Efficacy and optimal dose of sildenafil in primary pulmonary hypertension

Chockalingam, Anand; Gnanavelu, G.; Venkatesan, S.; Elangovan, Satheesh; Jagannathan, V.; Subramaniam, T.; Alagesan, R; Dorairajan, Smrita

doi:10.1016/j.ijcard.2003.12.023

Cited by 68 publications

(41 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A significant number of patients with acute or chronic PH have a minimal response to vasodilators including iNO and PDE inhibitors (26,27). It is conceivable that in some of these patients, sGC may have become oxidized, rendering it resistant to activation by endogenous and/or exogenous NO.…”

Section: Discussionmentioning

confidence: 99%

Inhaled Agonists of Soluble Guanylate Cyclase Induce Selective Pulmonary Vasodilation

Evgenov

Kohane²,

Bloch³

et al. 2007

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: Nitric oxide-independent agonists of soluble guanylate cyclase (sGC) have been developed. Objectives: We tested whether inhalation of novel dry-powder microparticle formulations containing sGC stimulators (BAY 41-2272, BAY 41-8543) or an sGC activator (BAY 58-2667) would produce selective pulmonary vasodilation in lambs with acute pulmonary hypertension. We also evaluated the combined administration of BAY 41-8543 microparticles and inhaled nitric oxide (iNO). Finally, we examined whether inhaling BAY 58-2667 microparticles would produce pulmonary vasodilation when the response to iNO is impaired. Methods: In awake, spontaneously breathing lambs instrumented with vascular catheters and a tracheostomy tube, U-46619 was infused intravenously to increase mean pulmonary arterial pressure to 35 mm Hg. Measurements and Main Results: Inhalation of microparticles composed of either BAY 41-2272, BAY 41-8543, or BAY 58-2667 and excipients (dipalmitoylphosphatidylcholine, albumin, lactose) produced dosedependent pulmonary vasodilation and increased transpulmonary cGMP release without significant effect on mean arterial pressure. Inhalation of microparticles containing BAY 41-8543 or BAY 58-2667 increased systemic arterial oxygenation. The magnitude and duration of pulmonary vasodilation induced by iNO were augmented after inhaling BAY 41-8543 microparticles. Intravenous administration of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), which oxidizes the prosthetic heme group of sGC, markedly reduced the pulmonary vasodilator effect of iNO. In contrast, pulmonary vasodilation and transpulmonary cGMP release induced by inhaling BAY 58-2667 microparticles were greatly enhanced after treatment with ODQ. Conclusions: Inhalation of microparticles containing agonists of sGC may provide an effective novel treatment for patients with pulmonary hypertension, particularly when responsiveness to iNO is impaired by oxidation of sGC.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhaled Agonists of Soluble Guanylate Cyclase Induce Selective Pulmonary Vasodilation

Evgenov

Kohane²,

Bloch³

et al. 2007

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…[22][23][24][25] Even among patients with a single genotype, the hemoglobin concentration is variable. In HbSS, the most common and clinically severe form of the disease, red cell 51 Cr survival ranges between 2 and 21 days and is reflected in similarly wide variations of hemoglobin concentration, reticulocyte count, bilirubin level, and LDH, all of which are clinical markers of hemolysis. 22,24 Recent work suggests that hemolytic anemia is the driving force behind some complications of SCD because of its effects on nitric oxide (NO) bioavailability.…”

Section: Hemolysis and Sickle Priapism 3265mentioning

confidence: 99%

“…49,50 Sildenafil, a PDE5 inhibitor, may also be effective in treating pulmonary hypertension. 51,52 Hydroxyurea appears to have little effect in sickle cell pulmonary hypertension, 28 and yet it may help prevent stroke in susceptible children 53 and also has an effect in some instances of priapism. Five patients with stuttering priapism, whose average age was 20 years, experienced relief during hydroxyurea treatment.…”

Section: Hemolysis and Sickle Priapism 3265mentioning

confidence: 99%

Hemolysis-associated priapism in sickle cell disease

Nolan

Wyszynski

Farrer

et al. 2005

Blood

182

150

View full text Add to dashboard Cite

Priapism, although uncommon in the general population, is one of the many serious complications associated with sickle cell disease (SCD). Few studies have described the clinical and hematologic characteristics of individuals with priapism and SCD. Using data from the Cooperative Study for Sickle Cell Disease, we assembled 273 case subjects with priapism and 979 control subjects. Case subjects, compared with control subjects, had significantly lower levels of hemoglobin; higher levels of lactate dehydrogenase, bilirubin, and aspartate aminotransferase; and higher reticulocyte, white blood cell, and platelet counts. These findings suggest an association of priapism with increased hemolysis. IntroductionSickle cell disease (SCD) is an inherited condition caused by a point mutation in the ␤-globin gene (HBB), resulting in the substitution of valine for glutamic acid at position 6 of the ␤-globin chain (Glu6Val). This mutation results in the abnormal sickle hemoglobin (HbS). When deoxygenated, HbS polymerizes, damaging the sickle erythrocyte. 1 These sickle cells are short lived and can interact with endothelial cells, leukocytes, platelets, and other plasma components to initiate the vasoocclusive manifestations associated with SCD.Priapism is a sustained, painful, and unwanted erection of the penis that pathophysiologically is the result of either increased arterial inflow (ie, high flow) or, more commonly, the failure of venous outflow (ie, low flow), resulting in blood trapping within the erectile bodies. Although uncommon in the general population, 2 priapism was recognized as a serious complication of SCD as early as 1934. 3 Since then, many researchers have estimated its incidence and prevalence in various populations and the choices for its treatment. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] In general, about 30% of males with SCD under the age of 20 years reported having had at least one episode of priapism, 8,11,17 whereas frequencies of 30% to 45% are estimated for adult men. 18 Among patients with priapism, about 75% had their first occurrence before the age of 20 with the mean age being around 12 to 15 years. 17,18 Few published studies, however, have described the clinical characteristics of their participants with priapism. Using data from the Cooperative Study of Sickle Cell Disease (CSSCD), we assembled a large cohort of patients with priapism to study their clinical, laboratory, demographic, and social characteristics. Patients, materials, and methods Patient databaseThe CSSCD enrolled and followed more than 4000 patients with SCD who had visited 1 of 23 participating clinical centers across the United States between 1978 and 1998. 19,20 One of the primary aims of the CSSCD was to collect data on the clinical course of SCD from birth to death. Because of the clinical variability of SCD, data were collected on a large number of possible manifestations of the disease, including priapism. All incident events of priapism causing a participant to seek medical care were carefully recorded, ...

show abstract

“…Эффект ИФДЭ5 зависит от концентрации эндогенного NO и цГМФ, уровни которых снижены у пациентов с ЛАГ [17]. Значительная часть пациентов (20-60%) с ЛАГ не достигают целей терапии или характе-ризуются нестабильным эффектом при применении тера-пии ИФДЭ5 [18][19][20]. Риоцигуат, обладающий двойным механизмом действия, увеличивает чувствительность рГЦ к низким концентрациям NO и также напрямую стимули-рует рГЦ, независимо от NO, что может обеспечить боль-шую эффективность у пациентов с ЛАГ, которые не дости-гают достаточного ответа на терапию ИФДЭ5 [20].…”

Section: рисунок 2 алгоритм лечения больных лаг [2]unclassified