Author(s): Yeung P K F, Seto D
Purpose: To study the effect of exercise preconditioning on cardiovascular toxicities and mortality induced by isoproterenol in a freely moving rat model in vivo. Methods: Sprague Dawley (SD) rats with a carotid artery catheter weighing between 250 and 300g were used. Each rat was acclimatized to the Carleton Animal Care Centre (CACC) and had free access to food and water for 48 hours before experiment. Each rat was housed in a freely moving caging environment during experiment with free access to drinking water. In the group with exercise precondidtioning (n = 8), each rat was exercised on a treadmill for 15 minutes at 14 m/min 2 hours before receiving isoproterenol (30 mg/kg) by subcutaneous injection. Two separate groups with one without receiving isoproterenol and exercise (n = 9); and the other without exercise (n = 10) were used as control. Blood samples were collected at 0, 0.05, 0.25, 1, 1.2, 1.5, 2, 3, 4, 5 and 6 hours for measurement of adenine nucleotides (ATP, ADP and AMP) by a validated HPLC. Hemodynamic recording (SBP, DBP, and HR) was collected for the duration of the experiment using a TruWave(registered trademark) disposable pressure transducer (Model PX601, Edwards Lifesciences Canada, Inc., Mississauga, ON, Canada) coupled to a Siemens hemodynamic monitor (Sirecust 400) and chart recorder (Siredoc) (Erlangen, FRG). Biomarker data were analysed using t-tests and difference considered significant at p < 0.05. Results: Exercise pre-conditioning reduced mortality induced by isoproterenol within 4 hours after injection from 50% to 20%. It reduced the abrupt rebound of mean SBP from +75 (plus or minus) 41 to +41 (plus or minus) 15 mmHg (t-test, p < 0.05) and DBP from + 76 (plus or minus) 37 to +39 (plus or minus) 25 mmHg (p < 0.05), but had no effect on the increase of HR. It also attenuated the increase of RBC AMP concentrations from +0.24 (plus or minus) 0.23 mM in non-exercise rat to + 0.07 (plus or minus) 0.11 mM in rats after the exercise pre-conditioning (t-test, p = 0.074). Conclusion: Exercise pre-conditioning reduced cardiovascular toxicities, RBC concentrations of AMP and mortality induced by isoproterenol.