Tocainide and mortality after myocardial infarction: a prospective study in conscious dogs.
The production of an anterior myocardial infarction as part of an experimental animal model for sudden death was burdened by a persistently elevated mortality rate (30%) despite the use of traditional antiarrhythmic drugs. Mortality was reduced when tocainide (600 mg three times daily) was empirically administered for 4 days before and 4 days after myocardial infarction. Retrospective analysis showed that mortality at 4 days after infarction was significantly lower in the tocainide-treated dogs than in the preceding large group of dogs that had not been so treated (5 [9%] of 55, versus 64 [32%] of 199, p less than 0.01). This difference was still evident 30 days after myocardial infarction (13 [24%] of 55 versus 83 [42%] of 199; p less than 0.05). This observation led to the present prospective study in 106 dogs with a similar protocol but with a randomized sequence. At 4 days after myocardial infarction, the mortality rate was 55% lower in the tocainide group than in the control group (7 [12.5%] of 56 versus 14 [28%] of 50; p less than 0.05). During the 10 days after treatment withdrawal 9 (18%) of 49 dogs in the tocainide group died compared with only 2 (5%) of 36 in the control group. This rebound in mortality produced similar survival figures in the two groups at 14 and at 30 days after infarction when mortality was 30% (17 of 56) in the tocainide group and 34% (17 of 50) in the control group. The tocainide plasma levels were 7.4 +/- 4 micrograms/ml the day before infarction and 7.2 +/- 3 micrograms/ml 3 days after infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
Vanoli
E
E
Unità di Studio delle Aritmie, degli Studi di Milano, Italy.
Hull
S S
SS
Stith
R D
RD
Adamson
P B
PB
Foreman
R D
RD
Schwartz
P J
PJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000627:therapeutic use*; D004285:Dogs; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality*; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D016677:Tocainide
D000889:Anti-Arrhythmia Agents; D016677:Tocainide; D008012:Lidocaine