Omitting 50 µg of intracoronary acetylcholine injection in the left coronary artery during spasm provocation test.

BACKGROUND: Although guidelines recommend intracoronary administration of acetylcholine (ACh) with incremental doses of 20, 50, and 100 µg into the left coronary artery (LCA) during spasm provocation test for diagnosing vasospastic angina, 50 µg of ACh rarely induced significant coronary vasospasm when no vasoconstriction was observed with 20 µg of ACh in a previous report. The aim of this study was to evaluate the safety and feasibility of omitting 50 µg according to the vasoreactivity by 20 µg of ACh in the LCA. METHODS: A total of 556 patients undergoing ACh provocation test with 20 µg followed by 50 and/or 100 µg were retrospectively included. Injection of 50 µg of ACh was primarily omitted when vasoconstriction <25 % was observed with 20 µg, which was left to operator's discretion. Adverse events were defined as a composite of ventricular fibrillation, sustained ventricular tachycardia, and cardiogenic shock during ACh test in the LCA. RESULTS: Positive ACh test in the LCA was observed in 245 (44.1 %) patients. Overall, patients with LCA constriction <25 % by 20 µg of ACh had a lower rate of positive ACh test than their counterpart (24.0 % vs. 88.4 %, p < 0.001). In patients with LCA constriction ≥25 % by 20 µg, the incidence of adverse events was significantly higher than in those with LCA constriction <25 % during the provocation test at doses of 50 and 100 µg (2.3 % vs. 0 %, p = 0.009). CONCLUSIONS: Omitting 50 µg of ACh in the LCA may be safe and feasible when little vasoconstriction was observed with preceding injection of 20 µg of ACh during spasm provocation test for diagnosing vasospastic angina. However, we believe that 50 µg of ACh should not be omitted when 20 µg of ACh induced LCA constriction ≥25 %.

Safety and potential usefulness of sequential intracoronary acetylcholine and ergonovine administration for spasm provocation testing.

BACKGROUND: Although guidelines recommend intracoronary acetylcholine (ACh) and ergonovine (ER) provocation testing for diagnosis of vasospastic angina, the feasibility and safety of sequential (combined) use of both pharmacological agents during the same catheterization session remain unclear. OBJECTIVES: In this study, we investigated the feasibility and safety of sequential intracoronary ACh and ER administration for coronary spasm provocation testing. METHODS: The study included 235 patients who showed positive results on ACh and ER provocation testing. Initial intracoronary ACh administration was followed by ER administration for left coronary artery (LCA) spasm provocation testing. Subsequently, the right coronary artery (RCA) was subjected to sequential ACh and ER administration for provocation testing. The primary outcome of the study was the safety of sequential intracoronary ACh and ER provocation testing, which was assessed based on a composite of all-cause death, sustained ventricular tachycardia and fibrillation, and cardiogenic shock. RESULTS: Even in patients with negative results on sequential intracoronary ACh and ER provocation testing in the LCA and only ACh administration into the RCA, additional administration of ER into the RCA showed a positive provocation test result in 33 of 235 (14.0%) patients; three (1.3%) patients developed adverse effects (cardiogenic shock occurred in all cases) during LCA provocation testing. We observed no deaths attributable to spasm provocation testing. CONCLUSION: Sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of vasospastic angina.

Safety and potential usefulness of novel coronary spasm provocation testing protocolCoronary spasm represents a subtype of ischemic heart disease, potentially leading to heart attack. Although guidelines recommend intracoronary administration of different pharmacological agents, acetylcholine (ACh) and ergonovine (ER), for coronary spasm provocation testing, the feasibility and safety of sequential (combined) use of both drugs are unclear. In the present study, we showed that sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of coronary vasospasm.

What is the meaning of provoked spasm phenotypes by vasoreactivity testing?

Coronary artery epicardial spasm is involved in the pathogenesis of many cardiac disorders. Vasoreactivity testing, such as intracoronary injection of acetylcholine (ACH) or ergonovine (ER), is the gold standard method for the diagnosis of vasospastic angina. Provoked epicardial spasm phenotypes are classified as focal spasm and diffuse spasm. Multiple factors, including sex, ethnicity, and use of coronary vasoactive stimulators, are related to the provoked phenotypes of epicardial spasm. Diffuse-provoked spasm is often observed in females, where focal-provoked spasm is markedly more common in males. ACH provokes more diffuse and distal spasms, whereas ER induces more focal and proximal spasms. Yellow plaque and coronary thrombi are often observed in lesions with focal spasms, and intimal thickness with a sonolucent zone is significantly more common in lesions with focal spasm. Furthermore, clinical outcomes in patients with focal spasm are unsatisfactory compared with those in patients with diffuse spasm. However, the reproducibility and eternality of provoked spasm phenotypes by vasoreactivity testing is uncertain. Coronary atherosclerosis or endothelial damage may affect coronary vasomotor tone. Although coronary artery spasm may persist in the same coronary artery, provoked coronary spasm phenotypes may exhibit a momentary coronary reaction by intracoronary ACH or ER testing.

Alguns aspectos da funçäo endotelial em cirurgia cardíaca / Some aspects of the endothelial function in cardiac surgery

Este estudo mostra alguns aspectos da funçäo endotelial relacionados, diretamente, com a cirurgia cardíaca: 1) Após isquemia miocárdica global seguida de reperfusäo, o endotélio coronariano perde a habilidade de expressar vasodilataçäo endotélio-dependente mediada por receptores, ao passo que o relaxamento endotélio-dependente mediado pelo cálcio ionóforo A23187 e a fosfolipasec C, que näo dependem de estimulaçäo de receptores, encontra-se inalterada. O relaxamento produzido pelo fluoreto de sódio, o qual atua através de G-proteína(s), encontra-se comprometido. Estes experimentos indicam que o comprometimento da produçäo de EDRF/NO mediada por receptores após a lesäo de reperfusäo possa ser devido a uma disfunçäo de G-proteínas que liga os receptores da célula endotelial à via da sínese de EDRF/NO; 2) Quarenta e cinco minutos de parada cardioplégica de coraçöes de cäes, pela soluçäo St. Thomas näo comprometem a produçäo de EDRF/NO em artérias epicárdicas coronárias. Estudos farmacológicos in vitro semelhantes, testando-se os efeitos da soluçäo UW, suportaram o conceito de que ela näo lesa o endotélio coronariano, sendo segura para a preservaçäo cardíaca durantes transplantes cardíacos; 3) Em segmentos de artérias coronárias, renais, femorais, e em segmentos de artéria pulmonar, a protamina induziu vasodilataçäo endotélio-dependente, mediada pela estimulaçäo da liberaçäo de EDRF/NO. Nas circulaçöes coronariana e sistêmica, ao contrário do que se verificou nos experimentos envolvendo a circulaçäo pulmonar, este efeito foi independente da presença de heparina; 4) Em 83 por cento dos ensaios biológicos, o efluente da AMI esquerda induziu um relaxamento maior do anel coronariano bioensaiado do que o efluente da AMI direita, por liberaçäo basal de EDRF/NO. Este inibe a adesividade e a agregaçäo plaquetárias e a aterogêne, contribuindo para os resultados superiores obtidos quando se utiliza esta artéria para a revascularizaçäo do miocárdi. Quando expostos à hipoxia, as atividades vasodilatadoras da AMI e da veia safena foram maiores. Esta acentuaçäo da vasodilataçäo causada pela hipóxia foi inibida pelo tratamento com a indometacina, e, rapidamente, revertida, quando se restabeleceu a normóxia.

Pressor effects of acetylcholine microinjected into forebrain nuclei of unanesthetized rats

The injection of 13.5-54 nmol/500 nl of acetylcholine (ACH) into different brain areas of unanesthetized freely-moving 200-250 g male Wistar rats caused only pressor responses. In the prosencephalon, the lateral septal area was the site at which ACH was more effective, whereas injections into surrounding areas, such as the accubens/bed nucleus striae terminalis, the medial septal area or the lateral ventricle were less effective. No effective. No blood pressure effects were observed after injection into the anterior amygdala. In the diencephalon, the ventromedial hypothalamic nucleus was the most sensitive site, whereas injection of ACH into surrounding areas, such as the posterior and lateral hypothalamic or the dorsal and ventral prtemammillary nuclei was less effective. At all sites tested, the local pretreatment with 138-276 nmol atropine abolished the pressor response to ACH, suggesting a mediation through muscarinic receptors. The sites of injection were confirmed histologically. The present data indicate the existence of a cholinergic-sensitive site involved in the control of blood pressure at the level of the lateral septal area

Neuromodulacao da morte subita / Neuromodulation of the sudden death

O autor apresenta a correlacao existente entre a morte subita e o Sistema Nervoso Autonomo atraves dos avancos recentes no conhecimento do ritmo circadiano e da interacao cerebro-coracao ocasionando nao so a morte subita como tambem infarto agudo do miocardio (IAM), arritmias, isquemia silenciosa e alteracoes sanguinias tais como aumento da coagulabilidade do sangue e lesoes nas paredes arteriais. E apresentado tambem de que maneira essa interacao ocorre, com explicacoes anatomo-fisiologicas que facilitam o entendimento da inervacao simpatica e parassimpatica e como a liberacao de acetilcolina e de catecolaminas age sobre o coracao, ressaltando-se seus efeitos deleterios. O autor apresenta ainda a conceituacao moderna sobre a morte subita e o seu impacto e consequencias no mundo moderno.

Potenciación cruzada entre antihistamínicos-H1 y atropina en el tratamiento de los síndromes respiratorios inducidos por histamina y por acetilcolina en acures / Cross-potentiation between H1-antihistamninies and atropine in the treatment of the respiratory syndrome induced by histamine and acetilcholine in guinea pigs

Se estudió el efecto de los antagonistas específicos sobre una condición experimental del acure que simula el asma, producida por dos agonistas distintos, acetilcolina (Ach) e histamina (H). Se midió el tiempo de aparición de los síntomas secuenciales (disnea, asfixia y colapso) y su variación bajo el efecto del antagonista específico de la H (feniltoloxamina, FTX) y de la Ach (atropina). En el asma producida por los dos agonistas, H y Ach, el antagonista específico fue potenciado por el antagonista no específico en sus efectos sobre todos los síntomas. Por el contrario, en la intoxicación de acure por H indovenosa, los efectos fueron estrictamente aditivos, al igual que sobre el músculo liso aislado. Los resultados fueron analizados estadísticamente para indicar la magnitud del sinergismo de potenciación. La potenciación es atribuida a la intervención de distintos receptores y/o a la variación de sensibilidad de un receptor bajo la acción de un agonista. Además, la liberación de varios mediadores por autoestimulación debida al agonista puede tener influencias

Transtornos do sono e suas relaçöes com as funçöes cognitivas / Sleep disorders and cognitive dysfunctions

É feita uma revisäo sobre o sono, sua arquitetura normal e as relaçöes existentes entre esta atividade, a memória e as funçöes cognitivas. As hipóteses que vinculam a memória ao sono REM e ao sono näo-REM säo avaliadas quanto à possível funçäo "consolidadora" desta atividade sobre a memória recente e aprendizado. Condiçöes de transtorno de sono ou situaçöes de supressäo de sono REM ou näo-REM que podem alterar as funçöes cognitivas säo criticamente analisadas. O papel desempenhado pela hipoxemia cerebral em condiçöes como a apnéia de sono é revisto quanto às disfunçöes cognitivas e seu retorno à normalidade uma vez que seja instituído tratamento eficaz. As correlaçöes entre narcolepsia, memória e cogniçäo säo também analisadas. As disfunçöes mnêmicas e cognitivas causadas por hipnoindutores, benzodiazepínicos e antidepressores säo revistas e discutidas

Rapidly recurring cortical seizures induce changes in neuronal responsiveness to acetylcholine

La mayoría de los mecanismos propuestos para explicar la descarga epiléptica sugieren un excesivo influjo sináptico o posibles cambios en la excitabilidad celular que resultan en una disminución del umbral conculsivo y en la presencia de actividad autosostenida. Es probable que estos cambios sean causados por modificaciones en la sensibilidad de los receptores de membrana a un neurotransmisor específico. En vista de lo anterior, el objetivo del presente estudio ha sido evaluar la sensibilidad del receptor postsináptico por medio de la aplicación microiontoforética de sustancias cuyo efecto farmacológico es bien conocido, para determinar su posible participación en el proceso epiléptico. Se provocaron cambios en la excitabilidad cortical por estimulación eléctrica en la corteza sensoriomotora de ratas anestesiadas con uretano (1 g/kg intraperitoneal), inmovilizadas con bromuro de pancuronio y mantenidas con respiración mecánica. Los estímulos eléctricos consistieron en trenes de pulsos bifásicos, cada uno con duración de un milisegundo con frecuencia de 100 pps y con duración del tren de 1 segundo. La respuesta de la neurona a la acetilcolina fue evaluada antes y después que se establecieron las descargas. La dosis se midió en monoampres de corriente microiontoforética. Los potenciales del campo extracelular se registraron con el barril central de micropipetas. Los barriles periféricos fueron usados para aplicaciones iontoforéticas de acetilcolina (Ach .1, 1M), atropina (25 mM). Uno de estos barriles conteniendo NaCl (2M) se empleó para el paso automático de corriente de balance; para 613 de estas células las descargas ya estaban establecidas; en las restantes 532 células, la corteza fue normal (sin descargas). Un aumento en la frecuencia promedio de descarga celular se obsevó después de la aplicación iontoforética de Ach. Intensidades de 2 a 50 nA de corriente se emplearon en la corteza con descargas establecidas. En la corteza con descargas no establecidad la respuesta celular a la aplicación de Ach fue menor cuando fueron aplicadas corrientes de igual intensidad. En ambas cortezas, las células respondieron con mucha menor intensidad a la aplicación de NaCl con corriente de magnitud similar a la usada para movilizar la Ach. Estos hallazgos muestran un cambio en la excitabilidad celualr que se refleja en un nivel más elevado de respuesta celular cuando la acetilcolina está presente, y sugieren que este neurotransmisor participa en el mecanismo de la epilep

Direct negative chronotropic and inotropic efects of curare on isolated and perfused frog's heart

It has been stated that curare has no direct effect upon the heart because the cardiac muscle is deprived of nicotine receptors. While performing an experimental work, we noticed that when high doses of curare were administered to frogs, a change in cardiac activity occurred. In order to elucidate whether the cardiac effects of curare wee the results of a direct action or a reflex response, we studie the effects of increasing doses of d-tubocurarine on the rate and contractility of 8 isolated and perfused frogs'hearts. After testing the d-tubocurarine effects on the heart rate and contractility, we added either acetylcholine, atropine, atenonol or verapamil in orden to find out whether any change ocurred in the cardiac effects produced byd-tubocurarine. Thirty seven measurements were carriet out and it wasfound that 1) high doses (between 1 and 15 micrograms) of d-tubocurarine produced a highly significant decrease in heart rate an contractility; 2) d-tubocurarine did not avoid the acetycholine effect; 3) atropine, atenonol and verapamil did not interfere with d-tubocurarine effects. We conclude that high doses of d-tubocurarine produce "dosis-dependent" heart rate and contratility reductions. These effects are not mediated by muscarinic receptors beta-1 receptors or the show calcium channels