Wayne N. McDonell

Epidural morphine reduces halothane MAC in the dog.

Morphine, 0.1 mg · kg−1 was administered epidurally on two different occasions to ten dogs to determine the effect of two different volumes of saline dilution, 0.13 and 0.26 ml · kg−1, on the minimum alveolar concentration (MAC) of halothane as determined by subcutaneous electrical current applied to the fore and hind limbs in a random order. Following MAC determination with halothane alone, epidural morphine was administered and MAC was redetermined. Epidural morphine significantly reduced, P < 0.001, the MAC of halothane for fore and hind legs in both volume groups; from 1.04 ± 0.038 to 0.68 ± 0.034 and 0.60 ± 0.017 for fore and hind limbs, respectively, in the large volume group, and from 0.96 ± 0.038 to 0.66 ± 0.088 and 0.60 ± 0.030 for fore and hind limbs, respectively, in the small volume group. The reduction in MAC was significantly greater, P < 0.025, in the hind limb. This study indicates that epidural morphine reduces the halothane requirements in the dog in a segmental manner. The volume of administration was not shown to be critical. Epidural morphine, 0.1 mg · kg−1, diluted in 0.13 to 0.26 ml · kg−1 saline produces significant analgesia in the dog as far forward as the fore limb and will reduce the halothane requirement to permit surgery.RésuméNous avons observé en deux fois l’effet du volume de dilution (0,13 et 0,26 ml · kg−1 ) d’une dose de morphine péridurale (0,1 mg · kg−1) sur la modification de la concentration alvéolaire minimale (MAC) de l’halothane de dix chiens, mesurée par application d’un courant électrique sous-cutané aux pattes avant et arrière, en ordre variable. Peu importe le volume de dilution, le MAC diminuait de façon significative (P < 0,001) apr’es l’injection de morphine péridurale et ce, pour les pattes avant et arrière. Respectivement pour les membres antérieurs et postérieurs, le MAC passait de 1,04 ± 0,038 à 0,68 ± 0,034 et 0,60 ± 0,017 avec le grand volume de dilution et de 0,96 ± 0,038 à 0,66 ± 0,088 et 0,60 ± 0,030 avec le petit volume. En fait, la baisse du MAC était plus marquée aux membres postérieurs (P < 0,025) et cela semble indiquer un effet segmentaire de la morphine péridurale. Cependant, qu’on utilise 0,13 ou 0,26 ml · kg−1 de salin pour diluer 0,1 mg · kg−1 de morphine péridurale importe peu chez le chien, car la réduction du MAC de l’halothane et l’atteinte d’une analgésie englobant les membres antérieurs est la même.

Effects of a peripheral α2 adrenergic-receptor antagonist on the hemodynamic changes induced by medetomidine administration in conscious dogs

OBJECTIVE To evaluate the effects of administration of a peripheral alpha(2)-adrenergic receptor antagonist (L-659,066), with and without concurrent administration of glycopyrrolate, on cardiopulmonary effects of medetomidine administration in dogs. ANIMALS 6 healthy adult dogs. PROCEDURES Dogs received saline (0.9% NaCl) solution (saline group), L-659,066 (group L), or L-659,066 with glycopyrrolate (group LG). These pretreatments were followed 10 minutes later by administration of medetomidine in a randomized crossover study. Hemodynamic measurements and arterial and mixed-venous blood samples for blood gas analysis were obtained prior to pretreatment, 5 minutes after pretreatment, and after medetomidine administration at intervals up to 60 minutes. RESULTS After pretreatment in the L and LG groups, heart rate, cardiac index, and partial pressure of oxygen in mixed-venous blood (PvO2) values were higher than those in the saline group. After medetomidine administration, heart rate, cardiac index, and PvO2 were higher and systemic vascular resistance, mean arterial blood pressure, and central venous pressure were lower in the L and LG groups than in the saline group. When the L and LG groups were compared, heart rate was greater at 5 minutes after medetomidine administration, mean arterial blood pressure was greater at 5 and 15 minutes after medetomidine administration, and central venous pressure was lower during the 60-minute period after medetomidine administration in the LG group. CONCLUSIONS AND CLINICAL RELEVANCE Administration of L-659,066 prior to administration of medetomidine reduced medetomidine-induced cardiovascular changes in healthy dogs. No advantage was detected with concurrent administration of L-659,066 and glycopyrrolate.

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 Students 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 and sedative effects of the peripheral α2-adrenoceptor antagonist MK 0467 administered intravenously or intramuscularly concurrently with medetomidine in dogs

OBJECTIVE To evaluate the cardiopulmonary and sedative effects of the peripheral α(2)-adrenoceptor antagonist MK 0467 when administered IM or IV concurrently with medetomidine in dogs. ANIMALS 8 adult dogs. PROCEDURES Dogs received 20 μg of medetomidine/kg, IM, alone or concurrently with MK 0467 (0.4 mg/kg, IM), and 10 μg of medetomidine/kg, IV, alone or concurrently with MK 0467 (0.2 mg/kg, IV), in a randomized crossover study. Sedation characteristics were scored and hemodynamic measurements and arterial and mixed-venous blood samples for blood gas analysis were obtained before (time 0; baseline) and for 90 minutes after treatment. RESULTS Heart rate (HR), mixed-venous partial pressure of oxygen (Pvo(2)), and cardiac index (CI) were significantly lower and mean arterial blood pressure (MAP), systemic vascular resistance (SVR), and oxygen extraction ratio (ER) were significantly higher after administration of medetomidine IM or IV, compared with baseline values. Administration of medetomidine and MK 0467 IM caused a significantly higher heart rate, CI, and Pvo(2) and significantly lower MAP, SVR, and ER for 60 to 90 minutes than did IM administration of medetomidine alone. Administration of medetomidine and MK 0467 IV caused a significantly higher CI and Pvo(2) and significantly lower MAP, SVR, and ER for 45 to 90 minutes than did IV administration of medetomidine alone. There was no significant difference in sedation scores among treatments. CONCLUSIONS AND CLINICAL RELEVANCE In dogs, MK 0467 administered concurrently with medetomidine IV or IM reduced the cardiovascular effects of medetomidine but had no detectable effect on sedation scores.

Cardiopulmonary effects of anesthetic induction with thiopental, propofol, or a combination of ketamine hydrochloride and diazepam in dogs sedated with a combination of medetomidine and hydromorphone.

OBJECTIVE To evaluate the cardiopulmonary effects of anesthetic induction with thiopental, propofol, or ketamine hydrochloride and diazepam in dogs sedated with medetomidine and hydromorphone. ANIMALS 6 healthy adult dogs. PROCEDURES Dogs received 3 induction regimens in a randomized crossover study. Twenty minutes after sedation with medetomidine (10 microg/kg, IV) and hydromorphone (0.05 mg/kg, IV), anesthesia was induced with ketamine-diazepam, propofol, or thiopental and then maintained with isoflurane in oxygen. Measurements were obtained prior to sedation (baseline), 10 minutes after administration of preanesthetic medications, after induction before receiving oxygen, and after the start of isoflurane-oxygen administration. RESULTS Doses required for induction were 1.25 mg of ketamine/kg with 0.0625 mg of diazepam/kg, 1 mg of propofol/kg, and 2.5 mg of thiopental/kg. After administration of preanesthetic medications, heart rate (HR), cardiac index, and PaO(2) values were significantly lower and mean arterial blood pressure, central venous pressure, and PaCO(2) values were significantly higher than baseline values for all regimens. After induction of anesthesia, compared with postsedation values, HR was greater for ketamine-diazepam and thiopental regimens, whereas PaCO(2) tension was greater and stroke index values were lower for all regimens. After induction, PaO(2) values were significantly lower and HR and cardiac index values significantly higher for the ketamine-diazepam regimen, compared with values for the propofol and thiopental regimens. CONCLUSIONS AND CLINICAL RELEVANCE Medetomidine and hydromorphone caused dramatic hemodynamic alterations, and at the doses used, the 3 induction regimens did not induce important additional cardiovascular alterations. However, administration of supplemental oxygen is recommended.

Cardiopulmonary effects of intravenous fentanyl infusion in dogs during isoflurane anesthesia and with concurrent acepromazine or dexmedetomidine administration during anesthetic recovery

OBJECTIVE To evaluate the cardiopulmonary effects of IV fentanyl administration in dogs during isoflurane anesthesia and during anesthetic recovery with or without dexmedetomidine or acepromazine. ANIMALS 7 sexually intact male purpose-bred hound-type dogs aged 11 to 12 months. PROCEDURES Dogs received a loading dose of fentanyl (5 μg/kg, IV) followed by an IV infusion (5 μg/kg/h) for 120 minutes while anesthetized with isoflurane and for an additional 60 minutes after anesthesia was discontinued. Dogs were randomly assigned in a crossover design to receive dexmedetomidine (2.5 μg/kg), acepromazine (0.05 mg/kg), or saline (0.9% NaCl) solution (1 mL) IV after anesthesia ceased. Cardiopulmonary data were obtained during anesthesia and for 90 minutes after treatment administration during anesthetic recovery. RESULTS Concurrent administration of fentanyl and isoflurane resulted in significant decreases in mean arterial blood pressure, heart rate, and cardiac index and a significant increase in Paco2. All but Paco2 returned to pretreatment values before isoflurane anesthesia was discontinued. During recovery, dexmedetomidine administration resulted in significant decreases in heart rate, cardiac index, and mixed venous oxygen tension and a significant increase in arterial blood pressure, compared with values for saline solution and acepromazine treatments. Acepromazine administration resulted in significantly lower blood pressure and higher cardiac index and Po2 in mixed venous blood than did the other treatments. Dexmedetomidine treatment resulted in significantly lower values for Pao2 and arterial pH and higher Paco2 values than both other treatments. CONCLUSIONS AND CLINICAL RELEVANCE Fentanyl resulted in transient pronounced cardiorespiratory effects when administered during isoflurane anesthesia. During anesthetic recovery, when administered concurrently with an IV fentanyl infusion, dexmedetomidine resulted in evidence of cardiopulmonary compromise and acepromazine transiently improved cardiopulmonary performance.

Effects of muscarinic receptor antagonists on acetylcholine-induced contractions of jejunal smooth muscle in horses.

This study investigated the effects of a muscarinic type 1 (M(1)), 2 (M(2)), and 3 (M(3)) antagonists (4-DAMP, pirenzepine, and methoctramine, respectively) on acetylcholine (Ach)-induced contractions of longitudinal jejunal muscle strips of horses. Strips were irrigated with Krebs-Henseleit solution gassed with 95% O(2) and 5% CO(2), and the developed tension in response to Ach was recorded before and after incubation with increasing concentrations of 4-DAMP (10(-8)-10(-6) M), pirenzepine (10(-6)-10(-4) M), and methoctramine (10(-5)-10(-3) M). When competitive antagonism was characterized, the affinity constant (pA(2)) was calculated by Schild plots. A parallel rightward shift in the concentration-response curves was observed after 4-DAMP and pirenzepine. Methoctramine presented a dual effect on the concentration-response curves: lower concentrations induced a parallel rightward shift without altering the maximum intensity of contraction (E(max)), while the highest concentration increased slope of the concentration-response curve and increased E(max). The pA(2) for 4-DAMP and pirenzepine was 9.18 and 7.13, respectively. Acetylcholine-induced contractions of longitudinal jejunal smooth muscle are mediated mainly via M(3) receptors. The complex role of M(2) receptors in jejunal smooth muscle contractions was evident because methoctramine potentiated the contractile response to higher doses of Ach.

Effects of hypercapnia, hypocapnia, and hyperoxemia on blood oxygenation level-dependent signal intensity determined by use of susceptibility-weighted magnetic resonance imaging in isoflurane-anesthetized dogs.

OBJECTIVE To assess the effects of alterations in PaCO(2) and PaO(2) on blood oxygenation level-dependent (BOLD) signal intensity determined by use of susceptibility-weighted magnetic resonance imaging in brains of isoflurane-anesthetized dogs. ANIMALS 6 healthy dogs. PROCEDURES In each dog, anesthesia was induced with propofol (6 to 8 mg/kg, IV) and maintained with isoflurane (1.7%) and atracurium (0.2 mg/kg, IV, q 30 min). During 1 magnetic resonance imaging session in each dog, targeted values of PaCO(2) (20, 40, or 80 mm Hg) and PaO(2) (100 or 500 mm Hg) were combined to establish 6 experimental conditions, including a control condition (PaCO(2), 40 mm Hg; PaO(2), 100 mm Hg). Dogs were randomly assigned to different sequences of conditions. Each condition was established for a period of >or= 5 minutes before susceptibility-weighted imaging was performed. Signal intensity was measured in 6 regions of interest in the brain, and data were analyzed by use of an ANCOVA and post hoc Tukey-Kramer adjustments. RESULTS Compared with control condition findings, BOLD signal intensity did not differ significantly in any region of interest. However, signal intensities in the thalamus and diencephalic gray matter decreased significantly during both hypocapnic conditions, compared with all other conditions except for the control condition. CONCLUSIONS AND CLINICAL RELEVANCE In isoflurane-anesthetized dogs, certain regions of gray matter appeared to have greater cerebrovascular responses to changes in PaCO(2) and PaO(2) than did others. Both PaO(2) and PaCO(2) should be controlled during magnetic resonance imaging procedures that involve BOLD signaling and taken into account when interpreting findings.

Platelet alterations in porcine stress syndrome

Platelets in blood collected from pigs identified as normal (21) or stress susceptible (25) on the basis of their response to halothane challenge, were subjected to electron microscopic examination in order to test whether the ultrastructural features of stress susceptible pigs exhibit any deviation from those of normal. The most striking feature of the platelets from stress susceptible pigs was the extent of dilatation of the open canalicular system (OCS). The difference in platelet morphology between normal and stress susceptible pigs was consistent regardless of the anticoagulants used for blood collection indicating that the platelet alteration may be an inherent component of the porcine stress syndrome.

Oxygen cost of ventilation in the resting horse

The purpose of this study was to develop a technique to measure the oxygen cost of ventilation and the values of ventilatory parameters in seven normal horses rebreathing carbon dioxide (CO2). All the horses responded to increased inspiratory levels of CO2 by increasing their tidal volume (VT) and frequency of breathing (Vf). The mean (SE) oxygen cost litre-1 of ventilation, measured at rates of ventilation greater than 200 litres min-1 was 1.7 (0.04) ml litre-1, similar to that of normal human subjects ventilating submaximally. It was concluded that the CO2 rebreathing test is a practical, non-invasive means of measuring the oxygen cost of breathing and the ventilatory response to CO2 in horses.