the effector of the renin-angiotensin system, influences the endothelial expression of E-selectin, VCAM-1, and ICAM-1. In coronary endothelial cells derived from explanted human hearts, angiotensin II (10(-11) to 10(-5) mol/L) induced a concentration-dependent increase in E-selectin expression. The effect was measured by cell ELISA and duplex reverse-transcription polymerase chain reaction (RT-PCR) and reached its maximum at 10(-7) mol/L. Angiotensin II induced only a small increase in E-selectin expression in cardiac microvascular endothelial cells. VCAM-1 and ICAM-1 were not affected by angiotensin II stimulation. In addition, the effect of angiotensin II-induced E-selectin expression on leukocyte adhesion was quantified under flow conditions. Angiotensin II (10(-7) mol/L) increased leukocyte adhesion significantly to 67% of the maximal effect by tumor necrosis factor-alpha at a wall shear stress of 2 dyne/cm2. This adhesion was found to be E-selectin dependent, as demonstrated by blocking antibodies. The AT1-receptor antagonist DUP 753 significantly reduced E-selectin-dependent adhesion, whereas the AT2-receptor antagonist PD 123177 had no inhibitory effect. In addition, only AT1-receptor, but not AT2-receptor, mRNA could be detected by RT-PCR in coronary endothelial cells. Therefore, it is suggested that AT1 receptors mediate the effects of angiotensin II on E-selectin expression and leukocyte adhesion on coronary endothelial cells.
Enhanced hepatocellular trafficking of cholesterol to the bile canaliculus and cholesterol hypersecretion appears critical for gallstone formation. Therefore, we studied in more detail the hepatic cholesterol transport pathways in a mouse model of cholesterol gallstone disease. Biliary lipid secretion rates, plasma lipoprotein levels, hepatic expression of lipoprotein receptors, lipid regulatory enzymes, and putative cholesterol transporting proteins were analyzed in gallstone-susceptible C57L/J and gallstone-resistant AKR/J mice, which were fed a lithogenic diet. Biliary cholesterol hypersecretion in C57L mice was associated with decreased plasma high-density lipoprotein (HDL) cholesterol levels and significant hepatic induction of the HDL receptor (SRBI) and cholesteryl ester hydrolase. In response to the lithogenic diet, fatty-acid binding protein of liver (FABPL) was markedly induced in both mouse strains. Caveolin 1 was elevated only in plasma membranes of gallstone-susceptible C57L mice, which also failed to down-regulate cholesterol synthesis. These data suggest a role of the reverse cholesterol transport pathway for genetically determined gallstone susceptibility in the mouse. (HEPATOLOGY 2001;33: 1451-1459.)
There were significant improvements in all measured variables in very old adults participating in CR soon after CABG. With additional functional exercise training, participants randomized to IG improved significantly more than those randomized to CG on 6-MWD, TUG time, and relative workload.
The increasing use of ventricular assist devices (VADs) in terminal heart failure patients provides new challenges to cardiac rehabilitation physicians. Structured cardiac rehabilitation strategies are still poorly implemented for this special patient group. Clear guidance and more evidence for optimal modalities are needed. Thereby, attention has to be paid to specific aspects, such as psychological and social support and education (e.g., device management, INR self-management, drive-line care, and medication).In Germany, the post-implant treatment and rehabilitation of VAD Patients working group was founded in 2012. This working group has developed clear recommendations for the rehabilitation of VAD patients according to the available literature. All facets of VAD patients' rehabilitation are covered. The present paper is unique in Europe and represents a milestone to overcome the heterogeneity of VAD patient rehabilitation.
Adequate physical and functional performance is an important prerequisite for renewed participation and integration in self-determined private and (where appropriate) professional lives following left ventricular assist device (LVAD) implantation. During cardiac rehabilitation (CR), individually adapted exercise programs aim to increase exercise capacity and functional performance. A retrospective analysis of cardiopulmonary exercise capacity and functional performance in LVAD patients at discharge from a cardiac rehabilitation program was conducted. The results from 68 LVAD patients (59 males, 9 females; 55.9 6 11.7 years; 47 HVAD, 2 MVAD, 15 HeartMate II, 4 HeartMate 3, and 4 different implanting centers) were included in the analysis. Exercise capacity was assessed using a cardiopulmonary exercise test on a bicycle ergometer (ramp protocol; 10 W/min). The 6-min walk test was used to determine functional performance. At discharge from CR (53 6 17 days after implantation), the mean peak work load achieved was 62.2 6 19.3 W (38% of predicted values) or 0.79 6 0.25 W/kg body weight. The mean cardiopulmonary exercise capacity (relative peak oxygen uptake) was 10.6 6 5.3 mL/kg/min (37% of predicted values). The 6-min walk distance improved significantly during CR (325 6 106 to 405 6 77 m; P < 0.01). No adverse events were documented during CR. The results show that, even following LVAD implantation, cardiopulmonary exercise capacity remains considerably restricted. In contrast, functional performance, measured by the 6-min walk distance, reaches an acceptable level. Light everyday tasks seem to be realistically surmountable for patients, making discharge from inpatient rehabilitation possible. Long-term monitoring is required in order to evaluate the situation and how it develops further. Key Words: Heart failure-Left ventricular assist deviceCardiac rehabilitation-Exercise capacity-Functional performance.In the last few years, left ventricular assist devices (LVADs) have been increasingly implanted as treatment for terminal heart failure (HF). Whereas initially these systems were only used as a bridge to transplantation (BTT), today approximately half of all recipients have them implanted as the ultimate destination therapy (DT) (1).The overriding therapeutic goal of LVAD implantation is to ensure patient survival and guarantee preservation of organ function (2). However, when patients become permanently dependent on the system, a return to everyday life and restoration of an acceptable quality of life acquire crucial significance. An optimum build-up of exercise capacity and adequate functional performance is therefore very significant. Cardiac rehabilitation (CR) can and should make an important contribution in this context (3,4). After being discharged from a CR center the patients should once more become able to autonomously manage the necessary tasks in their everyday lives back home.Over the last few years, several studies have emerged, most of them small, which report results following rehabilitat...
The results demonstrate a heterogeneous group with a high level of impairment and special needs in many CR domains. The development and evaluation of a special highly individualized approach of CR, which meets the special needs of these patients, is needed.
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