Endurance exercise training attenuates cardiac beta2-adrenoceptor responsiveness and prevents ventricular fibrillation in animals susceptible to sudden death.
Level 5 - mechanism / opinion, no new human data
Animal research (canine post-myocardial infarction model)
PubMed 16387787 · doi:10.1152/ajpheart.01220.2005
What was done
Dogs with healed myocardial infarctions were tested for ventricular fibrillation (VF) susceptibility using a 2-minute coronary occlusion during submaximal exercise, identifying 20 susceptible and 13 resistant dogs. Animals were assigned to a 10-week endurance exercise training program (9 susceptible, 8 resistant) or a 10-week sedentary period (11 susceptible, 5 resistant). In vivo peak contractile responses to isoproterenol before and after beta2-adrenoceptor blockade with ICI-118551 (0.2 mg/kg) were measured by echocardiography. In vitro isotonic shortening of isolated ventricular myocytes was assessed in response to the beta2-adrenoceptor agonist zinterol (1 microM), and VF inducibility was re-tested post-intervention.
What was found
Before training, ICI-118551 reduced peak contractile responses to isoproterenol by -45.5 +/- 6.5% in susceptible dogs versus -19.2 +/- 6.3% in resistant dogs. After training, reduction was -12.1 +/- 5.7% in susceptible and -16.2 +/- 6.4% in resistant dogs, whereas sedentary susceptible dogs had a -62.3 +/- 4.6% reduction. In isolated myocytes, zinterol increased shortening by +7.2 +/- 4.8% in trained susceptible dogs (n = 8) versus +42.8 +/- 5.8% in sedentary susceptible dogs (n = 7), matching resistant dogs (+3.0 +/- 1.4% trained [n = 6] and +3.2 +/- 1.8% sedentary [n = 5]). VF could no longer be induced in any trained susceptible dogs, whereas 4 sedentary susceptible dogs died during the 10-week period and VF remained inducible in all 7 surviving sedentary animals.
Why it matters
This study shows that exercise training reverses maladaptive cardiac beta2-adrenoceptor hyper-responsiveness and protects against lethal ischemia-induced arrhythmias in an animal model of sudden death.
Limits
The study was conducted in a canine infarction model, which may not translate directly to humans. Sample sizes per experimental subgroup were small (5 to 11 dogs), and four sedentary susceptible animals died before the end of the intervention period.
Cited by
- supports In canine models of exercise ischemia, vagal nerve stimulation or prior exercise training prevents ventricular fibrillation and sudden cardiac death during acute coronary artery occlusion.