Long-term follow-up of portopulmonary hypertension: effect of treatment with epoprostenol.

Moderate to severe portopulmonary hypertension (PPHTN) increases the risks of orthotopic liver transplantation (OLT). Epoprostenol is an effective treatment of PPHTN, but long-term effects on pulmonary hemodynamics or liver function in PPHTN are poorly defined. We sought to describe the long-term effects of treatment with or without epoprostenol on pulmonary hemodynamics, liver biochemistries, and survival in patients with moderate to severe PPHTN at a single center. A large retrospective cohort was identified with moderate to severe PPHTN diagnosed before OLT. Baseline and follow-up pulmonary hemodynamics and liver biochemistries were compared and outcomes assessed. Nineteen patients were treated with epoprostenol and 17 were not treated with epoprostenol. There were significant improvements in mean pulmonary artery pressure (MPAP, 48.4-36.1 mm Hg; P < 0.0001), pulmonary vascular resistance (PVR, 632-282 dynes . s . cm(-5); P < 0.0001), and cardiac output (5.7 to 7.7 L/min; P = 0.0009) with epoprostenol after a median of 15.4 months. Liver biochemistries did not change significantly, and survival did not seem to differ between the 2 groups (hazard ratio, 0.85; P = 0.77). In the epoprostenol group, patients who survived had greater absolute changes in MPAP, transpulmonary gradient, and PVR than those who died. Two patients in the epoprostenol group successfully underwent OLT. Long-term epoprostenol therapy greatly improves pulmonary hemodynamics in patients with PPHTN. Liver biochemistries are not greatly changed. Survival seemed not to differ between treatment groups. A minority of patients treated with epoprostenol will improve sufficiently to undergo OLT.     

Hemodynamic Profile of Portopulmonary Hypertension

Portopulmonary hypertension (PPHTN) refers to the development of pulmonary arterial hypertension in the setting of portal hypertension with or without chronic hepatic failure. This syndrome is characterized by marked alternations of pulmonary vascular tone and obstruction of pulmonary arterial blood flow. An increased pulmonary blood flow, which is a hallmark of the hyperdynamic circulation of cirrhotic patients, seems to be present in almost all patients who develop PPHTN. The elevations of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) along with the transpulmonary gradient (TPG) have been considered in diagnosing PPHTN. Only a high TPG reflects the severity of obstruction to pulmonary blood flow and differentiates an elevated PAP with concomitant elevated PVR from the situation where the increase in PAP is due only to the hyperdynamic flow and elevated volume. A considerable risk for cardiovascular death arises when PAP increases significantly; this may occur in rapidly evolving syndromes, in very advanced disease, or during a complicated liver transplantation. The distinction between PPHTN and elevated PAP in the context of a hyperdynamic state is of great importance; a PAP increase of hyperkinetic origin, as opposed to PPHTN, is apparently not associated with a high risk for adverse effects during and following liver transplantation.     

Postnatal pulmonary hypertension after repair of congenital diaphragmatic hernia: predicting risk and outcome

BACKGROUND: Pulmonary hypertension (PH) after congenital diaphragmatic hernia (CDH) repair remains a significant cause of morbidity and mortality. Although treatment advances have improved overall survival, a new cohort of patients is surviving with PH beyond the postnatal period. Because the clinical entity of postnatal persistent pulmonary hypertension (PPHTN) in CDH patients has not been published, the authors undertook a retrospective study of our neonatal CDH experience to characterize this group of infants. METHODS: Charts of all infants with CDH treated at this institution from January 1991 to June 1997 were reviewed (n = 51). Persistent pulmonary hypertension by echocardiographic (Echo) measurements at the time of discharge identified PPHTN patients. Control survivors had normal pulmonary artery pressures at discharge. Physiological parameters and the results of therapeutic interventions were analyzed to predict PPHTN. RESULTS: Seven infants (four boys, three girls) had PPHTN at discharge. Significant differences with the control group were noted in length of stay, duration of intubation, and duration of nitric oxide therapy. Extracorporeal membrane oxygenation (ECMO) duration was not significantly different between the groups. By 12 months of age, PPHTN resolved in six patients (87%), and one died at 13 months. Regardless of therapy, two parameters showed 100% positive predictive value for identifying patients with PPHTN (P < .001): an Echo demonstrating PH at 2 months of age or continued oxygen requirement at 3 months. Oxygen requirement at 2 months had a 67% predictive value of PPHTN. CONCLUSIONS: With current treatment strategies for CDH, infants can survive with persistent pulmonary hypertension beyond the newborn period. The long-term survival rate is excellent, and normalization of pulmonary artery pressures can be expected. PPHTN can be predicted in those infants with Echo-defined pulmonary hypertension at 2 months.     

Inhaled nitric oxide reduces pulmonary artery pressures in portopulmonary hypertension.

Pulmonary artery hypertension in association with liver failure (portopulmonary hypertension [PPHTN]) is a significant barrier to liver transplantation because patients with this condition have a very high mortality when transplantation is undertaken. Inhaled nitric oxide (NO), a potent pulmonary vasodilator, reduces pulmonary artery pressure (PAP) in some patients with primary pulmonary hypertension, but its effect in patients with PPHTN is controversial. We investigated the hemodynamic effects of inhaled NO in 6 patients with PPHTN. Five of 6 patients responded to NO inhalation with decreases in PAP and pulmonary vascular resistance of greater than 10%; these decreases were statistically significant at NO concentrations of 10 and 30 ppm. Cardiac output did not significantly change. We conclude that inhalation of NO reduces PAPs in some patients with PPHTN.     

Progressive splenomegaly after epoprostenol therapy in portopulmonary hypertension.

Patients with end-stage liver failure, portal hypertension, and associated pulmonary artery hypertension (portopulmonary hypertension [PPHTN]) have a high mortality when undergoing liver transplantation. Successful transplantation in these patients may depend on efforts to reduce pulmonary artery pressure (PAP). To this end, a number of centers are using a continuous intravenous (IV) infusion of epoprostenol, which has been shown to improve symptoms, extend life span, and reduce PAP in patients with primary pulmonary hypertension. We report four cases in which treatment of patients with PPHTN with continuous IV epoprostenol was followed by the development of progressive splenomegaly, with worsening thrombocytopenia and leukopenia. This finding may limit the usefulness of epoprostenol in PPHTN and influence the timing of transplantation in such patients.     

Sildenafil Monotherapy to Treat Portopulmonary Hypertension Before Liver Transplant

Portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis. Patients with severe PPHTN are contraindicated for liver transplant because of the associated risk of intraoperative acute right heart failure during reperfusion phase or massive volume infusion. Therefore, it has been recommended that patients with moderate to severe PPHTN undergo medical treatment to lower the pulmonary artery pressure before undergoing transplant. Herein, we report 3 patients with severe PPHTN who underwent sildenafil monotherapy before living donor liver transplant. None of the patients experienced associated adverse effects during sildenafil treatment, and the pulmonary artery pressure was effectively reduced before transplant. The first patient was diagnosed during anesthesia prior to transplant, and the mean pulmonary artery pressure was reduced by 34% after treatment. The second and third patients were followed-up with echography, and the estimated pulmonary artery systolic pressure were reduced by 34% and 47%, respectively. Pretransplant right heart catheterization also confirmed the reduction of the mean pulmonary artery pressure. Intraoperative hemodynamic parameters were stable, and the 3 patients were discharged uneventfully. After transplant, sildenafil was discontinued, and all patients remained in a stable clinical and functional status during follow-up.     

The Impact of Treatment of Portopulmonary Hypertension on Survival Following Liver Transplantation

Pulmonary hypertension in the setting of cirrhosis and portal hypertension is known as portopulmonary hypertension (PPHTN). Moderate or severe PPHTN is uncommon, but has a poor prognosis and is considered to be a contraindication to liver transplantation. We assessed the impact of vasodilation therapy on pulmonary hemodynamics and outcome after liver transplant in these patients. Eighty-six patients evaluated for liver transplant between 1997 and 2005 had an estimated right ventricular systolic pressure >40 mm Hg or a clinical suspicion of PPHTN. Right heart catheterization confirmed PPHTN in 30 patients (ten mild, eight moderate, and 12 severe). Sixteen of the 20 with moderate-to-severe pulmonary hypertension (mPAP >or= 35) were otherwise considered suitable liver transplant candidates and were treated with vasodilation therapy. mPAP fell to less than 35 mm Hg in 12 patients (75%) and 11 of them then underwent orthotopic liver transplantation. One- and five-year survivals in the transplanted patients were 91% and 67%, respectively. Nine of 11 were off vasodilator therapy after a median of 9.2 months following transplantation. None of the patients who failed vasodilator therapy survived (median survival, 8 months). Effective pharmacologic control of PPHTN before liver transplant is associated with excellent posttransplant survival that is similar to patients transplanted for other indications.     

Inhaled nitric oxide administration during one-lung ventilation in patients undergoing thoracic surgery

OBJECTIVE: To evaluate the effects of inhaled nitric oxide (iNO) on hemodynamics and oxygenation during one-lung ventilation (OLV) in the lateral decubitus position in patients undergoing elective thoracic surgery. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Thirty consecutive patients scheduled for thoracotomy. INTERVENTIONS: Anesthesia consisted of thoracic epidural analgesia combined with general anesthesia (isoflurane, fentanyl, and vecuronium bromide). Systemic and pulmonary circulations were monitored with a radial artery catheter and a pulmonary artery catheter. Inhaled NO, 40 ppm, was administered during OLV, and the inhaled gas mixture was monitored for NO and nitrogen dioxide (NO2). Hemodynamic and oxygenation data were collected before and during inhaled NO administration. MEASUREMENTS AND MAIN RESULTS: Inhaled NO caused a reduction of pulmonary vascular resistance index from 249 +/- 97.6 dyne. sec. cm(-5) to 199.3 +/- 68.9 dyne. sec. cm(-5) (p < 0.05), without effects on systemic hemodynamics or impairment of oxygenation. A stratification of the patients according to values of QS/QT (< 30%, 30% to 44%, > or = 45%), PaO(2)/fraction of inspired oxygen (> or = 200, 100 to 199, < 100), and pulmonary hypertension (mean pulmonary arterial pressure < 24 or > or = 24 mmHg) showed that inhaled NO causes a significant reduction of mean pulmonary artery pressure in patients with pulmonary hypertension, mainly as a result of a reduction of pulmonary vascular resistance index, and improves oxygenation by reducing intrapulmonary shunt in patients with severe hypoxemia during OLV. CONCLUSIONS: Inhaled NO administration neither significantly decreased mean pulmonary arterial pressure in patients with normal pulmonary artery pressure nor improved oxygenation in nonhypoxic patients. Nevertheless, inhaled NO is effective in patients with pulmonary hypertension and hypoxemia during OLV.     

Demographic features, BMPR2 status and outcomes in distal chronic thromboembolic pulmonary hypertension

BACKGROUND: Although pulmonary endarterectomy (PEA) is potentially curative in chronic thromboembolic pulmonary hypertension (CTEPH), some patients have distally distributed disease that is not amenable to surgery. The aetiology and characteristics of this patient group are currently not well understood. OBJECTIVES: This study compares the baseline demographic features and outcomes in subjects with distal CTEPH, those with proximal CTEPH and those with idiopathic pulmonary arterial hypertension (IPAH) to determine whether these conditions represent separate entities or whether they exist along the same spectrum of disease. METHODS: The medical history, clinical characteristics, bone morphogenetic protein receptor type II (BMPR2) mutation status and outcomes of 96 subjects with IPAH, 35 with distal CTEPH and 68 with proximal CTEPH referred to a single specialist centre between 1994 and 2005 were reviewed. RESULTS: There were significant differences between the distal CTEPH, proximal CTEPH and IPAH groups in age (55.9 years vs 54.8 years vs 46.2 years, p<0.001), proportion who were male (43% vs 69% vs 29%, p<0.001), previous deep vein thrombosis (28.6% vs 30.9% vs 3.1%, p<0.001), positive BMPR2 status (0% vs 0% vs 15%, p = 0.018), mean pulmonary artery pressure (47.3 mm Hg vs 45.4 mm Hg vs 54.8 mm Hg, p<0.001) and total pulmonary resistance (12.9 WU vs 12.4 WU vs 18.1 WU, p<0.001). Patients with distal CTEPH and those with IPAH were managed similarly and had comparable survival characteristics (1 year survival 77% vs 86%; 3 year survival 53% vs 60%; p = 0.68). CONCLUSIONS: Patients with distal CTEPH share certain demographic features with patients with proximal CTEPH that not only indicate a common aetiology but also help to differentiate them from patients with IPAH. Despite more favourable haemodynamic parameters in those with distal CTEPH, patients in this group had a poor long-term outcome which was similar to that of patients with IPAH.     

Pathophysiology of pulmonary edema following experimental brain death in the chacma baboon

Systemic and pulmonary hemodynamics have been studied during the induction of brain death in the chacma baboon. In 11 animals brain death was induced by acute intracranial hypertension. Continuous recording of blood flow through both the pulmonary artery and the aorta was obtained by electromagnetic flow meters placed around these vessels. Mean arterial, central venous, pulmonary arterial, and left atrial pressures were recorded continuously. Systemic and pulmonary vascular resistances were calculated. During the agonal period marked sympathetic activity occurred, with significant increases in circulating catecholamines and systemic vascular resistance. The great increase in systemic resistance resulted in acute left ventricular failure. Mean left atrial or pulmonary capillary wedge pressure rose above the mean pulmonary arterial pressure in 9 animals. As the systemic vascular resistance rose, a significant difference between pulmonary artery and aortic blood flows occurred, leading to blood pooling within the lungs. A mean of 72% of the total blood volume of the animal accumulated within these organs. The increase of left atrial pressure to levels higher than pulmonary artery pressure indicated a state of pulmonary capillary blood flow arrest. This, associated with the blood pooling within the lungs, almost certainly resulted in disruption of the anatomic integrity of the pulmonary capillaries (blast injury); 4 animals developed pulmonary edema, with alveolar septal interstitial hemorrhage.     

Pulmonale Hypertonie

Chronic pulmonary hypertension (PHT) is characterized by permanently increased pulmonary artery pressure. Diagnostic criteria are a mean pulmonary arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. Pulmonary arterial hypertension is characterized by progressive obliteration of the pulmonary vascular bed, which results in progressive right heart failure and death. Pathologic processes behind the complex vascular changes associated with PHT include vasoconstrictor/vasodilator imbalance, thrombosis, misguided angiogenesis and inflammation. The function of the pulmonary endothelium is altered with decreased production of vasodilators such as prostacyclin and nitric oxide and an increased production of endothelins, finally resulting in pulmonary vascular remodelling. A new diagnostic classification of pulmonary hypertension (PHT) was proposed at the World Health Organization (WHO) Pulmonary Hypertension Meetings held in Evian in 1998 and in Venice in 2003. This classification reflects recent advances in the understanding of pulmonary hypertensive diseases. Depending on the underlying disease and the localization of the vascular lesion, five different subgroups of PHT are formed. An exact diagnostic classification is necessary for application of the current treatment options for the different forms of PHT. Target of therapy is besides avoiding local thrombosis by anticoagulation and treatment of vasoconstriction, the prevention of vascular remodelling. For patients with advanced pulmonary arterial hypertension (PAH; NYHA stages III and IV) treatment with prostanoids (inhalative, oral, subcutaneous or intravenous), with endothelin-receptor antagonists or with a phosphodiesterase inhibitor can be indicated. Whether initial or adjunct combined therapy provides additional clinical benefits to patients with severe pulmonary arterial hypertension needs further investigation, but first results are promising.     

Response to nitric oxide during adult cardiac surgery.

Pulmonary hypertension is associated with significant morbidity and mortality in adult cardiac surgery patients. Inhaled nitric oxide is known to be a selective pulmonary vasodilator in this setting. However, it is not known which cardiac surgery patients benefit most from nitric oxide therapy. This study sought to prospectively determine whether a patient's baseline pulmonary vascular resistance could be used to predict responsiveness to inhaled nitric oxide therapy. Subjects were 30 consecutive cardiac surgery patients with pulmonary hypertension immediately prior to induction of anesthesia. There were 2 study groups: Group 1 (n = 15) had an initial pulmonary vascular resistance between 125 and 300 dyn-s/cm5, while group 2 (n = 15) had an initial pulmonary vascular resistance of greater than 300 dyn-s/cm5. Both groups were empirically treated with inhaled nitric oxide (30 ppm) upon separation from bypass. The conduct of anesthesia, surgery, and cardiopulmonary bypass were controlled. A therapeutic algorithm dictated the use of vasoactive substances for all patients. Heart rate, mean arterial pressure, pulmonary vascular resistance, peripheral vascular resistance, cardiac index, and right ventricular ejection fraction were monitored throughout the operative experience. Patients with a higher initial pulmonary vascular resistance had a significantly greater percent reduction in pulmonary vascular resistance after the initiation of nitric oxide therapy. This study suggests that pulmonary vascular resistance is more dramatically affected by inhaled nitric oxide in cardiac surgery patients with a greater degree of pulmonary hypertension.     

Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation.

BACKGROUND: Pre-transplant fixed pulmonary hypertension is associated with higher post-transplant mortality. In this study, we assessed the significance of pre-transplant reversible pulmonary hypertension in patients undergoing cardiac transplantation. METHODS: Overall, we studied 182 patients with baseline normal pulmonary pressures or reversible pulmonary hypertension, defined as a decrease in pulmonary vascular resistance (PVR) to < or =2.5 Wood units (WU), who underwent cardiac transplantation. Multiple recipient and donor characteristics were assessed to identify independent predictors of mortality. RESULTS: The average duration of follow-up was 42 +/- 28 months. Forty patients (22%) died during the follow-up period. Baseline hemodynamics for alive vs dead patients were as follows: pulmonary artery systolic (PAS) 42 +/- 15 vs 52 +/- 15 mm Hg; PA diastolic 21 +/- 9 vs 25 +/- 9 mm Hg; PA mean 28 +/- 11 vs 35 +/- 10 mm Hg; transpulmonary gradient (TPG) 9 +/- 4 vs 11 +/- 7 mm Hg (all p < 0.05); total pulmonary resistance 7.7 +/- 4.8 vs 8.8 +/- 3.2 WU (p = 0.08); and PVR 2.3 +/- 1.5 vs 2.9 +/- 1.6 WU (p = 0.06). In an unadjusted analysis, patients with PAS >50 mm Hg had a higher risk of death (odds ratio [OR] 5.96, 95% confidence interval [CI] 1.46 to 19.84 as compared with PAS < or =30 mm Hg). There was no significant difference in survival among patients with baseline PVR <2.5, 2.5 to 4.0 or >4.0 WU, but patients with TPG > or =16 had a higher risk of mortality (OR 4.93, 95% CI 1.84 to 13.17). PAS pressure was an independent predictor of mortality (OR 1.04, 95% CI 1.02 to 1.06). Recipient body mass index, history of sternotomy; and donor ischemic time were the other independent predictors of mortality. CONCLUSION: Pre-transplant pulmonary hypertension, even when reversible to a PVR of < or =2.5 WU, is associated with a higher mortality post-transplant.     

Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension

BACKGROUND: It has previously been shown that IgG antibodies from patients with limited cutaneous systemic sclerosis (SSc) bind to specific microvascular endothelial cell antigens. Since patients with limited cutaneous SSc are prone to develop pulmonary arterial hypertension (PAH), and since endothelial cell activation is involved in the pathogenesis of idiopathic PAH (IPAH), a study was undertaken to examine the presence of anti-endothelial cell antibodies in patients with idiopathic or SSc associated PAH. METHODS: PAH was confirmed by right heart catheterisation (mean pulmonary artery pressure at rest >25 mm Hg). Serum IgG and IgM reactivities were analysed by immunoblotting on human macrovascular and microvascular lung and dermal endothelial cells from patients with IPAH (n = 35), patients with PAH associated with SSc (n = 10), patients with diffuse (n = 10) or limited cutaneous (n = 10) SSc without PAH, and 65 age and sex matched healthy individuals. RESULTS: IgG antibodies from patients with IPAH bound to a 36 kDa band in macrovascular endothelial cell extracts with a higher intensity than IgG from other patient groups and controls. IgG antibodies from patients with IPAH bound more strongly to a 58 kDa band in microvascular dermal endothelial cells and to a 53 kDa band in microvascular lung endothelial cells than IgG antibodies from other patients and controls. IgG antibodies from patients with limited cutaneous SSc with or without PAH, but not from other groups or from healthy controls, bound to two major bands (75 kDa and 85 kDa) in microvascular endothelial cells. CONCLUSION: IgG antibodies from patients with idiopathic or SSc associated PAH express distinct reactivity profiles with macrovascular and microvascular endothelial cell antigens.     

Effect of nitroglycerin inhalation on patients with pulmonary hypertension undergoing mitral valve replacement surgery

BACKGROUND: The aim of this study was to investigate the postoperative hemodynamic effects of nitroglycerin inhalation on patients with pulmonary hypertension undergoing mitral valve replacement surgery. METHODS: Twenty patients who underwent mitral valve replacement surgery were included in the study. In the surgical intensive care unit, at T0 (before the inhalation of nitroglycerin), basal systemic and pulmonary hemodynamics were recorded. Then, 2.5 microg x kg-1 x min-1 nitroglycerin liquid nebulized by a 2-l gas flow of 40% oxygen and air mixture was administered to the patients who were diagnosed as having pulmonary hypertension (mean pulmonary arterial pressures > 25 mmHg). The same parameters were measured at the first (T1), third (T2), and fifth (T3) hours after the beginning of this treatment and 1 h after the end of nitroglycerin inhalation (T4). RESULTS: There were no statistically significant differences at T0, T1, T2, T3, or T4 with respect to heart rate, mean arterial pressure, systemic vascular resistance, cardiac index, mixed venous oxygen saturation, arteriovenous oxygen content difference, or arterial carbon dioxide tension. However, mean pulmonary artery pressure, pulmonary vascular resistance, and intrapulmonary shunt fraction were significantly lower, and the arterial oxygen tension/fraction of inspired oxygen ratio was higher at T1, T2, and T3 when compared to that of T0 and T4. CONCLUSION: The results suggest that nitroglycerin inhalation produces a significant reduction in both mean pulmonary artery pressure and pulmonary vascular resistance in patients after mitral valve operations without reducing mean arterial pressure and systemic vascular resistance. Therefore, it might be a safe and useful therapeutic intervention during the postoperative course.     

Effect of Nitroglycerin Inhalation on Patients with Pulmonary Hypertension Undergoing Mitral Valve Replacement Surgery

Background: The aim of this study was to investigate the postoperative hemodynamic effects of nitroglycerin inhalation on patients with pulmonary hypertension undergoing mitral valve replacement surgery.

Methods: Twenty patients who underwent mitral valve replacement surgery were included in the study. In the surgical intensive care unit, at T0 (before the inhalation of nitroglycerin), basal systemic and pulmonary hemodynamics were recorded. Then, 2.5 [mu]g [middle dot] kg-1 [middle dot] min-1 nitroglycerin liquid nebulized by a 2-l gas flow of 40% oxygen and air mixture was administered to the patients who were diagnosed as having pulmonary hypertension (mean pulmonary arterial pressures > 25 mmHg). The same parameters were measured at the first (T1), third (T2), and fifth (T3) hours after the beginning of this treatment and 1 h after the end of nitroglycerin inhalation (T4).

Results: There were no statistically significant differences at T0, T1, T2, T3, or T4 with respect to heart rate, mean arterial pressure, systemic vascular resistance, cardiac index, mixed venous oxygen saturation, arteriovenous oxygen content difference, or arterial carbon dioxide tension. However, mean pulmonary artery pressure, pulmonary vascular resistance, and intrapulmonary shunt fraction were significantly lower, and the arterial oxygen tension/fraction of inspired oxygen ratio was higher at T1, T2, and T3 when compared to that of T0 and T4.     

Portopulmonary hypertension and the liver transplant candidate

The management of the liver transplant (OLT) candidate with portopulmonary hypertension (PPHTN) has dramatically changed in the past 3 years. Careful preoperative evaluation with functional characterization of right ventricular function plays a critical role. The pulmonary vascular response to epoprostenol infusion serves as a deciding factor for OLT candidacy. Careful perioperative attention to avoid right ventricular failure from acutely elevated pulmonary artery pressures or sudden increases in right ventricular preload is a key physiologic tenet of management. With increased surgical expertise, anesthetic sophistication, and availability of epoprostenol, PPHTN is no longer considered an absolute contraindication for OLT.     

Preoperative and postoperative response to inhaled nitric oxide

The preoperative dose response to inhaled nitric oxide (NO) was compared with the need for and response to NO after cardiac surgery in patients with congenital heart defect and secondary pulmonary hypertension. In a preoperative vasodilator test with inhaled NO 20, 40 and 80 ppm and oxygen, mean pulmonary artery pressure (PAP) was at least 40 mmHg and/or the pulmonary vascular resistance index (PVRI) 4 Wood units. Preoperatively, NO 40 ppm and FiO2 0.9 reduced systolic pulmonary/systemic arterial pressure (PAPs/SAPs) from 0.89 (SD 0.10) to 0.80 (0.18) and pulmonary/systemic vascular resistance (PVR/SVR) from 0.26 (0.13) to 0.13 (0.08). Haemodynamic assessment was repeated in 11 patients postoperatively. NO treatment was started if PAPs/SAPs rose to 0.8 or the pulmonary oximetry fell below 40%. Postoperatively, eight of 11 patients, including 6 patients with Down's syndrome, needed NO. PAPs/SAPs decreased more than preoperatively: 48.5% vs 11.2, p = 0.0045. Pulmonary oximetry increased by 15.7%, p = 0.02. The degree of preoperative response to NO did not differ between the patients with postoperative pulmonary hypertension and the other children. Patients with early pulmonary hypertensive crisis (first 24 h; n = 6) had a higher PVRI (7.6 vs 4.4 Um2; p = 0.003) and PVR/SVR (0.34 VS 0.17; p = 0.02) preoperatively. Two patients died in pulmonary hypertensive crisis.     

The use of milrinone in pre-transplant assessment of patients with congestive heart failure and pulmonary hypertension.

BACKGROUND: Pulmonary hypertension in patients with congestive heart failure (CHF) is a risk factor for increased mortality after orthotopic cardiac transplantation. Reversibility of elevated pulmonary vascular resistance (PVR) by pharmacologic agents predicts improved outcomes. Milrinone, a phosphodiesterase inhibitor with vasodilating and positive inotropic properties, has been shown to lower PVR in one previous study. However, no study has documented outcomes after cardiac transplantation in patients in whom reversibility of pulmonary hypertension was demonstrated after administration of milrinone. METHODS: We retrospectively reviewed 19 patients with CHF and pulmonary hypertension defined as PVR > or = 3 Wood units, PVRI (pulmonary vascular resistance index) > or = 4 resistance units, or TPG (transpulmonary gradient = mean pulmonary artery pressure--mean capillary wedge pressure) > or = 12 mmHg being assessed for cardiac transplantation. A sub-group of 14 patients with severe pulmonary hypertension defined as PVR > or = 4, PVRI > or = 6 and TPG > or = 15 was also examined. Milrinone was administered as a bolus (50 ug/kg) and hemodynamic parameters were measured at 5, 10 and 15 minutes. Six patients received cardiac transplants. RESULTS: Administration of milrinone significantly lowered PVR, PVRI, mean pulmonary artery pressure (PAM)(all p = 0.002) and pulmonary capillary wedge pressure (PCWP)(p = 0.006). Cardiac output (CO) increased significantly (p = 0.001). TPG did not change (p = 0.33). In patients with severe pulmonary hypertension, the magnitude of these changes was greater. In addition, TPG was significantly lowered (p = 0.02). CONCLUSION: Milrinone lowered PVR by decreasing PAM and increasing CO significantly. In addition, PCWP was significantly lowered. These finding confirm both vasodilatory and inotropic effects of milrinone. Patients with severe pulmonary hypertension had more pronounced effects. There were no deaths in the group of patients proceeding to cardiac transplantation. Our study demonstrates the efficacy of milrinone in lowering PVR as well as suggesting safety in use in patients undergoing cardiac transplantation.     

Granulocyte elastase release and pulmonary hemodynamics in patients with mitral valvular disease

In patients with atrial septal defect in whom pulmonary hypertension could develop as a consequence of left-to-right shunt, the extent of neutrophil-mediated lung injury induced by cardiopulmonary bypass (CPB) is related to the degree of increase in the preoperative pulmonary artery pressure. In the present study, we investigated the relationship between levels of granulocyte elastase (GEL) after CPB and preoperative pulmonary hemodynamics or changes in pulmonary function after the operation in patients with mitral valve disease, in whom pulmonary hypertension could develop as a result of pulmonary venous congestion. The plasma levels of GEL were measured before and after CPB in patients who underwent mitral valve replacement. Respiratory index (RI) was evaluated preoperatively and postoperatively. Preoperative pulmonary hemodynamics were determined within one month of the operation. Granulocyte elastase level rose significantly after CPB from baseline (134.3 +/- 44.6 mg/L versus 2042.1 +/- 1215.0 mg/L; p <0.001). Peak level of GEL was significantly correlated with preoperative systolic pulmonary artery pressure (r = 0.71; p = 0.020), mean pulmonary artery pressure (r = 0.64; p = 0.046), pulmonary capillary wedge pressure (r = 0.68; p = 0.032), and pulmonary-to-systemic arterial pressure ratio (r = 0.64; p = 0.045), but not with the hemodynamic variables for pulmonary blood flow or pulmonary resistance. Moreover, the value of (Postoperative RI - Preoperative RI)/Preoperative RI was positively correlated with the peak level of GEL (r = 0.76; p = 0.011). In conclusion, in patients with mitral valvular disease, as in those with atrial septal defect, the increase in GEL level after CPB is proportional to the increase in preoperative pulmonary artery pressure, which may cause the accordant pulmonary vascular damage.