Flow-dependent antiarrhythmic properties of ammonia during catecholamine-driven ventricular tachycardia

Fifteen mongrel dogs weighing 22-34 kg were instrumented to investigate the antiarrhythmic effects of ammonia (0.1-0.2 mmol/min ammonium hydroxide), adenosine (1.87 mumol/min), and saline (0.9% NaCl) during norepinephrine-driven ventricular tachycardia, under conditions of controlled and natural coronary blood flow. Under natural flow conditions, the severe ectopy caused by norepinephrine (100-800 ng.kg-1.min-1) was reduced by 42 +/- 4% after 30 s of ammonia infusion. Adenosine infusion reduced percent ectopy by 97 +/- 2% at 30 s. Ammonia also significantly increased coronary blood flow by 26 +/- 4%, while adenosine increased blood flow by 72 +/- 14%. Saline infusion had no significant effect on either the severity of ventricular tachycardia or coronary blood flow. Norepinephrine consistently caused coronary functional hyperemia as previously reported. When coronary blood flow was controlled by a peristaltic pump to match natural coronary blood flow and to prevent norepinephrine-induced coronary functional hyperemia, the antiarrhythmic effects of ammonia were lost while those of adenosine were unaffected. Additionally, increasing coronary blood flow manually during norepinephrine-induced ventricular tachycardia, to a level seen with combined norepinephrine and ammonia under natural flow conditions, appeared to worsen the ventricular arrhythmias. We conclude that the antiarrhythmic properties of ammonia against norepinephrine-driven ventricular tachycardia might be dependent on coronary blood flow, while those of adenosine are independent of coronary blood flow.