P2Adrenoceptors in the Heart

The p2-AR subtype is also found in the human heart (Brodde 1991), albeit to a lesser extent than p1 ARs. Agonists for p2-ARs include salbutamol (Kelman et al. 1969), terbutaline (Burnell and Maxwell 1971), and salmeterol (Ullman and Svedmyr 1988). p2-ARs are more responsive to isoproterenol as compared to norepinephrine. When heart transplant patients are given isoproterenol, an increase in heart rate is observed, even in the presence of the highly selective p1 antagonist bisoprolol (Hakim et...

References

Abbott GW, Goldstein SA (2001) Potassium channel subunits encoded by the KCNE gene family physiology and pathophysiology of the MinK-related peptides (MiRPs). Mol Interv 1 95-107 Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA (1999) MiRPl forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97 175-187 Abitbol I, Peretz A, Lerche C, Busch AE, Attali B (1999) Stilbenes and fenamates rescue the loss of I(KS) channel...

Drug Induced Ventricular Arrhythmias

Supraventricular tachyarrhythmias are often treated with class III anti-arrhythmic drugs (Vaughan Williams 1984). These K+ channel blockers act by increasing the action potential duration and the effective refractory period in order to prevent premature re-excitation (Coumel et al. 1978). While these interventions can be useful in targeting tachyarrhythmias, they may predispose some patients to the development of other types of arrhythmia (Priori 2000). It has become apparent that drug-induced...

Factors That Modulate ECG and Arrhythmic Manifestations of the Brugada Syndrome

ST segment elevation in the Brugada syndrome is often dynamic. The Brugada ECG is often concealed and can be unmasked or modulated by sodium channel blockers, a febrile state, vagotonic agents, a-adrenergic agonists, -adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin, hyperkalemia, hypokalemia, hypercalcemia, and by alcohol and cocaine toxicity (Brugada et al. 2000bc Miyazaki et al. 1996 Babaliaros and Hurst 2002 Goldgran-Toledano et al. 2002...

Cellular and Ionic Basis

Coronary Perfusion Pressure Cpr

The ability of the RV action potential to lose its dome, giving rise to phase 2 reentry and other characteristics of the Brugada syndrome, were identified in the early 1990s and evolved in parallel with the clinical syndrome (Antzelevitch et al. 1991, 2002 Krishnan and Antzelevitch 1991 Krishnan and Antzelevitch 1993). The ST segment elevation in the Brugada syndrome is thought to be secondary to a rebalancing of the currents active at the end of phase 1, leading to accentuation of the action...

Clinical Features

Quinidine was introduced into clinical drug therapy in the early 1920s (Wenckebach 1923), and syncope following the initiation of the drug was recognized in occasional patients shortly thereafter. The advent of online electrocardiographic monitoring in the 1960s established that quinidine syncope was caused by what we now recognize as torsades de pointes (Selzer and Wray 1964). Interestingly, the actual term was coined to describe the arrhythmia in a different context, an elderly woman with...

Animal Models

Neonatal rat ventricle cell cultures have been employed to demonstrate both the ability of HCN isoforms to enhance automaticity and the contribution of HCN channels to normal automaticity. Qu and colleagues first demonstrated that over-expressing HCN2 in these cultures significantly increased spontaneous rate Fig. 6 Qu et al. 2001 . Er and colleagues subsequently confirmed this observation and extended it to HCN4 over-expression. They also demonstrated that expression of a dominant negative...