Myocardial electrotonic response to submaximal exercise in dogs with healed myocardial infarctions: evidence for β-adrenoceptor mediated enhanced coupling during exercise testing

Abstract

Introduction: Autonomic neural activation during cardiac stress testing is an established risk-stratification tool in post-myocardial infarction (MI) patients. However, autonomic activation can also modulate myocardial electrotonic coupling, a known factor to contribute to the genesis of arrhythmias. The present study tested the hypothesis that exercise-induced autonomic neural activation modulates electrotonic coupling (as measured by myocardial electrical impedance, MEI) in post-MI animals shown to be susceptible or resistant to ventricular fibrillation (VF).

Methods: Dogs (n = 25) with healed MI instrumented for MEI measurements were trained to run on a treadmill and classified based on their susceptibility to VF (12 susceptible, 9 resistant). MEI and ECGs were recorded during 6-stage exercise tests (18 min/test; peak: 6.4 km/h @ 16%) performed under control conditions, and following complete β-adrenoceptor (β-AR) blockade (propranolol); MEI was also measured at rest during escalating β-AR stimulation (isoproterenol) or overdrive-pacing.

Results: Exercise progressively increased heart rate (HR) and reduced heart rate variability (HRV). In parallel, MEI decreased gradually (enhanced electrotonic coupling) with exercise; at peak exercise, MEI was reduced by 5.3 ± 0.4% (or -23 ± 1.8Ω, P < 0.001). Notably, exercise-mediated electrotonic changes were linearly predicted by the degree of autonomic activation, as indicated by changes in either HR or in HRV (P < 0.001). Indeed, β-AR blockade attenuated the MEI response to exercise while direct β-AR stimulation (at rest) triggered MEI decreases comparable to those observed during exercise; ventricular pacing had no significant effects on MEI. Finally, animals prone to VF had a significantly larger MEI response to exercise.

Conclusions: These data suggest that β-AR activation during exercise can acutely enhance electrotonic coupling in the myocardium, particularly in dogs susceptible to ischemia-induced VF.

Keywords: arrhythmic risk; electrotonic coupling; exercise; myocardial infarction; β-adrenoceptor stimulation.

Figure 1

Schematic representation of the six-level submaximal exercise test (SMT).

Figure 2

Exercise-Induced changes in the heart-rate (HR, top-left) and ECG-derived vagal-tone index (bottom-left) and well as in the myocardial electrical impedance (MEI, bottom-right with representative response in top-right) of awake-unsedated dogs with healed left-anterior descending (LAD) myocardial infarcts (n = 25, except at recovery where n = 14).

Figure 3

Relationship(s) between the exercise-induced changes in the heart-rate (top) and ECG-derived vagal-tone index (bottom) with the concomitant reductions in myocardial electrical impedance (MEI); relationships were “centered,” i.e., deviations from each animal's mean values (over the whole exercise bout) were studied.

Figure 4

Effects of (non-selective) β-adrenoceptor blockade (+BB, propranolol) in the myocardial electrical impedance (MEI, right), and heart-rate (HR, left) response(s) to exercise; β-adrenoceptor blockade blunted the MEI response to exercise. SMT, submaximal exercise test.

Figure 5

Representative (top) and overall/mean (bottom) myocardial electrical impedance (MEI) response to direct β-adrenoceptor stimulation at rest (via escalating-dose infusion of isoproterenol), showing dose-dependent MEI decrease.

Figure 6

Comparative myocardial electrical impedance (MEI) response to either submaximal exercise (white) or acute rate-matched ventricular pacing (black); only exercise decreased MEI.

Figure 7

Effects of underlying arrhythmic susceptibility of each animal in the myocardial electrical impedance (MEI) response to exercise; animals prone to ischemia-induced VF (i.e., S; n = 12) had a significantly larger MEI response to submaximal exercise, when compared those that were resistant (i.e., R; n = 9).