Short-Term Effects of Hydroxyethylstarch Resuscitation on Systemic and Regional Hemodynamics and Metabolism in a Brain-Dead Canine Model

Background. Hydroxyethylstarch (HES) is a synthetic polymer of glucose that has been suggested for therapeutic use in long-term plasma expansion. The aim of this study was to test the hypothesis that the infusion of a small volume of HES may provide benefits in systemic and regional hemodynamics and metabolism in a brain-dead canine model compared with large volume crystalloid resuscitation. Methods. Fourteen mongrel dogs were subjected to a brain-death protocol by consecutive insufflations of a balloon catheter in the epidural space. One hour after induction of brain-death, the animals were randomly assigned to two groups: NS (0.9% NaCl, 33mL/kg), and HES (6% HES 450/0.7, 17mL/Kg). Systemic and regional hemodynamics were evaluated using Swan-Ganz, ultrasonic flowprobes, and arterial catheters. Serial blood samples were collected for blood gas, electrolyte, and serum chemistry analysis. Systemic, hepatic, and splanchnic O(2)-derived variables were also calculated. Results. Epidural balloon insufflations induced a significant increase in mean arterial pressure, cardiac output (MAP and CO, respectively), regional blood flow, and systemic vascular resistance. Following the hyperdynamic phase, severe hypotension with normalization of systemic and regional blood flow was observed. Fluid resuscitation induced a prompt increase in MAP, CO, and portal vein blood flow, and a significant reduction in systemic and pulmonary vascular resistance. There were no differences between groups in metabolic indices, liver function tests (LFTs), or renal function tests. HES was more effective than NS in restoring cardiac performance in the first 2h after fluid resuscitation (P < 0.05). Both tested solutions partially and temporarily restored systemic and regional oxygen delivery. Conclusion. Small volumes of 6% HES 450/0.7 improved cardiovascular performance and provided the same regional hemodynamic and metabolic benefits of large volumes of isotonic crystalloid solutions. (C) 2011 Elsevier Inc. All rights reserved.

Temporal evolution of epithelial, vascular and interstitial lung injury in an experimental model of idiopathic pulmonary fibrosis induced by butyl-hydroxytoluene

This study was undertaken to test whether the structural remodelling of pulmonary parenchyma can be sequentially altered in a model and method that demonstrate the progression of the disease and result in remodelling within the lungs that is typical of idiopathic pulmonary fibrosis. Three groups of mice were studied: (i) animals that received 3-5-di-tert-butyl-4-hydroxytoluene (BHT) and were killed after 2 weeks (early BHT = 9); (ii) animals that received BHT and were killed after 4 weeks (late BHT = 11); (iii) animals that received corn oil solution (control = 10). The mice were placed in a ventilated Plexiglas chamber with a mixture of pure humidified oxygen and compressed air. Lung histological sections underwent haematoxylin-eosin, immunohistochemistry (epithelial, endothelial and immune cells) and specific staining (collagen/elastic fibres) methods for morphometric analysis. When compared with the control group, early BHT and late BHT groups showed significant decrease of type II pneumocytes, lower vascular density in both and higher endothelial activity. CD4 was increased in late BHT compared with early and control groups, while CD8, macrophage and neutrophil cells were more prominent only in early BHT. The collagenous fibre density were significantly higher only in late BHT, whereas elastic fibre content in late BHT was lower than that in control group. We conclude that the BHT experimental model is pathologically very similar to human usual interstitial pneumonia. This feature is important in the identification of animal models of idiopathic pulmonary fibrosis that can accurately reflect the pathogenesis and progression of the human disease.

High-pressure phase diagram of the drug mitotane in compressed and/or supercritical CO(2)

This work provides experimental phase diagram of mitotane, a drug used in the chemotherapy treatment of adrenocortical carcinoma, in compressed and/or supercritical CO(2). The synthetic-static method in a high-pressure variable-volume view cell coupled with a transmitted-light intensity probe was used to measure the solid-fluid (SF) equilibrium data. The phase equilibrium experiments were determined in temperature ranging from (298.2 to 333.1) K and pressure up to 22 MPa. Peng-Robinson equation of state (PR-EoS) with classical mixing rule was used to correlate the experimental data. Excellent agreement was found between experimental and calculated values. (C) 2009 Elsevier Ltd. All rights reserved.

Peripartum Haemodynamic Status of Bitches with Normal Birth or Dystocia

There has been limited investigation of parturition in the bitch and there is little information published on clinical and obstetrical examination other than opinion and anecdote. While there are substantial data on haemodynamic and vascular changes during normal parturition in humans, little is known about the physiological events in the dog. This study was aimed at maternal haemodynamic changes occurring during normal parturition and to investigate how these were modified in bitches with dystocia (DYST) treated either medically or via assisted delivery and caesarean operation. Three groups of 10 bitches were investigated; those with normal parturition, those with DYST corrected by manipulative assistance or caesarean operation and those with uterine inertia treated by oxytocin administration. Heart rate, systolic and diastolic blood pressure, electrocardiogram and blood glucose concentration were measured pre-partum, intra-partum, immediately after parturition and 1 h later. Heart rate was high at all times throughout the study and the majority of bitches had normal sinus rhythm. Blood pressure was generally within the normal range, and although systolic and diastolic blood pressure was highest during the intra-partum period and sometimes during the immediate post-partum period, there were no significant differences between groups. All bitches had blood glucose concentrations within the normal range throughout the study although pre-partum concentrations were statistically lower than many of the other time periods. The study provides useful physiological data that will facilitate monitoring and clinical management of bitches throughout normal parturition and DYST.

Pulmonary Maturation in Canine Foetuses From Early Pregnancy to Parturition

Development of the foetal respiratory system includes both pulmonary growth and maturation. In human medicine, a higher incidence of respiratory distress is reported in newborn males. This study aimed to identify different phases of canine foetal lung maturation throughout pregnancy, to determine the stage of pregnancy in which surfactant production begins and to compare pulmonary development of male and female foetuses. Pregnant bitches (34) were subjected to elective ovariohysterectomy and allocated into four groups, according to the stage of pregnancy: 30-40 days of pregnancy (n = 10), 41-50 days (n = 10), 51-60 days (n = 10) and bitches in the first stage of parturition (n = 4). Foetal lungs were histologically processed and evaluated by optical microscopy. The pseudoglandular phase was identified between the 35th day and 46th day of gestation; the onset of canalicular and saccular periods was observed, respectively, from the 48th day and 60th day of pregnancy. Lungs from foetuses at term were in the saccular phase; thus, the development into the alveolar period occurs in the neonatal period. The histological analyses revealed that respiratory tract development is centrifugal, from upper to lower airways. Therefore, it is possible to identify distinct development periods in different portions of the same organ. In conclusion, the saccular phase of lung development begins around 57 and 60 days of pregnancy, the period in which surfactant production is believed to occur. Male and female foetuses present similar pulmonary development from early pregnancy until parturition.

Comparison of ketamine and S(+)-ketamine, with romifidine and diazepam, for total intravenous anesthesia in horses

Objective To compare the quality of induction and recovery, degree of muscle relaxation, clinically apparent potency and cardiopulmonary effects of racemic ketamine or S(+)-ketamine when used for total intravenous anesthesia in horses. Study design Prospective randomized clinical trial Animals Sixteen healthy stallions (323 +/- 99 kg), with a mean age of 6.2 years, undergoing castration. Methods Horses were pre-medicated with romifidine IV, 15 minutes before induction of anesthesia. Each animal was then randomly allocated to receive either diazepam and ketamine (DK) or diazepam and S(+)-ketamine (DKS) at similar doses to induce anesthesia. For maintenance of anesthesia, 1/4 of the initial bolus of ketamine alone or S(+)-ketamine alone was administered, as required. Heart rate (HR), respiratory rate (RR) and systolic blood pressure were measured before and at 10-minute intervals during recumbency. Time from induction to lateral recumbency, time from induction to first additional dose, time from last additional dose to return to sternal posture and time from last additional dose to standing were recorded, and a subjective evaluation of quality of induction, endotracheal intubation, muscle relaxation and quality of recovery was recorded. Results The quality of the induction and duration of anesthesia were similar in both groups. HR, RR and systolic blood pressure were not significantly different between groups. Although some animals which received DKS showed some minor excitatory effects (25% of them) during the induction of anesthesia, these animals received 32% fewer doses for the maintenance of anesthesia and the recovery scores were better. Conclusions and clinical relevance S(+)-ketamine showed some advantages over racemic ketamine, such as less anesthetic agent being required and better overall recovery from anesthesia. Further studies are needed to obtain the optimum induction dose for the S(+)-ketamine.