Laparoscopic repair of congenital pleuroperitoneal hernia using a polypropylene mesh in a dog / Correção laparoscópica de hérnia pleuroperitoneal utilizando malha de polipropileno em cão

Pleuroperitoneal hernias are the most uncommon type of diaphragmatic hernias in dogs and cats. The treatment of choice is surgery and may involve the use of prosthetic implant through celiotomy. In the current report, laparoscopic repair of a congenital pleuroperitoneal hernia using polypropylene mesh in a dog is described. The surgery was feasible. Appropriate reduction of the hernia was carried out and no complications were noted.

Hérnias pleuroperitoneais são o tipo mais incomum de hérnias diafragmáticas em cães e gatos. O tratamento de escolha é cirúrgico e pode envolver o uso de implantes protéticos na abordagem via laparotomia. No presente relato, é descrito o reparo de uma hérnia pleuroperitoneal congênita através de laparoscopia com utilização de malha de polipropileno. A cirurgia foi viável. Houve redução apropriada da hérnia sem observação de complicações.

Classical and recent advances in the treatment of inflammatory bowel diseases

Crohn's disease (CD) and ulcerative colitis (UC) are intestinal disorders that comprise the inflammatory bowel diseases (IBD). These disorders have a significant effect on the quality of life of affected patients and the increasing number of IBD cases worldwide is a growing concern. Because of the overall burden of IBD and its multifactorial etiology, efforts have been made to improve the medical management of these inflammatory conditions. The classical therapeutic strategies aim to control the exacerbated host immune response with aminosalicylates, antibiotics, corticosteroids, thiopurines, methotrexate and anti-tumor necrosis factor (TNF) biological agents. Although successful in the treatment of several CD or UC conditions, these drugs have limited effectiveness, and variable responses may culminate in unpredictable outcomes. The ideal therapy should reduce inflammation without inducing immunosuppression, and remains a challenge to health care personnel. Recently, a number of additional approaches to IBD therapy, such as new target molecules for biological agents and cellular therapy, have shown promising results. A deeper understanding of IBD pathogenesis and the availability of novel therapies are needed to improve therapeutic success. This review describes the overall key features of therapies currently employed in clinical practice as well as novel and future alternative IBD treatment methods.

Classical and recent advances in the treatment of inflammatory bowel diseases.

Crohn's disease (CD) and ulcerative colitis (UC) are intestinal disorders that comprise the inflammatory bowel diseases (IBD). These disorders have a significant effect on the quality of life of affected patients and the increasing number of IBD cases worldwide is a growing concern. Because of the overall burden of IBD and its multifactorial etiology, efforts have been made to improve the medical management of these inflammatory conditions. The classical therapeutic strategies aim to control the exacerbated host immune response with aminosalicylates, antibiotics, corticosteroids, thiopurines, methotrexate and anti-tumor necrosis factor (TNF) biological agents. Although successful in the treatment of several CD or UC conditions, these drugs have limited effectiveness, and variable responses may culminate in unpredictable outcomes. The ideal therapy should reduce inflammation without inducing immunosuppression, and remains a challenge to health care personnel. Recently, a number of additional approaches to IBD therapy, such as new target molecules for biological agents and cellular therapy, have shown promising results. A deeper understanding of IBD pathogenesis and the availability of novel therapies are needed to improve therapeutic success. This review describes the overall key features of therapies currently employed in clinical practice as well as novel and future alternative IBD treatment methods.

Ovariossalpingo-histerectomia em cadelas: comparação da dor e análises cardiorrespiratória, pressórica e hemogasométrica nas abordagens convencional, por NOTES híbrida e NOTES total / Ovariosalpingohisterectomy in bitches: comparison of pain, cardiopulmonary, pressure and arterial blood gas analysis of the conventional approaches, by NOTES hybrid and NOTES pure

A cirurgia endoscópica por orifícios naturais (NOTES) é um novo conceito de abordagem videocirúrgica, que surge como alternativa à cirurgia convencional, eliminando incisões abdominais e as possíveis complicações relacionadas a ela. A proposta deste artigo foi comparar técnicas de ovariossalpingo-histerectomia (OSH) em cadelas, buscando determinar o procedimento que oferece menores alterações hemodinâmicas e menos estímulos dolorosos trans e pós-operatório. Para tanto, foram utilizadas 21 cadelas alocadas em três grupos. No primeiro, os pacientes foram submetidos à OSH por celiotomia (GC), no segundo por meio da técnica de NOTES híbrida (GNH) e no terceiro (GNT), utilizando-se a técnica de NOTES total. O tempo cirúrgico do GNH foi significativamente maior que nos demais grupos. Em ambos os grupos de cirurgia NOTES, verificou-se diminuição das pressões arteriais médias e diastólicas no transoperatório. Apenas o grupo GNH desenvolveu acidose severa no transoperatório. Levando-se em consideração as avaliações da dor, apenas o grupo convencional necessitou de analgesia resgate transcirúrgica. No pós-operatório, observou-se que os cães do GC apresentaram índices mais elevados na escala visual analógica e na escala de Melbourne que os animais dos demais grupos, sendo necessária analgesia resgate em 100% deles. Em contraste, no GNT nenhum dos cães requereram complementação analgésica pós-operatória. Conclui-se que a técnica de OSH por NOTES total apresenta parâmetros cardiorrespiratórios e hemogasométricos semelhantes à técnica convencional e mais estáveis que a técnica de NOTES híbrida, bem como resulta em menor dor trans e pós-operatória que a técnica convencional...

The aim of the present study was to perform bacteriological and molecular methods for identification of Mycobacterium bovis in lesions derived from bovine carcasses detected during routine post-mortem examination in officially inspected slaughterhouses. We checked the slaughter and inspection of 825,394 bovines, health upon ante-mortem examination, by the official service in 10 slaughterhouses of Bahia state from April, 2009 to April 2012. Lesions suggestive of tuberculosis were collected from 180 bovines and further evaluated by bacteriology and multiplex PCR. The majority of lesions were located in the respiratory tract lymph nodes and 71% were from male bovines up to 32 months old. 13.9% of samples presented small, granular and creamy-yellowish colonies after being cultured in Stonebrink-Leslie with an average growth time of 34 days. All smears from the isolated samples were Acid Fast Bacilli (AFB) and among them 56% were identified by mPCR as M. bovis. Thus, the association between post-mortem examination, culture and multiplex PCR allowed the bacillus identification in a reduced time and in regions of low prevalence, pointing out its importance for bovine tuberculosis detection and as a supportive tool for the tuberculosis control and eradication program...

Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

Laparoscopic paracostal herniorrhaphy in a dog: case report / Herniorrafia paracostal laparoscópica em um cão: relato de caso

Traumatic paracostal hernia is classified as an abdominal hernia that protrudes from the abdomen to a non physiologic space over the ribs. Treatment requires surgical reconstruction of the disrupted musculature in the thoracoabdominal region. Laparoscopic paracostal herniorrhaphy was performed in an eight-month-old male Teckel, presented after a car accident injury. A three-portal laparoscopic access was used for definitive diagnosis and hernia correction. After traction of the herniated omentum, a thoracoabdominal communication caused a left side pneumothorax, which was successfully drained with a chest tube placement. The herniorrhaphy was accomplished with intracorporeal sutures by a combination of Ford interlocking and cross mattress patterns. The postoperative period was uneventful. The laparoscopic paracostal herniorrhaphy was satisfactory, allowing both diagnosis and correction of the paracostal defect, showing to be a feasible alternative to the open surgery.

A hérnia traumática paracostal é classificada como uma hérnia abdominal com abaulamento do abdômen formando um espaço não fisiológico sobre as costelas. O tratamento consiste em reconstituir cirurgicamente a musculatura rompida da região toracoabdominal. A herniorrafia paracostal laparoscópica foi realizada em um cão da raça Teckel, macho de oito meses de idade, com histórico de trauma automobilístico. Optou-se pela utilização da abordagem laparoscópica tanto para o diagnóstico definitivo quanto para a correção da mesma. Foi utilizado o acesso com três portais, permitindo a tração do omento herniado, momento este em que o animal apresentou pneumotórax devido a uma comunicação toracoabdominal esquerda. O paciente foi submetido à toracocentese e adaptação de dreno no hemitórax esquerdo. A herniorrafia foi realizada com sutura intracorpórea em padrão contínuo de colchoeiro e festonada de Ford com fio monofilamentar náilon zero. O paciente apresentou rápida recuperação pós-operatória, sem ocorrências de recidivas. Assim, a herniorrafia paracostal laparoscópica mostrou-se satisfatória, possibilitando o diagnóstico definitivo e concomitante correção do defeito abdominal e diafragmático, podendo ser indicada como uma alternativa à cirurgia convencional.

Fração total de células mononucleares intra-articular em cães submetidos à reconstrução do ligamento cruzado / Total fraction of mononuclear intra-articular cells in dogs undergoing cruciate ligament reconstruction

Avaliou-sea ação da fração total de células mononucleares autógenas da medula óssea (FCMO) por aplicação intra-articular, após a correção cirúrgica do ligamento cruzado rompido. Foram utilizados 20 cães, os quais sofreram desmotomia do ligamento cruzado cranial e caudal unilaterais, 21 dias antes do reparo cirúrgico. Dez animais receberam as células autógenas no momento da correção. As avaliações se deram por estudo radiográfico, exames clínicos e biópsias aos 50 e 90 dias pós-operatórios. O grupo que recebeu a FCMO apresentou crescimento ósseo intra-articular ao estudo radiográfico, contudo os 20 animais apresentaram célulasCD34 positivas em suas amostras biopsiadas, indicando haver presença de células-tronco em ambos os grupos. Conclui-se que,para o modelo experimental proposto, não se recomenda o uso da fração total de células mononucleares e que trabalhos experimentais com o uso de células-tronco nas articulações devem evitar modelos cujo foco de lesão mantenha contato direto com a medula óssea.

This study was performed to evaluate the action of the fraction of total mononuclear cells from the bone marrow (FCMO) applied intra-articularly after the surgical repair of an experimentally ruptured cruciate ligament. Twenty dogs which suffered one-sided cruciate desmotomy of the cranial and caudal cruciate ligament 21 days before the correction were used. Ten animals received the FCMO at the time of correction. The assessments were done through X-ray and clinical examinations, and biopsies at 50 and 90 days postoperatively. It was concluded that there was no clinical difference between the two groups until 90 days of evaluation. The group that received FCMO grew intra-articular bone shown on the X-ray study. All twenty animals, however, presented cells marked with CD34 antibodies on their biopsy samples, indicating the presence of stem cells in both groups. It is concluded thatfor theexperimental model, it is not recommended to use the mononuclear cell fraction,andin experimental studies with the use of stem cells in the joints models whose focus of injury keep direct contact with the bone marrow should be avoided.

Diferentes vias de administração da solução de fosfato monobásico e dibásico de sódio no preparo do cólon para colonoscopia rígida em cães / Different routes in administration of sodium phosphate monobasic and dibasic solution in bowel preparation for rigid colonoscopy in dogs

Foram comparadas duas vias de administração, oral e retal, com a solução de fosfato monobásico e dibásico de sódio (NaP), juntamente com bisacodil via oral, no preparo do cólon para colonoscopia rígida em cães, para avaliar parâmetros clínicos, qualidade do preparo e variações dos eletrólitos fósforo, cálcio, potássio (K+) sódio (Na+) e magnésio (Mg+), além da creatinina, albumina e hemograma. Todos os eletrólitos apresentaram alterações, sendo significativa a queda nos níveis de K+ e Mg+. Não houve alterações eletrocardiográficas, e a redução da microbiota bacteriana foi confirmada nos dois grupos de administração da solução. Os resultados foram similares quanto à incidência de efeitos colaterais, porém a via retal apresentou facilidade na administração, menor retenção fecal no cólon, maior rapidez para realização da colonoscopia, com menor desperdício de tempo na lavagem e na aspiração do conteúdo fecal. O preparo intestinal com bisacodil oral e solução de NaP por via retal foi mais eficaz, podendo ser recomendado em cães que serão submetidos à colonoscopia.

The efficacy of oral and rectal administration of sodium phosphate monobasic and dibasic solution (NaP) combined with bisacodil per oral, as drugs to prepare the colon for rigid colonoscopy in dogs was compa1ed. Clinical parameters; colonic cleaning, plasma concentration of calcium, potassium (K+), sodium (Na+), magnesium (Mg+), creatinine, and albumin, and complete blood count were evaluated. In both groups, all electrolytes presented alterations, with significant reduction of the levels of K+ and Mg+, but there were no electrocardiographic alterations. No difference in the reduction of bacterial population was observed between the two groups. The results were similar regarding the incidence of side effects; however, the rectal route presented less fecal retention in colon and could get patients ready for the procedure faster. The preparation of bowel with bisacodil and NaP solution by rectal route was more effective and could be recommended for colonoscopy in dogs.

Cirurgia laparoscópica no diagnóstico de gastrite crônica atrófica seguida de tratamento clínico em cadela: relato de caso / Laparoscopic surgery in the diagnosis of atrophic gastritis in a dog followed by clinical treatment: case report

Descrevem-se o diagnóstico e o tratamento de um caso de gastrite atrófica crônica, em uma cadela sem raça definida, de dois anos de idade. A paciente apresentava como principal sintomatologia vômito crônico. O hemograma, a urinálise e as avaliações bioquímicas séricas não revelaram alterações significativas. Os exames radiológicos e ultra-sonográficos abdominais também não foram sugestivos de alterações. Realizaram-se inspeção da cavidade peritoneal, gastrotomia, gastroscopia, gastrectomia para biopsia e gastrorrafia intracorpórea videolaparoscópicas. Constatou-se ausência de rugosidades estomacais. Ao exame histológico, observou-se atrofia das células principais e parietais da mucosa gástrica. O quadro clínico permitiu o diagnóstico de gastrite crônica atrófica. O animal foi medicado com terapia imunossupressora e apresentou remissão completa dos sinais clínicos

This report describes a case of chronic atrophic gastritis. A two-year-old female mongrel dog showed chronic emesis. The complete blood count serum chemistry and urinalysis values were within the normal limits. Radiographs revealed no alterations. Abdominal evaluation, gastrotomy, gastroscopy, gastrectomy and intracorporeal stomach suture were done by laparoscopic approach. Absence of gastric villous was noticed through laparoscopic biopsy. The microscopic analysis reveled parietal and principal gastric mucosal cells atrophy, which, associated with clinical signs, allowed the chronic atrophic gastritis diagnosis. The animal was treated and clinical signs complete remission was observed

Nitric oxide (NO) modulation of PAF-induced cardiopulmonary action: interaction between NO synthase and cyclo-oxygenase-2 pathways.

1. To further investigate into the mechanisms of PAF-induced cardiopulmonary actions, we examined the effects of the nitric oxide synthase (NOS) inhibitor L-N(omega)-nitro-L-arginine (L-NNA), of the specific cyclooxygenase-2 (COX-2) inhibitor NS 398, and of the combined presence of both COX and NOS inhibitors on the PAF responses in the heart lung preparation of guinea-pig (HLP). 2. In HLPs perfused with homologous blood, dose-response curves for the haemodynamic and bronchial effects of PAF (1 - 32 ng) were carried out in the absence or presence of L-NNA (200 microM). L-NNA caused an increase in the resting pulmonary arterial pressure (PAP) without affecting the other basal values, and strongly potentiated the bronchoconstriction and pulmonary hypertension elicited by PAF. An enhancement of the PAF-induced actions on right atrial pressure (RAP) and cardiac output (CO) was also observed. All the effects of L-NNA were antagonized by L-arginine (2 mM). 3. The presence of L-NNA in the perfusing blood of HLPs failed to affect the pulmonary hypertensive and bronchoconstrictor responses induced by the thromboxane A(2) mimetic U46619 (0.05 - 1.6 microg), 5-hydroxytryptamine (0.1 - 1.6 microg), and histamine (0.1 - 1.6 microg), thus suggesting that these PAF secondary mediators are not responsible for the hyper-responsiveness to PAF induced by L-NNA. 4. Blocking COX-2 pathway with NS 398 (15 - 30 microM) did not alter the cardiopulmonary resting variables. However, a reduction of the PAF-mediated pulmonary hypertension, but not of bronchoconstriction, was observed. When L-NNA was added to the perfusing medium of HLPs pre-treated with NS 398 or with indomethacin (15 microM), the basal PAP values were enhanced. However, in the combined presence of COX and NOS inhibitors, only a slight increase in the hypertensive responses to the highest doses of PAF was observed, whereas the PAF mediated actions at bronchial and cardiac level were unaffected. 5. This study indicates that (i) the cardiopulmonary actions induced by PAF are specifically modulated by endogenous NO through the NOS pathway, and (ii) COX-2 isoform is involved in the pulmonary hypertensive, but not bronchoconstrictor, effects of PAF. Furthermore, an interaction between PAF stimulated COX, particularly COX-2, and NOS pathways appears to take a functional role at both bronchial and cardiovascular level.

Spinal cord stimulation and early experimental cerebral spasm: the "functional monitoring" and the "preventing effect".

BACKGROUND: Clinical and experimental data on cerebral blood flow (CBF) changes during spinal cord stimulation (SCS) were published since 1986. The aims of the present work are: 1. To find an experimental model of reliable, simple and in vivo monitoring of "early" basilar artery spasm after subarachnoid haemorrhage (SAH) and 2. To investigate the effects of cervical spinal cord stimulation (CSCS) on it. Vasospasm due to SAH is both "acute" and "recurrent". Early spasm occurs within minutes of the SAH. its duration is approximately 1 hour. The need of different morphological and haemodynamic methods to evaluate experimental early spasm is reported. To overcome intracranial surgical manipulations and biological effects of contrast and fixation media we designed a model that allows "in vivo" functional monitoring of basilar blood flow far away from the spasm without direct surgical and chemical interference. Subsequently we investigated the effects of CSCS on the new model of "functional monitoring" of the "early" cerebral vasospasm. METHOD: 29 adult Burgundy rabbits were studied. Group 1: under homeostatic monitoring, "on-line" carotid blood flow (carotid BF) changes produced by SAH in cisterna magna of 12 (plus 5 sham treated) animals were studied from the common carotid artery after external carotid artery occlusion before, during SAH and up to the end of the experiments. All the animals underwent digital subtraction cerebral panangiography (CPA) after SAH obtaining a significant increase of carotid BF only when basilar vasospasm was shown by CPA. Carotid BF increase during basilar vasospasm was defined "functional monitoring" of early spasm. Group 2: Twelve animals wearing a cervical epidural electrode underwent carotid BF "functional monitoring" of early basilar spasm before and during CSCS. FINDINGS: Carotid BF changes during CSCS occurred in 10 animals. No carotid BF changes (i.e. no basilar vasospasm) occurred after SAH up to the end of the experiments in all the stimulated animals. INTERPRETATION: CSCS is able to prevent "early spasm" due to SAH in all the animals studied with the new model of "functional monitoring" described, independently from the occurence and the sign for stimulation-induced carotid BF variations. The role and the limits of reversible functional sympathectomy in mediating the effect of CSCS on early vasospam are discussed.

Neuropeptide Y-induced potentiation of noradrenergic vasoconstriction in the human saphenous vein: involvement of endothelium generated thromboxane.

1. We investigated the potentiating effect of low concentrations of neuropeptide Y (NPY) on the vasoconstriction induced by transmural nerve stimulation (TNS) and noradrenaline (NA) in human saphenous veins. The effects of (i) endothelium removal; (ii) the addition of the NO pathway precursor L-arginine; (iii) the ET(A)/ET(B) endothelin receptor antagonist Ro 47-0203; (iv) the cyclo-oxygenase inhibitor, indomethacin; (v) the selective thromboxane A2 (TxA2) receptor antagonists Bay u3405 and ifetroban, and (vi) the TxA2 synthase inhibitor, UK 38485, were studied in order to gain information about the mechanisms of NPY-induced potentiation. 2. Contractile response curves for TNS (0.5-8 Hz) and for exogenously administered NA (0.1-3 microM) were obtained in superfused saphenous vein rings. The contractions induced by both TNS and NA at all tested frequencies and concentrations, respectively, were significantly potentiated by 50 nM NPY in endothelium intact veins. Conversely, in endothelium-denuded vessel rings the contractile-response curves to TNS and NA overlapped both in the absence and presence of NPY, thus suggesting that a release of vasoactive substances from endothelial cells could account for the noradrenergic NPY-induced potentiation. 3. In vessels with intact endothelium, the potentiating action of NPY on TNS and NA was unaffected by the presence of high concentrations of the NO precursor L-arginine (3-10 mM) or the non-selective ET(A)/ET(B) endothelin receptor antagonist, Ro 47-0203 (10 microM). These data indicate that the NPY-induced effect does not involve either the endothelium-derived vasodilator nitric oxide or the vasoconstrictor endothelin. Conversely, in the presence of the cyclo-oxygenase inhibitor, indomethacin (30 microM), NPY failed to potentiate the vasoconstrictions produced by either nerve stimulation or by exogenous NA, thus providing evidence that arachidonic acid metabolites through the cyclo-oxygenase pathway are mainly responsible for the potentiation evoked by NPY. 4. When the TxA2 receptor antagonists, Bay u 3405 (1 microM) and ifetroban (1 microM) were added to the superfusing medium, NPY did not alter either the frequency- or the concentration-response curves for either TNS or NA. Accordingly, both TNS- and NA-induced contractions were not potentiated by NPY in the presence of the TxA2 synthase inhibitor, UK 38485 (10 microM). This clearly demonstrates the pivotal role of TxA2 in NPY-induced potentiation. 5. In superfused vein rings with endothelium, a subthreshold concentration (0.2 nM) of the TxA2 mimetic U 46619 potentiated both TNS- and NA-induced vasoconstrictions. This potentiation was higher at low stimulation frequencies and low NA concentrations, and resembled that produced by NPY. 6. Our results indicate that in the human saphenous vein NPY potentiates the contractions produced by sympathetic nerve stimulation acting at the postjunctional level, primarily on endothelial cells. In particular, the NPY-induced release of a cyclo-oxygenase metabolite, namely TxA2, may have a synergistic effect on the vasoconstriction induced by the noradrenergic mediator. Thus, such a mechanism may play a key role in the maintenance of the sympathetic tone of large human capacitance vessels.

Nitric oxide-dependent and -independent modulation of sympathetic vasoconstriction in the human saphenous vein.

The possible modulation by the endothelium of the contractile responses to sympathetic nerve stimulation was examined in isolated superfused human saphenous vein. Contractile response curves for transmural nerve stimulation and noradrenaline were higher in endothelium-denuded than in intact human saphenous vein rings. In vessels with endothelium, transmural nerve stimulation- and noradrenaline-induced contractions were unaffected by the cyclooxygenase inhibitor, indomethacin (10 microM), but were potentiated by the nitric oxide (NO) synthase inhibitor, L-N omega-nitro-L-arginine (L-NNA, 3 microM) even when combined with D-arginine (0.3 mM), but not with L-arginine (0.3 mM). As in the case of noradrenaline, contractile responses to 5-HT, but not to KCI, were enhanced by endothelium removal, L-NNA or L-NNA plus D-arginine, but were unaffected by L-NNA plus L-arginine. The guanylyl cyclase inhibitor, methylene blue (10 microM), potentiated both transmural nerve stimulation- and noradrenaline-induced contractions in endothelium intact rings, whereas it enhanced, although to a lesser degree, only the neurally evoked contractions in endothelium-denuded human saphenous vein. In the vessels without endothelium L-NNA failed to affect the vasoconstriction induced by both transmural nerve stimulation and noradrenaline. Our results suggest that at least two inhibitory factors are involved in modulating the sympathetic vasoconstriction in the human saphenous vein: (1) at a postjunctional level, NO, the release of which from endothelial cells is probably stimulated by the activation of specific receptors, and (2) at a prejunctional level, an unidentified vasodilator agent, which is unmasked by the removal of the endothelium layer and which is probably co-released along with noradrenaline, and which acts through the guanylyl cyclase pathway.

ETB receptor mediating pulmonary hypertension and bronchoconstriction induced by endothelin-1 in the guinea pig.

Endothelin (ET-1) caused dose-related contraction of isolated superfused bronchus and pulmonary artery and bronchoconstriction and pulmonary vascular hypertension of the heart lung preparation (HLP) of guinea pig. The specific ETA receptor antagonist BQ 123 completely blocked the responses of the pulmonary artery, but failed to affect those of bronchus and of HLPs. The specific ETB receptor agonist Sarafotoxin S6c caused contractions of bronchus, but not of pulmonary artery, and bronchoconstriction and pulmonary hypertension in HLPs. It is concluded that non-ETA subtype receptors, perhaps ETB, appear to be the main responsible for the potent pulmonary hypertensive effects of ET-1.

Mechanisms of pulmonary vasoconstriction and bronchoconstriction produced by PAF in the guinea-pig: role of platelets and cyclo-oxygenase metabolites.

1. The mechanisms of action of platelet activating factor (PAF) in the bronchial and cardiovascular systems have not yet been fully elucidated. In order to characterize better and to ascertain whether the effects of PAF in both these systems may be ascribed to the same mechanisms, we examined the actions of PAF in the heart-lung preparation of guinea-pig (HLP). The role of platelets and of cyclo-oxygenase metabolites was investigated. 2. In HLPs perfused with autologous blood, bolus injections of PAF (4-32 ng) produced major effects at the pulmonary vascular and bronchial levels. Both dose-related pulmonary vascular hypertension and bronchoconstriction produced by PAF were diminished to the same extent (46% and, respectively, 47%) when HLPs were perfused with a medium consisting of homologous red blood cells suspended in physiological solution containing 3.5% dextran (RBC). This suggests that the effects of PAF partially depend on the presence of formed elements. 3. When indomethacin (30 microM) was added to the perfusing blood, the dose-response curve for the pulmonary hypertensive responses produced by PAF was strongly reduced (90%) in comparison to control preparations, whereas the bronchoconstrictor effects of PAF were only partially diminished (23%). These data constitute direct evidence that products of the cyclo-oxygenase pathway exert a major role in the vascular, rather than in the bronchial actions of PAF. 4. In HLPs perfused with RBC containing indomethacin (30 microM), the pulmonary vascular hypertensive responses produced by PAF were almost completely abolished, thus indicating that cyclo-oxygenase products from tissues are involved in these effects. Conversely, PAF administration continued to cause dose-related bronchoconstrictor responses that were reduced only partially in comparison with HLPs perfused with RBC in the absence of the cyclo-oxygenase inhibitor. This implies that PAF also has direct action on the bronchoconstriction evoked.5. At the cardiac level, administration of PAF in HLPs perfused with blood caused a dose-related increase in right atrial pressure accompanied by a decrease in left atrial pressure and cardiac output,which were completely suppressed or attenuated by the absence of formed elements and the addition of indomethacin. This suggests that the progressive heart impairment is secondary to the severe pulmonary hypertension induced by PAF.6. The results of this study performed in the heart-lung preparation of the guinea-pig, which made it possible to simultaneously record cardiovascular and bronchial parameters, indicate that various components are involved in the responses produced by PAF. It is suggested that different mechanisms depending on the relative contribution of these components may account for the PAF-induced effects at the pulmonary vascular and airway levels.

Cardiopulmonary effects of endothelin-1 in the guinea pig: role of thromboxane A2.

The effects of endothelin-1 (ET-1) on the cardiovascular and bronchial systems were examined in a heart/lung preparation of guinea pig. The role of arachidonic acid metabolites through cyclo-oxygease (COX) and lipoxygenase (LOX) pathways was investigated. Bolus injection of ET-1 (25-400 ng) caused dose-related bronchoconstriction, pulmonary vascular hypertension, and cardiac output reduction. When indomethacin (30 microM) or the thromboxane receptor antagonist Bay u 3405 (1 microM) were added to the perfusing blood, the cardiopulmonary effects of ET-1 were almost completely abolished. Conversely, the presence of the LOX inhibitor Bay x 1005 (10 microM) did not affect the ET-1 produced actions. We concluded that ET-1 exerts both bronchial and pulmonary vascular effects through an indirect mechanism. COX products, most likely thromboxane A2 but not arachidonic acid metabolites via the LOX pathway, make the major contribution to the bronchoconstrictor and pulmonary vascular hypertensive effects of ET-1.