Sex-related changes in cardiac function following myocardial infarction in mice

Abstract

Shioura KM, Geenen DL, Goldspink PH. Sex-related changes in cardiac function following myocardial infarction in mice. Am J Physiol Regul Integr Comp Physiol 295: R528 -R534, 2008. First published June 11, 2008 doi:10.1152/ajpregu.90342.2008.-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 ϭ 48.7 Ϯ 8.0 vs. male ϭ 25.2 Ϯ 1.8 mmHg, P Ͻ 0.05) and maximum dP/dt vs. maximum end-diastolic volume (10 wk post-MI, femaleϭ359 Ϯ 58 vs. maleϭ149 Ϯ 28 mmHg ⅐ s Ϫ1 ⅐ l Ϫ1 , P Ͻ 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. contractility; pressure-volume loops DAMAGE TO THE MYOCARDIUM FOLLOWING myocardial infarction (MI) is associated with compensatory responses such as left ventricular (LV) hypertrophy and activation of the sympathetic nervous system to maintain cardiac output. Eventually, these changes are inadequate and contractile dysfunction along with subsequent chamber dilation underlie the transition to heart failure (HF) (11, 32).There are known sex-related responses to ischemia following myocardial infarction (MI) ranging from symptoms, diagnoses, preventions, courses of disease and outcomes of existing therapies. Women have more diverse symptoms than men, which are the major causes for delayed diagnoses and treatments (18,29,37). Also, women have poorer outcomes for a number of clinical complications such as a non-Q wave MI and invasive percutaneous transluminal coronary angioplasty (16,25). Despite these sex differences in incidence, manifestation and outcome, clinical data on cardiac function changes following MI are obscured by numerous baseline differences such as age, risk factors, symptoms, and the presence of coexisting disease...

Assessment of Myocardial Infarction and Postinfarction Scar Remodeling With an Elastin-Specific Magnetic Resonance Agent

“…It is known, however, that female mice undergo less extensive postinfarction scar remodeling than males, with less dilatation and preserved function. [29][30][31] Especially male mice are prone to early ventricular rupture within the first week after experimental MI. 32,33 Because our intent was to conduct serial MR imaging for several weeks after MI, we chose to use female C57BL/6J mice to minimize early animal loss.…”

Murine Cardiac Hemodynamics Following Manganese Administration Under Isoflurane Anesthesia

“…46 Cardiac hemodynamic indices include HR, SV, SW, CO, EF, P es , and dP/dt max whereas reliable indices of contractility and relaxation are (among others), [dP/ dt max ]/EDV, E a , PAMP, ESPVR, [dP/dt min ]/EDV, and s weiss , and s glantz , respectively.…”

“…HR can have a direct effect on cardiac contractility and relaxation and is a determinant of chronotropic changes (treppe phenomenon) 33,46 and of myocardial oxygen demand. 44 The minimal force-frequency inotropy modulation observed in various mouse strains (FVB, C57BL, Black Swiss) compared to human (rapid calcium cycling kinetics and SR dominance of Ca 2+ buffering), 20 in addition to the limited cardiac reserve in this species, downplay its potential role.…”

“…40,43,46 The possible dependence of ESPVR on heart size 43 is accounted for by the selection of age and weight-matched male mice studied.…”

“…In the presented studies, the closed-chest catheterization approach was utilized, which is more physiologically relevant (normal intra-thoracic pressures, no need for intubation procedures), 23,24,46 in comparison to open chest approaches, including apical stub procedures.…”