tailieunhanh - Handbook of Experimental Pharmacology - Part 8

Phong toả β làm giảm tỷ lệ SAN bằng cách giảm cả Ca I, L (giai đoạn chủ yếu 0 hiện nay trong SAN) và tôi e. Hành động làm giảm nhịp tim xuất hiện để góp phần quan trọng để giảm tỷ lệ tử vong bởi β-blockers ở những bệnh nhân nhồi máu cơ tim sau, có thể vì tác dụng chống thiếu máu cục bộ (Kjekshus 1986). | 250 S. Zicha et al. effects due to actions on targets other than ion channels may have important consequences for arrhythmias. Role of Anti-ischemic Actions P-Blockade reduces the SAN rate by decreasing both ICa L the principal phase 0 current in SAN and If. This heart-rate reducing action appears to contribute importantly to mortality reduction by P-blockers in post-myocardial infarction patients possibly because of anti-ischemic effects Kjekshus 1986 . Based on their lack of direct action on determinants of automaticity in atria and ventricles P-blockers have little direct effect on atrial and ventricular ectopic beat frequencies. However P-blockers may be quite effective in preventing ventricular tachyarrhythmias caused by acute ischemia in experimental models Khan et al. 1972 and are the most effective drugs available for preventing arrhythmic sudden death in patients with active coronary artery disease Nat-tel and Waters 1990 Reiter 2002 . These properties are much more likely due to anti-ischemic than direct electrophysiological actions. Role in Remodeling Neurohumoral stimulation plays a major role in the myocardial deterioration associated with CHF Katz 2003 . A variety of cardiac ion channels is remodeled by P-adrenergic stimulation Zhang et al. 2002 . Circulating norepinephrine concentrations are an important predictor of arrhythmic death in CHF patients and P-blockers are effective in preventing sudden death in the CHF population Reiter 2002 . Abnormal Ca2 handling likely central to the arrhythmic diathesis in CHF patients is normalized by chronic exposure to a P-blocker Plank et al. 2003 . 5 Types of Arrhythmia Treated by P-Blockers The major factor mediating the salutary effect of P-adrenergic blockers in cardiac arrhythmias is counteraction of the arrhythmogenic actions of catecholamine that facilitate 1 triggered activity due to intracellular Ca2 overload-induced delayed afterdepolarizations 2 automaticity in the conduction system and .