Hemodynamic effects of dexmedetomidine,with and without MK-467, following intramuscular administration in cats anesthetized with isoflurane

Objective

To characterize the hemodynamic effects of dexmedetomidine, with or without MK-467, following intramuscular (IM) administration in cats.

Pharmacokinetics of dexmedetomidine,MK-467 and their combination following intramuscular administration in male cats

Objective

To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats.

The impact of MK-467 on sedation,heart rate and arterial blood pressure after intramuscular coadministration with dexmedetomidine in conscious cats

Objective

To study the effects of MK-467, a peripheral α₂-adrenoceptor antagonist, on sedation, heart rate and blood pressure after intramuscular (IM) coadministration with 25 μg kg^?1 of dexmedetomidine in cats.

Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats

ObjectiveTo compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats.Study designRandomized, ‘blinded’ crossover study, with 1 month washout between treatments.AnimalsSix healthy neutered female cats, weighing 5.3–7.5 kg.MethodsA combination of dexmedetomidine (40 μg kg^?1) and buprenorphine (20 μg kg^?1) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat’s response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range.ResultsThere were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing.Conclusions and clinical relevanceIn healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats.     

Hemodynamic effects of dexmedetomidine in isoflurane-anesthetized cats

ObjectiveTo characterize the hemodynamic effects of dexmedetomidine in isoflurane-anesthetized cats.Study designProspective experimental study.AnimalsSix healthy adult female cats weighing 4.6 ± 0.8 kg.MethodsDexmedetomidine was administered intravenously using target-controlled infusions to maintain nine plasma concentrations between 0 and 20 ng mL^?1 in isoflurane-anesthetized cats. The isoflurane concentration was adjusted for each dexmedetomidine concentration to maintain the equivalent of 1.25 times the minimum alveolar concentration, based on a previous study. Heart rate, systemic and pulmonary arterial pressures, central venous pressure, pulmonary artery occlusion pressure, body temperature, and cardiac output were measured at each target plasma dexmedetomidine concentration. Additional variables were calculated. Arterial and mixed-venous blood samples were collected for blood gas, pH, and (on arterial blood only) electrolyte, glucose and lactate analysis. Plasma dexmedetomidine concentration was determined for each target. Pharmacodynamic models were fitted to the data.ResultsHeart rate, arterial pH, arterial bicarbonate concentration, mixed-venous PO₂, mixed-venous pH, mixed-venous hemoglobin oxygen saturation, cardiac index, stroke index, and venous admixture decreased following dexmedetomidine administration. Arterial blood pressure, central venous pressure, pulmonary arterial pressure, pulmonary arterial occlusion pressure, packed cell volume, PaO₂, PaCO₂, arterial hemoglobin concentration, mixed-venous PCO₂, mixed-venous hemoglobin concentration, ionized calcium concentration, glucose concentration, rate-pressure product, systemic and pulmonary vascular resistance indices, left ventricular stroke work index, arterial oxygen concentration, and oxygen extraction increased following dexmedetomidine administration. Most variables changed in a dexmedetomidine concentration-dependent manner.Conclusion and clinical relevanceThe use of dexmedetomidine as an anesthetic adjunct is expected to produce greater negative hemodynamic effects than a higher, equipotent concentration of isoflurane alone.     

Pharmacokinetics of dexmedetomidine,MK‐467, and their combination following intravenous administration in male cats

This study characterized the pharmacokinetics of dexmedetomidine, MK‐467, and their combination following intravenous bolus administration to cats. Seven 6‐ to‐year‐old male neutered cats, weighting 5.1 ± 0.7 kg, were used in a randomized, crossover design. Dexmedetomidine [12.5 (D12.5) and 25 (D25) μg/kg], MK‐467 [300 μg/kg (M300)] or dexmedetomidine (25 μg/kg) and MK‐467 [75, 150, 300 or 600 μg/kg—only the plasma concentrations in the 600 μg/kg group (D25M600) were analyzed] were administered intravenously, and blood was collected until 8 hours thereafter. Plasma drug concentrations were analyzed using liquid chromatography/mass spectrometry. A two‐compartment model best fitted the data. Median (range) volume of the central compartment (mL/kg), volume of distribution at steady state (mL/kg), clearance (mL min/kg) and terminal half‐life (min) were 342 (131–660), 829 (496–1243), 14.6 (9.6–22.7) and 48 (40–69) for D12.5; 296 (179–982), 1111 (908–2175), 18.2 (12.4–22.9) and 52 (40–76) for D25; 653 (392–927), 1595 (1094–1887), 22.7 (18.5–36.4) and 48 (35–60) for dexmedetomidine in D25M600; 117 (112–163), 491 (379–604), 3.0 (2.0‐4.5) and 122 (99‐139) for M300; and 147 (112‐173), 462 (403‐714), 2.8 (2.1–4.8) and 118 (97–172) for MK‐467 in D25M600. MK‐467 moderately but statistically significantly affected the disposition of dexmedetomidine, whereas dexmedetomidine minimally affected the disposition of MK‐467.     

Sedative and analgesic effects of buprenorphine,combined with either acepromazine or dexmedetomidine,for premedication prior to elective surgery in cats and dogs

ObjectiveTo evaluate the sedative and analgesic effects of intramuscular buprenorphine with either dexmedetomidine or acepromazine, administered as premedication to cats and dogs undergoing elective surgery.Study designProspective, randomized, blinded clinical study.AnimalsForty dogs and 48 cats.MethodsAnimals were assigned to one of four groups, according to anaesthetic premedication and induction agent: buprenorphine 20 μg kg^?1 with either dexmedetomidine (dex) 250 μg m^?2 or acepromazine (acp) 0.03 mg kg^?1, followed by alfaxalone (ALF) or propofol (PRO). Meloxicam was administered preoperatively to all animals and anaesthesia was always maintained using isoflurane. Physiological measures and assessments of pain, sedation and mechanical nociceptive threshold (MNT) were made before and after premedication, intraoperatively, and for up to 24 hours after premedication. Data were analyzed with one-way, two-way and mixed between-within subjects anova, Kruskall–Wallis analyses and Chi squared tests. Results were deemed significant if p ≤ 0.05, except where multiple comparisons were performed (p ≤ 0.005).ResultsCats premedicated with dex were more sedated than cats premedicated with acp (p < 0.001) and ALF doses were lower in dex cats (1.2 ± 1.0 mg kg^?1) than acp cats (2.5 ± 1.9 mg kg^?1) (p = 0.041). There were no differences in sedation in dogs however PRO doses were lower in dex dogs (1.5 ± 0.8 mg kg^?1) compared to acp dogs (3.3 ± 1.1 mg kg^?1) (p < 0.001). There were no differences between groups with respect to pain scores or MNT for cats or dogs.ConclusionChoice of dex or acp, when given with buprenorphine, caused minor, clinically detectable, differences in various characteristics of anaesthesia, but not in the level of analgesia.Clinical relevanceA combination of buprenorphine with either acp or dex, followed by either PRO or ALF, and then isoflurane, accompanied by an NSAID, was suitable for anaesthesia in dogs and cats undergoing elective surgery. Choice of sedative agent may influence dose of anaesthetic induction agent.     

Effects of constant rate infusions of dexmedetomidine or MK-467 on the minimum alveolar concentration of sevoflurane in dogs

Objective

To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral α₂-adrenoceptor antagonist, MK-467, on sevoflurane minimum alveolar concentration (MAC) in dogs.

Evaluation of the clinical efficacy and safety of dexmedetomidine or medetomidine in cats and their reversal with atipamezole

OBJECTIVE: To evaluate and compare the clinical effects of dexmedetomidine (DEX) and medetomidine (MED) in cats, and their reversal with atipamezole (ATI). Study design Prospective blinded randomized multi-centre clinical trial. Animals One hundred and twenty client-owned cats. METHODS: Cats were randomly allocated to receive a single intramuscular (IM) injection of either DEX (0.04 mg kg(-1), n = 62) or MED (0.08 mg kg(-1), n = 58) for minor procedures requiring sedation and analgesia. Afterwards, ATI (0.2 mg kg(-1)) was administered IM to half the cats, randomly assigned. Prior to, during and after the procedure the sedative, analgesic and cardiorespiratory effects and body temperature were assessed. RESULTS: Dexmedetomidine and MED produced clinically and statistically comparable effects. The intended procedure(s) could be performed in over 90% of cats. Sedation and analgesia were apparent within 5 minutes, peak effects were observed at approximately 30 minutes and spontaneous recovery occurred by 180 minutes of injection. Heart and respiratory rate and body temperature decreased significantly over time and had not returned to baseline values 180 minutes after administration. ATI administration completely reversed the sedative and analgesic effects, returned the heart rate to normal and prevented any further reductions in respiratory rate and body temperature in both DEX- and MED-treated cats. The reporting of adverse events was low and the most commonly observed event was vomiting (7%). No serious adverse events or concerns regarding safety were reported. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine (0.04 mg kg(-1)) produced comparable sedative and analgesic effects to MED (0.08 mg kg(-1)) in cats. DEX produced adequate sedation and analgesia for radiography, grooming, dental care and lancing of abscesses. ATI fully reversed the clinical effects of DEX.     

Cardiopulmonary and isoflurane‐sparing effects of epidural or intravenous infusion of dexmedetomidine in cats undergoing surgery with epidural lidocaine

ObjectiveTo compare the cardiorespiratory, anesthetic-sparing effects and quality of anesthetic recovery after epidural and constant rate intravenous (IV) infusion of dexmedetomidine (DEX) in cats given a low dose of epidural lidocaine under propofol-isoflurane anesthesia and submitted to elective ovariohysterectomy.Study designRandomized, blinded clinical trial.AnimalsTwenty-one adult female cats (mean body weight: 3.1 ± 0.4 kg).MethodsCats received DEX (4 μg kg^?1, IM). Fifteen minutes later, anesthesia was induced with propofol and maintained with isoflurane. Cats were divided into three groups. In GI cats received epidural lidocaine (1 mg kg^?1, n = 7), in GII cats were given epidural lidocaine (1 mg kg^?1) + DEX (4 μg kg^?1, n = 7), and in GIII cats were given epidural lidocaine (1 mg kg^?1) + IV constant rate infusion (CRI) of DEX (0.25 μg kg^?1 minute^?1, n = 7). Variables evaluated included heart rate (HR), respiratory rate (f_R), systemic arterial pressures, rectal temperature (RT), end-tidal CO₂, end-tidal isoflurane concentration (e′ISO), arterial blood gases, and muscle tone. Anesthetic recovery was compared among groups by evaluation of times to recovery, HR, f_R, RT, and degree of analgesia. A paired t-test was used to evaluate pre-medication variables and blood gases within groups. anova was used to compare parametric data, whereas Friedman test was used to compare muscle relaxation.ResultsEpidural and CRI of DEX reduced HR during anesthesia maintenance. Mean ± SD e′ISO ranged from 0.86 ± 0.28% to 1.91 ± 0.63% in GI, from 0.70 ± 0.12% to 0.97 ± 0.20% in GII, and from 0.69 ± 0.12% to 1.17 ± 0.25% in GIII. Cats in GII and GIII had longer recovery periods than in GI.Conclusions and clinical relevanceEpidural and CRI of DEX significantly decreased isoflurane consumption and resulted in recovery of better quality and longer duration, despite bradycardia, without changes in systemic blood pressure.     

Effect of dexmedetomidine and xylazine followed by MK-467 on gastrointestinal microperfusion in anaesthetized horses

Objective

To compare the effects of MK-467 during isoflurane anaesthesia combined with xylazine or dexmedetomidine on global and gastrointestinal perfusion parameters.

Cardiovascular,respiratory, electrolyte and acid–base balance during continuous dexmedetomidine infusion in anesthetized dogs

ObjectiveTo evaluate the cardiovascular, respiratory, electrolyte and acid–base effects of a continuous infusion of dexmedetomidine during propofol–isoflurane anesthesia following premedication with dexmedetomidine.Study designProspective experimental study.AnimalsFive adult male Walker Hound dogs 1–2 years of age averaging 25.4 ± 3.6 kg.MethodsDogs were sedated with dexmedetomidine 10 μg kg^?1 IM, 78 ± 2.3 minutes (mean ± SD) before general anesthesia. Anesthesia was induced with propofol (2.5 ± 0.5 mg kg^?1) IV and maintained with 1.5% isoflurane. Thirty minutes later dexmedetomidine 0.5 μg kg^?1 IV was administered over 5 minutes followed by an infusion of 0.5 μg kg^?1 hour^?1. Cardiac output (CO), heart rate (HR), ECG, direct blood pressure, body temperature, respiratory parameters, acid–base and arterial blood gases and electrolytes were measured 30 and 60 minutes after the infusion started. Data were analyzed via multiple linear regression modeling of individual variables over time, compared to anesthetized baseline values. Data are presented as mean ± SD.ResultsNo statistical difference from baseline for any parameter was measured at any time point. Baseline CO, HR and mean arterial blood pressure (MAP) before infusion were 3.11 ± 0.9 L minute^?1, 78 ± 18 beats minute^?1 and 96 ± 10 mmHg, respectively. During infusion CO, HR and MAP were 3.20 ± 0.83 L minute^?1, 78 ± 14 beats minute^?1 and 89 ± 16 mmHg, respectively. No differences were found in respiratory rates, PaO₂, PaCO₂, pH, base excess, bicarbonate, sodium, potassium, chloride, calcium or lactate measurements before or during infusion.Conclusions and clinical relevanceDexmedetomidine infusion using a loading dose of 0.5 μg kg^?1 IV followed by a constant rate infusion of 0.5 μg kg^?1 hour^?1 does not cause any significant changes beyond those associated with an IM premedication dose of 10 μg kg^?1, in propofol–isoflurane anesthetized dogs. IM dexmedetomidine given 108 ± 2 minutes before onset of infusion showed typical significant effects on cardiovascular parameters.     

Cardiovascular and renal effects of constant rate infusions of remifentanil, dexmedetomidine and their combination in dogs anesthetized with sevoflurane

We evaluated changes in cardiovascular and renal functions as well as arginine vasopressin (AVP) secretion, with remifentanil and dexmedetomidine administration alone or in combination in sevoflurane-anesthetized dogs. Six healthy adult Beagle dogs received one of the following four treatments in a randomized crossover study: saline (C), remifentanil alone at successively increasing doses (R; 0.15, 0.60, and 2.40 µg/kg/min), dexmedetomidine alone (D; 0.5 µg/kg intravenously for initial 10 min followed by a constant rate infusion at 0.5 µg/kg/hr), and a combination of remifentanil and dexmedetomidine at the above-mentioned doses (RD). Sevoflurane doses were adjusted to 1.5 times of minimum alveolar concentration (MAC) equivalent according to MAC-sparing effects with remifentanil and dexmedetomidine as previously reported. Cardiovascular measurements, renal function data, and plasma AVP concentrations were determined before and every 60 min until 180 min after drug administration as per each treatment. In the R, D and RD, heart rate significantly decreased and mean arterial pressure significantly increased from baseline or with C. Cardiac index significantly decreased and systemic vascular resistance index increased with D and RD. Oxygen extraction ratio, renal blood flow, and glomerular filtration rate were not affected. The plasma AVP concentrations significantly decreased in D and RD, but increased in R. Only in D, the natriuresis was elicited. The combination of remifentanil and dexmedetomidine in sevoflurane-anesthetized dogs was acceptable in terms of the hemodynamics, oxygenation, and renal function. Remifentanil may interfere with dexmedetomidine-induced diuresis and inhibition of AVP secretion.     

Evaluation of alfaxalone total intravenous anesthesia in rabbits (Oryctolagus cuniculus) premedicated with dexmedetomidine or dexmedetomidine and buprenorphine

ObjectiveTo evaluate alfaxalone for total intravenous anesthesia (TIVA) in rabbits premedicated with dexmedetomidine or dexmedetomidine and buprenorphine.Study designCrossover study (part 1) with observational study (part 2).AnimalsA total of eight New Zealand White rabbits (Oryctolagus cuniculus), four female and four male, aged 12–16 weeks and weighing 2.8–3.5 kg in part 1. Separately, four additional rabbits in part 2.MethodsCrossover study design with eight rabbits per treatment. Rabbits were administered treatment D, dexmedetomidine (0.2 mg kg^–1), or treatment DB, dexmedetomidine (0.1 mg kg^–1) and buprenorphine (0.05 mg kg^–1) intramuscularly. Anesthesia was induced with alfaxalone intravenously until a supraglottic airway device was placed to deliver 100% oxygen. Anesthesia was maintained with alfaxalone (TIVA). Infusion rates were adjusted to achieve an absent pedal withdrawal reflex. Heart rate, respiratory rate, noninvasive blood pressure, end-tidal carbon dioxide partial pressure and peripheral hemoglobin oxygen saturation (SpO₂) were recorded every 5 minutes. Subsequently, four rabbits underwent ovariohysterectomy using treatment DB and alfaxalone TIVA.ResultsThe mean ± standard deviation alfaxalone infusion rate was 9.6 ± 2.6 and 4.5 ± 1.3 mg kg^–1 hour^–1 for treatments D and DB, respectively. In both treatments, blood pressure remained within acceptable range and SpO₂ was > 95%. Postinduction apnea and respiratory depression were observed in both treatments and managed with manual positive pressure ventilation. Four separate rabbits underwent successful ovariohysterectomy with treatment DB and alfaxalone TIVA. One rabbit required supplementation with inhalant anesthesia; three rabbits were successfully maintained using alfaxalone TIVA alone.Conclusions and clinical relevancePremedication with dexmedetomidine–buprenorphine combined with alfaxalone TIVA may be a viable alternative for performing abdominal surgery in the rabbit. The use of supplemental oxygen and ability to provide respiratory support are advised.     

Pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol following a single induction dose administered intravenously in cats

ObjectiveTo compare the pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol administered intravenously (IV) as a single induction dose in cats.Study designProspective experimental study.AnimalsSix healthy adult cats, three female intact, three male castrated, weighing 4.8 ± 1.8 kg.MethodsCats received 8 mg kg⁻¹ IV of propofol (P) or propofol with 2% benzyl alcohol (P28) using a randomized crossover design. Venous blood samples were collected at predetermined time points to 24 hours after drug administration to determine drug plasma concentrations. Physiologic and behavioral variables were also recorded. Propofol and benzyl alcohol concentrations were determined using high pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were described using a 2-compartment model. Pharmacokinetic and pharmacodynamic parameters were analyzed using repeated measures anova (p < 0.05).ResultsPlasma concentrations of benzyl alcohol were below the lower limits of quantification (LLOQ) at all time points for two of the six cats (33%), and by 30 minutes for the remaining four cats. Propofol pharmacokinetics, with or without 2% benzyl alcohol, were characterized by rapid distribution, a long elimination phase, and a large volume of distribution. No differences were noted between treatments with the exception of clearance from the second compartment (CLD2), which was 23.6 and 38.8 mL kg⁻¹ minute⁻¹ in the P and P28 treatments, respectively. Physiologic and behavioral variables were not different between treatments with the exception of heart rate at 4 hours post administration.Conclusions and clinical relevanceThe addition of 2% benzyl alcohol as a preservative minimally altered the pharmacokinetics and pharmacodynamics of propofol 1% emulsion when administered as a single IV bolus in this group of cats. These data support the cautious use of propofol with 2% benzyl alcohol for induction of anesthesia in healthy cats.     

Dose-related thermal antinociceptive effects of intravenous hydromorphone in cats

OBJECTIVE: To describe the dose-related thermal antinociceptive effects of intravenous (i.v.) hydromorphone in cats. STUDY DESIGN: Randomized, blinded, crossover design. ANIMALS: Seven adult cats (3.5-7.4 kg), two spayed females, and five neutered males. METHODS: Hydromorphone (0.025, 0.05, or 0.1 mg kg(-1)) was administered i.v.. Skin temperature and thermal threshold were measured before and at selected time points to 720 minutes post-administration. Statistical analysis of mean thermal threshold and skin temperatures over time for each dose and between doses was by way of a split-plot model and post hoc Bonferroni t-tests. p < 0.05 was considered significant. RESULTS: A significant difference from baseline for mean thermal threshold was identified for the 0.05 mg kg(-1) dose (5-80 minutes, peak thermal threshold 46.9 +/- 6.2 degrees C) and 0.1 mg kg(-1) dose (5-200 minutes, peak thermal threshold 54.9 +/-0.2 degrees C). The thermal threshold was significantly greater after the 0.1 mg kg(-1) dose from 5 to 200 minutes compared to the 0.025 mg kg(-1) and 0.5 mg kg(-1) doses. The thermal threshold was significantly greater from 35 to 80 minutes for the 0.05 mg kg(-1) dose when compared with the 0.025 mg kg(-1) dose. Skin temperature was significantly increased from 35 to 140 minutes following the 0.1 mg kg(-1) dose. CONCLUSIONS: A dose-related antinociceptive effect was demonstrated for i.v. hydromorphone in cats. CLINICAL RELEVANCE: Hydromorphone at doses less than 0.1 mg kg(-1) has a modest antinociceptive effect and a short duration of action. At a dose of 0.1 mg kg(-1) i.v., onset of analgesia is rapid with a clinically useful duration of effect, but is associated with a rise in skin temperature.     

Correlation between serum concentrations following continuous intravenous infusion of dexmedetomidine or medetomidine in cats and their sedative and analgesic effects

Dexmedetomidine (DEX) may have some therapeutic advantages over the racemate medetomidine (MED). Here we have examined how serum concentrations of DEX correlate with some of its anaesthetic effects. Cats (n = 6) were administered with a continuous stepwise intravenous (i.v.) infusion of DEX or MED on different occasions in a cross-over design. Maintenance infusion rates (mg/kg/min) used were: DEX = 0.25 (MED = 0.50); DEX = 1 (MED = 2) and DEX = 4 (MED = 8) for infusion steps 1, 2 and 3, respectively. Each maintenance infusion lasted at least 50 min and was preceded with a loading dose. There was no significant difference between serum DEX and 0.5 serum MED concentrations at any dose level nor was there a significant difference between serum DEX and the (entire) serum MED concentrations. There was no significant difference between DEX and MED for sedation, analgesia, muscular relaxation and heart and respiratory rates. For both DEX and MED, serum drug concentration and analgesia were dose-dependent and sedation increased until the end of infusion step 2 (dose level 2) and decreased at the end of step 3 (dose level 3). Muscular relaxation was not dose-dependent. We conclude that increasing the blood concentration of DEX or MED beyond a certain level decreases the level of sedation instead of increasing it even though analgesia increases. The rate at which DEX and MED are metabolized in cats may not be the same.     

The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs

Different doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, with or without dexmedetomidine were compared in conscious dogs. Eight animals received either dexmedetomidine (10 μg/kg [D]), MK-467 (250 μg/kg [M250] or dexmedetomidine (10 μg/kg) with increasing doses of MK-467 (250 μg/kg [DM250], 500 μg/kg [DM500] and 750 μg/kg [DM750], respectively). Treatments were given intravenously (i.v.) in a randomized, crossover design with a 14-day washout period. Systemic hemodynamics and arterial blood gas analyses were recorded at baseline and at intervals up to 90 min after drugs administration. Dexmedetomidine alone decreased heart rate, cardiac index and tissue oxygen delivery and increased mean arterial pressure and systemic vascular resistance 5 min after administration. DM250 did not completely prevent these early effects, while DM750 induced a decrease in mean arterial pressure. With DM500, systemic hemodynamics remained stable throughout the observational period. MK-467 alone increased cardiac index and tissue oxygen delivery and had no deleterious adverse effects. No differences in arterial blood gases were observed between treatments that included dexmedetomidine. It was concluded that MK-467 attenuated or prevented dexmedetomidine's systemic hemodynamic effects in a dose-dependent manner when given simultaneously i.v. but had no effect on the pulmonary outcome in conscious dogs. A 50:1 dose ratio (MK-467:dexmedetomidine) induced the least alterations in cardiovascular function.