Regional alveolar hypoxia causes local vasoconstriction in the lung, shifting blood flow from hypoxic to normoxic areas, thereby maintaining gas exchange. This mechanism is known as hypoxic pulmonary vasoconstriction (HPV). Disturbances in HPV can cause life-threatening hypoxemia whereas chronic hypoxia triggers lung vascular remodeling and pulmonary hypertension. The signaling cascade of this vitally important mechanism is still unresolved. Using transient receptor potential channel 6 (TRPC6)-deficient mice, we show that this channel is a key regulator of acute HPV as this regulatory mechanism was absent in TRPC6 ؊/؊ mice whereas the pulmonary vasoconstrictor response to the thromboxane mimetic U46619 was unchanged. Accordingly, induction of regional hypoventilation resulted in severe arterial hypoxemia in TRPC6 ؊/؊ but not in WT mice. This effect was mirrored by a lack of hypoxiainduced cation influx and currents in smooth-muscle cells from precapillary pulmonary arteries (PASMC) of TRPC6 ؊/؊ mice. In both WT and TRPC6 ؊/؊ PASMC hypoxia caused diacylglycerol (DAG) accumulation. DAG seems to exert its action via TRPC6, as DAG kinase inhibition provoked a cation influx only in WT but not in TRPC6 ؊/؊ PASMC. Notably, chronic hypoxia-induced pulmonary hypertension was independent of TRPC6 activity. We conclude that TRPC6 plays a unique and indispensable role in acute hypoxic pulmonary vasoconstriction. Manipulation of TRPC6 function may thus offer a therapeutic strategy for the control of pulmonary hemodynamics and gas exchange.hypoxia-induced diacylglycerol accumulation ͉ precapillary pulmonary arterial smooth-muscle cells ͉ pulmonary hypertension ͉ transient receptor potential channel 6-deficient mouse model ͉ arterial hypoxemia A cute regional hypoxic pulmonary vasoconstriction (HPV) is necessary to maintain optimized gas exchange by directing blood flow from poorly ventilated to well ventilated areas of the lung. Under conditions of generalized hypoxia, however, total pulmonary vascular resistance rises with subsequent increase of right heart load (1-3). Chronic hypoxia, as occurring in ventilatory disorders induces chronic pulmonary hypertension, pulmonary vascular remodeling, and cor pulmonale (4). The underlying oxygen sensing and signal transduction mechanisms of the acute and chronic vascular responses are largely unknown. A rise of intracellular calcium ([Ca 2ϩ ] i ) in pulmonary artery smooth-muscle cells (SMCs) has been suggested to be the key event in these processes (5-8). However, the question how [Ca 2ϩ ] i is regulated has not yet been resolved. Among others, transient receptor potential (TRP) channels are regulators of [Ca 2ϩ ] i . The TRP protein superfamily consists of a diverse group of nonselective cation channels involved in many basic cellular processes (9). Whereas members of the TRPV and TRPM subfamilies have emerged as versatile cellular sensors, the functional importance of the seven members (TRPC1 to -7) of the TRPC (transient receptor potential cation channel subfamily C) subfamily...

Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion with ventilation to optimize pulmonary gas exchange. However, it remains unclear whether acute HPV (occurring within seconds) and the vasoconstrictor response to sustained alveolar hypoxia (developing over several hours) are triggered by identical mechanisms. We investigated the effect of mitochondrial and NADPH oxidase inhibitors on both phases of HPV in intact rabbit lungs. These studies revealed that the sustained HPV is largely dependent on mitochondrial complex I and totally dependent on complex IV, whereas NADPH oxidase dependence was only observed for acute HPV. These findings were reinforced by an alternative approach employing lungs from mice deficient in the NADPH oxidase subunit p 47(phox). In these mice (which lack a subunit suggested to be important for the function of most NADPH oxidase isoforms), but not in gp 91(phox)-deficient mice (which represent only one isoform of NADPH oxidases), acute HPV was significantly reduced, while non-hypoxia-induced vasoconstrictions elicited by the thromboxane mimetic U46619 were not affected. We concluded that the acute phase and the sustained phase of HPV are differentially regulated, with NADPH oxidase activity predominating in the acute phase, while a strong dependence on mitochondrial participation was observed for the second phase.

No abstract

The MitraClip percutaneous mitral valve repair system, developed as an option for percutaneous mitral repair, was clinically introduced in 2007. From 2010 through 2012, 6 of our patients underwent mitral valve surgery after MitraClip failure. Their mean age was 75 ± 7.7 years (range, 62–87 yr). Three had undergone cardiac surgery previously. In 5 of the 6 patients, mitral regurgitation recurred after initially successful MitraClip deployment and was the indication for surgery. The mean interval between MitraClip implantation and surgery was 106 ± 86 days (range, 0–238 d). Mitral valve repair was feasible in 3 patients; the others underwent valve replacement. All the patients underwent additional cardiac procedures, because the MitraClip worsened existing conditions. Echocardiograms revealed sufficient valvular repairs. Two patients died during hospitalization, one of cerebral infarction and the other of bowel ischemia. Mitral valve repair after failed MitraClip therapy can be complex and a surgical challenge. Careful consideration should be given to appropriate patient selection for MitraClip therapy, because the MitraClip can cause existing pathologic valvular conditions to deteriorate substantially. The interval between MitraClip failure and corrective surgery should be as short as possible. The primary indication is an issue of ongoing discussion.

Our preliminary data suggest that selective ACP during moderate-to-mild systemic hypothermic circulatory arrest (≥ 28°C) can safely be applied for more than 1 hour even in the setting of AAD.

Our data suggest that moderate systemic hypothermic circulatory arrest (≥ 28°C) in combination with antegrade cerebral perfusion can safely be applied for total aortic arch replacement with FET and offers sufficient neurologic and visceral organ protection.

No abstract

We demonstrated that serum TT levels were independently related to 24-hour urinary sodium amount.