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Bell JR, Curl CL, Harding TW, et al. Male and female hypertrophic rat cardiac myocyte functional responses to ischemic stress and β-adrenergic challenge are different. Biol Sex Differ. 2016;7:32doi: 10.1186/s13293-016-0084-8.
Bell, J. R., Curl, C. L., Harding, T. W., Vila Petroff, M., Harrap, S. B., & Delbridge, L. M. D. (2016). Male and female hypertrophic rat cardiac myocyte functional responses to ischemic stress and β-adrenergic challenge are different. Biology of sex differences, 732. https://doi.org/10.1186/s13293-016-0084-8
Bell, James R, et al. "Male and female hypertrophic rat cardiac myocyte functional responses to ischemic stress and β-adrenergic challenge are different." Biology of sex differences vol. 7 (2016): 32. doi: https://doi.org/10.1186/s13293-016-0084-8
Bell JR, Curl CL, Harding TW, Vila Petroff M, Harrap SB, Delbridge LMD. Male and female hypertrophic rat cardiac myocyte functional responses to ischemic stress and β-adrenergic challenge are different. Biol Sex Differ. 2016 Jul 07;7:32. doi: 10.1186/s13293-016-0084-8. eCollection 2016. PMID: 27390618; PMCID: PMC4936311.
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Biol Sex Differ. 2016 Jul 07;7:32. doi: 10.1186/s13293-016-0084-8. eCollection 2016.

Male and female hypertrophic rat cardiac myocyte functional responses to ischemic stress and β-adrenergic challenge are different.

Biology of sex differences

James R Bell, Claire L Curl, Tristan W Harding, Martin Vila Petroff, Stephen B Harrap, Lea M D Delbridge

Affiliations

  1. Department of Physiology, University of Melbourne, Melbourne, Victoria Australia.
  2. Centro de Investigaciones Cardiovasculares, Centro Cientifico Tecnologico La Plata, Facultad de Ciencias Medicas, Universidad Nacional de La Plata, La Plata, Argentina.
  3. Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Melbourne, Victoria 3010 Australia.

PMID: 27390618 PMCID: PMC4936311 DOI: 10.1186/s13293-016-0084-8

Abstract

BACKGROUND: Cardiac hypertrophy is the most potent cardiovascular risk factor after age, and relative mortality risk linked with cardiac hypertrophy is greater in women. Ischemic heart disease is the most common form of cardiovascular pathology for both men and women, yet significant differences in incidence and outcomes exist between the sexes. Cardiac hypertrophy and ischemia are frequently occurring dual pathologies. Whether the cellular (cardiomyocyte) mechanisms underlying myocardial damage differ in women and men remains to be determined. In this study, utilizing an in vitro experimental approach, our goal was to examine the proposition that responses of male/female cardiomyocytes to ischemic (and adrenergic) stress may be differentially modulated by the presence of pre-existing cardiac hypertrophy.

METHODS: We used a novel normotensive custom-derived hypertrophic heart rat (HHR; vs control strain normal heart rat (NHR)). Cardiomyocyte morphologic and electromechanical functional studies were performed using microfluorimetric techniques involving simulated ischemia/reperfusion protocols.

RESULTS: HHR females exhibited pronounced cardiac/cardiomyocyte enlargement, equivalent to males. Under basal conditions, a lower twitch amplitude in female myocytes was prominent in normal but not in hypertrophic myocytes. The cardiomyocyte Ca(2+) responses to β-adrenergic challenge differed in hypertrophic male and female cardiomyocytes, with the accentuated response in males abrogated in females-even while contractile responses were similar. In simulated ischemia, a marked and selective elevation of end-ischemia Ca(2+) in normal female myocytes was completely suppressed in hypertrophic female myocytes-even though all groups demonstrated similar shifts in myocyte contractile performance. After 30 min of simulated reperfusion, the Ca(2+) desensitization characterizing the male response was distinctively absent in female cardiomyocytes.

CONCLUSIONS: Our data demonstrate that cardiac hypertrophy produces dramatically different basal and stress-induced pathophenotypes in female- and male-origin cardiomyocytes. The lower Ca(2+) operational status characteristic of female (vs male) cardiomyocytes comprising normal hearts is not exhibited by myocytes of hypertrophic hearts. After ischemia/reperfusion, availability of activator Ca(2+) is suppressed in female hypertrophic myocytes, whereas sensitivity to Ca(2+) is blunted in male hypertrophic myocytes. These findings demonstrate that selective intervention strategies should be pursued to optimize post-ischemic electromechanical support for male and female hypertrophic hearts.

Keywords: Cardiac hypertrophy; Cardiomyocyte; Ischemia/reperfusion; Sex/gender; Stress response

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