Sex-related changes in cardiac function following myocardial infarction in mice
Krystyna M Shioura1, David L Geenen, Paul H Goldspink
1University of Illinois at Chicago, Department of Medicine/Section of Cardiology, 840 S. Wood St., M/C 715 Chicago, IL 60612, USA.
Insights
Female mice show improved cardiac contractility and delayed heart failure after myocardial infarction, unlike male mice. This highlights sex differences in cardiovascular disease progression and compensatory mechanisms.
Area of Science:
- Cardiovascular Biology
- Sex Differences in Disease
- Heart Failure Pathophysiology
Background:
- Cardiovascular diseases are a leading cause of death in middle-aged women.
- Understanding sex-based differences in heart failure (HF) is crucial for targeted therapies.
Purpose of the Study:
- To investigate sex-specific cardiac functional changes following myocardial infarction (MI) in mice.
- To compare the progression of heart failure between female and male mice.
Main Methods:
- Utilized the Millar pressure-volume (P-V) conductance system in vivo.
- Evaluated cardiac function at 2, 4, and 10 weeks post-MI in female and male mice.
- Assessed load-dependent and independent hemodynamic measurements.
Main Results:
- Both sexes showed initial hemodynamic deterioration post-MI.
- Female mice exhibited normalized volumes during compensatory hypertrophy compared to males.
- Females demonstrated significantly improved cardiac contractility during decompensation to HF compared to males.
- No sex differences were observed in heart weight-to-body weight ratio or infarct size.
Conclusions:
- Female compensatory hypertrophy is associated with improved contractility and delayed heart failure progression.
- Male compensatory hypertrophy appears compromised by declining contractility leading to heart failure.
- These findings underscore critical sex differences in heart failure development and response to injury.
Abstract:
Recent awareness of cardiovascular diseases as a number one killer of the middle-aged women has prompted interest in sex differences leading to heart failure (HF). Therefore, we evaluated cardiac function in female and male mice following myocardial infarction (MI) using the Millar pressure-volume (P-V) conductance system in vivo, at time points corresponding to early (2 wk), late compensatory hypertrophy (4 wk), and decompensation (10 wk) to HF. A significant deterioration of the load dependent and independent hemodynamic measurements occurred in both female and male mice during the early phase of hypertrophy. Later, compensatory hypertrophy was marked by a normalization of volumes to control levels in females compared with males. The most notable differences between sexes occurred in the measurements of cardiac contractility during the decompensation to HF. In females, there was a significant improvement in contractility compared with males, which was apparent in the load-independent measurements of preload recruitable stroke work (10 wk post-MI, female=48.7+/-8.0 vs. male=25.2+/-1.8 mmHg, P<0.05) and maximum dP/dt vs. maximum end-diastolic volume (10 wk post-MI, female=359+/-58 vs. male=149+/-28 mmHg.s(-1).microl(-1), P<0.05). Despite these differences, there were no differences in the heart weight to body weight ratio and infarct size between the sexes. These data demonstrate that compensatory hypertrophy is associated with an improvement in contractility and a delayed decompensation to HF in females. However, compensatory hypertrophy in males appears to be undermined by a steady decline in contractility associated with decompensation to HF.
