Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats

Objectives The present study aimed to assess the effect of the specific dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin on blood pressure and renal function in young prehypertensive (5-week-old) and adult spontaneously hypertensive rats (SHRs; 14-week-old). Methods Sitagliptin (40 mg/kg twice daily) was given by oral gavage to young (Y-SHR + IDPPIV) and adult (A-SHR R IDPPIV) SHRs for 8 days. Kidney function was assessed daily and compared with age-matched vehicle-treated SHR (Y-SHR and A-SHR) and with normotensive Wistar-Kyoto rats (Y-WKY and A-WKY). Arterial blood pressure was measured in these animals at the end of the experimental protocol. Additionally, Na(+)/H(+) exchanger isoform 3 (NHE3) function and expression in microvilli membrane vesicles were assessed in young animals. Results Mean arterial blood pressure of Y-SHR + IDPPIV was significantly lower than that of Y-SHR (104 +/- 3 vs. 123 +/- 5 mmHg, P < 0.01) and was similar to Y-WKY (94 +/- 4 mmHg, P > 0.05). Compared to Y-SHR, Y-SHR + IDPPIV exhibited enhanced cumulative urinary flow and sodium excretion and decreased NHE3 activity and expression in proximal tubule microvilli. In the A-SHR, sitagliptin treatment had no significant effect on either renal function or arterial blood pressure. Conclusion Our data suggest that DPPIV inhibition attenuates blood pressure rising in young prehypertensive SHRs, partially by inhibiting NHE3 activity in renal proximal tubule. J Hypertens 29:520-528 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Atmospheric pressure photoionization mass spectrometry as a tool for the investigation of the hydrolysis reaction mechanisms of phosphite antioxidants

The hydrolysis reaction mechanism of phosphite antioxidants is investigated by liquid chromatography-mass spectrometry (LC/MS). The phosphites were chosen because they differed in chemical structure and phosphorus content. Dopant assisted-atmospheric pressure photoionization (DA-APPI) is chosen as the ion source for (lie ionization of the compounds. [it our previous work, DA-APPI was shown to offer an attractive alternative to atmospheric pressure chemical ionization (APCI) since it provided background-ion free mass spectra and higher sensitivity [M. Papanastasiou, et al., Polymer Degradation and Stability 91 (11) (2006) 2675-2682]. In positive ion mode, the molecules are generally detected in their protonated form. In negative ion mode, the phosphites are unstable and only fragment ions are observed: these however, are characteristic of each phosphite and may be used for the identification of the analytes in complex mixtures. The analytes under investigation are exposed to accelerated humid ageing conditions and their hydrolytic pathway and stability is investigated. Different substituents around the phosphorus atom are shown to have a significant effect on the stability of the phosphites, with phenol substituents producing very hydrolytically stable structures. Alkanox P24 and PEP-36 follow a similar hydrolytic pathway via the scission of the first and then the second P-O-phenol bonds, eventually leading to the formation of phenol, Phosphorous acid and pentaerythritol as end products. HP-10 exhibits a rather different Structure and the products detected suggest scission of either the P-O-hydrocarbon or one of the P-O-phenol bonds. A phenomenon similar to that of autocatalysis is observed for all phosphites and is attributed to the formation of dialkyl phosphites as intermediate products. (C) 2008 Elsevier B.V. All rights reserved.

Cardiovascular effects of desflurane following acute hemorrhage in dogs

Objective: To determine the cardiovascular effects of desflurane in dogs following acute hemorrhage.Design: Experimental study.Animals: Eight mix breed dogs.Interventions: Hemorrhage was induced by withdrawal of blood until mean arterial pressure (MAP) dropped to 60 mmHg in conscious dogs. Blood pressure was maintained at 60 mmHg for 1 hour by further removal or replacement of blood. Desflurane was delivered by facemask until endotracheal intubation could be performed and a desflurane expiratory end-tidal concentration of 10.5 V% was maintained.Measurements and main results: Systolic, diastolic, and mean arterial blood pressure (SAP, DAP and MAP), central venous pressure (CVP), cardiac output (CO), stroke volume (SV), cardiac index (0), systemic vascular resistance (SVR), heart rate (HR), respiratory rate (RR), partial pressure of carbon dioxide in arterial blood (PaCO2), and arterial pH were recorded before and 60 minutes after hemorrhage, and 5, 15, 30, 45 and 60 minutes after intubation. Sixty minutes after hemorrhage, SAP, DAP, MAP, CVP, CO, Cl, SV, PaCO2, and arterial pH decreased, and HR and RR increased when compared with baselines values. Immediately after intubation, MAP and arterial pH decreased, and PaCO2 increased. Fifteen minutes after intubation SAP, DAP, MAP, arterial pH, and SVR decreased. At 30 and 45 minutes, MAP and DAP remained decreased and PaCO2 increased, compared with values measured after hemorrhage. Arterial pH increased after 30 minutes of desflurane administration compared with values measured 5 minutes after intubation.Conclusions: Desflurane induced significant changes in blood pressure and arterial pH when administered to dogs following acute hemorrhage.

The effects of 2 levels of the inspired oxygen fraction on blood gas variables in propofol-anesthetized dogs with high intracranial pressure

The influence of 2 different levels of the inspired oxygen fraction (FiO(2)) on blood gas variables was evaluated in dogs with high intracranial pressure (ICP) during propofol anesthesia (induction followed by a continuous rate infusion [CRI] of 0.6 mg/kg/min) and intermittent positive pressure ventilation (IPPV). Eight adult mongrel dogs were anesthetized on 2 occasions, 21 d apart, and received oxygen at an FiO(2) of 1.0 (G100) or 0.6 (G60) in a randomized crossover fashion. A fiberoptic catheter was implanted on the surface of the right cerebral cortex for assessment of the ICP. An increase in the ICP was induced by temporary ligation of the jugular vein 50 min after induction of anesthesia and immediately after baseline measurement of the ICP. Blood gas measurements were taken 20 min later and then at 15-min intervals for 1 h. Numerical data were submitted to Morrison's multivariate statistical methods. The ICP, the cerebral perfusion pressure and the mean arterial pressure did not differ significantly between FiO(2) levels or measurement times after jugular ligation. The only blood gas values that differed significantly (P < 0.05) were the arterial oxygen partial pressure, which was greater with G100 than with G60 throughout the procedure, and the venous haemoglobin saturation, that was greater with G100 than with G60 at M0. There were no significant differences between FiO(2) levels or measurement times in the following blood gas variables: arterial carbon dioxide partial pressure, arterial hemoglobin saturation, base deficit, bicarbonate concentration, pH, venous oxygen partial pressure, venous carbon dioxide partial pressure and the arterial-to-end-tidal carbon dioxide difference.

Bispectral index in dogs with high intracranial pressure, anesthetized with propofol and submitted to two levels of FiO2

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Intraocular pressure and its correlation with blood gas parameters in crested caracaras (Caracara plancus) anesthetized with isoflurane and sevoflurane

Avaliou-se a pressão intra-ocular (PIO) e estimaram-se as correlações entre PIO e pressão de dióxido de carbono (PaCO2) e pH arterial de cinco caracarás (Caracara plancus), anestesiados com isofluorano (ISO) ou sevofluorano (SEV). Valores basais da PIO foram aferidos em ambos os olhos (M0). Cateterizou-se previamente a artéria braquial para obtenção de parâmetros hemogasométricos e cardiorrespiratórios. Anestesia foi induzida com ISO a 5V% e mantida por 40 minutos com 2,5V%. PIO e amostras de sangue foram avaliadas em diferentes momentos até o final do procedimento. Após recuperação, uma segunda anestesia foi realizada com SEV a 6% e mantida com 3,5%. Os parâmetros foram aferidos nos mesmos momentos estabelecidos previamente. A PIO decresceu significativamente (P=0,012) de M0 em todos os momentos e não houve diferença estatística entre ISO e SEV. Correlações significativas entre PIO e PaCO2 e entre PIO e pH sangüíneo foram observadas apenas para a anestesia com SEV. O pH sangüíneo decresceu paralelamente a PIO, enquanto a PaCO2 aumentou, em carcarás anestesiados com isofluorano e sevofluorano.

Venous tone and cardiac function in the South American rattlesnake Crotalus durissus: mean circulatory filling pressure during adrenergic stimulation in anaesthetised and fully recovered animals

The effects of adrenergic stimulation on mean circulatory filling pressure (MCFP), central venous pressure (P-CV) and stroke volume (Vs), as well as the effects of altered MCFP through changes of blood volume were investigated in rattlesnakes (Crotalus durissus). MCFP is an estimate of the upstream pressure driving blood towards the heart and is determined by blood volume and the activity of the smooth muscle cells in the veins (venous tone). MCFP can be determined as the plateau in P-CV during a total occlusion of blood flow from the heart.Vs decreased significantly when MCFP was lowered by reducing blood volume in anaesthetised snakes, whereas increased MCFP through infusion of blood (up to 3 ml kg(-1)) only led to a small rise in Vs. Thus, it seems that end-diastolic volume is not affected by an elevated MCFP in rattlesnakes. To investigate adrenergic regulation on venous tone, adrenaline as well as phenylephrine and isoproterenol (alpha- and beta-adrenergic agonists, respectively) were infused as bolus injections (2 and 10 mu g kg(-1)). Adrenaline and phenylephrine caused large increases in MCFP and P-CV, whereas isoproterenol decreased both parameters. This was also the case in fully recovered snakes. Therefore, adrenaline affects venous tone through both alpha- and beta-adrenergic receptors, but the alpha-adrenergic receptor dominates at the dosages used in the present study. Injection of the nitric oxide donor SNP caused a significant decrease in P-CV and MCFP. Thus, nitric oxide seems to affect venous tone.

Pressure drop correlation for oil-refrigerant R134a mixture flashing flow in a small diameter tube

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of subcutaneous methadone, morphine, buprenorphine or saline on thermal and pressure thresholds in cats

This study compared pressure and thermal thresholds after administration of three opioids in eight cats. Pressure stimulation was performed via a bracelet taped around the forearm. Three ball-bearings were advanced against the forearm by inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was tested as previously reported using a heated probe held against the thorax [Dixon et al. (2002) Research in Veterinary Science, 72, 205]. After baseline recordings, each cat received subcutaneous methadone 0.2 mg/kg, morphine 0.2 mg/kg, buprenorphine 0.02 mg/kg or saline 0.3 mL in a four period cross-over study. Measurements were made at 15, 30, 45 min and 1, 2, 3, 4, 8, 12 and 24 h after the injection. Data were analysed by ANOVA (P < 0.05). There were no significant changes in thresholds after saline. Thermal threshold increased at 45 min after buprenorphine (maximum 2.8 +/- 3 degrees C), 1-3 h after methadone (maximum 3.4 +/- 1.9 degrees C) and 45 min to 1 h (maximum 3.4 +/- 2 degrees C) after morphine. Pressure threshold increased 30-45 min (maximum 238 +/- 206 mmHg) after buprenorphine, 45-60 min after methadone (maximum 255 +/- 232 mmHg) and 45-60 min and 3-6 h (maximum 255 +/- 232 mmHg) after morphine. Morphine provided the best analgesia, and methadone appears a promising alternative. Buprenorphines limited effect was probably related to the subcutaneous route of administration. Previously, buprenorphine has produced much greater effects when given by other routes.

High-Frequency Oscillatory Ventilation Associated With Inhaled Nitric Oxide Compared to Pressure-Controlled Assist/Control Ventilation and Inhaled Nitric Oxide in Children: Randomized, Non-Blinded, Crossover Study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Incidence of high blood pressure in a group of tannery workers in Brazil

O objetivo deste estudo foi medir a incidência de hipertensão arterial sistêmica em um curtume de médio porte em Botucatu, São Paulo, Sudeste do Brasil, onde havia sido observada, em estudo prévio, uma correlação positiva entre tempo de trabalho e níveis pressóricos, bem como uma alta prevalência de hipertensão. Para tanto, uma coorte de trabalhadores desse curtume foi acompanhada durante sete anos. Ao final do seguimento, estimou-se a taxa de incidência de hipertensão arterial como 0,0964.ano-1, valor considerado elevado se comparado com o encontrado em outros grupos profissionais.

Effect of intravenous propofol and remifentanil on heart rate, blood pressure and nociceptive response in acepromazine premedicated dogs

ObjectiveTo investigate the cardiorespiratory, nociceptive and endocrine effects of the combination of propofol and remifentanil, in dogs sedated with acepromazine.Study designProspective randomized, blinded, cross-over experimental trial.AnimalsTwelve healthy adult female cross-breed dogs, mean weight 18.4 +/- 2.3 kg.MethodsDogs were sedated with intravenous (IV) acepromazine (0.05 mg kg-1) followed by induction of anesthesia with IV propofol (5 mg kg-1). Anesthesia was maintained with IV propofol (0.2 mg kg-1 minute-1) and remifentanil, infused as follows: R1, 0.125 mu g kg-1 minute-1; R2, 0.25 mu g kg-1 minute-1; and R3, 0.5 mu g kg-1 minute-1. The same dogs were administered each dose of remifentanil at 1-week intervals. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (f(R)), end tidal CO(2) (Pe'CO(2)), arterial hemoglobin O(2) saturation, blood gases, and rectal temperature were measured before induction, and 5, 15, 30, 45, 60, 75, 90, and 120 minutes after beginning the infusion. Nociceptive response was investigated by electrical stimulus (50 V, 5 Hz and 10 ms). Blood samples were collected for plasma cortisol measurements. Statistical analysis was performed by anova (p < 0.05).ResultsIn all treatments, HR decreased during anesthesia with increasing doses of remifentanil, and increased significantly immediately after the end of infusion. MAP remained stable during anesthesia (72-98 mmHg). Antinociception was proportional to the remifentanil infusion dose, and was considered satisfactory only with R2 and R3. Plasma cortisol concentration decreased during anesthesia in all treatments. Recovery was smooth and fast in all dogs.Conclusions and clinical relevanceInfusion of 0.25-0.5 mu g kg-1 minute-1 remifentanil combined with 0.2 mg kg-1 minute-1 propofol produced little effect on arterial blood pressure and led to a good recovery. The analgesia produced was sufficient to control the nociceptive response applied by electrical stimulation, suggesting that it may be appropriate for performing surgery.

Development of a pressure nociceptive threshold testing device for evaluation of analgesics in cats

A pressure analgesiometric device was developed for unrestrained cats. Eleven cats were studied. Stimulation was via three rounded pins within a bracelet on the forearm. The pins were advanced by manual bladder inflation. Bladder pressure was measured using a strain gauge pressure transducer. The threshold was recorded at the behavioural end point. Thresholds were measured at 5 and 15 min intervals for 2-4 h, after removal/replacement of the cuff, for 120 min after SC butorphanol (0.4 mg/kg), and with mild skin inflammation at the testing site. Data were analysed using ANOVA. Pressure thresholds in untreated cats were around 150 mmHg. The minimum interval for testing was established as 15 min. Data were reproducible over 4 h and beyond 24 h. Thresholds in 5 cats increased (P < 0.05) above baseline for 45 min after butorphanol with a maximum increase of 270 +/- 182 mmHg at 10 min. Thresholds decreased with inflammation. The method appears suitable for feline analgesia investigations. (c) 2006 Elsevier Ltd. All rights reserved.

Evaluation of intraocular pressure in association with cardiovascular parameters in normocapnic dogs anesthetized with sevoflurane and desflurane

The objective of this study was to determine intraocular pressure (IOP) and cardiac changes in normocapnic dogs maintained under controlled ventilation and anesthetized using sevoflurane or desflurane. Sixteen healthy adult mixed-breed dogs, seven males and nine females, weighing 10-15 kg were used. The dogs were randomly assigned to one of two groups composed of eight animals anesthetized with sevoflurane (SEVO) or desflurane (DESF). In both groups, anesthesia was induced with propofol (10 mg/kg), and neuromuscular blockade was achieved with rocuronium (0.6 mg/kg/h IV). No premedication was given. Ventilation was adjusted to maintain end-tidal carbon dioxide partial pressure at 35 mmHg. Anesthesia was maintained with 1.5 minimum alveolar concentration (MAC) of sevoflurane or desflurane. In both groups IOP was measured by applanation tonometry (Tono-Pen) before induction of anesthesia. IOP, mean arterial pressure (MAP), heart rate (HR), cardiac index (CI) and central venous pressure (CVP) were also measured 45 min after the beginning of inhalant anesthesia and then every 20 min for 60 min. A one-way repeated measures ANOVA was used to compare data within the same group and Student's t-test was used to assess differences between groups. P < 0.05 was considered statistically significant. Measurements showed normal IOP values in both groups, even though IOP increased significantly from baseline during the use of desflurane. IOP did not differ between groups. CI in the desflurane group was significantly greater than in the sevoflurane group. Sevoflurane and desflurane have no clinically significant effects on IOP, MAP, HR, CI or VCP in the dog.

Nerve grafts prevent paraplegic pressure ulcers

We present an optimistic neural solution to the depressing challenge of decubitus pressure ulcers in the paraplegic patient. This is a limited study of two paraplegic men followed for several years. Sural nerve grafts, performed end-to-side, successfully bridged the sciatic nerve to intercostal nerves with surprising benefits for both men.