Journal of cardiovascular pharmacology · 2020
Pulmonary Delivery of Metoprolol Reduces Ventricular Rate During Atrial Fibrillation and Accelerates Conversion to Sinus Rhythm.
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Marum Alexandre A, Araujo Silva Bruna, Bortolotto Alexandre L, Pedreira Giovanna C, Tessarolo Silva Fernanda, Medeiros Sofia A, Nearing Bruce D, Belardinelli Luiz, Verrier Richard L
Аннотация
BACKGROUND: Safe, effective pulmonary delivery of cardioactive agents in humans is under development.
OBJECTIVES: We examined whether intratracheal delivery of metoprolol can reduce ventricular rate during atrial fibrillation (AF) and accelerate conversion to sinus rhythm.
METHODS: In 7 closed-chest, anesthetized Yorkshire pigs, AF was induced by intrapericardial infusion of acetylcholine (1 mL of 102.5-mM solution) followed by atrial burst pacing and was allowed to continue for 2 minutes before intratracheal instillation of sterile water or metoprolol (0.2-mg/kg bolus) using a catheter positioned at the bifurcation of the main bronchi. High-resolution electrograms were obtained from catheters fluoroscopically positioned in the right atrium and left ventricle.
RESULTS: Rapid intratracheal instillation of metoprolol caused a 32-beat/min reduction in ventricular rate during AF (from 272 ± 13.7 to 240 ± 12.6 beats/min, P = 0.008) and a 2.3-minute reduction in AF duration (from 10.3 ± 2.0 to 8.0 ± 1.4 minutes, P = 0.018) compared with sterile water control. Conversion of AF to sinus rhythm was associated with rapid restoration (5-6 minutes) of heart rate and arterial blood pressure toward control values. Intratracheal metoprolol reduced AF dominant frequency by 31% (from 8.7 ± 0.9 to 6.0 ± 1.1 Hz, P = 0.04) compared with control and resulted in a trend toward a 5% increase in PR interval (from 174 ± 11.2 to 182 ± 11.4 ms, P = 0.07).
CONCLUSIONS: Intratracheal delivery of metoprolol effectively reduces ventricular rate during AF and accelerates conversion to normal sinus rhythm in a pig model of acetylcholine-induced AF.
OBJECTIVES: We examined whether intratracheal delivery of metoprolol can reduce ventricular rate during atrial fibrillation (AF) and accelerate conversion to sinus rhythm.
METHODS: In 7 closed-chest, anesthetized Yorkshire pigs, AF was induced by intrapericardial infusion of acetylcholine (1 mL of 102.5-mM solution) followed by atrial burst pacing and was allowed to continue for 2 minutes before intratracheal instillation of sterile water or metoprolol (0.2-mg/kg bolus) using a catheter positioned at the bifurcation of the main bronchi. High-resolution electrograms were obtained from catheters fluoroscopically positioned in the right atrium and left ventricle.
RESULTS: Rapid intratracheal instillation of metoprolol caused a 32-beat/min reduction in ventricular rate during AF (from 272 ± 13.7 to 240 ± 12.6 beats/min, P = 0.008) and a 2.3-minute reduction in AF duration (from 10.3 ± 2.0 to 8.0 ± 1.4 minutes, P = 0.018) compared with sterile water control. Conversion of AF to sinus rhythm was associated with rapid restoration (5-6 minutes) of heart rate and arterial blood pressure toward control values. Intratracheal metoprolol reduced AF dominant frequency by 31% (from 8.7 ± 0.9 to 6.0 ± 1.1 Hz, P = 0.04) compared with control and resulted in a trend toward a 5% increase in PR interval (from 174 ± 11.2 to 182 ± 11.4 ms, P = 0.07).
CONCLUSIONS: Intratracheal delivery of metoprolol effectively reduces ventricular rate during AF and accelerates conversion to normal sinus rhythm in a pig model of acetylcholine-induced AF.