Mihály Ruppert1, Tamás Radovits1, Sevil Korkmaz-Icöz2, Sivakkanan Loganathan2, Weipeng Jiang2, Lorenz Lehmann3, Attila Oláh1, Alex Ali Sayour1, Bálint András Barta1, Béla Merkely1, Matthias Karck2, Gábor Szabó2
1Heart and Vascular Center, Semmelweis University, Budapest, Hungary
2Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
3Department of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany
Aims: Gender differences in pressure-overload (PO) induced left ventricular (LV) myocardial hypertrophy (LVH) have been intensely investigated. Nevertheless, gender-related disparities in LV function were not assessed by pressure-volume (P-V) analysis. Therefore, we aimed to provide a detailed characterization of LV hemodynamics during different stages of LVH in male and female rats.
Methods: Banding of the abdominal aorta (AB) was performed to induce PO for 6 or 12 weeks in male (M) and female (F) rats. Control animals underwent sham operation. The development of LVH was followed by serial echocardiography. Cardiac function was assessed by P-V analysis. Cardiomyocyte hypertrophy and fibrosis were evaluated by histology.
Results: At week 6, an adaptive form of LVH developed in both genders with marked myocardial hypertrophy (increased LV mass index, heart weight-to-tibial length, cardiomyocyte diameter), concentric LV geometry and interstitial fibrosis. Functionally, at this time point, impaired active relaxation, increased cardiac contractility and improved LV mechano-energetics were observed in male and female AB rats as well. In contrast, at week 12 structural and functional deterioration of LVH could be observed in male but not in female animals with sustained PO. Accordingly, at this later stage, LVH was associated with eccentric remodeling and further intensified collagen accumulation in male AB rats. On the functional level, augmented cardiac contractility declined in male (slope of end-systolic P-V relationship: 1.31±0.17 Sham-12wk-M vs. 1.59±0.12 AB-12wk-M n.s.; 2.08±0.17 Sham-12wk-F vs. 3.97±0.50 AB-12wk-F p<0.05) but not in female AB animals, resulting in impaired LV mechano-energetics only among males (ventricular-arterial coupling: 0.36±0.03 AB-6wk-M vs. 0.84±0.12 AB-12wk-M p<0.05; 0.35±0.05 AB-6wk-F vs. 0.39±0.06 AB-12wk-F n.s.).
Conclusion: Maintenance of contractility augmentation and preserved mechano-energetics in female rats contribute to gender differences in LV function during the development of PO-induced LVH.
Doctoral School: Basic and Translational Medicine
Program: Cardiovascular Disorders: Physiology and Medicine of Ischaemic Circulatory Diseases
Supervisor: Tamás Radovits
E-mail address: firstname.lastname@example.org