Disruption of the murine mdr2 gene leads to the complete absence of biliary phospholipids. We tested the hypothesis that the increase in biliary phospholipid output induced by fibrates is mediated via induction of the hepatic mdr2 gene and its encoded product, the P-glycoprotein canalicular flippase. Increased levels of mdr2 mRNA were observed in the liver of mice treated with different fibrates : ciprofibrate, 660p155 % (as compared with control group) ; clofibrate, 611p77 % ; bezafibrate, 410p47 % ; fenofibrate, 310p52 % ; gemfibrozil, 190p25 % (P 0n05 compared with control group). Induction of expression of the mdr gene family was specific to the mdr2 gene. Two-to three-fold increases in P-glycoprotein immunodetection were evident on the canalicular plasma-membrane domain of clofibrate-and ciprofibrate-treated mice. Biliary phospholipid output increased

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These data suggest the presence of rate-dependent transversal conduction block at the crista terminalis in patients with typical AFL. Block is usually observed at longer pacing cycle lengths with PW pacing than with LW pacing. This difference may be a critical determinant of the counterclockwise rotation of typical AFL.

Perinatal exposure to chronic hypoxia induces sustained hypertension and structural and functional changes in the pulmonary vascular bed. We hypothesized that highland newborn lambs (HLNB, 3600 m) have a higher pulmonary arterial pressure (PAP) due in part to a higher activity/expression of phosphodiesterase 5 (PDE5). We administered sildenafil, a PDE5 inhibitor, during basal and hypoxic conditions in the pulmonary hypertensive HLNB and compared them to lowland newborn lambs (LLNB, 580 m). Additionally, we compared the vasodilator responses to sildenafil in isolated small pulmonary arteries and the PDE5 mRNA expression and evaluated the vascular remodeling by histomorphometric analysis in these newborn lambs. Under basal conditions, HLNB had a higher PAP and cardiac output compared with LLNB. Sildenafil decreased the PAP during basal conditions and completely prevented the PAP increase during hypoxia in both groups. HLNB showed a greater contractile capacity and a higher maximal dilation to sildenafil. PDE5 mRNA expression did not show significant differences between HLNB and LLNB. The distal pulmonary arteries showed an increased wall thickness in HLNB. Our results showed that HLNB are more sensitive to sildenafil and therefore could be useful for treatment of pulmonary hypertension in high-altitude neonates. E xposure of lowland species to high altitude produces pulmonary vasoconstriction and remodeling resulting in pulmonary hypertension. Previously, we have shown that newborn lambs gestated and born at high altitude have an increased pulmonary arterial pressure (PAP) and vascular reactivity compared with those born at sea level (1). Appropriate increases in pulmonary vascular resistance (PVR) are adaptive, matching pulmonary perfusion to the reduced oxygenation. However, excessive increases in PVR, if maintained over time, lead to structural changes of the pulmonary vasculature, such as an increase in vascular muscle cells and fibrosis in the adventitia of the vessel (2-4). In newborns, either at altitude or sea level, this pulmonary arterial hypertension is ultimately due to a failure in the regulation of the PVR at birth by mechanisms not fully understood, which implies an imbalance in vasoconstrictors and vasodilators, leading to hypoxemia and sustained pulmonary hypertension. Indeed, one of the major causes of persistent pulmonary hypertension in the newborn is chronic hypoxia in utero (5) and is characterized by hypoxemia that is frequently refractory to conventional management, with a mortality rate near 10% (6). The incidence of this syndrome may be higher at high altitudes (7), an important issue considering that more than 140 million people worldwide live at more than 2500 m (8). Moreover, it has been suggested that during chronic hypoxia, production of vasoconstrictors is enhanced, while synthesis of vasodilators is reduced in the lung (9,10). A mechanism that favors this high vascular tone is the hydrolysis of cyclic guanosine monophosphate (cGMP) by phosphodiesterases (PDEs). The major ...

This study provides novel evidence that ultrastructural atrial remodeling characterized by an impaired cardiac autophagy is present in patients developing POAF after coronary artery bypass surgery.

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Sensitivity to oxygen levels reached within the organism is restricted to the peripheral arterial chemoreceptors, making ventilatory adaptations to changing oxygenation largely dependent on the information provided by these organs, of which the carotid body (CB) is the most important. The parenchyma of the CB is constituted by glomus (type I) cells and sustentacular (type II) cells. The CB is richly vascularized, and glomus cells are organized

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