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

ArticleinThe Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 24(11):1950-6 · November 2005with2 Reads
DOI: 10.1016/j.healun.2005.04.007 · Source: PubMed
Abstract
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.
    • "Because of the possibility of hemodynamic instability, short-acting vasodilator agents are generally preferred for diagnostic testing. Protocols using nitroprusside, milrinone, prostacyclins, nitric oxide, and nitroglycerin have all been reported [27,303132. After obtaining resting hemodynamics, the vasodilator is initiated and the dose is up-titrated incrementally with regular hemodynamic measurements and close monitoring for the development of hypotension (systolic blood pressure (SBP)<90 mmHg) or other evidence of hypoperfusion . "
    [Show abstract] [Hide abstract] ABSTRACT: Pulmonary hypertension (PH) is a common complication of left heart disease (LHD) and is associated with impaired functional capacity and decreased survival. Recent guidelines have proposed a new classification system for PH-LHD that is based on the diastolic pulmonary gradient. Despite a sound physiologic basis, subsequent studies have not found a significant correlation between the diastolic pulmonary gradient and meaningful outcomes. Treatment of PH-LHD focuses on optimizing the left heart disease. The use of medications for the treatment of combined post- and pre-capillary PH in left heart disease is controversial. While several small studies have shown hemodynamic or symptomatic improvement, none have been demonstrated to clearly improve long-term outcomes. Large, event-driven trials of PH-LHD are needed to guide the optimal management of this population.
    Article · Oct 2015
    • "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. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Apr 2013
    • "[7] The mechanisms of this LV filling pressure increase are unknown. However, studies have shown inter-individual variations in the inhaled-NO response that were independent from the cause of PH.7891011 NO signaling is mainly mediated by cyclic guanosine monophosphate (cGMP) accumulation within the cells as a consequence of increased guanylate cyclase activity. However, cGMP bioavailability is limited by the hydrolytic activity of phosphodiesterases (PDE), most notably PDE5. "
    [Show abstract] [Hide abstract] ABSTRACT: To evaluate the vasoconstrictor component of PH in CHF by investigating the hemodynamic response to inhaled nitric oxide (iNO) and to determine whether this response was influenced by the phosphodiesterase 5 gene (PDE5) G(1142)T polymorphism. CHF patients underwent right heart catheterization at rest and after 20 ppm of iNO and plasma cGMP and PDE5 G(1142)T polymorphism determinations. Of the 72 included CHF patients (mean age, 53±1 years; mean left ventricular ejection fraction, 29±1%; and mean pulmonary artery pressure, 25.5±1.3 mmHg), 54% had ischemic heart disease. Proportions of patients with the TT, GT, and GG genotypes were 39%, 42% and 19% respectively. Baseline hemodynamic characteristics were not significantly different across PDE5 genotype groups, although pulmonary capillary wedge pressure (PCWP) tended to be lower in the TT group (P=0.09). Baseline plasma cGMP levels were significantly lower in the TT than in the GG and GT patients. With iNO, PVR diminished in TT (-33%) but not GG (-1.6%) or GT (0%) patients (P=0.002); and PCWP increased more in TT than in GT (P<0.05) or GG (P<0.003) patients. The PDE5 G(-1142) polymorphism is therefore a major contributor to the iNO-induced PVR decrease in CHF.
    Full-text · Article · Jul 2011
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