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

Abstract 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.

Role of adenylyl cyclase in reduced ß-adrenoceptor-mediated vasorelaxation during maturation

Beta-adrenergic receptor (βAR)-dependent blood vessel relaxation is impaired in older animals and G protein activation has been suggested as the causative mechanism. Here, we investigated the role of βAR subtypes (β1AR, β2AR, and β3AR) and cAMP in maturation-dependent vasorelaxation impairment. Aortic rings from 15 Sprague-Dawley male rats (3 or 9 weeks old) were harvested and left intact or denuded of the endothelium. Vascular relaxation in aortic rings from younger and older groups was compared in the presence of βAR subtype agonists and antagonists along with cAMP and cGMP antagonists. Isolated aortic rings were used to evaluate relaxation responses, protein expression was evaluated by western blot or real time PCR, and metabolites were measured by ELISA. Expression of βAR subtypes and adenylyl cyclase was assessed, and cAMP activity was measured in vascular tissue from both groups. Isoproterenol- and BRL744-dependent relaxation in aortic rings with and without endothelium from 9-week-old rats was impaired compared with younger rats. The β1AR antagonist CGP20712A (10-7 M) did not affect isoproterenol or BRL744-dependent relaxation in arteries from either group. The β2AR antagonist ICI-118,551 (10-7 M) inhibited isoproterenol-dependent aortic relaxation in both groups. The β3AR antagonist SR59230A (10-7 M) inhibited isoproterenol- and BRL744-dependent aortic ring relaxation in younger but not in older rats. All βAR subtypes were expressed in both groups, although β3AR expression was lower in the older group. Adenylyl cyclase (SQ 22536) or protein kinase A (H89) inhibitors prevented isoproterenol-induced relaxation in younger but not in older rats. Production of cAMP was reduced in the older group. Adenylyl cyclase III and RyR3 protein expression was higher in the younger group. In conclusion, altered expression of β3AR and adenylyl cyclase III may be responsible for reduced cAMP production in the older group.

Comparison of bolus and continuous infusion of esmolol on hemodynamic response to laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft / Comparação de esmolol em bolus e infusão contínua na resposta hemodinâmica à laringoscopia, intubação orotraqueal e esternotomia em cirurgia de revascularização coronária / Comparación del esmolol en bolos e infusión continua en la respuesta hemodinámica a la laringoscopia, intubación orotraqueal y esternotomía en cirugía de revascularización coronaria

BACKGROUND AND OBJECTIVE: The aim of this randomized, prospective and double blinded study is to investigate effects of different esmolol use on hemodynamic response of laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft surgery. METHODS: After approval of local ethics committee and patients' written informed consent, 45 patients were randomized into three groups equally. In Infusion Group; from 10 min before intubation up to 5th minute after sternotomy, 0.5 mg/kg/min esmolol infusion, in Bolus Group; 2 min before intubation and sternotomy 1.5 mg/kg esmolol IV bolus and in Control Group; %0.9 NaCl was administered. All demographic parameters were recorded. Heart rate and blood pressure were recorded before infusion up to anesthesia induction in every minute, during endotracheal intubation, every minute for 10 minutes after endotracheal intubation and before, during and after sternotomy at first and fifth minutes. RESULTS: While area under curve (AUC) (SAP × time) was being found more in Group B and C than Group I, AUC (SAP × T int and T st) and AUC (SAP × T2) was found more in Group B and C than Group I (p < 0.05). Moreover AUC (HR × T st) was found less in Group B than Group C but no significant difference was found between Group B and Group I. CONCLUSION: This study highlights that esmolol infusion is more effective than esmolol bolus administration on controlling systolic arterial pressure during endotracheal intubation and sternotomy in CABG surgery. .

JUSTIFICATIVA E OBJETIVO: o objetivo deste estudo prospectivo, randômico e duplo-cego foi investigar os efeitos do uso diferente de esmolol na resposta hemodinâmica à laringoscopia, intubação orotraqueal e esternotomia em cirurgia de revascularização coronária. MÉTODOS: após obter a aprovação do Comitê de Ética local e consentimento informado assinado pelos pacientes, 45 pacientes foram randomicamente divididos em três grupos. O Grupo I (infusão) recebeu 0,5 mg/kg/min de esmolol em infusão a partir de 10 min antes da intubação até 5 minutos após a esternotomia; o Brupo B (bolus) recebeu 1,5 mg/kg de esmolol em bolus IV a partir de 2 min antes da intubação e esternotomia; o grupo C (controle) recebeu NaCl a 0,9%. Todos os parâmetros demográficos foram registados. Os valores de frequência cardíaca e pressão arterial foram registrados desde antes da infusão até a indução da anestesia a cada minuto, durante a intubação endotraqueal, a cada minuto durante 10 min após a intubação endotraqueal e antes, durante e após a esternotomia no primeiro e quinto minutos. RESULTADOS: enquanto a área sob a curva (ASC) (SAP × tempo) foi maior nos grupos B e C que no Grupo I, a ASC (SAP × T int e T st) e ASC (SAP × T2) foram maiores nos grupos B e C que no Grupo I (p < 0,05). Além disso, a ASC (FC × T st)) foi menor no Grupo B que no Grupo C, mas não houve diferença significante entre os grupos B e I. CONCLUSÃO: este estudo destaca que a administração de esmolol em infusão é mais eficaz que em bolus para controlar a pressão arterial sistólica durante a intubação endotraqueal e esternotomia em CRC. .

JUSTIFICACIÓN Y OBJETIVO: el objetivo de este estudio prospectivo, aleatorizado y doble ciego fue investigar los efectos del diferente uso del esmolol en la respuesta hemodinámica a la laringoscopia, intubación orotraqueal y esternotomía en cirugía de revascularización coronaria. MÉTODOS: después de obtener la aprobación del Comité de Ética local y el consentimiento informado firmado por los pacientes, 45 de ellos fueron aleatoriamente divididos en 3 grupos. El grupo I (infusión) recibió 0,5 mg/kg/min de esmolol en infusión desde 10 min antes de la intubación hasta 5 min después de la esternotomía; el grupo B (bolo), que recibió 1,5 mg/kg de esmolol en bolo iv a partir de 2 min antes de la intubación y esternotomía; el grupo C (control) recibió NaCl al 0,9%. Todos los parámetros demográficos fueron registrados. Los valores de frecuencia cardíaca y presión arterial fueron registrados ya antes de la infusión y hasta la inducción de la anestesia cada minuto durante la intubación endotraqueal, cada minuto durante 10 min después de la intubación endotraqueal, y antes, durante y después de la esternotomía en el primer y quinto minutos. RESULTADOS: mientras que el área bajo la curva (AUC) (presión arterial sistólica [PAS] × tiempo) fue mayor en los grupos B y C que en el grupo I, el AUC (PAS ×T int y T st ) y AUC (PAS × T 2 ) fueron mayores en los grupos B y C que en el grupo I (p < 0,05). Además, el AUC (frecuencia cardíaca × T st ) fue menor en el grupo B que en el grupo C, pero no hubo diferencia significativa entre los grupos B e I. CONCLUSIÓN: este estudio destaca que la administración del esmolol en infusión es más eficaz que en bolos para controlar la PAS durante la intubación endotraqueal ...

Adrenaline; the effects in presence of beta blocker in isolated mammalian heart

There is no doubt that the effects of the catecholamines of the heart are mainly due to the stimulation of beta-adrenoceptors but in the mid 1960' s the first evidence was presented that a-adrenoceptors mediating positive inotrpoism exists also in the myocardium beside well established beta -adrenoceptors. In our observation adrenaline shows a positive inotropic response. The response of adrenaline in presence of metoprolol [beta1blocker] showed negative inotropic effect

Efeitos de esmolol, lidocaína e fentanil nos intervalos dispersão da onda P, QT, QTc e respostas hemodinâmicas à intubação endotraqueal durante indução com propofol: um estudo comparativo / Effects of esmolol, lidocaine and fentanyl on P wave dispersion, QT, QTc intervals and hemodynamic responses to endotracheal intubation during propofol induction: a comparative study / Efectos del esmolol, de la lidocaína y del fentanilo en los intervalos dispersión de la onda, QT, QTc y respuestas hemodinámicas a la intubación endotraqueal durante inducción con propofol: un estudio comparativo

JUSTIFICATIVA E OBJETIVOS: Investigar o efeito de esmolol, lidocaína e fentanil na dispersão da onda P (DP), durações dos intervalos QT e QT corrigido (QTc) e as respostas hemodinâmicas à intubação endotraqueal durante a indução com propofol. MÉTODOS: Foram incluídos 80 pacientes adultos, estado físico ASA I ou II, idade entre 18 e 60 anos, neste estudo prospectivo, randômico e duplo-cego. Todos os pacientes foram submetidos a exame eletrocardiográfico (ECG) antes da indução da anestesia. Os pacientes foram randomicamente alocados em quatro grupos iguais. O grupo controle (Grupo C) recebeu 5 mL de solução salina; o grupo esmolol (Grupo E) recebeu 0,5 mg.kg-1 de esmolol; o grupo fentanil (Grupo F) recebeu 2 µg.kg-1 de fentanil e o grupo lidocaína (Grupo L) recebeu 1,5 mg.kg-1 de lidocaína antes da indução anestésica. A anestesia foi induzida com propofol. ECG foi feito em todos os pacientes durante o primeiro e o terceiro minutos de indução, 3 minutos após a administração de relaxante muscular e 5 e 10 minutos após intubação. A DP e intervalos QT foram medidos em todos os ECGs. Os intervalos QTc foram determinados com o uso da fórmula de Bazett. Frequência cardíaca (FC) e pressão arterial média (PAM) foram registradas antes e depois da indução anestésica, imediatamente após a intubação e em 1, 3, 5, 7 e 10 minutos após a intubação. RESULTADOS: Após a intubação, a FC aumentou significativamente nos Grupos C, L e F em comparação com o grupo controle. Porém, não houve diferença significativa nos valores da FC após a intubação entre os grupos E e controle. Nos Grupos C e L, a PAM aumentou significativamente após a intubação em comparação com o grupo controle. No entanto, nos Grupos L, F e E não houve diferença significativa entre os valores da PAM após a intubação em comparação com o grupo controle. A DP foi significativamente mais longa no Grupo C após a intubação em comparação com o grupo controle. Porém, nos grupos L, F e E não houve diferença significativa entre os valores de DP após a intubação em comparação com o grupo controle. A duração do intervalo QTc foi significativamente maior nos grupos C e L após a intubação em comparação com o grupo controle. Porém, não houve diferença significativa na duração do QTc nos grupos F e E após a intubação em comparação com o grupo controle. CONCLUSÃO: Concluímos que a administração de esmolol antes da intubação previne a taquicardia, o aumento da PAM e as durações da onda P e intervalo QTc causados pela laringoscopia e intubação traqueal.

BACKGROUND AND OBJECTIVES: In our study we aimed to investigate the effect of esmolol, lidocaine and fentanyl on P-wave dispersion (Pwd), QT and corrected QT (QTc) durations and hemodynamic responses to endotracheal intubation during propofol induction. METHODS: A total of eighty adult patients, American Society of Anesthesiologists (ASA) Physical Status I or II aged 18 to 60 years were included in this prospective, randomised, double-blind study. All patients had control electrocardiograms (ECGs) done before anesthesia induction. The patients were randomised into four equal groups. The control group (Group C) received saline 5 mL, the esmolol group (Group E) received esmolol 0.5 mg.kg-1, the fentanyl group (Group F) received fentanyl 2 µg.kg-1 and the lidocaine group (Group L) received lidocaine 1.5 mg.kg-1 before anesthesia induction. Anesthesia was induced with intravenous propofol. ECGs for all patients were performed during the 1st and 3rd minutes of induction, 3 minutes after administration of muscle relaxant, and at 5 minutes and 10 minutes after intubation. Pwd and QT intervals were measured on all ECGs. QTc intervals were determined using the Bazett formula. Heart rate (HR) and mean arterial pressure (MAP) were recorded before and after induction of anesthesia, immediately after intubation, and 1, 3, 5, 7 and 10 minutes after intubation. RESULTS: Compared with control, HR significantly increased in Group C, Group L and Group F after intubation. However, in Group E, there was no significant difference in HR values between control and after intubation. Compared with control, MAP significantly increased in Group C and Group L after the intubation. However, in Group E and Group F, there was no significant difference in MAP values between control and after the intubation. Compared with control, Pwd significantly increased in Group C after intubation. In Group L, Group F and Group E, there was no significant difference in Pwd values between control and after the intubation. Compared with control, QTc duration significantly increased in Group C and L after the intubation. In Group F and Group E, there was no significant difference in QTc durations between control and after the intubation. CONCLUSION: We concluded that administration of esmolol before intubation prevents tachycardia and an increase in MAP, Pwd and QTc duration caused by laryngoscopy and tracheal intubation.

JUSTIFICATIVA Y OBJETIVOS: Investigar el efecto del esmolol, lidocaína y fentanilo en la dispersión de la onda P (DOP), duraciones de los intervalos QT y QT corregido (QTc) y las respuestas hemodinámicas a la intubación endotraqueal durante la inducción con propofol. MÉTODOS: En este estudio prospectivo, aleatorio y doble ciego, fueron incluidos 80 pacientes adultos, con estado físico ASA I o II, y edad entre 18 y 60 años. Todos los pacientes se sometieron al examen electrocardiográfico (ECG) antes de la inducción de la anestesia. Los pacientes fueron aleatoriamente divididos en cuatro grupos iguales. El grupo control (Grupo C) recibió 5 mL de solución salina; el grupo esmolol (Grupo E) recibió 0,5 mg.kg-1 de esmolol; el grupo fentanilo (Grupo F) recibió 2 µg.kg-1 de fentanilo y el grupo lidocaína (Grupo L) recibió 1,5 mg.kg-1 de lidocaína antes de la inducción anestésica. La anestesia fue inducida con propofol. El ECG se hizo en todos los pacientes durante el primero y el tercer minuto de inducción, 3 minutos después de la administración del relajante muscular y 5 y 10 minutos después de la intubación. La DOP y los intervalos QT se midieron en todos los ECGs. Los intervalos QTc fueron determinados con el uso de la fórmula de Bazett. La frecuencia cardíaca (FC) y la presión arterial promedio (PAP) fueron registradas antes y después de la inducción anestésica, inmediatamente después de la intubación y en 1, 3, 5, 7 y 10 minutos después de la intubación. RESULTADOS: Después de la intubación, la FC aumentó significativamente en los Grupos C, L y F en comparación con el grupo control. Sin embargo, no hubo diferencia significativa en los valores de la FC después de la intubación entre los grupos E y control. En los Grupos C y L, la PAP aumentó significativamente después de la intubación en comparación con el grupo control. Sin embargo, en los Grupos L, F y E no hubo diferencia significativa entre los valores de la PAP posteriormente a la intubación en comparación con el grupo control. La DOP fue significativamente más larga en el Grupo C después de la intubación en comparación con el grupo control. No obstante, en los grupos L, F y E no hubo diferencia significativa entre los valores de DOP después de la intubación en comparación con el grupo control. La duración del intervalo QTc fue significativamente mayor en los grupos C y L después de la intubación en comparación con el grupo control. Sin embargo, no hubo diferencia significativa en la duración del QTc en los grupos F y E después de la intubación en comparación con el grupo control. CONCLUSIONES: Llegamos entonces a la conclusión, de que la administración del esmolol antes de la intubación previene la taquicardia, el aumento de la PAP y las duraciones de la onda P e intervalo QTc causados por la laringoscopia y por la intubación traqueal.