ABSTRACT
BACKGROUND: Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown. METHODS: We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants. Following diagnostic angiography, left anterior descending (LAD) coronary flow reserve and mean luminal diameter were quantified at baseline and during sequential intracoronary administration of adenosine (infusion and bolus), nitroglycerin (bolus), acetylcholine (infusion), acetylcholine coinfused with vitamin C, and, finally, sublingual nitroglycerin. RESULTS: Coronary flow reserve in those receiving nHD was augmented relative to iHD (3.28±0.26 versus 2.17±0.12 [mean±SEM]; P<0.03) but attenuated, relative to controls (4.80±0.63; P=0.011). Luminal dilatations induced by intracoronary adenosine and nitroglycerin were similar in nHD and controls but blunted in the iHD cohort (P<0.05 versus both). ACh elicited vasodilatation in controls but constriction in both dialysis groups (both P<0.05, versus control); vitamin C coinfusion had no effect. Sublingual nitroglycerin increased mid-left anterior descending diameter and reduced mean arterial pressure in controls (+15.2±2.68%; -16.00±1.60%) and in nHD recipients (+14.78±5.46%; -15.82±1.32%); iHD responses were markedly attenuated (+1.9±0.86%; -5.89±1.41%; P<0.05, all comparisons). CONCLUSIONS: Coronary and systemic vasodilator responsiveness to both adenosine and nitroglycerin is augmented in patients receiving nHD relative to those receiving iHD, whereas vasoconstrictor responsiveness to acetylcholine does not differ. By improving coronary conduit and microvascular function, nHD may reduce the cardiovascular risk of patients on dialysis.
Subject(s)
Nitroglycerin , Renal Dialysis , Vasodilation , Vasodilator Agents , Humans , Female , Male , Renal Dialysis/methods , Middle Aged , Vasodilator Agents/administration & dosage , Vasodilator Agents/pharmacology , Vasodilation/drug effects , Vasodilation/physiology , Nitroglycerin/pharmacology , Nitroglycerin/administration & dosage , Aged , Coronary Circulation/drug effects , Coronary Circulation/physiology , Acetylcholine/pharmacology , Acetylcholine/administration & dosage , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/physiopathology , Brachial Artery/drug effects , Brachial Artery/physiopathology , Adenosine/administration & dosage , Coronary Vessels/diagnostic imaging , Coronary Vessels/physiopathology , Coronary Vessels/drug effects , Coronary AngiographyABSTRACT
BACKGROUND: Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of multivessel, compared with single-vessel, invasive coronary function testing (CFT) in patients with angina and nonobstructive coronary arteries (ANOCA). METHODS: Multivessel CFT was systematically performed in patients with suspected ANOCA. Vasoreactivity testing was performed using acetylcholine provocation in the left (20 to 200 µg) and right (20 to 80µg) coronary arteries. A pressure-temperature sensor guidewire was used for coronary physiology assessment in all three epicardial vessels. RESULTS: This multicenter study included a total of 228 vessels from 80 patients (57.8 ± 11.8 years of age, 60% women). Compared with single-vessel CFT, multivessel testing resulted in more patients diagnosed with coronary vasomotor dysfunction (86.3% vs 68.8%; P = 0.0005), coronary artery spasm (60.0% vs 47.5%; P = 0.004), and CMD (62.5% vs 36.3%; P < 0.001). Coronary artery spasm (n = 48) predominated in the left coronary system (n = 38), though isolated right coronary spasm was noted in 20.8% (n = 10). Coronary microvascular dysfunction (CMD), defined by abnormal index of microcirculatory resistance and/or coronary flow reserve, was present 62.5% of the cohort (n = 50). Among the cohort with CMD, 27 patients (33.8%) had 1-vessel CMD, 15 patients (18.8%) had 2-vessel CMD, and 8 patients (10%) had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery = 36.3%, left circumflex coronary artery = 33.8%, right coronary artery = 31.3%; P = 0.486). CONCLUSIONS: Multivessel CFT resulted in an increased diagnostic yield in patients with ANOCA compared with single-vessel testing. The results of this study suggest that multivessel CFT has a role in the management of patients with ANOCA.
Subject(s)
Acetylcholine , Angina Pectoris , Coronary Artery Disease , Coronary Circulation , Coronary Vasospasm , Coronary Vessels , Predictive Value of Tests , Vasodilator Agents , Humans , Female , Male , Middle Aged , Aged , Coronary Vessels/physiopathology , Coronary Vessels/diagnostic imaging , Vasodilator Agents/administration & dosage , Coronary Vasospasm/physiopathology , Coronary Vasospasm/diagnosis , Acetylcholine/administration & dosage , Angina Pectoris/physiopathology , Angina Pectoris/diagnosis , Angina Pectoris/etiology , Coronary Artery Disease/physiopathology , Coronary Artery Disease/diagnosis , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Cardiac Catheterization , Coronary Angiography , Reproducibility of Results , Vasodilation , VasoconstrictionABSTRACT
Aldosterone has been suggested to be involved in the microvascular complications observed in type 2 diabetes. We aimed to investigate the effect of mineralocorticoid receptor (MR) blockade on endothelial function in individuals with type 2 diabetes compared to healthy controls. We included 12 participants with type 2 diabetes and 14 controls. We measured leg hemodynamics at baseline and during femoral arterial infusion of acetylcholine and sodium nitroprusside before and 8 weeks into treatment with MR blockade (eplerenone). Acetylcholine infusion was repeated with concomitant n-acetylcysteine (antioxidant) infusion. No difference in leg blood flow or vascular conductance was detected before or after the treatment with MR blockade in both groups and there was no difference between groups. Infusion of n-acetylcysteine increased baseline blood flow and vascular conductance, but did not change the vascular response to acetylcholine before or after treatment with MR blockade. Skeletal muscle eNOS content was unaltered by MR blockade and no difference between groups was detected. In conclusion, we found no effect of MR blockade endothelial function in individuals with and without type 2 diabetes. As the individuals with type 2 diabetes did not have vascular dysfunction, these results might not apply to individuals with vascular dysfunction.
Subject(s)
Diabetes Mellitus, Type 2 , Receptors, Mineralocorticoid , Humans , Acetylcholine/administration & dosage , Acetylcholine/pharmacology , Acetylcholine/therapeutic use , Acetylcysteine , Aldosterone , Diabetes Mellitus, Type 2/drug therapyABSTRACT
The diagnosis of vasospastic angina (VSA) according to Japanese guidelines involves an initial intracoronary acetylcholine (ACh) provocation test in the left coronary artery (LCA) followed by testing in the right coronary artery (RCA). However, global variations in test protocols often lead to the omission of ACh provocation in the RCA, potentially resulting in the underdiagnosis of VSA. This study assessed the validity of the LCA-only ACh provocation approach for the VSA diagnosis and whether vasoreactivity in the LCA aids in determining further provocation in the RCA. A total of 273 patients who underwent sequential intracoronary ACh provocation testing in the LCA and RCA were included. Patients with a positive ACh provocation test in the LCA were excluded. Relations between vasoreactivity in the LCA and ACh test outcomes (positivity and adverse events) in the RCA were evaluated. In patients with negative ACh test results in the LCA, subsequent ACh testing was positive in the RCA in 23 of 273 (8.4%) patients. In patients with minimal LCA vasoconstriction (<25%), only 3.0% had a positive ACh test in the RCA, whereas the ACh test in the RCA was positive in 13.5% of those with LCA constriction of 25% to 90% (p = 0.002). No major adverse events occurred during ACh testing in the RCA. In conclusion, for the VSA diagnosis, the omission of ACh provocation in the RCA may be clinically acceptable, particularly when vasoconstriction induced by ACh injection was minimal in the LCA. Further studies are needed to define ACh provocation protocols worldwide.
Subject(s)
Acetylcholine , Coronary Vasospasm , Coronary Vessels , Vasoconstriction , Humans , Acetylcholine/administration & dosage , Acetylcholine/pharmacology , Female , Male , Coronary Vasospasm/diagnosis , Coronary Vasospasm/physiopathology , Coronary Vasospasm/chemically induced , Coronary Vessels/physiopathology , Coronary Vessels/drug effects , Aged , Middle Aged , Vasoconstriction/physiology , Vasoconstriction/drug effects , Coronary Angiography , Vasodilator Agents/administration & dosage , Retrospective Studies , Angina Pectoris/physiopathology , Angina Pectoris/diagnosisABSTRACT
Abstract Objective: To test the efficacy of Acetylcholine chloride use in obtaining intraoperative miosis on phacoemulsification cataract surgery. Methods: Patients with cataract diagnosis and elected for surgical phacoemulsification procedure were selected. All patients underwent conventional phacoemulsification procedure performed by a single surgeon and all patients had 0.2 ml of Acetylcholine chloride 1% irrigated in the anterior chamber at the end of the surgery. The pupillary diameter was measured immediately before the beginning of surgery, immediately before and two minutes after the use of acetylcholine chloride 1%. Results: A total of 30 eyes from 30 patients were included in the study. 18 were female, and mean age was of 69.5 years with a 7.2y standard deviation on the population study. The mean pupillary diameter immediately before the beginning of surgery was 7.5 mm with a standard deviation of 0.56 mm; the mean pupillary diameter immediately before the acetylcholine chloride 1% use (after the intraocular lens im-plantation) was 7.1 mm with a standard deviation of 0.57 mm. The mean pupillary diameter two minutes after the use of acetylcholine chloride 1% in the anterior chamber was 3.4 mm with standard deviation of 0.66 mm. The mean maximum action time of ACH chloride 1% was 64 seconds, with a standard deviation of 8 seconds. The mean intraocular pressure on the first postoperative day was 19.1 mmHg with a standard deviation of 2.45 mmHg. Conclusion: We conclude that acetylcholine chloride 1% is an important drug to obtaining intraoperative miosis in cataract surgery.
Resumo Objetivo: Demonstrar a eficácia do cloridrato de acetilcolina 1% na obtenção da miose intraoperatória na cirurgia de catarata pela técnica de facoemulsificação. Métodos: Pacientes com diagnóstico de catarata e indicação de cirurgia foram selecionados para participar do presente estudo. Todos os pacientes foram operados pela técnica de facoemulsificação convencional pelo mesmo cirurgião, todos foram submetidos à aplicação de 0,2 ml do cloridrato de acetilcolina 1% na câmara anterior ao final do procedimento cirúrgico. A medida do diâmetro pupilar foi realizada imediatamente antes do início da cirurgia, imediatamente antes do uso do cloridrato de acetilcolina 1% e após 2 minutos. Resultados: Foram estudados 30 olhos de 30 pacientes, destes, 18 eram do sexo feminino, a média de idade do estudo foi de 69,5 anos com desvio padrão de 7,2 anos. A média do diâmetro pupilar imediatamente antes do início da cirurgia foi 7,55 mm com desvio padrão de 0,56mm, a média do diâmetro pupilar imediatamente antes do uso do cloridrato de acetilcolina 1% (após implante da lente intraocular no saco capsular) foi 7,1mm com desvio padrão de 0,57mm. A média do diâmetro pupilar após 2 minutos da aplicação da acetilcolina na câmara anterior foi de 3,4 mm com desvio padrão de 0,66mm. O tempo médio de ação máxima do medicamento foi de 64 segundos, com desvio padrão de 8 segundos. A média da pressão intraocular no primeiro dia do pós-operatório foi de 19,1 mmHg com desvio padrão de 2,45mmHg. Conclusão: O estudo acima mostrou que a acetilcolina apresenta boa eficácia na obtenção de miose intraoperatória na cirurgia de facoemulsificação, permitindo uma maior facilidade na confecções das suturas corneanas ou corneo-escleral, reduzindo a incidência de sinéquias anteriores periféricas. Concluimos que o cloridrato de acetilcolina 1% é um importante medicamento na obtenção da miose intraoperatória na cirurgia de catarata.
Subject(s)
Humans , Male , Female , Aged , Acetylcholine/administration & dosage , Miosis/chemically induced , Pupil/drug effects , Phacoemulsification/methods , Miotics/administration & dosage , Acetylcholine/pharmacology , Lens Implantation, Intraocular/methods , Intraoperative Care , Therapeutic Irrigation/methods , Lenses, Intraocular , Anterior Chamber/drug effects , Miotics/pharmacologyABSTRACT
Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.
Subject(s)
Animals , Male , Rabbits , Acetylcholine/administration & dosage , Acidosis/physiopathology , Blood Pressure/drug effects , Endothelium, Vascular/physiopathology , Hypotension/chemically induced , Acute Disease , Acid-Base Imbalance/metabolism , Acidosis/chemically induced , Acidosis/metabolism , Blood Pressure Determination , Bicarbonates/blood , Blood Pressure/physiology , Chronic Disease , Carbon Dioxide/analysis , Endothelium, Vascular/metabolism , Hemodynamics/physiology , Hyperventilation/metabolism , Luminescence , Nitrates/blood , Nitric Oxide/metabolism , Nitrites/bloodABSTRACT
PURPOSE: To assess the probable actions of ropivacaine, 50% enantiomeric excess bupivacaine mixture (S75-R25) and levobupivacaine on neuromuscular transmission in vitro. METHODS: Thirty rats were distributed into groups (n=5) according to the drug used: ropivacaine, bupivacaine (S75-R25) and levobupivacaine. The concentration used for the three local anesthetics (LA) was 5 µg.mL.-1The following parameters were evaluated: 1) LA effects on membrane potential (MP) and miniature end plate potential (MEPP). A chick biventer cervicis preparation was also used to evaluate LA effects on the contracture response to acetylcholine. RESULTS: LA did not alter MP values and decreased the frequency and amplitude of MEPP. In a chick biventer cervicis preparation, bupivacaine (S75-R25) and levobupivacaine decreased the contracture response to acetylcholine with statistical significance, in comparison to ropivacaine. CONCLUSIONS: In the concentrations used, levobupivacaine and bupivacaine (S75-R25) exhibited presynaptic and postsynaptic actions evidenced by alterations in miniature end plate potentials and contracture response to acetylcholine. Ropivacaine only had a presynaptic action.
Subject(s)
Animals , Male , Rats , Amides/pharmacology , Anesthetics, Local/pharmacology , Bupivacaine/analogs & derivatives , Bupivacaine/pharmacology , Synapses/drug effects , Synaptic Transmission/drug effects , Acetylcholine/administration & dosage , Acetylcholine/pharmacology , Amides/administration & dosage , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Membrane Potentials/drug effects , Rats, Wistar , Synapses/physiology , Synaptic Transmission/physiologyABSTRACT
El Trolox es un análogo hidrofílico de la vitamina E y un agente que secuestra radicales libres. El etanol disminuye la amplitud de las contracciones espontáneas y las contracciones inducidas a la acetilcolina en el duodeno de conejo. El objetivo de este trabajo era estudiar el efecto del Trolox en las alteraciones inducidas por el etanol sobre la contractilidad y la peroxidación lipídica en el duodeno. Los estudios de contractilidad duodenal in vitro se realizaron en un baño de órganos y los niveles de MDA+4-HDA se midieron por espectofotometría. El Trolox aumentó la reducción inducida por el etanol sobre la amplitud de las contracciones espontáneas en el músculo longitudinal pero no en el músculo circular de duodeno. El Trolox 4 mM redujo los efectos del etanol sobre las contracciones inducidas a la acetilcolina y sobre las concentraciones de MDA+4-HDA. Se concluye que el Trolox podría prevenir el estrés oxidativo inducido por el etanol en el duodeno(AU)
Trolox is a hydrophilic analogue of vitamin E and a free radical scavenger. Ethanol diminishes the amplitude of spontaneous contractions and acetylcholine (ACh)-induced contractions in rabbit duodenum. The aim of this work was to study the effect of Trolox on the alterations induced by ethanol on contractility and lipid peroxidation in the duodenum. The duodenal contractility studies in vitro were carried out in an organ bath and the levels of malondialdehyde and 4-hydroxyalkenals (MDA+4-HAD) were measured by spectrophotometry. Trolox increased the reduction induced by ethanol on the amplitude of spontaneous contractions in longitudinal muscle but not in circular muscle. Trolox 4 mM decreased the effects of ethanol on ACh-induced contractions and on MDA+4-HDA concentrations. We conclude that Trolox might prevent oxidative stress induced by ethanol in the duodenum(AU)
Subject(s)
Animals , Male , Ethanol/therapeutic use , Vitamin E/analogs & derivatives , Acetylcholine/administration & dosage , Oxidative Stress , Gastrointestinal Motility , Gastrointestinal Motility/physiology , Oxidative Stress/physiology , Duodenum/anatomy & histology , Duodenum , Duodenum/pathology , IntestinesABSTRACT
A cirurgia de revascularização do miocárdio, realizada com o auxílio da circulação extracorpórea, está associada a alterações importantes na microcirculação e na produção e circulação de citocinas e marcadores inflamatórios. No presente estudo, foram avaliados 23 pacientes com indicação de revascularização do miocárdio, no dia do procedimento e 7 e 28 dias após a cirurgia. A microcirculação cutânea, enquanto reflexo da microcirculação coronariana, foi estudada através da hiperemia térmica e/ou reativa pós oclusiva e da iontoforese de substâncias vasoativas por mecanismos dependentes e independentes do endotélio. A rigidez arterial foi aferida através da análise da onda de pulso digital. Foi avaliado ainda o impacto da doença e do procedimento cirúrgico sobre a produção e circulação sérica de citocinas e marcadores inflamatórios, tais como: PCR-HS, nitrito/nitrato, IL-6, II-7, IL-10, IFN-y, TNT-alfa e G-CSF. Foi observada uma tendência à redução da vasodilatação da microcirculação cutânea após a administração de doses acumulativas de acetilcolina (endotélio dependente) através da iontoforese de 7 e 28 dias após o procedimento cirúrgico. A hiperemia térmica foi mais pronunciada na avaliação basal do que aos 7 e 28 dias. A hiperemia reativa pós oclusiva não demonstrou alterações 7 dias após o procedimento. Aos 28 dias, houve um aumento da condutância microvascular cutânea. Quando avaliada a vasodilatação endotélio-independente (nitroprussiato de sódio), observamos aumento do fluxo microvascular cutâneo diretamente proporcional à carga/dose aplicada, sem diferenças nos valores obtidos no basal e 7 e 28 dias após o procedimento. A rigidez arterial não apresentou alterações. A análise dos fatores inflamatórios e das citocinas demonstrou aumento marcante da IL-6 e da IL-8 após 7 dias do procedimento cirúrgico, com retorno parcial aos níveis basais da IL-6 e total da IL-8 após 28 dias. O IFN-y, TNF-alfa e G-CSF apenas apresentaram níveis detectáveis...
Myocardial revascularization with cardiopulmonary bypass is associated with important modifications in the microcirculation and in the production and circulation of cytokines and inflammatory markers. In the present study 23 patients were evaluated on the day of the myocardial revascularization (baseline) and 7 and 28 days after the surgical procedure. The skin microcirculation that is in close relationship with coronary microcirculation was evaluated by iontophoresis of vasoactive substances, thermal hyperemia and post occlusive reactive hyperemia. The arterial stiffness was studied by digital pulse wave analysis. Cytokines and inflammatory markers such as C-reactive protein, nitrite/nitrate, IL-6, II-7, IL-8, IL-10, IFN-y, TNF-alfa e G-CSF were also analyzed. A reduction in the skin microvascular vasodilatation was observed after iontophoresis of cumulative doses of acetylcholine (endothelium dependent) 7 and 28 days after the surgical procedure. Skin vasodilation after thermal hyperemia was more important before the surgery than 7 and 28 days after the procedure. The post occlusive reactive hyperemia did not cause vasodilation after 7 days of the surgery. After 28 days, the cutaneous microvascular conductance was higher than before. The iontophoresis of sodium nitroprusside (endothelium independent) showed increasing vasodilation according to the doses/charge applied but there was no difference among the days of the study. The level of IL-6 and IL-8 increased after 7 days and the level of IL-8 returned to baseline after 28 days. IL-6 showed a reduction after 28 days but did not reach the baseline. INF-y, TNF-alfa e G-CSF were detected only on the day of the surgical procedure and the level of IL-7 and IL-10 was similar before, 7 days and 28 days after the surgery. Nitrite/nitrate was reduced after 7 days of the surgical procedure. In conclusion we observed that the small difference between endothelium dependent vasodilation 7 days after the surgical...
Subject(s)
Humans , Male , Female , Acetylcholine/administration & dosage , Arteries/physiopathology , Extracorporeal Circulation/methods , Endothelium, Vascular/physiology , Iontophoresis , Myocardial Revascularization , Microcirculation/physiology , Cardiovascular Surgical Procedures , Systemic Inflammatory Response SyndromeABSTRACT
Introducción: Se han comunicado casos de orgasmo espontáneo como efecto secundario de algunos antidepresivos. Con venlafaxina conocemos un caso de orgasmo en varones y ninguno en mujeres. Caso clínico: Paciente de 51 años diagnosticada de trastorno depresivo recurrente, episodio actual grave sin síntomas psicóticos (F33.2 - CIE10). Fue tratada con venlafaxina (75 mgld) y diacepam (20 mgld) y a los pocos días comenzó a desarrollar orgasmos espontáneos. El cuadro desapareció tras la retirada del antidepresivo. Discusión y conclusiones: La venlafaxina, inhibidor de la recaptación de serotonina y noradrenalina, podría ocasionar efectos estimulantes o inhibidores de la función sexual, dada la acción de dichos neurotransmisores (AU)
Subject(s)
Female , Middle Aged , Humans , Orgasm , Antidepressive Agents/adverse effects , Antidepressive Agents/therapeutic use , Depression/diagnosis , Depression/drug therapy , Depression/psychology , Diazepam/administration & dosage , Diazepam/adverse effects , Receptors, Neurotransmitter , Selective Serotonin Reuptake Inhibitors/adverse effects , Fluoxetine/adverse effects , Acetylcholine/adverse effects , Acetylcholine/administration & dosage , Dopamine/administration & dosage , Dopamine/adverse effectsABSTRACT
El óxido nítrico (ON) es un neuromodulador ampliamente distribuido en el sistema nervioso central (SNC). Es sintetizado por las óxido nítrico sintasas, enzimas que convierten el aminoácido L-arginina en L-citrulina y óxido nítrico. Desde su descubrimiento, numerosos estudios han analizado la implicación del ON en una gran variedad de procesos fisiológicos y patológicos. Aunque en los últimos años se han publicado numerosas investigaciones que sugieren un importante papel regulador del ON en el ciclo sueño/vigilia, los resultados no siempre son consistentes. En este sentido, se ha observado: (a) que el ON podría constituir una sustancia vigilantígena, con un papel excitatorio sobre la vigilia posiblemente explicado por la modulación de la transmisión excitatoria; (b) que el ON podría tener una función hipnógenica, facilitando la liberación de acetilcolina y la generación y mantenimiento del sueño paradójico; (c) que el ON podría estar involucrado en la generación de las oscilaciones tálamo- corticales y del ritmo theta. Las discrepancias en los resultados observados pueden estar asociadas al uso de diferentes sustancias farmacológicas, variaciones en las dosis, vías, y periodo administración (luz vs oscuridad), junto a las propias características del ON (AU)
Subject(s)
Adolescent , Adult , Female , Male , Middle Aged , Child , Humans , Nitric Oxide/administration & dosage , Nitric Oxide/therapeutic use , Wakefulness/physiology , Wakefulness , Sleep Wake Disorders/drug therapy , Acetylcholine/administration & dosage , Acetylcholine/therapeutic use , Citrulline/administration & dosage , Citrulline/therapeutic use , Nitroarginine/administration & dosage , Nitroarginine/therapeutic use , Neurotransmitter Agents/therapeutic use , Thalamus/physiopathology , Light , Darkness , Sleep/physiology , Sleep , Sleep Stages/physiology , Sleep Wake Disorders/physiopathologyABSTRACT
La nortriptilina potencia la respuesta del conducto deferente de rata incubado en solución de Krebs-Henseleit normal a norepinefrina, pero antagoniza su efecto cuando a este medio de incubación se añade: cocaína, 17 beta estradiol y propranolol que bloquean la recaptación neuronal y extraneuronal de catecolaminas, en relación con la interacción con dopamina se comporta como antagonista no competitivo empleando ambos medios de incubación. La nortriptilina antagoniza de forma no competitiva las respuestas del ileon aislado de cobaya a 4-aminopiridina. Antagoniza de forma no competitiva el efecto contracturante de oxitocina, acetilcolina, serotonina, cloruro de bario y cloruro de potasio en la preparación de útero aislado de rata. En todos los casos se ha calculado la Concentración inhibitoria 5OM (CI,50M). Estos resultados inducen a pensar que la nortriptilina se comporta como un fármaco estabilizador inespecífico de membrana (AU)
Subject(s)
Rats , Guinea Pigs , Animals , Acetylcholine/administration & dosage , Acetylcholine/therapeutic use , Serotonin/administration & dosage , Barium Compounds/administration & dosage , Nortriptyline/administration & dosage , Nortriptyline/therapeutic use , Antidepressive Agents/administration & dosage , Antidepressive Agents/adverse effects , Antidepressive Agents/pharmacology , Drug Therapy/methodsABSTRACT
OBJECTIVE: This study was performed to investigate the endothelium-dependent relaxation and contractile responses to endothelin-1 in subcutaneous resistive arteries from Caribbean patients with advanced atherosclerotic femoro-crural arterial disease. DESIGN AND METHODS: Small subcutaneous arteries (inner diameter 200 um) from control subjects (n=8) and atherosclerotic patients (n=8) were dissected from fat biopsies obtained at routine vascular surgery and mounted in vitro on a wire-myograph measuring parietal tension under isometric conditions. RESULTS: Acetylcholine-induced relaxation (10-6 M) was significantly reduced in pre-contracted arteries from atherosclerotic patients (24 + or - 16 percent vs 17 percent in control, p<0.001). Smooth muscle relaxation to sodium nitroprusside was comparable in both groups. Contractions elicited by endothelin-1 (10-9 M) were significantly lower and almost suppressed in both the atherosclerotic group (1.2 + or - 0.8 Kpa) and in the hypertensive subgroup of control subjects (n=4, 1.2= 0r - 1.2 Kpa) comparatively to normotensive control subjects (12.3 + or - 6.9 Kpa, p<0.001). Contractile responses induced by endothelin-1 at higher concentrations (10-8 - 10-7 M), noradrenaline and hyperosmolar potassium were comparable in both groups. CONCLUSIONS: These data suggest a specific impairment of both endothelium-dependent relaxation and contractility in lower limb subcutaneous resistive arteries from Caribbean patients with atherosclerotic femoro-crural arterial disease. These changes in vessels which largely determine proximal vascular resistance may contribute to ischaemic complications in this vascular bed including skin ulcerations and gangrene.(Au)
Subject(s)
Humans , Nitric Oxide/therapeutic use , Arteriosclerosis/drug therapy , Acetylcholine/administration & dosage , Endothelin-1/drug effects , Caribbean Region , Myocardial Ischemia/complicationsABSTRACT
We performed a randomized, prospective study to evaluate the effect of intraoperative, intracameral carbachol or acetylcholine on early postoperative intraocular pressure(IOP) after extracapsular cataract extraction(ECCE) and posterior chamber lens(PCL) implantation. Fifty-six eyes of 56 patients scheduled for routine ECCE and PCL implantation were randomly assigned into three groups: (1)carbachol infusion (19 eyes) (2) acetylcholine infusion (15 eyes) (3)balanced salt solution (BSS) infusion (control, 22 eyes). We compared the preoperative IOP, early postoperative IOP, postoperative 24 hours IOP and postoperative 1 week IOP. In the measurement of early postoperative IOP, IOP was measured at least twice at 3, 6 or 9 hours postoperatively. There was no significant difference in IOP between the three groups preoperatively, at postoperative 3 hours, and 1 week. At postoperative 6 hours, both the carbachol infusion group and acetylcholine infusion group were significantly different from the BSS infusion group. At postoperative 9 and 24 hours, only carbachol infusion group had a significant difference from BSS infusion group in suppression of postoperative IOP increase. Our results suggest that intraoperative, intracameral administration of carbachol or acetylcholine prevents early postoperative IOP increase, and that carbachol has a more lasting effect.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Acetylcholine/administration & dosage , Anterior Chamber/drug effects , Carbachol/administration & dosage , Cataract Extraction/adverse effects , Intraocular Pressure/drug effects , Lenses, Intraocular , Ocular Hypertension/etiology , Postoperative Complications , Prospective StudiesABSTRACT
Con el objeto de caracterizar y comparar las respuestas hemodinámicas del Ventrículo Derecho (VD) con respecto a las del Ventrículo Izquierdo (VI) frente a maniobras fisiológicas y farmacológicas, se estudió el efecto de la inyección intravenosa de acetilcolina ACh) en 32 perros mestizados anestesiados. La ACh luego de producir la disminución de a presión aórtica y de la presión sistólica del ventrículo isquierdo (PSVI), provocó siempre aumento significativo de la pressión sistólica del ventrículo derecho (PSVD) precedida o no de una disminución de la misma. La atropinización y la denervación de los barorreceptores carotídeos y aórticos suprimió este aumento de la PSVD. Se sugiere que el aumento de la PSVD sería secundario a una respuesta simpática refleja a partir de los barorreceptores una vez que estos detectan la hipotensión aórtica producida por la ACh luego de vasodilatar los lechos vasculares perifáricos sistémicos. La descarga simpática produciría una venoconstricción sistémica con el consiguiente aumento del retorno venoso al VD, así como a un efecto inotrópico directo sobre el miocardio ventricular. Ambas acciones, periférica y miocárdica, serían las responsables del aumento de la [SVD. No es posible descartar totalmente un probable efecto vasoconstrictor pulmonar agregado como parte de la respuesta simpática refleja (AU)
Subject(s)
Animals , Comparative Study , Dogs , Acetylcholine/pharmacology , Ventricular Function, Right/drug effects , Ventricular Function, Left/drug effects , Acetylcholine/administration & dosage , Ventricular Function, Right/physiology , Ventricular Function, Left/physiology , Injections, Intravenous , Atropine/administration & dosage , Atropine/pharmacology , Myocardial Contraction/drug effects , Myocardial Contraction/physiology , Heart Ventricles/drug effects , Heart Ventricles/physiology , Blood Pressure/drug effects , Blood Pressure/physiologyABSTRACT
Con el objeto de caracterizar y comparar las respuestas hemodinámicas del Ventrículo Derecho (VD) con respecto a las del Ventrículo Izquierdo (VI) frente a maniobras fisiológicas y farmacológicas, se estudió el efecto de la inyección intravenosa de acetilcolina ACh) en 32 perros mestizados anestesiados. La ACh luego de producir la disminución de a presión aórtica y de la presión sistólica del ventrículo isquierdo (PSVI), provocó siempre aumento significativo de la pressión sistólica del ventrículo derecho (PSVD) precedida o no de una disminución de la misma. La atropinización y la denervación de los barorreceptores carotídeos y aórticos suprimió este aumento de la PSVD. Se sugiere que el aumento de la PSVD sería secundario a una respuesta simpática refleja a partir de los barorreceptores una vez que estos detectan la hipotensión aórtica producida por la ACh luego de vasodilatar los lechos vasculares perifáricos sistémicos. La descarga simpática produciría una venoconstricción sistémica con el consiguiente aumento del retorno venoso al VD, así como a un efecto inotrópico directo sobre el miocardio ventricular. Ambas acciones, periférica y miocárdica, serían las responsables del aumento de la [SVD. No es posible descartar totalmente un probable efecto vasoconstrictor pulmonar agregado como parte de la respuesta simpática refleja
Subject(s)
Animals , Dogs , Acetylcholine/pharmacology , Ventricular Function, Right , Ventricular Function, Left , Acetylcholine/administration & dosage , Atropine/administration & dosage , Atropine/pharmacology , Myocardial Contraction , Myocardial Contraction/physiology , Ventricular Function, Right/physiology , Ventricular Function, Left/physiology , Injections, Intravenous , Arterial Pressure , Arterial Pressure/physiology , Heart Ventricles , Heart Ventricles/physiologyABSTRACT
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
Subject(s)
Animals , Acetylcholine/administration & dosage , Acetylcholine/adverse effects , Heart/drug effects , Curare/administration & dosage , Curare/therapeutic use , Myocardium/metabolism , Myocardium/pathology , Tubocurarine , Tubocurarine/adverse effectsABSTRACT
Se probó el efecto de la inyección intracerebroventricular de varios neurotransmisores, dados en forma independiente y combinada (Ang. II, 200 ng; ACh., 6 Ag; y met-encefalina, 50 Ag) sobre la presión arterial media (PAM) de ratas albinas de la cepa Sprague-Dawley. Bajo anestesia con nembutal (35mg/Kg), se implantó una cánula metálica en el tercer ventrículo por los medios esteriotáxicos usuales y al tercer día el animal se anestesió de nuevo para la medición de la presión carótidea mediante un transductor de presión y registro continuo en un polígrafo fisiológico. La Ang. II aumentó la PAM; la acetilcolina mostró un aumento significativo en los primeros cinco minutos luego de la inyección y la met-encefalina no mostró ningún cambio significativo en al PAM. El efecto combinado mostró resultados interesantes. En vez de una potenciación del aumento de la presión arterial media, cuando ACh. y Ang. II se administrarón conjuntamente, no se observaron cambios estadísticamente significativos, por lo que su efecto se neutralizó. También, la met-encefalina bloqueó la respuesta hipertensora de la Ag. II al darse en forma combinada. Esto es compatible con la acción inhibitoria de la met-encefalinaen el sistema neuronal angiotensinérgico. Se especula acerca de un modelo hipotético que explica los hallazgos observados (AU)
Subject(s)
Rats , Animals , Male , Comparative Study , Acetylcholine/pharmacology , Angiotensin II/pharmacology , Blood Pressure/drug effects , Enkephalin, Methionine/pharmacology , Acetylcholine/administration & dosage , Angiotensin II/administration & dosage , Drug Combinations , Enkephalin, Methionine/administration & dosage , Injections, Intraventricular , Rats, Inbred StrainsABSTRACT
Se probó el efecto de la inyección intracerebroventricular de varios neurotransmisores, dados en forma independiente y combinada (Ang. II, 200 ng; ACh., 6 µg; y met-encefalina, 50 µg) sobre la presión arterial media (PAM) de ratas albinas de la cepa Sprague-Dawley. Bajo anestesia con nembutal (35mg/Kg), se implantó una cánula metálica en el tercer ventrículo por los medios esteriotáxicos usuales y al tercer día el animal se anestesió de nuevo para la medición de la presión carótidea mediante un transductor de presión y registro continuo en un polígrafo fisiológico. La Ang. II aumentó la PAM; la acetilcolina mostró un aumento significativo en los primeros cinco minutos luego de la inyección y la met-encefalina no mostró ningún cambio significativo en al PAM. El efecto combinado mostró resultados interesantes. En vez de una potenciación del aumento de la presión arterial media, cuando ACh. y Ang. II se administrarón conjuntamente, no se observaron cambios estadísticamente significativos, por lo que su efecto se neutralizó. También, la met-encefalina bloqueó la respuesta hipertensora de la Ag. II al darse en forma combinada. Esto es compatible con la acción inhibitoria de la met-encefalinaen el sistema neuronal angiotensinérgico. Se especula acerca de un modelo hipotético que explica los hallazgos observados