Vascular pharmacology
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Vascular pharmacology · Dec 2005
Nitroglycerin-patch induced tolerance is associated with reduced ability of nitroglycerin to increase exhaled nitric oxide.
Nitroglycerin (GTN), used in the treatment of ischemic heart disease, acts through the liberation of nitric oxide (NO). However, its clinical use is limited due to tolerance development. Expired NO was used as an indicator of GTN-bioactivation and was measured together with plasma nitrite and mean arterial pressure (MAP) during GTN indicator infusions. ⋯ This indicates that expired NO could serve as an indicator of NO generation from GTN in the vascular system. We conclude that GTN tolerance is associated with reduced capacity to generate NO from GTN. Care should be taken in using MAP-reduction to evaluate tolerance since high indicator doses could liberate sufficient amounts of NO to elicit maximal MAP decrease even in tolerant animals.
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Vascular pharmacology · Oct 2005
Profiling biochemical and hemodynamic markers using chronically instrumented, conscious and unrestrained rats undergoing severe, acute controlled hemorrhagic hypovolemic shock as an integrated in-vivo model system to assess new blood substitutes.
The aim of the present study was to assess several biochemical and physiological endpoint parameters alongside controlled hemorrhagic and recovery phases of chronically instrumented, conscious and unrestrained healthy rats. Male Sprague-Dawley rats (12-14 weeks; 430+/-20 g; n=22-18) were instrumented with a saline-perfused femoral arterial catheter and placed individually in a metabolic cage for up to 20 days, allowing instant assessments of the hemodynamic profile and blood and urine sampling for hematological profile and biochemical measurements to assess hepatic, renal and metabolic functions. In addition, body weight, food and water intake, and diuresis were monitored daily. ⋯ Diuresis increased in both groups (by 45+/-7% on day 1) but presented distinct electrolytic profiles. Hepatic and renal functions were normal in AB rats whereas altered in SA rats. The present set of experiments enabled us to validate a model of HS in conscious rats and the use of an integrated in vivo platform as a valuable tool to characterize HS-induced stress and to test new classes of blood substitutes in real time, post-event, over days.
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Vascular pharmacology · Aug 2005
Comparative StudyEffects of budesonide and N-acetylcysteine on acute lung hyperinflation, inflammation and injury in rats.
Leukocyte activation and production of inflammatory mediators and reactive oxygen species are important in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury. The present study investigated acute lung hyperinflation, edema, and lung inflammation 4 h after an intratracheal instillation of LPS (0.5, 2.5, 5, 10, 50, 100, 500, 1000, and 5000 microg/ml/kg). Effects of budesonide, an inhaled anti-inflammatory corticosteroids, and N-acetylcysteine (NAC), an antioxidant, were evaluated in Wistar rats receiving either low (2.5 microg/ml/kg) or high (50 microg/ml/kg) concentrations of LPS. ⋯ Budesonide failed to prevent BALF levels of macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant 1 (GRO/CINC-1) as well as lung hyperinflation induced by both low and high concentrations of LPS. Pretreatment with budesonide totally prevented the formation of lung edema at the low concentration of LPS and had partial effects on acute lung injury and leukocyte influx at the high concentrations. Thus, our data indicate that therapeutic effects of budesonide and NAC are dependent upon the severity of the disease.
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Preconditioning describes a very powerful endogenous mechanism by which the heart may be protected against ischemia and reperfusion injury. Transient administration of a volatile anesthetic before a prolonged ischemic episode reduces myocardial infarct size to a degree comparable to that observed during ischemic preconditioning. ⋯ Several clinical studies also suggest that preconditioning by volatile anesthetics exerts beneficial effects in patients undergoing cardiac surgery. This review summarizes some of the recent major developments in the understanding of cardioprotection by volatile anesthetics.
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Vascular pharmacology · Jan 2005
Early haemodynamic benefit of sildenafil in patients with coexisting chronic thromboembolic pulmonary hypertension and left ventricular dysfunction.
Sildenafil, a phosphodiesterase type-5 inhibitor, offers potential to treat pulmonary hypertension associated with a variety of conditions. We assessed the early impact of sildenafil on a cohort of patients referred to our unit who had severe pulmonary hypertension secondary to chronic thromboembolic disease which was not amenable to pulmonary thromboendarterectomy and who also had coexisting left ventricular dysfunction. Six patients were studied. ⋯ All patients demonstrated an improvement in mean pulmonary artery pressure, mean pulmonary capillary wedge pressure, MRC dyspnoea score, NYHA class and gas transfer. No adverse effects of sildenafil were noted. Our data suggests that sildenafil is an effective and well-tolerated therapy for patients with severe pulmonary hypertension associated with pulmonary thromboembolic disease and impaired left ventricular function, producing beneficial effects as early as 6 weeks.