Scholarly Works, Biomedical Sciences and Pathobiology

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Blood Gas Tension Changes in Dogs Anesthetized with Two Different Oxygen Flow Rates Using a Nonrebreathing Bain Anesthetic System
Natalini, Claudio Corrêa; Futema, Fábio; Serpa, Priscila B. S.; Nogueira Estrella, Jose Pedro; Pires, Jefferson da Silva D. S. (Universidade Federal do Rio Grande do Sul, 2010-01-01)
Background: The non-rebreathing anesthetic system is one of the most used in veterinary medicine in small animals due to the low resistance to breathing. The Bain System is constructed with one corrugated external hose, one internal conducting duct for fresh gases, an optional pop-off valve and two connections (one for the breathing bag and the other for the patient). According to the literature recommendations, this system requires an oxygen flow rate between 130-200 mL/kg/min. This present work aims to evaluate the arterial blood gases tension changes in dogs anesthetized with two different oxygen flow rates (100 mL/kg/min or 200 ml/kg/min) using a nonrebreathing Bain System, in adult healthy dogs. Materials, Methods & Results: Fourteen adult healthy mongrel dogs (10 males and 4 females) ranging from 3.5 to 4.5 years old, with average body weight of 12.5 + 0.81 kg, were submitted to preanesthetic medication with acepromazine maleate (0.1 mg/kg IM) and fentanyl citrate (5 mcg/kg IM) and after 15 min induction of anesthesia was performed using sodium thiopental (9 mg/ kg, IV). An anesthetic state using the Bain System was maintained using oxygen 100 mL/kg/min and isoflurane 1.5 V% in group I and oxygen 200 mL/kg/min and isoflurane 1.5V% in group II. Heart and respiratory rates, oxygen saturation, arterial pH, blood gases and bicarbonate were the variables analyzed after induction and before intubation (T0), immediately after intubation (T1), at 10 min of anesthesia (T2), at 20 min of anesthesia (T3), at 30 min of anesthesia (T4), at 40 min of anesthesia (T5), at 50 min of anesthesia (T6), and after 60 min of anesthesia in the end of the procedure (T7). The results indicated that animals submitted to both protocols showed a significant decrease in arterial pH values from T1 to T7 in relation to T0. The differences found between the values from times T1 to T7 were statistically significant between them. The values of PaCO2 demonstrated statistically significant differences from T1 to T7 in both protocols. Protocol I showed statistically significant difference between T0 with respect to the times T1 to T7. For the parameter PaO2 there were statistically significant differences between protocols in T0 and not from T0 in comparison with T1 to T7 in both protocols. However, there were no significant differences between protocols due to inhalation of pure O2, that even using different flows causes an increase in PaO2The values of heart rate showed significant differences from T1 to T7 between protocols I, and protocol II. The values of base excess, O2 saturation and respiratory rate showed no statistically significant between protocols and time points. Discussion: Oxygen flow rate is the mean by which the CO2 is eliminated from nonrebrathing systems. Higher flow rates than those used in circle anesthetic systems are recommended in order to avoid carbon dioxide rebreathing within the nonrebrathing system. In our study we did demonstrate that the use of oxygen flow rate of 200 mL/kg/min with a Bain system kept the blood gas values and pH within acceptable range in healthy dogs submitted to general anesthesia with isoflurane 1.5V%. A lower flow rate of 100 mL/kg did produce arterial hypercapnia and academia of respiratory origin. The explanation for such result is probably due to the physical property of the inhalant anesthetic carrier gas flow. The use of higher flow rates will force exhaled carbon dioxide through the pop off valve, reducing its absorption. According to our findings a flow rate of 200 mL/kg/min should be recommended for the Bain system in dogs.
Can levamisole upregulate the equine cell-mediated macrophage (M1) dendritic cell (DC1) T-helper 1 (CD4 Th1) T-cytotoxic (CD8) immune response in vitro?
Witonsky, Sharon G.; Buechner-Maxwell, Virginia A.; Santonastasto, Amy; Pleasant, R. Scott; Werre, Stephen R.; Wagner, Bettina; Ellison, Siobhan; Lindsay, David S. (Wiley, 2019-03-01)
Background: Equine protozoal myeloencephalitis (EPM) is a common and devastating neurologic disease of horses in the United States. Because some EPM-affected horses have decreased immune responses, immunomodulators such as levamisole have been proposed as supplemental treatments. However, little is known about levamisole's effects or its mechanism of action in horses. Objective: Levamisole in combination with another mitogen will stimulate a macrophage 1 (M1), dendritic cell 1 (DC1), T-helper 1 (CD4 Th1), and T-cytotoxic (CD8) immune response in equine peripheral blood mononuclear cells (PBMCs) in vitro as compared to mitogen alone. Animals: Ten neurologically normal adult horses serologically negative for Sarcocystis neurona. Methods: Prospective study. Optimal conditions for levamisole were determined based on cellular proliferation. Peripheral blood mononuclear cells were then cultured using optimal conditions of mitogen and levamisole to identify the immune phenotype, based on subset-specific activation markers, intracellular cytokine production, and cytokine concentrations in cell supernatants. Subset-specific proliferation was determined using a vital stain. Results: Concanavalin A (conA) with levamisole, but not levamisole alone, resulted in a significant decrease (P <.05) in PBMC proliferation compared to conA alone. Levamisole alone did not elicit a specific immune phenotype different than that induced by conA. Conclusion and Clinical Importance: Levamisole co-cultured with conA significantly attenuated the PBMC proliferative response as compared with conA. If the mechanisms by which levamisole modulates the immune phenotype can be further defined, levamisole may have potential use in the treatment of inflammatory diseases.
Clinical outcomes in dogs with localized splenic histiocytic sarcoma treated with splenectomy with or without adjuvant chemotherapy
Latifi, Max; Tuohy, Joanne L.; Coutermarsh-Ott, Sheryl; Klahn, Shawna L.; Leeper, Haley; Dervisis, Nikolaos G. (Wiley, 2020-09-28)
Background: Localized splenic histiocytic sarcoma (HS) in dogs is a poorly understood disease, and could have longer survival times than disseminated or hemophagocytic HS. Understanding the clinical behavior of localized splenic HS can refine treatment recommendations. Objective: To describe the clinical characteristics and outcomes of dogs with localized splenic HS. Animals: Fourteen client-owned dogs with histologically confirmed splenic HS that received splenectomy. Methods: Multi-institutional retrospective case series—medical records of dogs with splenic HS were reviewed. Dog signalment, clinicopathologic data, primary and adjuvant treatments, and outcomes were obtained. Survival data were calculated using Kaplan-Meier analysis. Dog variables such as age, weight, platelet counts were reported using descriptive statistics. The Cox proportional hazards regression method was used to determine whether potential risk factors (weight, age, albumin level, hematocrit, and platelet count) were associated with PFI. Results: Median survival time for the dogs in this study was 427 days. Twelve dogs received adjuvant lomustine-based chemotherapy. Five dogs (35.7%) were suspected or confirmed to have developed metastatic disease. Eleven dogs died of disease, 1 dog died of unrelated cause, and 2 dogs were alive at final follow-up. Conclusions and Clinical Significance: Histiocytic sarcoma in dogs can manifest as a localized form in the spleen. Dogs with localized splenic HS treated with surgery ± chemotherapy can experience survival times over a year.
Effects of a convertible to-and-fro and circle anesthetic system on cardiopulmonary variables in isoflurane anesthetized horses
Natalini, Claudio Corrêa; Polydoro, Alexandre da Silva D. S.; Cavalcanti, Ruben Lundgren; Branquinho, Luciana Queiroga; Crosignani, Nadia; Serpa, Priscila B. S.; Schallenberger, Rodrigo Gonçalves; Pellin de Molnar, Bruna Favieiro; Carregaro, Adriano; Futema, Fábio (Universidade Federal do Rio Grande do Sul, 2018-03-30)
Six healthy adult horses two male and four female, mean body weight of 424 + 44.1kg, were anesthetized with xylazine, ketamine/diazepam and isoflurane for 60 minutes using a convertible to-and-fro and circle system. Variables analyzed were arterial blood pH, carbon dioxide partial pressure (PaCO2) and oxygen partial pressure (PaO2), respiratory rate(RR), and blood pressure. The horses were allowed to breath spontaneously, and were positioned in right lateral recumbency. The arterial O2 values were significantly higher during isoflurane anesthesia when compared to the baseline values, and significantly lower after induction with ketamine/diazepam although arterial hypoxemia were not present. The arterial PCO2 values were significantly higher from baseline values during isoflurane anesthesia occurring arterial hypercapnia and mild respiratory acidosis. The arterial pH changes paralleled the changes in PaCO2. Respiratory rate values were significantly lower during isoflurane anesthesia when compared to baseline values. All values remained within accepted range for lateral recumbent spontaneously breathing anesthetized horses. There were no significant differences between the circle and the to-and-fro system, demonstrating that either system is safe to maintain isoflurane anesthesia in adult horses.
Effects of Detomidine Constant Rate Infusion on Blood Glucose and Lactate in Sevoflurane Anesthetized Horses
Serpa, Priscila B. S.; Natalini, Claudio Corrêa; Cavalcanti, Ruben Lundgren; Nogueira Estrella, Jose Pedro; Pellin de Molnar, Bruna Favieiro; Bezerra, Daniele Pankowski; Pires, Ananda da Rocha D. R.; Fernandes, Viviane Conde (Universidade Federal do Rio Grande do Sul, 2012-01-01)
Background: The drugs that promote sedation, analgesia, and anesthesia, as inhalatory agents, phenothiazines, benzodiazepines, alpha-2 adrenergic agonists, and opioids, can promote different kinds of side effects. The concept of a balanced anesthesia in equine was developed in order to minimize adverse effects inherent to anesthesia, creating a combination of lower doses of these drugs in comparison with the doses of each one used alone. Alpha-2-adrenoceptor agonists such as xylazine, detomidine, and others, are drugs used for standing sedation, analgesia, and reduction of volatile anesthetic requirement in the equine as well as an agent used to maintenance of arterial blood pressure during anesthesia. Alpha-2 agonists works stimulating receptors of autonomic neurons inducing reduction of heart rate, cardiac output and vascular resistance, hypertension, behavioral changes, and inhibition of insulin secretion. This reduction in insulin levels increases blood glucose concentration in horses due to its lower utilization in insulin-dependent tissues, as muscular and adipose tissues. Muscular tissue is capable to maintain a constant lactate production even in a well oxygenated environment in order to maintain its cellular activity, especially in cases when glucose is not available. To evaluate the effect on blood glucose and lactate, horses were submitted to one hour of detomidine constant rate infusion during sevoflurane inhalatory anesthesia with controlled ventilation, in order to assess blood concentration of glucose and lactate Materials, Methods & Results: Four adult horses were studied. Detomidine 20 μg.kg-1 was used as premedication followed by an association of ketamine and diazepam intravenously as anesthetic induction. After intubation, sevoflurane was vaporized at approximately 2.3 V%. Mechanical ventilation was established. After stabilization, an intravenous continuous rate infusion (CRI) of detomidine 5 μg.kg.h-1 was started. Venous blood samples were collected before premedication, prior to detomidine continuous infusion, 20, 40, and 60 min after beginning of infusion, in order to determination of glucose and lactate serum concentrations. After 60 min of detomidine infusion, the horses were allowed to recovery. There was statistical significant hyperglycemia in the horses under CRI of detomidine. There was no significant increase in blood lactate, despite of the hyperlactatemia in some animals. Discussion: Detomidine CRI of 5 μg.kg.h-1 does increase blood glucose levels over normal values but not to levels that could be toxic to tissues, mainly CNS. With low levels of serum insulin, body tissues, mainly muscular and adipose tissues, are unable to capture this available blood glucose and these cells depend on lactate metabolism. The lactate serum concentrations below normal range observed in studied horses suggest that all lactate produced by the tissues is being utilized in the energetic metabolism. In according to many authors, lactate is produced and utilized for mitochondrias as energetic source even in fully oxygenated tissues, which seems to be what happened in this experiment. The present study helps to understand energetic metabolism in horses under general inhaled anesthesia with detomidine CRI, a selective alpha-2-adrenoceptor agonist. In order to better evaluate energetic metabolism during inhaled anesthesia under detomidine influence, other studies are suggested, as prolonged anesthesia duration to evaluate a longer adrenergic stimulus induced by detomidine. Besides, other investigations with detomidine CRI in horses submitted to surgical procedures could provide different responses in energetic metabolism.
Hemodynamic and Respiratory Effects of Positive End-expiratory Pressure during a Pulmonary Distress Model in Isoflurane Anesthetized Swine
Cavalcanti, Ruben Lundgren; Serpa, Priscila B. S.; Natalini, Claudio Corrêa (Universidade Federal do Rio Grande do Sul, 2014-10-24)
Background: Several pulmonary and hemodynamic complications may occur during mechanical ventilation of the lungs. The use of a positive end-expiratory pressure (PEEP) can improve oxygenation and prevent atelectasis, although this method can cause important hemodynamic side effects. Mostly, these hemodynamic effects are due to increased airway pressure that is transferred to the intrapleural space, increasing the intrathoracic pressure, which decreases venous return to the heart. Cardiac output is significantly reduced with high PEEP levels which in turn precludes the improvement effects on blood oxygenation. The aim of this study was to evaluate hemodynamic and respiratory effects of different levels of carbon dioxide insufflations associated with different levels of PEEP under conventional two-lung ventilation in isoflurane anesthetized pigs. Materials, Methods & Results: Twelve juvenile pigs were anesthetized with ketamine and midazolam, and end tidal isoflurane 2.0 V% for maintenance. Animals were submitted to tension pneumothorax through an acute intrathoracic insufflation with carbon dioxide at 0, 5, and 10 mmHg. Mechanical lung ventilation with 100% oxygen was started with zero PEEP then increased to 5 and 10 cmH2O. Ventilatory, respiratory and hemodynamic parameters were measured, as well as blood gases. Tension pneumothorax of 10 mmHg, with both PEEP levels, induced a significant decrease in cardiac index, stroke volume, right ventricular stroke work index, dynamic compliance, arterial pH, arteriovenous oxygen difference, arterial blood pressure, in addition to significance increase in heart rate. Moreover, tension pneumothorax of 5 or 10 mmHg combined with 5 or 10 cmH2O PEEP produced a significant increase in alveolar-arterial oxygen difference, a significant decrease in arterial oxygen content, and arterial partial pressure of O2. Central venous pressure, mean pulmonary arterial pressure, physiologic dead space, and arterial partial pressure of CO2 significantly increased with tension pneumothorax of 5 or 10 cmH2O when 5 or 10 mmHg PEEP was used. Arterial oxygenation improved significantly when 10 cmH2O PEEP was applied to 5 or 10 mmHg tension pneumothorax. Discussion: In this study, a thoracoscopic trocar was used to produce the acute respiratory function impairment. All animals showed the hemodynamic effects of an increased intrapleural pressure (IPP), such as hypotension and decreased SpO2. The major change observed was the increased shunt fraction, due to increased physiologic dead space. The hemodynamic changes observed were mainly due to compression of the large thoracic vessels as well as lung compression. When PEEP was applied without increased IPP, the hemodynamic depressive effects were less important. Levels of ETCO2 in our study did not present a significant increase, demonstrating that recruitment maneuvers are not always effective when there is a concomitant increased IPP. Dead space and V/Q mismatch significantly increased, demonstrating an important respiratory depressant effect. We have demonstrated in this study that while arterial oxygenation and tissue oxygen extraction is improved when high PEEP strategy is used in a swine tension pneumothorax model, the mechanical ventilation of the lungs with low PEEP or high PEEP strategy produced significant depression of the hemodynamic function during tension pneumothorax.
Incidental diagnosis of a spindle cell type gastrointestinal stromal tumor in a dog with ethylene glycol intoxication
Serpa, Priscila B. S.; Santos, Andrea P. (Wiley, 2021-11-21)
A 6-year-old castrated male American Pit Bull Terrier dog was presented for evaluation of acute onset of tonic-clonic seizures, anorexia, and vomiting. On physical examination, neurologic signs, such as generalized proprioceptive ataxia, salivation, circling to the right, and absent patellar reflexes bilaterally, were noted. A complete blood cell count revealed mild hemoconcentration and an inflammatory leukogram, while a chemistry panel showed severe azotemia, marked hypochloremia, and a severe titrational metabolic acidosis, suggesting possible ethylene glycol intoxication. However, an irregularly round, small mass was identified in the large intestine on abdominal ultrasound. Additionally, bilateral hyperechoic renal cortices with medullary rim sign were suggestive of acute nephritis or tubular necrosis. The cytologic evaluation of a fine-needle aspiration biopsy of the abdominal mass revealed a large population of mesenchymal cells, suggesting the presence of neoplasia. Due to the worsening of symptoms, the dog was humanely euthanized. Necropsy confirmed ethylene glycol intoxication, and the incidental finding of a neoplastic intestinal mass was diagnosed as spindle cell sarcoma. Immunohistochemical staining showed strong, diffuse positivity for CD117, smooth muscle actin, and S-100, indicating the final diagnosis of a spindle cell type gastrointestinal stromal tumor (GIST). This report briefly discusses the classifications of nonlymphoid, nonangiogenic intestinal mesenchymal tumors, characteristics of GISTs, and the importance of the immunohistochemical classification of mesenchymal tumors of the gastrointestinal tract.
Pharmacokinetic Parameters and Estimating Extra-Label Tissue Withdrawal Intervals Using Three Approaches and Various Matrices for Domestic Laying Chickens Following Meloxicam Administration
Richards, Emily D.; Dutch, Rachel S.; Burmas, Nathaniel C.; Davis, Jennifer L.; Lin, Zhoumeng; Clapham, Maaike O.; Wetzlich, Scott E.; Tell, Lisa A. (Frontiers, 2022-03-03)
Meloxicam is commonly prescribed for treating chickens in backyard or small commercial operations despite a paucity of scientific data establishing tissue withdrawal interval recommendations following extra-label drug use (ELDU). Historically, ELDU withdrawal intervals (WDIs) following meloxicam administration to chickens have been based on the time when meloxicam concentrations fall below detectable concentrations in plasma and egg samples. To date, no studies have addressed tissue residues. ELDU WDIs are commonly calculated using terminal elimination half-lives derived from pharmacokinetic studies. This study estimated pharmacokinetic parameters for laying hens following meloxicam administration and compared ELDU WDIs calculated using tissue terminal elimination half-lives vs. those calculated using FDA tolerance and EMA's maximum regulatory limit statistical methods, respectively. In addition, ELDU WDIs were calculated using plasma meloxicam concentrations from live birds to determine if plasma data could be used as a proxy for estimating tissue WDIs. Healthy domestic hens were administered meloxicam at 1 mg/kg intravenous (IV) once, 1 mg/kg orally (PO) once daily for eight doses or 1 mg/kg PO twice daily for 20 doses. Analytical method validation was performed and meloxicam concentrations were quantified using high-performance liquid chromatography. In general, the terminal elimination technique resulted in the longest ELDU WDIs, followed by the FDA tolerance and then EMA's maximum residue limit methods. The longest ELDU WDIs were 72, 96, and 384 (or 120 excluding fat) h for the IV, PO once daily for eight doses, and PO twice daily for 20 doses, respectively. Plasma data are a possible dataset for estimating a baseline for tissue ELDU WDI estimations when tissue data are not available for chickens treated with meloxicam. Finally, pharmacokinetic parameters were similar in laying hens to those published for other avian species.
Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part I: Cattle and swine
Lin, Zhoumeng; Li, Miao; Wang, Yu-Shin; Tell, Lisa A.; Baynes, Ronald E.; Davis, Jennifer L.; Vickroy, Thomas W.; Riviere, Jim E. (Wiley, 2020-04-08)
Physiologically based pharmacokinetic (PBPK) models for chemicals in food animals are a useful tool in estimating chemical tissue residues and withdrawal intervals. Physiological parameters such as organ weights and blood flows are an important component of a PBPK model. The objective of this study was to compile PBPK-related physiological parameter data in food animals, including cattle and swine. Comprehensive literature searches were performed in PubMed, Google Scholar, ScienceDirect, and ProQuest. Relevant literature was reviewed and tables of relevant parameters such as relative organ weights (% of body weight) and relative blood flows (% of cardiac output) were compiled for different production classes of cattle and swine. The mean and standard deviation of each parameter were calculated to characterize their variability and uncertainty and to allow investigators to conduct population PBPK analysis via Monte Carlo simulations. Regression equations using weight or age were created for parameters having sufficient data. These compiled data provide a comprehensive physiological parameter database for developing PBPK models of chemicals in cattle and swine to support animal-derived food safety assessment. This work also provides a basis to compile data in other food animal species, including goats, sheep, chickens, and turkeys.
Use of Calcium Chloride as an Adjuvant in Cardiopulmonary Cerebral Resuscitation (CPCR) in Dogs
Natalini, Claudio Corrêa; Nogueira Estrella, Jose Pedro; Polydoro, Alexandre da Silva D. S.; Futema, Fábio; Serpa, Priscila B. S. (Universidade Federal do Rio Grande do Sul, 2011-01-01)
Background: Treatment of cardiopulmonary arrest has been a source of discussion in both medicine as in veterinary with an emphasis on the use of solutions with calcium because of its importance as an ion essential for heart's functionality. Only a few studies have showed the use of Ca 2+ in CPCR. Based on this, the present study aimed to evaluate the use of calcium chloride as an adjuvant therapy in CPCR in dogs. Materials, Methods & Results: Eighteen cases of CPCR from the hospital routine of HCV-UFRGS were studied. Cases were selected from those in which occurred a cardiopulmonary arrest with reversal to a ventricular asystole in dogs. These animals were divided into two groups. In nine animals from the group called EPI, epinephrine was administered intravenously at a dose of 0.1 mg.kg -1 or by pulmonary route in a dose of 0.2 mg.kg -1. In the remaining nine animals, named EPIC group, the protocol was similar to the previous group, with the addition of the administration of calcium chloride 10% immediately after administration of epinephrine. In EPI group, the overall rate of success was 55.6%, and three of the cases treated showed reversion to normal sinus rhythm asystole. In the remaining six cases, four progressed to nonresponsive transient ventricular tachycardia (VT) and death, and two progressed to junctional rhythm. In the EPIC group, the overall rate of success was 22.2%. Four animals had VF from an asystole, in which in two of them were reversed by electric defibrillation, and in two of them the reversal was not obtained. In the other five treated animals, a ventricular tachycardia was developed followed by an irreversible cardiac arrest. Discussion: The incidence and prevalence of cardiac arrest diagnosed in animals in both hospitals and outpatients are still scarce data. However when it comes to patients under anesthesia, the success rate of CPCR are low compared to medicine. Calcium ion is indispensable in order to generate activation of the cardiac myofilaments to produce contraction of the heart. Cardiopulmonary arrest leads to a series of physiological changes that decrease the ability of the myocardium to maintain their automaticity and, in turn, generate a cardiac pacemaker, as well as its contractility. Several studies show that such these changes could be because of a severe hypocalcemia, found in both humans and dogs. Despite of the recent consensus against its use, calcium chloride in CPCR can increase the intracellular levels of this ion, which can cause inhibition of cellular respiration and energy production in mitochondrias, triggering an enzymatic proteolytic reaction, leading to cell death. However there is a clear exception in cases where the patient is in a framework of hypocalcemia. The EPI group has reached better rates of success; however, in the EPIC group was observed a reversal of asystole to VF, a fact that did not occur in group EPI. The treatment for VF is electric defibrillation, with a better prognosis when compared to asystole. Although the EPI group has obtained the best result and epinephrine rather is the best treatment of choice to CPCR, the EPIC group demonstrated that the use of calcium chloride may be an alternative to try to transform a VF in an asystole, with the possibility of using electric defibrillator in patients unresponsive to epinephrine alone.
What is your diagnosis? Abdominal mass in a rat
Serpa, Priscila B. S.; Corriveau, Lorraine A.; Santos, Andrea P. (Wiley, 2022-01-01)
A pet rat (Rattus novergicus) was diagnosed with sarcoma after cytologic and histologic evaluation of a subcutaneous, ventrally-located abdominal mass. Immunohistochemistry revealed neoplastic cells positive for Iba-1 and CD204, indicating a final diagnosis of histiocytic sarcoma. The tumor was aggressive and spread in a few weeks, leading to humane euthanasia.

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