Decrease In mPAP Research Articles

Pulmonary Hemodynamic Responses to Brain Natriuretic Peptide and Sildenafil in Patients With Pulmonary Arterial Hypertension

Brain natriuretic peptide (BNP) blunts hypoxic pulmonary hypertension in animal models, but its acute hemodynamic effects in patients with pulmonary arterial hypertension (PAH) are not known. The aim of this study was to determine if human B-type natriuretic peptide is a safe and efficacious pulmonary vasodilator in patients with PAH and if the pulmonary hemodynamic effects are potentiated by phosphodiesterase inhibition. Open-label study. Medical ICUs of three tertiary care hospitals in New England. Thirteen consecutive adult patients undergoing right-heart catheterization and a pulmonary vasodilator trial for the initial evaluation of PAH. Patients were administered inhaled nitric oxide (iNO), i.v. epoprostenol, and a 3-h infusion of BNP alone and 1 h after an oral dose of the phosphodiesterase-5 inhibitor sildenafil. iNO and sildenafil alone decreased mean pulmonary artery pressure (mPAP) without a significant fall in pulmonary vascular resistance (PVR). Epoprostenol decreased both mPAP and PVR. BNP alone had no significant effect on pulmonary hemodynamics, but the combination of sildenafil plus BNP decreased mPAP and PVR for up to 6 h after stopping BNP. The decrease in mPAP with sildenafil plus BNP (+/- SE) was greater than after 1 h of sildenafil alone (44.6 +/- 3.8 to 40.6 +/- 3.9 mm Hg, p = 0.027). An acute vasodilator response, defined as a decrease in mPAP > 10 mm Hg and end mPAP < 40 mm Hg, was seen in 0 of 8 patients with iNO, 1 of 13 patients with epoprostenol, 0 of 13 patients with BNP, and 4 of 12 patients with sildenafil plus BNP. BNP decreased mean systemic arterial pressure (5.6 +/- 2.8 mm Hg) but had no effect on cardiac output or systemic vascular resistance. A 3-h BNP infusion does not significantly improve pulmonary hemodynamics in most patients with PAH but is well tolerated and augments the acute pulmonary vasodilator effect of sildenafil.

232 Treatment of Chronic Lung Disease Associated Pulmonary Hypertension with Inhaled Nitric Oxide Administered via Nasal Cpap

Background: Pulmonary hypertension (PH) is a major complication of chronic lung disease (CLD), and its treatment is based on the use of oxygen. Inhaled nitric oxide (iNO) is a highly selective pulmonary vasodilator and it has been used in the therapy of this condition via endotrachal tube during mechanical ventilation. Its use in CLD associated PH with non-invasive delivering methods has not yet been documented to our knowledge.Methods: We report the case of a newborn born prematurely (GA 27 wks BW 475 gms) who developed CLD. At 43 wks post conceptional age oxygen need increased to FiO2=0.7 in nasal CPAP (nCPAP) to maintain O2 saturation (SaO2) within the normal range. Chest X-ray showed cardiomegaly (CTI=0.66). Echocardiography showed indirect signs of PH (hypertrophy of the right ventricle, systolic “D” shaped interventricular septum, moderate pulmonary valve insufficiency) and the value of the mean pulmonary arterial pressure (mPAP) measured through pulmonary insufficiency (PI) was 40– 45 mm Hg immediately before starting iNO. INO (INOmax-INO Therapeutics) was administered via nCPAP (Infant Flow System-EME) in conjunction with a iNO delivery system (INOvent-Datex Ohmeda) at a starting dose of 10 ppm.Results: 5 minutes after starting iNO at 10 ppm via nCPAP, echocardiography showed a decrease of mPAP to 14–15 mm Hg and a significant reduction of PI. After 30 min the oxygen need decreased to FiO2=0.5 to keep SaO2 normal. Subsequently the dose of iNO was progressively decreased with no rebounds in mPAP and stopped 13 days from the start. At the end of treatment echocardiography showed a stable mPAP of 14–15 mm Hg. Met Hb on blood and NO2 in the inspiratory line of nCPAP circuit were never beyond safety levels. On the fifth day of iNO treatment, therapy with dexamethasone was started at the dose of 0.25 mg/kg/day in two doses. Dexamethasone dose was progressively decreased and stopped the day after iNO suspension. At the end of treatment the patient was off nCPAP and oxygen was needed only during feeding. 50 days after the start of iNO treatment echocardiographic PH was absent, chest X-ray showed a reduction of cardiomegaly (CTI=0.52) and the clinical status was stable with a minimal oxygen need.Conclusion: INO administered via nCPAP has been shown to be effective and safe in reducing CLD associated PH in our patient. On the basis of this experience non-invasive iNO administration can be suggested as an alternative therapy associated with CLD.

Correlation of inhaled nitric-oxide induced reduction of pulmonary artery pressure and vascular changes.

The purpose of the present study was to determine the relationship between hypertensive pulmonary vascular remodelling and the changes in mean pulmonary artery pressure (mPAP) during low-dose nitric oxide (NO) inhalation. Rats were exposed to chronic hypobaric hypoxia (air at 50.5 kPa (380 mmHg), 10% oxygen, for 5-29 days) to induce chronic pulmonary hypertension (PH) with pulmonary vascular structural changes. After the chronic hypoxic exposure, the rats had an indwelling pulmonary artery catheter inserted and changes in mPAP with NO were correlated to morphometrical analysis of pulmonary vascular changes. All concentrations of inhaled NO (0.1-2.0 parts per million) reduced mPAP with a similar per cent reduction from baseline mPAP in PH rats, while no changes were observed in control rats. During NO inhalation in PH rats, the absolute value of the decrease in mPAP, but not per cent reduction in mPAP, significantly correlated with baseline mPAP, the percentage of muscularised arteries at the alveolar wall level and at the alveolar duct level, and the per cent medial wall thickness of muscularised arteries. In the chronic hypoxic pulmonary hypertension model, the severity of pulmonary vascular remodelling did not alter the reactivity of the pulmonary arteries to nitric oxide and might, in part, determine the magnitude of nitric-oxide induced absolute reduction in mean pulmonary artery pressure.

Combined inhalation of nitric oxide and oxygen in chronic obstructive pulmonary disease.

Inhaled nitric oxide (NO) has been shown to reduce the mean pulmonary artery pressure (mPAP) and to improve PaO2 in patients with acute respiratory failure undergoing oxygen (O2) therapy. However, inhaled NO reduced pulmonary hypertension without improving PaO2 in patients with chronic obstructive pulmonary disease (COPD). This study was intended to compare the hemodynamic and gas exchange responses during inhalation of NO or O2 with those observed during the combined inhalation of NO and O2 in 10 spontaneously breathing COPD patients. Hemodynamic and blood gas parameters were measured after breathing: (1) room air; (2) NO added to room air; (3) O2 (1 L/min); or (4) NO and O2. During inhalation of 2 ppm NO added to room air, the mPAP (23.1 +/- 2.5 versus 20.6 +/- 2.2 mm Hg) and the pulmonary vascular resistance (PVR) (434 +/- 70 versus 378 +/- 50 dyne s/cm5) were significantly (p < 0.05) lower than those measured with room air. However, the values of PaO2 did not improve. The combined inhalation of NO and O2 was associated not only with a significant (p < 0.05) decrease of mPAP (21.4 +/- 2.3 versus 19.7 +/- 1.8 mm Hg) and PVR (431 +/- 72 versus 370 +/- 44 dyne s/cm5), but also with a remarkable improvement (p < 0.05) in the values of PaO2 (91.4 +/- 6.6 versus 111.5 +/- 7.8 mm Hg) as compared with values obtained during the inhalation of O2 alone. These findings suggest that combined therapy with NO and O2 may constitute an alternative approach to treating patients with COPD and pulmonary hypertension.

Adenosine triphosphate: A potential therapy for hypoxic pulmonary hypertension

In this study we investigated whether a low-dose infusion of ATP-MgCl2 could ameliorate the pulmonary hypertension resulting from hypoxic pulmonary vasoconstriction. Three-week-old piglets were anesthetized, intubated, ventilated with room air, and cannulated for the measurement of pulmonary and systemic arterial pressure and pulmonary artery flow (cardiac output). The ventilator inflow was then changed to a mixture containing 10% oxygen, 4% CO2, and balance nitrogen. Serial infusions of ATP-MgCl2 at 0.1, 0.5 and 1.0 mg/kg/min were compared to preinfusion hypoxia baselines. Hypoxia alone produced a significant elevation in pulmonary artery pressure. Although all dose rates of ATP-MgCl2 produced a significant decrease (30%) in mean pulmonary artery pressure, we observed a maximum decrease in MPAP at the lowest rate of ATP infusion. Pulmonary artery flow rose slightly during ATP infusion; therefore, it was the change in pulmonary vascular resistance that accounted for the decrease in pulmonary artery pressure. In contrast, the systemic pressure was significantly decreased only during the 1.0 mg/kg/min infusion. The predominant pulmonary effects are a result of the virtual clearance of ATP-MgCl2 in a single pass through the circulation. Adenosine in the presence or absence of MgCl2 produced only a 10% reduction in mean pulmonary artery pressure, and MgCl2 had no effect when infused alone. From these results, we conclude that a low-dose infusion of ATP-MgCl2 could ameliorate the vasoconstriction associated with hypoxic pulmonary hypertension without significant deleterious systemic side effects.