Mesenchymal Stem Cells Improve Heart Rate Variability and Baroreflex Sensitivity in Rats with Chronic Heart Failure

Abstract

Heart failure induced by myocardial infarct (MI) attenuates the heart rate variability (HRV) and baroreflex sensitivity, which are important risk factors for life-threatening cardiovascular events. Therapies with mesenchymal stem cells (MSCs) have shown promising results after MI. However, the effects of MSCs on hemodynamic (heart rate and arterial pressure) variability and baroreflex sensitivity in chronic heart failure (CHF) following MI have not been evaluated thus far. Male Wistar rats received MSCs or saline solution intravenously 1 week after ligation of the left coronary artery. Control (noninfarcted) rats were also evaluated. MI size was assessed using single-photon emission computed tomography (SPECT). The left ventricular ejection fraction (LVEF) was evaluated using radionuclide ventriculography. Four weeks after MSC injection, the animals were anesthetized and instrumented for chronic ECG recording and catheters were implanted in the femoral artery to record arterial pressure. Arterial pressure and HRVs were determined in time and frequency domain (spectral analysis) while HRV was also examined using nonlinear methods: DFA (detrended fluctuation analysis) and sample entropy. The initial MI size was the same among all infarcted rats but was reduced by MSCs. CHF rats exhibited increased myocardial interstitial collagen and sample entropy combined with the attenuation of the following cardiocirculatory parameters: DFA indices, LVEF, baroreflex sensitivity, and HRV. Nevertheless, MSCs hampered all these alterations, except the LVEF reduction. Therefore, 4 weeks after MSC therapy was applied to CHF rats, MI size and myocardial interstitial fibrosis decreased, while baroreflex sensitivity and HRV improved.

Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model

“…The time of paMSC transplant also influences effectiveness; the optimal range varies from the time of AMI to 1 week later, although a specific suitable time point remains to be established [ 68 ]. Beneficial effects have been reported following in vivo transfer of modified MSC or recombinant factors from 1 week to 1 month post-infarct induction.…”

Regional Myocardial Perfusion Disturbance in Experimental Chronic Chagas Cardiomyopathy

“…Radiotracer accumulation in the myocardium was analyzed semiquantitatively using polar maps (21). Hypoperfusion was defined as less than 50% uptake compared with the maximum.…”

The implication of protein malnutrition on cardiovascular control systems in rats

“…Furthermore, data from our group indicated that cardiovascular reflexes are impaired by protein dietary restriction, see below (Tropia et al, 2001 ; Loss et al, 2007 ; Penitente et al, 2007 ; Bezerra et al, 2011a ). Since cardiovascular reflexes are required to modulate MAP and HR (Morais et al, 2015 ), defective cardiovascular reflex sensitivity is correlated to abnormal variability of these parameters (Oliveira et al, 2004 ). Studies have also indicated that the risk to cardiovascular complications may depend on BP increase, as well as changes in MAP and HR variabilities (Shaffer et al, 2014 ; Parati et al, 2015 ).…”