Pharmacokinetic and pharmacodynamic evaluation of propofol administered to cats in a novel, aqueous, nano-droplet formulation or as an oil-in-water macroemulsion.

This study evaluated pharmacokinetic and pharmacologic properties of a novel, non-lipid microemulsion, 1% w/v formulation of propofol to a conventional macroemulsion formulation of propofol (Rapinovet) in cats. The study utilized a two-period crossover design with two treatments and 10 female, intact, purpose bred domestic shorthair cats. Cats were fitted with telemetry transmitters for direct measurement of arterial blood pressure, pulse rate, electrocardiogram (ECG, lead II), and body temperature. At least 7 days separated treatments. Orotracheal intubation was the clinical endpoint utilized to evaluate adequate depth of anesthesia. Blood samples were drawn from jugular vascular access ports before propofol treatment; 3, 5, 15, 25, 35, 45, and 60 min and then 2, 3, 6, 8, 12, 18, and 24 h after administration of propofol into a cephalic vein. Whole blood samples were assayed for propofol concentrations using a gas chromatography/mass spectrometry method validated for feline blood at a limit of quantification of 5 ng/mL. Pulse rate, ECG, heart rhythm, respiratory rate, systolic, diastolic and mean arterial blood pressures, SpO2, and body temperature were monitored continuously during each anesthetic episode. Time to lateral recumbency, orotracheal intubation, and extubation, time to sternal recumbency during recovery, times to adverse events, and doses of propofol required for induction to anesthesia were documented. Cats required 6.96 +/- 0.90 mg propofol/kg from the novel microemulsion formulation of propofol and 7.07 +/- 1.55 mg propofol/kg from Rapinovet to achieve anesthesia adequate to allow orotracheal intubation (P > 0.05). Areas under the dose-normalized propofol concentration by time curves (AUC(0-LOQ)) and maximum propofol concentrations (C(max)) were equal for the novel microemulsion formulation of propofol and Rapinovet (P > 0.05). Effects of anesthesia induction doses on cardiorespiratory values were comparable between treatments, and consistent with known effects of propofol anesthesia. Results provide evidence that the novel microemulsion formulation of propofol and Rapinovet macroemulsion produced comparable pharmacodynamic, physiological, and pharmacokinetic responses in cats. The unique composition of the microemulsion formulation, and the presence of an antimicrobial preservative minimize the potential for bacterial contamination and prolong shelf life.

Mask induction of anaesthesia with isoflurane or sevoflurane in premedicated cats.

A comparison was made of the time to and quality of induction of anaesthesia when sevoflurane (n=14) or isoflurane (n=14) was delivered by mask in premedicated healthy adult cats presented for elective surgery. Times to induction and intubation were significantly shorter with sevoflurane (210 +/- 57 seconds and 236 +/- 60 seconds, respectively) than with isoflurane (264 +/- 75 seconds and 292 +/- 73 seconds). The quality of induction was similar for both agents. Two cats in each group developed opisthotonus of less than 45 seconds' duration. Both sevoflurane and isoflurane produced mask induction of anaesthesia of a similar quality in this species. Sevoflurane provided more rapid induction of anaesthesia and establishment of a controlled airway than isoflurane.

The effects of a hemoglobin-based oxygen carrier (HBOC-301) on left ventricular systolic function in anesthetized dogs.

OBJECTIVE: To evaluate the effects of a hemoglobin-based oxygen carrier (HBOC-301) on left ventricular preload, afterload, contractility, and ventriculo-arterial coupling in anesthetized dogs. STUDY DESIGN: A prospective experimental study. ANIMALS: Seven adult male dogs weighing 2.3 to 2.7 kg. METHODS: The study was performed on intact, closed-chest, chloralose-anesthetized dogs. Heart rate, left ventricular end-systolic and end-diastolic volume and pressure, cardiac output, stroke volume, blood resistivity, mean arterial pressure (MAP), dP/dtmax, end-systolic elastance (Ees), systemic vascular resistance (SVR), effective arterial elastance (Ea), left ventricular-arterial coupling (Ees/Ea), and myocardial oxygen consumption (MVO2) were determined during a 90-minute infusion of 30 mL/kg (20 mL/kg/h) of HBOC-301 and for 90 minutes thereafter. RESULTS: The administration of HBOC-301 significantly decreased packed cell volume, blood resistivity, heart rate, cardiac output, and dP/dtmax and significantly increased left ventricular end-diastolic and end-systolic pressure, MAP, and SVR. The Ea, Ees, Ees/Ea and MVO2 did not change. CONCLUSIONS: HBOC-301 produced insignificant changes in load independent indexes of cardiac performance (Ees, E, Ees/Ea) in anesthetized dogs. The collective directional changes in these variables, however, in conjunction with significant increases in SVR were most likely responsible for a decrease in cardiac output. Increases in SVR and the volume load (30 mL/kg) contributed to increases in left ventricular end-diastolic pressure. CLINICAL RELEVANCE: HBOC-301 infusion should be monitored and administered cautiously to dogs with poor ventricular function.

Comparison of four drug combinations for total intravenous anesthesia of horses undergoing surgical removal of an abdominal testis.

OBJECTIVE: To evaluate anesthetic effects of 4 drug combinations used for total intravenous anesthesia of horses undergoing surgical removal of an abdominal testis. DESIGN: Clinical trial. ANIMALS: 32 healthy cryptorchid horses. PROCEDURE: Horses were sedated with xylazine and butorphanol and were randomly assigned to 1 of 4 groups: induction of anesthesia with ketamine and diazepam and maintenance with bolus administration of ketamine and xylazine (KD/KX); induction and maintenance of anesthesia with bolus administration of tiletamine-zolazepam, ketamine, and detomidine (TKD); induction and maintenance of anesthesia with continuous infusion of xylazine, guaifenesin, and ketamine; and induction and maintenance of anesthesia with continuous infusion of guaifenesin and thiopental. Horses that moved 3 consecutive times in response to surgical stimulation or for which surgery time was > 60 minutes were administered an inhalant anesthetic, and data from these horses were excluded from analysis. RESULTS: Quality of induction was not significantly different among groups. Muscle relaxation and analgesia scores were lowest for horses given KD/KX, but significant differences among groups were not detected. Horses anesthetized with TKD had a significantly greater number of attempts to stand, compared with the other groups, and mean quality of recovery from anesthesia for horses in the TKD group was significantly worse than for the other groups. Anesthesia, surgery, and recovery times were not significantly different among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that all 4 drug combinations can be used to induce short-term anesthesia for abdominal cryptorchidectomy in horses. However, horses receiving TKD had a poorer recovery from anesthesia, often requiring assistance to stand.

Effect of platelet-activating factor antagonist L-691,880 on low-flow ischemia-reperfusion injury of the large colon in horses.

OBJECTIVE: To determine the effect of platelet-activating factor (PAF) antagonist L-691,880 on low-flow ischemia and reperfusion (I-R) of the large colon in horses. ANIMALS: 12 adult horses. EXPERIMENTAL DESIGN: Horses were anesthetized, and the large colon was exteriorized through a ventral median celiotomy and instrumented. Colonic arterial blood flow was reduced to 20% of baseline (BL) and maintained for 3 hours; flow was then restored, and the colon was reperfused for 3 hours. One of two solutions was administered intravenously 30 minutes before reperfusion: group 1, 10 mL/kg 0.9% NaCl; and group 2, 5 mg/kg PAF antagonist L-691,880 in 0.9% NaCl. Hemodynamic variables were monitored and recorded at 30-minute intervals. Systemic arterial and colonic venous blood were collected for measurement of blood gas tensions, oximetry analyses, packed cell volume, and total plasma protein concentrations. Colonic venous blood was collected for determination of lactate, 6-keto prostaglandin F1 alpha (6-kPG), prostaglandin E2 (PGE2), and thromboxane B2 (TXB2) concentrations. Full-thickness biopsy specimens were harvested from the left ventral colon for histological evaluation. RESULTS: There were no significant differences between the two groups for any hemodynamic or metabolic variables. Colonic venous pH decreased, and carbon dioxide tension and lactate concentration increased during ischemia but returned to BL values during reperfusion. Colonic venous 6-kPG concentration was significantly increased above BL value at 2 hours and remained increased through 6 hours in horses of both groups. Colonic venous PGE2 concentration was significantly greater in group 2 compared with group 1 throughout the study. Colonic venous PGE2 concentration was increased above BL value from 3 to 6 hours in horses of both groups. Colonic venous TXB2 concentration was not different between groups but was significantly increased above the BL value for the first hour of reperfusion. Low-flow I-R of the large colon caused significant mucosal necrosis, hemorrhage, edema, and neutrophil infiltration; however, there were no differences in histological variables between vehicle-control and PAF antagonist-treated horses. CONCLUSION: No protective effects of PAF antagonist L-691,880 were observed on colonic mucosa associated with low-flow I-R. Additionally, deleterious drug-induced effects on hemodynamic and metabolic variables and colonic mucosal injury were not observed.

Cell trafficking, mediator release, and articular metabolism in acute inflammation of innervated or denervated isolated equine joints.

OBJECTIVES: To describe the acute cellular response, inflammatory mediator release, and effect on chondrocyte metabolism of interleukin 1 beta (IL-1 beta) in isolated innervated or denervated equine metacarpophalangeal joints. ANIMALS: One metacarpophalangeal joint of 24 adult horses. PROCEDURES: The metacarpophalangeal joint was isolated for 6 hours in a pump-perfused, auto-oxygenated, innervated or denervated metacarpophalangeal joint preparation. Isolated joints were assigned to 4 groups: control, control-denervated, inflamed, and inflamed-denervated, and inflammation was induced by intra-articular injection of IL-1 beta. Synovial fluid was collected for cytologic examination and determination of IL (IL)-1 beta, (IL-6), prostaglandin E2 (PGE2), and substance P (SP) values. Synovial membrane was immunostained with SP and nerve-specific enolase (NSE) antibodies. Cartilage was collected for determination of proteoglycan (PG) synthesis and degradation. RESULTS: IL-1 beta induced significant neutrophilic leukocytosis in synovial and synovial membrane. IL-1 beta concentration and returned to baseline by 5.5 hours, but IL-6 concentration significantly increased throughout the study. Total SP content was significantly higher in inflamed joints. There was a significant increase in 24- and 48-hour PG degradation in inflamed innervated joints. CONCLUSION: Cellular response to IL-1 beta was rapid and sustained; joint clearance of IL-1 beta was rapid, and endogenous production of IL-1 beta did not follow. The IL-6 and PGE2 concentrations significantly increased, and SP content was increased in association with inflammation but not denervation. A degradative response of cartilage of IL-1 beta was observed, and was enhanced by innervation. This model was useful for investigation of the articular response to acute inflammation and the influence of denervation in modulating this response.

Effect of high-molecular weight dextran macromolecules on low-flow ischemia and reperfusion of the large colon in horses.

OBJECTIVE: To evaluate the effect of high-molecular weight (MW) dextran macromolecules on low-flow ischemia and reperfusion of the large colon in horses. DESIGN: Horses subjected to low-flow ischemia and reperfusion of the large colon were treated with either 0.9 NaCl (group 1, n = 6) or high-MW dextran (group 2, n = 6) solutions. ANIMALS: 12 adults horses. PROCEDURE: Horses were subjected to 3 hours' low-flow ischemia followed by 3 hours' reperfusion. A dose of either 0.9% NaCl or a 6% solution of high-MW (250,000) dextran (10 ml/kg of body weight) was administered i.v., 30 minutes prior to reperfusion. Hemodynamic variables were recorded at 30-minute intervals. Systemic arterial and colonic venous blood were collected for determination of PCV, plasma total protein, and whole blood lactate concentrations, and for blood gas and oximetry analyses. Histologic examination of large-colon biopsy specimens was performed. RESULTS: Mean arterial pressure was greater in group-2 horses, compared with group-1 horses, from 3 to 3.25 hours, but there were no significant differences between groups for any of the other hemodynamic variables. Compared with baseline values, colonic blood flow was significantly lower from 0.5 to 3 hours and was significantly greater from 3.25 to 6 hours. Arterial and colonic venous PCV were significantly lower than baseline values from 3 to 3.25 hours, and at 3 hours, respectively, in group-2 horses. These values were significantly lower in group-2 horses, from 3 to 6 and 3 to 5 hours, respectively. There was significant mucosal necrosis, hemorrhage, edema, and neutrophil infiltration in horses of both groups; however, there were no significant differences between the 2 groups. CONCLUSIONS: High-MW dextran did not protect the colonic mucosa from low-flow ischemia and reperfusion; there were no deleterious effects on colonic mucosa or on systemic hemodynamic or metabolic variables. CLINICAL RELEVANCE: Reperfusion with high-MW dextran solution probably would not protect the large colon from ischemia-reperfusion injury associated with large-colon volvulus.

[Sedation and anesthesia in dogs and cats with cardiovascular diseases. III. Ventilation, respiratory monitoring, treatment for postoperative pain]. / Sedation und Narkose bei Hund und Katze mit Herzkreislaufkrankheit. III. Teil: Ventilation, Uberwaching der Atmung, postoperative Schmerzbehandlung.

The purpose of this study was to review ventilation and postoperative analgesic technics in 137 dogs and 13 cats with congenital or acquired heart disease. The animals were referred to the Department of Veterinary Clinical Sciences at The Ohio State University, U.S.A, for the following surgical interventions: correction of patent ductus arteriosus (PDA-ligation, 28%), cardiac catheterization with angiogram and angioplasty (22%), pacemaker implantation (18%), exploratory lateral thoracotomy (8.7%), correction of right aortic arch ring anomaly (3.3%), correction of subvalvular aortic stenosis (2.7%), correction of PDA with coil in patients with mitral regurgitation and congestive heart failure (2%), pericardectomy and removal of heart base tumor (2%), and palliative surgery for ventricular septal defect (VSD, 0.7%). Controlled ventilation was used in all animals during thoracotomy. Anesthesia was maintained over 2.3 +/- 1.3 hours by using either isoflurane, halothane, propofol, or diazepam-ketamine in 64%, 32%, 2%, and 0.7% of animals, respectively. Postoperative analgesia was necessary in 20% of animals and was provided by using different technics over several hours. The technics and respective percentages of animals in which they were used, were: intravenous buprenorphine (3.3%), intercostal nerve blocks (8.7%), epidural morphine (4%), and interpleural regional analgesia (4%).

The effects of medetomidine on cardiac contractility in autonomically blocked dogs.

The effects of medetomidine on load-dependent and relatively load-independent indices of left ventricular contractility and hemodynamics were studied in 8 chloralose-anesthetized, autonomic-blocked dogs. Left ventricular contractility was assessed by the maximum rate of increase in pressure (dP/dtmax), the slope of the end-systolic pressure volume relationship (Ees), preload recruitable stroke work (PRSW), and dP/dtmax-end-diastolic volume relation (SdPV). Dogs received 5 or 10 micrograms/kg of medetomidine IV. The dP/dtmax decreased significantly 30 minutes after both doses of medetomidine. The Ees did not change. Both SdPV and PRSW increased 5 minutes after both doses of medetomidine. Mean arterial pressure, left-ventricular end-diastolic and end-systolic pressures, peripheral vascular resistance and effective arterial elastance increased 5 minutes after both doses of medetomidine. Stroke volume, cardiac output, and stroke work decreased 5 minutes after medetomidine administration. End-diastolic volume did not change. End-systolic volume increased but the difference was not significant. Our study suggests that medetomidine increases inotropy and vascular resistance in autonomic-blocked dogs and that both ventricular and vascular responses to pharmacological manipulation must be considered for a complete assessment of the inotropic effects of a drug.

Mural blood flow distribution in the large colon of horses during low-flow ischemia and reperfusion.

Six horses were subjected to 3 hours of low-flow ischemia and 3 hours of reperfusion of the large colon. After induction of anesthesia, the large colon was exteriorized through a ventral midline celiotomy. Colonic blood flow was measured continuously, using Doppler ultrasonic flow probes placed on the colonic arteries supplying the dorsal and ventral colons and was allowed to stabilize for 15 to 30 minutes after instrumentation. Low-flow ischemia was induced by reducing colonic arterial blood flow to 20% of baseline (BL) flow. Colonic mucosal, seromuscular, and full-thickness blood flow were determined on a tissue-weight basis by injecting colored microspheres proximally into the colonic artery supplying the ventral colon. Reference blood samples were obtained at a known flow rate from the colonic artery and vein at a site more distal to the site of injection. Left ventral colon biopsy specimens were harvested at BL, 3 hours of ischemia, and 15 minutes of reperfusion. Blood and tissue samples were digested and filtered to collect the microspheres, and dimethylformamide was added to release the colored dyes. Dye concentration in blood and tissue samples was measured by use of spectrophotometry, and tissue-blood flow was calculated. Data were analyzed, using two-way ANOVA for repeated measures; statistical significance was set at P < 0.05. Doppler blood flow decreased to approximately 20% of BL, whereas microsphere blood flow ranged between 13.7 and 15.5% of BL at 3 hours of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood gas values during intermittent positive pressure ventilation and spontaneous ventilation in 160 anesthetized horses positioned in lateral or dorsal recumbency.

One hundred sixty horses were anesthetized with xylazine, guaifenesin, thiamylal, and halothane for elective soft tissue and orthopedic procedures. Horses were randomly assigned to one of four groups. Group 1 (n = 40): Horses positioned in lateral (LRG1; n = 20) or dorsal (DRG1; n = 20) recumbency breathed spontaneously throughout anesthesia. Group 2 (n = 40): Intermittent positive pressure ventilation (IPPV) was instituted throughout anesthesia in horses positioned in lateral (LRG2; n = 20) or dorsal (DRG2; n = 20) recumbency. Group 3 (n = 40): Horses positioned in lateral (LRG3; n = 20) or dorsal (DRG3; n = 20) recumbency breathed spontaneously for the first half of anesthesia and intermittent positive pressure ventilation was instituted for the second half of anesthesia. Group 4 (n = 40): Intermittent positive pressure ventilation was instituted for the first half of anesthesia in horses positioned in lateral (LRG4; n = 20) or dorsal (DRG4; n = 20) recumbency. Spontaneous ventilation (SV) occured for the second half of anesthesia. The mean time of anesthesia was not significantly different within or between groups. The mean time of SV and IPPV was not significantly different in groups 3 and 4. Variables analyzed included pH, PaCO2, PaO2, and P(A-a)O2 (calculated). Spontaneous ventilation resulted in significantly higher PaCO2 and P(A-a)O2 values and significantly lower PaO2 values in LRG1 and DRG1 horses compared with LRG2 and DRG2 horses. Intermittent positive pressure ventilation resulted in normocarbia and significantly lower P(A-a)O2 values in LRG2 and DRG2 horses. In LRG2 the PaO2 values significantly increased from 20 minutes after induction to the end of anesthesia. The PaO2 and P(A-a)O2 values were not significantly different from the beginning of anesthesia after IPPV in DRG2 or DRG3. The PaO2 values significantly decreased and the P(A-a)O2 values significantly increased after return to SV in horses in LRG4 and DRG4. The PaO2 values were lowest and the P(A-a)O2 values were highest in all horses positioned in dorsal recumbency compared with lateral recumbency and in SV horses compared with IPPV horses. The pH changes paralleled the changes in PaCO2. Blood gas values during right versus left lateral recumbency in all groups were also evaluated. The PaO2 values were significantly lower and the P(A-a)O2 values were significantly higher during SV in horses positioned in left lateral (LRLG1) compared with right lateral (LRRG1) recumbency.(ABSTRACT TRUNCATED AT 400 WORDS)

Systemic and colonic venous plasma eicosanoid and endotoxin concentrations, and colonic venous serum tumor necrosis factor and interleukin-6 activities in horses during low-flow ischemia and reperfusion of the large colon.

Twenty-four horses were randomly allocated to 3 groups. Horses were anesthetized, subjected to a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls. Group-2 horses were subjected to 6 hours of low-flow colonic arterial ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline (BL) samples were collected, then low-flow ischemia was induced by reducing ventral colonic arterial blood flow to 20% of BL. All horses were monitored for 6 hours after BL data were collected. Blood samples were collected from the colonic vein and main pulmonary artery (systemic venous [SV]) for measurement of plasma endotoxin, 6-keto prostaglandin F1 alpha (6-kPG), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2) concentrations. Tumor necrosis factor and interleukin-6 activities were measured in colonic venous (CV) serum samples. Data were analyzed, using two-way ANOVA, and post-hoc comparisons were made, using Dunnett's and Tukey's tests. Statistical significance was set at P < 0.05. Endotoxin was not detected in CV or SV plasma at any time. There was no detectable tumor necrosis factor or interleukin-6 activity in CV samples at any time. There were no differences at BL among groups for CV or SV 6-kPG, PGE2, or TXB2 concentrations, nor were there any changes across time in group-1 horses.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dimethyl sulfoxide, allopurinol, 21-aminosteroid U-74389G, and manganese chloride on low-flow ischemia and reperfusion of the large colon in horses.

Thirty horses were randomly assigned to 1 of 5 groups. All horses were anesthetized and subjected to ventral midline celiotomy, then the large colon was exteriorized and instrumented. Colonic arterial blood flow was reduced to 20% of baseline (BL) and was maintained for 3 hours. Colonic blood flow was then restored, and the colon was reperfused for an additional 3 hours. One of 5 drug solutions was administered via the jugular vein 30 minutes prior to colonic reperfusion: group 1, 0.9% NaCl; group 2, dimethyl sulfoxide: 1 g/kg of body weight; group 3, allopurinol: 25 mg/kg; group 4, 21-aminosteroid U-74389G: 10 mg/kg; and group 5, manganese chloride (MnCl2): 10 mg/kg. Hemodynamic variables were monitored and recorded at 30-minutes intervals. Systemic arterial, systemic venous (SV), and colonic venous (CV) blood samples were collected for measurement of blood gas tensions, oximetry, lactate concentration, PCV, and plasma total protein concentration. The eicosanoids, 6-keto prostaglandin F1 alpha, prostaglandin E2, and thromboxane B2, were measured in CV blood, and endotoxin was measured in CV and SV blood. Full-thickness biopsy specimens were harvested from the left ventral colon for histologic evaluation and determination of wet weight-to-dry weight ratios (WW:DW). Data were analyzed, using two-way ANOVA for repeated measures, and statistical significance was set at P < 0.05. Heart rate, mean arterial pressure, and cardiac output increased with MnCl2 infusion; heart rate and cardiac output remained increased throughout the study, but mean arterial pressure returned to BL values within 30 minutes after completion of MnCl2 infusion. Other drug-induced changes were not significant. There were significant increases in mean pulmonary artery and mean right atrial pressures at 2 and 2.5 hours in horses of all groups, but other changes across time or differences among groups were not observed. Mean pulmonary artery pressure remained increased through 6 hours in all groups, but mean right atrial pressure had returned to BL values at 3 hours. Mean colonic arterial pressure was significantly decreased at 30 minutes of ischemia and remained decreased through 6 hours; however, by 3.25 hours it was significantly higher than the value at 3 hours of ischemia. Colonic arterial resistance decreased during ischemia and remained decreased throughout reperfusion in all groups; there were no differences among groups for colonic arterial resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

[Sedation and anesthesia in dogs and cats with cardiovascular diseases. I. Anesthesia plan considering risk assessment, hemodynamic effects of drugs and monitoring]. / Sedation und Narkose bei Hund und Katze mit Herzkreislaufkrankheit. I. Teil: Narkoseplanung nach Risikobeurteilung, hämodynamische Wirkung der Pharmaka, Monitoring.

The purpose of this study was to review the effects of sedatives and anesthetics in 137 dogs and 13 cats with congenital or acquired heart disease which were referred for diagnostic, therapeutic, and surgical interventions: correction of patent ductus arteriosus (PDA-ligation, 28%), cardiac catheterization with angiogram and angioplasty (22%), pacemaker implantation (18%), exploratory lateral thoracotomy (8.7%), correction of right aortic arch (ring anomaly, 3.3%), correction of subvalvular aortic stenosis (2.7%), correction of PDA with coil in patients with mitral regurgitation and congestive heart failure (2%), pericardectomy and removal of heart-base tumors (2%), palliative surgery for ventricular septal defect (VSD, 0.7%), and sick patients with deleterious cardiac arrhythmias (0.7%). The anesthetic plan considered the risks of anesthesia based upon preoperative patient assessment, classification scheme for functional phases of heart failure, and anesthetic drug effects of the cardiovascular system. The effects of sedatives and anesthetic drugs on determinants of cardiac output are described. The most commonly used drugs for premedication, induction, and maintenance of anesthesia were midazolam-oxymorphone (20%), thiopental or etomidate (30%), and isoflurane (64%). Prompt therapy was given to control arrhythmias and provide organ perfusion, pain relief, muscle relaxation and renal diuresis, using lidocaine, dopamine, fentanyl, atracurium, and furosemide in 17.3% 14.7%, 12%, 10%, and 8.7% of animals, respectively. Methods of routine and advanced patient monitoring are described.

[Sedation and anesthesia in dogs and cats with cardiovascular disease. II. Anesthesia planning with respect to pathophysiology, heart arrhythmia]. / Sedation und Narkose bei Hund und Katze mit herzkreislaufkrankheit. II. Teil: Narkoseplanung an Hand der Pathophysiologie, Herzarrhythmien.

The purpose of this study was to review the incidence of cardiac arrhythmias in 137 anesthetized dogs and 13 anesthetized cats with congenital or acquired heart disease that were referred for correction of following procedures: patent ductus arteriosus (PDA-ligation, 28%), cardiac catheterization with angiogram and angioplasty (22%), pacemaker implantation (18%), exploratory lateral thoracotomy (8.7%), correction of right aortic arch (ring anomaly, 3.3%), correction of subvalvular aortic stenosis (2.7%), correction of PDA with coil in patients with mitral regurgitation and congestive heart failure (2%), pericardectomy and removal of heart base tumor (2%), and palliative surgery for ventricular septal defect (VSD, 0.7%). The anesthetic plan considered the risks of anesthesia based upon the pathophysiology of cardiac lesions and the anesthetic drug effects on the cardiovascular system. Recommendations are made for dogs with decreased cardiac contractility, cardiac disease with volume overload, cardiac disease with pressure overload, and pericardial tamponade. The percentages of animals and their associated cardiac arrhythmias after premedication and during and after anesthesia were: sinus bradycardia (15.3%), sinus tachycardia (3.3%), atrial flutter (0.7%), atrial fibrillation (0.7%), premature ventricular contraction (14%), and ventricular tachycardia (1.3%). Prompt therapy was given to a percentage of animals in order to control arrhythmia and support cardiovascular system, by using atropine or glycopyrrolate (14%), lidocaine (17.3%), and dopamine (14.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Emergency analgesia and chemical restraint in the horse.

Clinical examination of the equine patient with acute abdominal pain should identify the affected body system and yield a provisional diagnosis. Determination of signalment, history, physical examination, and basic laboratory tests should assist in classification of the gastrointestinal disorder and direct the therapeutic plan. Determination of the definitive diagnosis of abdominal pain based on clinical examination is not crucial. For a successful outcome, efforts should be directed toward early recognition of the need for surgery and treatment of cardiovascular compromise in horses with severe gastrointestinal disease.

Histopathologic evidence of reperfusion injury in the large colon of horses after low-flow ischemia.

Effects of low-flow ischemia and reperfusion of the large colon on mucosal architecture were determined in horses. Twenty-four adult horses were randomly allocated to 3 groups: sham-operated (n = 6), 6 hours of ischemia (n = 9), and 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline values. Systemic hemodynamic and metabolic variables were maintained constant and in a normal physiologic range. Full-thickness biopsy specimens were obtained from the left ventral colon for histomorphologic and morphometric examination at baseline and at 30-minute intervals for 6 hours; additional biopsy specimens were collected at 185, 190, and 195 minutes (corresponding to 5-, 10-, and 15-minute periods of reperfusion in group-3 horses). There were no differences among groups at baseline or across time in group-1 horses for any of the histopathologic variables. There were significant (P < 0.05) increases in percentage of surface mucosal disruption, estimated and measured percentage depth of mucosal loss, mucosal hemorrhage, mucosal edema, and cellular debris index during 0 hour to 3 hours, compared with baseline, and from 3 hours to 6 hours, compared with 3 hours in horses of groups 2 and 3. Estimated percentage depth of mucosal loss and cellular debris index were significantly (P < 0.05) greater in group-3 horses, compared with group-2 horses during the interval from 3 to 6 hours. There were trends toward greater percentage of surface mucosal disruption and mucosal edema during the early phase of reperfusion (3 to 4 hours) and greater mucosal hemorrhage, measured percentage depth of mucosal loss, and mucosal interstitial-to-crypt ratio during the late phase (4 to 6 hours) of reperfusion in group-3 horses vs group-2 horses. Reestablishment of colonic arterial blood flow after low-flow ischemia caused greater mucosal injury than did a comparable period of continued ischemia. Thus, reperfusion injury was detected in the large colon of horses after low-flow arterial ischemia. The serial mucosal alterations that developed in the colon were comparable in horses of groups 2 and 3; however, reperfusion exacerbated colonic mucosal injury.

Neutrophil accumulation in the large colon of horses during low-flow ischemia and reperfusion.

Histomorphologic/morphometric evaluation, leukocyte scintigraphy, and myeloperoxidase activity were used to determine whether neutrophils accumulate in the large colon of horses during low-flow ischemia and reperfusion. Twenty-four adult horses were assigned to 1 of 3 groups: group 1, sham-operated (n = 6); group 2, 6 hours of ischemia (n = 9); and group 3, 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia of the large colon was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline. Radiolabeled (99mTc) autogenous neutrophils were injected at 175 minutes, which corresponded to 5 minutes prior to reperfusion in group-3 horses. Full-thickness biopsy specimens of the left ventral colon were collected at baseline and at 30-minute intervals for 6 hours; a portion of the biopsy specimen was placed in formalin for histologic examination, and the remainder was used to measure mucosal radioactivity and myeloperoxidase activity. There were no differences in baseline mucosal neutrophil index, mucosal neutrophil numbers, submucosal venular neutrophil numbers, mucosal radioactivity, or mucosal myeloperoxidase activity among groups, or over time in group-1 horses. Neutrophils accumulated in the colonic mucosa during ischemia and further increased at reperfusion, as indicated by neutrophil index (morphology) and mucosal neutrophil numbers (morphometry); mucosal neutrophil index was significantly (P < 0.05) greater in group-3 horses during reperfusion than at the corresponding periods of ischemia in group-2 horses. Neutrophil numbers were significantly (P < 0.05) increased in submucosal venules at 10 minutes of reperfusion in group-3 horses and were significantly (P < 0.05) greater in group-3 than in group-2 horses during the interval from 3 to 6 hours. Mucosal radioactivity significantly (P < 0.05) increased at reperfusion in group-3 horses; there was a trend (P = 0.076) toward greater mucosal radioactivity in group-3, compared with group-2 horses, throughout the 3- to 6-hour interval. There were no differences in mucosal myeloperoxidase activity among or within any of the 3 groups over time. Neutrophils accumulated in the large colon of horses during low-flow ischemia and reperfusion. Neutrophil infiltration was detected by histologic examination and leukocyte scintigraphy, but not by measurement of myeloperoxidase activity. The accumulation of neutrophils during ischemia and the further neutrophil infiltration during reperfusion indicate that neutrophils may contribute to reperfusion injury of the large colon.

Effects of halothane, enflurane, and isoflurane on supraventricular and ventricular rate in dogs with complete atrioventricular block.

Complete atrioventricular (AV) block was produced in 32 chloralose-anesthetized autonomically intact dogs to determine the effects of halothane, enflurane, and isoflurane on supraventricular and ventricular rate. Halothane (n = 17), enflurane (n = 6), and isoflurane (n = 9) were administered in three separate experiments in sequential minimum alveolar concentration (MAC) multiples of 0.5, 1.0, 1.5, 2.0, 1.5, and 1.0. Supraventricular rate, ventricular rate, and mean arterial blood pressure (MAP) were measured and recorded at baseline and after a 20-minute equilibration period of each inhalation anesthetic at each MAC multiple. Increasing concentrations of enflurane and isoflurane significantly decreased supraventricular rate (P < .05). Ventricular rate was not significantly changed by sequential MAC multiples of halothane, enflurane, and isoflurane. Increasing concentrations of halothane, enflurane, and isoflurane significantly decreased MAP with enflurane producing the most significant decrease (P < .05). Ventricular arrhythmias occurred in 5 of 17 dogs anesthetized with halothane and 1 of 9 dogs anesthetized with isoflurane. Inhalation anesthesia can significantly decrease supraventricular rate and MAP, does not alter ventricular rate, and can produce ventricular arrhythmias in dogs with complete AV block.

A review of laboratory animal anesthesia with chloral hydrate and chloralose.

Chloral hydrate (CH) and alpha-chloralose (CS) are often used to anesthetize laboratory animals although, to our knowledge, there have been no controlled studies of their anesthetic or analgesic effects. Induction of and recovery from anesthesia can be stressful, and anesthesia and analgesic quality have been questioned. Intraperitoneal (i.p.) administration of CH has resulted in adynamic ileus and peritonitis in rats, gastric ulcers in rats, and peritonitis in swine. Light anesthesia is induced in rats. In dogs, CH induces sedation to deep anesthesia when given intravenously. Gastric irritation in dogs can occur when CH is given orally. Chloral hydrate is considered a good sedative-hypnotic for farm animals. Intravenously administered CS anesthetizes dogs and cats for 5 to 10 hours, but the animals may require respiratory support. Chloralose appears to be a satisfactory anesthetic for dogs when stage III thiobarbiturate anesthesia is first induced. It is difficult to gauge the depth of anesthesia and analgesia with CS. In our clinical experience with swine and calves, CH given i.p. leads to adynamic ileus. We have found that CS given i.p. causes an inflammatory response in guinea pigs, rats, and calves. We observed that CS analgesia varies with the type of surgical procedure performed. Based on a literature review and our clinical experience, we suggest that CH or CS anesthesia should be preceded by administration of barbiturates, opioids, alpha-2 agonists, or phenothiazine tranquilizers. Chloral hydrate should only be used as a sedative or hypnotic for dogs; CS should not be used as a sole anesthetic agent. Neither drug should be used i.p. for survival surgery.