Some metabolic and hormonal changes associated with general anaesthesia and surgery in the horse

Three different anaesthetic techniques were studied in normal, healthy Thoroughbred or Thoroughbred type horses. These were (a) acepromazine, thiopentone and suxamethonium; (b) acepromazine, glyceryl guaiacolate and a 'half-dose' of thiopentone; and (c) xylazine and ketamine. Anaesthesia was maintained with halothane vaporized in oxygen and nitrous oxide. All horses underwent either laryngeal or body surface surgery. Heart rate, packed cell volume, blood glucose and lactate, plasma non-esterified fatty acids, insulin and cortisol were measured before, during and after surgery. The greatest metabolic and hormonal changes occurred immediately after anaesthetic induction and were different in each group. The combination of acepromazine, glyceryl guaiacolate and a 'half-dose' of thiopentone was associated with the least change in the physiological and metabolic variables measured.     

Changes in factor VIII activity and von Willebrand factor antigen concentration with age in dogs.

The factor VIII activity of 38 German shepherd puppies, 6-12 weeks old, submitted for diagnosis of haemophilia A was measured. Eight of these puppies had values higher than would be expected for haemophiliacs, but less than the reference range for adult dogs. A further sequential study of 21 puppies (6-26 weeks of age) indicated that the factor VIII activity of puppies is generally less than that of adult dogs until about 14 weeks of age. Changes in the concentration of von Willebrand factor antigen in the puppies were irregular. These variations are probably not sufficient to interfere with accurate diagnosis of haemophilia A in most affected young dogs, but may interfere with the detection of heterozygotes in young bitches.     

Effect of desmopressin on plasma factor VIII and von Willebrand factor concentrations in Greyhounds

Objective To determine the effect of 1-Deamino-8-D-argi-nine vasopressin on plasma concentrations of von Willebrand factor and factor VIII in Greyhound blood donors, and to compare the response of 1-Deamino-8-D-arginine vaso-pressin injection on plasma concentrations of von Willebrand factor between groups with different resting plasma concentrations of von Willebrand factor.
Animals Fifteen Greyhound blood donors were used. Dogs were grouped into three categories depending on their von Willebrand factor concentrations.
Procedure Desmopressin was administered subcuta-neously at 1 mg/kg to all dogs. Plasma von Willebrand factor and factor VIII concentrations were measured before and 10, 20, 30, 45, 60, 90 and 120 min after desmopressin injection.
Results The von Willebrand factor and factor VIII concentrations in all dogs increased significantly and remained higher than base-line throughout the 2 h period.
Conclusion Desmopressin is useful in increasing von Willebrand factor concentrations in Greyhound blood donors, including those with low resting concentrations.     

Stability of canine factor VIII activity and von Willebrand factor antigen concentration in vitro

The in vitro stability of canine factor VIII activity, von Willebrand factor antigen concentration and the ratio of these two factors was studied. Samples were stored for up to 48 hours, either as plasma or as whole blood, at 4 degrees, 20 degrees and 37 degrees C. Factor VIII activity was generally stable in both plasma and whole blood samples for up to 48 hours at 4 degrees or 20 degrees C. The concentration of von Willebrand factor antigen was more stable in samples stored as plasma than whole blood, and for a shorter time than factor VIII activity. Consequently, the stability of the ratio of these two factors was relatively poor in vitro.     

Plasma von Willebrand factor concentration and thyroid function in dogs

Plasma von Willebrand factor antigen concentration was determined in 15 dogs with suspected hypothyroidism, in 1 dog with hyperthyroidism, and in 14 euthyroid dogs. The mean +/- SEM von Willebrand factor:antigen concentration in hypothyroid dogs (47.1% +/- 12.6%) was significantly decreased (P less than 0.0005), compared with that in euthyroid dogs (94.7 +/- 5.6%). Four hypothyroid dogs were given thyroxine for 1 month and all 4 had an increase in von Willebrand factor:antigen concentration. The plasma von Willebrand factor:antigen concentration was 200% in the hyperthyroid dog. Seemingly, reduced concentrations of plasma von Willebrand factor:antigen can be found in dogs in association with congenital von Willebrand disease or with von Willebrand disease acquired through hypothyroidism.     

DDAVP-induced increases in coagulation factor VIII and von Willebrand factor in the plasma of conscious dogs

Infusion of the vasopressin analogue DDAVP into five normal dogs at doses of 0.1-2.0 micrograms DDAVP per kg body weight induced dose-dependent increases in the plasma content of coagulation factor VIII and von Willebrand factor. Plasma concentrations of von Willebrand factor (determined antigenically as factor VIII-related antigen and functionally as coagglutinin cofactor activity) and coagulation factor VIII were measured immediately before and at 10, 30, and 120 min after 10-min intravenous infusions of DDAVP. The greatest increases in coagulation factor VIII were produced with the 2.0 micrograms/kg dose. Ten minutes after infusion the mean increase in coagulation factor VIII was 32 units/dl (concentrations of all indices were reported relative to concentrations in a standard canine plasma pool, arbitrarily assigned a concentration of 100 units/dl) and this increase did not change significantly throughout the duration of the experiment. At 10 min post-infusion, the mean factor VIII-related antigen concentration increased 81 units/dl (dose = 2.0 micrograms/kg) and did not change significantly for the duration of the experiment. The maximum mean increase in coagglutinin cofactor activity, 141 units/dl, occurred 10 min after infusion (dose = 1.0 microgram/kg). Coagglutinin cofactor activity decreased significantly from peak activity by 120 min post-infusion.     

Failure of sodium pentobarbital anesthesia to alter 1-desamino-8-D-arginine vasopressin-induced elevations of plasma factor VIII/ von Willebrand factor in normal dogs.

The vasopressin analog 1-desamino-8-D-arginine stimulates elevations in plasma Factor VIII/ von Willebrand factor in normal dogs. In order to study the effects of general anesthesia on this response, six dogs were anesthetized with sodium pentobarbital or given an equivalent amount of saline then challenged with an intravenous dose of 1-desamino-8-D-arginine (0.6 micrograms/kg body weight). Factor VIII coagulant activity, von Willebrand factor antigen, and ristocetin cofactor activity were quantitated before anesthesia (or saline infusion), 20 min after induction (pre-1-desamino-8-D-arginine), and at 30 and 60 min post-1-desamino-8-D-arginine. Anesthesia did not significantly affect the elevations in plasma Factor VIII/ von Willebrand factor induced by 1-desamino-8-D-arginine. Sodium pentobarbital appeared however to prevent the rise in Factor VIII coagulant activity seen following saline treatment. The results of this study suggest that when 1-desamino-8-D-arginine is to be used in normal dogs to boost basal plasma von Willebrand factor levels, it is not necessary to administer it prior to induction of general anesthesia with sodium pentobarbital.     

Von Willebrand's disease in dogs in the United Kingdom

An assay for the measurement of von Willebrand factor antigen has been established. In a period of 18 months, 13 dogs have been identified as suffering from von Willebrand's disease. The affected animals had levels of von Willebrand factor antigen which ranged from undetectable to 43 per cent of normal. Factor VIII levels were also reduced. Haemorrhagic episodes were usually associated with trauma or surgery, and often required transfusion with fresh blood or plasma to arrest haemorrhage.     

von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers

OBJECTIVE: To define the relationship between clinical expression of a type-1 von Willebrand disease phenotype and genotype at 2 von Willebrand factor marker loci in Doberman Pinschers. ANIMALS: 102 client-owned Doberman Pinschers. PROCEDURES: Dogs were recruited on the basis of plasma von Willebrand factor concentration, clinical history, and pedigree. Blood samples and response to a history questionnaire were obtained for each dog. Plasma von Willebrand factor concentration was measured by use of an ELISA, and genotyping was performed via polymerase chain reaction for 1 intragenic and 1 extragenic von Willebrand factor marker. Amplification product size was determined by use of polyacrylamide gel electrophoresis (intragenic marker) or automated sequence analysis (extragenic marker). Western blots were prepared from a subset of dogs with low plasma von Willebrand factor concentration to evaluate multimer distribution. RESULTS: Strong associations were detected between plasma von Willebrand factor concentration and von Willebrand factor marker genotype. Twenty-five dogs had substantial reduction in plasma von Willebrand factor concentration and multiple hemorrhagic events. All were homozygous for a 157-base-pair intragenic marker allele and homozygous or compound heterozygous for 1 of 4 extragenic marker alleles. These marker genotypes were exclusively detected in dogs with low plasma von Willebrand factor concentration, although some dogs with these genotypes did not have abnormal bleeding. CONCLUSIONS AND CLINICAL RELEVANCE: Type-1 von Willebrand disease in Doberman Pinschers is associated with the von Willebrand factor gene locus; however, the expression pattern in this breed appears more complex than that of a simple recessive trait.     

Effects of thiopentone and propofol on lower oesophageal sphincter and barrier pressure in the dog

The effects of thiopentone and propofol on oesophageal pressures were examined in 39 bitches. The dogs were premedicated with either atropine (n = 13), acepromazine maleate (n = 13) or a combination of atropine and acepromazine. Anaesthesia was induced with either thiopentone (15 dogs) or propofol (24 dogs), both given intravenously. Immediately following the induction of anaesthesia, gastric pressure and lower oesophageal sphincter pressure (LOSP) were measured and oesophageal barrier pressure determined. There were no significant differences attributable to the premedication regimens used but both LOSP and barrier pressure were significantly lower in the dogs anaesthetised with propofol compared to the animals given thiopentone (LOSP 12-2 ± 4-2 cm H₂O propofol group versus 26-8 ± 6-5 cm H₂O thiopentone group).     

Heritability of plasma von Willebrand factor antigen concentration in German Wirehaired pointers

We applied quantitative genetic analyses to a population of German Wirehaired pointer dogs affected with type 2 von Willebrand disease. Plasma von Willebrand factor (vWF) protein concentration measured as vWF antigen (vWF:Ag), clinical history, and pedigree data were compiled for 331 dogs over a 5-year test period. Eight dogs had histories of abnormal bleeding and had markedly decreased plasma vWF:Ag concentrations (<1%). Four per cent of the dogs were inbred, with an average inbreeding of 2.52%. The estimated heritability of plasma vWF concentration was 0.52. We found a major gene effect on vWF concentration. Using a single gene locus model and two different prediction methods, the upper threshold value for the aa genotype was less than 1% vWF:Ag, and the optimal threshold value for discrimination between the AA and Aa genotypes was between 68% and 72% vWF:Ag. Our analyses indicate that phenotype, assigned on the basis of a single vWF:Ag determination, is heritable and can be applied for selective breeding in a von Willebrand disease test programme.     

Hemostatic response to surgical neutering via ovariectomy and ovariohysterectomy in dogs

Objective-To investigate the hemostatic response to surgery and compare the response for ovariohysterectomy with that for ovariectomy and to evaluate the usefulness of thromboelastography on plasma samples. Animals-42 female dogs. Procedures-Dogs were assigned to undergo ovariohysterectomy or ovariectomy. Blood samples were collected immediately before and 1, 6, and 24 hours after surgery and stored at -80°C for subsequent analysis. Plasma samples were subjected to thromboelastography after thawing. In addition, coagulation variables were measured, including concentrations of von Willebrand factor antigen, fibrinogen, antithrombin, and protein C; activity of factor VIII; activated partial thromboplastin time; prothrombin time; and thrombin time. The fibrinolytic response was assessed via concentrations of D-dimer, plasminogen, and α-2-antiplasmin (plasmin inhibitor). Results-Substantial hemostatic and fibrinolytic activation was evident after surgery in both groups, as characterized by significantly increased global clot strength and an overall hypercoagulable state at 4 hours after surgery in addition to decreases in von Willebrand factor antigen and factor VIII concentrations and shortened prothrombin and thrombin times. The dogs also typically had activation of the fibrinolytic system, as evidenced by increased postoperative concentrations of D-dimer, plasminogen, and plasmin inhibitor. Differences between the 2 groups could not be detected for any variables. Conclusions and Clinical Relevance-Elective surgery with limited tissue trauma induced hemostatic activation in dogs, which led to hypercoagulability after surgery. A difference between the ovariohysterectomy and ovariectomy groups was not detected. Thromboelastography can be used on plasma samples and may be useful for evaluating patterns over time.     

Effects of oxypolygelatin and dextran 70 on hemostatic variables in dogs

Objective To evaluate and compare coagulation variables following the administration of oxypolygelatin and dextran 70 to clinically healthy dogs. Study design Randomized cross‐over experimental study. Animals A total of eight healthy adult female Beagles aged 2–4 years old and weighing 11.8 ± 2.7 kg. Methods The dogs received a 15‐minute intravenous (IV) infusion of 5 mL kg^?1 oxypolygelatin or 10 mL kg^?1 6% dextran 70. Before (PRE) and at 2, 5, and 24 hours after administration, packed cell volume (PCV), total solids concentration (TS), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen concentration (FIB), platelet numbers (Plat), factor VIII coagulant activity (VIII:C), von Willebrand factor antigen concentration (vWf:Ag) and platelet function and buccal mucosal bleeding time (BMBT) were measured. Platelet function was assessed using aggregation and by measuring ATP release from aggregating platelets over 6 minutes, with 20, 10, and 5 µm ADP and 5 and 10 µg of collagen mL^?1 as platelet activation agonists. Results All baseline values were within our normal ranges, except for one dog that had low vWf:Ag PRE values prior to both dextran and oxypolygelatin administration. Following dextran and oxypolygelatin administration, the PCV and TP were significantly (p < 0.05) decreased. Plat, FIB, and vWf:Ag decreased, while BMBT and VIII:C increased following dextran administration. Dextran also caused a significant decrease in platelet aggregation in response to ADP. Oxypolygelatin caused a significant decrease in vWf:Ag, Plat, and FIB compared to PRE values. The total amount of ATP released, standardized to platelet number, did not vary significantly for either group at any sampling time from PRE values. No significant changes from PRE values were noted at any time in either group for PT or APTT. Conclusion At the doses administered, both dextran and oxypolygelatin can interfere with hemostatic variables in healthy dogs, but dextran's effect is more profound and prolonged when compared to oxypolygelatin. Clinical relevance Oxypolygelatin causes fewer hemostatic abnormalities when compared to dextran, making it a superior colloid for administration at the doses tested.     

Effect of desmopressin on von Willebrand factor multimers in Doberman Pinschers with type 1 von Willebrand disease

OBJECTIVE: To assess the effect of desmopressin (DDAVP) administration in Doberman Pinschers with type 1 von Willebrand disease (vWD) on plasma von Willebrand factor (vWF) multimers through determination of vWF collagen binding activity (vWF:CBA; a functional vWF assay dependent on the presence of high-molecular-weight [HMWI multimers), comparison of vWF antigen concentration (vWF:Ag) to vWF:CBA, and vWF multimer size distribution. ANIMALS: 16 Doberman Pinschers with type 1 vWD and 5 clinically normal control dogs. PROCEDURE: Plasma vWF:Ag and vWF:CBA assays and vWF multimer analysis were performed before and 1 hour after administration of DDAVP (1 microg/kg, SC). RESULTS: Following DDAVP administration, dogs with type 1 vWD had an increase in mean baseline values of plasma vWF:Ag and vWF:CBA from 10% to 17% for both variables. The mean vWF Ag:CBA ratio at baseline (0.95) was similar after DDAVP administration (0.97), indicating concordant increases in plasma vWF concentration and activity. In control dogs, mean plasma vWF:Ag and vWF:CBA increased from baseline values of 64% to 113% and 58% to 114%, respectively, and the vWF Ag:CBA ratios were unchanged (1.1 vs 1.0) after DDAVP administration. Plasma vWF multimer analysis revealed proportional increases in band intensity for all multimer sizes following DDAVP administration, in comparison to baseline for the control dogs and Doberman Pinschers with vWD, consistent with vWF Ag:CBA ratios of approximately 1. CONCLUSIONS AND CLINICAL RELEVANCE: Beneficial effects of DDAVP on primary hemostasis in Doberman Pinschers with type 1 vWD cannot be explained by preferential increases in HMW vWF multimers.     

Effect of Desmopressin Acetate on Bleeding Times and Plasma von Willebrand Factor in Doberman Pinscher Dogs with von Willebrand''s Disease

Effects of desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]) on plasma von Willebrand factor (vWf) were studied in 12 purebred Doberman pinschers confirmed to have von Willebrand's disease (vWd) (plasma vWf antigen [vWf:Ag] concentrations, less than 30 U/dl). Twelve dogs had subnormal plasma botrocetin cofactor (BCf) activity and 11 dogs had prolonged buccal mucosa bleeding times. Tranquilization of three dogs with lenperone and three dogs with xylazine did not induce significant changes in mean plasma vWf:Ag concentrations or mean BCf activities. Thirty and 120 minutes after administration of DDAVP (1 micrograms/kg subcutaneously), there was significant shortening of the mean buccal mucosa bleeding time. Ten dogs responded to DDAVP with increases in BCf activity which exceeded 10 U/dl at 30 or 120 minutes, or both, after the drug was administered. At the same time, increases in plasma vWf:Ag concentrations were smaller than the increases in BCf activity. It was shown by multimeric analysis that primarily the higher molecular weight forms of vWf increased in plasma in response to DDAVP.     

Effects of 6% hetastarch (600/0.75) or lactated Ringer's solution on hemostatic variables and clinical bleeding in healthy dogs anesthetized for orthopedic surgery

ObjectiveTo evaluate and compare hemostatic variables and clinical bleeding following the administration of 6% hetastarch (600/0.75) or lactated Ringer’s solution (LRS) to dogs anesthetized for orthopedic surgery.Study designRandomized blinded prospective study.AnimalsFourteen, healthy adult mixed-breed hound dogs of either sex, aged 11–13 months, and weighing 20.8 ± 1.2 kg.MethodsThe dogs were randomly assigned to receive a 10 mL kg^?1 intravenous (IV) bolus of either 6% hetastarch (600/0.75) or LRS over 20 minutes followed by a maintenance infusion of LRS (10 mL kg^?1hour^?1) during anesthesia. Before (Baseline) and at 1 and 24 hours after bolus administration, packed cell volume (PCV), total protein concentration (TP), prothrombin time (PT), activated partial thromboplastin time (APTT), von Willebrand’s factor antigen concentration (vWF:Ag), factor VIII coagulant activity (F VIII:C), platelet count, platelet aggregation, colloid osmotic pressure (COP) and buccal mucosal bleeding time (BMBT) were measured. In addition a surgeon who was blinded to the treatments assessed bleeding from the incision site during the procedure and at 1 and 24 hours after the bolus administration.ResultsFollowing hetastarch or LRS administration, the PCV and TP decreased significantly 1-hour post-infusion. APTT did not change significantly compared to baseline in either treatment group, but the PT was significantly longer at 1-hour post-infusion than at 24 hours in both groups. No significant change was detected for vWF:Ag, FVIII:C, platelet aggregation or clinical bleeding in either group. The BMBT increased while platelet count decreased significantly at 1-hour post-infusion in both groups. The COP decreased significantly in both treatment groups 1-hour post-infusion but was significantly higher 1-hour post-infusion in the hetastarch group compared to the LRS group.Conclusions and clinical relevanceAt the doses administered, both hetastarch and LRS can alter hemostatic variables in healthy dogs. However, in these dogs undergoing orthopedic surgery, neither fluid was associated with increased clinical bleeding.     

Comparative stability of canine and feline hemostatic proteins in freeze‐thaw‐cycled fresh frozen plasma

Objective – To evaluate the stability of canine and feline hemostatic proteins in freeze‐thaw‐cycled (FTC) fresh frozen plasma (FFP). Design – Prospective study. Setting – Veterinary Teaching Hospital. Animals – Nine blood donor dogs and 10 blood donor cats. Interventions – Whole blood was collected and separated into packed RBC and plasma units according to standard methods. Each unit of plasma was divided into 2 equal aliquots and frozen (?41°C). One aliquot from each donor (FTC) was then thawed and then refrozen (?41°C) until time of analysis. The second aliquot (nonfreeze‐thaw‐cycled; NFTC) remained frozen until time of analysis. The hemostatic proteins assessed included coagulation factors, anticoagulant factors (antithrombin and Protein C), and adhesive proteins (fibrinogen and von Willebrand Factor). The coagulant activities of factors II, VII, VIII, IX, X, XI, and XII were measured in modified one‐stage activated partial thromboplastin time or prothrombin time assays. Antithrombin and Protein C activities were measured in chromogenic substrate assays. Clottable fibrinogen was measured via the Clauss method, and von Willebrand Factor concentration (vWF:Ag) was measured in an ELISA. A paired t‐test was utilized to identify differences in factor activity or concentration between FTC FFP and NFTC FFP. Measurements and Main results – No clinically or statistically significant differences (all P>0.05) were identified between FTC FFP and NFTC FFP. Conclusions – Refreezing FFP within 1 hour of initial thawing appeared to have no deleterious effects on the hemostatic protein activity or content of that unit. Transfusion of FTC FFP is expected to provide the recipient with comparable replacement of hemostatic proteins as FFP that has remained frozen.     

Experimental investigation of the cardiovascular and respiratory effects of increasing concentrations of isoflurane in the dog

The cardiovascular and respiratory effects of the new inhalational anaesthetic agent isoflurane were investigated in dogs. Anaesthesia was induced with thiopentone after premedication with acepromazine. Isoflurane was administered with nitrous oxide and oxygen by spontaneous ventilation after base line values had been determined. Arterial blood pressure decreased as the concentration of administered isoflurane increased. Isoflurane produced a profound and dose related respiratory depression as measured by the increase in end tidal carbon dioxide levels. Isoflurane administration did not produce any visible muscle twitching.     

Evaluation of the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication

OBJECTIVE: To compare the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication. ANIMALS: 42 client-owned dogs that underwent elective ovariohysterectomy. PROCEDURE: Each dog was randomly allocated to receive medetomidine and butorphanol tartrate (20 microgram/kg and 0.2 mg/kg, respectively, IM) or acepromazine maleate and butorphanol (0.05 and 0.2 mg/kg, respectively, IM) for preanesthetic medication. Approximately 80 minutes later, anesthesia was induced by administration of propofol and maintained by use of isoflurane in oxygen. Each dog was also given carprofen before surgery and buprenorphine after surgery. Plasma concentrations of epinephrine, norepinephrine, cortisol, and beta-endorphin were measured at various stages during the perioperative period. In addition, cardiovascular and clinical variables were monitored. RESULTS: Concentrations of epinephrine, norepinephrine, and cortisol were significantly lower for dogs administered medetomidine. Concentrations of beta-endorphin did not differ between the 2 groups. Heart rate was significantly lower and mean arterial blood pressure significantly higher in dogs administered medetomidine, compared with values for dogs administered acepromazine. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that for preanesthetic medications, medetomidine may offer some advantages over acepromazine with respect to the ability to decrease perioperative concentrations of stress-related hormones. In particular, the ability to provide stable plasma catecholamine concentrations may help to attenuate perioperative activation of the sympathetic nervous system.     

Expression of von Willebrand factor in plasma and platelets of cats

Immunochemical methods that are used to assess von Willebrand factor in human beings and dogs were used to assess von Willebrand factor in 3 cat species. Our findings indicated that the expression and multimeric composition of von Willebrand factor in plasma and platelets of cats were similar to those reported in human beings and dogs. We suggest that these methods may be used to evaluate von Willebrand disease in members of the cat family used in this study.