Análise quantitativa das lesões cardíacas na cardiomiopatia chagásica crônica canina

Lesions observed in chronic chagasic cardiopathy frequently produce electrocardiographic alterations and affect cardiac function. Through a computerized morphometrical analysis we quantified the areas occupied by cardiac muscle, connective and adipose tissues in the right atrium of dogs experimentally infected with Trypanosoma cruzi. All of the infected dogs showed chronic myocarditis with variable reduction levels of cardiac muscle, fibrosis and adipose tissue replacement. In the atrial myocardium of dogs infected with Be78 and Be62 cardiac muscle represented 34 and 50%, fibrosis 28 and 32% and adipose tissue 38 and 18%, respectively. The fibrosis observed was both diffuse and focal and mostly intrafascicular, either partially or completely interrupting the path of muscle bundles. Such histological alterations probably contributed to the appearance of electrocardiographic disturbances verified in 10 out 11 dogs which are also common in human chronic chagasic cardiopathy. Fibrosis was the most important microscopic occurrence found since it produces rearrangements of collagen fibers in relation to myocardiocytes which causes changes in anatomical physiognomy and mechanical behavior of the myocardium. These abnormalities can contribute to the appearance of cardiac malfunction, arrythmias and congestive cardiac insufficiency as observed in two of the analyzed dogs. Strain Be78 caused destruction of atrial cardiac muscle higher than that induced by strain Be62.As lesões observadas na cardiopatia chagásica crônica frequentemente produzem alterações eletrocardiográficas e afetam a função cardíaca. Através de uma análise morfométrica computadorizada nós quantificamos as áreas ocupadas por músculo cardíaco, tecido conjuntivo fibroso e tecido adiposo no átrio direito de cães experimentalmente infectados pelo Trypanosoma cruzi. Todos os cães infectados apresentaram miocardite crônica fibrosante com graus variáveis de redução de músculo cardíaco, fibrose e substituição por tecido adiposo. No miocárdio atrial dos cães infectados pelas cepas Be78 e Be62 foram observados 34 e 50% de músculo cardíaco, 28 e 32% de fibrose e, 38 e 18% de tecido adiposo, respectivamente. A fibrose observada era tanto difusa quanto focal e, principalmente intrafascicular interrompendo total ou parcialmente o percurso dos feixes musculares. Tais alterações histológicas provavelmente contribuiram para o surgimento dos distúrbios eletrocardiográficos verificados em 10 dos 11 cães estudados e que são comuns na cardiopatia chagásica crônica humana. De todos os achados microscópicos encontrados, a fibrose foi a mais importante por produzir rearranjos na fibras colágenas em relação aos miocardiócitos, modificando a fisionomia anatômica e o comportamento mecânico do miocárdio. Tais anormalidades estruturais podem contribuir para o surgimento à disfunção cardíaca, arritmias e à insuficiência cardíaca congestiva como verificado em dois cães analisados. A cepa Be78 produziu uma destruição de músculo cardíaco atrial estatisticamente superior à induzida pela cepa Be62

Quantitative analysis of cardiac lesions in chronic canine chagasic cardiomyopathy.

Lesions observed in chronic chagasic cardiopathy frequently produce electrocardiographic alterations and affect cardiac function. Through a computerized morphometrical analysis we quantified the areas occupied by cardiac muscle, connective and adipose tissues in the right atrium of dogs experimentally infected with Trypanosoma cruzi. All of the infected dogs showed chronic myocarditis with variable reduction levels of cardiac muscle, fibrosis and adipose tissue replacement. In the atrial myocardium of dogs infected with Be78 and Be62 cardiac muscle represented 34 and 50%, fibrosis 28 and 32% and adipose tissue 38 and 18%, respectively. The fibrosis observed was both diffuse and focal and mostly intrafascicular, either partially or completely interrupting the path of muscle bundles. Such histological alterations probably contributed to the appearance of electrocardiographic disturbances verified in 10 out 11 dogs which are also common in human chronic chagasic cardiopathy. Fibrosis was the most important microscopic occurrence found since it produces rearrangements of collagen fibers in relation to myocardiocytes which causes changes in anatomical physiognomy and mechanical behavior of the myocardium. These abnormalities can contribute to the appearance of cardiac malfunction, arrhythmias and congestive cardiac insufficiency as observed in two of the analyzed dogs. Strain Be78 caused destruction of atrial cardiac muscle higher than that induced by strain Be62

Renovascular hypertension increases serum TNF and CX3CL1 in experimental Trypanosoma cruzi infection.

Trypanosoma cruzi triggers a progressive inflammatory response affecting cardiovascular functions in humans and experimental models. Angiotensin II, a key effector of the renin-angiotensin system, plays roles in mediating hypertension, heart failure, and inflammatory responses. T. cruzi and AngII can induce inflammatory responses by releasing inflammatory mediators. The aim of this study was to evaluate systemic AngII, tumor necrosis factor (TNF), and CX3CL1 mediators in a two-kidney one-clip (2K1C) renovascular hypertension model using Wistar rats infected with T. cruzi. Our data showed an increase in serum AngII in uninfected and T. cruzi-infected rats 1 week after 2K1C surgery compared to non-2K1C (Sham) animals. The baseline systolic blood pressure was higher in both uninfected and infected 2K1C rats. Despite no difference in circulating parasites in the acute phase of infection, elevated serum TNF and CX3CL1 were observed at 8 weeks post-infection in 2K1C rats in association with higher cardiac inflammatory infiltration. In summary, AngII-induced hypertension associated with T. cruzi infection may act synergistically to increase TNF and CX3CL1 in the 2K1C rat model, thereby intensifying cardiac inflammatory infiltration and worsening the underlying inflammation triggered by this protozoan

Altered renal response to acute volume expansion in transgenic rats harboring the human tissue kallikrein gene.

The renal response to acute volume expansion was investigated in transgenic (TGR) rats harboring the human tissue kallikrein gene. After a primer injection of 0.9% NaCl (3 ml/100 g, i.v), Sprague–Dawley (SD) or TGR rats received a continuous infusion of 0.9% NaCl (15 Al/ 100 g/min, i.a.) through a catheter placed into the carotid artery. Acute volume expansion was produced by a second injection of 0.9% NaCl (2 ml/100 g, i.v.) 65 min after the first injection. Plasma vasopressin (AVP) and atrial natriuretic peptide (ANP) concentration was measured before and within 10 min of volume expansion. TGR animals presented a blunted response to acute volume expansion evidenced by an attenuated increase in total and fractional water and sodium excretion. Before or after volume expansion, plasma AVP and ANP did not differ between SD and TGR. Pre-treatment with the BK-B2 antagonist HOE-140 (7.5 Ag/100 g. i.a) partially improved the renal response of TGRs and severely blunted the response in SD rats. These data show that TGR (hKLK1) rats have an impaired renal response to acute volume expansion that can not be accounted for by changes in the release of AVP or ANP

Evidence for a role of AT 2 receptors at the CVLM in the cardiovascular changes induced by low-intensity physical activity in renovascular hypertensive rats.

In the present study, we evaluated the involvement of the rennin–angiotensin system (RAS) in the control of the blood pressure (BP), baroreceptor-mediated bradycardia and the reactivity of caudal ventrolateral medulla (CVLM) neurons to Ang II and to AT2 receptor antagonist in sedentary or trained renovascularhypertensive rats. Physical activity did not significantly change the baseline mean arterial pressure (MAP), heart rate (HR) or the sensitivity of the baroreflex bradycardia in normotensive Sham rats. However, in 2K1C hypertensive rats, physical activity induced a significant fall in baseline MAP and HR and produced an improvement of the baroreflex function (bradycardic component). The microinjections of Ang II into the CVLM produced similar decreases in MAP in all groups, Sham and 2K1C, sedentary and trained rats. The hypotensive effect of Ang II at the CVLM was blocked by previous microinjection of the AT2 receptors antagonist, PD123319, in all groups of rats. Unexpectedly, microinjection of PD123319 at the CVLM produced a depres-sor effect in 2K1C sedentary that was attenuated in 2K1C trained rats. No significant changes in MAP were observed after PD123319 i n Sham rats, sedentary or trained. These data showed that low-intensity physical activity is effective in lowering blood pressure and restoring the sensitivity of t he baroreflex bradycardia, however these cardiovascular effects are not accompanied by changes i n the responsiveness to Ang II at CVLM in normotensive or hypertensive, 2K1C rats. In ad dition, the blood pressure changes observed after AT 2 blockade in 2K1C rats suggest that hypertension may trigger an imbalance of AT1 /AT 2 receptors at the CVLM that may be restored, at least in part, by low-intensity physical activit

Evidence for a role of AT 2 receptors at the CVLM in the cardiovascular changes induced by low-intensity physical activity in renovascular hypertensive rats.

In the present study, we evaluated the involvement of the rennin–angiotensin system (RAS) in the control of the blood pressure (BP), baroreceptor-mediated bradycardia and the reactivity of caudal ventrolateral medulla (CVLM) neurons to Ang II and to AT2 receptor antagonist in sedentary or trained renovascularhypertensive rats. Physical activity did not significantly change the baseline mean arterial pressure (MAP), heart rate (HR) or the sensitivity of the baroreflex bradycardia in normotensive Sham rats. However, in 2K1C hypertensive rats, physical activity induced a significant fall in baseline MAP and HR and produced an improvement of the baroreflex function (bradycardic component). The microinjections of Ang II into the CVLM produced similar decreases in MAP in all groups, Sham and 2K1C, sedentary and trained rats. The hypotensive effect of Ang II at the CVLM was blocked by previous microinjection of the AT2 receptors antagonist, PD123319, in all groups of rats. Unexpectedly, microinjection of PD123319 at the CVLM produced a depres-sor effect in 2K1C sedentary that was attenuated in 2K1C trained rats. No significant changes in MAP were observed after PD123319 i n Sham rats, sedentary or trained. These data showed that low-intensity physical activity is effective in lowering blood pressure and restoring the sensitivity of t he baroreflex bradycardia, however these cardiovascular effects are not accompanied by changes i n the responsiveness to Ang II at CVLM in normotensive or hypertensive, 2K1C rats. In ad dition, the blood pressure changes observed after AT 2 blockade in 2K1C rats suggest that hypertension may trigger an imbalance of AT1 /AT 2 receptors at the CVLM that may be restored, at least in part, by low-intensity physical activit

Angiotensin-(1-7) antagonist, A-779, microinjection into the caudal ventrolateral medulla of renovascular hypertensive rats restores baroreflex bradycardia.

In the present study we evaluated the effect of caudal ventrolateral medulla (CVLM) microinjection of the main angiotensin (Ang) peptides, Ang II and Ang-(1-7), and their selective antagonists on baseline arterial pressure (AP) and on baroreceptor-mediated bradycardia in renovascular hypertensive rats (2K1C). Microinjection of Ang II and Ang-(1-7) into the CVLM of 2K1C rats produced similar decrease in AP as observed in Sham rats. In both Sham and 2K1C, the hypotensive effect of Ang II and Ang-(1-7) at the CVLM was blocked, for up to 30 min, by previous CVLM microinjection of the Ang II AT 1 receptor antagonist, Losartan, and Ang-(1-7) Mas antagonist, A-779, respectively. As expected, the baroreflex bradycardia was lower in 2K1C in comparison to Sham rats. CVLM microinjection of A-779 improved the sensitivity of baroreflex bradycardia in 2K1C hypertensive rats. In contrast, Losartan had no effect on the baroreflex bradycardia in either 2K1C or Sham rats. These results suggest that Ang-(1-7) at the CVLM may contribute to the low sensitivity of the baroreflex control of heart rate in renovascular hypertensive rat

Angiotensin-(1-7) antagonist, A-779, microinjection into the caudal ventrolateral medulla of renovascular hypertensive rats restores baroreflex bradycardia.

In the present study we evaluated the effect of caudal ventrolateral medulla (CVLM) microinjection of the main angiotensin (Ang) peptides, Ang II and Ang-(1-7), and their selective antagonists on baseline arterial pressure (AP) and on baroreceptor-mediated bradycardia in renovascular hypertensive rats (2K1C). Microinjection of Ang II and Ang-(1-7) into the CVLM of 2K1C rats produced similar decrease in AP as observed in Sham rats. In both Sham and 2K1C, the hypotensive effect of Ang II and Ang-(1-7) at the CVLM was blocked, for up to 30 min, by previous CVLM microinjection of the Ang II AT 1 receptor antagonist, Losartan, and Ang-(1-7) Mas antagonist, A-779, respectively. As expected, the baroreflex bradycardia was lower in 2K1C in comparison to Sham rats. CVLM microinjection of A-779 improved the sensitivity of baroreflex bradycardia in 2K1C hypertensive rats. In contrast, Losartan had no effect on the baroreflex bradycardia in either 2K1C or Sham rats. These results suggest that Ang-(1-7) at the CVLM may contribute to the low sensitivity of the baroreflex control of heart rate in renovascular hypertensive rat

Cardiac and renal effects induced by different exercise workloads in renovascular hypertensive rats.

We examined the effect of exercise training (Ex) without (Ex 0%) or with a 3% workload (Ex 3%) on different cardiac and renal parameters in renovascular hypertensive (2K1C) male Fisher rats weighing 150-200 g. Ex was performed for 5 weeks, 1 h/day, 5 days/week. Ex 0% or Ex 3% induced similar attenuation of baseline mean arterial pressure (MAP, 119 ± 5 mmHg in 2K1C Ex 0%, N = 6, and 118 ± 5 mmHg in 2K1C Ex 3%, N = 11, vs 99 ± 4 mmHg in sham sedentary (Sham Sed) controls, N = 10) and heart rate (HR, bpm) (383 ± 13 in 2K1C Ex 0%, N = 6, and 390 ± 14 in 2K1C Ex 3%, N = 11 vs 371 ± 11 in Sham Sed, N = 10). Ex 0%, but not Ex 3%, improved baroreflex bradycardia (0.26 ± 0.06 ms/mmHg, N = 6, vs 0.09 ± 0.03 ms/mmHg in 2K1C Sed, N = 11). Morphometric evaluation suggested concentric left ventricle hypertrophy in sedentary 2K1C rats. Ex 0% prevented concentric cardiac hypertrophy, increased cardiomyocyte diameter and decreased cardiac vasculature thickness in 2K1C rats. In contrast, in 2K1C, Ex 3% reduced the concentric remodeling and prevented the increase in cardiac vasculature wall thickness, decreased the cardiomyocyte diameter and increased collagen deposition. Renal morphometric analysis showed that Ex 3% induced an increase in vasculature wall thickness and collagen deposition in the left kidney of 2K1C rats. These data suggest that Ex 0% has more beneficial effects than Ex 3% in renovascular hypertensive rats