Advanced liver disease with portal hypertension may be associated with pulmonary hypertension. A review of 1,205 consecutive liver transplant patients was made to assess the incidence and severity of pulmonary hypertension in patients with end-stage liver disease. Postoperative data were reviewed to determine if outcome was influenced and, in patients with severe pulmonary hypertension, whether pulmonary hypertension was reversed after transplantation. The hemodynamic data of 5 patients who were found to have severe pulmonary hypertension before transplantation and did not receive transplants were also reviewed. The incidence of pulmonary hypertension in the patients who received transplants was 8.5% (n ‫؍‬ 102; mean pulmonary artery pressure, G25 mmHg). The incidence of mild pulmonary hypertension was 6.72% (n ‫؍‬ 81; systolic pulmonary artery pressure, 30 to 44 mmHg); that of moderate pulmonary hypertension was 1.16% (n ‫؍‬ 14; systolic pulmonary artery pressure, 45 to 59 mmHg); and that of severe pulmonary hypertension was 0.58% (n ‫؍‬ 7; systolic pulmonary artery pressure, G60 mmHg). Mild and moderate pulmonary hypertension did not influence the outcome of the procedure. Severe pulmonary hypertension was associated with mortality rates of 42% at 9 months posttransplantation and 71% at 36 months posttransplantation. Only 2 of 7 patients with severe pulmonary hypertension have survived liver transplantation with a good quality of life. The remaining 5 patients continued to deteriorate with progressive right heart failure with no evidence of amelioration of the pulmonary hypertension. This experience supports the view that in most patients who have severe pulmonary hypertension associated with advanced liver disease, it is caused by fixed pathological changes in the pulmonary vasculature, is not reversible with liver transplantation, and is associated with a very high perioperative mortality rate. Copyright 1997 by the American Association for the Study of Liver DiseasesA review of perioperative data was undertaken to establish the incidence of pulmonary hypertension in the first 1,205 consecutive orthotopic liver transplant (OLT) patients at Baylor University Medical Center (BUMC) and to elucidate whether the presence of pulmonary hypertension influenced the clinical outcome. Mild to moderate pulmonary hypertension has not been reported to contribute to mortality after transplant or to influence the clinical outcome. 1-3 On the other hand, severe primary pulmonary hypertension carries a significant perioperative risk and in many cases limits the quality of postoperative survival. 4 All records of OLT patients with severe pulmonary hypertension were studied in detail in an attempt to establish criteria for likely success of OLT in these patients. Patients and MethodsWe have defined pulmonary hypertension as a mean pulmonary artery pressure of 25 mmHg or greater and a pulmonary vascular resistance (PVR) of greater than 120 dyne · s Ϫ1 · cm Ϫ5 . 3 Pulmonary hypertension was then arbitrarily divided into three gro...

value because of their hypotensive effects on the systemic Pulmonary hypertension is a well known, though uncirculation. [4][5][6] In contrast, inhaled nitric oxide is a potent pulcommon complication of end-stage liver disease (ESLD).monary vasodilator without apparent systemic effects as it Patients with severe pulmonary hypertension and ESLD is removed from circulation rapidly by hemoglobin. 6 Nitric undergoing orthotopic liver transplantation (OLT) may oxide is a lipophilic gas, which can be introduced into the develop right ventricular failure and death. This study inspiratory limb of a breathing circuit and delivered to the investigates the reversibility of pulmonary hypertension alveoli. 7 Here it is absorbed by the capillaries supplying the by the inhalation of nitric oxide in patients under evaluventilated alveoli where it activates guanylate cyclase that ation for OLT. Ten patients with ESLD who were discovleads to an increase in cyclic 3 5 -monophosphate that causes ered to have moderate to severe pulmonary hypertensmooth muscle relaxation and vasodilation. 8 Nitric oxide has sion were administered nitric oxide via face mask in been used successfully in infants with persistent pulmonary concentrations ranging from 0 to 80 ppm. Inhaled nitric hypertension and also to treat pulmonary hypertension and oxide is a potent pulmonary vasodilator without apparshunting in adult respiratory distress syndrome. 7,9 The preent systemic effects. Nitric oxide had no demonstrable transplantation evaluation of patients with ESLD and puleffect on mean pulmonary artery pressure (PAP) (37 vs.monary hypertension with nitric oxide might determine those 37 mm Hg), transpulmonary gradient (TPG) (26 vs. 26 patients that have reversible pulmonary hypertension, which mm Hg), or pulmonary vascular resistance (PVR) (295 might be an indicator of resolution following OLT. It might vs. 288 dynesrsecrcm 05 ). Two patients were discovered also provide evidence of a potential mechanism for treating to have an elevated pulmonary artery occlusion presan exacerbation of pulmonary pressures during transplantasure (PAOP) on baseline readings. The cause of pulmotion. 10 nary hypertension in these two patients was secondary to volume overload as a result of hepato-renal syndrome rather than primary pulmonary arteriolar pathology PATIENTS AND METHODS and was responsive to diuresis or dialysis but not toTen patients under evaluation for OLT were found to have pulmonitric oxide therapy. In conclusion nitric oxide does not nary hypertension determined by clinical symptoms, chest radioreverse pulmonary hypertension associated with ESLD.graphs, precordial echocardiograms, and right-heart catheterization.(HEPATOLOGY 1997;25:524-527.)After institutional review board approval and informed consent each patient underwent a repeat right-heart catheterization so that pulAdvanced liver disease is associated with a hyperdynamic monary artery pressures could be monitored during the administracirculatory state. It is characterized by a decreased systemic tion...

The prolongation of vecuronium-induced neuromuscular block has been reported as a predictor of hepatic allograft dysfunction. This study investigates the duration of action of rocuronium, which also relies on hepatic clearance, to examine whether it also is prolonged with allograft dysfunction. Fifty-seven patients undergoing orthotopic liver transplant were given rocuronium (0.6 mg/kg) prior to allograft placement and the recovery of contraction of the orbicularis oculi muscle to a 2-Hz train-of-four stimulus was recorded. Fifteen minutes after reperfusion of the allograft, rocuronium (0.6 mg/kg) was administered and the time to recovery of muscle contraction to a train-of-four stimulus (train-of-four time) was again recorded. The patients were divided into two groups according to posttransplant liver function. Group I consisted of 50 patients with immediate normal liver function. Group II contained 7 patients with primary dysfunctional livers. Primary dysfunction was determined by peak serum aspartate aminotransferase and alanine aminotransferase levels > 2000 U/L, and prothrombin time > 16 s. The train-of-four time in Group II was prolonged compared with Group I (P < 0.05). Immediate graft function testing using the recovery time from rocuronium of > 150 min has a positive predictive value of 100% and a negative predictive value of 96%. The sensitivity and specificity is 71% and 100%, respectively. Receiver operating characteristic analysis supports this conclusion.

To examine the effect of gender and polymorphisms of CYP46 and apo E on plasma levels of 24S-hydroxycholesterol in Alzheimer's disease (AD) patients and to determine whether these factors contribute to the variability in responses to statin treatment. Fifty-three AD patients had measurement of plasma levels of 24S-hydroxycholesterol, plasma and lipoprotein cholesterol and genotyping of CYP46 and apo E. Thirty-nine of the subjects subsequently participated in a statin trial for 6 weeks, and had a repetition of the baseline measurements. Baseline levels of 24S-hydroxycholesterol were higher in women than in men. There was a positive and significant correlation of plasma oxysterol levels with levels of total plasma cholesterol (women: r = .72, P < .0001; men: r = .47, P = .02) and non-HDL cholesterol (women: r = .68, P < .0001; men: r = 0.51, P = .01) (and LDL cholesterol) but not HDL cholesterol levels. There was no association of CYP46 or apo E polymorphisms with plasma levels of 24S-hydroxycholesterol. AD subjects treated with statins had a similar percent reduction in lathosterol, 24S-hydroxycholesterol, total cholesterol and non-HDL (and LDL) cholesterol regardless of gender and polymorphisms of CYP46. Subjects with the 4/4 polymorphism had less reduction in the ratios of 24S-hydroxycholesterol-LDL cholesterol. Women with AD had higher levels of plasma 24S-hydroxycholesterol levels than men. Women also showed a very strong correlation of plasma levels of 24S-hydroxycholesterol-to-total and non-HDL cholesterol. This may suggest that the oxysterol may be an important marker of AD risk instead of total cholesterol, as suggested by others. Polymorphisms of CYP46 or apo E do not explain levels of oxysterol or non-HDL cholesterol or the responsiveness to statin treatment in this study.

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