Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume

Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.

Avaliação da aptidão cardiorrespiratória de crianças com displasia broncopulmonar / Cardiorespiratory capacity assessment on children with bronchopulmonary dysplasia

OBJETIVO: Avaliar a aptidão cardiorrespiratória e verificar a presença de broncoespasmo induzido pelo exercício (BIE) em crianças com displasia broncopulmonar (DBP). MÉTODO: Foram realizadas prova de função pulmonar e análise de gases em um teste cardiopulmonar, em 46 crianças com idade entre 7 a 10 anos, formando três grupos: crianças nascidas pré-termo com DBP, (DBP, n= 13); crianças nascidas pré-termo sem DBP, (RNPT, n= 13); e crianças saudáveis nascidas a termo, (Controle, n= 20). RESULTADOS: A duração dos testes foi 7,70 ± 1,49; 9,1 ± 2,02 e 8,4 ± 2,12 min; o VO2máximo foi 35,98 ± 5,33; 38,99 ± 6,73 e 34,91 ± 6,09 ml/kg/min; e a VE foi 28,54 ± 7,39; 28,84 ± 5,98 e 28,96 ± 6,96 l/min para os grupos DBP, RNPT e Controle, respectivamente. Não foram encontradas diferenças significantes entre os grupos (p> 0,05). A FCmáxima foi 188 ± 9,37; 196 ± 5,15 e 197 ± 10,90 bpm; a taxa de troca gasosa máxima (R) foi 1,21 ± 0,22; 1,10 ± 0,06 e 1,05 ± 0,05 para os grupos DBP, RNPT e Controle, respectivamente, sendo esses valores diferentes entre o grupo Controle e DBP (p< 0,05). Os valores do VEF1 pré e VEF1 pós-exercício foram de 99 ± 12 por cento e 94 ± 14 por cento; 100 ± 14 por cento e 100 ± 15 por cento; e 102 ± 15 por cento e 101 ± 15 por cento, para os grupos DBP, RNPT e Controle, respectivamente. Na comparação do VEF1 pré e pós-exercício não houve diferenças significantes e nem caracterização de BIE nos grupos. CONCLUSÃO: A diferença encontrada no R pode ser relacionada a alterações ventilatórias e à difusão pulmonar. A aptidão cardiorrespiratória das crianças com DBP é semelhante à dos grupos RNPT e Controle.

OBJECTIVE: To assess cardiorespiratory capacity and investigate the presence of exercise-induced bronchospasm among children with bronchopulmonary dysplasia. METHOD: Pulmonary function tests and gas analyses were performed in a cardiopulmonary test on 46 children aged 7-10 years. Three groups were formed: children born prematurely with bronchopulmonary dysplasia (BPD; n= 13), children born prematurely without bronchopulmonary dysplasia (Preterm; n= 13) and healthy children born at full term (Control; n= 20). RESULTS: The test duration was 7.70 ± 1.49; 9.1 ± 2.02 and 8.4 ± 2.12 min; VO2max was 35.98 ± 5.33; 38.99 ± 6.73 and 34.91 ± 6.09 ml/kg/min; and VE was 28.54 ± 7.39; 28.84 ± 5.98 and 28.96 ± 6.96 l/min for the BPD, Preterm and Control groups respectively. There were no significant differences between the groups (p> 0.05). The maximum heart rate was 188 ± 9.37; 196 ± 5.15 and 197 ± 10.90 beats/min and the respiratory exchange ratio (RER) was 1.21 ± 0.22; 1.10 ± 0.06 and 1.05 ± 0.05, for the BPD, Preterm and Control groups respectively, and there was a significant difference between the BPD and Control groups (p< 0.05). The FEV1 values before and after exercise were 99 ± 12 percent and 94 ± 14 percent; 100 ± 14 percent and 100 ± 15 percent; and 102 ± 15 percent and 101 ± 15 percent, for the BPD, Preterm and Control groups respectively. Comparison of FEV1 before and after exercise did not show any significant differences and exercise-induced bronchospasm was not characterized, in any of the groups. CONCLUSION: The difference in RER may be related to abnormal ventilation and pulmonary diffusion. The cardiorespiratory capacity of children with BPD was similar to that of the Preterm and Control groups.

Performance of two-dimensional Doppler echocardiography for the assessment of infarct size and left ventricular function in rats

Although echocardiography has been used in rats, few studies have determined its efficacy for estimating myocardial infarct size. Our objective was to estimate the myocardial infarct size, and to evaluate anatomic and functional variables of the left ventricle. Myocardial infarction was produced in 43 female Wistar rats by ligature of the left coronary artery. Echocardiography was performed 5 weeks later to measure left ventricular diameter and transverse area (mean of 3 transverse planes), infarct size (percentage of the arc with infarct on 3 transverse planes), systolic function by the change in fractional area, and diastolic function by mitral inflow parameters. The histologic measurement of myocardial infarction size was similar to the echocardiographic method. Myocardial infarct size ranged from 4.8 to 66.6 percent when determined by histology and from 5 to 69.8 percent when determined by echocardiography, with good correlation (r = 0.88; P < 0.05; Pearson correlation coefficient). Left ventricular diameter and mean diastolic transverse area correlated with myocardial infarct size by histology (r = 0.57 and r = 0.78; P < 0.0005). The fractional area change ranged from 28.5 ± 5.6 (large-size myocardial infarction) to 53.1 ± 1.5 percent (control) and correlated with myocardial infarct size by echocardiography (r = -0.87; P < 0.00001) and histology (r = -0.78; P < 00001). The E/A wave ratio of mitral inflow velocity for animals with large-size myocardial infarction (5.6 ± 2.7) was significantly higher than for all others (control: 1.9 ± 0.1; small-size myocardial infarction: 1.9 ± 0.4; moderate-size myocardial infarction: 2.8 ± 2.3). There was good agreement between echocardiographic and histologic estimates of myocardial infarct size in rats.

Teste de caminhada de seis minutos em adultos eutroficos e obesos / The six minute walk test in normal and obese adults

O teste de caminhada frequentemente e utilizado para demonstrar os efeitos das doencas cardiovasculares e respiratorias sobre a capacidade fisica, como tambem para tederminar os efeitos de tratamentos aplicados. Participaram do estudo 46 pessoas, divididas em 5 grupos por faixa de IMC. O grupo 1 foi constituido por 18 pesoas com IMC de 20 a 24,9 Kg/m o grupo 2, por 12 pessoas com IMC de 25 a 29,9 Kg/m, o grupo 3, por 6 pessoas com IMC de 30 a 34,9 Kg/m o grupo 4, por 1 pessoas com IMC de 35 a 39,9 Kg/m e o grupo 5, por 9 pessoas com IMC > 40 kg/m. Os voluntarios realizaram um total de quatro testes de caminhada, de forma padronizada com acompanhamento do avaliador durante a caminhada. Os resultados mostraram que no 4§ teste a distancia percorrida foi maior que no 1§ teste (p< 0,01) no intervalo de tempo de 0 a 2 minutos, a distancia caminhada foi maior que nos demais intervalos de tempo (p< 0,01) com o auento do peso corporal houve diminuicao da distancia caminhada (p < 0,01), em media, distancia caminhada de 760m +50,6m (grupo 1), 731 m +71,9m (grupo 2), 680 m +56,7 m (grupo 3), 663 m (grupo 4) e 596 m + 61,8 m (grupo 5). O porcentual de gordura foi a medida antropometrica que melhor se correlacionou com distancia caminhada (r= -0,85 e p < 0,05), seguindo pelo de massa corporal (r = -0, 65) e pela relacao cintura/quadril (r= -0,56),somente para o sexo masculino. Concluiu-se que o aumento do peso corporal interfere na capacida fisica, diminuindo a distancia caminhada. no intervalo de tempo de 0 a 2 minutos, ocorre o melhor desempenho fisico. o efeito aprendizado influencia a distancia percorrida. e o porcentual de gordura e a medida antropometrica que melhor se correlaciona com distancia percorrida

Respiratory effects of kynurenic acid microinjected into the ventromedullary surface of the rat

Several studies demonstrate that, within the ventral medullary surface (VMS), excitatory amino acids are necessary components of the neural circuits involved in the tonic and reflex control of respiration and circulation. In the present study we investigated the cardiorespiratory effects of unilateral microinjections of the broad spectrum glutamate antagonist kynurenic acid (2 nmol/200 nl) along the VMS of urethane-anesthetized rats. Within the VMS only one region was responsive to this drug. This area includes most of the intermediate respiratory area, partially overlapping the rostral ventrolateral medulla (IA/RVL). When microinjected into the IA/RVL, kynurenic acid produced a respiratory depression, without changes in mean arterial pressure or heart rate. The respiratory depression observed was characterized by a decrease in ventilation, tidal volume and mean inspiratory flow and an increase in respiratory frequency. Therefore, the observed respiratory depression was entirely due to a reduction in the inspiratory drive. Microinjections of vehicle (200 nl of saline) into this area produced no significant changes in breathing pattern, blood pressure or heart rate. Respiratory depression in response to the blockade of glutamatergic receptors inside the rostral VMS suggests that neurons at this site have an endogenous glutamatergic input controlling the respiratory cycle duration and the inspiratory drive transmission.

Evidence for neuronal release of isotopically labelled glycine from the rat ventral medullary surface in vivo

Spontaneous and stimulus-induced release of isotopically labelled glycine was studied in the superfused rat dorsal or ventral medullary surface in vivo. Superfusion of the ventral medullary surface of anesthetized (urethane, 1.2 g/kg, ip) male adult Wistar rats (250-350 g) with high K+ (40 mM) surrogate cerebrospinal fluid (CSF) produced an average increase of 45 per cent over the spontaneous efflux of exogenously applied glycine (N = 5, P<0.01). In experiments in which the calcium of the CSF was replaced by an equimolar amount of magnesium, the increase in glycine efflux in response to high K+ was reduced to 15 per cent, a value not statistically different from that observed in control experiments (N = 6). Veratridine stimulation evoked a large (80 per cent) increase in glycine efflux (N = 5, P<0.001), which was inhibited by tetrodotoxin. High potassium or veratridine failed to modify spontaneous release of glycine on the dorsal medullary surface. Results obtained in control experiments showed that neither high K+ nor veratridine is effective in modifying spontaneous efflux of [(3)H]-leucine or [(3)H]-inulin on the ventral or dorsal medullary surface. These data support the hypothesis that glycine is a neurotransmitter on the ventral medullary surface and that it may be part of neural pathways involved in cardiorespiratory regulation present in this region.

Cardiovascular adjustments in limb retraction provoked by noxious stimulation in decerebrate and spinal cats: evidence for a somatotopic organization

Arterial blood pressure, heart rate and iliac blood flow were continuously recorded in 61 adult cats and their alteration induced by noxious stimulation of the interdigital spaces of the four limbs was studied in intact (anesthetized) and in decerebrate and spinal preparations. Noxious stimulation of any limb in the decerebrate animals provoked retraction 61 percent of the times and an increase of blood pressure and heart rate in approximately 80 percent of the stimulations. Stimulations of a hindlimb provoked an increase of blood flow in the same limb in about 80 percent of the stimulations, due to active vasodilation. Contralateral stimulation provoked as smaller increase of blood flow but with an increase in vascular resistance, indicating some degree of vasoconstriction. Stimulation of the forelimbs induced small increases of blood flow in the hindlimbs but the calculated vascular resistance was higher than the basal values, also indicating vasoconstriction. Neuromuscular blockade with gallamine did not affect the increase of hindlimb blood flow, suggesting a central regulation of the intricate distribution of blood to the limbs...

Putative pathways involved in cardiovascular responses evoked from the caudal pressor area

1. The caudal pressor area (CPA) is a recently identified site within the ventrolateral medulla which is involved in cardiovascular regulation. CPA chemical stimulation by L-glutamate produces an increase in arterial blood pressure (ABP) while its inhibition by GABA or glycine evokes marked hypotension. In the present study, we sought to determine the potential neural pathways underlyng these responses. 2. In urethane-anesthetized, paralyzed, artificially ventilated rats, CPA inhibition by bilateral microinjection of the inhibitory amino acid glycine (Gly, 100 nmol 200 nl-1 site-1) produced an average decrease of -38 + or - 4.3 mmHg in ABP (n = 6). Ten min after bilateral microinjection of the broad-spectrum glutamate antagonist kynurenic acid (KYN, 2 nmol 200 nl-1 site-1) into the cauldal ventrolateral medulla (CVLM) depressor responses to CPA inhibition were virtually abolished (-3 + or - 1.7 mmHg, P<0.05). Similar microinjection of KYN into the rostral ventrolateral medulla (RVLM) or into the CPA itself did not modify depressor responses to CPA inhibiton by glycine. 3. CPA stimulation by bilateral microinjection of the excitatory amino acid L-glutamate (L-glu, 50 nmol 200 nl-1 site-1) produced an increase in ABP (+43 + or - 5.4 mmHg, N= 6). Bilateral microinjection of the GABA A antagonist bicuculline methiodide (BIC, 200 pmol 200 nl-1 site-1) into the CVLM markedly reduced pressor responses to CPA stimulation (+6 + or - 2.7 mmHg, P<0.05). Similar application of BIC into the RVLM or CPA did not modify pressor responses to CPA stimulation by glutamic acid