Effects of cholinergic stimulation with pyridostigmine bromide on chronic chagasic cardiomyopathic mice

The aim of the present study was to assess the effects of an anticholinesterase agent, pyridostigmine bromide (Pyrido), on experimental chronic Chagas heart disease in mice. To this end, male C57BL/6J mice noninfected (control:Con) or chronically infected (5 months) with Trypanosoma cruzi (chagasic:Chg) were treated or not (NT) with Pyrido for one month. At the end of this period, electrocardiogram (ECG); cardiac autonomic function; heart histopathology; serum cytokines; and the presence of blood and tissue parasites by means of immunohistochemistry and PCR were assessed. In NT-Chg mice, significant changes in the electrocardiographic, autonomic, and cardiac histopathological profiles were observed confirming a chronic inflammatory response. Treatment with Pyrido in Chagasic mice caused a significant reduction of myocardial inflammatory infiltration, fibrosis, and hypertrophy, which was accompanied by a decrease in serum levels of IFN\u3b3 with no change in IL-10 levels, suggesting a shift of immune response toward an anti-inflammatory profile. Lower nondifferent numbers of parasite DNA copies were observed in both treated and nontreated chagasic mice. In conclusion, our findings confirm the marked neuroimmunomodulatory role played by the parasympathetic autonomic nervous system in the evolution of the inflammatory-immune response to T. cruzi during experimental chronic Chagas heart disease in mice

Effects of long-term angiotensin converting enzyme inhibition on cardiovascular variability in aging rats

We studied the effects of chronic (4 weeks) angiotensin converting enzyme inhibition with captopril on arterial pressure (AP) and heart rate (HR) variability, as well as on cardiac baroreflex sensitivity (BRS), in aged (20 months) rats. Series of basal RR interval (RRi) and systolic AP (SAP) were Studied by autoregressive spectral analysis with oscillations quantified in low (LF: 0.2-0.8 Hz) and high frequency (HF: 0.8-2.5 Hz). BRS was measured by linear regression between HR and MAP changes. Captopril did not affect the spectra of RRi or SAP in young rats. Aged rats presented a reduction in variance (time domain) and in LF and HF oscillations of RRi and SAP. Captopril induced, in aged rats, a decrease in absolute and normalized LF oscillations and in LF/HF ratio of RRi. Captopril also reduced the variance, without changing its LF or HIP components of SAP. Reflex tachycardia was reduced in aged as compared to young rats (-1.1 +/- 0.2 versus -3.4 +/- 0.5 bpm/mm Hg) and captopril did not affect it. Reflex bradycardia was also reduced in aged rats (-0.7 +/- 0.5 versus -2.0 +/- 0.4 bpm/mm Hg), but captopril prevented this attenuation in aged rats (-2.3 +/- 0.3 versus -0.7 +/- 0.5 bpm/mm Hg). These data indicate that there is a reduction in HR and SAP variability during aging, suggesting impairment of cardiovascular autonomic control. Captopril was able to change the power of oscillatory components of RRi, Suggesting a shift in cardiac sympatho/vagal balance toward parasympathetic predominance. In addition, blockage of ACE improved the reflex bradycardia, but not the reflex tachycardia in aged rats

Intravenous amiodarone modifies autonomic balance and increases baroreflex sensitivity in conscious rats

Amiodarone is an antiarrhythmic agent commonly used to treat cardiac arrhythmias. This study was designed to investigate the effects of intravenous amiodarone on the neural control of heart rate and arterial pressure and spontaneous baroreflex sensitivity (BRS). Experiments were carried out on conscious freely moving normotensive Wistar (WR) and spontaneously hypertensive rats (SHR). Arterial pressure was continuously monitored before and after amiodarone (50 mg/kg i.v.) or vehicle for 30 min. Heart rate (expressed as the pulse interval, PI) and systolic arterial pressure (SAP) variabilities were assessed using autoregressive spectral analysis. BRS was calculated as the alpha-index (the square root of the ratio between the PI and SAP powers). Amiodarone induced bradycardia and hypotension in both strains, with these effects being more intense in SHR. The variability profile of PI was characterized by a significant reduction of normalized low frequency (LF) and LF/HF ratio, while the high frequency (HF) component both in absolute and normalized units (nu) was increased in both WR and SHR strains. A significant decrease in SAP variance and its LF oscillation was observed. In addition, BRS was also increased in both groups, being more intense in SHR. In both WR and SHR, intravenous amiodarone had a considerable effect on heart rate variabilities (HRV), shifting cardiac sympathovagal balance toward a sympathetic inhibition and/or vagal activation, which were associated with an increase in spontaneous BRS. Decreases of SAP variance and LF(SAP) suggest sympatholytic effects on peripheral vessels. Besides the direct ion channel effects, these changes in the autonomic balance could contribute to the antiarrhythmic action of the intravenous amiodarone

Biological properties of cardiac mesenchymal stem cells in rats with diabetic cardiomyopathy

Cardiomyopathy is a major outcome in patients with diabetes mellitus (DM) and contributes to the high morbidity/mortality observed in this disease. AIMS: To evaluate several biological properties of cardiac mesenchymal stem cells (cMSCs) in a rat model of streptozotocin-induced DM with concomitant diabetic cardiomyopathy. MAIN METHODS: After 10weeks of DM induction, diabetic and control rats were assessed using ECG and ventricular hemodynamics monitoring. Then, the hearts were excised and processed for histology and for extracting non-cardiomyocytic cells. A pool of these cells was plated for a colony forming units-fibroblasts (CFU-F) assay in order to estimate the number of cMSCs. The remaining cells were expanded to assess their proliferation rate as well as their osteogenic and adipogenic differentiation ability. KEY FINDINGS: DM rats presented intense hyperglycemia and changes in ECG, LV hemodynamic, cardiac mass index and fibrosis, indicating presence of DCM. The CFU-F assay revealed a higher number of cardiac CFU-Fs in DM rats (10.4\ub11.1CFU-F/105 total cells versus 7.6\ub10.7CFU-F/105 total cells in control rats, p<0.05), which was associated with a significantly higher proliferative rate of cMSCs in DM rats. In contrast, cMSCs from DM rats presented a lower capacity to differentiate into both osteogenic (20.8\ub14.2% versus 10.1\ub11.0% in control rats, p<0.05) and adipogenic lineages (4.6\ub11.0% versus 1.3\ub10.5% in control rats, p<0.05). SIGNIFICANCE: The findings suggest, for the first time, that in chronic DM rats with overt DCM, cMSCs increase in number and exhibit changes in several functional properties, which could be implicated in the pathogenesis of diabetic cardiomyopathy