Absence of prejunctional sympathetic effect of amiodarone in hearts of open-chest anesthetized dogs.
The effect of amiodarone (30 mg/kg p.o. each day for 3 weeks) on noradrenaline (NA) overflow into coronary sinus (CS) blood during left stellate stimulation (15 V, 2-ms square waves, 30 s duration at 1, 2, 4, and 8 Hz in random order) was investigated in an open-chest dog preparation. CS blood samples were taken before and during the stimulation period for plasma NA and hematocrit determinations. CS blood flow was monitored (extracorporal circulation with an electromagnetic flow meter) and used for NA output computation. The right atrium was paced throughout the experimental period. However, because AV block occurred at a high pacing rate in some amiodarone-treated dogs, pacing rate was lower in that group than in control dogs (132 +/- 13 vs. 161 +/- 10 min-1, ns). Mean arterial pressure was also lower in the treated group (95 +/- 9 vs. 110 +/- 13 mmHg, but increased in every dog upon stimulation (p less than 0.05). Basal left ventricular dP/dtmax was comparable in the two groups of dogs and increased in a similar fashion upon stimulation (p less than 0.05). The increase in plasma NA concentration upon stimulation was comparable between the control and the amiodarone-treated group (0.38 +/- 0.08 vs 0.40 +/- 0.12 ng/mL at 1 Hz and 12.7 +/- 3.1 vs 11.3 +/- 2.3 ng/mL at 8 Hz, ns). The increase in NA output was also comparable (7.0 +/- 1.6 vs. 10.7 +/- 5.4 ng/min at 1 Hz and 356 +/- 124 vs. 334 +/- 102 ng/min at 8 Hz, ns). Amiodarone did not alter the myocardial NA content. We conclude that amiodarone, administered orally for 3 weeks, does not interfere with neural NA release, or with the positive inotropic response, following sympathetic nerve stimulation in dogs.
Lamontagne
D
D
Centre de recherche, Hôpital du Sacré-Coeur de Montréal, Québec, Canada.
Yamaguchi
N
N
Lambert
C
C
de Champlain
J
J
Nadeau
R
R
D000638:Amiodarone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012849:Sinoatrial Node / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects*
D011506:Proteins; C036116:desethylamiodarone; D000638:Amiodarone; D009638:Norepinephrine