Inhaled amyl nitrite effectively reverses acute catastrophic thromboxane-mediated pulmonary hypertension in pigs

Acute catastrophic pulmonary vasoconstriction frequently leads to cardiovascular collapse. Rapid and selective pulmonary vasodilation is desired in order to restore haemodynamic stability. This pilot study examined the effectiveness of inhaled amyl nitrite as a selective pulmonary vasodilator. Nine adult swine were anaesthetized. Acute pulmonary hypertension with haemodynamic collapse was induced with a bolus administration of a thromboxane analogue, U46619. Six animals then received a capsule of amyl nitrite. The administration of inhaled amyl nitrite decreased mean pulmonary artery pressure from 42 +/- 3 to 22 +/ 3 mmHg at five minutes (p < 0.05), with a concomitant increase in cardiac output and mean arterial pressure. Pulmonary vascular resistance decreased from 4889 +/- 1338 to 380 +/- 195 dyne. sec. cm(-5) (by 92% from the maximal pulmonary hypertension change), with significant improvement in systemic haemodynamics. During acute thromboxane-mediated pulmonary hypertension with cardiovascular collapse, prompt administration of inhaled amyl nitrite was effective in restoring pulmonary and systemic haemodynamics within five minutes.     

Assessment of the vasodilator response in primary pulmonary hypertension. Comparing prostacyclin and iloprost administered by either infusion or inhalation.

AIMS: To directly compare the differential effects of oxygen, prostacyclin and iloprost (aerosolized and intravenous) in primary pulmonary hypertension. METHODS AND RESULTS: Twenty-one patients with severe primary pulmonary hypertension underwent right heart catheterization following oxygen inhalation, inhalation of aerosolized iloprost, intravenous prostacyclin or intravenous iloprost. The stability of the iloprost solution was tested for up to 4 weeks. Oxygen slightly decreased pulmonary vascular resistance. Intravenous prostacyclin (7.2+/-3.4 ng kg(-1) min(-1)) reduced pulmonary (1772+/-844 vs 1325+/-615 dyn s cm(-5), P<0.001) and systemic vascular resistance, and arterial and right atrial pressure, while cardiac output increased. Iloprost inhalation diminished pulmonary (1813+/-827 vs 1323+/-614 dyn s cm(-5), P<0.001) and systemic vascular resistance, and pulmonary artery (58+/-12 vs 50+/-12 mmHg,P<0.001) and right atrial pressure, while cardiac output increased. With intravenous iloprost (1.2+/-0.5 ng kg(-1) min(-1), n=8) a decrease in pulmonary (2202+/-529 vs 1515+/-356 dyn s cm(-5), P<0.05) and systemic vascular resistance and right a trial pressure occurred while cardiac output increased. Iloprost solution remained stable for 33 days while losing <10% (4 degrees C) of its active drug concentration.Conclusions Intravenous iloprost and prostacyclin have very similar haemodynamic profiles. In contrast, only inhaled iloprost exerted selective pulmonary vasodilation, reducing pulmonary vascular resistance and pulmonary artery pressure without systemic vasodilation. The longer half-life and extended stability despite lower costs render iloprost an attractive alternative to chronic prostacyclin treatment in primary pulmonary hypertension.     

Bolus nicardipine in the hemodynamic assessment for heart transplantation of patients with severe failure of ischemic origin and high pulmonary resistance]

Nicardipine i.v. bolus (5 mg/5 min) was administered in the pulmonary artery trunk in 13 patients (2 f, 11 m), mean age 48 +/- 8 yrs, affected by ischemia congestive heart failure, with pulmonary hypertension (pulmonary vascular resistances greater than 6 U.W. and/or systolic pulmonary artery blood pressure greater than or equal to 60 mmHg). The vasodilatation induced by nicardipine caused a rapid improvement of all hemodynamic parameters, with a significant reduction of systemic and pulmonary pressures and resistances; in addition, cardiac output increased significantly. Even if heart rate decreased and mean right atrial pressure fell, their variation did not reach statistical significance. These beneficial effects are attributable to the vasodilator action of nicardipine on the systemic and pulmonary vascular districts. Therefore, in the hemodynamic evaluation of patients with ischemic cardiomyopathy proposed for heart transplantation, we propose the employment of nicardipine in testing the vascular reactivity in cases with secondary pulmonary hypertension.     

Cardiovascular and hormonal effects of calcitonin gene-related peptide in congestive heart failure

The effects of infusing human alpha-calcitonin gene-related peptide were studied in eight patients with congestive heart failure, five normal rabbits and five rabbits with adriamycin-induced cardiomyopathy. In patients with heart failure, calcitonin gene-related peptide caused a dose-dependent increase in cardiac output and decrease in pulmonary and systemic vascular resistance and pulmonary artery pressure. The systemic blood pressure and right atrial and pulmonary wedge pressures decreased only at the highest infusion rate (16 ng/kg per min). Heart rate remained unchanged. Plasma epinephrine increased (p less than 0.05), whereas aldosterone, atrial natriuretic peptide and prolactin concentrations decreased (p less than 0.05). Plasma norepinephrine, renin activity, cortisol and growth hormone concentrations remained unchanged. In both groups of rabbits, the drug decreased blood pressure and increased cardiac output and heart rate. There was a significant increase in renal blood flow (p less than 0.05). The peptide did not affect the contraction amplitude of human and rabbit ventricular myocytes. These findings suggest that calcitonin gene-related peptide is a vasodilator in the rabbit and humans with little direct effect on ventricular myocardium. This peptide may be useful in some forms of heart failure.     

Comparative actions of hydralazine, nifedipine and amrinone in primary pulmonary hypertension

The effects of 3 types of vasoactive agents, hydralazine, nifedipine and amrinone, were evaluated in 7 patients with primary pulmonary hypertension (PPH). Hemodynamic values were measured before and after drug administration in every patient. All drugs increased cardiac output and reduced both systemic and pulmonary resistance in the patients studied. Only nifedipine significantly reduced pulmonary artery (PA) pressure (6 +/- 5 mm Hg). In addition, it decreased pulmonary resistance to a greater degree than systemic resistance in 2 of the 7 patients, suggesting that nifedipine can cause selective pulmonary vasodilation in some patients. Hydralazine appeared to increase cardiac output and stroke volume by reducing systemic resistance. There was no evidence of direct pulmonary vasodilating effects; it decreased systemic resistance more than pulmonary resistance in every case. The increase in cardiac output from amrinone was secondary to a decrease in systemic arterial pressure with reflex tachycardia; stroke volume was unchanged. Amrinone had little pulmonary effect in all but 1 patient, in whom it substantially reduced PA pressure and pulmonary resistance. The mechanism of action of these 3 drugs in PPH differs. Nifedipine holds the most promise as an effective pulmonary vasodilator. A study of the effects of long-term administration of nifedipine in PPH is warranted.     

Altered endothelial function in lambs with pulmonary hypertension and acute lung injury

Acute lung injury produces pulmonary hypertension, altered vascular reactivity, and endothelial injury. To determine whether acute lung injury impairs the endothelium-dependent regulation of pulmonary vascular tone, 16 lambs were studied during U46619-induced pulmonary hypertension without acute lung injury, or air embolization-induced pulmonary hypertension with acute lung injury. The hemodynamic responses to endothelium-dependent (acetylcholine, ATP, ET-1, and 4 Ala ET-1 [an ETb receptor agonist]) and endothelium-independent (nitroprusside and isoproterenol) vasodilators were compared. During U46619-induced pulmonary hypertension, all vasodilators decreased pulmonary arterial pressure and vascular resistance (P < 0.05). During air embolization-induced pulmonary hypertension, the pulmonary vasodilating effects of acetylcholine, ATP, and 4 Ala ET-1 were attenuated (P < 0.05); the pulmonary vasodilating effects of nitroprusside and isoproterenol were unchanged; and the pulmonary vasodilating effects of ET-1 were reversed, producing pulmonary vasoconstriction (P < 0.05). During air embolization, the pulmonary vasoconstricting effects of ET-1 were blocked by BQ 123, an ETa receptor antagonist. The systemic effects of the vasoactive drugs were similar during both conditions. We conclude that pulmonary hypertension with acute lung injury induced by air embolization results in endothelial dysfunction; there is selective impairment of endothelium-dependent pulmonary vasodilation and an altered response to ET-1 from pulmonary vasodilation to vasoconstriction. This altered response to ET-1 is associated with decreased ETb receptor-mediated vasodilation and increased ETa receptor-mediated vasoconstriction. Endothelial injury and dysfunction account, in part, for the altered regulation of pulmonary vascular tone during pulmonary hypertension with acute lung injury.     

Hemodynamic effects of urapidil in patients with pulmonary hypertension. A comparative study with hydralazine

Vasodilator therapy for pulmonary hypertension ideally should cause a proportionately greater reduction of resistance in the pulmonary vascular bed than in the systemic circulation. This should limit the occurrence of systemic hypotension, which can complicate the use of most vasodilator drugs. Urapidil is a new vasodilator that acts by postsynaptic alpha 1-blockade while inhibiting the aortic pressure baroreceptor reflex and reducing central sympathetic tone. We investigated and compared the short-term effects of Urapidil and hydralazine in 10 patients suffering varying degrees of pulmonary hypertension. Each patient received either 0.35 mg/kg hydralazine or 0.75 mg/kg Urapidil intravenously on 2 sequential days in a randomized order. The main effect of Urapidil was to decrease the mean pulmonary artery pressure in all 10 patients from 44 +/- 4 to 37 +/- 3.5 mm Hg (p less than 0.001). After Urapidil infusion, the mean decrease of resistance in the pulmonary vascular bed (32%) exceeded that in the systemic circulation (25%). In contrast, pulmonary artery pressure remained unchanged with hydralazine, and predominant systemic vasodilation occurred: systemic vascular resistance decreased by 45%, whereas pulmonary vascular resistance decreased by 25%. Hydralazine markedly increased the cardiac index and induced tachycardia. Urapidil maintained the heart rate nearly constant and only slightly increased the cardiac index, thereby fostering the diastolic emptying of the pulmonary circulation. No significant change in arterial oxygenation occurred with either drug, although arterial oxygen partial pressure tended to increase with hydralazine. Urapidil may be a promising drug in the treatment of patients with pulmonary hypertension.     

Hemodynamic effects of inhaled nitric oxide in women with mitral stenosis and pulmonary hypertension

Mitral stenosis (MS) is associated with elevated left atrial pressure, increased pulmonary vascular resistance (PVR), and pulmonary hypertension (PH). The hemodynamic effects of inhaled nitric oxide (NO) in adults with MS are unknown. We sought to determine the acute hemodynamic effects of inhaled NO in adults with MS and PH. Eighteen consecutive women (mean age 58 +/- 15 years) with MS and PH underwent heart catheterization. Hemodynamic measurements were recorded at baseline, after NO inhalation at 80 ppm, and after percutaneous balloon valvuloplasty (n = 10). NO reduced pulmonary artery systolic pressure (62 +/- 14 mm Hg [baseline] vs 54 +/- 15 mm Hg [NO]; p <0.001) and PVR (3.7 +/- 2.5 Wood U [baseline] vs 2.2 +/- 1.4 Wood U [NO]; p <0.001). NO had no effect on mean aortic pressure, left ventricular end-diastolic pressure, left atrial pressure, cardiac output, or systemic vascular resistance. Mitral valve area increased after valvuloplasty (0.9 +/- 0.2 cm2 [baseline] vs 1.6 +/- 0.3 cm2 [postvalvuloplasty]; p <0.001). A decrease in left atrial pressure (25 +/- 4 mm Hg [baseline] vs 17 +/- 4 mm Hg [after valvuloplasty]; p <0.001) and pulmonary artery systolic pressure (58 +/- 12 mm Hg [baseline] vs 45 +/- 8 mm Hg [after valvuloplasty]; p <0.001) was observed after valvuloplasty. No change in cardiac output or PVR was observed. Thus inhaled NO, but not balloon valvuloplasty, acutely reduced PVR in women with MS and PH. This suggests that a reversible, endothelium-dependent regulatory abnormality of vascular tone is an important mechanism of elevated PVR in MS.     

Systemic vasoconstrictor effects of oxygen administration in obliterative pulmonary vascular disorders

Although oxygen is frequently administered to patients with obliterative pulmonary vascular disorders (OPVD) for diagnostic and therapeutic purposes, its hemodynamic effects in these patients have not been systematically evaluated. The response to administration of 50 to 70% oxygen was studied in 14 patients with pulmonary hypertension secondary to OPVD. Mean pulmonary artery pressure decreased (from 62 +/- 5 to 57 +/- 5 mm Hg, p less than 0.01) after oxygen inhalation secondary to a decrease in cardiac index (1.9 +/- 0.2 to 1.8 +/- 0.2 liters/min/m2, p less than 0.01), without changes in pulmonary arteriolar resistance. This decline in forward output appeared to result from a systemic vasoconstrictor effect of oxygen (change in systemic vascular resistance from 1,965 +/- 275 to 2,297 +/- 336 dynes s cm-5, p less than 0.01), which decreased heart rate (from 93 +/- 3 to 89 +/- 2 beats/min, p less than 0.01) by stimulation of baroreceptor reflexes and decreased stroke volume (from 22 +/- 3 to 21 +/- 2 ml/beat/m2, p less than 0.05) by increasing impedance to left ventricular ejection. The decrease in left-sided cardiac output likely led to a decline in venous return to the right side of the heart and, consequently, to a decrease in right atrial and pulmonary arterial pressures. Accordingly, the percent decrease in mean pulmonary artery pressure varied linearly and directly with the percent increase in systemic vascular resistance (r = 0.84), but not with changes in pulmonary arteriolar resistance (r = 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nifedipine dilates the pulmonary vasculature without producing symptomatic systemic hypotension in upright resting and exercising patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease

Vasodilator therapy may lower pulmonary vascular resistance in patients with chronic air-flow limitation. However, the effects of these agents on left ventricular afterload, cardiac output, and bronchial smooth muscle could lower the calculated pulmonary vascular resistance without specifically affecting pulmonary vascular tone. In addition, systemic hypotension in the upright position and worsening ventilation/perfusion heterogeneity could limit their use. We determined the pulmonary driving pressure (pulmonary arterial-pulmonary arterial wedge pressure) to flow relationship, as well as the transmural pulmonary arterial pressure in 9 patients with severe chronic air-flow limitation with pulmonary hypertension while in a clinically stable condition. Measurements were made at rest and during 3 stages of progressively increasing upright exercise on a bicycle before and after a single 20-mg dose of nifedipine. Nifedipine displaced both the driving pressure to flow and the pulmonary arterial transmural pressure to flow relationships towards higher flows in every subject, suggesting an active vasodilation. In the upright position, PaO2 did not change, and the systemic arterial pressure was only mildly reduced. In patients with pulmonary hypertension from chronic air-flow limitation, acute administration of nifedipine to upright patients causes pulmonary, as well as systemic vasodilation without causing symptomatic hypotension or reducing arterial oxygenation.     

Hydralazine does not inhibit canine hypoxic pulmonary vasoconstriction

Clinical experience with hydralazine has led to conflicting data concerning its effect on the pulmonary vasculature. We studied the effects of hydralazine on the hypoxic pulmonary vasoconstrictor response in 9 dogs challenged with inhalation of 10% oxygen in the presence and absence of hydralazine. Prior to administration of the drug, hypoxia increased cardiac output from 174 +/- 13 to 209 +/- 21 ml/kg/min (p less than 0.05) and pulmonary artery pressure from 9 +/- 1 to 19 +/- 1 mmHg (p less than 0.05). After hydralazine, cardiac output rose during normoxia to 275 +/- 30 and during hypoxia to 305 +/- 34 ml/kg/min (p less than 0.05). Pulmonary artery pressure continued to respond to hypoxia, rising from 11 +/- 1 to 21 +/- 1 mmHg (p less than 0.05) in the presence of hydralazine. Hydralazine reduced pulmonary vascular resistance during normoxia from 173 +/- 14 to 136 +/- 13 dynes X s X cm-5 (p less than 0.05) but even after the drug, pulmonary vascular resistance rose sharply during hypoxia. There was no significant difference in the response to hypoxia of pulmonary artery pressure or pulmonary vascular resistance after hydralazine when compared with that before hydralazine. In a second set of 6 dogs, we repeated these experiments but volume-depleted the dogs after the administration of hydralazine to prevent the passive pulmonary vasodilation that occurs because of the rise in cardiac output with the drug. We again found no inhibition of hypoxic pulmonary vasoconstriction by hydralazine. Finally, we administered sodium nitroprusside to 4 dogs using the same model and found a significant inhibition of hypoxic pulmonary vasoconstriction. Hydralazine, unlike nitroprusside, does not inhibit the pulmonary vascular response to hypoxia.     

Short- and long-term hemodynamic effects of captopril in patients with pulmonary hypertension and selected connective tissue disease.

To assess the pulmonary and systemic hemodynamic effects of oral captopril in patients with connective tissue disease and pulmonary hypertension, we performed right heart catheterization in eight patients with diffuse systemic sclerosis, the CREST syndrome, or mixed connective tissue diseases prior to and immediately following administration of captopril (dose range 12.5 to 50.0 mg, short-term study). Four of these patients underwent repeat right heart catheterization after three to six months of oral captopril therapy (long-term study). In the short-term study, oral captopril produced a significant decrease in mean pulmonary vascular resistance from 6.2 +/- 3.6 to 4.6 +/- 3.8 units (p < 0.01). This was accompanied by a significant decrease in mean pulmonary artery pressure, mean blood pressure, mean systemic vascular resistance and a significant increase in cardiac output. Similar changes in pulmonary hemodynamics were noted in the long-term study. Thus, oral captopril is capable of producing an acute and sustained reduction in pulmonary vascular resistance in patients with pulmonary hypertension associated with the aforementioned connective tissue diseases.     

A comparison of the acute hemodynamic effects of prostacyclin and hydralazine in primary pulmonary hypertension

In patients with primary pulmonary hypertension the administration of a vasodilating drug is often used to test pulmonary vasoreactivity. Hydralazine has been employed as a test drug, but because of its long duration of action there is a risk of sustained systemic arterial hypotension in patients with a fixed pulmonary vascular resistance. In this study we compared the acute hemodynamic effects of intravenous prostacyclin, a potent, short-acting vasodilator, with the effects of oral or intravenous hydralazine. Both prostacyclin and hydralazine increased cardiac output and decreased systemic pressure without changing pulmonary arterial pressure in seven patients with primary pulmonary hypertension. The average decrease in total pulmonary resistance with prostacyclin (-46% +/- 5%) was more than that with hydralazine (-32% +/- 6%). The respective decreases in total systemic resistance were -50% +/- 4% vs -43% +/- 6%. The percent changes in individual responses to the two agents were correlated (p less than 0.05) for pulmonary arterial pressure, systemic arterial pressure, total pulmonary resistance, and total systemic resistance. We concluded that the pulmonary hemodynamic effects of prostacyclin resembled those of hydralazine. Prostacyclin may predict the acute pulmonary hemodynamic effects of hydralazine in primary pulmonary hypertension and because of its prompt, brief action may provide greater patient safety.     

Combined effects of nitric oxide and oxygen during acute pulmonary vasodilator testing

OBJECTIVES: We compared the ability of inhaled nitric oxide (NO), oxygen (O2) and nitric oxide in oxygen (NO+O2) to identify reactive pulmonary vasculature in pulmonary hypertensive patients during acute vasodilator testing at cardiac catheterization. BACKGROUND: In patients with pulmonary hypertension, decisions regarding suitability for corrective surgery, transplantation and assessment of long-term prognosis are based on results obtained during acute pulmonary vasodilator testing. METHODS: In group 1, 46 patients had hemodynamic measurements in room air (RA), 100% O2, return to RA and NO (80 parts per million [ppm] in RA). In group 2, 25 additional patients were studied in RA, 100% O2 and 80 ppm NO in oxygen (NO+O2). RESULTS: In group 1, O2 decreased pulmonary vascular resistance (PVR) (mean+/-SEM) from 17.2+/-2.1 U.m2 to 11.1+/-1.5 U.m2 (p < 0.05). Nitric oxide caused a comparable decrease from 17.8+/-2.2 U.m2 to 11.7+/-1.7 U.m2 (p < 0.05). In group 2, PVR decreased from 20.1+/-2.6 U.m2 to 14.3+/-1.9 U.m2 in O2 (p < 0.05) and further to 10.5+/-1.7 U.m2 in NO+O2 (p < 0.05). A response of 20% or more reduction in PVR was seen in 22/25 patients with NO+O2 compared with 16/25 in O2 alone (p = 0.01). CONCLUSIONS: Inhaled NO and O2 produced a similar degree of selective pulmonary vasodilation. Our data suggest that combination testing with NO + O2 provides additional pulmonary vasodilation in patients with a reactive pulmonary vascular bed in a selective, safe and expeditious fashion during cardiac catheterization. The combination of NO+O2 identifies patients with significant pulmonary vasoreactivity who might not be recognized if O2 or NO were used separately.     

Natural history of primary pulmonary hypertension elucidated by pulmonary hemodynamics

The present study was undertaken to clarify the natural history of primary pulmonary hypertension (PPH) from a hemodynamic point of view. The subjects consisted of 83 patients (18 men and 65 women), whose ages ranged from 14 to 69 years and averaged 33 years. They were contacted through a nationwide survey. All patients underwent right-sided cardiac catheterization; cardiac output was measured in 52 patients and pulmonary capillary wedge pressure, in 40 patients. The following results were obtained. 1. The patients who died within three months of their cardiac catheterization were in severe right ventricular failure as shown by their elevated right atrial pressures and decreased cardiac indices. 2. The patients who died suddenly within two years of their cardiac catheterization had the same degree of right ventricular failure. The only difference was severe hypoxia in the patients with cardiac failure (54 +/- 21 vs 66 +/- 4 mmHg, p less than 0.05). 3. The patients who survived more than two years had normal right ventricular function. 4. Among the hemodynamic variables used to estimate prognosis; namely, pulmonary artery diastolic pressure, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance and pulmonary to systemic vascular resistance ratio, the cardiac index was the best predictor of prognosis.     

Acute effects of sildenafil in patients with primary pulmonary hypertension receiving epoprostenol

Epoprostenol therapy has improved survival in primary pulmonary hypertension; however, only two thirds of patients are alive 3 years after starting treatment. Combined therapy with sildenafil, a phosphodiesterase 5 inhibitor, may provide additional benefit. The authors prospectively evaluated the acute hemodynamic and biochemical effects of sildenafil and inhaled nitric oxide, alone and in combination, in 8 patients with primary pulmonary hypertension receiving chronic epoprostenol. Average duration of epoprostenol therapy was 2.9 +/- 1.6 years (mean +/- SD) and mean dose was 25.7 +/- 10.8 ng/kg/min. A single 50 mg dose of sildenafil decreased mean pulmonary arterial pressure 10% (P<.05), increased cardiac output 8%, and decreased pulmonary vascular resistance 24% (P<.005). Although nitric oxide led to a similar decrease in mean pulmonary arterial pressure of 10% (P<.05), cardiac output was unchanged, resulting in a decrease in pulmonary vascular resistance of only 13%, which was not statistically different from baseline. These results suggest that sildenafil has greater acute hemodynamic effects than nitric oxide and that it can further reduce pulmonary vascular resistance in patients already demonstrating a benefit from chronic epoprostenol.     

Comparative effects of nifedipine, verapamil, and diltiazem on experimental pulmonary hypertension

The role of calcium-channel blocking agents in the treatment of pulmonary hypertension is not well defined. Consequently, the effects of diltiazem, nifedipine, and verapamil were compared in 3 groups of anesthetized dogs (n = 6 for each group). In each group, normoxic hemodynamic variables were recorded before and after increasing doses of diltiazem, nifedipine, and verapamil (5 X 10(-8) M/kg, low; 10(-7) M/kg, medium; and 10(-6) M/kg, high dose; given intravenously over 2 minutes). In addition, the effect of these doses on the pulmonary pressor responses to hypoxia (fractional inspired oxygen concentration [FIO2] 12%) and prostaglandin F2 alpha (PGF2 alpha) (5 micrograms/kg/min, intravenously for 4 minutes) was measured. During normoxia, high-dose nifedipine and verapamil decreased mean aortic pressure and systemic vascular resistance while increasing cardiac output in all dogs in both groups (p less than 0.01). Pulmonary vascular resistance, however, remained unchanged. High-dose diltiazem did not significantly alter cardiac output or pulmonary vascular resistance. During acute hypoxic pulmonary hypertension, verapamil decreased cardiac output by 30% (p less than 0.01) without appreciably altering pulmonary arterial pressure; thus pulmonary vascular resistance increased slightly (4.9 +/- 0.6 to 6.4 +/- 1.0 mm Hg/liter/min, difference not significant [NS]). Nifedipine decreased hypoxic pulmonary vascular resistance to normoxic values (p less than 0.01). Cardiac output increased 71% while pulmonary arterial pressure remained unchanged. Diltiazem administration produced no change in hypoxic pulmonary hemodynamic variables. The responses to diltiazem, nifedipine, and verapamil during acute pulmonary vasoconstriction induced by PGF2 alpha were similar to those induced by hypoxia. After verapamil, pulmonary vascular resistance tended to increase (7.3 +/- 1.3 to 8.1 +/- 1.4 mm Hg/liter/min, NS). Nifedipine, however, completely blocked pulmonary vasoconstriction by decreasing pulmonary vascular resistance to pre-PGF2 alpha levels (p less than 0.01). This was accompanied by a 157% increase in cardiac output and only a small increase in pulmonary arterial pressure (7 mm Hg). Again, diltiazem produced no change in pulmonary hemodynamic variables. In these acute studies, nifedipine appeared to be a more effective pulmonary vasodilator than verapamil or diltiazem.     

Acute hemodynamic response to the S2-serotonergic receptor antagonist, ketanserin, in patients with primary pulmonary hypertension

The acute hemodynamic effect of intravenous ketanserin, an S2-serotonergic receptor antagonist, was evaluated during right heart catheterization in 20 patients with primary pulmonary hypertension. Pulmonary and systemic vascular resistance and pressure and cardiac output were measured before and after infusion of low and high dose ketanserin. A small decrease in pulmonary vascular resistance occurred after high dose drug infusion (28.4 to 25.0 U X m2; P less than 0.001), and mean pulmonary arterial pressure was unchanged. Decreases in systemic arterial pressure (91.9 to 85.9 mm Hg; P less than 0.0005) and systemic resistance (46.2 to 38.6 U X m2; P less than 0.001) were more pronounced. Cardiac index increased significantly (2.16 to 2.42 l/min/m2; P less than 0.01) due to reduced ventricular afterload. This study indicates that ketanserin has a small pulmonary vasodilating effect in primary pulmonary hypertension of doubtful clinical significance, similar to conventional vasodilators.     

Evaluation of the responsiveness of elevated pulmonary vascular resistance in children by Doppler echocardiography

Changes in the Doppler indexes, acceleration time (AcT), right ventricular ejection time (RVET), AcT/RVET ratio and pulmonary artery peak velocity were measured as were changes in pulmonary artery pressure and pulmonary vascular resistance in 21 children with pulmonary hypertension due to a large interventricular communication. In 11 children pulmonary vascular resistance was greater than 4.6 U/m2 (mean 8.6 +/- 1.6), whereas in 10 it was less than 4.5 U/m2 (mean 3.4 +/- 0.2). Although both groups demonstrated acceleration time and AcT/RVET values above normal, there were no significant differences in these values between the groups with high and low pulmonary vascular resistance. With administration of a pulmonary vasodilator pulmonary vascular resistance decreased in 11 responders by greater than 50% of baseline values (from 5.3 +/- 0.7 to 1.6 +/- 0.3 U/m2), whereas in the 10 nonresponders mean pulmonary vascular resistance decreased from 7.0 +/- 1.9 to 4.9 +/- 1.1 U/m2. There was no significant change in the Doppler indexes except for an increase in pulmonary artery peak velocity in the responders from 1.34 +/- 0.07 to 1.66 +/- 0.06 m/s (p less than 0.001). The results indicate that Doppler echocardiography cannot predict either the level of increased pulmonary vascular resistance or the degree of responsiveness sufficiently to obviate the need for cardiac catheterization in patients with interventricular communication and pulmonary hypertension.     

Differential effects of terlipressin on pulmonary and systemic hemodynamics in patients with cirrhosis and pulmonary hypertension: an echo study

Terlipressin has been associated with pulmonary arterial vasodilation in patients with pulmonary hypertension (PH). We investigated the effects of terlipressin on pulmonary vascular resistance (PVR) in patients with cirrhosis without and with PH. Pulmonary vascular resistance and cardiac output (CO) by Doppler ultrasound, mean arterial pressure (MAP), and systemic vascular resistance (SVR) were evaluated in patients with cirrhosis with PVR -120 dyne s cm?? (group 1, n = 20) and PVR >120 dyne s cm?? (group 2, n = 10) before and 30 minutes after terlipressin infusion (2 mg). After terlipressin, PVR increased significantly in group 1 (96.1 ± 20.2 vs 85.1 ± 18 dyne s cm??; P = .004) but decreased significantly in group 2 (170.4 ± 37.8 vs 157.8 ± 28.1 dyne s cm??; P= .04). Pulmonary vascular resistance changes in group 2 correlated significantly with baseline PVR (r = -0.632; P = .04). Terlipressin induced a significant increase in MAP and SVR and a significant decrease in CO in both groups. Terlipressin significantly reduces pulmonary pressures in patients with cirrhosis having PH together with systemic hemodynamic improvement.