Key result
Pacing acceleration plus isoproterenol shortens ventricular action potential duration by up to ~31%.
Why the study?
Understanding of ventricular action potential adaptation to physiological stress is generally based on non-physiological rates and conditions isolating rate effects from escalating adrenergic stimulation.
Does varying physiological pacing frequency and adding isoproterenol shorten action potential duration in isolated rat ventricular myocytes?
Does varying physiological pacing frequency and adding isoproterenol shorten action potential duration in isolated rat ventricular myocytes?
Changes in action potential plateau and late repolarization predominantly underlie simulated exercise responses in the rat heart, providing novel reference data for computational modeling.
Findings from rat myocytes should not yet inform clinical practice; extends modeling data while leaving open human translation.
PURPOSE: Current understanding of ventricular action potential adaptation to physiological stress is generally based on protocols using non-physiological rates and conditions isolating rate effects from escalating adrenergic stimulation. To permit refined understanding, ventricular action potentials were assessed across physiological pacing frequencies in the presence and absence of adrenergic stimuli. Isolated and combined effects were analyzed to assess their ability to replicate in-vivo responses. METHODS: ) was compared before and after 5 nM, 100 nM and 1 µM isoproterenol doses. RESULTS: (29%). CONCLUSION: These results demonstrate modest action potential shortening in response to adrenergic stimulation and elevations in pacing beyond physiological resting rates. Our findings indicate changes in action potential plateau and late repolarization predominantly underlie simulated exercise responses in the rat heart. This work provides novel action potential reference data and will help model cardiac responses to physiological stimuli in the rat heart via computational techniques.
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Howlett et al. (2022) studied this question. Isoproterenol and varying physiological pacing frequencies vs. Control (absence of isoproterenol and 1 Hz pacing) was evaluated on Action potential duration (APD 50-100). Increases in pacing frequency to mimic exercise, alongside adrenergic stimulation by isoproterenol, induced modest action potential shortening (16-31%) in rat ventricular myocytes.
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