Safe administration of noradrenaline by the peripheral route: A systematic review. / Administración segura de noradrenalina por vía periférica: una revisión sistemática.

PURPOSE: To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety. METHODS: Systematic review on the databases PubMed, ISI Web of Science, SCOPUS and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1,040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included. RESULTS: NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischemia and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA. CONCLUSIONS: Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.

Tratamiento crónico ambulatorio con sevoflurano tópico en pacientes con úlceras vasculares / Chronic outpatient treatment with topical sevoflurane in patients with vascular ulcers

Objetivo mostrar la efectividad y seguridad del sevoflurano tópico tras la administración ambulatoria y prolongada en los pacientes con úlceras vasculares refractarias. Métodos estudio observacional retrospectivo de pacientes con úlceras vasculares dolorosas refractarias a terapias habituales y que fueron tratados con sevoflurano tópico durante al menos 36 meses. Se recogieron las variables: edad, sexo, antecedentes médicos, comorbilidad asociada, etiología de úlcera y tratamiento médico. Se analizó la mejoría clínica y la variación de la superficie de las úlceras vasculares. Para cuantificar la intensidad del dolor basal e irruptivo antes y después del tratamiento se utilizó la escala visual analógica. Resultados del total de pacientes tratados, 9 cumplían los criterios de inclusión. La edad media fue de 74,8 ± 7,5 años. Los casos 2 y 9 fallecieron durante el seguimiento. La acción analgésica del sevoflurano tópico fue rápida (3,1 ± 2,1 min), intensa (escala visual analógica: 7 ± 1,1 a 1,4 ± 1,1 puntos) y duradera (de 6 a 24 h). Salvo el caso 4, todos experimentaron una reducción de la superficie (15,1 ± 5,0 a 2,7 ± 4,2) de las úlceras vasculares y no se observó tolerancia a lo largo del tiempo. Conclusión la aplicación de sevoflurano tópico es una estrategia analgésica y reepitelizante para las úlceras vasculares que presenta un perfil correcto de seguridad (AU)

Objective To show the effectiveness and safety of topical sevoflurane after ambulatory and prolonged administration in patients with refractory vascular ulcers. Methods Retrospective observational study analyzing clinical improvement and vascular ulcers surface area variation after topical application of sevoflurane. Inclusion criteria were patients with painful vascular ulcers refractory to usual therapies and who were treated with topical sevoflurane for at least 36 months. The following variables were collected: age, sex, medical history, associated comorbidity, ulcer etiology and medical treatment. The visual analog scale was used to measure baseline and break through pain intensity before and after treatment. Results Nine patients met the inclusion criteria of the total number of patients treated whose median age was 74.8 ± 7.5 years. Cases 2 and 9 died during follow-up. In all cases, the analgesic action of topical sevoflurane was rapid (3.1 ± 2.1 minutes), intense (visual analog scale: 7 ± 1.1 to 1.4 ± 1.1 points) and long-lasting (6 to 24 h). With the exception of case 4, all patients experienced a large reduction in vascular ulcers surface area (15.1 ± 5.0 a 2.7 ± 4.2) and tolerance was not observed over time. Conclusion Topical application of sevoflurane is an analgesic and re-epithelializing strategy for vascular ulcers with a successful safety profile (AU)

Chronic outpatient treatment with topical sevoflurane in patients with vascular ulcers. / Tratamiento crónico ambulatorio con sevoflurano tópico en pacientes con úlceras vasculares.

OBJECTIVE: To show the effectiveness and safety of topical sevoflurane after ambulatory and prolonged administration in patients with refractory vascular ulcers. METHODS: Retrospective observational study analyzing clinical improvement and vascular ulcers surface area variation after topical application of sevoflurane. Inclusion criteria were patients with painful vascular ulcers refractory to usual therapies and who were treated with topical sevoflurane for at least 36 months. The following variables were collected: age, sex, medical history, associated comorbidity, ulcer etiology and medical treatment. The visual analog scale was used to measure baseline and break through pain intensity before and after treatment. RESULTS: Nine patients met the inclusion criteria of the total number of patients treated whose median age was 74.8 ± 7.5 years. Cases 2 and 9 died during follow-up. In all cases, the analgesic action of topical sevoflurane was rapid (3.1 ± 2.1 minutes), intense (visual analog scale: 7 ± 1.1 to 1.4 ± 1.1 points) and long-lasting (6 to 24 h). With the exception of case 4, all patients experienced a large reduction in vascular ulcers surface area (15.1 ± 5.0 a 2.7 ± 4.2) and tolerance was not observed over time. CONCLUSION: Topical application of sevoflurane is an analgesic and re-epithelializing strategy for vascular ulcers with a successful safety profile.

At-home Topical Sevoflurane Added to the Conventional Analgesic Treatment for Painful leg Ulcers Greatly Improved the Analgesic Effectiveness and Reduced Opioid Consumption in a Single-Center Retrospective Comparative Study with one-Year Follow-up.

The general anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. This study was aimed to compare the analgesic effectiveness and safety of systemic analgesics alone or plus at-home topical sevoflurane for the management of patients with painful nonrevascularizable leg ulcers who were referred to a Pain Clinic by their attending vascular surgeons. We reviewed charts of patients treated in a single Pain Clinic with analgesic Standard of Care either alone (group SoC) or plus at-home topical sevoflurane (group SoC + Sevo), according to safety criteria. The area under the curve of pain over a year (AUC-Pain) was the primary outcome for analgesic effectiveness. Opioids were converted into Oral Morphine Milligram Equivalents. Groups SoC (n = 26) and SoC + Sevo (n = 38) were similar in baseline characteristics. Compared to SoC, median values [interquartile range] of area under the curve of pain for one-year follow-up were markedly lower for SoC + Sevo (54 [35-65] vs. 15 [11-23]; p < 0.000001, U Mann-Whitney test). Oral Morphine Milligram Equivalents were similar at baseline (SoC: 78.5 [22.5-135] vs. SoC + Sevo: 101.3 [30-160]; p = 0.753), but significantly lower for SoC + Sevo at three (120 [22.5-202.5] vs. 30 [0-80]; p = 0.005), six (120 [11.3-160] vs. 20 [0-67.5]; p = 0.004), nine (114.4 [0-154] vs. 0 [0-37]; p = 0.018), and 12 months (114.4 [0-154] vs. 0 [0-20]; p = 0.001). Multiple linear regression analysis revealed the addition of sevoflurane to be the most likely variable to explain this difference in outcome (ß:-33.408; p < 0.000001). Nine patients (24%) in SoC + Sevo had adverse effects attributed to sevoflurane, but only one patient needed to stop using sevoflurane due severe dermatitis. In conclusion, the addition of topical sevoflurane to the analgesic standard of care in patients with painful nonrevascularizable leg ulcers was a well-tolerated therapy that significantly improved pain control and allowed for a significant reduction in opioid consumption.

Sevoflurane topical analgesia for intractable pain with suicidal ideation.

Proper symptom management to improve quality of dying is mandatory in palliative care patients. Home-based control of pain caused by leg ulcers is challenging, especially when the pain is severe and refractory to conventional analgesics, the patient is intolerant to opioids and refuses invasive measures. This was the case for an 87-year-old woman under oncological palliative care who suffered from a leg ulcer causing refractory pain, which produced suicidal ideation. Leg amputation was indicated, but she had signed a living will refusing any invasive measures. After obtaining written informed consent, sevoflurane was applied topically on the ulcer, which resulted in a rapid and long-lasting reduction of pain. Daily self-administration of sevoflurane successfully controlled the wound pain and the patient abandoned her suicidal ideation, the wound healed 35 days later, and her quality of dying improved remarkably. Topical sevoflurane deserves further research on ulcers of vascular and also neoplastic aetiology.

Pain management & opioid dose reduction with topical sevoflurane instillations in intractable venous ulcers: a case report

Abstract Vascular ulcers (VU) constitute a major cause of pain and disability, and significantly compromise quality of life. VU have a natural tendency to become chronic and in many cases exhibit anunsatisfactoryresponse to many of the standard therapeutic options.The case of a 73 year-old Caucasian female with severe pain and poorly-controlled pain (Visual Analogic Scale-VAS- of 8-9) due to three lower leg long-standing VUs is reported and discussed herein. The patient was treated with topical instillations of undiluted sevoflurane as per institutional off-label protocol (starting doses of 1mL/cm2 twice a day, and up-titrated according to response to a maximum of 7 mL twice daily). The VAS score dropped to 0-1 shortly after initiation of therapy and remained stable throughout treatment up until the closure of the observations. Subsequently, opioid therapy was gradually tapered down and ultimately abandoned.Sevoflurane application resulted on adequate and sustained pain management of refractory VU, with no significant side effects. On account of its beneficial effectivity and safety profiles, topical sevoflurane emerges as an add-on alternative for the long-term management of VU, and potentially other painful conditions.

Topical sevofluran: a galenic experience.

Sevoflurane is a volatile liquid from the family of ether-derived alogenated hydrocarbons that is approved for the induction and  maintenance of inhalational general anesthesia in the hospital setting. This review describes the pioneering experience of a Spanish Pain Unit in the  home treatment of complicated painful wounds using topical sevoflurane  instillations according to a protocol approved for off-label use. Aspects of  safety and efficacy, both analgesic, antimicrobial and pro-healing are  addressed, and some future lines of research are discussed in terms of  new formulations for topical use. After more than seven years of use of the protocol, an experience of over 70,000 applications of topical sevoflurane  has been gained. In general terms, the analgesic effect appears quickly, is  highly intense and persists for several hours. As a result, patients can  reduce their consumption of systemic analgesics and benefit from an  improvement in their quality of life. In addition, there are signs that  suggest sevoflurane also possesses antimicrobial and pro-healing  properties. Regarding safety, pruritus at the level of the periulcerous skin  is the most frequently reported adverse effect, although it is usually  transient and well-tolerated, and no systemic toxicity has been reported.  Overall, the risk-benefit balance of the drug has so far been very  favorable. To avoid manipulation of this volatile liquid, we have developed  a new formulation of sevoflurane in gel form, which has made it possible  to successfully apply sevoflurane in the context of painful pathologies  where the skin remains intact. Furthermore, these types of new  formulations, including sevoflurane microspheres, which we have also  developed, could improve the efficacy and safety of topical sevoflurane  while reducing the occupational exposure of healthcare staff. This means  that the development of new formulations is a field with a very promising  future.

El sevoflurano es un líquido volátil de la familia de los hidrocarburos  alogenados derivados del éter que está aprobado para realizar la inducción y el mantenimiento de la anestesia general inhalatoria en ambiente  exclusivamente hospitalario. En esta revisión se expone la experiencia  pionera de nuestra Unidad del Dolor en el tratamiento domiciliario de  heridas dolorosas complejas mediante irrigaciones de sevoflurano tópico  según un protocolo aprobado para su uso fuera de ficha técnica. Se  abordan aspectos de seguridad y eficacia, tanto analgésica como  antimicrobiana y procicatrizante, y se comentan algunas líneas de futuro  en cuanto a nuevas formulaciones para uso tópico. Tras más de 7 años de  vigencia del referido protocolo, contamos con una experiencia acumulada  de más de 70.000 aplicaciones de sevoflurano tópico. En líneas generales,  el efecto analgésico aparece rápidamente en cuestión de minutos, es de  gran intensidad, y de duración prolongada por espacio de varias horas;  gracias a ello los pacientes pueden reducir el consumo de analgésicos sistémicos y, en general, su calidad de vida mejora. Además,  existen indicios que sugieren que también ejerce acción antimicrobiana y  procicatrizante. En cuanto a seguridad, el prurito a nivel de la piel  periulcerosa es el efecto adverso más frecuentemente comunicado,  aunque suele ser transitorio y bien tolerado, y no hay signos sugerentes  de toxicidad sistémica. Globalmente, el balance beneficio-riesgo es muy  favorable para los pacientes hasta el momento. Para evitar la manipulación de la presentación líquida y volátil hemos desarrollado una nueva  formulación de sevoflurano en tipo gel, lo cual ha permitido tratar  satisfactoriamente patologías dolorosas que cursan con piel íntegra;  además, este tipo de nuevas formulaciones, incluyendo las microesferas de sevoflurano que también desarrollamos, podrían mejorar la eficacia y la  seguridad del fármaco tópico a la vez que se reduce la exposición  ocupacional del personal sanitario, por lo que el desarrollo de nuevas  formulaciones es un campo con un futuro muy prometedor.

Cost-effectiveness analysis of domiciliary topical sevoflurane for painful leg ulcers.

OBJECTIVES: The general anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. We conducted a Bayesian cost-effectiveness analysis (CEA) comparing the addition of domiciliary topical sevoflurane to conventional analgesics (SEVOFLURANE, n = 38) versus conventional analgesics alone (CONVENTIONAL, n = 26) for the treatment of nonrevascularizable painful leg ulcers in an outpatient Pain Clinic of a Spanish tertiary hospital. METHODS: We used real-world data collected from charts to conduct this CEA from a public healthcare perspective and with a one-year time horizon. Costs of analgesics, visits and admissions were considered, expressed in €2016. Analgesic effectiveness was measured with SPID (Sum of Pain Intensity Difference). A Bayesian regression model was constructed, including "treatment" and baseline characteristics for patients ("arterial hypertension") and ulcers ("duration", "number", "depth", "pain") as covariates. The findings were summarized as a cost-effectiveness plane and a cost-effectiveness acceptability curve. One-way sensitivity analyses, a re-analysis excluding those patients who died or suffered from leg amputation, and an extreme scenario analysis were conducted to reduce uncertainty. RESULTS: Compared to CONVENTIONAL, SEVOFLURANE was associated with a 46% reduction in costs, and the mean incremental effectiveness (28.15±3.70 effectiveness units) was favorable to SEVOFLURANE. The estimated probability for SEVOFLURANE being dominant was 99%. The regression model showed that costs were barely influenced by any covariate, whereas effectiveness was noticeably influenced by "treatment". All sensitivity analyses showed the robustness of the model, even in the extreme scenario analysis against SEVOFLURANE. CONCLUSIONS: SEVOFLURANE was dominant over CONVENTIONAL as it was less expensive and much more effective.

Pain reduction of topical sevoflurane vs intravenous opioids in pressure ulcers.

Recently, it has been reported that topical irrigations of liquid sevoflurane on the bed of painful wounds produce a rapid, intense, and lasting analgesic effect. In this paper, A cohort of 112 patients with painful pressure ulcers who were refractory to opioids (or who exhibited undesirable adverse events to them) was treated with topical sevoflurane as per local institutional policy. These patients were recruited from an intensive care unit for a period of 3 years. The main aim was to determine the effectiveness of topical sevoflurane in reducing the pain of PUs and reducing the ulcer area. Study findings are reported and discussed herein and suggest that sevoflurane is a viable and promising treatment option for PUs.

Palliative analgesia with topical sevoflurane in cancer-related skin ulcers: a case report.

A Caucasian 39-year-old male patient with a poorly-differentiated infiltrating epidermoid penile carcinoma with urethral invasion was diagnosed. The patient received concomitant adjuvant chemotherapy with radiotherapy in the palliative setting, which produced painful ulceration of tumour lesions at loco-regional level (Numerical Rate Scale, NRS=9). The patient consented for treatment with direct topical sevoflurane instillations, at initial doses of 1 mL/cm2 of ulcerated area, as per unit protocol. The local use of undiluted sevoflurane achieved a marked reduction of the pain score in both nociceptive and irruptive pains (average NRS=3 immediately post-application). This improvement was corroborated by a decline in total morphine needs, any adverse events associated with major opiates. PGI-I and CGI-I scales were used before and after treatment with topical sevoflurane to assess patient and clinician perceptions of improvement in the quality of life. The pharmacy of our hospital had the responsibility to elaborate pre-loaded syringes with sevoflurane so that the patient was instilled simply and comfortably.

Sevoflurano tópico: una nueva opción terapéutica paliativa en las úlceras cutáneas / Topical sevoflurane: A new palliative therapeutic option for skin ulcers

La presencia de úlceras cutáneas, con tendencia a la cronicidad y con mala respuesta al arsenal terapéutico-analgésico clásico, conllevan un alto grado de dolor, discapacidad y merma en la calidad de vida. Presentamos el caso de una paciente terminal con un cuadro álgico debido a la presencia de múltiples úlceras vasculares en miembros inferiores de 3 meses de evolución y de difícil manejo por mala tolerancia a anticomiciales y opioides mayores. Las instilaciones tópicas de forma periódica del anestésico halogenado sevoflurano sobre el lecho ulceroso lograron un excelente control del dolor basal e irruptivo a los pocos minutos de su administración, y una progresiva mejoría en la cicatrización de las úlceras sin evidenciar efectos secundarios asociados

The presence of cutaneous ulcers, with a tendency to become chronic and without a response to the therapeutic-analgesic arsenal available, carry a heightened degree of pain and disability and significantly compromise patient quality of life. A case is reported of a terminally ill woman with a painful condition due to the presence of multiple vascular ulcers of 3 months onset in lower right limb, and difficult to manage because of poor tolerance to anticonvulsants and major opioids. Periodically administered topical applications of halogenated anaesthetic sevoflurane on the ulcer bed achieved good results in baseline and breakthrough pain management within a few minutes after application and a progressive improvement in the healing of ulcers without associated adverse effects

Efficacy and safety of topical sevoflurane in the treatment of chronic skin ulcers.

PURPOSE: Results of efficacy and safety assessments of topical sevoflurane use in patients with long-term treatment-refractory vascular ulcers are reported. METHODS: Patients were randomly assigned to receive sevoflurane instillations (1 mL per cm2 of ulcer area 1-4 times daily) plus standard wound care (ulcer cleaning, debridement, and dressing changes) or standard care only. Topical sevoflurane was initiated during hospitalization, with self- or nurse-administered instillations continued after discharge. Study participants were evaluated at least once weekly for 1 month and then every 2 weeks for up to 90 days. The primary efficacy measures were debridement-related and overall pain (assessed using a 10-point visual analog scale), daily opioid use, and ulcer size; secondary measures were patient and clinician impressions of improvement and ulcer-related admissions during treatment. The primary safety endpoint was intolerable sevoflurane-related adverse effects. RESULTS: Compared with the group receiving standard care alone (n = 5), the sevoflurane group (n = 10) had significant (p = 0.001) reductions in mean ± S.D. scores for debridement-related pain on day 1 of treatment and at subsequent time points; the sevoflurane group also had significant reductions in overall pain, daily opioid use, and ulcer size. Outcomes in terms of patient- and clinician-rated improvement and emergency admissions also favored the sevoflurane group. Mild localized reddening in the area surrounding ulcers occurred in 4 sevoflurane-treated patients. CONCLUSION: Direct application of sevoflurane onto vascular ulcers resulted in an intense and long-lasting analgesia and was associated with a progressive reduction of ulcer size.

Concentraciones de glucemia e insulinemia en pollos broilers machos y hembras de cuatro semanas de edad y su relación con el peso / Glycemia and insulinemia concentrations in four-weeks-old male and female broilers and their relationship to weight / Concentrações de glicemia e insulina em broilers machos e fêmeas de quatro semanas de idade e sua relação com o peso

Introducción: el metabolismo de la glucosa en aves se relaciona directamente con la secreción de insulina, ya que esta hormona ejerce una función anabólica y a la vez esa respuesta se refleja en el crecimiento de las aves. Es escasa la información que se tiene sobre variables como sexo, edad y peso y su incidencia en la secreción de insulina y su regulación sobre las concentraciones de glucosa. Objetivo: comparar las concentraciones de insulina, glucosa y peso en pollos broiler de cuatro semanas de edad analizando sus valores entre hembras y machos; establecer valores de referencia para los niveles de insulina, glucosa y peso en pollos broiler de cuatro semanas de edad. Materiales y métodos: muestras de sangre en ayunas de ochenta pollos de engorde de ambos sexos (línea Cobb 500 de cuatro semanas de edad). Se determinaron los niveles de insulina mediante inmunoensayo enzimático tipo sandwich, la glucemia mediante glucómetro; para el peso se utilizó una balanza. Los resultados fueron analizados a través del programa estadístico Stata; se acepta una diferencia estadísticamente significativa cuando p es < 0,05. Resultados: los valores de la insulina son de 0,60 ± 0,63 ng/ml; en relación con los niveles de glucemia los machos reportaron valores de 415,45 ± 40,52 mg/dl; las hembras reportaron valores de 350,72 ± 68,37 mg/dl y, finalmente, los valores de peso en machos fue de 963,73 g y en hembras de 865,64 g. Conclusiones: los machos tienen mayor peso que las hembras. Las concentraciones de glucemia en los machos es mayor que las hembras y se determina que los valores de referencia de acuerdo con el sexo son: hembras (mg/dl) 350,72 ± 68,37 y machos (mg/dl) 415 ± 40,52, y, finalmente, los niveles de insulina son mayores en las hembras que en los machos.

Introduction: Glucose metabolism in birds is directly related to insulin secretion, given that this hormone exerts an anabolic function and this response is reflected in the growth of poultry. There is little information on variables such as sex, age and weight, and their effect on insulin secretion and the regulation of glucose concentrations. Objective: To compare concentrations of insulin, glucose, and weight in four-weeks-old male and female broiler chickens, in order to establish reference values for them. Materials and methods: Fasting blood samples were collected from 80 broilers of both sexes (four-weeks-old Cobb 500 line). Enzyme immunoassay (sandwich method) was used to determine levels of insulin, glucometer for glycemia levels, and scales for weight. Results were analyzed using the Stata statistical program; a statistically significant difference is accepted when p is <0.05. Results: Insulin values are 0.60 ± 0.63 ng/mL; regarding glucose levels, males reported values between 415.45 ± 40.52 mg/dL, and females between 350.72 ± 68.37 mg/dL; finally, weight values were 963.73 g in males and 865.64 g in females. Conclusions: Males are heavier than females. Glycemia concentrations are higher in males than in females; reference values according to sex are: in females (mg/dL) 350.72 ± 68.37, and in males (mg/dL) 415 ± 40.52; finally, insulin levels are higher in females than in males.

Introdução: o metabolismo da glucose em aves se relaciona diretamente com a secreção de insulina, já que este hormona exerce uma função anabólica e ao mesmo tempo essa resposta se reflete no crescimento das aves. É escassa a informação que se tem sobre variáveis como sexo, idade e peso e sua incidência na secreção de insulina e sua regulação sobre as concentrações de glucose. Objetivo: comparar as concentrações de insulina, glucose e peso em frangos broiler de quatro semanas de idade analisando seus valores entre fêmeas e machos; estabelecer valores de referência para os níveis de insulina, glucose e peso em frangos broiler de quatro semanas de idade. Materiais e métodos: amostras de sangue em jejum de oitenta frangos de corte de ambos os sexos (linha Cobb 500 de quatro semanas de idade). Puderam-se determinar os níveis de insulina mediante imuno ensaio enzimático tipo sanduíche, a glicemia mediante glicômetro; para o peso se utilizou uma balança. Os resultados foram analisados através do programa estatístico Stata; se aceita uma diferença estatisticamente significativa quando p é < 0,05. Resultados: os valores da insulina são de 0,60 ± 0,63 ng/ml; em relação com os níveis de glicemia os machos reportaram valores de 415,45 ± 40,52 mg/dl; as fêmeas reportaram valores de 350,72 ± 68,37 mg/dl e, finalmente, os valores de peso em machos foi de 963,73 g e em fêmeas de 865,64 g. Conclusões: os machos têm maior peso que as fêmeas. As concentrações de glicemia nos machos são maiores que nas fêmeas e se determina que os valores de referência de acordo com o sexo são: fêmeas (mg/dl) 350,72 ± 68,37 e machos (mg/dl) 415 ± 40,52, e, finalmente, os níveis de insulina são maiores nas fêmeas que nos machos.

Smooth muscle role on pulmonary arterial function during acute pulmonary hypertension in sheep.

AIM: We determined the wall mechanical response of the pulmonary artery (PA) to acute pulmonary hypertension induced pharmacologically and by an occlusion maneuver, to study the vascular response of the local segment and its influence in the whole pulmonary circulation. METHODS: Pulmonary pressure and diameter were measured in six anaesthetized sheep under steady-state conditions. Transient hypertension in the PA was induced by phenylephrine (PHE) and a high pressure (HP) mechanical occlusion aimed at producing the same pulse and mean pressure responses. A viscoelastic arterial wall model was applied and the elastic (E(pd)) and viscous (micro) indexes were obtained. The micro/E(pd) ratio was adopted to quantify the damping performance of the arterial wall segment. The diastolic time constant was used as an indicator of the whole pulmonary buffering function. The systemic pressure was always measured. RESULTS: The pulmonary mean, systolic and pulse pressure increases (P < 0.05) were similar during PHE and HP, with respect to control. PHE also induced a systemic pressure rise (P < 0.05). The E(pd) elastic index increased during HP (P < 0.05) and tended to increase during PHE with respect to control. The viscous index micro only increased with PHE (P < 0.05) with respect to control and occlusion. The diastolic time constant increased with PHE with respect to control (P < 0.05). CONCLUSIONS: A pressure rise in the PA, induced by an occlusion maneuver, increased local stiffness. Similar pressure rises with smooth muscle activation (PHE), produced both a stiffness and viscous index increase. In PHE resistance increases more than compliance decreases so that the global net effect is a longer decay time. Smooth-muscle activation enhances the local damping effect (micro/E(pd)), concomitant with the buffering function improvement.

Ehrlichiosis canina / Canine ehrlichiosis

En este artículo se reporta un caso de Ehrlichiosis canina, diagnosticado mediante la detección de antígenos de Dirofilaria immitis, Borrelia burgdorferi y anticuerpos de Ehrlichia canis.1 en un caninomacho labrador dorado, con un peso de 36 kg y 6 años de edad. Se mencionan los procedimientos realizados para el diagnóstico, incluida la valoración clínica, exámenes de laboratorio y seguimiento terapéutico.

[Synchronization of the contraction of the right ventricle against an acute afterload increase. Left ventricle-like mechanical function of the right ventricle]. / Sincronización de la contracción del ventrículo derecho frente a un aumento agudo de su poscarga. Izquierdización del comportamiento mecánico del ventrículo derecho.

AIM: The aim of this study was to demonstrate right ventricular contraction synchronization during acute and moderate afterload increase. MATERIAL AND METHOD: Right and left ventricular pressures, pulmonary and aortic pressures, pulmonary flow, and ventricular volumes by sonomicrometry were measured in seven anesthetized sheep. Pulmonary arterial hypertension was induced by Escherichia coli endotoxemia. RESULTS: Acute increase of the right ventricular afterload, measured as the mean arterial pulmonary pressure (11.9 1.3 to 24 3.6 mmHg) produced the following changes in the right ventricle without preload and contractility changes: a) maximal elastance shifted towards the end of the ejection (127.5 18.5 ms) and the ejection time shortened (57.5 20.3 ms), so that the negative peak of the first ventricular pressure derivative occurred at the end of the ejection; b) the pressure-volume loop became rectangular, i.e.; the systolic and diastolic phases were isovolumic, and c) the ejection showed a single phase. CONCLUSIONS: Asynchronous and sequential right ventricular contraction with normal afterload changed to a synchronic contraction pattern as in the left ventricle during an acute and moderate afterload increase. This left ventricle-like mechanical property establishes a novel mechanical reserve mechanism of the right heart, since it allows the right ventricle to maintain its systolic function during an afterload increase, independently of the preload and contractility.

[Study of the relaxation phase of the right ventricle]. / Estudio de la fase de relajación del ventrículo derecho.

The purpose of our study was to investigate the existence or not of an isovolumic relaxation period in the right ventricle in experimental animals with normal pressures in the pulmonary artery. Right and left ventricular pressures, pulmonary and aortic pressures (microtransducers), pulmonary flow, ventricular diameters (sonomicrometer), were recorded at the same time, in 10 sheep anesthetized intravenously with pentobarbital. We obtained "off line" the first ventricular pressures derivative, the ventricular volumes and the pressure-volume loops of both ventricles. The minimum systolic right ventricular volume coincided with 0 pulmonary flow, and both with a diastolic pressure value of 0-5 mmHg in that ventricle. Once the minimum systolic volume was reached, a rapid increase of the right ventricular volume started. The right ventricular pressure-volume loop, unlike the left ventricular one, adopted a non-rectangular shape. The right ventricular ejection period lasted until the beginning of the next filling phase. We concluded that there is no right ventricular isovolumic relaxation period.

[The characteristics proper of the cardiac cycle phases of the right ventricle]. / Características propias de las fases del ciclo cardíaco del ventrículo derecho.

AIMS: The purpose of our study was to define at physiological conditions, the existence or not of an isovolumic relaxation phase in the right ventricle and its ejective phase properties. MATERIAL AND METHODS: Right and left ventricular pressures, pulmonary and aortic pressures, pulmonary flow and ventricular diameters by sonomicrometry were measured in nine anesthetized sheep. The first ventricular pressure derivative, ventricular volumes, and the right and left pressure-volume loops, were calculated "off line". An abrupt preload reduction was generated by a posterior vena caval occlusion. RESULTS: Right ventricle showed an ejection phase which can be subdivided in two phases (early and late). The end of the ejection phase was established by the temporal coincidence of the zero pulmonary flow, the minimum systolic value of the right ventricular volume and a right ventricular pressure of 0-4 mmHg. The time between the beginning of the ejection phase and: a) the end of systole; b) the negative peak of the first derivative of ventricular pressure and c) the end of ejection, were different for the right ventricle (67 +/- 15 ms, 274 +/- 30 ms, 412 +/- 33 ms, respectively), meanwhile the left ventricle showed the following values: 204 +/- 33 ms, 262 +/- 23 ms, 266 +/- 24 ms, respectively. CONCLUSIONS: Right ventricle exhibits a long lasting ejection phase which can be subdivided in two phases, spreading at the beginning of the next filling phase. This fact allows us to affirm that right ventricle does not show an isovolumic relaxation phase in comparison to left ventricle.

Right ventricle systolic pressure increase following intravenous acetylcholine injection.

In order to characterize and compare right ventricle (RV) and left ventricle (LV) and left ventricle (LV) hemodynamic responses to physiological and pharmacological maneuvers, we studied the effect of the intravenous injection of acetylcholine (ACh) in 32 anaesthetized mongrel dogs. After producing a decrease in aortic pressure and in left ventricle systolic pressure (LVSP). ACh always determined a significant increase in the right ventricle systolic pressure (RVSP) preceded or not by a fall in this parameter. Atropine and denervation of carotid and aortic pressure receptors suppressed this rise in RVSP. It is suggested that the RVSP increase is secondary to a sympathetic reflex response parting from the pressure receptors after detecting the aortic hypotension elicited by ACh following peripheral vascular bed vasodilation. Sympathetic discharge could produce a systemic venoconstriction that increases the venous return to the RV, together with a direct inotropic effect on the ventricular muscle. Both actions, peripheral and myocardial, would account for the RVSP increase. We cannot totally disconsider a probable additional pulmonary vasoconstrictor effect included as part of the sympathetic reflex response.