Effects of 2.0% end-tidal isoflurane with and without atropine prior to dexmedetomidine administration on cardiovascular variables in dogs

The purpose of this study was to determine the cardiovascular effects of 2.0% end‐tidal isoflurane in dogs administered dexmedetomidine (DEX). Using a randomized crossover design and allowing at least 2 weeks between treatments 12 adult hound dogs of either sex weighing 22 ± 1.7 SD kg were anesthetized by face mask administration of either sevoflurane or isoflurane to facilitate instrumentation prior to administration of treatment drugs. Dogs were intubated and instrumented to enable measurement of heart rate (HR), systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures, mean pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), pulmonary arterial temperature (TEMP), and cardiac output (CO) via thermodilution using 5 mL of 5% dextrose, and recording the average of three replicate measurements. Cardiac index (CI) and systemic (SVR) and pulmonary vascular resistances were calculated. Following completion of instrumentation, dogs were allowed to recover for 40 minutes. After collection of baseline data, dogs were administered one of four treatments at T‐10 minutes prior to injection of DEX (500? g M^–2 IM): 1) saline (SAL); 2) atropine [ATR, 0.02 (n = 6) or 0.04 (n = 6) mg kg^–1 IM]; 3) ISO (2.0% end tidal concentration); or 4) ISO + ATR. Cardiovascular data were collected at T‐20 and T‐5 minutes prior to administration of DEX, and at 5, 10 , 20, 30, 40, and 60 min following DEX. Data were analyzed using anova for repeated measures with post‐hoc differences between means identified using Bonferroni's method (p < 0.05). Differences in ATR dose were not found to be significant and thus results for ATR dose groups were pooled. Administration of SAL (dexmedetomidine alone) was associated with decreases in HR and CO and increases in SAP, MAP, DAP, CVP, and SVR. Administration of ATR was associated with an increase in HR and CO compared with SAL. Administration of ISO was associated with an increase in HR and a decrease in SVR, MAP and CVP compared with SAL. Administration of ISO + ATR was associated with effects similar to that of ISO or ATR alone. We conclude that administration of ISO reduces the increase in SVR associated with administration of DEX and does not adversely affect CO.     

The effects of L‐659,066, a peripheral α2‐adrenoceptor antagonist,and verapamil on the cardiovascular influences of dexmedetomidine in conscious sheep

Raekallio M. R., Honkavaara J. M., Vainio O. M. The effects of L‐659,066, a peripheral α₂‐adrenoceptor antagonist, and verapamil on the cardiovascular influences of dexmedetomidine in conscious sheep. J. vet. Pharmacol. Therap. 33 , 434–438. We investigated whether administration of L‐659,066, a peripheral α₂‐adrenoceptor antagonist, or verapamil, a calcium‐channel antagonist, would prevent the cardiovascular effects of dexmedetomidine. Eleven sheep received three intravenous treatments with a randomized, cross‐over design: dexmedetomidine (5 μg/kg, DEX); DEX with L‐659,066 (250 μg/kg, DEX + L); and verapamil (0.05 mg/kg) 10 min prior to DEX (Ver + DEX). Haemodynamics were recorded at intervals upto 40 min. Acute increases in mean arterial pressure (MAP) (106 ± 10.7 to 120.8 ± 11.7 mmHg), central venous pressure (CVP) (3.3 ± 3.2 to 14.7 ± 5.0 mmHg) and systemic vascular resistance (SVR) (1579 ± 338 to 2301 ± 523 dyne s/cm⁵), and decreases in cardiac output (CO) (5.36 ± 0.87 to 3.93 ± 1.30 L/min) and heart rate (HR) (88.6 ± 15.3 to 49.7 ± 5.5/min) were detected with DEX. The peak SVR remained lower after Ver + DEX (1835 ± 226 dyne s/cm⁵) than DEX alone, but the other parameters did not significantly differ between these treatments. 2 min after drug delivery, differences between DEX and DEX + L were statistically significant for all measured haemodynamic parameters. With DEX + L, an early decrease in MAP (99.9 ± 6.8 to 89.3 ± 6.6 mmHg) was detected, and DEX + L induced a slight but significant increase in CVP and a decrease in HR at the end of the observation period, while SVR and CO did not significantly change. All animals were assessed as deeply sedated from 2–20 min with no differences between treatments. L‐659,066 has great potential for clinical use to prevent the cardiovascular effects of dexmedetomidine mediated by peripheral α₂‐adrenoceptors, whereas the effects of verapamil were marginal.     

Comparative cardiovascular, analgesic, and sedative effects of medetomidine, medetomidine–hydromorphone, and medetomidine–butorphanol in dogs

The purpose of this study was to determine the cardiovascular, analgesic, and sedative effects of IV medetomidine (M, 20 µg kg^?1), medetomidine–hydromorphone (MH, 20 µg kg^?1 ? 0.1 mg kg^?1), and medetomidine–butorphanol (MB, 20 µg kg^?1 ? 0.2 mg kg^?1) in dogs. Using a randomized cross‐over design and allowing 1 week between treatments, six healthy, mixed‐breed dogs (five males and one female) weighing 20 ± 3 kg, were induced to anesthesia by face‐mask administration of 2.9% ET sevoflurane to facilitate instrumentation prior to administration of the treatment combinations. Dogs were intubated and instrumented to enable measurement of heart rate (HR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (PAP), pulmonary arterial occlusion pressure (PAOP), central venous pressure (CVP), pulmonary arterial temperature (TEMP), and cardiac output via thermodilution using 5 mL of 5% dextrose, and recording the average of the three replicate measurements. Cardiac index (CI) and systemic (SVR) and pulmonary vascular resistances were calculated. After instrumentation was completed, administration of sevoflurane was discontinued, and the dogs were allowed to recover for 30 minutes prior to administration of the treatment drugs. After collection of the baseline samples for blood gas analysis and recording the baseline cardiovascular variables, the test agents were administered IV over 10 seconds and the CV variables recorded at 5, 10, 15, 30, 45, and 60 minutes post‐injection. In addition, arterial blood was sampled for blood gas analysis at 15 and 45 minutes following injection. Intensity and duration of analgesia (assessed by toe‐pinch response using a hemostat) and level of sedation were evaluated at the above time points and at 75 and 90 minutes post‐injection. Data were analyzed using anova for repeated measures with posthoc differences between means identified using Bonferroni's method (p < 0.05). Administration of M, MH, or MB was associated with increases in SAP, MAP, DAP, PAP, PAOP, CVP, SVR, and TEMP and with decreases in HR and CI. No differences in CV variables between treatment groups were identified at any time. PaO₂ increased over time in all groups and was significantly higher when MH was compared with M. At 45 minutes, PaO₂ tended to decrease over time and was significantly lower when MH and MB were compared with M at 15 minutes. Analgesia scores for MH and MB were significantly higher compared with M through 45 minutes, while analgesia scores for MH were significantly higher compared with M through 90 minutes. Sedation scores were higher for MH and MB compared with M throughout 90 minutes. Durations of lateral recumbency were 108 ± 10.8, 172 ± 15.5, and 145 ± 9.9 minutes for M, MH, and MB, respectively. We conclude that MH and MB are associated with improved analgesia and sedation and have similar CV effects when compared with M.     

Cardiovascular effects of desflurane following acute hemorrhage in dogs

Objective: To determine the cardiovascular effects of desflurane in dogs following acute hemorrhage. Design: Experimental study. Animals: Eight mix breed dogs. Interventions: Hemorrhage was induced by withdrawal of blood until mean arterial pressure (MAP) dropped to 60 mmHg in conscious dogs. Blood pressure was maintained at 60 mmHg for 1 hour by further removal or replacement of blood. Desflurane was delivered by facemask until endotracheal intubation could be performed and a desflurane expiratory end‐tidal concentration of 10.5 V% was maintained. Measurements and main results: Systolic, diastolic, and mean arterial blood pressure (SAP, DAP and MAP), central venous pressure (CVP), cardiac output (CO), stroke volume (SV), cardiac index (CI), systemic vascular resistance (SVR), heart rate (HR), respiratory rate (RR), partial pressure of carbon dioxide in arterial blood (PaCO₂), and arterial pH were recorded before and 60 minutes after hemorrhage, and 5, 15, 30, 45 and 60 minutes after intubation. Sixty minutes after hemorrhage, SAP, DAP, MAP, CVP, CO, CI, SV, PaCO₂, and arterial pH decreased, and HR and RR increased when compared with baselines values. Immediately after intubation, MAP and arterial pH decreased, and PaCO₂ increased. Fifteen minutes after intubation SAP, DAP, MAP, arterial pH, and SVR decreased. At 30 and 45 minutes, MAP and DAP remained decreased and PaCO₂ increased, compared with values measured after hemorrhage. Arterial pH increased after 30 minutes of desflurane administration compared with values measured 5 minutes after intubation. Conclusions: Desflurane induced significant changes in blood pressure and arterial pH when administered to dogs following acute hemorrhage.     

Comparative cardiovascular, analgesic, and sedative effects of medetomidine, medetomidine-hydromorphone, and medetomidine-butorphanol in dogs

OBJECTIVE: To compare sedative, analgesic, and cardiopulmonary effects after IV administration of medetomidine (20 microg/kg), medetomidine-hydromorphone (20 microg of medetomidine/kg and 0.1 mg of hydromorphone/kg), and medetomidine-butorphanol (20 microg of medetomidine/kg and 0.2 mg of butorphanol tartrate/kg) in dogs. ANIMALS: 6 dogs healthy mixed-breed dogs. PROCEDURE: Instruments were surgically inserted, and heart rate (HR), respiratory rate (RR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), core body temperature, and cardiac output (CO) were measured 0, 5, 10, 15, 30, 45, and 60 minutes after injection. Cardiac index (CI), stroke volume (SV), stroke index (SI), systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR) were calculated. Arterial samples for blood gas analysis were collected 0, 15, and 45 minutes after injection. Intensity of analgesia, degree of sedation, and degree of muscle relaxation were evaluated at aforementioned time points and 75, 90, 120, 150, 180, and 210 minutes after injection. RESULTS: Administration of medetomidine, medetomidine-hydromorphone, and medetomidine-butorphanol was associated with increases in SAP, MAP, DAP, MPAP, PCWP, CVP, SVR, PVR, core body temperature, and PaCO2 and decreases in HR, CO, CI, SV, SI, RR, pH, and PaO2. Clinically important differences were not detected among treatments. Medetomidine-hydromorphone and medetomidine-butorphanol provided a longer duration of sedation and better quality of analgesia, compared with medetomidine alone. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine-hydromorphone or medetomidine-butorphanol is associated with improved analgesia and sedation but has cardiopulmonary effects comparable to those for medetomidine alone.     

Cardiovascular effects of epidurally administered oxymorphone and an oxymorphone-bupivacaine combination in halothane-anesthetized dogs

OBJECTIVE: To evaluate cardiovascular effects of epidurally administered oxymorphone (OXY) and an OXY-bupivacaine combination (O/B) in halothane-anesthetized dogs. ANIMALS: 6 dogs. PROCEDURE: In a randomized crossover design study, dogs were anesthetized with halothane and given OXY, O/B, and saline solution (SAL). Eucapnia and end-tidal halothane concentration of 1.2% were established. Heart rate (HR), systemic and pulmonary arterial pressures, central venous pressure (CVP), and cardiac output were measured at baseline and 5, 15, 30, 45, 60, and 75 minutes after treatment. At 90 minutes, glycopyrrolate was administered IV, and measurements were repeated at 95 minutes. Cardiac index (CI), stroke volume, stroke index, systemic vascular resistance (SVR), and left ventricular work were calculated. End-tidal halothane concentration was decreased to 0.8% from 17 to 45 minutes and to 0.5% from 47 to 95 minutes for OXY and O/B, whereas for SAL, it was maintained at 1.5 and 1.2%, respectively. Samples were obtained at 0, 2, 5, 15, 30, 45, 60, and 95 minutes for measurement of serum opiate concentration and comparison with values after IM administration of OXY. RESULTS: HR decreased, but CVP and SVR increased in response to OXY and O/B. These changes were reversed after IV administration of glycopyrrolate, resulting in significant increase in CI, compared with that in response to SAL. Serum opiate concentration increased markedly and peaked within 15 minutes after OXY and O/B administration but did not differ from values after IM administration. CONCLUSIONS: Epidural administration of OXY results in rapid systemic uptake and decreased HR. Glycopyrrolate administration improves HR, resulting in improved CI at equipotent halothane concentrations.     

Effects of intramuscular vatinoxan (MK-467), co-administered with medetomidine and butorphanol,on cardiopulmonary and anaesthetic effects of intravenous ketamine in dogs

ObjectiveTo investigate the impact of intramuscular (IM) co-administration of the peripheral α₂-adrenoceptor agonist vatinoxan (MK-467) with medetomidine and butorphanol prior to intravenous (IV) ketamine on the cardiopulmonary and anaesthetic effects in dogs, followed by atipamezole reversal.Study designRandomized, masked crossover study.AnimalsA total of eight purpose-bred Beagle dogs aged 3 years.MethodsEach dog was instrumented and administered two treatments 2 weeks apart: medetomidine (20 μg kg^–1) and butorphanol (100 μg kg^–1) premedication with vatinoxan (500 μg kg^–1; treatment MVB) or without vatinoxan (treatment MB) IM 20 minutes before IV ketamine (4 mg kg^–1). Atipamezole (100 μg kg^–1) was administered IM 60 minutes after ketamine. Heart rate (HR), mean arterial (MAP) and central venous (CVP) pressures and cardiac output (CO) were measured; cardiac (CI) and systemic vascular resistance (SVRI) indices were calculated before and 10 minutes after MVB or MB, and 10, 25, 40, 55, 70 and 100 minutes after ketamine. Data were analysed with repeated measures analysis of covariance models. A p-value <0.05 was considered statistically significant. Sedation, induction, intubation and recovery scores were assessed.ResultsAt most time points, HR and CI were significantly higher, and SVRI and CVP significantly lower with MVB than with MB. With both treatments, SVRI and MAP decreased after ketamine, whereas HR and CI increased. MAP was significantly lower with MVB than with MB; mild hypotension (57–59 mmHg) was recorded in two dogs with MVB prior to atipamezole administration. Sedation, induction, intubation and recovery scores were not different between treatments, but intolerance to the endotracheal tube was observed earlier with MVB.Conclusions and clinical relevanceHaemodynamic performance was improved by vatinoxan co-administration with medetomidine–butorphanol, before and after ketamine administration. However, vatinoxan was associated with mild hypotension after ketamine with the dose used in this study. Vatinoxan shortened the duration of anaesthesia.     

The effect of medetomidine and its antagonism with atipamezole on stress-related hormones, metabolites, physiologic responses, sedation, and analgesia in goats

Six 3‐year‐old goats (three males and three females) weighing 60.0 ± 18 kg (mean ± SD) were used to investigate the effect of medetomidine (MED; 20 µg kg^?1 IV) and its antagonism with atipamezole (ATI; 100 µg kg^?1 IV) on physiologic responses (heart rate (HR; beats minute^?1), respiratory rate (RR; breaths minute^?1), electrocardiogram (ECG), rectal temperature (T; °C), blood pressure (oscillometric; mm Hg), sedation (SED), posture (REC), analgesia (ALG), and stress‐related hormonal and metabolic responses (epinephrine and norepinephrine (high performance liquid chromatography with electrochemical detection), cortisol (COR; µg dL^?1; radioimmunoassay), glucose (GLU; mg mL^?1; enzymatic colorimetric assay), and free fatty acids (modified enzymatic colorimetric assay)); each goat received ATI or SAL in random order separated by 1 week. Jugular catheters were placed for drug administration and blood sampling (10–12 mL sample^?1) using a lidocaine skin block (20 mg) 2 hours prior to beginning of each trial; during this trial, goats breathed room air. Physiologic parameters were measured, SED, REC, and ALG were scored, and blood samples were collected from jugular catheters at baseline (time = ?30 minutes), 5 minutes post‐MED administration (time = ?25 minutes), 25 minute post‐MED administration and immediately prior to antagonism (time = 0 minute), and at 5, 30, 60, and 120 minutes after administering ATI or SAL. ALG was tested by clamping the withers and metacarpus with hoof testers fitted with a force transducer to measure applied isometric force (lb) (a technique used previously in goats to evaluate analgesia). Continuous variables were analyzed by Repeated Measures analysis of variance (anova ); categorical data were analyzed using a Friedman Repeated Measures anova on ranks. A p‐value of <0.05 was considered significant. If a significant difference was found, a Dunnett's pair‐wise comparison of means was conducted. Differences between ATI and SAL were examined at 5, 30, 60, and 120 minutes using a paired t‐test with a Bonferroni correction. Administration of MED resulted in a decrease in T (38.7 ± 0.3 to 34.5 ± 0.4 °C), HR (78 ± 19 to 55 ± 9), and RR (31 ± 12 to 14 ± 5) over time; an increase in mean arterial blood pressure (90 ± 19 to 132 ± 23), COR (0.254 ± 0.125 to 4.327 ± 1.233), and GLU (82.0 ± 13.2 to 255.9 ± 38.9); and changes in SED (alert to marked sedation), REC (standing to recumbent), and ALG (metacarpus = 5 ± 2 to 14 ± 0; withers = 3 ± 2 to 14 ± 0). GLU was 62–70% higher at 60 and 120 minutes and COR was 336% higher after SAL than after ATI at 120 minutes; at 30, 60, and 120 minutes, T was 4–10% higher after ATI than SAL. There were no other significant differences. REC, SED, and ALG were antagonized after ATI. ATI did not antagonize the effect of MED on HR, RR, or MAP, but stabilized T and antagonized the increase in GLU and COR.     

Controlled Cross Circulation in Dogs: Effects on Donor Hemodynamics

Controlled cross circulation (CCC) was performed in six pairs of dogs for 45 minutes with aortic cross clamping and cardioplegia. Data were collected in donor dogs at 10 minute intervals three times before, three times during, and three times after CCC and included arterial blood pressure, pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac index (CI), heart rate (HR), blood gas analysis, temperature, maximum rate of rise of left ventricular pressure dP/dt max/End diastolic volume (EDV), blood volume (BV), complete blood count (CBC) and activated clotting times (ACT). Pulse pressure (PP), systemic vascular resistance (SVR), oxygen delivery (Do₂), and left ventricular cardiac work (LVCW) were calculated. Arterial blood pressure, CVP, blood gas analysis, temperature, BV, CBC, and ACT were measured in recipient dogs. During CCC, donor hemodynamic changes resembled those observed in models of acute onset arteriovenous fistulas. Insidious BV shifts can occur despite the use of occlusive roller pumps. After CCC, donor hemodynamics resembled acute blood loss, characterized by decreases in mean arterial pressure (MAP), CVP, PCWP, and CI, and increases in SVR and dP/dt max/EDV. These changes were probably caused by pump imbalance and BV shift to the recipient dog.     

Hemodynamic effects of butorphanol in desflurane-anesthetized dogs

ObjectiveTo evaluate the effects of butorphanol on cardiopulmonary parameters in dogs anesthetized with desflurane and breathing spontaneously.Study designProspective, randomized experimental trial.AnimalsTwenty dogs weighing 12 ± 3 kg.MethodsAnimals were distributed into two groups: a control group (CG) and butorphanol group (BG). Propofol was used for induction and anesthesia was maintained with desflurane (10%). Forty minutes after induction, the dogs in the CG received sodium chloride 0.9% (0.05 mL kg^?1 IM), and dogs in the BG received butorphanol (0.4 mg kg^?1 IM). The first measurements of body temperature (BT), heart rate (HR), arterial pressures (AP), cardiac output (CO), cardiac index (CI), central venous pressure (CVP), stroke volume index (SVI), pulmonary arterial occlusion pressure (PAOP), mean pulmonary arterial pressure (mPAP), left ventricular stroke work (LVSW), systemic (SVR) and pulmonary (PVR) vascular resistances, respiratory rate (f_R), and arterial oxygen (PaO₂) and carbon dioxide (PaCO₂) partial pressures were taken immediately before the administration of butorphanol or sodium chloride solution (T0) and then at 15-minute intervals (T15–T75).ResultsIn the BG, HR, AP, mPAP and SVR decreased significantly from T15 to T75 compared to baseline. f_R was lower at T30 than at T0 in the BG. AP and f_R were significantly lower than in the CG from T15 to T75. PVR was lower in the BG than in the CG at T30, while PaCO₂ was higher compared with T0 from T30 to T75 in the BG and significantly higher than in the CG at T30 to T75.Conclusions and clinical relevanceAt the studied dose, butorphanol caused hypotension and decreased ventilation during desflurane anesthesia in dogs. The hypotension (from 86 ± 10 to 64 ± 10 mmHg) is clinically relevant, despite the maintenance of cardiac index.     

Cardiovascular effects of butorphanol in isoflurane-anesthetized alpacas

Butorphanol has been used clinically to provide analgesia in alpacas, but cardiovascular effects have not been reported. Using a randomized cross‐over design, eight healthy, young adult female alpacas (3 ± 1 SD years) weighing 64 ± 9 SD kg were anesthetized with isoflurane by mask followed by tracheal intubation and maintenance of anesthesia with 1.75% et (isoflurane) in oxygen. Two treatments, butorphanol (0.1 mg kg^–1 IV) and control (saline, IV) were assigned to the animals in a randomized manner allowing a minimum of two weeks between treatments. While anesthetized, animals were instrumented for measurement of cardiovascular variables including systolic, diastolic, and mean arterial blood pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac output (CO) and pulmonary temperature (TEMP). CO was measured via thermodilution using 5 mL of iced 5% dextrose and recording the average of three replicate measurements. Cardiac index, systemic vascular resistance (SVR) and pulmonary vascular resistance were also calculated. Arterial and mixed venous blood samples were collected for blood gas analysis [pH, pO₂, pCO₂, (HCO₃^?), BE, Hb_sat]. Variables were collected at baseline (time 0) and at 5, 10, 15, 30, 45, and 60 minutes following injection. Variables were analyzed by anova for repeated measures with post‐hoc differences between means identified using the Bonferroni comparison (p < 0.05). SVR decreased five minutes after administration of butorphanol (Huynh Feldt corrected p = 0.045) and remained decreased for 60 minutes. TEMP decreased with time in both groups (Huynh Feldt corrected p = 0.000027), but groups were not different between each other. Other cardiovascular and blood gas variables were not different between groups. We conclude that butorphanol (0.1 mg kg^–1 IV) had minimal effects on the cardiovascular system of these alpacas, causing a mild decrease in SVR.     

The cardiovascular effects of dexmedetomidine given by continuous infusion during isoflurane anesthesia in dogs

In a previous study we showed that the MAC of isoflurane was decreased by 18 ± 12% and 59 ± 7% by constant rate infusions of dexmedetomidine at 0.5 and 3 μg kg^–1 hour^–1. The purpose of this study was to document the cardiovascular changes associated with these infusions of dexmedetomidine at 1.3 MAC isoflurane/ dexmedetomidine. Dogs were anesthetized with isoflurane in oxygen given by mask. A cephalic venous catheter, a dorsal pedal arterial catheter and a balloon tipped, Swan–Ganz, pulmonary arterial catheter were placed percutaneously. After instrumentation the dogs were maintained at 1.3 MAC isoflurane for 60 minutes. At this time a set of measurements was made including, heart rate, respiratory rate, core body temperature, pulmonary and systemic arterial blood pressures (SAP, MAP, DAP, CVP, SPAP, MPAP, DPAP and PAOP), cardiac output and arterial and mixed venous blood samples were collected for the measurement of blood gases, pH, hemoglobin concentration, PCV and total protein. Calculated variables included base excess (BE), (HCO₃^?), cardiac index, systemic and pulmonary vascular resistance indices, oxygen delivery, oxygen consumption, oxygen utilization ratio and shunt fraction. After these measurements to dogs were randomly assigned to receive a loading dose of 0.5 or 3 μg kg^–1 of dexmedetomidine given over 6 minutes followed by an infusion of 0.5 (LD) or 3 μg kg^–1 hour^–1 (HD), respectively. The concentration of isoflurane was reduced by the above percentages, respectively, to maintain 1.3 MAC. Full sets of measurements were repeated at 10, 30, 60, 90, 120, 150 and 180 minutes after the start of the loading dose. Measured and calculated variables were compared with baseline using an anova and a post‐hoc Tukey's test. Significance was set at p = 0.05 and results are given as mean ± SD. The initial concentration of isoflurane was 1.73 ± 0.02% and was reduced to 1.41 ± 0.02 and 0.72 ± 0.09% for the LD and HD, respectively. Heart rate decreased with both doses but no other parameter changed significantly with the LD. With the HD there were significant changes in SAP, MAP, DAP, CVP, MPAP, PAOP, CI, SVRI, PCV, DO₂ and shunt fraction. The LD appeared to have minimal effect on the cardiopulmonary values measured, whereas the HD caused typical changes expected with an alpha‐2 agonist.     

The cardiopulmonary effects of romifidine in dogs with and without prior or concurrent administration of glycopyrrolate

Objective To determine the electrocardiographic and cardiopulmonary effects of romifidine with and without prior or concurrent administration of glycopyrrolate. Study design Randomized crossover experimental study. Animals Six (three male, three female) cross‐bred dogs weighing 23 ± 2.4 kg. Methods Baseline cardiopulmonary measurements were obtained in conscious dogs and one of five treatments was administered. Glycopyrrolate (G) 0.01 mg kg^?1, or saline (S) 0.5 mL, were administered IM as premedication (Gp or Sp), or G was administered concurrently (Gc) with romifidine (RO). Treatments were as follows T1, Sp + RO 40 µg kg^?1; T2, Gp + RO (40 µg kg^?1); T3, Sp + RO 120 µg kg^?1; T4, Gp + RO (120 µg kg^?1); T5, Sp + Gc + RO (120 µg kg^?1). Romifidine or RO + Gc was administered subcutaneously 20 minutes after premedication (time 0), and further measurements were taken 10, 20, 30, 60 and 90 minutes after RO. The main treatment effect was evaluated using two‐way anova for repeated measures, followed by one‐way anova and a post‐hoc least squares difference test with a modified Bonferroni correction (p < 0.02). A Student's t‐test was used to compare the effect of romifidine at 20 and 60 minutes versus baseline values (p < 0.05). Results Both low‐ and high‐dose RO (T1, T3) significantly decreased heart rate (HR), respiratory rate (RR), cardiac index (CI) and stroke volume index, and increased arterial blood pressure (SAP), systemic vascular resistance (SVR), pulmonary arterial occlusion pressure (PAOP) and central venous pressure. High‐dose RO produced greater increases in SVR and SAP measurements. Neither dose of RO produced an alteration in blood gas values or the alveolar to arterial oxygen gradient. Glycopyrrolate significantly increased HR and CI from 10 to 90 minutes between T1/T2 and T3/T4. Increases in SAP were dose related with significant differences between T1/T3 and T2/T4 at 90 and 10 minutes, respectively, and were highest in animals receiving Gp or Gc. High‐dose RO groups (T3, T4) had higher values for SVR than low‐dose RO groups (T1, T2), unrelated to G administration. There was an increase in PAOP in all treatments. The oxygen extraction ratio was increased with all treatments: larger increases were observed in T1, T3 and T4 compared with only minimal changes in T2. Concurrent G administration was associated with an increased frequency of high‐grade second‐degree atrioventricular heart block with variable conduction at 10 and 20 minutes. Conclusions Romifidine produced effects consistent with other selective α₂‐adrenoreceptor agonists. Glycopyrrolate offset the decrease in HR and partially offset the decrease in CI associated with RO administration. Glycopyrrolate premedication produced an initial tachycardia and added to the increase in SAP associated with RO. Concurrent G administration was associated with a higher frequency of dysrhythmias and is not recommended. Despite the decrease in RR, RO sedation did not alter blood gas values. Clinical relevance It appears likely that G administration prior to or concurrent with RO produces an increase in myocardial workload and oxygen demand suggesting that this combination should not be used in dogs with cardiomyopathy or heart failure. The improvement in oxygen extraction ratio with T2 suggests that G may be beneficial with lower doses of RO, nevertheless, the use of G and RO in cardiovascularly compromised patients is not advised.     

Cardiopulmonary effects of medetomidine, oxymorphone, or butorphanol in selegiline-treated dogs

OBJECTIVES: To determine if chronic selegiline HCl administration affects the cardiopulmonary response to medetomidine, oxymorphone, or butorphanol in dogs. STUDY DESIGN: Prospective randomized experimental study. ANIMALS: Twenty-eight adult, random source, hound dogs weighing 21-33 kg. METHODS: Dogs were assigned to the following treatment groups: selegiline + medetomidine (MED; n = 6); placebo + MED (n = 6), selegiline + oxymorphone (OXY; n = 6); placebo + OXY (n = 6); selegiline + butorphanol (BUT; n = 7) or placebo + BUT (n = 6). Nine dogs were treated with two of the three pre-medicants. Dogs were treated with selegiline (1 mg kg(-1) PO, q 24 hours) or placebo for at least 44 days prior to pre-medicant administration. On the day of the experiment, arterial blood for blood gas analysis, blood pressure measurements, ECG, cardiac ultrasound (mM-mode, 2-D, and continuous wave Doppler), and behavioral observations were obtained by blinded observers. An IV injection of MED (750 micro g m(-2)), OXY (0.1 mg kg(-1)) or BUT (0.4 mg kg(-1)) was given. Cardiopulmonary and behavioral data were collected at 1, 2, 5, 15, 30, and 60 minutes after injection. RESULTS: Selegiline did not modify responses to any of the pre-medicant drugs. Medetomidine caused a significant decrease in heart rate (HR), cardiac output (CO), and fractional shortening (FS). Mean arterial pressure (MAP), systemic vascular resistance (SVR), and central venous pressure (CVP) were increased. Level of consciousness and resistance to restraint were both decreased. Oxymorphone did not affect MAP, CO, CVP, or SVR, but RR and PaCO(2) were increased. Level of consciousness and resistance to restraint were decreased. BUT decreased heart rate at 1 and 5 minutes. All other cardiovascular parameters were unchanged. BUT administration was associated with decreased arterial pH and increased PaCO(2). BUT decreased level of consciousness and resistance to restraint. CONCLUSIONS AND CLINICAL RELEVANCE: Although pre-medicants themselves altered cardiopulmonary and behavioral function, selegiline did not affect the response to medetomidine, oxymorphone, or butorphanol in this group of normal dogs.     

Hemodynamic Effects of Intravenous Midazolam-Xylazine-Butorphanol in Dogs

The hemodynamic effects of a mixture of midazolam (1.0 mg/kg), xylazine (0.44 mg/kg), and butorphanol (0.1 mg/kg) were evaluated in six adult dogs. The dogs were anesthetized with isoflurane for instrumentation. As the dogs returned to consciousness, baseline values were recorded and the midazolam-xylazine-butorphanol mixture and glycopyrrolate (0.01 mg/kg) were administered intravenously (IV). Hemodynamic data were recorded 3, 10, 20, 30, 40, 50, and 60 minutes after injection. Mean arterial pressure (AP), mean pulmonary arterial pressure (PAP), heart rate (HR), rate-pressure product (RPP), mean pulmonary capillary wedge pressure (PCWP), systemic vascular resistance (SVR), and right ventricular stroke work index (RVSWI) were increased significantly above baseline values. Cardiac output (CO), stroke volume (SV), cardiac index (CI), stroke index (SI), mean central venous pressure (CVP), and left ventricular stroke work index (LVSWI) were decreased significantly below baseline values. When administered IV at the dosages used in this study, midazolam-xylazine-butorphanol-glycopyrrolate induced profound acute alterations in several critical hemodynamic variables.     

Cardiorespiratory effects of a cardioselective muscarinic antagonist in anesthetized horses

Treatment of bradycardia in horses has been historically ignored because of the motility depressant effects of nonselective antimuscarinics. This study evaluated the cardiopulmonary effects of a cardioselective (M2) muscarinic antagonist, methoctramine (MET), in anesthetized horses. In a previous in vitro study, we determined that supraphysiological doses of MET were necessary to inhibit acetylcholine‐induced longitudinal jejunal smooth muscle contractions in this species. Six adult horses were allocated to two treatments in a randomized complete block design. Anesthesia was induced with xylazine/ketamine, and maintained with halothane (1% end‐tidal) and a constant infusion of xylazine (1 mg kg^?1 hour^?1) under mechanical ventilation. Invasive hemodynamic variables were monitored at baseline (approximately 45 minutes after induction) and for 120 minutes after MET or saline (control) had been injected. MET was titrated at 10‐minute intervals (10 µg kg^?1 IV) until the heart rate (HR) increased at least 30% above the baseline, or a maximum cumulative dose of 30 µg kg^?1 had been injected. A person blinded to the treatment evaluated recovery scores and monitored intestinal auscultation until 24 hours after the end of anesthesia using previously published methods. Cardiovascular parameters were analyzed by anova followed by a Dunnet's test, and nonparametrical data were analyzed by a Mann–Whitney U‐test (p < 0.05). Values were mean ± SEM unless otherwise stated. MET significantly increased HR from baseline to 120 minutes post‐injection (from 29 ± 1 to 36 ± 2 beats minute^?1 at 20 minutes). Thermodilution cardiac output (CO) and mean arterial pressure (MAP) were increased from baseline to 75 minutes post‐MET injection (from 13.9 ± 0.8 to 19.4 ± 2.0 L minute^?1 for CO at 20 minutes, and from 82 ± 3 to 103 ± 5 mm Hg for MAP at 20 minutes). Recovery characteristics and bowel auscultation scores did not differ among the groups. The return to at least 75% of the maximum auscultation score occurred at 10 (8–18) hours [median (range)] for controls and at 9 (8–12) hours for MET. It was concluded that MET increased HR and improved hemodynamic function during halothane/xylazine anesthesia with no apparent effect on return to full‐bowel motility, as assessed by auscultation. Accordingly, M2 muscarinic antagonists might be represented as a safer alternative to treat intraoperative bradycardia in horse.     

Comparative evaluation of sedative and clinical effects of dexmedetomidine and xylazine in dromedary calves (Camelus dromedarius)

ObjectiveTo compare the sedative and clinical effects of intravenous (IV) administration of dexmedetomidine and xylazine in dromedary calves.Study designExperimental, crossover, randomized, blinded study.AnimalsA total of seven healthy male dromedary calves aged 14 ± 2 weeks and weighing 95 ± 5.5 kg.MethodsCalves were assigned three IV treatments: treatment XYL, xylazine (0.2 mg kg⁻¹); treatment DEX, dexmedetomidine (5 μg kg⁻¹); and control treatment, normal saline (0.01 mL kg⁻¹). Sedation scores, heart rate (HR), respiratory rate (f_R), rectal temperature (RT) and ruminal motility were recorded before (baseline) and after drug administration. Sedation signs were scored using a 4-point scale. One-way anova and Mann–Whitney U tests were used for data analysis.ResultsCalves in treatments XYL and DEX were sedated at 5–60 minutes. Sedation had waned in XYL calves, but not DEX calves, at 60 minutes (p = 0.037). Sedation was not present in calves of any treatment at 90 minutes. HR decreased from baseline in XYL and DEX at 5–90 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.017). HR was lower in DEX (p = 0.001) and XYL (p = 0.013) than in control treatment at 90 minutes. f_R decreased from baseline in XYL and DEX at 5–60 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.013). RT was unchanged in any treatment over 120 minutes. Ruminal motility was decreased in XYL at 5, 90 and 120 minutes and absent at 10–60 minutes. Motility was decreased in DEX at 5, 10 and 120 minutes and was absent at 15–90 minutes.Conclusion and clinical relevanceThe duration of sedation from dexmedetomidine (5 μg kg^–1) and xylazine (0.2 mg kg^–1) was similar in dromedary calves.     

Cardiovascular Effects After Epidural Injection of Xylazine in Isoflurane-Anesthetized Dogs

The cardiovascular effects following epidural injection of xylazine or isotonic saline during isoflurane anesthesia were assessed in six healthy dogs. Dogs were anesthetized with isoflurane in O₂ and maintained at 2.0% end-tidal concentration. Ventilation was controlled to maintain PaCO₂ at 35 to 45 mm Hg. The dorsal pedal artery was cannulated for measurement of arterial blood pressure (AP)(systolic AP, mean AP, diastolic AP) and for blood sample collection. Arterial pH and blood gas tensions (PaO₂ and PaCO₂) were determined. Cardiac output was measured by thermodilution. The electrocardiogram (ECG), heart rate (HR), core body temperature, central venous pressure (CVP), mean pulmonary AP, and end-tidal isoflurane concentration (ETISO) and CO₂ tension (ETCO₂) were monitored. Systemic vascular resistance (SVR), arterial HCO₂ concentration, base balance, and cardiac index (CI) were calculated. After baseline measurements were taken, either xylazine (0.2 mg/kg) in 5 mL isotonic saline or 5 mL of isotonic saline was injected into the lumbosacral epidural space. Data were then recorded at 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after epidural injection. Data were analyzed by two-way analysis of variance (ANOVA) for repeated measures. When significant differences were encountered, mean values were compared using Bonferroni's test. The level of significance was set at P <.05. Mean values for diastolic AP decreased at 90 and 120 minutes compared with the mean value at 15 minutes after epidural injection of xylazine. No differences were detected at any time or between treatments for HR, systolic AP, mean AP, CVP, CI, SVR, mean pulmonary AP, temperature, ETCO₂, ETISO, arterial pH, PaCO₂, PaO₂, plasma bicarbonate concentration, or base balance. Results of this study indicate that epidural injection of xylazine (0.2 mg/kg) is associated with minimal cardiovascular side effects during isoflurane anesthesia in mechanically ventilated dogs.     

Cardiopulmonary effects of combined xylazine-guaiphenesin-ketamine infusion and extradural (inter-coccygeal lidocaine) anaesthesia in calves

Objective To investigate the cardiopulmonary effects of a xylazine–guaiphenesin–ketamine infusion combined with inter‐coccygeal extradural (lidocaine) anaesthesia in calves. Study design Prospective study. Animals Five Holstein Friesian calves (one steer, four heifers) aged 6 weeks weighing 65.2 ± 2.7 kg. Materials and methods Calves were anaesthetized with isoflurane in oxygen for instrumentation. At least 12 hours later, xylazine (0.2 mg kg^?1 IM) was given. After 15 minutes, an infusion of xylazine hydrochloride (0.1 mg mL^?1), guaiphenesin (50 mg mL^?1) and ketamine (1 mg mL^?1) (X–G–K) was infused at a rate of 1.1 mL kg^?1 hour^?1 IV. Oxygen (4 L minute^?1) was delivered by nasotracheal tube 30 minutes later. Inter‐coccygeal (Co₁–Co₂) extradural anaesthesia (lidocaine 2%, 0.18 mL kg^?1) was administered 30 minutes later. Cardiopulmonary variables were obtained in the unsedated standing calves 10 minutes after xylazine, 15 and 30 minutes after X–G–K without O₂, 15 and 30 minutes after X–G–K with O₂ and 5, 15, 30, 45 and 60 minutes after extradural anaesthesia. Data were analysed using a repeated measurement analysis of variance including an autoregressive covariance structure of order 1 (correlations at different time intervals). Results Xylazine caused significant (p < 0.05) decreases in heart rate (HR), cardiac output (Qt) and index (CI), stroke volume and stroke index, mean, systolic and diastolic arterial blood pressure (MAP, SAP, DAP), left (LVWSI) and right ventricular stroke work index (RVWSI), mean, systolic and diastolic pulmonary arterial pressure (MPAP, SPAP, DPAP), arterial pH, arterial oxygen tension (P_aO₂), arterial base excess, arterial HCO₃^? concentration, arterial saturation, packed cell volume, arterial and venous oxygen content (C_aO₂, C_vO₂), O₂ consumption and O₂ delivery (V?O₂, ?O₂). Increases in systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were observed. During X–G–K infusion without O₂, HR, Qt and CI increased gradually while SVR, PVR and MAP decreased. Left ventricular stroke work index and P_aO₂ remained constant, while O₂ supplementation improved P_aO₂. Coccygeal extradural anaesthesia had little effect on cardiopulmonary variables. Respiratory rate (f) and P_aCO₂ significantly increased over the experiment. Conclusions and clinical relevance Xylazine caused adverse cardiopulmonary effects in calves. Improvement occurred during xylazine–guiaphenesin–ketamine infusion. Cardiac index and arterial blood pressure remained below baseline values while sustained increases in respiration rate and P_aCO₂ were observed. Inter‐coccygeal extradural anaesthesia had only minor effects. Oxygen supplementation proved advantageous during guiaphenesin, ketamine and xylazine infusion in healthy calves in combination with coccygeal extradural anaesthesia induced persistent cardiopulmonary depression.     

Cardiovascular effects of a proprietary l-methadone/fenpipramide combination (Polamivet) alone and in addition to acepromazine in healthy Beagle dogs

ObjectiveTo determine the cardiovascular effects of a proprietary l-methadone/fenpipramide combination (Polamivet) alone and in addition to acepromazine in dogs.Study designProspective, randomized, experimental crossover study.AnimalsFive adult healthy Beagle dogs (one male and four females, weighing 12.8–16.4 kg).MethodsDogs were instrumented for haemodynamic measurements whilst anaesthetized with isoflurane. Three hours after recovery dogs received 0.025 mg kg^?1 acepromazine (AP) or saline (SP) IM followed by 0.5 mg kg^?1L-methadone/ 0.025 mg kg^?1 fenpipramide IV after 30 minutes. Cardiac output using thermodilution, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (MPAP), pulmonary artery occlusion pressure (PAOP), haemoglobin concentration, arterial and mixed-venous blood gas analysis were measured and sedation evaluated at baseline (BL), 30 minutes after acepromazine or saline IM (A/S), 5 minutes after L-methadone/fenpipramide IV application (35), every 15 minutes for 1 hour (50, 65, 80, 95 minutes) and every hour until baseline cardiac output was regained. Standard cardiovascular parameters were calculated. Data were analyzed by repeated measures anova and paired t-tests with p < 0.05 considered significant.ResultsBaseline measurements did not differ. Cardiac index decreased after acepromazine administration in treatment AP (p = 0.027), but was not significantly influenced after l-methadone/fenpipramide injection in either treatment. In both treatments heart rate did not change significantly over time. Stroke volume index increased after A/S in both treatments (p = 0.049). Systemic vascular resistance index, MAP, CVP, MPAP, and pulmonary vascular resistance index did not change significantly after either treatment and did not differ between treatments. Dogs were deeply sedated in both treatments with a longer duration in treatment AP.Conclusions and clinical relevanceIn healthy dogs the dose of l-methadone/fenpipramide used in this study alone and in combination with acepromazine induced deep sedation without significant cardiovascular changes.