ABSTRACT The purpose of study was to determine the effect of diltiazem on the hemodynamic response to adenosine using an in vivo rabbit model. Male New Zealand white rabbits (n = 6) weighing between 4 - 6 kg will be used. Each rabbit will receive diltiazem (Biovail Corp, Mississauga, Ont. Canada) 5 mg/kg s.c. bid for 5 doses. A separate group of animals (n = 7) will be used as control. On the day of experiment, a modified butterfly catheter with a 21G 3/4 in needle was inserted into a central ear artery for hemodynamic recording, and an unmodified butterfly catheter into a marginal vein for infusion. Adenosine (Sigma Chem Co.) was given to each rabbit by constant iv infusion at 200 ug/kg and 500 ug/kg over a 10-min period. A washout period of 2 hrs between each infusion was used to allow haemodynamic variables returning to pre-treatment levels. BP and HR were determined continuously during the infusion, and for 20 min after the infusion. The results showed that diltiazem decreased MAP from 76 to 62 mm Hg, but had no effect on HR. In the diltiazem treated rabbits, adenosine (200 ug/kg) decreased MAP from 62 to 56 mm Hg at the end of infusion (10 min). Mean HR was increased from 239 to 251 bpm during infusion. At the higher dose (500 ug/kg), adenosine decreased MAP from 62 to 50 mm Hg, and increased mean HR from 250 to 266 bpm. It is concluded that the hemodynamic effects of adenosine were significantly higher during the constant iv infusion of 500 ug/kg vs 200 ug/kg in rabbits pretreated with diltiazem. This dose effect was not apparent in control rabbits.
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