Year: 2018
Type: dissertation
Abstract: The pleomorphic benefits of regular endurance exercise are well-established. Recent studies have suggested that ‘extreme’ endurance exercise may adversely affect cardiac structure and function, particularly the right ventricle (RV), leading to transient RV impairment that, with repetitive bouts and inadequate recovery, may promote an exercise-induced proarrhythmic and cardiomyopathic phenotype. However, the clinical significance of exhaustive exercise-induced transient RV impairment is unclear, and a causal link between exercise and proarrhythmic RV remodeling remains controversial. The first project characterized the naive insult of acute exhaustive exercise on RV and LV structure and function in mice to determine whether exhaustive exercise disproportionately impacts the RV and if so, whether these effects persist into recovery. Using pressure-volume (P-V) analysis, acute exhaustive swim exercise was shown to predominantly impact the RV, with evidence of transient and persistent (24-hour) RV dilation and inotropic and lusitropic impairment (steady-state and dobutamine) compared to sedentary and 30 minute swim mice. These findings suggest RV recovery may be incomplete following an exhaustive exercise bout that may, after repetitive bouts, impact the long-term pattern of RV remodeling. The second and third projects prospectively determined whether chronic (7-weeks), exhaustive swim training promoted a proarrhythmic and cardiomyopathic pattern of RV remodeling. While the majority of exhaustively swim trained mice exhibited evidence of physiological remodeling, a subset of mice had evidence of proarrhythmic RV remodeling, characterized by significant RV dilation, inotropic and lusitropic impairment (steady-state and with dobutamine), fibrotic remodeling, heterogeneities of repolarization, and increased ventricular tachyarrhythmia (VT) vulnerability. All arrhythmias were of RV origin, though the morphology and inducing mechanism (i.e., re-entry, triggered) was variable. Our results demonstrate that acute exhaustive exercise disproportionately impacts the RV, with chronic exhaustive training promoting a heterogeneous pattern of RV remodeling, with a subset of mice presenting with excessive RV dilation, functional abnormalities, and proarrhythmic RV remodeling.
Source: TSpace (University of Toronto)
Author: Robert Lakin
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2925398960