Effects of water deprivation on renal hydroelectrolytic excretion in chronically Trypanosoma cruzi-infected rats

The effect of an 8 hour-period of water deprivation on fluid and electrolyte renal excretion was investigated in male Wistar rats infected with the strain Sao Felipe (12SF) of Trypanosoma cruzi, in comparison with age and sex matched non-infected controls. The median percent reductions in the urinary flow (-40 per cent v -63 per cent) and excretion of sodium (-57 per cent v - 79 per cent) were smaller in chagasic than in control rats, respectively. So, chagasic rats excereted more than controls. On the other hand, the median percent decrement in the clearance of creatinine was higher in chagasic (-51 per cent) than in controls (-39 per cent). Thus, chagasic rats showed some disturbed renal hydroelectrolytic responses to water deprivation, expressed by smaller conservation, or higher excretion of water and sodium in association with smallerglotmerular filtration rate. This fact denoted an elevation in the fractional excretion of sodium and water.

Effects of water deprivation on renal hydroelectrolytic excretion in chronically Trypanosoma cruzi-infected rats.

The effect of an 8 hour-period of water deprivation on fluid and electrolyte renal excretion was investigated in male Wistar rats infected with the strain São Felipe (12SF) of Trypanosoma cruzi, in comparison with age and sex matched non-infected controls. The median percent reductions in the urinary flow (-40% v-63%) and excretion of sodium (-57% v -79%) were smaller in chagasic than in control rats, respectively. So, chagasic rats excreted more than controls. On the other hand, the median percent decrement in the clearance of creatinine was higher in chagasic (-51%) than in controls (-39%). Thus, chagasic rats showed some disturbed renal hydroelectrolytic responses to water deprivation, expressed by smaller conservation, or higher excretion of water and sodium in association with smaller glomerular filtration rate. This fact denoted an elevation in the fractional excretion of sodium and water.

[Doppler echocardiographic comparison of valvular dynamics in bicycling, running, and football athletes, and sedentary subjects]. / Comparação ecodopplercardiográfica da dinâmica valvar entre atletas ciclistas, corredores e futebolistas e indivíduos sedentários.

PURPOSE: To compare the patterns of valvar dynamics expressed by the mitral prolapse and regurgitation across the valves, between competitive athletes players of distinctive sport modalities, and between these and sedentary control subjects. METHODS: Pulsed and continuous wave non-colour Doppler echocardiographic evaluation of mitral valvular movements and flow patterns across the different valves was comparatively performed in 10 cyclists, 10 runners, 19 football players, and in 17 sedentary nonathletes controls, all males with ages ranging between 16 and 28 years old (p > 0.05). Valvar dynamics was evaluated from the apical two and four-chamber and parasternal short-axis and long-axis views. The proportions of valvar functional patterns in each group were compared using the chi-square test. RESULTS: Similar (p > 0.05) and high frequency of mitral prolapse were detected in the cyclists (30%), runners (50%), football players (32%), and controls (47%). Mitral, tricuspid and pulmonary regurgitations were very frequent and their proportions similar (p > 0.05) in the cyclists (40%, 80% and 40%, respectively), runners (50%, 70% and 60%), football players (37%, 58% and 58%), and controls (41%, 35% and 35%). No significant difference (p > 0.05) was observed between cyclists (20%), runners (20%), football players (16%), and controls (35%) for the frequency of mitral prolapse plus regurgitation. Aortic regurgitation was not observed in any athlete or control subject. CONCLUSION: Neither the practice, nor the sport modalities studied appears to influence the prevalence of mitral prolapse and mitral, tricuspid and pulmonary valvar regurgitation. In all likelihood, these manifestations represent physiological variants of valvar dynamic which can be better detected by means of Doppler echocardiography.

Cardiac autonomic dysfunction and neuroganglionitis in a rat model of chronic Chagas' disease.

OBJECTIVE: The aim was to evaluate whether the cardiac parasympathetic function in a rat model of chronic Chagas' disease is impaired as in the human disease, and to correlate the functional state to histopathology of the intrinsic autonomic innervation of heart. METHODS: 70 male Wistar rats 8 months infected with strains Y (n = 22), São Felipe (n = 18), and Colombia (n = 30) of Trypanosoma cruzi, were compared with 20 age and sex matched non-infected controls. Baroreflex bradycardia was quantified after multiple bolus injections of phenylephrine (3 to 12 micrograms). For each rat studied a mean was obtained of the absolute and relative (delta %) ratio (index) between the maximum heart rate decrease and the maximum systolic blood pressure increase. RESULTS: For the relative index the means were smaller (p less than 0.05) in the Y [-0.52(SD 0.19)%], São Felipe [-0.45(0.28)%], and Colombia [-0.53(0.21%)] subgroups, as well as in the pooled chagasic group [-0.51(0.22)%], than in the control group [-0.64(0.13)%]. In 32% (7/22), 33% (6/18), and 20% (6/30) of rats infected with Y, São Felipe, and Colombia strains, respectively, and in 27% (19/70) of the pooled group rats, the index exceeded the control group mean by -2 SD. After atropinisation, a similar pronounced reduction (p less than 0.01) in the index was observed in all groups [-84(28)% to -95(17)%]; however, rats with depressed bradycardia showed a smaller (p less than 0.05) reduction in the relative index than control rats, at -70(34) v -92(16%). Inflammatory and degenerative lesions of the intrinsic cardiac innervation were observed in 87% of the rats with autonomic dysfunction. Rats with the lesions showed a mean relative index that was smaller than those without lesions, at -0.44(0.23) v -0.64(0.20)% (p less than 0.01), and also smaller than in the controls. CONCLUSIONS: Cardiac autonomic dysfunction expressed by reduced baroreflex bradycardia was detected in rats chronically infected with T cruzi, as in human Chagas' disease. The disturbance, shown for the first time in an animal model of chagasic infection, resulted primarily from impaired efferent parasympathetic activity caused by intrinsic neuroganglionar lesions.

[A quantitative analysis of the mastocytes and eosinophilic granulocytes in the myocardium of Wistar rats chronically infected by Trypanosoma cruzi. A contribution to the knowledge of myocardial fibrosis]. / Análise quantitativa de mastócitos e de granulócitos eosinófilos no miocárdio de ratos Wistar cronicamente infectados pelo Trypanosoma cruzi. Contribuição ao conhecimento da fibrose miocárdia.

We did mast cell and eosinophil granulocyte counts in the myocardium of forty chronic chagasic Wistar albino rats. We used 10 controls rats and 30 animals with late-stage (8th month) infection of São Felipe, Y and Colombian Trypanosoma cruzi strains, with variable degree of chronic myocarditis. We found chronic fibrosing myocarditis (fibrosis) in 40% of the infected animals. It was detected increased mast cell count in the chagasic rats associated with infection and not related with myocardial fibrosis. There was no increase in the eosinophil counts.

Neuronal counting and parasympathetic dysfunction in the hearts of chronically Trypanosoma cruzi infected rats

Dez ratos machos Wistar cronicamente infectados pelas cepas Colombiana, Sao Felipe (12SF), e Y do Trypanosoma cruzi, foram submetidos, apos 8 meses de infeccao, juntamente com dez animais controles, ao teste da resposta bradicardica barorreflexa pela injecao endovenosa de fenilefrina. Seis ratos chagasicos exibiram disfuncao cardiaca parassimpatica, caracterizada pela depressao do indice da resposta bradicardica barorreflexa. Embora o estudo histologico dos coracoes chagasicos mostrasse lesoes dos ganglios atriais, a contagem dos neuronios em cortes seriados, nao apresentou reducao numerica significativa dos mesmos.

Neuronal counting and parasympathetic dysfunction in the hearts of chronically Trypanosoma cruzi-infected rats.

Ten male Wistar rats, chronically infected with Colombian, São Felipe (12SF) and Y strains of Trypanosoma cruzi and ten non-infected control animals were submitted to the bradycardia responsiveness test, an assessment of heart parasympathetic function, after phenylephrine injection. Six chagasic animals showed heart parasympathetic dysfunction characterized by reduction in the index of bradycardia baroreflex responsiveness, as compared with the control group. Microscopic examination of the atrial heart ganglia of chagasic rats showed ganglionitis, but no statistically significant reduction in the number of neurons.

Pentavalent antimonial nephrotoxicity in the rat

Estudou-se a funcao renal de ratos tratados com Glucantime (Antimoniato de Meglumine, Rhodia) e Pentostam (estibogloconato de Sodio, Wellcome) na dose de 30 mg de "Sb POT v" por 100g de peso por dia, durante 30 dias. Observou-se um disturbio na concentracao urinaria, que foi reversivel 7 dias apos cessada a administracao das drogas. O estudo histopatologico do rim, por meio da microscopia optica, nao evidenciou alteracoes significativas. Por outro lado, ratos tratados com altas doses dos antimoniais (220mg de "Sb POT v" por 100g de peso por dia) mostraram alteracoes funcionais e histopatologicas renais compativeis com necrose tubular aguda

Pentavalent antimonial nephrotoxicity in the rat.

Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia) or Pentostam (Sodium Stibogluconate, Wellcome). In dose of 30 mg of Sbv (Glucantime or Pentostam) by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day) showed the functional and the histopathological alterations of the acute tubular necrosis.

Ambulatory assessment of cardiac autonomic function in Chagas' heart disease patients based on indexes of R-R interval variation in the Valsalva maneuver.

1. The reflex cardiac autonomic function of Chagas' heart disease patients was evaluated by a simple, noninvasive and inexpensive ambulatory method as an alternative to the complex or invasive methods or drug tests hitherto used. Variations in the R-R interval during the Valsalva maneuver was quantified in 33 outpatients with Chagas' cardiopathy without heart failure aged 38 +/- 9 years, and compared to 30 healthy control subjects aged 31 +/- 8 years (P greater than 0.05). 2. Each subject carried out 3 to 4 Valsalva maneuvers in the supine position for 20 s at an intraoral pressure of 40 mmHg. Variations of R-R interval were calculated from the electrocardiogram which was recorded continuously from 10 s before to 90 s after the maneuver when the recovery phase had already started. 3. The chagasic group presented lower relative tachycardia (shortest R-R minus control R-R/control R-R) (-27.9 +/- 8.4%, mean +/- SD) and Valsalva ratio (longest R-R/shortest R-R) (1.67 +/- 0.3) than the control group (-34.2 +/- 6.5% and 1.93 +/- 0.3, respectively) (P less than 0.01). The time for maximum R-R interval variation (shortest R-R to longest R-R) was longer (18.0 +/- 7.2 s), and the velocity of this variation (longest R-R minus shortest R-R divided by shortest R-R/time for the maximum R-R variation) was lower (4.8 +/- 3.5%/s) in the chagasic patients (P less than 0.01) than in the controls (11.1 +/- 5.4 s and 10.8 +/- 6.0%/s, respectively). The mean relative bradycardia (longest R-R minus control R-R/control R-R) of the chagasic group (18.5 +/- 13.5%) was statistically similar (P greater than 0.05) to that of the control group (25.6 +/- 16.5%). 4. In 51% (17/33) of the chagasic patients, at least one significantly altered index was observed to exceed +/- 2 SD of the respective control mean, and for 3 of them (10% of the total) all the indexes were abnormal. In 49% (16/33) of the patients no abnormal index was observed. 5. These data show that varying degrees of cardiac autonomic dysfunction may be detected in a simple manner in ambulatory outpatients with Chagas' heart disease, with results similar to those obtained with application of complex or invasive tests. In all likelihood, the altered Valsalva R-R interval variation indexes in the present chagasic patients resulted from depressed parasympathetic activity on the heart consequent to the Chagas' cardiac denervation.(ABSTRACT TRUNCATED AT 400 WORDS)

Ambulatory assessment of cardiac autonomic function in chagas's heart disease patients based on indexes of R-R interval variation in the valsalva maneuver

1. The reflex cardiac autonomic function of Chagas' heart disease patients was evaluated by a simple, nonivasive and inexpensive ambulatory method as an alternative to the complex or invasive methods or drug tests hitherto used. Variations in the R-R interval during the Valsava maneuver was quantified in 33 outpatients with Chagas's cardiopathy without heart failure aged 38 ñ 9 yers, and compared to 30 healthy control subjects aged 31 ñ 8 years (P > 0.05). 2. Each subject carried out 3 to 4 Valsalva maneuvers in the supine position for 20 s at an intraoral pressure of 40 mmHg. Variations of R-R interval were calculated from the electrocardiogram whic was recorded continuously from 10 s before to 90 s after the maneuver when the recovery phase had alredy started. 3. The chagasic group presented lower relative tachycardia (shortest R-R minus control R-R/control R-R) (-27.9 ñ 8.4%, mean ñ SD) and Valsalva ratio (longest R-R/shortest R-R) (1.67 ñ 0.3) than the control group (34.2 ñ 6.5% and 1.93 ñ 0.3, respectively) (P < 0.01). The time for maximum R-R interval variation (shortest R-R to longest R-R) was longer (18.0 ñ 7.2s), and the velocity of this variations (longest R-R minus shortest R-R divided by shortest R-R/time for the maximum R-R variation) was lower (4.8 ñ3.5%/s) in the chagasic patients (P < 0.01) than in the controls (11.1 ñ 5.4 s and 10.8 ñ 6.0%/s, respectively). The mean relative bradycardia (longest R-R minus control R-R/control R-R) of the chagasic group (18.5 ñ 13.5%) was statistically similar (P > 0.05) to that of the control group (25.6 ñ 16.5%). 4. In 51% (17/33) of the chagasic patients, at least one significantly altered index was observed to exceed ñ 2 SD of the respective control mean, and for 3 of them (10% of the total) all the indexes were abnormal. In 49% (16/33) of the patients no abnormal index was observed. 5. These date show that varyng degress of cardiac autonomic dysfunction may be detected in a simple manner in ambulatory outpatients with Chagas's heart disease, with results similar to those obtained with application of complex or invasive tests. In all likelihood, the altered Valsalva R-R interval variation indexes in the present chagasic patients resulted from depressed parasympathetic activity on the heart consequent to the Chagas cardiac devervation. However, associated sympathetic dysfunction should not be ruled out as a possible secondary secondary cause

Lesöes cardíacas em ratos Wistar inoculados com diferentes cepas do Trypanosoma cruzi / Cardiac lesions in Wistar rats infected with different strains of Trypanosoma cruzi

Ratos albinos Wistar infectados com diferentes inóculos das cepas Y, Colombiana (COL) e Säo Felipe (12SF) do Trypanosoma cruzi desenvolveram parasitemia elevada entre 14 e 21 dias, a qual tornou-se desprezível ou desapareceu completamente ao final da 4ª semana. As lesöes do coraçäo foram avaliadas, semiquantitativamente, pelo sistema de "scores", conforme a intensidade e a extensäo da inflamaçäo, nas diferentes estruturas do órgäo, tendo sido observado que: a) na fase inicial (aguda) da infecçäo, os animais mortos espontaneamente ou em conseqüência do acidente anestésico apresentaram cardite de intensidade moderada a acentuada, näo havendo diferença em relaçäo as cepas utilizadas; as diferentes estruturas do coraçäo estavam uniformemente comprometidas; b) na fase crônica da infecçäo observou-se cardite de grau leve a moderado e as lesöes foram mais freqüentes e intensas quanto maior o inóculo empregado; no entanto, inóculos baixos só produziram lesöes quando a cepa utilizada foi a Colombiana. Trombose mural nos átrios e dilataçäo da ponta do ventrículo esquerdo foram observadas em 20% dos animais, independetemente da cepa. Na fase crônica 15% dos animais apresentaram miocardite crônica com fibrose, associada a hipertrofia das miocélulas. Os AA confirmam ser o rato albino suscetível a infeccäo chagásica e, portanto, um modelo útil no estudo das manifestaçöes cardíacas da Doença de Chagas

Effect of parasympathetic impairment on the haemodynamic response to handgrip in Chagas's heart disease.

Haemodynamic responses to sustained isometric exercise (handgrip at 30% of maximum voluntary capacity) were studied in 10 patients with Chagas's cardiopathy without previous or current heart failure. Five of the patients (group 1) had profound impairment of parasympathetic control of heart rate. They had no tachycardia in response to intravenous administration of atropine and no bradycardia during phase IV of the Valsalva manoeuvre. The other five (group 2) showed normal vagal regulation of heart rate, as judged by chronotropic responses to these tests. The heart rate change (mean (SD] elicited by the handgrip test was significantly lower in group 1 (from 93.0 (14.1) to 95.0 (16.7) beats/min) than in group 2 (from 78.2 (15.8) to 92.8 (18.1) beats/min). Pressor responses to handgrip were of similar magnitude (from 91.6 (7.8) to 109.0 (8.0) mm Hg in group 1 and from 88.6 (11.9) to 106.8 (20.9) mm Hg in group 2). In both groups no significant change in stroke index was detected during handgrip. Cardiac index increased during handgrip from 4.0 (1.2) to 4.8 (1.3) 1/min/m2 in group 2, but there was no significant change in group 1 (from 4.9 (0.7) to 4.8 (1.1) 1/min/m2). Changes in calculated systemic vascular resistance were significantly higher in group 1 (from 934 (175) to 1176 (383) dyn s cm-5) than in group 2 (from 1109 (404) to 1112 (424). This study shows that parasympathetic impairment adversely influences the haemodynamic pattern of response to isometric exercise in patients with Chagas's heart disease. In such conditions, the pressor response to handgrip is predominantly mediated by an increase in systemic vascular resistance rather than an increase in cardiac output.

Subtle cardiac autonomic impairment in Chagas' disease detected by baroreflex sensitivity testing.

The sensitivity of baroreflex bradycardia and tachycardia was determined in fourteen patients with Chagas' disease who seemed to be normal with respect to cardiac autonomic control evaluated in terms of heart rate responses to the conventional atropinization and Valsalva maneuver tests. Eleven normal subjects were studied for comparison. Baroreflex sensitivity was determined by relating the beat-to-beat pulse intervals to systolic pressure values during transient phenylephrine- and amyl nitrite-induced changes in arterial pressure. Chagasic patients showed mean bradycardia sensitivity (10.1 +/- 1.3 ms/mmHg) which was significantly lower than that obtained for the control group (16.7 +/- 2.1 ms/mmHg). When only the subgroup of ten patients with overt disease (cardiac and/or digestive form) was considered, the value fell to 8.6 +/- 1.4 ms/mmHg. The lowest individual values were exhibited by the majority of patients with exclusive cardiac or associated cardiac and digestive disease. Patients with only digestive disease or without overt disease (indeterminate form) had values within the normal range. Tachycardia sensitivity (6.3 +/- 0.8 ms/mmHg) was similar to that obtained for the control group (6.6 +/- 1.0 ms/mmHg). Only one patient with associated disease presented a reduced value. These data show that the estimation of baroreflex sensitivity can be used to identify impaired cardiac autonomic control in chronic Chagas' disease not detectable by conventional tests. The reduced baroreflex sensitivity appears to be due to the subtle impairment of the parasympathetic influence on the heart. Furthermore, there is a relationship between the degree of baroreflex sensitivity and the clinical form of organic involvement in Chagas' disease.