Balancing Outcome vs. Urgency in Modern Liver Transplantation.

Background: Current allocation mechanisms for liver transplantation (LT) overemphasize emergency, leading to poorer longtime outcomes. The utility was introduced to recognized outcomes in allocation. Recently, Molinari proposed a predictive outcome model based on recipient data.

Sphingosine-1-Phosphate Enhances α-Adrenergic Vasoconstriction via S1P2-G-ROCK Mediated Signaling.

Sphingosine-1-phosphate (S1P) has been implicated recently in the physiology and pathology of the cardiovascular system including regulation of vascular tone. Pilot experiments showed that the vasoconstrictor effect of S1P was enhanced markedly in the presence of phenylephrine (PE). Based on this observation, we hypothesized that S1P might modulate α-adrenergic vasoactivity.

Shear stress-induced endothelial adrenomedullin signaling regulates vascular tone and blood pressure.

Hypertension is a primary risk factor for cardiovascular diseases including myocardial infarction and stroke. Major determinants of blood pressure are vasodilatory factors such as nitric oxide (NO) released from the endothelium under the influence of fluid shear stress exerted by the flowing blood. Several endothelial signaling processes mediating fluid shear stress-induced formation and release of vasodilatory factors have been described.

LPA receptor-mediated thromboxane A release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction.

Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA, LPA, LPA, and LPA In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and the LPA agonist VPC31143 induced dose-dependent vasoconstriction. VPC31143-induced AA contraction was sensitive to pertussis toxin (PTX), the LPA antagonist Ki16425, and genetic deletion of LPA but not that of LPA or inhibition of LPA, by diacylglycerol pyrophosphate.

Lysophosphatidic acid induces vasodilation mediated by LPA1 receptors, phospholipase C, and endothelial nitric oxide synthase.

Lysophosphatidic acid (LPA) has been implicated as a mediator of several cardiovascular functions, but its potential involvement in the control of vascular tone is obscure. Here, we show that both LPA (18:1) and VPC31143 (a synthetic agonist of LPA1-3 receptors) relax intact mouse thoracic aorta with similar Emax values (53.9 and 51.