Antioxidant protection against adrenaline-induced arrhythmias in rats with chronic heart hypertrophy.
Effects of vitamin E on adrenaline-induced arrhythmias were examined in rats with chronic heart hypertrophy subsequent to narrowing of the abdominal aorta. After 60 weeks of pressure overload, the rats showed an increase of about 21% in heart/body weight ratio and a small but significant rise in left ventricular end diastolic pressure (LVEDP) (sham control 1.7 +/- 0.67 mmHg; hypertrophy 7.1 +/- 2.7 mmHg) without any change in left ventricular peak systolic pressure (LVSP). Intravenous infusion of adrenaline caused rhythm disorders in a dose-dependent manner and pathological arrhythmias (occurrence of six premature ventricular complexes/min) were observed at doses of 2.9 +/- 0.6 and 3.8 +/- 1.0 micrograms/kg of the drug in control and hypertrophy animals, respectively. Administration of two doses of vitamin E (50 mg/kg intraperitoneally), given 24 h and 1 h before adrenaline infusion, significantly increased the amount of adrenaline required to produce pathological arrhythmias (control 8.0 +/- 3.0; hypertrophy 7.7 +/- 2.0 micrograms/kg). Vitamin E pretreatment did not have any detrimental effect on the pressure readings nor did it have any influence on adrenaline-induced pressure changes. The data suggest that a combination therapy with vitamin E may allow therapeutic use of higher concentrations of adrenaline required to improve function in failing hearts with a reduced risk of arrhythmias.
Kirshenbaum
L A
LA
Division of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Winnipeg, Manitoba.
Gupta
M
M
Thomas
T P
TP
Singal
P K
PK
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D004837:Epinephrine / Q000633:toxicity*; D005609:Free Radicals; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000627:therapeutic use*
D005609:Free Radicals; D014810:Vitamin E; D004837:Epinephrine