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Cardiac Hypertrophy and Myocyte Remodeling Are Exacerbated with Multiple Pregnancies
Author(s) -
Wagner Marcus,
Nelson Aaron,
Flake Caela,
Eaton Deborah,
Bailey Beth A
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.688.7
Subject(s) - pregnancy , muscle hypertrophy , medicine , hemodynamics , endocrinology , cardiology , myocyte , biology , genetics
Background The female heart is adapted to support the hemodynamic load of pregnancy; it hypertrophies during pregnancy then returns to its pre‐pregnancy size relatively soon after delivery. This cardiac hypertrophy has generally been categorized as physiologic hypertrophy similar to that seen with exercise, however a reduction in cardiac function in late pregnancy has been suggested. In addition, the hemodynamic stress of pregnancy can induce a maladaptive, pathologic hypertrophy in a small number of women, and multiparity is thought to increase the risk for this maladaptive response. Because prolonged, persistent hemodynamic stress is associated with the development of pathological hypertrophy, multiple pregnancies may exacerbate any contractile changes seen in a single pregnancy. This study seeks to characterize the contractile properties of the pregnant myocardium during the first versus the third pregnancy. Methods and Results Late Pregnancy (LP) Female Swiss‐Webster mice were bred then studied at near term (Embryonic day 17–19). Multi‐pregnant mice (MP) were bred two times and allowed to wean each litter for 3 weeks then bred a third time and studied at embryonic day 17–19. LP and MP were compared to age‐matched, non‐pregnant (NP) controls. Significant cardiac hypertrophy occurred in LP vs NP (253 ± 7mg vs 216 ± 9mg, p<.05), and MP hearts were significantly larger than both LP and NP (339 ±18 mg, p<.01). Individual cardiac myocytes were isolated using collagenase‐based perfusion technique. Sarcomere length (light diffraction) and Ca 2+ transients (fluo‐3) were measured at pacing rates of 1 Hz and at bath [Ca] of 1.5mM. Duration of twitch contraction was prolonged (p<.05) in MPM as measured by Time to 75% Recovery (.62 ± .05 vs .43 ± .04 sec in NPM). While twitch duration was prolonged in LPM (.53 ± .04 sec), the difference did not reach significance. Interestingly, the duration of the fluo‐3 calcium transients were similar in LPM (.24 ± .01 sec) and NPM (.25 ± .02 sec), but the MPM calcium transient duration (.34 ± .03 sec) was significantly prolonged (p<.05) compared to both NPM and LPM. There were no differences in other contractile parameters measured or in the fluo‐3 calcium transient properties. 10 −7 M Isoproterenol (ISO) was used to determine the responsiveness to adrenergic stimulation. ISO induced significantly enhanced contractility in NPM, LPM, and MPM, and the response was heightened in LPM and MPM such that the presence of ISO normalized the differences in the durations of twitch contractions between NPM, LPM, and MPM. Conclusions These results suggest that the cardiac hypertrophic response to pregnancy and subsequent alterations in contractile duration are exacerbated after multiple pregnancies. Enhanced response to ISO normalizes the contractile differences and suggests and increased cardiac reserve in LPM and MPM. Support or Funding Information Howard Hughes Medical Institute American Physiological Society