Prolonged dipyridamole administration reduces myocardial perfusion defects in experimental chronic Chagas cardiomyopathy.

BACKGROUND: Myocardial perfusion defects (MPD) due to coronary microvascular dysfunction is frequent in chronic Chagas cardiomyopathy (CCC) and may be involved with development of myocardial damage. We investigated whether MPD precedes left ventricular systolic dysfunction and tested the hypothesis that prolonged use of dipyridamole (DIPY) could reduce MPD in an experimental model of CCC in hamsters. METHODS AND RESULTS: We investigated female hamsters 6-months after T. cruzi infection (baseline condition) and control animals, divided into T. cruzi-infected animals treated with DIPY (CH + DIPY) or placebo (CH + PLB); and uninfected animals treated with DIPY (CO + DIPY) or placebo (CO + PLB). The animals were submitted to echocardiogram and rest SPECT-Sestamibi-Tc99m myocardial perfusion scintigraphy. Next, the animals were treated with DIPY (4 mg/kg bid, intraperitoneal) or saline for 30 days, and reevaluated with the same imaging methods. At baseline, the CH + PLB and CH + DIPY groups showed larger areas of perfusion defect (13.2 ± 13.2% and 17.3 ± 13.2%, respectively) compared with CO + PLB and CO + DIPY (3.8 ± 2.2% e 3.5 ± 2.7%, respectively), P < .05. After treatment, we observed: reduction of perfusion defects only in the CH + DIPY group (17.3 ± 13.2% to 6.8 ± 7.6%, P = .001) and reduction of LVEF in CH + DIPY and CH + PLB groups (from 65.3 ± 9.0% to 53.6 ± 6.9% and from 69.3 ± 5.0% to 54.4 ± 8.6%, respectively, P < .001). Quantitative histology revealed greater extents of inflammation and interstitial fibrosis in both Chagas groups, compared with control group (P < .001), but no difference between Chagas groups (P > .05). CONCLUSIONS: The prolonged use of DIPY in this experimental model of CCC has reduced the rest myocardial perfusion defects, supporting the notion that those areas correspond to viable hypoperfused myocardium.

Pilot study testing the effect of physical training over the myocardial perfusion and quality of life in patients with primary microvascular angina.

BACKGROUND: Primary microvascular angina (PMA) is a common clinical condition associated to negative impact on quality of life (QOL) and reduced physical capacity. This study aimed at evaluating the effects of aerobic physical training (APT) on myocardial perfusion, physical capacity, and QOL in patients with PMA. METHODS: We investigated 12 patients (53.8 ± 9.7 years old; 7 women) with PMA, characterized by angina, angiographycally normal coronary arteries, and reversible perfusion defects (RPDs) detected on (99m)Tc-sestamibi-SPECT myocardial perfusion scintigraphy (MPS). At baseline and after 4 month of APT, the patients underwent MPS, cardiopulmonary test, and QOL questionnaire. Stress-rest MPS images were visually analyzed by attributing semi-quantitative scores (0 = normal; 4 = absent uptake), using a 17-segment left ventricular model. Summed stress, rest, and difference scores (SDS) were calculated. RESULTS: In comparison to the baseline, in the post-training we observed a significant increase in peak-VO2 (19.4 ± 4.8 and 22.1 ± 6.2 mL·kg(-1)·minute(-1), respectively, P = .01), reduction of SDS (10.1 ± 8.8 and 2.8 ± 4.9, P = .008), and improvement in QOL scores. CONCLUSIONS: Physical training in patients with PMA is associated with reduction of myocardial perfusion abnormalities, increasing of physical capacity, and improvement in QOL. The findings of this hypothesis-generating study suggest that APT can be a valid therapeutic option for patients with PMA.

Histopathological Correlates of Global and Segmental Left Ventricular Systolic Dysfunction in Experimental Chronic Chagas Cardiomyopathy.

BACKGROUND: Chronic Chagas cardiomyopathy in humans is characterized by segmental left ventricular wall motion abnormalities (WMA), mainly in the early stages of disease. This study aimed at investigating the detection of WMA and its correlation with the underlying histopathological changes in a chronic Chagas cardiomyopathy model in hamsters. METHODS AND RESULTS: Female Syrian hamsters (n=34) infected with 3.5×10(4) or 10(5) blood trypomastigote Trypanosoma cruzi (Y strain) forms and an uninfected control group (n=7) were investigated. After 6 or 10 months after the infection, the animals were submitted to in vivo evaluation of global and segmental left ventricular systolic function by echocardiography, followed by euthanasia and histological analysis for quantitative assessment of fibrosis and inflammation with tissue sampling in locations coinciding with the left ventricular wall segmentation employed at the in vivo echocardiographic evaluation. Ten of the 34 infected animals (29%) showed reduced left ventricular ejection fraction (<73%). Left ventricular ejection fraction was more negatively correlated with the intensity of inflammation (r=-0.63; P<0.0001) than with the extent of fibrosis (r=-0.36; P=0.036). Among the 24 animals with preserved left ventricular ejection fraction (82.9±5.5%), 8 (33%) showed segmental WMA predominating in the apical, inferior, and posterolateral segments. The segments exhibiting WMA, in comparison to those with normal wall motion, showed a greater extent of fibrosis (9.3±5.7% and 7±6.3%, P<0.0001) and an even greater intensity of inflammation (218.0±111.6 and 124.5±84.8 nuclei/mm², P<0.0001). CONCLUSIONS: Isolated WMA with preserved global systolic left ventricular function is frequently found in Syrian hamsters with experimental chronic Chagas cardiomyopathy whose underlying histopathological features are mainly inflammatory.

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

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.

Contribution of cardiopulmonary exercise testing to the identification of latent systolic dysfunction in chronic aortic regurgitation.

Chronic aortic regurgitation (AR) is a valvulopathy of slow and insidious evolution, and patients may remain asymptomatic for a long period of time. Exercise-induced systolic dysfunction occurs during the natural history of chronic AR and is related to changes in both preload and afterload. We describe the case of a 58-year-old woman with a diagnosis of chronic AR who reported progressive dyspnea of six years' duration. A cardiopulmonary exercise test to assess functional capacity showed flattening of both oxygen uptake and oxygen pulse curves, suggesting latent systolic dysfunction related to chronic AR, which was later confirmed by stress Doppler echocardiogram with dynamic physical exercise.