Nitric oxide does not reverse pulmonary hypertension associated with end-stage liver disease: A preliminary report

Abstract

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...

Severe pulmonary hypertension in liver transplant candidates

“…In our experience, inhaled nitric oxide does not reverse pulmonary hypertension associated with ESLD. 16 This finding is in keeping with the hypothesis of Whittle and Moncado 17 that the hyperdynamic state found in advanced liver disease is related to increased endogenous nitric oxide. If vasodilator therapy does not decrease pulmonary hypertension, the likelihood that OLT will reverse this condition is very low.…”

Diagnosis of portopulmonary hypertension in candidates for liver transplantation: A prospective study

“…When severe, this condition is a major risk factor for transplantation because, in most cases, patients are at best partially responsive to medical therapies. 1 If it is impossible to lower mean pulmonary artery pressure below 40 to 50 mm Hg during transplantation procedure, any significant hemodynamic changes, such as those observed at the time of caval clamping and reperfusion of the graft, may result in irreversible cardiac arrest, especially if right ventricular function is impaired. 2 As a consequence, many authors consider that severe portopulmonary hypertension (i.e., mean pulmonary artery pressure [MPAP] above 40 mm Hg) represents a contraindication for liver transplantation because it would carry an unacceptable mortality rate.…”

Inhaled nitric oxide reduces pulmonary artery pressures in portopulmonary hypertension

“…The first, by Ramsay et al, 14 describes 10 patients, 9 patients with primary liver disease (4 patients, ethanylic cirrhosis; 2 patients, hepatitis C; 2 patients, cirrhosis; 1 patient, primary biliary cirrhosis) and 1 patient with chronic graft rejection. Eight patients were aged 50 years or older and 5 patients were women.…”

“…12 An initial report suggested it could acutely reduce PAPs in patients with PPHTN, 13 but subsequent series have reported its apparent ineffectuality in this circumstance. 14,15 Supplemental oxygen has been shown to decrease PAPs in pulmonary hypertension when hypoxemia is a significant contributor to the disease process 16 ; in primary pulmonary hypertension, it does not usually produce benefit. 17 The only report of its effect in PPHTN is in the case reported by Mandell and Duke, 13 in which increased oxygen concentrations did not influence PAPs.…”