The Role Of Mineralocorticoid Receptors In The Adaptation Of Cardiac Myocytes To Pregnancy

Abstract

Ventricular fibrillation (VF) is the main cause of sudden cardiac death. We hypothesized that VF induced by large scars in an isolated porcine heart model could aid the understanding of VF in human hearts associated with structural disease. The explanted hearts were perfused with blood and Tyrode solution at 37C, and optically imaged with a voltage-sensitive fluorescence dye (di4-ANEPPS excited at 530nm with 150W halogen lamp). The emitted signal was filtered (610nm) and recorded with high speed cameras (MiCAM02, Brain-Vison, Jp) at 0.7mm spatial resolution. No optical signals could be recorded from the core of chronic infarcts or RF lesions. A total of 10 hearts were used: 4 controls, 3 with lesions generated via RF ablation and 3 with chronic infarcts. We observed the propagation of the depolarization waves and analyzed the VF waveforms at the border zone (BZ) and normal myocardium. We analyzed the VF waves in the frequency domain by calculating the dominant frequency (DF) on select regions of interest using Matlab (Mathworks, Ca). Our results showed that DF is smaller at the BZ compared to healthy tissue. Referenced to the average DF in the control hearts (10.07þ/-0.54 Hz), the DF was slightly smaller in healthy myocardium of infarct hearts (i.e., 8.9þ/ -0.71Hz) and significantly smaller at the border zone (i.e., 6.03 þ/-0.86Hz). In ablated hearts, mean DF in normal myocardium was 9.16þ/-0.7Hz and 7.24þ/-0.66Hz at BZ, respectively. We suggest that these differences are related to the heterogeneous restitution properties as well as the changes in tissue structure at the BZ. The BZ of chronic scars is comprised of a mixture of viable and necrotic fibers; whereas in the acute settings of RF lesions, inflammation and edema are present at the BZ without alteration of fiber directions.

Regulation of the sodium pump during cardiomyocyte adaptation to pregnancy

“…These findings prompted our investigation of the possible contribution of the sodium pump inhibition to cardiac adaptations during pregnancy. Our previous work (Bassien-Capsa et al 2006) showed that pregnancy is characterized by a metabolic remodelling of the maternal heart and adaptations of haemodynamic and cardiac parameters, including cardiomyocyte dimensions. We demonstrated adaptive hypertrophic remodelling of the heart, as well as of its cells, during pregnancy.…”

“…Left ventricular (LV) myocytes were isolated after retrograde perfusion of the heart with proteolytic enzymes, as described previously (Chorvatova et al 2004;Bassien-Capsa et al 2006). Myocytes were maintained in storage solution at 4 • C until used.…”

“…Data are presented as means + SEM (number of cells in parentheses); * P < 0.05 versus NP. size following measurement in picofarads of capacitance current by hyperpolarizing voltage steps to −50 mV from a holding potential of −40 mV (Bassien-Capsa et al 2006). To evaluate the sodium pump current, we applied an experimental protocol inspired by Gao et al (1995), in which rapid changes in [K + ] o from 0.5 to 5.4 mM in the presence of elevated [Na + ] i were used to identify the pump current.…”