Pharmacological modulation of b-adrenoceptors as a new cardioprotective strategy for therapy of myocardial dysfunction induced by ischemia and reperfusion

Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. Results: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). Conclusion: The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.(AU)

Tormenta eléctrica en síndrome de Brugada tratada exitosamente con infusión de isoproterenol / Electrical storm in Brugada syndrome successfully treated with isoproterenol. Report of a case

We report a 22-year-old male who experienced several episodes of syncope within a timeframe of few hours. In the emergency room, multiple ventricular fibrillation episodes where documented along with a type 1 Brugada ECG pattern. Isoproterenol in continuous infusion was started, normalizing the ECG and avoiding further arrhythmia recurrences. The patient was implanted with an automated defibrillator and discharged 3 days after admission.

[Electrical storm in Brugada syndrome successfully treated with isoproterenol. Report of a case]. / Tormenta eléctrica en síndrome de Brugada tratada exitosamente con infusión de isoproterenol.

We report a 22-year-old male who experienced several episodes of syncope within a timeframe of few hours. In the emergency room, multiple ventricular fibrillation episodes where documented along with a type 1 Brugada ECG pattern. Isoproterenol in continuous infusion was started, normalizing the ECG and avoiding further arrhythmia recurrences. The patient was implanted with an automated defibrillator and discharged 3 days after admission.

Proteção miocárdica pelo ramipril na hipertrofia ventricular esquerda: estudo experimental / Protective effect of ramipril on the left ventricle hypertrophy: experimental study

Introdução: A hipertrofia patológica do ventrículo esquerdo é um poderoso e independente fator de risco para complicações cardiovasculares, estando relacionada com aumento de duas a cinco vezes o risco de infarto do miocárdio, seis a dezessete vezes o risco de insuficiência cardíaca e três a dez vezes o risco de acidente vascular cerebral. Objetivo: avaliar em ratos se o ramipril na dose de 1mg/kg/dia apresenta efeito protetor sobre a hipertrofia do ventrículo esquerdo (HVE), induzida pelo isoproterenol (ISO), administrado por via subcutânea (0,3mg/kg/dia). Método: formados quatro grupos de ratos machos e adultos, com 14 exemplares em cada um, sendo o primeiro o grupo controle (CON), segundo o tratado com ramipril (RAM); o grupo seguinte com isoproterenol (ISO) e o último tratado com ambas as drogas (RAM + ISO). Aferidos: o peso úmido do ventrículo esquerdo (PUVE), peso seco do ventrículo esquerdo (PSVE), relação PSVE pelo peso do animal (PSVE/P) e o índice de massa do ventrículo esquerdo (IMVE). Retiradas amostras do ventrículo esquerdo dos animais para estudo morfológico pela microscopia de luz, e em três animais de cada grupo um fragmento foi processado para estudo ultra-estrutural. Resultados: em relação ao PSVE obtiveram-se os seguintes resultados: Grupo CON: 0,14486; Grupo RAM: 0,13771; Grupo ISO: 0,20400; Grupo RAM + ISO: 0,16000; com diferença significante entre o grupo ISO e os demais (p<0, 05). A análise do PSVE/P demonstrou o mesmo comportamento. Na avaliação microscópica de luz e eletrônica de transmissão, observou-se proteção da HVE no Grupo RAM+ISO, em relação ao grupo ISO Conclusões: as análises morfológica e ultra-estrutural demonstraram que isoproterenol induz hipertrofia dos cardiomiócitos e aumento do tecido conjuntivo, com acentuados depósitos de fibras colágenas No grupo RAM + ISO observou-se ação protetora em relação à hipertrofia muscular e a depósitos de colágeno O uso isolado de ramipril não provocou alterações no que diz respeito ao...

Decreased baroreflex sensitivity in isoproterenol-treated mice with cardiac hypertrophy.

The baroreflex has been shown to be impaired in rat models of cardiac hypertrophy. In the present study, we investigated the effects of beta-adrenoceptor-induced cardiac hypertrophy on the baroreflex in mice. Male Swiss Webster mice weighing 20-25 g were treated with the beta-adrenoceptor agonist isoproterenol (IPM; 15 microg/g/day, s.c.) for 7 days or with vehicle (control, CM). After treatment, IPM (n=9) and CM (n=9) were anesthetized with ketamine + xylazine (91.0: 9.1 mg/kg, i.p.) and had their carotid artery and jugular vein cannulated to test the arterial baroreflex. The baroreflex was evaluated by measuring changes in heart rate (HR) in response to acute increases and decreases in mean arterial pressure (MAP) induced by bolus injections of phenylephrine and sodium nitroprusside (1.5-24.0 microg/kg, i.v.) in conscious animals. IPM showed an increased cardiac weight/body weight (1.18 +/- 0.03 mg/g) ratio compared to CM (0.95 +/- 0.03 mg/g, p<0.05), but similar values of resting MAP (108 +/- 4 vs. 111 +/- 2 mm Hg) and HR (606 +/- 25 vs. 629 +/- 26 bpm). Sigmoidal barocurve analysis showed that isoproterenol treatment significantly reduced the following parameters: baroreflex sensitivity (IPM: -4.26 +/- 0.19 vs. CM: -5.92 +/- 0.54 bpm/mm Hg, p<0.05), reflex bradycardia plateau (IPM: 387 +/- 26 vs. CM: 318 +/- 19 bpm, p<0.05) and HR range (IPM: 369 +/- 30 vs. CM: 442 +/- 20 bpm, p<0.05). Linear regression analysis of baroreflex function also showed a diminished reflex bradycardia (CM: -8.92 +/- 0.87 bpm/mm Hg vs. IPM: -4.94 +/- 0.52 bpm/mm Hg, p<0.05), but similar reflex tachycardia (CM: -3.88 +/- 0.45 bpm/mm Hg vs. IPM: -3.52 +/- 0.43 bpm/mm Hg). In conclusion, beta-adrenoceptor-induced cardiac hypertrophy in mice led to impaired sensitivity of the cardiac baroreflex, which could be due to a diminished vagal activity to the heart.

Orientación hacia el diagnóstico causal en un caso de taquicardia ventricular polimorfa y síndrome de QT largo / Orientation towards etiologic diagnosis in a case of polymorphic ventricular tachycardia and long QT syndrome

Las arritmias cardíacas son comunes en los pacientes críticos, pudiendo ser benignas, en un comienzo, o fatales. Requieren de un diagnóstico rápido y exacto. Los intensivistas debemos estar familiarizados con su rápida identificación y manejo para una buena práctica clínica. Presentamos el caso de una mujer de 86 años, con antecedentes de Diabetes Mellitus II B e hipertensión arterial que ingresó a nuestra clínica con una neumonía basal derecha y brusca falla respiratoria, cuyo ecocardiograma muestra mínima insuficiencia aórtica, mitral y tricuspídea, con función sistólica global-segmentaria conservadas y cuya tomografía axial computada de tórax con énfasis vascular descartó tromboembolismo. Durante su evolución hospitalaria presentó arritmia extrasistólica supraventricular, fibrilación auricular, taquicardia ventricular y fibrilación ventricular, las que unidas a cambios electrocardiográficos, QT corregido de 714 mseg y troponina T de 0,018 llevaron al estudio coronario, demostrando su origen isquémico. Se analizan los electrocardiogramas y se discute el diagnóstico diferencial etiológico.

[Neurocardiogenic syncope in children]. / Síncope neurocardiogénico en población pediátrica.

Between december of 1994 and june 1997, 90 children and adolescents were referred to the Shaio Clinic Foundation for evaluation of recurrent unexplained syncope. Head-up tilt testing was positive in 45 (50%), 23 male, with a mean age of 12.7 years (range 5-17 years). The response during Head-up tilt testing was predominantly vasodepressor (57%), followed by mixed in 24% and cardioinhibitory in the remaining 17%. The majority of patients had a positive response during pharmacological phase with isoproterenol infusion at a mean time of 17 +/- 8 minutes. Head-up tilt is a safe diagnostic test and defines the cause of unexplained syncope in up to 50% of children and young adults with recurrent syncope. The management was based on education, control of risk factors and psychological and/or physical rehabilitation. In the 15.2 months follow up we observed complete remission or a significant reduction of symptoms in 95% of the cases. Only 5% of the patients persisted or had worsening of their symptoms.

Prevençäo da hipertrofia ventricular esquerda em ratos induzida pelo isoproterenol: comparaçäo entre Ramipril e Losartan / Prevention of left ventricular hypertrophy in rats induced by isoproterenol: the relationship between Ramipril and Losartan

Obetivo: Avaliar comparativamente a capacidade do losartan (bloqueador do receptor AT1 da angiotensina II) e o ramipril (inibidor da enzima de conversäo da angiotensina) em prevenir a hipertrofia ventricular esquerda induzida por isoproterenol em ratos. Métodos: Foram estudados 64 ratos divididos em 4 grupos por um período de 15 dias, após foram sacrificados e comparados através dos pesos dos ventrículos e estudo anatomo-patologico. Resultados: Os animais tratados com losartan apresentaram pesos dos ventrículos esquerdos menores com significância estatística, assim como menor tamanho das fibras miocárdicas e menos colágeno quando comparados aos tratados com ramipril. Conclusäo: O losartan foi superior ao ramipril na prevençäo da hipertrofia ventricular esquerda induzida por isoproterenol em ratos.

Síncope Neurocardiogénico en población pediátrica / Neurocardiogenic syncope in children

Entre diciembre de 1994 y junio de 1997, 90 niños y adolescentes fueron enviados a la Fundación Clínica Shaio para evaluación de síncope recurrente e inexplicable. La prueba de mesa basculante fue positiva en 45 (50 por ciento) de los casos. 23 hombres y 22 mujeres con una edad media de 12,7 años (rango 5-17 años). La respuesta durante la prueba de mesa basculante fue predominantemente vasodepresora (57 por ciento) seguida por la respuesta tipo mixta en 24 por ciento de los casos y cardioinhibitoria en el 17 por ciento. La mayoría de los pacientes presentaron la respuesta positiva durante la fase farmacológica con infusión de isoproterenol. La duración de la prueba fue en promedio de 17 ñ 8 minutos. La prueba de mesa basculante es un método diagnóstico seguro y determina la causa del síncope inexplicable en el 50 por ciento de los niños y adolescentes con síncope recurrente. El manejo incluyó educación, control de los factores de riesgo y rehabilitación física y/o psicológica. En los 15,2 meses de seguimiento se observó una remisión completa o reducción significativa de los síntomas en el 95 por ciento de los casos. Solamente en el 5 por ciento de los casos persistieron o empeoraron los síntomas

Effect of enalapril treatment on the heart of normal rats.

Previous experiments showed that enalapril (EN) treatment as well as enalaprilic acid, when added to the perfusion bath, diminish the inotropic response of the papillary muscles to isoproterenol (ISO). The main objective of this study was to evaluate, in normal rats, the effect of EN on basal contractility and inotropic response to ISO on the whole perfused ventricles (Langendorff preparation). Blood pressure (BP), increase in body weight (IBW), ventricular weight/body weight ratio (R) and concentration of ventricular proteins and DNA were also analyzed. Five groups were studied: EN10: 5 mg/kg/day, 10 days; EN21(L): 5mg/kg/day, 21 days; EN21(H): 15 mg/kg/day, 21 days. C10 and C21 were untreated controls. Cardiac contractility was evaluated by the maximal developed pressure, maximal rate of rise of pressure and maximal velocity of relaxation; no changes were found due to EN treatments either on basal conditions or on ISO stimulation. Significant differences (p<0.05 vs C21) were: lower BP and R in EN21(L) and EN21(H), slower IBW in EN21(H), decreased ventricular DNA in EN21(H). In conclusion, daily treatment for ten or twenty one days with enalapril does not change either basal cardiac contractile performance or inotropic response to ISO in the Langendorff preparation. Longterm treatment with EN seems to modify nuclear processes involved in cardiomyocite DNA content.

Bromocriptine-induced tachycardia in conscious rats: blunted response following isoproterenol pretreatment for 5 days.

Previous studies have shown that tachycardia induced by intravenous injection of bromocriptine, which persisted after adrenalectomy, was mediated by central dopamine D2 receptor stimulation. Such stimulation could activate central sympathetic outflow to the heart. To test this hypothesis, we investigated whether pretreatment with isoproterenol, known to induce cardiac beta-adrenoceptor desensitization, could reduce bromocriptine-induced tachycardia. A 5 day pretreatment with isoproterenol (5 mg/kg/day) induced a 21% increase in the ratio of ventricular dry weight to body weight, compared with saline-pretreated rats. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced increase in left ventricular systolic pressure and heart rate was significantly reduced, compared with saline-pretreated rats (the isoproterenol concentration producing 50% of the maximal positive inotropic and chronotropic responses was increased approximately 5- and 4-fold, respectively). In conscious control rats, intravenous injection of bromocriptine (50, 150 and 250 micrograms/kg) decreased mean aortic pressure and increased heart rate in a dose-related manner. Pretreatment with isoproterenol for 5 days reduced bromocriptine-induced tachycardia without affecting hypotension. Cardiac autonomic tone remained of the same order of magnitude irrespective of whether the animal was pretreated with isoproterenol. These results indicate that isoproterenol pretreatment reduces bromocriptine-induced tachycardia mainly through desensitization of cardiac beta-adrenoceptors rather than via an impairment of autonomic regulation of the heart. This supports the hypothesis that bromocriptine-induced activation of central dopamine D2 receptors increases heart rate via activation of central sympathetic outflow to the heart.

Bromocriptine-induced tachycardia in conscious rats: blunted response followin isoproterenol pretreatment for 5 days

Previous studies have shown that tachycardia induced by intravenous injection of bromocriptine, which persisted after adrenalectomy, was mediated by central dopamine D2 receptor stimulation. Such stimulation could activate central sympathetic outflow to the heart. To test this hypothesis, we investigated whether pretreatment with isoproterenol, known to induce cardiac beta-adrenoceptor desensitization, could reduce bromocriptine-induced tachycardia. A 5 day pretreatment with isoproterenol (5 mg/Kg/day) induced a 21 per cent increase in the ratio of ventricular dry weight to body weight, compared with saline-pretreated rats. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced increase in left ventricular systolic pressure and heart rate was significantly reduced, compared with saline-pretreated rats (the isoproterenol concentration producing 50 per cent of the maximal positive inotropic and chronotropic responses was increased 5-and 4- fold, respectively). In conscious control rats, intravenous injection of bromocriptine (50, 150 and 250 mug/Kg) decreased mean aortic pressure and increased heart rate in a dose-related manner. Pretreatment with isoproterenol for 5 days reduced bromocriptine-induced tachycardia without affecting hypotension. Cardiac autonomic tone remained of the same order of magnitude irrespective of whether the animal was pretreated with isoproterenol. These results indicate that isoproterenol pretreatment reduces bromocriptine-induced tachycardia mainly through desensitization of cardiac beta-adrenoceptors rather than via an impairment of autonomic regulation of the heart. This support the hypothesis that bromocriptine-induced activation of central dopamine D2 receptors increases heart rate via activation of central sympathetic outflow to the heart. (AU)

Bromocriptine-induced tachycardia in conscious rats: blunted response followin isoproterenol pretreatment for 5 days

Previous studies have shown that tachycardia induced by intravenous injection of bromocriptine, which persisted after adrenalectomy, was mediated by central dopamine D2 receptor stimulation. Such stimulation could activate central sympathetic outflow to the heart. To test this hypothesis, we investigated whether pretreatment with isoproterenol, known to induce cardiac beta-adrenoceptor desensitization, could reduce bromocriptine-induced tachycardia. A 5 day pretreatment with isoproterenol (5 mg/Kg/day) induced a 21 per cent increase in the ratio of ventricular dry weight to body weight, compared with saline-pretreated rats. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced increase in left ventricular systolic pressure and heart rate was significantly reduced, compared with saline-pretreated rats (the isoproterenol concentration producing 50 per cent of the maximal positive inotropic and chronotropic responses was increased ~5-and 4- fold, respectively). In conscious control rats, intravenous injection of bromocriptine (50, 150 and 250 mug/Kg) decreased mean aortic pressure and increased heart rate in a dose-related manner. Pretreatment with isoproterenol for 5 days reduced bromocriptine-induced tachycardia without affecting hypotension. Cardiac autonomic tone remained of the same order of magnitude irrespective of whether the animal was pretreated with isoproterenol. These results indicate that isoproterenol pretreatment reduces bromocriptine-induced tachycardia mainly through desensitization of cardiac beta-adrenoceptors rather than via an impairment of autonomic regulation of the heart. This support the hypothesis that bromocriptine-induced activation of central dopamine D2 receptors increases heart rate via activation of central sympathetic outflow to the heart.

Crescimento de glândulas salivares maiores de roedores induzido pelo isoproterenol: uma revisäo / Growth of major salivary glands of rodents induced by isoproterenol: a review

Revisäo sobre vários aspectos do enorme crescimento de glândulas salivares de roedores sob estímulos crônico com isoproterenol