Journal article
Atrial-paced, exercise-similar heart rate envelope induces myocardial protection from ischaemic injury
Europace (London, England), Vol.24(6), pp.1025-1035
06/2022
DOI: 10.1093/europace/euab273
PMCID: PMC9282913
PMID: 34792112
Abstract
Aims The study investigates the role and mechanisms of clinically translatable exercise heart rate (HR) envelope effects, without dyssynchrony, on myocardial ischaemia tolerance compared to standard preconditioning methods. Since the magnitude and duration of exercise HR acceleration are tightly correlated with beneficial cardiac outcomes, it is hypothesized that a paced exercise-similar HR envelope, delivered in a maximally physiologic way that avoids the toxic effects of chamber dyssynchrony, may be more than simply a readout, but rather also a significant trigger of myocardial conditioning and stress resistance. Methods and results For 8 days over 2 weeks, sedated mice were atrial-paced once daily via an oesophageal electrode to deliver an exercise-similar HR pattern with preserved atrioventricular and interventricular synchrony. Effects on cardiac calcium handling, protein expression/modification, and tolerance to ischaemia-reperfusion (IR) injury were assessed and compared to those in sham-paced mice and to the effects of exercise and ischaemic preconditioning (IPC). The paced cohort displayed improved myocardial IR injury tolerance vs. sham controls with an effect size similar to that afforded by treadmill exercise or IPC. Hearts from paced mice displayed changes in Ca2+ handling, coupled with changes in phosphorylation of calcium/calmodulin protein kinase II, phospholamban and ryanodine receptor channel, and transcriptional remodelling associated with a cardioprotective paradigm. Conclusions The HR pattern of exercise, delivered by atrial pacing that preserves intracardiac synchrony, induces cardiac conditioning and enhances ischaemic stress resistance. This identifies the HR pattern as a signal for conditioning and suggests the potential to repurpose atrial pacing for cardioprotection.
Details
- Title: Subtitle
- Atrial-paced, exercise-similar heart rate envelope induces myocardial protection from ischaemic injury
- Creators
- Zhiyong Zhu - University of IowaZhan Gao - University of IowaBiyi Chen - University of IowaDuane D. Hall - University of IowaRachel Minerath - University of IowaOlha Koval - University of IowaAna Sierra - University of IowaEkaterina Subbotina - University of IowaXiaoyi Zhu - University of IowaYoung-Rae Kim - University of IowaJun Yang - University of IowaIsabella Grumbach - University of IowaKaikobad Irani - University of IowaChad Grueter - University of IowaLong-Sheng Song - University of IowaDenice M. Hodgson-Zingman - University of IowaLeonid Zingman - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Europace (London, England), Vol.24(6), pp.1025-1035
- DOI
- 10.1093/europace/euab273
- PMID
- 34792112
- PMCID
- PMC9282913
- NLM abbreviation
- Europace
- ISSN
- 1099-5129
- eISSN
- 1532-2092
- Publisher
- Oxford Univ Press
- Number of pages
- 11
- Grant note
- Carver Trust (Medical Research Initiative Grant) HL144199; HL113089; HL108932; DK092412 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA I01BX000163; 1I0BX004840 / Veterans Affairs Merit Review Program; US Department of Veterans Affairs
- Language
- English
- Electronic publication date
- 11/18/2021
- Date published
- 06/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Radiation Oncology; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984288719702771
Metrics
21 Record Views