Extent of rescue of F508del-CFTR function by VX-809 and VX-770 in human nasal epithelial cells correlates with SNP rs7512462 in SLC26A9 gene in F508del/F508del Cystic Fibrosis patients.

BACKGROUND: We analyzed the CFTR response to VX-809/VX-770 drugs in conditionally reprogrammed cells (CRC) of human nasal epithelium (HNE) from F508del/F508del patients based on SNP rs7512462 in the Solute Carrier Family 26, Member 9 (SLC26A9; MIM: 608481) gene. METHODS: The Isc-eq measurements of primary nasal epithelial cells from F508del/F508del patients (n = 12) for CFTR function were performed in micro Ussing chambers and compared with non-CF controls (n = 2). Data were analyzed according to the rs7512462 genotype which were determined by real-time PCR. RESULTS: The CRC-HNE cells from F508del/F508del patients evidenced high variability in the basal levels of CFTR function. Also, the rs7512462*C allele showed an increased basal CFTR function and higher responses to VX-809 + VX-770. The rs7512462*CC + CT genotypes together evidenced CFTR function levels of 14.89% relatively to wt/wt (rs7512462*CT alone-15.29%) i.e., almost double of rs7512462*TT (7.13%). Furthermore, sweat [Cl-] and body mass index of patients also evidenced an association with the rs7512462 genotype. CONCLUSION: The CFTR function can be performed in F508del/F508del patient-derived CRC-HNEs and its function and responses to VX-809 + VX-770 combination as well as clinical data, are all associated with the rs7512462 variant, which partially sheds light on the generally inter-individual phenotypic variability and in personalized responses to CFTR modulator drugs.

Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats / Mecanismos Neurais e Retardo do Esvaziamento Gástrico de Liquido Induzido no Infarto Agudo do Miocárdio em Ratos

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN. .

Fundamento: Distúrbios da motilidade do intestino proximal no infarto agudo do miocárdio podem desencadear sintomas digestivos como náuseas e vômitos. O infarto do miocárdio ocasiona retardo do esvaziamento gástrico (EG) de líquido em ratos. Objetivo: Investigar se existe a influência do nervo vago (VGX), adrenoreceptores α-1, receptores GABAB do sistema nervoso central e participação do núcleo paraventricular (NPV) do hipotálamo no esvaziamento gástrico (EG) e complacência gástrica (CG) em ratos infartados. Métodos: Ratos Wistar (n = 8-15) foram divididos em: grupo infarto (INF), sham (SH) e subdivididos. O infarto foi realizado por ligadura da artéria coronária descendente anterior. A complacência gástrica foi estimada com curvas pressão-volume. Realizada vagotomia por secção dos ramos dorsal e ventral. Para verificar a ação dos receptores GABAB foi injetado baclofeno por via intra ventrículo-cerebral. Simpatectomia química foi realizada com prazosina intravenosa (iv), e na lesão do núcleo paraventricular do hipotálamo foi utilizada corrente elétrica de 1mA/10s, com esvaziamento gástrico determinado por medição da retenção gástrica (% RG) de uma refeição salina. Resultados: Não houve diferença significativa na CG. A vagotomia (VGX) reduziu significativamente a %RG; no grupo INF, o tratamento intra ventrículo-cerebral (ivc) com baclofeno reduziu significativamente a % RG; não houve conclusivamente envolvimento dos receptores GABAB em retardar o EG; o tratamento intravenoso com prazosina reduziu significativamente a %RG no grupo INF. A lesão do NPV aboliu o efeito do infarto do miocárdio no EG. Conclusão: O nervo vago, receptores α-adrenérgicos e núcleo paraventricular estão envolvidos no retardo do esvaziamento gástrico no infarto agudo do miocárdio em ratos. .

Neural mechanisms and delayed gastric emptying of liquid induced through acute myocardial infarction in rats.

BACKGROUND: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. OBJECTIVE: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. METHODS: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1 mA/10 s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. RESULTS: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. CONCLUSION: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

Pulsed direct and constant direct currents in the pilocarpine iontophoresis sweat chloride test.

BACKGROUND: The classic sweat test (CST) is the golden standard for cystic fibrosis (CF) diagnosis. Then, our aim was compare the production and volume of sweat, and side effects caused by pulsed direct current (PDC) and constant direct current (CDC). To determine the optimal stimulation time (ST) for the sweat collection. To verify the PDC as CF diagnosis option. METHODS: Prospective study with cross-sectional experimental intervention. Experiment 1 (right arm): PDC and CDC. ST at 10 min and sweat collected at 30 min. Currents of 0.5; 0.75; 1.0 and 1.5 mA and frequencies of 0, 200, 1,000 and 5,000 Hz applied. Experiment 2 (left arm): current of 1.0 mA, ST at 5 and 10 min and sweat collected at 15 and 30 min with frequencies of 0; 200; 1,000 and 5,000 Hz applied Experiments 1 and 2 were performed with current density (CD) from 0.07 to 0.21 mA/cm2. Experiment 3: PDC was used in typical CF patients with two CFTR mutations screened and or with CF diagnosis by rectal biopsy and patients with atypical CF. RESULTS: 48 subjects (79.16% female) with average of 29.54 ± 8.87 years old were enrolled. There was no statistical difference between the interaction of frequency and current in the sweat weight (p = 0.7488). Individually, positive association was achieved between weight sweat and stimulation frequency (p = 0.0088); and current (p = 0.0025). The sweat production was higher for 10 min of stimulation (p = 0.0023). The sweat collection was better for 30 min (p = 0.0019). The skin impedance was not influenced by ST and sweat collection (p > 0.05). The current frequency was inversely associated with the skin impedance (p < 0.0001). The skin temperature measured before stimulation was higher than after (p < 0.0001). In Experiment 3 (29 subjects) the PDC showed better kappa index compared to CDC (0.9218 versus 0.5205, respectively). CONCLUSIONS: The performance of the CST with CDC and PDC with CD of 0.14 to 0.21 mA/cm2 showed efficacy in steps of stimulation and collection of sweat, without side effects. The optimal stimulation time and sweat collection were, respectively, 10 and 30 min.

Effect of baclofen on liquid and solid gastric emptying in rats.

CONTEXT: Gamma-aminobutyric acid (GABA) is a potent inhibitory neurotransmitter. There is evidence that GABA(B) receptors located in the dorsal complex and in afferent fibers of the vagus nerve participate in the control of gastrointestinal motility. OBJECTIVE: To assess the intracerebroventricularly (ICV) and intravenously (IV) effect of baclofen, a GABA(B) receptor agonist, on liquid and solid gastric emptying in rats. METHODS: Adult male Wistar rats weighing 250-300 g (n = 6-8 animals) were used. Gastric emptying of liquid test meals labeled with phenol red was evaluated by the determination of percent gastric retention (%GR) 10 and 15 min after orogastric administration of saline and 10% glucose meals, respectively. Baclofen was injected ICV (1 and 2 µg/animal) through a tube implanted into the lateral ventricle of the brain and was injected IV (1 and 2 mg/kg) into a tail vein. The gastric emptying of liquid was determined 10 or 30 min after ICV and IV baclofen administration, respectively. The gastric emptying of the solid meal was assessed by the determination of percent gastric retention 2 h after the beginning of the ingestion of the habitual ratio by the animal, consumed over a period of 30 min. Baclofen was administered ICV (1 and 2 µg/animal) or IV (1 and 2 mg/kg) immediately after the end of the ingestion of the solid meal. The control groups received vehicle (sterile saline solution) ICV or IV. RESULTS: The group of animals receiving baclofen ICV (2 mg/animal) presented a significantly lower (P<0.05, Tukey test) %GR (mean ± SEM) of the saline (18.1 ± 2.5%) compared to control (33.2 ± 2.2%). In the group receiving the drug IV, the gastric retention of the same test meal did not differ from control. ICV and IV administration of baclofen had no effect on the gastric emptying of the 10% glucose solution compared to control. ICV administration of 1 or 2 mg baclofen/animal significantly increased the gastric retention of the solid test meal (57.9 ± 6.5% and 66.6 ± 6.3%, respectively) compared to control (35.1 ± 4.4%). The same phenomenon was observed only with the IV dose of 2 mg/kg (71.9 ± 2.6%) compared to control (52.7 ± 2.8%). CONCLUSION: Baclofen administered: 1. ICV (2 µg/animal), but not IV, increased gastric emptying of a non-caloric isotonic liquid test meal (saline); 2. when administered ICV or IV, it had no effect of gastric emptying of a 10% glucose solution; 3) when administered ICV (1 and 2 mg/animal) and IV (2 mg/kg) it delayed the gastric emptying of the solid meal.

Effect of baclofen on liquid and solid gastric emptying in rats / Efeito do baclofen no esvaziamento gástrico de líquido e de sólidos em rato

CONTEXT: Gamma-aminobutyric acid (GABA) is a potent inhibitory neurotransmitter. There is evidence that GABA B receptors located in the dorsal complex and in afferent fibers of the vagus nerve participate in the control of gastrointestinal motility. OBJECTIVE: To assess the intracerebroventricularly (ICV) and intravenously (IV) effect of baclofen, a GABA B receptor agonist, on liquid and solid gastric emptying in rats. METHODS: Adult male Wistar rats weighing 250-300 g (n = 6-8 animals) were used. Gastric emptying of liquid test meals labeled with phenol red was evaluated by the determination of percent gastric retention ( percentGR) 10 and 15 min after orogastric administration of saline and 10 percent glucose meals, respectively. Baclofen was injected ICV (1 and 2 µg/animal) through a tube implanted into the lateral ventricle of the brain and was injected IV (1 and 2 mg/kg) into a tail vein. The gastric emptying of liquid was determined 10 or 30 min after ICV and IV baclofen administration, respectively. The gastric emptying of the solid meal was assessed by the determination of percent gastric retention 2 h after the beginning of the ingestion of the habitual ratio by the animal, consumed over a period of 30 min. Baclofen was administered ICV (1 and 2 µg/animal) or IV (1 and 2 mg/kg) immediately after the end of the ingestion of the solid meal. The control groups received vehicle (sterile saline solution) ICV or IV. RESULTS: The group of animals receiving baclofen ICV (2 mg/animal) presented a significantly lower (P<0.05, Tukey test) percentGR (mean ± SEM) of the saline (18.1 ± 2.5 percent) compared to control (33.2 ± 2.2 percent). In the group receiving the drug IV, the gastric retention of the same test meal did not differ from control. ICV and IV administration of baclofen had no effect on the gastric emptying of the 10 percent glucose solution compared to control. ICV administration of 1 or 2 mg baclofen/animal significantly increased the gastric retention of the solid test meal (57.9 ± 6.5 percent and 66.6 ± 6.3 percent, respectively) compared to control (35.1 ± 4.4 percent). The same phenomenon was observed only with the IV dose of 2 mg/kg (71.9 ± 2.6 percent) compared to control (52.7 ± 2.8 percent). CONCLUSION: Baclofen administered: 1. ICV (2 µg/animal), but not IV, increased gastric emptying of a non-caloric isotonic liquid test meal (saline); 2. when administered ICV or IV, it had no effect of gastric emptying of a 10 percent glucose solution; 3) when administered ICV (1 and 2 mg/animal) and IV (2 mg/kg) it delayed the gastric emptying of the solid meal.

CONTEXTO: O ácido gama-aminobutírico (GABA) é um potente neurotransmissor inibitório. Há evidências que receptores GABA>B localizados no complexo dorsal do vago e em fibras aferentes do nervo vago participam no controle da motricidade gastrointestinal. OBJETIVO: Avaliar o efeito intracerebroventricular (ICV) e intravenoso (IV) do baclofen, um agonista para receptores GABA B, sobre o esvaziamento gástrico de líquidos e de sólidos em ratos. MÉTODOS: Foram utilizados ratos adultos Wistar, machos, de 250-300 g (n = 6-8 animais). O esvaziamento gástrico das refeições de prova líquidas, marcadas com fenol vermelho, foi avaliado através da determinação da por cento de retenção gástrica, 10 e 15 min após administração orogástrica das refeições salina e de glicose a 10 por cento, respectivamente. As injeções ICV de baclofen (1 e 2 µg/animal) foram feitas através de uma sonda implantada no ventrículo lateral do cérebro e as injeções IV de baclofen (1 e 2 mg/kg) numa veia da cauda. O esvaziamento gástrico das refeições de prova líquidas foi determinado 10 ou 30 min após a administração de baclofen ICV ou IV, respectivamente. O esvaziamento gástrico da refeição sólida foi avaliado através da determinação da por cento de retenção gástrica 2 h após o início da ingestão da ração habitual do animal, ingerida durante 30 min. As administrações de baclofen ICV (1 e 2 µg/animal) e IV (1 e 2 mg/kg) foram feitas imediatamente após o término da ingestão da refeição sólida. Os grupos controles receberam ICV ou IV veículo (solução salina estéril). RESULTADOS: O grupo de animais que recebeu baclofen 2 mg/animal ICV apresentou retenção gástrica (média ± SEM) de salina (18.1 ± 2.5 por cento) significantemente menor (P<0.05, teste de Tukey) em relação ao grupo controle (33.2 ± 2.2 por cento). No grupo com administração IV da droga, a retenção gástrica da mesma refeição de prova não diferiu do seu controle. As administrações ICV e IV de baclofen não tiveram qualquer efeito no esvaziamento gástrico da solução de glicose a 10 por cento, em relação aos seus controles. A administração ICV de 1 ou 2 µg/animal de baclofen aumentou significativamente as retenções gástricas da refeição de prova sólida (57.9 ± 6.5 por cento e 66.6 ± 6.3 por cento, respectivamente) em relação ao grupo controle (35.1 ± 4.4 por cento). O mesmo fenômeno somente foi observado com a dose IV de 2 mg/kg (71.9 ± 2.6 por cento) em relação ao grupo controle (52.7 ± 2.8 por cento). CONCLUSÃO: O baclofen administrado: 1. ICV (2 µg/animal), mas não IV, aumentou o esvaziamento gástrico de uma refeição de prova líquida isotônica não-calórica (salina); 2. ICV ou IV, não teve efeito sobre o esvaziamento da solução de glicose a 10 por cento; 3) ICV (1 e 2 µg/animal) e IV (2 mg/kg) retardou o esvaziamento gástrico da refeição sólida.

[The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using Nw-nitro-L-arginine methyl ester (L-NAME)]. / Efeito do lipopolissacarídio bacteriano sobre o esvaziamento gástrico de ratos: avaliação do pré-tratamento com Nw-nitro-L-arginine methyl ester (L-NAME).

BACKGROUND: There is evidence that nitric oxide plays a role in the decrease in gastric emptying induced by bacterial lipopolysaccharide. AIM: To evaluate the effect of pretreatment with Nw-nitro-L-arginine methyl to ester, one competitive inhibitor of the nitric oxide synthases, on the gastric emptying delay induced by lipopolysaccharide. MATERIAL AND METHODS: Male Wistar rats, SPF, were used after 24 h fast and 1 h-water withdrawn. The pretreatment was done intravenously with vehicle (saline) or N(w)-nitro-L-arginine methyl to ester in the doses of 0.5, 1, 2.5 e 5 mg/kg. After 10 min, the animals were treated iv with lipopolysaccharide (50 microg/kg) or received vehicle (saline). The gastric emptying was evaluated 1 h after the lipopolysaccharide administration. A saline solution containing phenol red was used as the test meal. The gastric emptying was indirectly assessed by the determination of percent gastric retention of the test meal 10 min after orogastric administration. RESULTS: The animals pretreated with vehicle and treatment with lipopolysaccharide have significant rise of the gastric retention (average = 57%) in comparison with the controls receiving only vehicle (38.1%). The pretreatment with the different doses of N(w)-nitro-L-arginine methyl to ester did not modify per se the gastric retention in comparison with the animals pretreated with vehicle. Pretreatment with N(w)-nitro-L-arginine methyl to ester with the dose of 1 mg/kg determined a discrete but significant reduction in the gastric retention (52%) of animals treated with lipopolysaccharide in comparison with vehicle-pretreated rats. Paradoxically, animals pretreated with 2.5 or 5 mg of N(w)-nitro-L-arginine methyl to ester/kg followed by treatment with lipopolysaccharide displayed a significantly higher gastric retention (74.7% and 80.5%, respectively) as compared to their controls, pretreated with the same doses of the inhibitor and treated with vehicle (40.5% and 38.7%, respectively) and to those pretreated with vehicle and treated with the same toxin. CONCLUSION: The pretreatment with N(w)-nitro-L-arginine methyl to ester at low dose (1 mg/kg) resulted in a discrete inhibition of the gastric emptying delay induced by lipopolysaccharide. Nevertheless, N(w)-nitro-L-arginine methyl to ester at higher doses (2.5 and 5 mg/kg) induced an enhancement of the lipopolysaccharide effect on gastric emptying, despite not interfering with the gastric emptying per se.

Efeito do lipopolissacarídio bacteriano sobre o esvaziamento gástrico de ratos: avaliação do pré-tratamento com Nw-nitro-L-arginine methyl ester (L-NAME) / The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using Nw-nitro-L-arginine methyl ester (L-NAME) / The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using Nw-nitro-L-arginine methyl ester (L-NAME)

RACIONAL: Há evidências de que o óxido nítrico participa do mecanismo de retardo do esvaziamento gástrico determinado pelo lipopolissacarídio bacteriano. OBJETIVO: Avaliar o efeito do pré-tratamento com Nw-nitro-L-arginine methyl ester, um inibidor competitivo das óxido nítrico-sintetases, sobre o fenômeno. MATERIAL E MÉTODOS: Utilizaram-se ratos, Wistar, machos, SPF ("specific-pathogen free"), adultos, adaptados às condições do laboratório, que após 24 horas de jejum alimentar foram pré-tratados endovenosamente com veículo (salina) ou Nw-nitro-L-arginine methyl ester nas doses de 0,5, 1, 2,5 e 5 mg/kg. No tratamento, administrou-se endovenosamente veículo (salina) ou lipopolissacarídio (50 µg/kg). O intervalo entre o pré-tratamento e o tratamento foi de 10 minutos, e entre este e a avaliação do esvaziamento gástrico foi de 60 minutos. O esvaziamento gástrico foi avaliado indiretamente através da determinação da retenção gástrica da solução salina marcada com fenol vermelho 10 minutos após administração por via orogástrica. RESULTADOS: Entre os animais pré-tratados com veículo, o tratamento com lipopolissacarídio determinou elevação significativa da retenção gástrica (média = 57 por cento) em relação aos tratados com veículo (38,1 por cento). O pré-tratamento com as diferentes doses de Nw-nitro-L-arginine methyl ester não modificou a retenção gástrica nos animais controles do tratamento. O pré-tratamento com Nw-nitro-L-arginine methyl ester com a dose de 1 mg/kg determinou redução discreta, mas significativa, na retenção gástrica (52 por cento) nos animais tratados com lipopolissacarídio, em relação ao observado naqueles com pré-tratamento e tratamento com veículo (35,9 por cento). Nos animais pré-tratados com 2,5 e 5 mg/kg de Nw-nitro-L-arginine methyl ester e tratados com lipopolissacarídio, houve aumento significante da retenção gástrica (74,7 por cento e 80,5 por cento, respectivamente) em relação aos seus controles pré-tratados com as mesmas doses...

BACKGROUND: There is evidence that nitric oxide plays a role in the decrease in gastric emptying induced by bacterial lipopolysaccharide. AIM: To evaluate the effect of pretreatment with Nw-nitro-L-arginine methyl to ester, one competitive inhibitor of the nitric oxide syntases, on the gastric emptying delay induced by lipopolysaccharide. MATERIAL AND METHODS: Male Wistar rats, SPF, were used after 24 h fast and 1 h-water withdrawn. The pretreatment was done intravenously with vehicle (saline) or Nw-nitro-L-arginine methyl to ester in the doses of 0.5, 1, 2.5 e 5 mg/kg. After 10 min, the animals were treated iv with lipopolysaccharide (50 mg/kg) or received vehicle (saline). The gastric emptying was evaluated 1 h after the lipopolysaccharide administration. A saline solution containing phenol red was used as the test meal. The gastric emptying was indirectly assessed by the determination of percent gastric retention of the test meal 10 min after orogastric administration. RESULTS: The animals pretreated with vehicle and treatment with lipopolysaccharide have significant rise of the gastric retention (average = 57 percent) in comparison with the controls receiving only vehicle (38.1 percent). The pretreatment with the different doses of Nw-nitro-L-arginine methyl to ester did not modify per se the gastric retention in comparison with the animals pretreated with vehicle. Pretreatment with Nw-nitro-L-arginine methyl to ester with the dose of 1 mg/kg determined a discrete but significant reduction in the gastric retention (52 percent) of animals treated with lipopolysaccharide in comparison with vehicle-pretreated rats. Paradoxically, animals pretreated with 2.5 or 5 mg of Nw-nitro-L-arginine methyl to ester/kg followed by treatment with lipopolysaccharide displayed a significantly higher gastric retention (74.7 percent and 80.5 percent, respectively) as compared to their controls, pretreated with the same doses of the inhibitor and treated with vehicle (40.5 percent and...

[Gastric emptying of liquids in rats submitted to acute myocardial infarction]. / Vaciamiento gástrico de líquidos en ratas sometidas a infarto del miocardio.

Gastric Emptying (GE) is food transition from the stomach to the upper small intestine. Haemodynamics changes modify gastric emptying and the gastroduodenal motor activity. Myocardial Infarction is a pathological condition in which there are haemodynamics changes. Therefore, the objective of the present investigation was to study the effect of acute myocardial infarction on rat gastric emptying of an isosmotic and inert liquid meal. We conducted a study involving male Wistar rats (varying in body weight from 220 g to 250 g), that were allowed to habituate in a laboratory environment and then divided into 3 groups: group INF, rats in which the myocardial infarction was produced by left anterior coronary artery ligation; group SH, rats in which the myocardial infarction was simulated without ligating the anterior coronary artery; and group NA, rats which were not given any anesthesia or surgical procedures. After group constitution, animals were fasted with access to water ad libitum. 24 hours later, the Gastric Retention (GR) of 1.5 ml/100 g animal weight of a test meal of 0.9% NaCl plus the marker phenol red was evaluated. GE was indirectly evaluated in conscious animals, through determining the percentage of gastric retention (% GR) of a test meal, measured 10 minutes after orogastric infusion. Results of the present study showed that animals from the INF group presented GR (median=48.0%), significantly higher than the NA group (30.6%) and SH group (36.6%). No statistical difference in GR was observed between the SH and NA groups. Infarcted area, expressed in percentages, in animals of the INF group was 51.3+/-4.7% (mean SEM, N=17) which not presented correlation with results of GR of the same group (r=-0.05). From a caloric viewpoint, the results suggested that acute myocardial infarct in rats induce delay of the gastric emptying of an isosmotic and inert liquid meal.

Vaciamiento gástrico de líquidos en ratas sometidas a infarto del miocardio / Gastric emptying of liquids in rats submitted to acute myocardial infarction

El vaciamiento gástrico (VG) es la transferencia del contenido gástrico al intestino delgado. Las alteracioneshemodinámicas modifican el VG y la actividad motora gastroduodenal. El infarto del miocardio (IM) es una condición patológica en la que hay alteraciones hemodinámicas. Siendo así, el objetivo de este trabajo fue evaluar el efecto del infarto agudo del miocardio sobre el vaciamiento gástrico de una comida líquida isosmótica e inerte desde el punto de vista calórico (soluciónsalina). Fueron utilizadas ratas Wistar machos, con un peso de 220-250g, adaptados a condiciones de laboratorioy divididos en 3 grupos: grupo INF (N=17), ratas con infarto del miocardio por ligadura de la arteria coronaria descendiente anterior izquierda; grupoSH (N=15), Sham en las que fue simulado el proceso quirúrgico, sin ligadura de la arteria coronaria; grupoNA (N=15), ratas en las que no fue hecho ningún procedimiento de sedación o quirúrgico. Los animales, después de la constitución de los grupos, permanecieron en ayuno recibiendo agua ad libitum. Veinticuatro horas después fue evaluado el VG de 1,5 ml/100g de peso de animal de una comida de prueba (CP) salinamarcada con fenol rojo. El VG fue evaluado indirectamente en los animales despiertos a través de la determinacióndel porcentaje de retención gástrica (RG) de la CP, 10 minutos después de administración de oro gástrico.Los resultados mostraron que los animales del grupo INF presentaron RG (media=48,0%) significativamentemás alta con relación a los animales del grupo NA (30,6%,) y el grupo SH (36,6%). No hubo diferenciaentre animales del grupo SH con relación a los del grupo NA. El área de infarto, expresada en porcentaje,en los animales del grupo INF fue de 51,3±4,7% ( ±SE, N=17) y no presentó correlación con los resultadosde RG del mismo grupo (r=-0,05).

Gastric Emptying (GE) is food transition from the stomach to the upper small intestine. Haemodynamics changes modify gastric emptying and the gastroduodenal motor activity. Myocardial Infarction is a pathological condition in which there are haemodynamics changes. Therefore, the objective of the present investigation was to study the effect of acute myocardial infarction on rat gastric emptying of an isosmotic and inert liquid meal. We conducted a study involving male Wistar rats (varying in body weight from 220 g to 250 g), that were allowed to habituate in a laboratory environment and then divided into 3 groups: group INF, rats in which the myocardial infarction was produced by left anterior coronary artery ligation; group SH, rats in which the myocardial infarction was simulated without ligating the anterior coronary artery; and group NA, rats which were not given any anesthesia or surgical procedures. After group constitution, animals were fasted with access to water ad libitum. 24 hours later, the Gastric Retention (GR) of 1.5 ml/100 g animal weight of a test meal of 0.9% NaCl plus the marker phenol red was evaluated. GE was indirectly evaluated in conscious animals, through determining the percentage of gastric retention (% GR) of a test meal, measured 10 minutes after orogastric infusion. Results of the present study showed that animals from the INF group presented GR (median=48.0%), significantly higher than the NA group (30.6%) and SH group (36.6%). No statistical difference in GR was observed between the SH and NA groups. Infarcted area, expressed in percentages, in animals of the INF group was 51.3+/-4.7% (mean SEM, N=17) which not presented correlation with results of GR of the same group (r=-0.05). From a caloric viewpoint, the results suggested that acute myocardial infarct in rats induce delay of the gastric emptying of an isosmotic and inert liquid meal.

Vaciamiento gástrico de líquidos en ratas sometidas a infarto del miocardio / Gastric emptying of liquids in rats submitted to acute myocardial infarction

El vaciamiento gástrico (VG) es la transferencia del contenido gástrico al intestino delgado. Las alteracioneshemodinámicas modifican el VG y la actividad motora gastroduodenal. El infarto del miocardio (IM) es una condición patológica en la que hay alteraciones hemodinámicas. Siendo así, el objetivo de este trabajo fue evaluar el efecto del infarto agudo del miocardio sobre el vaciamiento gástrico de una comida líquida isosmótica e inerte desde el punto de vista calórico (soluciónsalina). Fueron utilizadas ratas Wistar machos, con un peso de 220-250g, adaptados a condiciones de laboratorioy divididos en 3 grupos: grupo INF (N=17), ratas con infarto del miocardio por ligadura de la arteria coronaria descendiente anterior izquierda; grupoSH (N=15), Sham en las que fue simulado el proceso quirúrgico, sin ligadura de la arteria coronaria; grupoNA (N=15), ratas en las que no fue hecho ningún procedimiento de sedación o quirúrgico. Los animales, después de la constitución de los grupos, permanecieron en ayuno recibiendo agua ad libitum. Veinticuatro horas después fue evaluado el VG de 1,5 ml/100g de peso de animal de una comida de prueba (CP) salinamarcada con fenol rojo. El VG fue evaluado indirectamente en los animales despiertos a través de la determinacióndel porcentaje de retención gástrica (RG) de la CP, 10 minutos después de administración de oro gástrico.Los resultados mostraron que los animales del grupo INF presentaron RG (media=48,0%) significativamentemás alta con relación a los animales del grupo NA (30,6%,) y el grupo SH (36,6%). No hubo diferenciaentre animales del grupo SH con relación a los del grupo NA. El área de infarto, expresada en porcentaje,en los animales del grupo INF fue de 51,3±4,7% ( ±SE, N=17) y no presentó correlación con los resultadosde RG del mismo grupo (r=-0,05).(AU)

Gastric Emptying (GE) is food transition from the stomach to the upper small intestine. Haemodynamics changes modify gastric emptying and the gastroduodenal motor activity. Myocardial Infarction is a pathological condition in which there are haemodynamics changes. Therefore, the objective of the present investigation was to study the effect of acute myocardial infarction on rat gastric emptying of an isosmotic and inert liquid meal. We conducted a study involving male Wistar rats (varying in body weight from 220 g to 250 g), that were allowed to habituate in a laboratory environment and then divided into 3 groups: group INF, rats in which the myocardial infarction was produced by left anterior coronary artery ligation; group SH, rats in which the myocardial infarction was simulated without ligating the anterior coronary artery; and group NA, rats which were not given any anesthesia or surgical procedures. After group constitution, animals were fasted with access to water ad libitum. 24 hours later, the Gastric Retention (GR) of 1.5 ml/100 g animal weight of a test meal of 0.9% NaCl plus the marker phenol red was evaluated. GE was indirectly evaluated in conscious animals, through determining the percentage of gastric retention (% GR) of a test meal, measured 10 minutes after orogastric infusion. Results of the present study showed that animals from the INF group presented GR (median=48.0%), significantly higher than the NA group (30.6%) and SH group (36.6%). No statistical difference in GR was observed between the SH and NA groups. Infarcted area, expressed in percentages, in animals of the INF group was 51.3+/-4.7% (mean SEM, N=17) which not presented correlation with results of GR of the same group (r=-0.05). From a caloric viewpoint, the results suggested that acute myocardial infarct in rats induce delay of the gastric emptying of an isosmotic and inert liquid meal.(AU)

Vaciamiento gástrico de líquidos en ratas sometidas a infarto del miocardio / Gastric emptying of liquids in rats submitted to acute myocardial infarction

El vaciamiento gástrico (VG) es la transferencia del contenido gástrico al intestino delgado. Las alteracioneshemodinámicas modifican el VG y la actividad motora gastroduodenal. El infarto del miocardio (IM) es una condición patológica en la que hay alteraciones hemodinámicas. Siendo así, el objetivo de este trabajo fue evaluar el efecto del infarto agudo del miocardio sobre el vaciamiento gástrico de una comida líquida isosmótica e inerte desde el punto de vista calórico (soluciónsalina). Fueron utilizadas ratas Wistar machos, con un peso de 220-250g, adaptados a condiciones de laboratorioy divididos en 3 grupos: grupo INF (N=17), ratas con infarto del miocardio por ligadura de la arteria coronaria descendiente anterior izquierda; grupoSH (N=15), Sham en las que fue simulado el proceso quirúrgico, sin ligadura de la arteria coronaria; grupoNA (N=15), ratas en las que no fue hecho ningún procedimiento de sedación o quirúrgico. Los animales, después de la constitución de los grupos, permanecieron en ayuno recibiendo agua ad libitum. Veinticuatro horas después fue evaluado el VG de 1,5 ml/100g de peso de animal de una comida de prueba (CP) salinamarcada con fenol rojo. El VG fue evaluado indirectamente en los animales despiertos a través de la determinacióndel porcentaje de retención gástrica (RG) de la CP, 10 minutos después de administración de oro gástrico.Los resultados mostraron que los animales del grupo INF presentaron RG (media=48,0%) significativamentemás alta con relación a los animales del grupo NA (30,6%,) y el grupo SH (36,6%). No hubo diferenciaentre animales del grupo SH con relación a los del grupo NA. El área de infarto, expresada en porcentaje,en los animales del grupo INF fue de 51,3±4,7% ( ±SE, N=17) y no presentó correlación con los resultadosde RG del mismo grupo (r=-0,05).(AU)

Gastric Emptying (GE) is food transition from the stomach to the upper small intestine. Haemodynamics changes modify gastric emptying and the gastroduodenal motor activity. Myocardial Infarction is a pathological condition in which there are haemodynamics changes. Therefore, the objective of the present investigation was to study the effect of acute myocardial infarction on rat gastric emptying of an isosmotic and inert liquid meal. We conducted a study involving male Wistar rats (varying in body weight from 220 g to 250 g), that were allowed to habituate in a laboratory environment and then divided into 3 groups: group INF, rats in which the myocardial infarction was produced by left anterior coronary artery ligation; group SH, rats in which the myocardial infarction was simulated without ligating the anterior coronary artery; and group NA, rats which were not given any anesthesia or surgical procedures. After group constitution, animals were fasted with access to water ad libitum. 24 hours later, the Gastric Retention (GR) of 1.5 ml/100 g animal weight of a test meal of 0.9% NaCl plus the marker phenol red was evaluated. GE was indirectly evaluated in conscious animals, through determining the percentage of gastric retention (% GR) of a test meal, measured 10 minutes after orogastric infusion. Results of the present study showed that animals from the INF group presented GR (median=48.0%), significantly higher than the NA group (30.6%) and SH group (36.6%). No statistical difference in GR was observed between the SH and NA groups. Infarcted area, expressed in percentages, in animals of the INF group was 51.3+/-4.7% (mean SEM, N=17) which not presented correlation with results of GR of the same group (r=-0.05). From a caloric viewpoint, the results suggested that acute myocardial infarct in rats induce delay of the gastric emptying of an isosmotic and inert liquid meal.(AU)

Vaciamiento gástrico de líquidos en ratas sometidas a infarto del miocardio. / [Gastric emptying of liquids in rats submitted to acute myocardial infarction]

Gastric Emptying (GE) is food transition from the stomach to the upper small intestine. Haemodynamics changes modify gastric emptying and the gastroduodenal motor activity. Myocardial Infarction is a pathological condition in which there are haemodynamics changes. Therefore, the objective of the present investigation was to study the effect of acute myocardial infarction on rat gastric emptying of an isosmotic and inert liquid meal. We conducted a study involving male Wistar rats (varying in body weight from 220 g to 250 g), that were allowed to habituate in a laboratory environment and then divided into 3 groups: group INF, rats in which the myocardial infarction was produced by left anterior coronary artery ligation; group SH, rats in which the myocardial infarction was simulated without ligating the anterior coronary artery; and group NA, rats which were not given any anesthesia or surgical procedures. After group constitution, animals were fasted with access to water ad libitum. 24 hours later, the Gastric Retention (GR) of 1.5 ml/100 g animal weight of a test meal of 0.9

NaCl plus the marker phenol red was evaluated. GE was indirectly evaluated in conscious animals, through determining the percentage of gastric retention (

GR) of a test meal, measured 10 minutes after orogastric infusion. Results of the present study showed that animals from the INF group presented GR (median=48.0

), significantly higher than the NA group (30.6

) and SH group (36.6

). No statistical difference in GR was observed between the SH and NA groups. Infarcted area, expressed in percentages, in animals of the INF group was 51.3+/-4.7

(mean SEM, N=17) which not presented correlation with results of GR of the same group (r=-0.05). From a caloric viewpoint, the results suggested that acute myocardial infarct in rats induce delay of the gastric emptying of an isosmotic and inert liquid meal.

Efeito do lipopolissacarídio bacteriano sobre o esvaziamento gástrico de ratos: avaliaçäo do pré-tratamento com dexametasona e azul de metileno / The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using dexamethasone and methylene blue

RACIONAL: O óxido nítrico pode estar envolvido no retardo do esvaziamento gástrico produzido pelo lipopolissacarídio bacteriano. OBJETIVO: Avaliar o efeito do pré-tratamento com a dexametasona, bloqueadora da induçäo do óxido nítrico-sintetase induzida e com o azul de metileno, que bloqueia a guanilato-ciclase, inibe as óxido nítrico-sintetases e inativa o óxido nítrico, sobre o retardo do esvaziamento gástrico determinado pelo lipopolissacarídio em ratos. MATERIAL E MÉTODOS: Foram utilizados ratos Wistar, machos, ''specific patogen free'', após 24 horas de jejum alimentar. No pré-tratamento foram empregadas, via intravenosa, soluções de dexametasona (3 e 6 mg/kg), azul de metileno (2 mg/kg) e veículo estéril. O tratamento constou da administraçäo, via intravenosa, de lipopolissacarídio (50 mig/kg) e veículo. O intervalo entre o pré-tratamento e o tratamento foi de 10 minutos, exceto no estudo com dexametasona 6 mg/kg, que foi de 1 hora. O intervalo entre a administraçäo do lipopolissacarídio e a avaliaçäo do esvaziamento gástrico foi de 1 hora, exceto nos dois estudos com dexametasona 3 mg/kg que foram de 2 e 8 horas. O esvaziamento gástrico foi avaliado, indiretamente, através da determinaçäo da percentagem de retençäo gástrica de soluçäo salina marcada com fenol vermelho. RESULTADOS: Os valores de retençäo gástrica, nos animais pré-tratados com dexametasona ou azul de metileno e tratados com veículo, näo diferiram significativamente dos observados nos que receberam veículo nos dois momentos. Os animais pré-tratados com veículo e tratados com lipopolissacarídio apresentaram valores de retençäo gástrica significativamente mais elevados que nos controles. O pré-tratamento com dexametasona näo interferiu no aumento da retençäo gástrica determinado pelo lipopolissacarídio, nas primeiras 2 horas após administraçäo da endotoxina. Oito horas após a administraçäo da endotoxina, foi observada diminuiçäo significativa da retençäo gástrica nos animais pré-tratados com dexametasona e tratados com lipopolissacarídio em relaçäo aos que receberam veículo + lipopolissacarídio. O mesmo fenômeno foi observado nos animais pré-tratados com azul de metileno e tratados com lipopolissacarídio. CONCLUSÄO: Os resultados sugerem o envolvimento do óxido nítrico no efeito do lipopolissacarídio sobre o esvaziamento gástrico em ratos

[The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using dexamethasone and methylene blue]. / Efeito do lipopolissacarídio bacteriano sobre o esvaziamento gástrico de ratos: avaliação do pré-tratamento com dexametasona e azul de metileno.

BACKGROUND: The nitric oxide might be a putative mediator of the decrease in gastric emptying induced by bacterial lipopolysaccharide in rats. AIM: For that, we evaluated the effect of the pretreatment intravenous with dexamethasone and methylene blue in the retardation process of gastric emptying induced by intravenous application of lipopolysaccharide in rats. Dexamethasone has been shown to inhibit the induction of NOS II (induced NO-synthase) while the methylene blue, that blocks the soluble guanylyl cyclase, inhibits nitric oxide synthases and, in addition, inactivates nitric oxide directly. MATERIAL AND METHODS: Male Wistar rats, specific patogenic free, were used after a 24 hour fast and 1 hour-water withdrawn. The pretreatment was performed using dexamethasone solutions (3 and 6 mg/kg), methylene blue (2 mg/kg) or sterile vehicle. The treatment consisted in the application of lipopolysaccharide (50 mug/kg) or vehicle. The time period between the pretreatment and treatment was 10 minutes, excluding the study with dexamethasone 6 mg/kg that was 1 hour. The gastric emptying was evaluated 1 hour after the lipopolysaccharide application, except for two studies with dexamethasone 3 mg/kg in which the time periods were 2 and 8 hours. A saline solution containing phenol red was used as the test meal. The gastric emptying was determined by measuring gastric retention 10 minutes after the orogastric infusion of the test meal. RESULTS: The pretreatment with dexamethasone or methylene blue and treatment with vehicle did not have effect in the gastric emptying comparing to the control group. We found that pretreatment with dexamethasone in the studies for 1 hour and 2 hours did not interfere in the retardation of the gastric emptying produced by endotoxin. Nevertheless, in the eighth period study with this drug there was a significant reduction of gastric retention in the endotoxin-treated animals in relation to the unpretreated ones. Meanwhile, the pretreatment with the methylene blue completely blocked the action of endotoxin on the gastric emptying in rats. CONCLUSION: These results suggest a possible involvement of nitric oxide on the effect of lipopolysaccharide in rat gastric emptying.