Comparative Acute Effects of Adenosine and Prostacyclin in Primary Pulmonary Hypertension

doi:10.1378/chest.107.1.54

Chest

Volume 107, Issue 1, January 1995, Pages 54-57

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Vasodilators have been a main focus of therapy for primary pulmonary hypertension. Adenosine and prostacyclin have been shown to reduce pulmonary vascular resistance acutely in these patients. In order to compare the acute hemodynamic effects of adenosine and prostacyclin, ten patients with severe primary pulmonary hypertension, unresponsive to medical therapy, were studied. After baseline hemodynamics were obtained, an adenosine infusion, 50 to 100 ng/kg/min, was begun and titrated to the maximum tolerated dose. Hemodynamics were allowed to return to baseline, and thereafter, a prostacyclin infusion was begun at 2 ng/kg/min, and titrated to the maximum tolerated dose. Overall, adenosine (200±53 ng/kg/min) produced a 33±18% (p<0.001) fall in pulmonary vascular resistance and a 52±25% (p<0.001) increase in cardiac output with no effect on pulmonary or systemic arterial pressures. Prostacyclin (8±4 ng/kg/min) caused a 22±18% (p<0.01) fall in pulmonary vascular resistance and a 25±26% (p<0.05) increase in cardiac output with a 14±6% (p<0.001) decrease in systemic arterial pressure, but no change in pulmonary arterial pressure. The effects of adenosine and prostacyclin on pulmonary vascular resistance were similar (r=0.70, r²=0.49, p=0.02). Adenosine and prostacyclin have similar hemodynamic effects acutely in primary pulmonary hypertension. Adenosine may be useful as a test of the potential for long-term prostacyclin therapy in patients with primary pulmonary hypertension.

Section snippets

Study Patients

Ten patients with primary pulmonary hypertension referred to the University of Illinois were entered into this study (nine female, one male; mean age 43±15 years). All patients were evaluated by clinical history, physical examination, chest radiography, lung scan, pulmonary function testing, echocardiography, and cardiac catheterization. Their conditions were diagnosed based on the criteria used in the National Institute of Health Registry on primary pulmonary hypertension.⁶ Patients were also

Responses to Adenosine

Overall there was a 33±18% (p<0.001) fall in pulmonary vascular resistance (from 13 U to 9 U) and a 52±25% (p<0.001) increase in cardiac output (from 3.5 L/min to 5.4 L/min) in response to adenosine, with no significant change in mean pulmonary, systemic arterial, or pulmonary capillary wedge pressures (Fig 1). There was, however, a 35±23% (p<0.01) fall in systemic vascular resistance (from 23 to 14 U) with slight but significant increases in right atrial pressure (from 10 mm Hg to 14 mm Hg,

Mechanism of Adenosine

Adenosine is a purine nucleoside with potent coronary and systemic vasodilatory effects.⁷ These effects are mediated by specific cell membrane receptors (A₁ and A₂) that are coupled to the adenylate cyclase system via G-proteins.8, 9 Vasodilatory effects are thought to be mediated by activation of subtype A2, which results in increased intracellular cAMP. Several effects of adenosine have also been found to be independent of cAMP, including activation of K⁺ channels following activation of

References (14)

SchraderBJ et al.
Comparison of the effects of adenosine and nifedipine in pulmonary hypertension
J Am Coll Cardiol
(1992)
DustingGJ et al.
Prostacyclin and vascular function: implications for hypertension and atherosclerosis
Pharmacol Ther
(1990)
InbarS et al.
The effects of adenosine in combination with calcium channel blockers in patients with primary pulmonary hypertension
J Am Coll Cardiol
(1993)
D'AlonzoGE et al.
Survival in patients with primary pulmonary hypertension: results from a National Prospective Registry
Ann Intern Med
(1991)
MorganJM et al.
Adenosine as a vasodilator in primary pulmonary hypertension
Circulation
(1991)
JonesDK et al.
Treatment of primary pulmonary hypertension with intravenous epoprostenol (prostacyclin)
Br Heart J
(1987)
RubinLJ et al.
Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol): results of a randomized trial
Ann Intern Med
(1990)

There are more references available in the full text version of this article.

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: Supported in part by the Department of Veterans Affairs (Office of Research ana Development, Medical Research Service) and by Burrough Wellcome Co.

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Chest

Clinical Investigations: Cardiology: ArticlesComparative Acute Effects of Adenosine and Prostacyclin in Primary Pulmonary Hypertension

Section snippets

Study Patients

Responses to Adenosine

Mechanism of Adenosine

J Am Coll Cardiol

Pharmacol Ther

J Am Coll Cardiol

Survival in patients with primary pulmonary hypertension: results from a National Prospective Registry

Ann Intern Med

Adenosine as a vasodilator in primary pulmonary hypertension

Circulation

Treatment of primary pulmonary hypertension with intravenous epoprostenol (prostacyclin)

Br Heart J

Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol): results of a randomized trial

Ann Intern Med

Clinical Investigations: Cardiology: Articles
Comparative Acute Effects of Adenosine and Prostacyclin in Primary Pulmonary Hypertension