Pharmacological agents that increase gap junctional communication, such as GAP-134 and connexin mimetic peptides, show promise for treating arrhythmias in patients with ischemic cardiomyopathy.
Do connexin-modulating compounds reduce the risk of arrhythmias in patients with ischemic cardiomyopathy?
Connexin-modulating compounds represent a promising, potentially safer new class of antiarrhythmic drugs for patients with ischemic cardiomyopathy by specifically targeting gap junctional communication.
Coordinated electrical activity in the heart is supported by gap junction channels located at the intercalated discs of cardiomyocytes. Impaired gap junctional communication between neighbouring cardiomyocytes contributes to the development of re-entry arrhythmias after myocardial ischaemia. Current antiarrhythmic therapy is hampered by a lack of efficiency and side effects, creating the need for a new generation of drugs. In this review, we focus on compounds that increase gap junctional communication, thereby increasing the conduction velocity and decreasing the risk of arrhythmias. Some of these compounds also inhibit connexin 43 (Cx43) hemichannels, thereby limiting adenosine triphosphate loss and volume overload following ischaemia/reperfusion, thus potentially increasing the survival of cardiomyocytes. The compounds discussed in this review are: (i) antiarrythmic peptide (AAP), AAP10, ZP123; (ii) GAP-134; (iii) RXP-E; and (vi) the Cx mimetic peptides Gap 26 and Gap 27. None of these compounds have effects on Na(+) , Ca(2+) and K(+) channels, and therefore have no proarrhythmic activity associated with currently available antiarrhythmic drugs. GAP-134, RXP-E, Gap 26 and Gap 27 are pharmalogical agents with a favorable clinical safety profile, as already confirmed in phase I clinical trials for GAP-134. These agents show an excellent promise for treatment of arrhythmias in patients with ischaemic cardiomyopathy.
Vuyst et al. (Wed,) conducted a review in Arrhythmias after myocardial ischaemia. Connexin-modulating compounds (AAP, ZP123, GAP-134, RXP-E, Gap 26, Gap 27) was evaluated. Pharmacological agents that increase gap junctional communication, such as GAP-134 and connexin mimetic peptides, show promise for treating arrhythmias in patients with ischemic cardiomyopathy.