Resting Mean Pulmonary Artery Pressure Research Articles

Transpulmonary prostaglandin F 2α metabolism in sheep: an in vivo model

We investigated transpulmonary enzymatic conversion of prostaglandin F 2α (PGF) to the 13,14-dihydro-15-keto metabolite (PGFM) in normal and acutely lung injured sheep. PGF was infused directly into the right ventricle. Sequential, simultaneous blood samples were drawn from the pulmonary artery (PA) and aorta (A). PGF and PGFM plasma concentrations were quantitated by double antibody radioimmunoassay (RIA). The pulmonary conversion rate of PGF in normal lung was established over a wide range of concentrations in intubated, normoxic, and hemodynamically stable sheep. Both zero and first order kinetics were present. PGF had no physiological effects on either pulmonary or systemic hemodynamics at any infusion rate studied. Acute lung injury was produced by intravenous injections of oleic acid into the PA until the resting mean pulmonary artery pressure doubled. Infusions were then repeated and fractional metabolism of PGF across the lung was assessed. PGF, at infusion rates of 2 micrograms/kg/min and 8 micrograms/kg/min, was metabolized > 70% respectively. Thus, there was no difference between control or experimental groups in PGF conversion. We conclude that the in vivo sheep lung has an extensive substrate-dependent capacity to metabolize PGF and this mechanism is resistant to severe acute oleic acid lung injury.

Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease: Multivariate Analysis

The severity of pulmonary hypertension was evaluated by right cardiac catheterization in 89 patients with stable chronic obstructive pulmonary disease, both at rest and during maximum treadmill exercise. Thirty-one patients were found to have pulmonary hypertension at rest, defined as a mean pulmonary arterial pressure of 20 mm Hg or more. Although the remaining 58 patients had normal mean pulmonary arterial pressure at rest, three developed pulmonary hypertension during exercise (mean pulmonary arterial pressure greater than or equal to 35 mm Hg). Multiple anthropometric, spirometric, radiographic, and gas-exchange variables were analyzed and correlated with the hemodynamic data to define their value in predicting mean pulmonary arterial pressure. While arterial oxygen pressure (PaO2) at maximum exercise was the variable most highly correlated with resting mean pulmonary arterial pressure (r = -0.67), stepwise multiple linear regression analysis indicated that measurement of the diameter of the right descending pulmonary artery and arterial carbon dioxide tension (PaCO2) also contributed to the prediction of mean pulmonary arterial pressure. Spirometric indices of airflow obstruction, hyperinflation, and the diffusing capacity of the lung for carbon monoxide correlated poorly with the severity of pulmonary hypertension and consequently were not useful predictors of mean pulmonary arterial pressure. The threshold criteria of a PaO2 less than 60 mm Hg or a PaCO2 more than 40 mm Hg were reasonably accurate for a diagnosis of pulmonary hypertension. These arterial blood gas criteria were superior to the spirometric and radiographic variables examined in predicting pulmonary hypertension prior to the development of clinically overt cor pulmonale.

Effect of vasodilators at rest and during exercise in young adults with cystic fibrosis and chronic cor pulmonale.

Six clinically stable patients with cystic fibrosis (24 to 31 yr of age) and severe pulmonary impairment, right ventricular hypertrophy, and previous right-sided heart failure underwent cardiac catheterization to assess the hemodynamic effects of oxygen (fraction of inspired O2, 0.31, 0.50), phentolamine (5 mg intravenously), hydralazine (0.33 mg/kg intravenously), and nifedipine (20 mg sublingually). Measurements during dynamic exercise were also obtained before and after hydralazine therapy. Studies after 5 to 8 wk of continuous, orally administered hydralazine therapy were performed in 3 patients. The resting mean pulmonary artery pressure was 31 +/- 4 mmHg. At rest, only oxygen was a selective pulmonary vasodilator, decreasing pulmonary artery pressure and pulmonary vascular resistance in all patients. Systemic arterial pressure and resistance were not significantly changed. Phentolamine, hydralazine, and nifedipine did not alter pulmonary artery pressure or selectively affect the pulmonary vascular bed, reducing both calculated pulmonary and systemic vascular resistance, the latter to a similar or greater degree. Hydralazine and nifedipine significantly increased cardiac index and decreased systemic arterial pressure. Nifedipine mildly decreased systemic oxygenation. During exercise, the mean pulmonary artery pressure increased to 51 +/- 15 mmHg. Hydralazine increased systemic and mixed venous oxygenation both at rest and during exercise but did not alter the elevation in pulmonary artery pressure observed during exercise. After orally administered hydralazine therapy, oxygen delivery and cardiac index remained increased in 2 patients. These data support the use of oxygen but not of the other agents in patients with cystic fibrosis and chronic cor pulmonale unless the ability of hydralazine to increase oxygen delivery is determined to improve prognosis.

Effects of hypoxia on pulmonary vascular reactivity in pneumonectomized puppies and minipigs.

Pneumonectomy was performed on 25 1-month old beagle puppies and 13 2-month old minipigs. Three weeks or more later, pulmonary blood flow and pulmonary artery pressure were measured in the survivors and total pulmonary vascular resistance was calculated in each animal. These measurements were made at normal arterial Po 2 and at an arterial Po 2 of 31 ± 5 mm Hg produced by ventilating the animals with 10% oxygen in nitrogen. Seven normal puppies and seven normal minipigs of ages comparable to the pneumonectomized animals were studied as controls. The mean pulmonary artery pressure in the pneumonectomized puppies was not significantly different from that of the normal puppies. There was no significant pulmonary vascular response to hypoxia in the pneumonectomized puppies. The pneumonectomized minipigs had a significantly higher resting mean pulmonary artery pressure than the normals ( P < 0.005). They did not, however, show a greater reactivity to hypoxia than did their normal litter mates. Both pneumonectomized and normal minipigs were more reactive to hypoxia than puppies. The minipigs were restudied approximately 16 weeks after the initial study. Four out of five animals showed a further rise in resting pulmonary artery pressure. Histological studies showed arteriolar medial hypertrophy in the minipig lungs.

THE REVERSIBILITY OF PULMONARY HYPERTENSION IN PATIENTS WITH CYSTIC FIBROSIS

1. The present study was concerned with the evaluation of the acute and chronic effects of tolazoline, O2, and sleep on the pulmonary circulation of six subjects with cystic fibrosis and pulmonary hypertension. 2. Right heart catheterization was performed and observations were made at rest, after tolazoline and after O2. In four subjects, changes in pulmonary artery pressure (PAP) induced by various agents and sleep were observed for periods ranging from 3 hours to 4 days. 3. Resting mean PAP ranged from 22 to 67 mm Hg; arterial PO2 from 37 to 47 mm Hg; pH from 7.252 to 7.408, cardiac index from 2.64 to 3.91 1/min/m2, and total pulmonary resistance (TPR) from 440 to 1,330 dynes sec cm-5-m2. 4. Following tolazoline, the average mean PAP dropped from 51 to 28 mm Hg, average cardiac output rose from 3.20 to 4.08 1/min/m2; TPR dropped from 880 to normal. This decrease in PAP and TPR was achieved with little change in either pH or arterial pO2. 5. The addition of O2 to tolazoline lowered the mean PAP further by 8 mm Hg. 6. Observations were made during sleep in three of the patients. In each, there was an increase in PAP ranging from 9 to 23 mm Hg. 7. Repeated administration of tolazoline resulted both in progressively lower PAP and less tendency for its return to control level. 8. Postmortem pulmonary arteriograms and histological examination of the pulmonary vessels were performed in one patient. Despite the presence of numerous abscesses and diffuse bronchopneumonia, the pulmonary vessel was found to be relatively normal. Only medial hypertrophy of the small arterioles was seen. 9. The factors involved in the development of hypoxic pulmonary hypertension and possible mechanisms by which tolazoline effects acute and sustained reduction of PAP are discussed. 10. It is concluded that acute and repetitive pharmacologic treatment is effective in the reduction of pulmonary hypertension in patients with cystic fibrosis. Further, it is suggested that patients with cystic fibrosis and reactive pulmonary hypertension would benefit from residing at sea level.