Continuous monitoring of intrinsic PEEP based on expired CO2 kinetics: an experimental validation study.

BACKGROUND: Quantification of intrinsic PEEP (PEEPi) has important implications for patients subjected to invasive mechanical ventilation. A new non-invasive breath-by-breath method (etCO2D) for determination of PEEPi is evaluated. METHODS: In 12 mechanically ventilated pigs, dynamic hyperinflation was induced by interposing a resistance in the endotracheal tube. Airway pressure, flow, and exhaled CO2 were measured at the airway opening. Combining different I:E ratios, respiratory rates, and tidal volumes, 52 different levels of PEEPi (range 1.8-11.7 cmH2O; mean 8.45 ± 0.32 cmH2O) were studied. The etCO2D is based on the detection of the end-tidal dilution of the capnogram. This is measured at the airway opening by means of a CO2 sensor in which a 2-mm leak is added to the sensing chamber. This allows to detect a capnogram dilution with fresh air when the pressure coming from the ventilator exceeds the PEEPi. This method was compared with the occlusion method. RESULTS: The etCO2D method detected PEEPi step changes of 0.2 cmH2O. Reference and etCO2D PEEPi presented a good correlation (R2 0.80, P < 0.0001) and good agreement, bias - 0.26, and limits of agreement ± 1.96 SD (2.23, - 2.74) (P < 0.0001). CONCLUSIONS: The etCO2D method is a promising accurate simple way of continuously measure and monitor PEEPi. Its clinical validity needs, however, to be confirmed in clinical studies and in conditions with heterogeneous lung diseases.

Comparative effects of clomipramine and duloxetine on detrusor and striated sphincter function in male and female rabbits.

OBJECTIVE: Serotonin and norepinephrine systems are involved in the neural control of lower urinary tract function. The aim of this study was to compare the response on striated anal sphincter electromyographic (SAS-EMG) activity and cystometric parameters, when duloxetine and clomipramine were intravenously administrated. METHODS: The effects of intravenous 1 and 2 mg./Kg. duloxetine or clomipramine on lower urinary tract function were studied in a total of 32 male and 32 female rabbits, under nonirritative conditions (intravesical infusion of saline) and in a model of bladder irritation (i.e., transvesical infusion of 0.5% acetic acid). A transurethral double-lumen catheter in male rabbits, and a subcutaneous cystostomy in female rabbits, were used for liquid infusion and recording of intravesical pressure during a cystometrogram. Simultaneously, SAS-EMG was recorded through electromyography electrodes placed in the perianal striated muscle. RESULTS: Cystometric parameters: Under irritative conditions, 2 mg./Kg. clomipramine in male rabbits and 1 or 2 mg./Kg. in female rabbits, depending on the dose, increased bladder capacity (BC), contraction duration (CD) and intercontraction interval (ICI), and decreased baseline pressure (BP). In male and female rabbits, duloxetine dose-dependently increased BC, CD and ICI. Under nonirritative conditions, clomipramine at 2 mg./Kg. and duloxetine dose-dependently solely increased BC in female rabbits. Electromyographic activity: A marked effect on SAS-EMG activity of duloxetine under irritative conditions was revealed in male and female rabbits. Under these conditions, clomipramine increased SAS-EMG activity only in female rabbits. Under nonirritative conditions, 2 mg./Kg. duloxetine increased SAS-EMG activity only in female rabbits. CONCLUSIONS: The stronger effects on the SAS-EMG activity were produced by duloxetine in female rabbits under irritated bladder conditions. Clomipramine, under irritative conditions, had a relaxing effect on intravesical pressure, which is not the case with duloxetine.

Comparative effects of clomipramine and duloxetine on detrusor and striated sphincter function in male and female rabbits

OBJECTIVE: Serotonin and norepinephrine systems are involved in the neural control of lower urinary tract function. The aim of this study was to com- pare the response on striated anal sphincter electromyographic (SAS-EMG) activity and cystometric parameters, when duloxetine and clomipramine were intravenously administrated. METHODS: The effects of intravenous 1 and 2 mg./Kg. duloxetine or clomipramine on lower urinary tract function were studied in a total of 32 male and 32 female rabbits, under nonirritative conditions (intravesical infusion of saline) and in a model of bladder irritation (i.e., transvesical infusion of 0.5% acetic acid). A transurethral double-lumen catheter in male rabbits, and a subcutaneous cystostomy in female rabbits, were used for liquid infusion and recording of intravesical pressure during a cystometrogram. Simultaneously, SAS-EMG was recorded through electromyography electrodes placed in the perianal striated muscle. RESULTS: Cystometric parameters: Under irritative conditions, 2 mg./Kg. clomipramine in male rabbits and 1 or 2 mg./Kg. in female rabbits, depending on the dose, increased bladder capacity (BC), contraction duration (CD) and intercontraction interval (ICI), and decreased baseline pressure (BP). In male and female rabbits, duloxetine dose-dependently increased BC, CD and ICI. Under nonirritative conditions, clomipramine at 2 mg./ Kg. and duloxetine dose-dependently solely increased BC in female rabbits. Electromyographic activity: A marked effect on SAS-EMG activity of duloxetine under irritative conditions was revealed in male and female rabbits. Under these conditions, clomipramine increased SAS-EMG activity only in female rabbits. Under nonirritative conditions, 2 mg./Kg. duloxetine increased SAS- EMG activity only in female rabbits. CONCLUSIONS: The stronger effects on the SAS-EMG activity were produced by duloxetine in female rabbits under irritated bladder conditions. Clomipramine, under irritative conditions, had a relaxing effect on intravesical pressure, which is not the case with duloxetine (AU)

OBJETIVO: Neurotransmisores como la serotonina y la norepinefrina están involucrados en el control neural del tracto urinario inferior. El objetivo de este trabajo consistió en comparar los efectos de du- loxetina y clomipramina sobre parámetros cistométricos y la actividad electromiográfica del esfínter anal estriado (SAS-EMG). MÉTODOS: Los efectos de dosis progresivas (1 y 2 mg./Kg.) de duloxetina o clomipramina, administrados intravenosamente, sobre el tracto urinario inferior se estudiaron en un total de 32 conejos machos y 32 hembras, en condiciones normales (infundiendo continuamente suero salino en la vejiga) y mediante un mo- delo de irritación vesical (infusión continua de ácido acético al 0,5% en la vejiga). Un catéter transuretral de doble lumen en machos, y una cistostomía subcutánea en hembras, se utilizaron para la infusión de líquido y para recoger la presión intravesical durante el cistometrograma. Simultaneamente, SAS-EMG fué registrada a través de dos electrodes situados en el músculo estriado perianal. RESULTADOS: Parámetros cistométricos: En condiciones irritativas, clomipramina tras 2 mg./Kg. en los machos y de forma dosis-dependiente en las hembras, incrementó la capacidad vesical (CV), la duracion de la con- tracción (DC) y el intervalo entre contracciones (IC), y redujo la presión vesical (PB). Por otro lado, duloxetina incrementó la CV, la DC y el IC, de forma dosis-dependiente, tanto en conejos machos como en hembras, cuando fueron estudiados en condiciones irritativas. En condiciones normales, duloxetina, de forma dosis- dependiente, y clomipramina, tras la administración de 2 mg./Kg., sólo aumentaron la CV en los conejos hembra. Electromigrafía: Un potente efecto de duloxetina sobre la SAS-EMG, en condiciones de irritabilidad vesical, se vio tanto en machos como en hembras. En estas condiciones, la clomipramina incrementó, de forma dosis-dependiente, la SAS-EMG sólo en hembras. Por otro lado, en condiciones normales, el único efecto significativo sobre la SAS-EMG que se vio, fue con 2 mg./Kg. de duloxetina en hembras. CONCLUSIONES: Duloxetina produce un efecto mar- cado sobre la SAS-EMG en conejas en condiciones irritativas. En estas mismas condiciones, clomipramina tiene mayor efecto relajante sobre el detrusor, reduciendo la presión intravesical (AU)

Experimental methods for "in vivo" study of detruso-sphincteric pharmacological response: a critical review.

OBJECTIVE: We review "in vivo" methods most commonly used for the investigation of detruso-sphincteric pharmacological response. We compare this information with the procedures used in our Institution for these purposes. METHODS: The medical databases MEDLINE, EMBASE and Pascal Biomed were searched to identify articles on this subject. The methods used have been critically analyzed and compared with the methods used in our experiments. RESULTS: The "in vivo" dynamic investigation of vesico-sphincteric function began at our Institution in the late 70s. Methods for the study of vesical or urethral dynamic behaviour have been devised to be applied independently or simultaneously. Great difficulties have been encountered, both in our experience and in the work of revised authors, in the integrated investigation of Lower Urinary Tract function. Methods to overcome these drawbacks have been proposed. CONCLUSIONS: Methods for "in vivo" studies of physiological and pharmacological detruso-sphincteric function are presented and compared with current procedures found in the literature. It is highlighted that an integrated method for the simultaneous study of vesico-sphincteric function is a difficult challenge yet to be taken up.

Métodos experimentales para el estudio "in vivo" de la respuesta farmacológica detruso-esfinteriana: revisión crítica / Experimental methods for "in vivo" study of detruso-sphincteric pharmacological response: a critical review

OBJETIVOS: Revisamos los métodos "in vivo" utilizados con mayor frecuencia en la investigación de la respuesta farmacológica detruso-esfinteriana. Comparamos esta información con los procedimientos utilizados en nuestra Institución. MÉTODOS: Se realizó una búsqueda en las bases de datos médicas MEDLINE, EMBASE y Pascal Biomed para identificar artículos sobre esta materia. Se han analizado críticamente los métodos y se han comparado con los utilizados en nuestros experimentos. RESULTADOS: La investigación dinámica "in vivo" de la función vésico-esfinteriana comenzó en nuestra Institución a finales de los 70. Se han ideado métodos para estudio del comportamiento dinámico vesical o uretral que pueden aplicarse independiente o simultáneamente. Tanto en nuestra experiencia como en el trabajo de los autores revisados se han encontrado grandes dificultades para la investigación integrada de la función del tracto urinario inferior. Se han propuesto métodos para superar estos problemas. CONCLUSIONES: Se presentan los métodos para los estudios "in vivo" de la fisiología y de la farmacología de la función detruso-esfinteriana y se comparan con procedimientos actuales encontrados en la literatura. Se destaca que el desarrollo de un método integrado para el estudio simultáneo de la función vésico-esfinteriana es todavía un desafío (AU)