Inhaled therapy for the management of perioperative pulmonary hypertension.

Patients with pulmonary hypertension (PH) are at high risk for complications in the perioperative setting and often receive vasodilators to control elevated pulmonary artery pressure (PAP). Administration of vasodilators via inhalation is an effective strategy for reducing PAP while avoiding systemic side effects, chiefly hypotension. The prototypical inhaled pulmonary‑specific vasodilator, nitric oxide (NO), has a proven track record but is expensive and cumbersome to implement. Alternatives to NO, including prostanoids (such as epoprostenol, iloprost, and treprostinil), NO‑donating drugs (sodium nitroprusside, nitroglycerin, and nitrite), and phosphodiesterase inhibitors (milrinone, sildenafil) may be given via inhalation for the purpose of treating elevated PAP. This review will focus on the perioperative therapy of PH using inhaled vasodilators.

Iloprost inhalado, un vasodilatador pulmonar selectivo. Evidencia clínica de su uso en la hipertensión pulmonar del perioperatorio de cirugía cardiovascular / Inhaled iloprost, a selective pulmonary vasodilator. Clinical evidence from its use in perioperative pulmonary hypertension cardiovascular surgery

El iloprost inhalado es uno de los fármacos más recientes del grupo de prostanoides en el tratamiento de la hipertensión arterial pulmonar. No se ha definido su importancia en la hipertensión pulmonar en el perioperatorio de cirugía cardiovascular. En esta revisión se analizan los grupos con hipertensión pulmonar susceptibles de cirugía cardiaca, la importancia de la hipertensión pulmonar en cirugía cardiaca y, además, la evidencia clínica actual del uso del fármaco en este contexto.

Inhaled iloprost is one of the most recent drugs from prostanoids group's in the treatment of pulmonary arterial hypertension. His place in pulmonary hypertension seen in the perioperative cardiovascular surgery has not been defined. In this review we analyze pulmonary hypertension group's susceptibles of cardiac surgery and its importance, besides the current clinical evidence from drug use in this context.

Effects of exercise training on stress-induced vascular reactivity alterations: role of nitric oxide and prostanoids

Background: Physical exercise may modify biologic stress responses. Objective: To investigate the impact of exercise training on vascular alterations induced by acute stress, focusing on nitric oxide and cyclooxygenase pathways. Method: Wistar rats were separated into: sedentary, trained (60-min swimming, 5 days/week during 8 weeks, carrying a 5% body-weight load), stressed (2 h-immobilization), and trained/stressed. Response curves for noradrenaline, in the absence and presence of L-NAME or indomethacin, were obtained in intact and denuded aortas (n=7-10). Results: None of the procedures altered the denuded aorta reactivity. Intact aortas from stressed, trained, and trained/stressed rats showed similar reduction in noradrenaline maximal responses (sedentary 3.54±0.15, stressed 2.80±0.10*, trained 2.82±0.11*, trained/stressed 2.97± 0.21*, *P<0.05 relate to sedentary). Endothelium removal and L-NAME abolished this hyporeactivity in all experimental groups, except in trained/stressed rats that showed a partial aorta reactivity recovery in L-NAME presence (L-NAME: sedentary 5.23±0,26#, stressed 5.55±0.38#, trained 5.28±0.30#, trained/stressed 4.42±0.41, #P<0.05 related to trained/stressed). Indomethacin determined a decrease in sensitivity (EC50) in intact aortas of trained rats without abolishing the aortal hyporeactivity in trained, stressed, and trained/stressed rats. Conclusions: Exercise-induced vascular adaptive response involved an increase in endothelial vasodilator prostaglandins and nitric oxide. Stress-induced vascular adaptive response involved an increase in endothelial nitric oxide. Beside the involvement of the endothelial nitric oxide pathway, the vascular response of trained/stressed rats involved an additional mechanism yet to be elucidated. These findings advance on the understanding of the vascular processes after exercise and stress alone and in combination. .

Utilidad clínica del iloprost inhalado en la hipertensión arterial pulmonar / Clinical utility of inhaled iloprost in pulmonary arterial hypertension

El iloprost inhalado es un fármaco del grupo de las prostaciclinas utilizado en el tratamiento de la hipertensión arterial pulmonar. La eficacia y seguridad de su administración han permitido su uso como monoterapia y en terapia combinada. En esta revisión se describen las características del medicamento, los grupos susceptibles de tratamiento y la evidencia clínica actualizada del uso del fármaco.

Inhaled iloprost is a drug from the group of prostacyclins used in the treatment of pulmonary arterial hypertension. Its efficacy and safety have allowed its use as monotherapy and combination therapy. This review describes the product characteristics, amenable to treatment groups, and updated clinical evidence of drug use.

Effects of the chronic ingestion of an infusion of Ruta chalepensis on the vasomotor responses of rat aortic rings / Efectos de la ingestión crónica de una infusión de Ruta chalepensis sobre las respuestas vasomotoras de anillos de aorta de rata

Ruta chalepensis, is used, in traditional medicine, as emmenagogue, abortive, and analgesic. We analyzed, in male Wistar rats, the effects of the chronic intake of an infusion of Ruta chalepensis (20 g/L) on the vasomotor responses of, either intact or endothelium-denuded aortic rings, to phenylephrine or carbachol. Only in rings with endothelium significant effects were observed. The infusion induced a leftward shift of the concentration-response curve to phenylephrine and an increase in maximal tension development. These effects were abolished by indomethacin. In these rings, inhibiting the synthesis of nitric oxide, in the presence of indomethacin, induced a leftward shift of the concentration response curve to phenylephrine, as well as an increase in maximal tension. These results suggest that the chronic ingestion of a Ruta chalepensis infusion induces an endothelium dependent increase in the synthesis/release of cyclooxygenase-dependent vasoconstrictor prostanoids, and an increase in the basal synthesis/release of nitric oxide.

Ruta chalepensis se utiliza en la medicina tradicional como emenagogo, abortivo y analgésico. Se analizaron, en ratas Wistar macho, los efectos de la ingesta crónica de una infusión de Ruta chalepensis (20 g /L), sobre las respuestas vasomotoras de anillos de aorta con y sin endotelio, a la fenilefrina o al carbacol Se observaron efectos significativos sólo en anillos con endotelio. La infusión indujo un desplazamiento a la izquierda de la curva de concentración-respuesta a fenilefrina y un incremento en la tensión máxima desarrollada. Estos efectos fueron abolidos por la indometacina. La inhibición de la síntesis de óxido nítrico, en presencia de indometacina, produjo un desplazamiento a la izquierda de la curva de concentración-respuesta a la fenilefrina, así como un incremento en la tensión máxima. Estos resultados sugieren que la ingesta crónica de una infusión de Ruta chalepensis induce un incremento en la síntesis/liberación de prostanoides vasoconstrictores dependientes de la ciclooxigenasa y un aumento en la síntesis /liberación basal de óxido nítrico.

Hipertensión pulmonar: la mirada del especialista / Pulmonary hypertension: the specialist opinion / Hipertensão pulmonar: a opinião do especialista

La hipertensión pulmonar constituye una de las enfermedades con creciente prevalencia en la actualidad, con pronóstico ominoso y deterioro en la calidad de vida de los pacientes. El fracaso de la función del ventrículo derecho, consecuencia del remodelado en el lecho vascular pulmonar, que provoca un estado hemodinámico caracterizado por elevación sostenida de la presión en el circuito arterial pulmonar, es el resultado final del aumento de la poscarga. En las últimas décadas, los avances en el conocimiento de esta enfermedad, así como las nuevas investigaciones, han logrado brindar información para llegar al diagnóstico precoz y el tratamiento más adecuado. Ambos constituyen la base para lograr un cambio en la evolución de esta enfermedad, mejorando la calidad de vida y supervivencia de los pacientes. Si bien, es importante el conocimiento por parte de los equipos de salud, la derivación a centros especializados en el manejo de estos pacientes con médicos capacitados contribuirá significativamente a cambiar el curso evolutivo natural de esta enfermedad. La presente revisión tiene como objetivo brindar información actualizada, aportando datos que permitan facilitar la detección precoz, el diagnóstico y el tratamiento de estos pacientes, permitiendo una correcta atención o, en su defecto, realizar la derivación a centros especializados de referencia.

Pulmonary hypertension is a disease with currently increasing relevance, poor prognosis and impaired quality of life of patients. The right heart failure is the end result of the remodeling in pulmonary vascular tree causing a hemodynamic state with sustained elevation of pressure in pulmonary arteries and the subsequent afterload increase. In recent decades, advances in our understanding of this disease, as well as new research has been able to provide information to make an early diagnosis and the most appropriate treatment. Both are the basis for change in the evolution of the disease, improving patient's quality of life and survival. It's also important to change the natural history of the disease, the knowledge of health team and the timely consultation with clinics and physicians with special trainee in management of these patients. This review aims to provide updated information, providing data to facilitate the early detection, diagnosis and treatment of these patients allowing a proper attention or, alternatively, make referrals to specialized referral centers.

A hipertensão pulmonar é uma das doenças com maior relevância no momento, com prognóstico desfavorável nos pacientes e deterioração da qualidade de vida. A falha do ventrículo direito, resultado da remodelação do leito vascular pulmonar causando estado hemodinâmico com elevação sustentada da pressão nas artérias pulmonares e ao aumento da pós-carga é o resultado final. Nos últimos tempos, avanços no conhecimento desta doença bem como a investigação têm fornecido informações para obter o diagnóstico precoce e o tratamento mais adequado. Ambos são a base para as alterações sobre a evolução desta doença, melhorando a qualidade de vida e sobrevida. Embora seja importante o conhecimento das equipes de saúde, ir à clínica e os médicos com estagiário especial na gerência destes pacientes é uma contribuição significativa para alterar a história natural dessa doença. Esta revisão tem como objetivo fornecer informações atualizadas, fornecendo dados para facilitar a detecção precoce, diagnóstico e tratamento destes pacientes permitindo uma atenção adequada ou, em alternativa, fazer encaminhamentos para centros de referência especializados.

Prostaglandin E2 Receptors on Upper Respiratory Tract / 대한이비인후과학회지

Prostaglandin (PG) E2 exerts its actions by acting on a group of G-protein-coupled receptors (GPCRs). GPCRs responding to PGE2 consist of four subtypes namely E-prostanoid 1 (EP1), E-prostanoid 2 (EP2), E-prostanoid 3 (EP3), and E-prostanoid 4 (EP4) and multiple splicing isoforms of the subtype EP3. The EP subtypes exhibit differences in signal transduction pathway, tissue localization, and regulation of expression. This molecular and biochemical heterogeneity of PGE2 receptors leads to PGE2 being the most variable prostanoid. Studies on knockout mice deficient in each EP subtype and selective agonist and antagonist have defined PGE2 actions mediated by each subtype and identified the role each EP subtype plays in various physiological and pathophysiological responses. We summarize and review PGE2 receptor research.

The Role of Prostanoids in vivo Feline Penile Erection / 대한비뇨기과학회지

PURPOSE: The widespread use of intracorporeal prostaglandin E1 (PGE 1) injection for the treatment of erectile dysfunction has focused interest on the physiological functions of prostanoids with the mechanism of action. We investigated in vivo feline penile erectile and contractile responses to prostanoids. MATERIALS AND METHODS: Under the general anesthesia, 26 mature male cats were conditioned normoxia and hypoventilated hypoxia with ventilator in room air(PH: 7.14+/- 0.47, PO2: 25.52+/-5.89mmHg, PCO2: 74.27+/-10.86mmHg). Vasoactive substances were infused via internal pudendal artery and the changes of intracavernous pressure to vasoactive substances were monitored with physiograph under normoxia and hypoxia with acidosis. RESULTS: Under normoxia, PGE1 induced dose-dependent cavernous relaxation and PGE1 was more potent than papaverine but less than acetylcholine. PGE1- induced cavernous relaxation was blocked by the K+-channel blockers, tetraethylammonium(TEA) and 4-aminopyridine, in dose-dependent manner but was completely reversed by the K+-channel opener, pinacidil. Calcium ionophore, ionomycin(10-3M/0.2ml) prevented the cavernous relaxation by PGE1 under hypoxia(n=6, p<0.01). PGI2 showed minimal cavernous relaxation with tumescence. Thromboxane A2(TXA2) attenuated the acetylcholine-induced relaxation CONCLUSIONS: This study showed that PGE2 relax feline cavernous smooth muscle. But the mechanism of PGE2 on feline cavernosum should be elucidated by the receptor binding study. These results suggest that PGE2 induced smooth muscle relaxation by the opening of Maxi-K+ (Kca) channel and subsequent hyperpolarization. It would be followed by a reduced opening of voltage-dependent Ca2+-channel and subsequent decrease of intracellular Ca2+concentration.