Dilated cardiomyopathy (DCM) is a myocardial disease of dogs and humans characterized by progressive ventricular dilation and depressed contractility and it is a frequent cause of heart failure. Conventional pharmacological therapy cannot reverse the progression of the disease and, in humans, cardiac transplantation remains the only option during the final stages of cardiac failure. Cytoprotective gene therapy with the Vascular Endothelial Growth Factor-B167 (VEGF-B167) has proved an effective alternative therapy, halting the progression of the disease in experimental studies on dogs [1,2]. The aim of this work was to test the tolerability and feasibility of intracoronary inoculation under fluoroscopic guidance of VEGF-B167 carried by adeno-associated viral vectors in canine DCM patients. Ten patients underwent the gene delivery procedure. The intraoperative phase was well tolerated by all dogs. Clinical and echocardiographic assessment at 7 days post-procedure in all dogs showed stable clinical conditions that could be superimposed to those pre-procedure. The results of this work indicate that intracoronary gene delivery is feasible and tolerated in dogs with DCM. Further monitoring/investigations are ongoing to evaluate the effects of this procedure on disease progre

The aim of this study was to evaluate the correlation of commonly used oxygenation indices with venous admixture (Qs/Qt) in anaesthetised horses under different infusion rates of dobutamine. Six female horses were anaesthetised with acepromazine, xylazine, diazepam, ketamine, and isoflurane, and then intubated and mechanically ventilated with 100% O2. A Swan-Ganz catheter was introduced into the left jugular vein and its tip advanced into the pulmonary artery. Horses received different standardised rates of dobutamine.For each horse, eight samples of arterial and mixed venous blood were simultaneously obtained at fixed times. Arterial and venous haemoglobin (Hb) concentration and O2 saturation, arterial oxygen partial pressure (PaO2), venous oxygen partial pressure (PvO2), and barometric pressure were measured. Arterial (CaO2), mixed venous (CvO2), and capillary (Cc'O2) oxygen contents were calculated using standard formulae. The correlations between F-shunt, arterial oxygen tension to fraction of inspired oxygen ratio (PaO2/FiO2), arterial to alveolar oxygen tension ratio (PaO2/PAO2), alveolar to arterial oxygen tension difference (P[A - a]O2), and respiratory index (P[A - a]O2/PaO2) were tested with linear regression analysis. The goodness-of-fit for each calculated formula was evaluated by means of the coefficient of determination (r2). The agreement between Qs/Qt and F-shunt was analysed with the Bland-Altman test.All tested oxygen tension-based indices were weakly correlated (r2 < 0.2) with the Qs/Qt, whereas F-shunt showed a stronger correlation (r2 = 0.73). F-shunt also showed substantial agreement with Qs/Qt independent of the dobutamine infusion rate. F-shunt better correlated with Qs/Qt than other oxygen indices in isoflurane-anaesthetised horses under different infusion rates of dobutamine

General anesthesia impairs respiratory functionby the development of atelectasis in association with alteredventilation at pulmonary bases1. Applying Continuous Positive Airways Pressure (CPAP) in spontaneously breathing patients reduce the work of breathing, increases functional residualcapacity and is often recommended to prevent orreduce alveolar collapse1. In human medicine it has been widely recognized that an increase in intra-thoracic pressure is associated with a decrease in cardiac outputbecause of the reduction of venous return2. Nevertheless, conflictingresults (increases, decreases, or no change) in CO have beenreported and it was studied that the effects of CPAP on cardiac function were influenced by increasing CPAP levels. Doppler echocardiography represents a way to investigate how cardiac parameters can be affected and can change during CPAP application. What about CPAP application and its cardiovascular consequences in dogs? Aim of the study The aim of this study is to investigate by Doppler echocardiographythe cardiovascular effects of a low level of CPAP(5 cm H2O) in dogs under anesthesia. Materials and Methods 20 dogs have been enrolled in the study and divided into two groups. Both groups underwent anesthesia with a standard protocol and in Group A (10 dogs) CPAP was administered (5 cmH2O). Group B (10 dogs) served as control group and did not receive CPAP. Cardiovascular parameters (heart rate, mean arterial pressure and echocardiographic indices) were registered before (T0) and 15 minutes after anesthesia induction (T1), during anesthesia with or without CPAP(T2) and during recovery (T3).All patients were anesthetizedwith acepromazine (20 µg/kg), morphine (0.3 mg/kg), propofol (4 mg/kg) and isoflurane (end-tidal concentration 1.3 %)in spontaneous ventilation. Standard echocardiography (Esaote ultrasound system MyLab30) was performed usinga 2.5 MHz transducer. The following parameters were calculated as indicators of cardiovascular function: ejection fraction (EF%), left and right cardiac index (CI), left ventricle end diastolic volume index (LV-EDVI ml/m2), ratio of isovolumetric contraction time to ejection time (IVCT/ET), ratio of early rapid filling peak to atrial peak filling of transatrioventricular inflow (E/A), time velocity integral of atrioventricular inflow (TVI), aortic max velocity (AoVmax) and pulmonary max velocity (P Vmax). Results and Conclusions On the whole no statistical differences have been revealed in cardiovascular parameters at T2 compared to T1 in both groups.Interestingly a significant difference was revealed in EF between CPAP group and control group at T2. Myocardial diastolic properties remained unchanged. The right cardiac index do not change.Results of this study suggest not only that application of low levels of CPAP during anesthesia of healthy dogs does not negatively affect cardiac function and hemodynamic parameters, but also that it could positivelyinfluence the global left ventricular systolic function. In conclusion the application of this level of CPAP during anesthesia in healthy dogs could be considered safe. References 1Russo et al, 2013. J. CLIN. ANESTH. 25, 314-320.2Huemer et al, 1994. CHEST 106, 67-73

The aim of this study was to compare intravenous regional anesthesia (IVRA) and brachial plexus block (BPB) for intra-operative analgesia in dogs undergoing pancarpal arthrodesis (PA). Twenty dogs scheduled for PA were intramuscularly sedated with acepromazine (0.03mg/kg), general anesthesia was intravenously (IV) induced with thiopental (10mg/kg) and, after intubation, maintained with isoflurane in oxygen. In 10 dogs (GIVRA) IVRA was performed on the injured limb administering 0.6ml/kg of 0.5% lidocaine. In 10 dogs (GBPB) the BPB was performed at the axillary level with the help of a nerve stimulator and 0.3ml/kg of a 1:1 solution of 2% lidocaine and 1% ropivacaine was injected. During surgery fentanyl (0.002mg/kg IV) was administered if there was a 15% increase of HR and/or MAP compared to the values before surgical stimulation. All the standard cardiovascular and respiratory parameters were continuously monitored during surgery. The duration of surgery and the time of extubation were recorded. Data were compared with a 1-way ANOVA test (P<0.05). No patients required fentanyl administration during surgery. All the recorded parameters were similar in the two groups. The two techniques were similar in providing intra-operative analgesia in dogs undergoing orthopaedic surgery.

The aim of this study was to compare the postoperative analgesic effects of robenacoxib and buprenorphine alone or in combination, in cats after ovariohysterectomy. Thirty healthy cats were randomly assigned to receive buprenorphine (0.02 mg/kg, n = 10; GB), robenacoxib (2 mg/kg, n = 10; GR) or their combination at the same dosages (n = 10; GBR) SC. After 30 min cats were sedated with an IM administration of medetomidine (0.02 mg/kg) and ketamine (5 mg/kg). General anaesthesia was induced with propofol and after intubation was maintained with isoflurane. Before premedication and at 1, 2, 3, 4, 6, 8, 12 and 24 h after extubation, pain and sedation were assessed using a simple descriptive pain scale, ranging from 0 (no pain/no sedation) to 4 (intense pain/ deep sedation). If the pain score was ≥3, rescue analgesia was provided using buprenorphine (0.02 mg/kg) administered IM. Pain score was higher in GB at 2, 3, 4, 6 and 8 h compared to baseline and compared to GBR at the same study times. Moreover, the pain score was also higher in GB compared to GR at 2, 3, 4 and 6 h. Pain score was similar at all study times between GR and GBR. Sedation at 1 and 2 h was higher than baseline values in all groups. Cats in GB received rescue analgesia more often than cats assigned to GR or GBR. Robenacoxib was an effective analgesic drug in cats up to 24 h after ovariohysterectomy. The addition of buprenorphine did not provide any additional analgesic effects compared to robenacoxib alone. © 2013 Elsevier Ltd. All rights reserved.

Klotho is an anti-aging factor mainly produced by renal tubular epithelial cells (TEC) with pleiotropic functions. Klotho is down-regulated in acute kidney injury in native kidney; however, the modulation of Klotho in kidney transplantation has not been investigated. In a swine model of ischemia/reperfusion injury (IRI), we observed a remarkable reduction of renal Klotho by 24 h from IRI. Complement inhibition by C1-inhibitor preserved Klotho expression in vivo by abrogating nuclear factor kappa B (NF-kB) signaling. In accordance, complement anaphylotoxin C5a led to a significant down-regulation of Klotho in TEC in vitro that was NF-kB mediated. Analysis of Klotho in kidneys from cadaveric donors demonstrated a significant expression of Klotho in pre-implantation biopsies; however, patients affected by delayed graft function (DGF) showed a profound down-regulation of Klotho compared with patients with early graft function. Quantification of serum Klotho after 2 years from transplantation demonstrated significant lower levels in DGF patients. Our data demonstrated that complement might be pivotal in the down-regulation of Klotho in IRI leading to a permanent deficiency after years from transplantation. Considering the anti-senescence and anti-fibrotic effects of Klotho at renal levels, we hypothesize that this acquired deficiency of Klotho might contribute to DGF-associated chronic allograft dysfunction.

NADPH oxidase plays a central role in mediating oxidative stress during heart, liver, and lung ischemia/reperfusion injury, but limited information is available about NADPH oxidase in renal ischemia/reperfusion injury. Our aim was to investigate the activation of NADPH oxidase in a swine model of renal ischemia/reperfusion damage. We induced renal ischemia/reperfusion in 10 pigs, treating 5 of them with human recombinant C1 inhibitor, and we collected kidney biopsies before ischemia and 15, 30, and 60 min after reperfusion. Ischemia/reperfusion induced a significant increase in NADPH oxidase 4 (NOX-4) expression at the tubular level, an upregulation of NOX-2 expression in infiltrating monocytes and myeloid dendritic cells, and 8-oxo-7,8-dihydro-2'-deoxyguanosine synthesis along with a marked upregulation of NADPH-dependent superoxide generation. This burden of oxidative stress was associated with an increase in tubular and interstitial expression of the myofibroblast marker α-smooth muscle actin (α-SMA). Interestingly, NOX-4 and NOX-2 expression and the overall NADPH oxidase activity as well as α-SMA expression and 8-oxo-7,8-dihydro-2'-deoxyguanosine synthesis were strongly reduced in C1-inhibitor-treated animals. In vitro, when we incubated tubular cells with the anaphylotoxin C3a, we observed an enhanced NADPH oxidase activity and α-SMA protein expression, which were both abolished by NOX-4 silencing. In conclusion, our findings suggest that NADPH oxidase is activated during ischemia/reperfusion in a complement-dependent manner and may play a potential role in the pathogenesis of progressive renal damage in this setting. Copyright © 2014 Elsevier Inc. All rights reserved.

The aim of this study was to compare the cardiovascular effects of medetomidine, acepromazine and their combination administered intravenously in healthy dogs. Ten dogs were included in this study and randomly assigned to the three different sedative protocols: medetomidine (2 μg/kg, protocol M), acepromazine (20 μg/kg, protocol A) and acepromazine followed by medetomidine with the same doses as above (protocol AM), in three different times. In all subjects before (Tbase) and 15 (T15), 50 (T50) and 80 (T80) minutes after the administration of the drugs, the following non-invasive measurements were obtained: blood pressure with oscillometric method, ECG, and echocardiography. Blood pressure and echocardiography evidenced decrease in left ventricular afterload secondary to acepromazine and an increase in right ventricular afterload due to medetomidine. The combination of the two drugs mitigated the effects expected by the single drugs used alone, and prevented the onset of atrioventricular blocks, such as seen in protocol M. The three protocols were eligible for sedation and premedication in healthy dogs. Moreover they had little impact on the echocardiographic variables evaluated in this study.

To evaluate the effects of 10 cm H(2)O of positive end-expiratory pressure (PEEP) on lung aeration and gas exchange in mechanically ventilated sheep during general anesthesia induced and maintained with propofol. ANIMALS: 10 healthy adult Bergamasca sheep. PROCEDURES: Sheep were sedated with diazepam (0.4 mg/kg, IV). Anesthesia was induced with propofol (5 mg/kg, IV) and maintained with propofol via constant rate infusion (0.4 mg/kg/min). Muscular paralysis was induced by administration of vecuronium (25 microg/kg, bolus IV) to facilitate mechanical ventilation. After intubation, sheep were positioned in right lateral recumbency and mechanically ventilated with pure oxygen and zero end-expiratory pressure (ZEEP). After 60 minutes, 10 cm H(2)O of PEEP was applied for 20 minutes. Spiral computed tomography of the thorax was performed, and data were recorded for hemodynamic and gas exchange variables and indicators of respiratory mechanics after 15 (T(15)), 30 (T(30)), and 60 (T(60)) minutes of ZEEP and after 20 minutes of PEEP (T(PEEP)). Computed tomography images were analyzed to determine the extent of atelectasis before and after PEEP application. RESULTS: At T(PEEP), the volume of poorly aerated and atelectatic compartments was significantly smaller than at T(15), T(30), and T(60), which indicated that there was PEEP-induced alveolar recruitment and clearance of anesthesia-induced atelectasis. Arterial oxygenation and static respiratory system compliance were significantly improved by use of PEEP. CONCLUSIONS AND CLINICAL RELEVANCE: Pulmonary atelectasis can develop in anesthetized and mechanically ventilated sheep breathing pure oxygen; application of 10 cm H(2)O of PEEP significantly improved lung aeration and gas exchange.

OBJECTIVE: To evaluate the effectiveness of reduction of inspired oxygen fraction (Fio(2)) or application of positive end-expiratory pressure (PEEP) after an alveolar recruitment maneuver (ARM) in minimizing anesthesia-induced atelectasis in dogs. ANIMALS: 30 healthy female dogs. PROCEDURES: During anesthesia and neuromuscular blockade, dogs were mechanically ventilated under baseline conditions (tidal volume, 12 mL/kg; inspiratory-to-expiratory ratio, 1:2; Fio(2), 1; and zero end-expiratory pressure [ZEEP]). After 40 minutes, lungs were inflated (airway pressure, 40 cm H(2)O) for 20 seconds. Dogs were then exposed to baseline conditions (ZEEP100 group), baseline conditions with Fio(2) reduced to 0.4 (ZEEP40 group), or baseline conditions with PEEP at 5 cm H(2)O (PEEP100 group; 10 dogs/group). For each dog, arterial blood gas variables and respiratory system mechanics were evaluated and CT scans of the thorax were obtained before and at 5 (T5) and 30 (T30) minutes after the ARM. RESULTS: Compared with pre-ARM findings, atelectasis decreased and Pao(2):Fio(2) ratio increased at T5 in all groups. At T30, atelectasis and oxygenation returned to pre-ARM findings in the ZEEP100 group but remained similar to T5 findings in the other groups. At T5 and T30, lung static compliance in the PEEP100 group was higher than values in the other groups. CONCLUSIONS AND CLINICAL RELEVANCE: Application of airway pressure of 40 cm H(2)O for 20 seconds followed by Fio(2) reduction to 0.4 or ventilation with PEEP (5 cm H(2)O) was effective in diminishing anesthesia-induced atelectasis and maintaining lung function in dogs, compared with the effects of mechanical ventilation providing an Fio(2) of 1.

Objective To compare the effects of two fractions of inspired oxygen (FiO 2) (0.4 and 1) on lung aeration and gas exchange during general anaesthesia in cats.Study design Randomized, blinded, controlled study.Animals Thirty healthy, mixed breed, client owned female cats.Materials and methods Cats were premedicated intramuscularly with acepromazine (0.03 mg kg -1) and medetomidine (0.015 mg kg -1). Anaesthesia was induced with propofol (5 mg kg -1) and, after orotracheal intubation, maintained with isoflurane carried by either 100% oxygen (G100, n = 15) or an oxygen-air mixture with 40% oxygen (G40, n = 15). All cats were placed in dorsal recumbency and breathed spontaneously throughout the entire procedure. Following surgery (ovariectomy), a spiral computed tomography (CT) of the thorax was performed, arterial oxygen (PaO 2) and carbon dioxide (PaCO 2) tensions were measured and alveolar-arterial gradient of oxygen [P(A-a)O 2] calculated. The CT images were analysed for lung aeration by the analysis of radiograph attenuations (Hounsfield units, HU), according to the following classification: hyperinflated area (-1000 to -900 HU), normally aerated area (-900 to -500 HU), poorly aerated area (-500 to -100 HU) and non-aerated area (-100 to +100 HU). The groups were compared using one-way anova.Results Compared to G100, the normally-aerated lung area was significantly greater and the poorly-aerated and non-aerated areas were significantly smaller in G40. PaCO 2 was similar in both groups. PaO 2 and P(A-a)O 2 were significantly higher in G100. In both groups, pulmonary atelectasis developed preferentially in the caudal lung fields.Conclusion In cats anaesthetised with isoflurane, the administration of an FiO 2 of >0.9 significantly impaired lung aeration and gas exchange as compared to an FiO 2 of 0.4.Clinical relevance An FiO 2 of 0.4 may better preserve lung aeration and gas exchange in anaesthetised spontaneously breathing cats but monitoring is essential to ensure oxygenation is adequate

Field immobilization of captive antelope may be required for medical examination, blood sample collection, and animal identification. The aim of this study was to evaluate the effects of a combination of butorphanol, detomidine, and midazolam (BDM) and its partial reversibility in Nile Lechwe antelope (NLA; Kobus megaceros). Nine captive NLAs, weighing 28-64 kg, were immobilized, in February 2011, with butorphanol 0.20±0.05 (meanSD) mg/kg, detomidine 0.20±0.05 mg/kg and midazolam 0.31±0.08 mg/kg administered intramuscularly (IM) with a blowpipe. Physiologic parameters and depth of anesthesia were recorded when the animals became recumbent at 19.55±8.36 min after darting (T0) and after 10 (T10), 20 (T20) and 30 (T30) min. An arterial blood sample was collected at T20. At the end of the procedures, immobilization was partially reversed with atipamezole 0.25 mg/kg IM. Quality of induction, immobilization, and recovery were scored. The BDM combination induced immobilization and lateral recumbency in 13.44±5.61 min. Median induction score [scored 1 (excellent) to 4 (poor)] was 1 (range 1–2). Heart rate varied 40–104 beats/min, respiratory rate 16–108 breaths/min and rectal temperature 36.5–40.3 C. Hyperthermia observed and rapidly treated in three animals that demonstrated insufficient immobilization after darting. Arterial blood gas analyses revealed a mean pH of 7.43±0.07, PaCO2 of 44.1±6.0 mmHg, PaO2 of 74.0±13.5 and a SaO2 of 94.77±3.96 mmHg. Recovery was smooth and animals were walking in 13.44±7.85 min. Median recovery score [scored 1 (excellent) to 4 (poor)] was 1 (range 1–2). The BDM was effective in immobilizing captive healthy NLAs with minimal cardiorespiratory changes.

The purpose of this study was to evaluate changes in echocardiographic parameters during increasing infusion rates of dobutamine in isoflurane-anesthetized horses and to compare our results with those of previous studies. Six Standardbred female healthy horses were included in this study. All animals were anesthetized and infused with dobutamine at different rates. mean arterial pressure (MAP), heart rate (HR), and some echocardiographic measurements were recorded. Statistical analysis was applied. Under basal conditions (time 0 [T0]), HR ranged between 32 and 42 beats per minute (bpm), and MAP was between 39 and 63 mm Hg. MAP increased significantly from T0 compared with values at T2, T2, and T3 in a dose-dependent manner, while HR increased significantly only at T3 if compared to the other measuring times. Left ventricular internal diameter during diastole (LVDs) decreased significantly in a dose-dependent manner, with increasing of the infusion rate of dobutamine. Interventricular septal dimension during diastole (IVSs) increased significantly, and end-systole left ventricular volumes (LVVols) decreased significantly at T2 and T3 compared to T1. Ejection fraction (%) increased significantly between T0 and T1, T2, and T3. Cardiac output increased significantly only at the higher dosage (T3 vs. others) of dobutamine, but cardiac power output was enhanced significantly at T2 versus that at T0 and T1 and at T3 versus all the previous measurements. Arrhythmias were diagnosed in 5 of 6 (83.3%). In this study, the increase of MAP was found to be dose-dependent, according with literature. The HR and MAP values registered at T0 were comparable to previous results obtained both in anesthetized and conscious horses, while at T1, T2, and T3, HR and MAP values were similar only too those reported in anesthetized horses. IVSs increased and LVDs decreased significantly with the increment of dobutamine infusion rate. These findings suggest that dobutamine, even at low infusion rates, induces an enhancement in cardiac systolic function. The dose-dependent increase of IVSs and decrease of LVDs measurements are in line with those reported for dobutamine administered in conscious horses but with lower values. The LVVols dose-dependent reduction obtained in this study is in line with that in other reports, but both LVold and LVVols values after dobutamine infusion at different dosages are lower if compared to previous studies. The low LVol values and the wide standard deviation have influenced consequently the derived indices values (stroke volume [SV], EF, cardiac output [CO]). In the present study, SV did not significantly increase during dobutamine infusion. These results disagree with those reported by others. The increment of CO might be due mainly to the enhanced HR rather than to the weak changes of SV. Cardiac power output increased significantly from the 5 mcg/kg/min dosage in a dose-dependent manner, as reported by others.

The aims of this study were to evaluate the effects of the administration of a combination of tiletamine-zolazepam and detomidine (TZD) in 9 tigers (Panthera tigris). Nine captive tigers were immobilized with tiletamine-zolazepam and detomidine administered intramuscularly. At the end of the procedure immobilization was partially reversed with atipamezole. Lateral recumbency was achieved in 15.6±5.9min. The median induction score [scored 1 (excellent) to 4 (poor)] was 1. The immobilization score [scored 1 (poor) to 6 (too deep)] was 5 (4-5) at all study times. After atipamezole administration, all tigers experienced severe ataxia and incoordination. Median recovery score [scored 1 (excellent) to 4 (poor)] was 2.5 (range 2-3). No neurologic and/or important adverse reactions were noticed within 5 days after recovery. The combination tiletamine-zolazepam with detomidine proved to be effective in immobilizing captive healthy tigers but it maybe associated with hypertension and ataxia during recovery.

The anesthesia records (n = 30) of 5 experimental male dogs affected with Duchenne Muscular Dystrophy (DMD) that periodically underwent general anaesthesia for magnetic resonance imaging (MRI) studies of the heart were retrospectively reviewed. General anaesthesia was induced in all dogs with an intravenous (IV) administration of fentanyl (range; 0.010 – 0.012 mg kg-1) followed by propofol (3 – 4 mg kg-1). After orotracheal intubation all dogs’ lungs were mechanically ventilated with 100% oxygen. General anaesthesia was maintained with a constant rate infusion of propofol (0.1 – 0.2 mg kg-1 min-1) and fentanyl (0.5 – 0.7 mg kg-1 min-1) titrated to maintain an adequate level of anaesthesia. A continuous lead II ECG; heart rate (HR); systolic (SAP), diastolic, and mean arterial pressures, haemoglobin oxygen saturation, respiratory rate and end-tidal CO2 were recorded measure continuously and recorded every 5 minutes throughout anaesthesia. In order to improve the quality of the thoracic images, a 2 min-long apnea was induced was induced with a IV bolus of cisatracurium (0.1 mg kg-1) and by discontinuing mechanical ventilation. Immediately after the administration of cisatracurium, an increase of HR and SAP was observed in all dogs, with a mean (SD) percentage and absolute increase of 115.4 ± 64.9% and 78.3 ± 37.0 beats/min and 33.5 ± 31.2 % and 33.0 ± 28.3 mmHg, respectively. No other major cardiovascular or respiratory changes were observed. All dogs recovered from general anaesthesia without complications. Reactions to general anesthesia, including a high sensibility to selected non-depolarizing neuromuscual blockers, have been reported for human patients affected with DMD. To our knowledge, this is the first report of increases in HR and SAP related to the administration of cis-atracurium in either human or animal patients affected with DMD. This cardiovascular changes in DMD patients deserve further investigation.

The aim of this study was to evaluate the influence of abdominal surgery on atelectasis formation in healthy dogs. After the induction of general anesthesia (GA), 20 dogs, scheduled for elective ovariohysterectomy, were positioned in dorsal recumbency: 10 dogs underwent immediate surgery (S group), while 10 dogs (NS group) were maintained under anesthesia for 60 min before surgery. In both groups, a helical computed tomography (CT) scan of the thorax and an arterial blood gas analysis were performed 60 min after the induction of GA. Lung aeration was estimated by analyzing the radiographic attenuation of the CT images. The atelectasic and poorly aerated lung compartments were significantly larger, and the normally aerated lung compartment was smaller in the S group compared to the NS group. The PaO2 was similar in both groups. Abdominal surgery significantly increases pulmonary atelectasis in healthy dogs under GA

The aim of this study was to evaluate the influence of a recruiting maneuver (RM) on the effects of PEEP on lung function in healthy horses under general anaesthesia. Fifteen horses were sedated with acepromazine (0.02 mg kg-1 IV) and detomidine (0.005 mg kg-1 IV), general anaesthesia was intravenously induced with midazolam (0.1 mg kg-1) and ketamine (2.2 mg kg-1) and maintained with isoflurane in 100% oxygen. After intubation all horses lungs were mechanically ventilated in a volume controlled mode: Vt (12 ml kg-1) and I:E (1:2) were unchanged during the study while RR was titrated to maintain the PE’CO2 between 40 and 45 mmHg. Three different ventilatory strategies were applied in all horses during the same anaesthetic episode: zero PEEP (ZEEP), 10 cmH2O of PEEP (PEEP) and a RM followed by the application of 10 cmH2O of PEEP (RMPEEP). The RM was performed applying 50 cmH2O for 20 seconds to the respiratory system. Thirty minutes after each ventilatory strategy was initiated, HR and MAP were recorded, an arterial blood sample was collected [PaO2, P(A-a)O2], static compliance of the respiratory system (CRSstat) and the PEEP recruited lung volume (RLV) (Grasso S et al 2005) were calculated. Data were compared with the ANOVA test (P<0.05). The PaO2 and Crsstat were higher while P(A-a)O2 lower at RMPEEP (60.7 ± 6.8 kPa, 473.5 ± 89.1 ml cmH2O-1 and 23.8 ± 7.5 kPa) compared to ZEEP (40.8 ± 16.9 kPa, 339.7 ± 81.9 ml cmH2O-1 and 44.5 ± 16.8 kPa) and PEEP (41.2 ± 17.8 mmHg, 360.9 ± 54.9 ml cmH2O-1 and 44.4 ± 17.6 mmHg). The RLV was larger at RMPEEP (5.5 ± 2.4 L) than at PEEP (2.6 ± 1.6 L). A RM significantly improved the effects of 10 cmH2O of PEEP on lung function in horses under general anaesthesia.

This report details a bubble echocardiographic study carried out during the surgical treatment of a congenital single extrahepatic portosystemic shunt (PSS) in a Labrador Retriever. After celiotomy, agitated saline was injected through a jejunal vein and microbubbles appeared rapidly in the right cardiac chambers. The test confirmed the presence of a PSS, helping the surgeon to identify the vessel concerned and to rule out a second shunt. Successively, portography confirmed what the exploratory celiotomy had revealed before with the aid of the bubble study: a single shunt was located between the portal vein and the right renal vein. It was completely ligated, as all the criteria for this solution were met. Intraoperative contrast echocardiography (ICE) was easy to perform, helpful and undemanding. It is proposed here as an intraoperative ancillary test to diagnose all PSS and to confirm successful treatment when complete shunt closure is possible.

An 11-year-old male German shepherd dog was referred for possible pacemaker implantation. A routine 6-lead electrocardiogram revealed a third-degree atrio-ventricular block with a heart rate of 40 to 45beats/minute. A transvenous pacemaker implantation procedure was scheduled. The dog was premedicated with 10 μg/kg acepromazine and 5 mg/kg pethidine. A dose of 5 mg/kg ketamine and 0·2mg/kg diazepam were used for induction and isoflurane in O2 and a constant rate infusion of ketamine (20 to 30 μg/kg/minute) were administered for maintenance of general anaesthesia. Due to a twiddler's syndrome, the pacemaker had to be repositioned. For the second procedure, the same protocol was employed except for a lower dose of ketamine both for induction (3 mg/kg) and constant rate infusion (10 to 15 μg/kg/minute). Ketamine appeared to be useful for both management of anaesthesia and cardiac pacemaker implantation in the absence of a temporary pacemaker

LPS-induced sepsis is a leading cause of acute kidney injury (AKI) in critically ill patients. LPS may induce CD80 expression in podocytes with subsequent onset of proteinuria, a risk factor for progressive chronic kidney disease (CKD) frequently observed after AKI. This study aimed to investigate the therapeutic efficacy of LPS removal in decreasing albuminuria through the reduction of podocyte CD80 expression. Between January 2015 and December 2017, 70 consecutive patients with Gram-negative sepsis-induced AKI were randomised to either have Coupled Plasma Filtration and Adsorption (CPFA) added to the standard care (n=35) or not (n=35). To elucidate the possible relationship between LPS-induced renal damage, proteinuria and CD80 expression in Gram- sepsis, a swine model of LPS-induced AKI was set up. 3-hours after LPS infusion, animals were treated or not with CPFA for 6-hours. Treatment with CPFA significantly reduced serum cytokines, CRP, procalcitonin and endotoxin levels in patients with Gram-negative sepsis-induced AKI. CPFA significantly lowered also proteinuria and CD80 urinary excretion. In the swine model of LPS-induced AKI, CD80 glomerular expression, which was undetectable in control pigs, was markedly increased at the podocyte level in LPS-exposed animals. CPFA significantly reduced LPS-induced proteinuria and podocyte CD80 expression in septic pigs. Our data indicate that LPS induces albuminuria via podocyte expression of CD80 and suggest a possible role of timely LPS removal in preventing the maladaptive repair of the podocytes and the consequent increased risk of CKD in sepsis-induced AKI.

Abstract Objective – To evaluate the feasibility and efficacy of noninvasive continuous positive airway pressure (CPAP) administered with a pediatric helmet in healthy dogs recovering from general anesthesia. Design – Randomized, cross-over, clinical study. Setting – University teaching hospital Animals – Fifteen healthy female, client-owned dogs recovering from general anesthesia following elective ovariohysterectomy. Interventions – All dogs received the same standardized anesthetic protocol (acepromazine, morphine, propofol, and isoflurane in oxygen). After extubation, a pediatric helmet was placed on all dogs and connected to a venturi valve supplied with medical air. In all patients, the gas flow was set to 50 L/minute and the FiO2 to 0.21. Dogs received the following sequence of treatments, each lasting 20 minutes: 0 CPAP (pre-CPAP), CPAP of 5 cm H2O (CPAP), and again 0 CPAP (post-CPAP). Measurements and Main Result – During the entire study, the following data were collected: pressure and FiO2 inside the helmet, mean arterial pressure, respiratory rate, heart rate, sedation score (0 = awake, 10 = deep sedation), and tolerance to the helmet (0 = excellent, 4 = poor). At the end of each phase, an arterial blood sample was sampled. As compared with the pre-CPAP and the post-CPAP periods, during the CPAP period, the PaCO2, alveolar-arterial oxygen gradient (P[A−a]O2), and respiratory rate significantly decreased. The PaO2 was higher at CPAP (105.6±4.0mmHg) compared with pre-CPAP (80.6±6.9mmHg) and post-CPAP (86.7 ± 5.8 mm Hg). Tolerance and sedation scores during the CPAP period were not different from those in the pre-CPAP and post-CPAP periods. Conclusions – Noninvasive CPAP applied through a helmet is a feasible and effective supportive technique in dogs recovering from general anesthesia.

RATIONALE: In the presence of increased chest wall elastance, the airway pressure does not reflect the lung-distending (transpulmonary) pressure. OBJECTIVE: To compare the physiological effects of a conventional open lung approach titrated for an end-inspiratory airway opening plateau pressure (30 cm H2O) with a transpulmonary open lung approach titrated for a elastance-derived end-inspiratory plateau transpulmonary pressure (26 cm H2O), in a pig model of acute respiratory distress syndrome (HCl inhalation) and reversible chest wall mechanical impairment (chest wall and abdomen restriction). METHODS: In eight pigs, physiological parameters and computed tomography were recorded under three conditions: 1) conventional open lung approach, normal chest wall; 2) conventional open lung approach, stiff chest wall; and 3) transpulmonary open lung approach, stiff chest wall. MEASUREMENTS AND MAIN RESULTS: As compared with the normal chest wall condition, at end-expiration non aerated lung tissue weight was increased by 116 ± 68 % during the conventional open lung approach and by 28 ± 41 % during the transpulmonary open lung approach (p < .01), whereas cardiac output was decreased by 27 ± 19 % and 22 ± 14 %, respectively (p = not significant). CONCLUSION: In this model, the end-inspiratory transpulmonary open lung approach minimized the impact of chest wall stiffening on alveolar recruitment without causing hemodynamic impairment.

Objective: The aim of this study was to track the survival and efficacy of allogeneic bone marrow mesenchymal stem cells (BM-MSC) marked with red fluorescent protein (BM-MSCRFP) in an ovine model of collagenaseinduced tendinopathy. Methods: Bone marrow was harvested from one donor sheep and BM-MSC were isolated, cultivated and transfected with red fluorescent protein (BM-MSCRFP). Collagenase was injected into both Achilles tendons in the remaining nine sheep. After two weeks the left tendon was injected with a solution of 6 × 106 BM-MSCRFP and fibrin glue, while only fibrin glue was administered to the contralateral tendon in each sheep. After three, four and six weeks the tendons were harvested and evaluated for morphology, collagen I deposition, presence of CD34+ cells, and fluorescent labelled BM-MSC. Results: We demonstrated that delivery of BM-MSC into tendon lesions had positive effects on the injured tendons. The BM-MSCRFP survived at three, four and six weeks after treatment, leading to better quality healing of tendons as compared to the controls, where no labelled cells were detected. Interestingly, we demonstrated high expression of CD34+ cells in tendons that had been treated with BM-MSCRFP. Clinical relevance: Mesenchymal stem cell allografts have a positive effect on tendon healing and local injection of BM-MSC directly into the tendon allows the homing of BM-MSC for good efficiency of engraftment.

In the presence of risk factors, the anastomosis in the small intestine and in the colon are at risk for dehiscence and peritonitis. The apposition of a biological patch around the anastomosis might improve wound healing and therefore might prevent harmful, potentially life-threatening and costy complications. Aim: to verify if Tutomesh® facilitates the functional recovery of the intestinal anastomotic wound area (mucosa) in the pig ileum and colon. Methods: 24 Large White pigs (B.W. 25 kg; age 4-5 months) underwent ileal and colonic anastomosis with or without application of Tutomesh® and compared with healthy (intact) control intestinal segments. At days 2, 7, 14, 30 and 90 following surgery, ileal and colonic mucosa were isolated from similar anastomized and control tracts and mounted in Ussing chambers containing Krebs oxygenated solution at pH 7.4. Electrophysiological parameters, i.e. short circuit current (Isc) and transepithelial resistance (Rt), as markers of mucosal function, were continously measured by a digital voltage clamp system. Results: Ileal mucosa from control showed Isc of -17.10±4.72 μA/cm2 and Rt of 105.91±11.98 Ohm*cm2. In anastomized ileum Isc decreased by 52% and Rt increased by 58% (n=6 tissues); with Tutomesh® the Isc reduction was only 16.3% while Rt increased by 46% (for both n=6; p&lt;0.001 vs. control). In colonic mucosa from 13 control tissues, Isc was -10.67±2.29 μA/ cm2, Rt 140.94±14.38 Ohm*cm2. Colonic Isc and Rt (n=6) remained stable with anastom- osis, while Tutomesh® significantly increased the current by 47.0% (n=7; p&lt;0.001 vs. control). Conclusions: Our observations suggest that transport properties of intestinal mucosa improve significantly with Tutomesh® , a useful resorbable bio-patch which therefore helps the functional recovery of anastomoses, mainly in the ileum. Further studies are ongoing to assess the translational value of Tutomesh® in surgical patients.

Ischemia-reperfusion injury is the major cause of delayed graft function in transplanted kidneys, an early event significantly affecting long-term graft function and survival. Several studies in rodents suggest that the alternative pathway of the complement system plays a pivotal role in renal ischemia-reperfusion injury. However, limited information is currently available from humans and larger animals. Here we demonstrated that 30 minutes of ischemia resulted in the induction of C4d/C1q, C4d/MLB, and MBL/MASP-2 deposits in a swine model of ischemia-reperfusion injury. The infusion of C1-inhibitor led to a significant reduction in peritubular capillary and glomerular C4d and C5b-9 deposition. Moreover, complement-inhibiting treatment significantly reduced the numbers of infiltrating CD163(+), SWC3a(+), CD4a(+), and CD8a(+) cells. C1-inhibitor administration led to significant inhibition of tubular damage and tubular epithelial cells apoptosis. Interestingly, we report that focal C4d-deposition colocalizes with C1q and MBL at the peritubular and glomerular capillary levels also in patients with delayed graft function. In conclusion, we demonstrated the activation and a pathogenic role of classical and lectin pathways of complement in a swine model of ischemia-reperfusion-induced renal damage. Therefore, inhibition of these two pathways might represent a novel therapeutic approach in the prevention of delayed graft function in kidney transplant recipients.

Objective-To evaluate the use of the oxygen content-based index, Fshunt, as an indicator of venous admixture (Qs/Qt) at various fractions of inspired oxygen (FIO2s) in anesthetized sheep undergoing 1-lung or 2-lung ventilation. Animals-6 healthy adult female sheep. Procedures-Sheep were anesthetized and administered 5 different FIO2s (0.21, 0.40, 0.60, 0.80, and 1.00) in random order during 2-lung mechanical ventilation. Arterial and mixed venous blood samples were obtained at each FIO2 after a 15-minute stabilization period. Vital capacity alveolar recruitment maneuvers were performed after blood collection. The previously used FIO2 sequence was reversed for sample collection during 1-lung ventilation. Blood samples were analyzed for arterial, pulmonary end-capillary, and mixed venous oxygen content and partial pressure and for hemoglobin concentration. Oxygen hemoglobin saturation, Qs/Qt, Fshunt, and oxygen tension-based indices (OTIs; including PaO2:FIO2, alveolar-arterial difference in partial pressure of oxygen [PAO2 -PaO2], [PAO2 -PaO2]:FIO2, [PAO2 -PaO2]:PaO2, and PaO2:PAO2) were calculated at each FIO2; associations were evaluated with linear regression analysis, concordance, and correlation tests. Intermethod agreement between Qs/Qt and Fshunt was tested via Bland-Altman analysis. Results-Strong and significant associations and substantial agreement were detected between Fshunt and Qs/Qt. Relationships between OTIs and Qs/Qt varied, but overall correlations were weak. Conclusions and Clinical Relevance-Whereas OTIs were generally poor indicators of Qs/Qt, Fshunt was a good indicator of Qs/Qt at various FIO2s, regardless of the magnitude of Qs/Qt, and could be potentially used as a surrogate for Qs/Qt measurements in healthy sheep.