Pulmonary hypertension hemodynamics

Meyrick, B., Gamble, W. and Reid, L. (1980). Development of crotalaria pulmonary hypertension hemodynamic and structural study. Am. J. Physiol, 239, H692-702... 

Inhaled NO has been used for treatment of persistent pulmonary hypertension of newborn infants, critical respiratory failure of preterm infants, and acute hypertension of adult cardiac surgery patients. PDE-5 inhibitors such as sildenafil are also effective for treatment of pulmonary hypertension. The combination of PDE-5 and NO inhalation yields additive beneficial effects on pulmonary hemodynamics. On the other hand, measurement of exhaled NO is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with bronchial asthma. 

Intravenous epoprostenol increases exercise tolerance, improves pulmonary hemodynamics, and improves survival in patients with primary pulmonary hypertension. However, there are limitations to intravenous administration, and a significant proportion of patients develop catheter-related problems, such as thrombosis, pump failure, and catheter-related sepsis. In an attempt to improve delivery, several trials of aerosolized prostacyclin have been undertaken, primarily in patients with primary pulmonary hypertension. 

Hadengue, A., Benhayoun, M.K., Lebrec, D., Benhamou, J.-R Pulmonary hypertension complicating portal hypertension prevalence and relation to splanchnic hemodynamics. Gastroenterology 1991 100 520-528... 

Robalino, B.J., Moodie, D.S. Association between primary pulmonary hypertension and portal hypertension analysis of its pathophysiology and chnical, laboratory and hemodynamic manifestations. J. Amer. Coll. Cardiol. 1991 17 492-498... 

In pulmonary hypertension, both verapamil and nifedipine increase mean right atrial pressure in association with hypotension, chest pain, dyspnea, and hypoxemia the severe hemodynamic upset resulted in cardiac arrest in two patients after verapamil and death in another after nifedipine (54). A patient with pulmonary hypertension also developed pulmonary edema whilst taking nifedipine (55) and another seems to have developed this as an allergic reaction (56). 

Packer M, Medina N, Yushak M. Adverse hemodynamic and clinical effects of calcium channel blockade in pulmonary hypertension secondary to obliterative pulmonary vascular disease. J Am Coll Cardiol 1984 4(5) 890-901. 

In another study the acute response to inhaled nitric oxide and high doses of oral nifedipine or verapamil was assessed in 33 consecutive patients with primary pulmonary hypertension (2). Ten patients responded acutely to nitric oxide, nine of whom responded acutely to calcium channel blockers, without any complications. The other 23 patients failed to respond to nitric oxide and calcium channel blockers. In these non-responders there were nine serious adverse effects with calcium channel blockers. There was no clinical or baseline hemodynamic feature that predicted the acute vasodilator response. Long-term oral treatment with calcium channel blockers was restricted to the nine acute responders, and there was a sustained clinical and hemodynamic improvement in only six patients. It was concluded that nitric oxide may be used as a screening agent for safely identifying patients with primary pulmonary hypertension who may benefit from long-term treatment with calcium channel blockers. 

A 72-year-old woman, who underwent emergency resection of a giant left atrial myxoma, had pulmonary hypertension (pulmonary artery pressure 40 mmHg) and a low cardiac output (2.21/minute). Inhaled nitric oxide, 40 ppm, before cardiopulmonary bjrpass resulted in pulmonary vasodilatation and a fall in pulmonary artery pressure from 39 to 31 mmHg. This was accompanied by a fall in cardiac output from 2.4 to 1.5 1/minute and a fall in mixed venous oxygen saturation. After bypass, inhaled nitric oxide improved pulmonary and systemic hemodynamics and resulted in a rise in cardiac output from 3.0 to 3.5 l/minute. 

Hoeper MM, Olschewski H, Ghofrani HA, Wilkens H, Winkler J, Borst MM, Niedermeyer J, Fabel H, Seeger W, Grimminger F, et al. A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group. J Am CoU Cardiol 2000 35(l) 176-82. 

For the growing number of patients with combined pulmonary hypertension and abnormal left ventricular hemodynamics, a careful hemodynamic study can help to delineate the subtleties of both diseases and response to therapies. Exercise catheterization is recommended in those patients with normal hemodynamics at rest, but with a pretest likelihood of PAH and/or other data suggesting exercise-induced symptoms, for instance, exercise echo or cardiopulmonary stress test. Unfortunately, to date there is no consensus as to the best exercise protocols for an appropriate hemodynamic assessment. Among those used include upright bicycle with neck pulmonary arterial (PA) lines at 75% predicted maximum exercise, supine bicycle, supine arm exercise, and supine volume loading. In all cases, it is essential to carefully measure PCWP, cardiac outputs, and PA pressures at consistent parts of the respiratory cycle, and not merely PA pressures. 

Pulmonary hypertension is characterized by a chronically elevated pulmonary artery pressure. As described in previous sections of this chapter, under normal conditions, the pulmonary artery pressure has a systolic value of 18 to 25 mm Hg, a diastolic value of 6 to 10 mm Hg, and a mean value ranging from 12 to 16 mm Hg. Pulmonary hypertension exists when the pulmonary artery systolic and mean pressures exceed 30 and 20 mm Hg, respectively. In the disease state, the pressure in the pulmonary artery may fluctuate widely and is often so high that it equals the blood pressure in the systemic arterial bed. As would be expected, pulmonary vascular resistance is also extremely high in patients with pulmonary hypertension. In addition, patients with this disease exhibit an enlarged right ventricle and an enlargement of the main pulmonary artery and its branches. Systemic hemodynamic parameters, however, such as cardiac output, cardiac index, systemic artery pressure, and pulmonary artery wedge pressure are usually not elevated. 

Direct vascular smooth-muscle relaxants evaluated in primary pulmonary hypertension include hydralazine, isosorbide dinitrate, and diazoxide. In general, the hemodynamic effects of these drugs include modest reduction in mean pulmonary artery pressure, which parallels a significant reduction in systemic arterial pressure, decreased pulmonary vascular resistance, and increased cardiac output. 

Hydralazine is the first systemic vasodilator drug advocated for initial treatment in patients with primary pulmonary hypertension. Rubin and Peter (1980) reported that short-term and long-term administration of hydralazine (200-300 mg/day) improved hemodynamics during rest and exercise in patients with primary pulmonary hypertension. The use of hydralazine, however, is not without hazard. In one study with 13 patients (Danahy et al., 1979), hydralazine produced only modest decreases in pulmonary arteriolar resistance and serious adverse effects that included hypotension (resulting in one death), renal insufficiency, and systemic arterial hypoxemia. 

Very few animal studies have addressed the question of whether addition of NO to inhaled gas has benefits in addition to improved gas exchange and/or central hemodynamics. Zayek et al. (1993) randomized newborn near-term lambs with experimentally induced persistent pulmonary hypertension by ductus ligation. They compared the effect of prolonged inhalation of 80 ppm NO to that of a control group, with both groups mechanically ventilated postnatally for 23 hr. A significant increase in the survival of lambs by inhaling NO was reported. 

Adnot, S., Kouyoumdjian, C., Defouiiloy, C., Andrivet, P., Sediame, S., Herigault, R., and Fratacci, M.-D. (1993). Hemodynamic and gas exchange responses to infusion of acetylcholine and inhalation of nitric oxide in patients with chronic obstructive lung disease and pulmonary hypertension. Am. Rev. Respir. Dis. 148, 310-316. 

Adatia, I., Perry, S., Landzberg, M., Moore, P., Thompason, J. E., and Wessel, D. L. (1994). Inhaled nitric oxide and hemodynamic evaluation of patients with pulmonary hypertension before transplantation. /. Am. Coll. Cardiol, in press. 

Some of the profound hemodynamic changes seen in endotoxin induced shock, viz. pulmonary hypertension, platelet aggregation and systemic hypotension, have also been correlated with an increased thromboxane biosynthesis [379-384]. Mortality in endotoxic shock was significantly reduced following administration of the thromboxane synthetase inhibitors, imidazole and carboxyheptyl-imidazole, as well as of the thromboxane Aj antagonist, 13-azaprostanoic acid [380,381]. However, the increased PGIj production associated with the systemic arterial hypotension is more likely the cause of the often fatal outcome of this event [384]. 

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