Combined Administration of Intravenous Dipyridamole and Inhaled Nitric Oxide to Assess Reversibility of Pulmonary Arterial Hypertension in Potential Cardiac Transplant Recipients

Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation (Impact Factor: 6.65). 11/2005; 24(11):1950-6. DOI: 10.1016/j.healun.2005.04.007
Source: PubMed


Irreversible, severe pulmonary hypertension (PH) can produce right heart failure and early mortality after cardiac transplantation. We hypothesized that dipyridamole, an inhibitor of Type 5 phosphodiesterase, would augment the ability of inhaled nitric oxide (NO) to identify reversibility of PH.
In 9 patients with congestive heart failure (CHF) and severe PH who were breathing 100% oxygen during right heart catheterization, we administered inhaled NO (80 ppm) alone and in combination with intravenous dipyridamole (0.2-mg/kg bolus, with an infusion of 0.0375 mg/kg/min).
Compared with breathing oxygen alone, NO inhalation decreased pulmonary artery pressure and pulmonary vascular resistance (PVR) (by 10 +/- 4% and 26 +/- 12% [mean +/- SEM], respectively; both p < 0.05). The combination of NO and dipyridamole reduced PVR (43 +/- 7%; p < 0.05) to a greater extent than did administration of NO alone, and increased the duration of pulmonary vasodilation produced by NO inhalation. Combined administration of inhaled NO and intravenous dipyridamole increased cardiac index (by 23 +/- 10%) and reduced SVR (by 19 +/- 6%, both p < 0.05) without changing systemic arterial pressure. NO inhalation reduced PVR to <200 dyne x s/cm5 in 3 of 7 patients who had a PVR of >200 dyne x s/cm5 when breathing oxygen alone, whereas the combination of NO and dipyridamole decreased PVR to <200 dyne.s/cm(5) in 2 additional patients.
Intravenous dipyridamole augments and prolongs the pulmonary vasodilator effects of inhaled NO in CHF patients with severe PH and, when administered in combination with NO inhalation, can identify PH reversibility in potential cardiac transplant recipients in whom a pulmonary vasodilator response to inhalation of NO alone is not observed.

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    • "Not surprisingly, the combination of agents resulted in more profound hemodynamic changes than in using separate drugs. Combinations of sildenafil and inhaled NO[12] and NO and dipyridomole[12] were well-tolerated and resulted in more profound favorable changes than each of the individual drugs. "
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    ABSTRACT: Multiple drugs are used for reversibility testing of pulmonary hypertension (PH) in advanced heart failure (HF), especially in the process of heart transplant evaluation. Effects of these drugs were never systematically compared. The aim of this meta-analysis was to compare hemodynamic effects of different drugs. We identified 20 prospective studies reporting hemodynamic variables before and after acute pharmacologic testing for PH reversibility in patients with advanced HF. The data from individual studies were grouped by an outcome measure and analyzed. A mixed model meta-analysis was performed using SAS to give weighted mean effect of pre- and post-test change and inverse variance. The mean effects were weighted by the published sample size. Prostacyclin, inhaled or intravenous, and prostaglandin E1 (PGE1) had the most potent effect on pulmonary vascular resistance (PVR). Sodium nitroprusside and nitroglycerin decreased pulmonary capillary wedge pressure (PCWP), and mean pulmonary arterial pressure (MPAP) better than other drugs. Sildenafil provided overall good hemodynamic outcomes but was not the strongest drug with regard to any particular outcome. PCWP, MPAP, and systolic pulmonary arterial pressure respond better to nitroglycerin and sodium nitroprusside than to other drugs in the setting of reversibility testing. Prostacyclin and PGE1 are superior to other drugs in their acute effects on PVR.
    04/2013; 3(2):406-13. DOI:10.4103/2045-8932.113180
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    • "In pediatric patients with pulmonary hypertension dipyridamole decreased PVR index to similar values as INO did, but with signifi cant systemic vasodilatation (Ziegler et al 1998). Intravenous dipyridamole has been used to identify reversibility of pulmonary hypertension in potential cardiac transplant recipients with CHF in whom a pulmonary vasodilator response to inhalation of NO alone is not observed (Lepore et al 2005a). Intravenous dipyridamole was also used in acute management of pulmonary hypertension in combination either with INO or intravenous nitroglycerin (Sulica et al 2005). "
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    ABSTRACT: Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in combinations with other agents, and must be individualized based on patient response.
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    ABSTRACT: Pulmonary hypertension is a condition frequently seen and associated to many cardiovascular diseases and can become a hemodynamic complication in postoperative period. This can require the integral management in the intensive care room. In the last years we have many new concepts about the pathophysiology of this condition and new therapeutic options. In this paper we review the current strategies for the management of this condition.
    Archivos de cardiología de México 04/2006; 76 Suppl 2:S76-80.
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