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β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure.

Wang Y, Yuan J, Qian Z, Zhang X, Chen Y, Hou X, Zou J - Sci Rep (2015)

Bottom Line: These effects could be prevented by the selective β2-AR antagonist, ICI118551.Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes.However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

ABSTRACT
β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways.

No MeSH data available.


Related in: MedlinePlus

Effects of β2-AR stimulation on APD in myocytes from isolated failing heart.(A) Representative AP traces stimulated by salbutamol (Sal) in left ventricular myocytes from control (Con, left) and HF guinea pigs (HF, right). (B) Summarized data from change of APD90 () and APD50 () in control (Con, left) and HF (HF, right) myocytes (**p < 0.01, HF vs. Con, n = 6 cells, 6 hearts). Test pulses were applied at various voltages from −40 to +40 mV (step width 10 mV, step duration 200 ms) before returning to −40 mV for tail current recording.
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f4: Effects of β2-AR stimulation on APD in myocytes from isolated failing heart.(A) Representative AP traces stimulated by salbutamol (Sal) in left ventricular myocytes from control (Con, left) and HF guinea pigs (HF, right). (B) Summarized data from change of APD90 () and APD50 () in control (Con, left) and HF (HF, right) myocytes (**p < 0.01, HF vs. Con, n = 6 cells, 6 hearts). Test pulses were applied at various voltages from −40 to +40 mV (step width 10 mV, step duration 200 ms) before returning to −40 mV for tail current recording.

Mentions: APD at 90% repolarization (APD90) was prolonged to a greater extent by salbutamol in the HF group compared to the control group (14.11 ± 1.10 ms vs. 7.04 ± 1.59 ms, n = 6 p < 0.01) (Fig. 4B). However, no significant difference was observed in change of 50% repolarization (APD50) between the HF and control groups (9.44 ± 1.85 ms vs. 4.61 ± 2.65 ms, n = 6, p > 0.05) (Fig. 4B).


β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure.

Wang Y, Yuan J, Qian Z, Zhang X, Chen Y, Hou X, Zou J - Sci Rep (2015)

Effects of β2-AR stimulation on APD in myocytes from isolated failing heart.(A) Representative AP traces stimulated by salbutamol (Sal) in left ventricular myocytes from control (Con, left) and HF guinea pigs (HF, right). (B) Summarized data from change of APD90 () and APD50 () in control (Con, left) and HF (HF, right) myocytes (**p < 0.01, HF vs. Con, n = 6 cells, 6 hearts). Test pulses were applied at various voltages from −40 to +40 mV (step width 10 mV, step duration 200 ms) before returning to −40 mV for tail current recording.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4286790&req=5

f4: Effects of β2-AR stimulation on APD in myocytes from isolated failing heart.(A) Representative AP traces stimulated by salbutamol (Sal) in left ventricular myocytes from control (Con, left) and HF guinea pigs (HF, right). (B) Summarized data from change of APD90 () and APD50 () in control (Con, left) and HF (HF, right) myocytes (**p < 0.01, HF vs. Con, n = 6 cells, 6 hearts). Test pulses were applied at various voltages from −40 to +40 mV (step width 10 mV, step duration 200 ms) before returning to −40 mV for tail current recording.
Mentions: APD at 90% repolarization (APD90) was prolonged to a greater extent by salbutamol in the HF group compared to the control group (14.11 ± 1.10 ms vs. 7.04 ± 1.59 ms, n = 6 p < 0.01) (Fig. 4B). However, no significant difference was observed in change of 50% repolarization (APD50) between the HF and control groups (9.44 ± 1.85 ms vs. 4.61 ± 2.65 ms, n = 6, p > 0.05) (Fig. 4B).

Bottom Line: These effects could be prevented by the selective β2-AR antagonist, ICI118551.Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes.However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

ABSTRACT
β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways.

No MeSH data available.


Related in: MedlinePlus