Constant Infusion Research Articles

Non-lethal sonodynamic therapy mitigates hypertensive renal fibrosis through the PI3K/AKT/mTORC1-autophagy pathway

Hypertension constitutes a significant public health concern, characterized by a high incidence and mortality rate. Hypertensive kidney disease is a prevalent complication associated with hypertension and is the second leading cause of end-stage renal disease (ESRD). Renal fibrosis linked to hypertension has emerged as the third leading cause of disease in dialysis patients. Autophagy activity is crucial for maintaining homeostasis, vitality, and physiological function of kidney cells, while also protecting the kidneys from fibrosis. The deficiency of autophagy will increase the sensitivity of the kidney to the damage, leading to impaired renal function, accumulation of damaged mitochondria and more severe of renal fibrosis. However, enhancing autophagy by activating the PI3K/AKT, AMPK, and mTOR pathways, improves podocyte injury and renal pathological changes, and ameliorates renal function. Current clinical interventions aimed at halting or reversing renal fibrosis in hypertensive patients are notably limited in their efficacy. Here, we present Non-lethal Sonodynamic Therapy (NL-SDT), in which ultrasound is used to activate locally sonosensitizers, thereby stimulating the production of reactive oxygen species for the purpose of modulating cell function or fate, as a novel methodology to inhibit progression of hypertensive renal fibrosis.To confirm whether NL-SDT can reduce hypertensive renal fibrosis and its mechanism. The mice model of hypertensive renal fibrosis was established by using osmotic minipumps (Alzet model 2004, Cupertino, CA) equipped with angiotensin-II (Ang II). The pumps were implanted in mice, ensuring constant infusion of Ang II at a dose of 1.0 µg/kg per minute for 4 weeks. The mice were exposed to 0.4 W/cm2 intensity ultrasonic radiation for 15 min at 4 h post injection of sinoporphyrin sodium (DVDMS) (4 mg/kg) into the caudal vein was repeated weekly for 4 treatments. The kidney from mice was stained with masson’s trichrome staining for collagen fiber expression, while alpha-smooth muscle actin (α-SMA) expression was determined via immunohistochemical staining. The protein levels of fibrosis parameters (α-SMA, collagen I, vimentin), pathway-related proteins (PI3K, AKT, mTORC1) and autophagy-related protein LC3B were determined using western blotting. Intracellular reactive oxygen species (ROS) levels were detected using DCFH-DA probe. Immunofluorescence was also used to observe the expression of α-SMA and E-cadherin in cells. Pathway-related protein inhibitors (the autophagy-related inhibitor 3-methyladenine (3-MA), chloroquine (CQ), ROS inhibitor N-acetyl-L-cysteine (NAC) were applied, and autophagosome changes were observed under transmission electron microscopy. Immunofluorescence was used to observe LC3 spot formation within cells.We obtained the following results via animal and cellular research. In vivo, (1) The collagen area of renal tissue was increased significantly in Ang II group (50.6%). The positive expression of α-SMA was increased significantly (37.8%). (2) The collagen area decreased after NL-SDT treatment (34.8%). The expression of α-SMA was decreased too (48.9%). The expression of LC3B increased in NL-SDT group. (3) The effect of NL-SDT on reducing renal fibrosis can be changed by rapamycin and CQ. In vitro. (1) The expression of α-SMA, collagen I and vimentin were increased significantly in TGF-β1-induced NRK-52E cells. (2) The increase of autophagosomes was observed in TGF-β1-induced NRK-52E cells after NL-SDT. The levels of ROS were increased after NL-SDT (24.8%). The effect of NL-SDT on autophagy was reversed after administration of NAC. The expression of PI3K, P-AKT and P-mTORC1 was decreased in TGF-β1-induced NRK-52E cells after NL-SDT. NL-SDT inhibited the transition of epithelial cells into myofibroblasts by activating PI3K-AKT-mTORC1-autophagy pathway in TGF-β1-induced NRK-52E cells. (3) The administration of the pathway inhibitors showed a reciprocal effect on NL-SDT-inhibited epithelial-mesenchymal transition (EMT).(1) NL-SDT reduced blood pressure temporarily in mice model of hypertensive renal fibrosis induced by Ang II. (2) NL-SDT alleviated renal fibrosis in mice model of hypertensive renal fibrosis induced by Ang II. (3) NL-SDT promoted autophagy by inhibiting PI3K-AKT-mTORC1 signaling pathway and alleviated renal fibrosis in mice model of hypertensive renal fibrosis induced by Ang II. NL-SDT is a non-invasive and efficacious regimen to inhibit renal fibrosis. It may be a new approach for clinical treatment of renal fibrosis, delaying or reducing the occurrence of ESRD.

Case report: Suspected propofol associated Heinz body anemia in five mechanically ventilated dogs: a historical case series

ObjectiveThe aim of this report is to raise awareness of the risk of oxidant-induced erythrocyte injury, including Heinz body (HB) anemia, in critically ill dogs by describing the condition in five dogs receiving constant rate infusions of propofol.Case summaryThis case series describes five dogs with suspected propofol-induced HB anemia undergoing mechanical ventilation (MV) for lower motor neuron disease. Four of the five dogs were treated for tick paralysis (Ixodes holocyclus) and one was treated for suspected eastern brown snake (Pseudonaja textilis) envenomation. Propofol constant rate infusions were administered as part of total intravenous anesthesia. All five dogs became anemic, and a complete blood count and blood smear interpretation by a specialist clinical pathologist confirmed the presence of oxidative red blood cell injury (eccentrocytosis and HBs). The duration of MV ranged from 76 to 131 h, with HBs identified within 47–96 h of commencing propofol. All five dogs survived to discharge, with one dog requiring a blood transfusion.DiscussionWhile propofol-induced HB anemia is a recognized phenomenon in cats, to the author’s knowledge, this is the first case series detailing multiple occurrences in dogs. Veterinarians should be aware of the risk of propofol-induced oxidative erythrocyte injury in dogs receiving prolonged infusions of propofol, and consider risk mitigation by using propofol as part of multiagent intravenous anesthesia, keeping dose rates as low as possible, and daily monitoring of blood smears and red blood cell indices.

Perioperative analgesic effects of a modified supratemporal retrobulbar block in dogs undergoing corneal and endocular surgery.

To evaluate the perioperative efficacy of a modified supratemporal retrobulbar block in dogs undergoing ocular surgery. In this prospective randomized clinical trial, dogs were premedicated with dexmedetomidine (1 mcg/kg im) and methadone (0.1 mg/kg im), induced with propofol to effect and maintained with isoflurane (FE'Iso 1.1%). In the retrobulbar group a mixture of lidocaine 2% (5.5 mL) and ropivacaine 0.75% (2 mL) was administered at 0.1 mL/kg, via a modified supratemporal technique using a Tuohy needle. No block was performed in the controls. When heart rate or mean arterial pressure increased above 30% of the pre-incisional values, fentanyl (1 mcg/kg iv) was administered. Propofol (1 mg/kg iv) was injected when anaesthesia was deemed too light. After a total of three administrations regardless of the type of drugs (fentanyl/propofol), a constant rate infusion of fentanyl (5 mcg/kg/h iv) was started. Quality of recovery (blindly assessed using a descriptive score scale), postoperative eye rubbing and complications were studied. Eighteen dogs were included. The retrobulbar group (nine) dogs had significantly less risk of receiving fentanyl than controls (nine) (Relative risk: 0.142, 95% CI: 0.021 to 0.936) and a recovery score > 2 (RR: 0.058, 95% CI: 0.003 to 0.887). The median amount of fentanyl (mcg/kg) was statistically lower in the retrobulbar group than in the controls: 0 mcg/kg (range, 0 to 1) versus 2 mcg/kg (range, 0 to 8.49), respectively. Only controls showed eye rubbing. The modified supratemporal retrobulbar block reduced the intraoperative rescue analgesia and improved the quality of recovery.

Effect of a constant rate infusion of ketamine on left ventricular systolic and diastolic function in dogs anesthetized with propofol

ObjectiveTo evaluate the effect of a constant rate infusion of ketamine on left ventricular systolic and diastolic function in dogs anesthetized with propofol. Study designProspective randomized, blinded clinical study. AnimalsSixteen healthy dogs. MethodsDogs were randomized into two groups, the propofol-ketamine group (GPK) and propofol group (GP), with eight animals each. Anesthesia was induced with propofol and maintained with a constant rate infusion (CRI) of propofol at a rate of 0.8 mg/kg/min. All dogs were mechanically ventilated throughout the study. Thirty-five minutes after anesthesia started, the GPK received a bolus of ketamine (0.5 mg/kg IV, over 2 minutes) followed by the CRI of ketamine at 30 μg/kg/min, while the GP received the same volume of 0.9% NaCl over 2 minutes followed by the CRI of 0.9% NaCl at the same rate. Hemodynamic and echocardiographic variables were recorded 15 min after initiating CRI of propofol (M0), immediately after each treatment bolus (M1), and 20 (M2) and 40 min (M3) after initiating CRI of ketamine or 0.9% NaCl solution in both groups. ResultsCardiac index, stroke index, and peripheral vascular resistance index were not significantly different between treatments. No significant differences in left ventricular systolic and diastolic functions derived from echocardiographic variables were observed between groups. Conclusions and clinical relevanceDuring treatment with CRI of ketamine at the proposed rate, hemodynamic parameters and echocardiographic variables, used to measure left ventricular systolic and diastolic function, were maintained stable in healthy dogs anesthetized with propofol.

Pain intensity and stress indicators after cemented total knee replacement with epidural application of morphine: prospective randomized study

The objective to perform the objective assessment of the intensity of pain syndrome after cemented total knee replacement with epidural analgesia with 0.2% ropivacaine solution and epidural analgesia with a combination of 0.2% ropivacaine solution with morphine was performed.Materials and methods. The study included 60 patients who underwent cemented total knee replacement for gonarthrosis under combined spinal-epidural anesthesia. In patients of the control group (n = 30), postoperative anesthesia was performed with 0.2% ropivacaine solution epidural through a catheter at the L2–3–L1–2 level in the form of a bolus followed by constant infusion. In patients of the main group (n = 30), analgesia was performed according to the same technique, but using a morphine solution of 1% – 0.3 ml (3mg) as part of a bolus of 0.2% ropivacaine solution epidural. The hemodynamics of the patients, the volume of intraoperative blood loss, and infusion therapy were homogeneous due to the carefully developed surgical procedure, had no significant differences and were not taken into account when publishing the data. The level of glycemia and cortisol in venous blood on the day of surgery (1 hour before surgery and 4 hours after surgery), age, and pain intensity on a numerical rating scale (NRS) were studied. Statistical processing was performed by MedCalc Software Ltd.Results. In the postoperative period, the level of venous blood cortisol in patients of the main group was 486.2 [470.6; 494.5] nmol/l, and in patients of the control group – 876.8 [803.7; 918.7] nmol/l (p < 0.001 according to the Mann–Whitney U-criterion); pain intensity on the numerical rating scale in the main group was 1 [1; 1.5] score, in the control group was 4 [3; 5] scores (p < 0.001, U–Mann–Whitney criterion). There was also a correlation between the value of glycemia and the pain intensity by NRS in the postoperative period (Spearman’s coefficient r = 0.669, 95% CI = 0.499–0.789, p < 0.0001).Conclusions. As a result of the study, it was found that epidural analgesia with morphine leads to a lower increase in glucose and cortisol levels in the postoperative period, lower pain intensity when subjectively assessed using the numerical rating scale, which indicates a high quality of anesthesia.

Effects of continuous pecto-intercostal fascial block for management of post-sternotomy pain in patients undergoing cardiac surgery: a randomized controlled trial.

Managing postoperative pain following median sternotomy has long been a notable challenge for anesthesiologists. The administration of postoperative analgesia traditionally relies on intravenous pumps for the delivery of opioids. With the development of regional block techniques and postoperative multimodal analgesia, pecto-intercostal fascial block (PIFB) has gained widespread utilization due to its distinctive advantages. However, its application is limited to a single block. This study aimed to indicate whether continuous PIFB analgesia in cardiac surgery via sternotomy could possess clinical advantages compared with intravenous analgesia in terms of postoperative pain management. If continuous PIFB analgesia was the priority, the secondary objective would involve determining the most effective administration method, making it a critical area of exploration. Totally, 114 patients were randomly allocated to three groups: the PCIA group, receiving intravenous opioid infusion exclusively via pump, and the C-PIFB and I-PIFB groups, where ultrasound-guided PIFB with a nerve blocking pump was administered. The C-PIFB group received a constant basal infusion, while programmed intermittent boluses were administered in the I-PIFB group. The primary endpoint was postoperative visual analogue scale (VAS) scores, and secondary outcomes included intraoperative sufentanil consumption, time to extubation, mobilization, length of stay in intensive care unit (ICU) and hospital, and the incidence of postoperative complications. The VAS scores at rest and during coughing were noticeably diminished in the two block groups relative to the intravenous pump group at 12, 24, 48, and 72h postoperatively. Notably, intraoperative sufentanil consumption was significantly reduced in the C-PIFB group (3.12 [0.93] ug.kg-1) and the I-PIFB group (3.42 [0.77] ug.kg-1) compared with the PCIA group (4.66 [1.02] ug.kg-1, P<0.001). Time to extubation, mobilization, length of stay in ICU and hospital, and use of rescue analgesics did not exhibit statistically significant differences among the three groups. However, the postoperative complication rates were markedly lower in the C-PIFB group (42.11%) and I-PIFB group (36.84%) relative to the PCIA group (81.58%, P<0.001). There were no significant differences between C-PIFB and I-PIFB groups regarding VAS score, secondary outcomes, and postoperative complications. Continuous PIFB can provide satisfactory postoperative analgesia while reducing perioperative opioid consumption, diminishing the risk of postoperative complications, and accelerating postoperative recovery for patients undergoing median sternotomy in cardiac surgery. The constant basal infusion method may be the optimal approach for administering continuous PIFB.

Effect of intravenous and intraperitoneal lignocaine on post operative pain scores in dogs undergoing ovariohysterectomy

The study was conducted in twelve female dogs of different breeds, randomly divided into two groups of six dogs each. All dogs underwent a comprehensive pre-anaesthetic evaluation prior to surgery. One hour before the procedure, the dogs received firocoxib orally. Pre-anaesthetic medication included injections of xylazine and buprenorphine, followed by induction with ketamine and midazolam. In Group I, lignocaine was administered during induction followed by a constant rate infusion (CRI), while in Group II, lignocaine was applied directly to the peritoneal cavity and viscera during surgery. Anaesthesia was maintained with isoflurane in both the groups. The quality of sedation, induction and recovery from anaesthesia was noted as excellent in both groups. Haematological and serum biochemical parameters varied within normal acceptable ranges and showed no significant differences between the groups. Electrocardiographic parameters, blood pressure values and blood gas parameters also remained within normal limits, without significant differences between the groups. Pain scores were lower in Group II compared to Group I, although the difference was not statistically significant. Both multimodal anaesthetic protocols proved effective in managing postoperative pain in dogs. Keywords: Pain, multimodal anaesthesia, multimodal analgesia, OHE, GCMPS

Acute and circadian feedforward regulation of agouti-related peptide hunger neurons.

When food is freely available, eating occurs without energy deficit. While agouti-related peptide (AgRP) neurons are likely involved, their activation is thought to require negative energy balance. To investigate this, we implemented long-term, continuous invivo fiber-photometry recordings in mice. We discovered new forms of AgRP neuron regulation, including fast pre-ingestive decreases in activity and unexpectedly rapid activation by fasting. Furthermore, AgRP neuron activity has a circadian rhythm that peaks concurrent with the daily feeding onset. Importantly, this rhythm persists when nutrition is provided via constant-rate gastric infusions. Hence, it is not secondary to a circadian feeding rhythm. The AgRP neuron rhythm is driven by the circadian clock, the suprachiasmatic nucleus (SCN), as SCN ablation abolishes the circadian rhythm in AgRP neuron activity and feeding. The SCN activates AgRP neurons via excitatory afferents from thyrotrophin-releasing hormone-expressing neurons in the dorsomedial hypothalamus (DMHTrh neurons) to drive daily feeding rhythms.

Comparison of Ketamine/Diazepam and Tiletamine/Zolazepam Combinations for Anaesthesia Induction in Horses Undergoing Partial Intravenous Anaesthesia (PIVA): A Retrospective Clinical Study.

The aim of this retrospective clinical study was to compare the combinations of ketamine/diazepam (KD group) and tiletamine/zolazepam (TZ group) for the induction of general anaesthesia in horses undergoing elective surgery. The data from the clinical and the anaesthetic records of 138 horses from 2021 to 2023 were evaluated, and the horses were divided in two groups: KD (n = 60) and TZ (n = 72). The horses were premedicated with romifidine and methadone IV; anaesthesia was induced with ketamine/diazepam for the KD group and tiletamine/zolazepam for the TZ group and was maintained with isoflurane and a constant rate infusion of romifidine. The data encompassed sex and neuter status, age, breed, weight, American Society of Anaesthesiologists physical status, type of surgical procedure performed under anaesthesia, induction time, induction score, surgery time, recovery time, and the recovery score using a descriptive scale. Baseline heart rate (HR), intraoperative HR, baseline respiratory rate (fR), intraoperative fR, mean arterial pressure (MAP), oxygen saturation (SpO2), and fraction of expired isoflurane (FE'Iso) were also recorded. The induction time was significantly longer (p = 0.004) in the TZ group (60 (40-120)) as compared to the KD group (50 (30-120)). Recovery time was also significantly longer (p ≤ 0.001) in the TZ group (46.5 (15-125)) as compared to the KD group (30 (5-105)). These findings suggested that, in adult horses undergoing elective surgery, TZ could be considered a valid alternative to KD for the induction of general anaesthesia. Additional experimental studies comparing the two induction regimens and their pharmacokinetic and pharmacodynamic characteristics are needed.

Cardiorespiratory, hemodynamic, and sedative effects of dexmedetomidine in sheep.

An alternative in an attempt to minimize the effects triggered by intravenous (IV) bolus administration of α-2 adrenergic receptor agonists are continuous rate infusions (CRI). The requirement for sedation protocols in sheep for procedures to be performed without physical restraint and with reduced adverse effects, commonly observed with bolus use, justifies the study of CRI. The aim of study was to compare the cardiopulmonary and sedative effects of IV bolus injection and CRI of dexmedetomidine (DEX) in sheep. Six adult male sheep (38.3 ± 7.6 kg) received DEX as a bolus (5 µg kg-1, DEXbolus treatment) or CRI (5 µg kg-1 h-1 for 1 h, DEXCRI treatment). We recorded heartrate (HR), respiratory rate, systemic arterial blood pressure, pulse oximetry, hemodynamic parameters, blood gases and sedation scores over 120 min. HR was significantly lower in DEXbolus at 5 and 15 min than in DEXCRI, with HR reduction observed for 30 min in DEXbolus. Hypoxemia was noted in DEXbolus at 10 and 30 min. Pulmonary vascular resistance index increased at 5 min, and cardiac index (CI) decreased at all timepoints compared with baseline in DEXbolus. In DEXCRI, CI decreased only at 45 min. Sedation scores were higher in DEXbolus at 15 and 30 min. DEX CRI administration resulted in fewer cardiorespiratory and hemodynamic changes compared with bolus injection and lower sedation scores (<4/10), which would not allow animal handling without a reaction. The load dose used in CRI was a limitation to constant infusion.

Effects of a synergic interaction between magnesium sulphate and ketamine on the perioperative nociception in dogs undergoing tibial plateau leveling osteotomy: a pilot study.

Magnesium Sulphate (MgSO4) is commonly used in human medicine for the management of perioperative pain in different types of procedures. However, in veterinary medicine, the use of MgSO4 has not been evaluated for its analgesic efficacy in dogs, which has generated conflicts of opinion in this area of veterinary anesthesiology. The aim of this study was to evaluate the perioperative analgesic efficacy of MgSO4 in combination with Ketamine in dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO). Our hypothesis is that MgSO4 plus ketamine have a synergistic action in the management of intra-and postoperative pain. Twenty adult mixed breed dogs with average age 5.9 ± 2.6 years and weight 27.8 ± 9.2 kg were included in this prospective, clinical, randomized study. Dogs were randomly assigned to two groups. The MK group received ketamine (0.5 mg/kg as starting bolus followed by continuous infusion rate at 1 mg/kg/h). At the end of the ketamine bolus, MgSO4 (50 mg/kg over 15 min) was administered by the same route, followed by a constant rate infusion (CRI) at 15 mg/kg/h, IV. K group received a bolus of ketamine followed by a CRI at the same dosage described in MK group. Main cardiorespiratory parameters were recorded 10 min before the start of surgery (BASE), after the ketamine bolus (T1) and the MgSO4 bolus (T2), during the skin incision (SKIN), the osteotomy (OSTEOTOMY) and skin suturing (SUTURE). In the postoperative period, the short form of Glasgow Composite Pain scale (SF-CMPS) was used to assess pain at 30, 60, 120, and 180 min after extubation (Post30, Post60, Post120, and Post180, respectively). The main blood electrolytes (Mg2+, Ca2+, Na+, K+) were analyzed at BASE, T2, OSTEOTOMY, SUTURE and T3 (one hour after stopping MgSO4 infusion). Number of rescue analgesia and administration times were recorded both in the intra-and postoperative period. In K group 7 out of 10 dogs required intraoperatory rescue analgesia compared to MK group (3/10). Furthermore, mean arterial pressure (MAP) and heart rate (HR) were significantly higher at OSTEOTOMY compared to BASE time in both groups. In the postoperative period, at T120, ICMPS-SF score was higher in K group than MK group. The administration of MgSO4 could guarantee better analgesia in the perioperative period in dogs undergoing TPLO, performing a synergistic action with ketamine.

Comparison of the Effectiveness of Warmed Versus Room Temperature Intravenous Fluids Administration to Prevent Intraoperative Heat Loss in Anaesthetised Calves Undergoing Umbilical Herniorrhaphy.

Warmed intravenous (IV) fluids administration to prevent hypothermia provide controversial results in humans, cats and dogs, but its effect on calves is unknown. To evaluate the effectiveness of warmed IV fluids administered to prevent intraoperative heat loss in anaesthetised calves undergoing umbilical herniorrhaphy. Thirty Simmental breed calves (aged 10-30days) were randomly divided between two equal groups, wherein the infusion fluid (Ringer's lactate, 5mL/kg/h) was administered either at room temperature (Group RoT) or warmed (Group WF). Pulse rate (PR), respiratory rate (fR), peripheral haemoglobin oxygen saturation (SpO2) and rectal temperature (RT) were recorded immediately after the onset of anaesthesia induction (T0) at T5, T10, T15, T30, T45 and T60. Duration of anaesthesia, surgery time and recovery scores were also noted. The PR, RT and fR values showed no significant difference between groups over time (p>0.05). There was no significant difference in duration of anaesthesia, surgery time or recovery score between groups (p>0.05). The findings of the current study suggest that warmed IV fluid as the warming method did not prevent intraoperative hypothermia in calves. A constant-rate infusion of warmed fluid (5mL/kg/h) is insufficient to prevent intraoperative hypothermia in calves.

On the analysis of functional PET (fPET)-FDG: baseline mischaracterization can introduce artifactual metabolic (de)activations.

Functional Positron Emission Tomography (fPET) with (bolus plus) constant infusion of [18F]-fluorodeoxyglucose FDG), known as fPET-FDG, is a recently introduced technique in human neuroimaging, enabling the detection of dynamic glucose metabolism changes within a single scan. However, the statistical analysis of fPET-FDG data remains challenging because its signal and noise characteristics differ from both classic bolus-administration FDG PET and from functional Magnetic Resonance Imaging (fMRI), which together compose the primary sources of inspiration for analytical methods used by fPET-FDG researchers. In this study, we present an investigate of how inaccuracies in modeling baseline FDG uptake can introduce artifactual patterns to detrended TAC residuals, potentially introducing spurious (de)activations to general linear model (GLM) analyses. By combining simulations and empirical data from both constant infusion and bolus-plus-constant infusion protocols, we evaluate the effects of various baseline modeling methods, including polynomial detrending, regression against the global mean time-activity curve, and two analytical methods based on tissue compartment model kinetics. Our findings indicate that improper baseline removal can introduce statistically significant artifactual effects, although these effects characterized in this study (~2-8%) are generally smaller than those reported by previous literature employing robust sensory stimulation (~10-30%). We discuss potential strategies to mitigate this issue, including informed baseline modeling, optimized tracer administration protocols, and careful experimental design. These insights aim to enhance the reliability of fPET-FDG in capturing true metabolic dynamics in neuroimaging research.

Intravenous Lipid Emulsion for the Treatment of Ivermectin Toxicity in a Cat: A Case Report

A two-years-old male cat weighing three kg was presented to the Referral Veterinary Polyclinic of ICAR – Indian Veterinary Research Institute (IVRI), Izatnagar with history of anorexia, no water intake, ataxia, head tilting downward, sudden recumbency and loss of vision. While taking history the owner declared about the use of off-label oral ivermectin preparation @ 2.5 mg/kg total dose (5 times the recommended dose) once only. Cat had high rectal temperature (105° F), normal mucus membrane, tachypnoea (70/min), tachycardia(145/min). At the beginning, the patient received 20% lipid emulsion (Intralipid) at 1.5 mL/kg body weight, Diazepam 0.5 mg/kg b. wt. IV once, dexamethasone 0.5 mg/kg b. wt., and 25 mg/kg b. wt. bid of cefotaxime. The patient also received constant rate infusion therapy at 0.25 ml/kg/h, OD, and isotonic crystalloid solution (0.9% NS) at 30 ml/kg body weight for a total of 10 minutes. After three days, the cat's clinical condition returned to normal state. This case reports helps to readers in managing an emergency condition of ivermectin toxicity.

Meals Containing Equivalent Total Protein from Foods Providing Complete, Complementary, or Incomplete Essential Amino Acid Profiles do not Differentially Affect 24-h Skeletal Muscle Protein Synthesis in Healthy, Middle-Aged Women

BackgroundDietary protein quality can be assessed by skeletal muscle protein synthesis (MPS) stimulation. Limited knowledge exists on how consuming isonitrogenous meals with varied protein qualities affects postprandial and 24-h MPS. ObjectivesWe assessed the effects of protein quality and complementary proteins on MPS. We hypothesized that meals containing a moderate amount of high-quality, complete protein would stimulate postprandial and 24-h MPS. Meals containing two complementary, plant-based incomplete proteins would stimulate MPS less, and meals containing plant-based incomplete proteins at each meal, but complementary over 24 h would not stimulate MPS. MethodsThis quasi-experimental study included a randomized, crossover design to assess protein quality and a nonrandomized low-protein control. We measured postprandial and 24-h MPS responses of healthy middle-aged women (n = 9, age 56 ± 4 y), to 3 dietary conditions: isonitrogenous meals containing 23 g protein/meal from 1) complete protein (lean beef), 2) 2 incomplete, but complementary protein sources (navy/black beans and whole wheat bread), and 3) single incomplete protein sources (black beans or whole wheat bread at 1 meal), but providing a complete amino acid profile over 24 h. In the low-protein group women (n = 8, 54 ± 5 y) consumed a single breakfast meal containing 5 g of protein. Venous blood and vastus lateralis samples were obtained during primed, constant infusions of L-[ring-13C6]phenylalanine to measure mixed muscle fractional synthetic rates (FSR). ResultsMeals containing complete, complementary, or incomplete proteins did not differentially influence FSR responses after breakfast (P = 0.90) or 24 h (P = 0.38). At breakfast, the complete (P = 0.030) and complementary (P = 0.031) protein meals, but not the incomplete protein meal (P = 0.38), had greater FSR responses compared with the low-protein control meal. ConclusionsIsonitrogenous meals containing a moderate serving of total protein from foods providing complete, complementary, or incomplete essential amino acid profiles do not differentially stimulate muscle protein synthesis after a meal and daily. Trial registration numberThis clinical trial was registered at clinicaltrials.gov as NCT03816579. URLhttps://www.clinicaltrials.gov/ct2/show/NCT03816579?term=NCT03816579&draw=2&rank=1.

476 Induced hindgut acidosis in sheep affected gut permeability and ruminal fermentation

Abstract Leaky gut may be caused by acidotic conditions in the hindgut and lead to systemic inflammation and negative effects on the gastrointestinal tract. The objective was to determine the effects of induced hindgut acidosis in sheep on cecal pH, ruminal fermentation, and gut permeability. Ruminally and cecally cannulated ewes [n = 11; body weight (BW) = 49 ± 4 kg] were assigned to one of two treatments: control (CON; n = 5) or induced hindgut acidosis (HGA; n = 6). To induce hindgut acidosis, 3 g wheat starch/kg BW per 24 h was continuously infused via the cecal cannula for 4 d. Control ewes received a constant infusion of deionized water. The diet contained 40% grass hay pellets, 35% whole shelled corn, 15% dried distillers grains, and 10% alfalfa cubes. Chromium EDTA was dosed once daily via the cecal cannula as a marker of gut permeability. Rumen, cecal, and fecal samples were collected to determine pH and volatile fatty acids (VFA). Rumen fluid was collected on d 4 for an ex vivo fermentation. Flasks were incubated for 24 h to determine pH, VFA, ammonia and in vitro dry matter digestibility. Tissue samples from the ileum, cecum, and colon were mounted in Ussing chambers to measure transepithelial electrical resistance (TEER). There was a treatment × time effect (P = 0.05) for cecal pH with HGA ewes having lesser cecal pH after d 1. By d 4, cecal pH had declined to 5.07 for HGA ewes compared with CON ewes which remained above 6.40 throughout the experiment. A treatment × time interaction was also observed (P &amp;lt; 0.01) for fecal pH and followed the same trend as cecal pH. Rumen pH was not affected (P = 0.87) by the interaction of treatment and time but was affected (P &amp;lt; 0.01) by treatment as ewes on the HGA treatment had a lesser rumen pH than CON ewes. Control ewes had lesser ruminal VFA and ammonia concentrations than HGA ewes (P &amp;lt; 0.01). Urinary Cr recovery was not affected by the interaction of treatment and time, or treatment (P ≥ 0.13). In vitro dry matter disappearance was not affected by cecal infusion treatment (P = 0.60). There was no effect (P = 0.78) of treatment on ex vivo pH. There were no effects (P ≥ 0.11) of treatment, time, or their interaction on ex vivo ammonia or total VFA concentration. In cecal tissue, TEER tended (P = 0.09) to be greater in CON ewes than HGA ewes. In contrast, TEER was not different (P ≥ 0.83) in ileal or colonic tissues between treatments. Induced hindgut acidosis in sheep altered rumen fermentation and tended to increase ex vivo measures of cecal permeability, but did not affect ex vivo rumen fermentation.

Hepato-splanchnic fluxes during exercise in patients with cirrhosis-a pilot study.

In cirrhotic patients, compromised hepatocyte function combined with disturbed hepatic blood flow could affect hepato-splanchnic substrate and metabolite fluxes and exacerbate fatigue during exercise. Eight cirrhotic patients performed incremental cycling trials (3 × 10 min; at light (28 [19-37] W; median with range), moderate (55 [41-69] W), and vigorous (76 [50-102] W) intensity). Heart rate increased from 68 (62-74) at rest to 95 (90-100), 114 (108-120), and 140 (134-146) beats/min (P < 0.05), respectively. The hepatic blood flow, as determined by constant infusion of indocyanine green with arterial and hepatic venous sampling, declined from 1.01 (0.75-1.27) to 0.69 (0.47-0.91) L/min (P < 0.05). Hepatic glucose output increased from 0.6 (0.5-0.7) to 1.5 (1.3-1.7) mmol/min, while arterial lactate increased from 0.8 (0.7-0.9) to 9.0 (8.1-9.9) mmol/L (P < 0.05) despite a rise in hepatic lactate uptake. Arterial ammonia increased in parallel to lactate from 47.3 (40.1-54.5) to 144.4 (120.5-168.3) μmol/L (P < 0.05), although hepatic ammonia uptake increased from 19.5 (12.4-26.6) to 69.5 (46.5-92.5) μmol/min (P < 0.05). Among the 14 amino acids measured, glutamate was released in the liver, while the uptake of free fatty acids decreased. During exercise at relatively low workloads, arterial lactate and ammonia levels were comparable to those seen in healthy subjects at higher workloads, while euglycemia was maintained due to sufficient hepatic glucose production. The accumulation of lactate and ammonia may contribute to exercise intolerance in patients with cirrhosis.

Pain related syndrome of inappropriate antidiuretic hormone secretion in a kitten

A 2-month-old domestic shorthair kitten was presented for evaluation of weakness, gait abnormalities, and signs of pain after trauma. On admission, the patient was found laterally recumbent with obvious gait abnormalities: difficulty rising from sitting and marked unilateral left hind limb lameness. On orthopedic examination, severe pain, crepitations, and swelling of the left hind limb were detected. Results of the first diagnostic work-up were all consistent with hyponatremia, hypochloremia and a Salter-Harris type I fracture.The kitten initially received isotonic fluids, analgesia, and antiemetic treatment. Twelve hours after admission, the analgesic plan was considered insufficient, and the general patient's condition worsened, showing severe mental depression. Blood and urine samples were collected for a more in-depth diagnostic evaluation; the patient showed worsening hyponatremia (113 mmol/L; [RR: 146,2-156,2]), severe plasma hypoosmolality (218.2 mOsm/kg; [RR: 287-307 mOsm/kg]), high natriuresis (Na: 74.9 mmol/L; [RR: <40 mmol/L]), and urinary hyperosmolality (630 mOsm/kg; [RR: <150 mOsm/kg]). Based on these new clinical findings syndrome of inappropriate antidiuretic hormone (SIADH) secretion was diagnosed.Emergency treatment with hypertonic saline was then instituted, a constant rate infusion of 3% hypertonic saline infusion to increase plasma sodium was initiated and a loop diuretic, furosemide (1 mg/kg/IV), was administered at 12-hour intervals to induce diuresis. Discharge occurred 4 days after admission as the patient was clinically stable and the hyponatremia progressively resolved. To the author's knowledge this is the first report of a kitten developing pain related SIADH associated to orthopedic trauma.

The effect of intravenous magnesium sulphate infusion on total intravenous anesthesia with propofol in adult dogs: A randomized, blinded trial

ObjectiveTo evaluate cardiopulmonary, arterial blood gas and propofol-sparing effects of magnesium sulfate (MgSO4) constant rate infusion (CRI) in mechanically ventilated dogs maintained under total intravenous anesthesia with propofol. Study designBlinded, randomized, clinical trial. AnimalsA total of 24 healthy adult dogs. MethodsDogs were premedicated with intramuscular acepromazine (0.05 mg kg–1) and morphine (0.5 mg kg–1), followed by an intravenous (IV) bolus of saline or MgSO4 (50 mg kg–1 over 15 minutes) and propofol (given to effect to induce anesthesia). Anesthesia was maintained with an IV propofol infusion (beginning at 0.3 mg kg–1 minute–1, adjusted as necessary). Concurrently, one of three IV infusions were administered: GS (0.9% NaCl), GM30 (MgSO4, 30 mg kg–1 hour–1) or GM80 (MgSO4, 80 mg kg–1 hour–1). Propofol induction and maintenance doses were recorded. The following variables were recorded at baseline (T0), after bolus treatment (T1), after beginning mechanical ventilation (T5) and every 15 minutes until the end of the procedure (T15–T120): mean arterial pressure, heart rate, peripheral oxygen saturation, end-tidal partial pressure of CO2, temperature, blood gas variables, indirect calorimetry and extubation time. Values of p < 0.05 were considered significant. ResultsPropofol induction bolus dose was lower in GM30 (31.2%, p = 0.04) and GM80 (38.9%, p = 0.003) than in GS. The maintenance propofol infusion rate in GM80 was 16.9% lower (p = 0.03), resulting in fewer propofol CRI rescues during the perioperative period. GM30 and GM80 exhibited faster extubation times than GS (46.2%, p = 0.002 and 48.9%, p = 0.001, respectively). Conclusions and clinical relevanceInfusion of a 50 mg kg–1 bolus, followed by CRI of MgSO4 (30 and 80 mg kg–1 hour–1), reduces the propofol induction and maintenance (CRI) requirement, maintaining cardiorespiratory stability and reducing the time required to extubation.

Effect of dexmedetomidine constant rate infusion on the analgesic duration of peripheral nerve blocks in dogs: a randomized clinical study

The aim of this study was to evaluate whether a constant rate infusion of dexmedetomidine could prolong the analgesic effect of peripheral nerve blocks. Twenty client-owned dogs were enrolled and randomly divided into 2 groups. The DEX group received dexmedetomidine infusion at 1 mcg kg−1 h−1, and the NaCl group received an equivalent volume infusion of saline. Infusions were started after securing vascular access and continued for 10 min, after which intravenous (IV) methadone at 0.2 mg kg−1 and propofol to effect were administered. All animals were maintained with isoflurane in 70% oxygen. Sciatic, saphenous and obturator nerve blocks were performed using 0.1 mL kg−1 0.5% ropivacaine/block. Intraoperative fentanyl was administered if the heart rate and/or mean arterial pressure (MAP) increased > 15% from the previous measurement, and vasopressors were administered if MAP was ≤ 70 mmHg. Postoperative pain was assessed every hour using the Glasgow Composite Pain Scale (GCPS) until the first rescue analgesia administration. Postoperative rescue analgesia (methadone (0.2 mg kg−1 IV) and carprofen (2 mg kg−1 IV)) was administered if the pain score was higher than 6/24 or 5/20. Duration of analgesia was defined as the time between the nerve block procedure and initial postoperative rescue analgesia. Ambulation, proprioception, and skin sensitivity were evaluated to assess the duration of the motor and sensory block. A Student T and chi-square test were used to compare groups for duration of postoperative analgesia and intraoperative fentanyl and vasopressor use, respectively (p values ≤ 0.5 considered significant). A greater number of dogs in the NaCl group required fentanyl (5/10 p = 0.03) and vasopressors (8/10, p = 0.02) than did those in the DEX group (0/10 and 2/10, respectively). The duration of postoperative analgesia was significantly longer (604 ± 130 min) in the DEX group than in the NaCl group (400 ± 81 min, p = 0.0005).Dexmedetomidine infusion at 1 mcg kg−1 h−1 delays the time to first administration of rescue analgesia and reduces intraoperative analgesic and vasopressor requirements during Tibial Tuberosity Advancement surgery.