American journal of physiology. Heart and circulatory physiology
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Am. J. Physiol. Heart Circ. Physiol. · Oct 2014
Observational StudySystemic microvascular shunting through hyperdynamic capillaries after acute physiological disturbances following cardiopulmonary bypass.
Previously we showed that cardiopulmonary bypass (CPB) during cardiac surgery is associated with reduced sublingual microcirculatory perfusion and oxygenation. It has been suggested that impaired microcirculatory perfusion may be paralleled by increased heterogeneity of flow in the microvascular bed, possibly leading to arteriovenous shunting. Here we investigated our hypothesis that acute hemodynamic disturbances during extracorporeal circulation indeed lead to microcirculatory heterogeneity with hyperdynamic capillary perfusion and reduced systemic oxygen extraction. ⋯ Hyperdynamic microcirculatory perfusion was associated with reduced arteriovenous oxygen difference and systemic oxygen consumption during and after CPB. The current study provides the first direct human evidence for a microvascular shunting phenomenon through hyperdynamic capillaries following acute physiological disturbances after onset of CPB. The hypothesis of impaired systemic oxygen offloading caused by hyperdynamic capillaries was supported by reduced blood arteriovenous oxygen difference and low systemic oxygen extraction associated with CPB.
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Am. J. Physiol. Heart Circ. Physiol. · Sep 2014
Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection.
Cholesterol-rich caveolar microdomains and associated caveolins influence sarcolemmal ion channel and receptor function and protective stress signaling. However, the importance of membrane cholesterol content to cardiovascular function and myocardial responses to ischemia-reperfusion (I/R) and cardioprotective stimuli are unclear. We assessed the effects of graded cholesterol depletion with methyl-β-cyclodextrin (MβCD) and lifelong knockout (KO) or overexpression (OE) of caveolin-3 (Cav-3) on cardiac function, I/R tolerance, and opioid receptor (OR)-mediated protection. ⋯ These data reveal the membrane cholesterol dependence of normoxic myocardial and coronary function, I/R tolerance, and OR-mediated cardioprotection in murine hearts (all declining with cholesterol depletion). In contrast, baseline function appears insensitive to Cav-3, whereas cardiac I/R tolerance parallels Cav-3 expression. Novel SLP appears unique, being less sensitive to cholesterol depletion than acute OR protection and arising independently of Cav-3 expression.
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Am. J. Physiol. Heart Circ. Physiol. · Aug 2014
β(2)-Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats.
Early hyperglycemia after trauma increases morbidity and mortality. Insulin is widely used to control posttrauma glucose, but this treatment increases the risk of hypoglycemia. We tested a novel method for early posttrauma hyperglycemia control by suppressing hepatic glycogenolysis via β2-adrenoreceptor blockade [ICI-118551 (ICI)]. ⋯ Lung wet-to-dry weight ratios were increased in OZ rats but not in LZ rats. ICI treatment reduced the early hyperglycemia, lung neutrophil retention, MPO activity, and wet-to-dry weight ratio in OZ rats to levels comparable with those seen in LZ rats, with no effect on blood pressure or heart rate. These results demonstrate that β2-adrenoreceptor blockade effectively reduces the early posttrauma hyperglycemia, which is associated with decreased lung injury in OZ rats.
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Am. J. Physiol. Heart Circ. Physiol. · Aug 2014
Direct and indirect protection of right ventricular function by estrogen in an experimental model of pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) results in right ventricular (RV) dysfunction and failure. Paradoxically, women are more frequently diagnosed with PAH but have better RV systolic function and survival rates than men. The mechanisms by which sex differences alter PAH outcomes remain unknown. ⋯ Consequently, when compared with the placebo-treated SuHx group, estrogen improved RV ejection fraction and cardiac output (ejection fraction: 57 ± 2% vs. 44 ± 2% and cardiac output: 9.7 ± 0.4 ml/min vs. 7.6 ± 0.6 ml/min; P < 0.05). Our study demonstrates for the first time that estrogen protects RV function in the SuHx model of PAH in mice directly by stimulating RV contractility and indirectly by protecting against pulmonary vascular remodeling. These results underscore the therapeutic potential of estrogen in PAH.
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Am. J. Physiol. Heart Circ. Physiol. · Aug 2014
Sildenafil treatment in established right ventricular dysfunction improves diastolic function and attenuates interstitial fibrosis independent from afterload.
Right ventricular (RV) function is an important determinant of prognosis in congenital heart diseases, pulmonary hypertension, and heart failure. Preventive sildenafil treatment has been shown to enhance systolic RV function and improve exercise capacity in a model of fixed RV pressure load. However, it is unknown whether sildenafil has beneficial effects when treatment is started in established RV dysfunction, which is clinically more relevant. ⋯ Sildenafil treatment also attenuated RV fibrosis (30 ± 6 vs. 17 ± 3‰, P < 0.05) but did not affect end-systolic elastance, exercise capacity, or PKG or PKA activity. In conclusion, sildenafil improves RV diastolic function and attenuates interstitial fibrosis in rats with established RV dysfunction, independent from afterload. These results indicate that sildenafil treatment has therapeutic potential for established RV dysfunction.