The first clinical studies on the use of electrochemotherapy to treat liver tumours that were not amenable to surgery or thermal ablation techniques have recently been published. However, there is still a lack of data on the effects of electrochemotherapy on normal liver tissue. Therefore, we designed a translational animal model study to test whether electrochemotherapy with bleomycin causes clinically significant damage to normal liver tissue, with emphasis on large blood vessels and bile ducts. We performed electrochemotherapy with bleomycin or delivered electric pulses alone using a potentially risky treatment strategy in eight pigs. Two and seven days after treatment, livers were explanted, and histological analysis was performed. Blood samples were collected before treatment and again before euthanasia to evaluate blood biomarkers of liver function and systemic inflammatory response. We found no thrombosis or other clinically significant damage to large blood vessels and bile ducts in the liver. No clinical or laboratory findings suggested impaired liver function or systemic inflammatory response. Electrochemotherapy with bleomycin does not cause clinically significant damage to normal liver tissue. Our study provides further evidence that electrochemotherapy with bleomycin is safe for treatment of patients with tumours near large blood vessels in the liver.
Indirect blood pressure measurements using high definition oscillometric (HDO) and Doppler devices were compared in 50 anaesthetised client-owned cats presented for various surgical procedures. Sites of cuff placement for Doppler were identified as forelimb and hindlimb and for HDO as forelimb and tail. Oscillometric and Doppler readings were obtained in 90.05% and 100% of attempts, respectively. Both devices enabled precise measurement of systolic arterial pressure (SAP), although the Doppler device gave higher precision. In the low pressure group (SAP<100 mmHg; n=30), 66.7% biases were within 10 mmHg of discrepancy, but in groups of normal (100 mmHg ≤ SAP ≤ 150 mmHg; n=120) and high measurements (SAP>150 mmHg; n=62), 86.7% and 75.0% of discrepancy, respectively, were lower than 10 mmHg. Frequency of discrepancy at the range of 15 mmHg showed similar differences between pressure groups. There were significantly higher discrepancies when the cuff was positioned on the tail rather than on the leg. The SAP value obtained by HDO can be calculated from the Doppler measurement from SAP (HDO)=0.8515 × SAP (Doppler)+19.221 mmHg. Compared to Doppler, HDO overestimated low pressure and underestimated high pressure values.
The cardiorespiratory parameters, the depth of anaesthesia and the quality of recovery were evaluated in six spontaneously breathing dogs that had been premedicated with medetomidine (40 microg/kg, supplemented with 20 microg/kg an hour later), administered with either propofol (1 mg/kg followed by 0.15 mg/kg/minute, intravenously), or with ketamine (1 mg/kg followed by 2 mg/kg/hour, intravenously) and propofol (0.5 mg/kg followed by 0.075 mg/kg/minute, intravenously). The dogs' heart rate and mean arterial blood pressure were higher and their minute volume of respiration and temperature were lower when they were anaesthetised with propofol plus ketamine, and a progressive hypercapnia leading to respiratory acidosis was more pronounced. When the dogs were anaesthetised with propofol/ketamine they recovered more quickly, but suffered some unwanted side effects. When the dogs were anaesthetised with propofol alone they recovered more slowly but uneventfully.
BackgroundRadiologic findings after electrochemotherapy of large hepatic blood vessels and healthy hepatic parenchyma have not yet been described.Materials and methodsWe performed a prospective animal model study with regulatory approval, including nine grower pigs. In each animal, four ultrasound-guided electroporated regions were created; in three regions, electrodes were inserted into the lumen of large hepatic vessels. Two types of electrodes were tested; variable linear- and fixed hexagonal-geometry electrodes. Ultrasonographic examinations were performed immediately and up to 20 minutes after the procedure. Dynamic computed tomography was performed before and at 60 to 90 minutes and one week after the procedure.ResultsRadiologic examinations of the treated areas showed intact vessel walls and patency; no hemorrhage or thrombi were noted. Ultrasonographic findings were dynamic and evolved from hyperechogenic microbubbles along electrode tracks to hypoechogenicity of treated parenchyma, diffusion of hyperechogenic microbubbles, and hypoechogenicity fading. Contrast-enhanced ultrasound showed decreased perfusion of the treated area. Dynamic computed tomography at 60 to 90 minutes after the procedure showed hypoenhancing areas. The total hypoenhancing area was smaller after treatment with fixed hexagonal electrodes than after treatment with variable linear geometry electrodes.ConclusionsRadiologic findings of porcine liver after electrochemotherapy with bleomycin did not show clinically significant damage to the liver, even if a hazardous treatment strategy, such as large vessel intraluminal electrode insertion, was employed, and thus further support safety and clinical use of electrochemotherapy for treatment of hepatic neoplasia.
Data on the values of selected blood antioxidant parameters, i.e. total antioxidant capacity, glutathione peroxidase, and superoxide dismutase in healthy dogs, are lacking. There are no published accepted standard reference methods for their determination. The aim of this study was to determine the values of plasma total antioxidant capacity and the activities of whole blood glutathione peroxidase and erythrocyte superoxide dismutase in 30 healthy client-owned dogs (19 females, 11 males). The effect of age and sex on the measured antioxidant parameters was also investigated. Antioxidant parameters were determined with an automated biochemical analyser, using the commercially available Randox kits. No signifi cant difference in age, weight, and antioxidant parameters was determined between females and males. A signifi cant positive effect of age (p = 0.002, r² = 0.284) on superoxide dismutase activity was confi rmed. There was no effect of sex on any of the antioxidant parameters measured. However, we observed a tendency of the effect of sex (p = 0.063, r² = 0.118), as well as age (p = 0.073, r² = 0.111), on the activity of glutathione peroxidase. Our results are in part comparable with the results of other studies in which the same types of methods and samples were used to determine antioxidant parameters. In conclusion, the sex and age of dogs should be taken into consideration when planning a study on antioxidant status parameters.
SummaryLiposomal bupivacaine is a prolonged‐release local anaesthetic, the neurotoxicity of which has not yet been determined. We used quantitative histomorphometric and immunohistochemical analyses to evaluate the neurotoxic effect of liposomal bupivacaine after perineural and intraneural (extrafascicular) injection of the sciatic nerve in pigs. In this double‐blind prospective randomised trial, 4 ml liposomal bupivacaine 1.3% was injected either perineurally (n = 5) or intraneurally extrafascicularly (n = 5). Intraneural–extrafascicular injection of saline (n = 5) was used as a control. After emergence from anaesthesia, neurological examinations were conducted over two weeks. After harvesting the sciatic nerves, no changes in nerve fibre density or myelin width indicative of nerve injury were observed in any of the groups. Intraneural injections resulted in longer sensory blockade than perineural (p < 0.003) without persistent motor or sensory deficit. Sciatic nerve block with liposomal bupivacaine in pigs did not result in histological evidence of nerve injury.
Analysis of mixed venous blood is preferable to analysis of arterial blood in the assessment of metabolic derangement. In a clinical setting, occluded portal blood is released to the systemic circulation, and the degree of reperfusion injury may depend on the metabolic status of pooled portal blood.
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