Effects of epidural anesthesia on microcirculatory blood flow in free medial saphenous fasciocutaneous flaps in dogs.

OBJECTIVE: To assess the effects of epidural anesthesia using lidocaine on microcirculatory blood flow, volume, and velocity in free fasciocutaneous flaps in dogs. Study Design-In vivo experimental investigation. Animal Population-Ten adult dogs weighing 20 to 25 kg. METHODS: A medial saphenous fasciocutaneous free flap was removed and an orthotopic transfer was performed by anastomosing the primary flap vessels back to the medial saphenous vessels. Blood flow (mL(LD)/min/100 g), volume (%volume or tissue hematocrit) and velocity (mm/s) in the flap were recorded throughout the procedure. After epidural anesthesia, blood flow, volume, and velocity values were again recorded. RESULTS: Microcirculatory blood flow, volume, and velocity, as measured by a laser-Doppler flowmeter, failed to reveal any significant changes over time. Immediately after epidural anesthesia, mean arterial pressure was significantly reduced and remained depressed throughout the experimental procedure. CONCLUSIONS: Epidural anesthesia combined with general anesthesia does not improve microcirculatory flow in free flaps in the pelvic limbs of dogs. No significant change in blood flow to the medial saphenous fasciocutaneous free flap occurred after division and anastomosis of the vascular pedicle. CLINICAL RELEVANCE: We recommend that epidural anesthesia with 2% lidocaine be used with caution in dogs undergoing microvascular free-flap transfer.

The clinical, cerebrospinal fluid, and histopathologic effects of epidural ketorolac in dogs.

OBJECTIVE: To evaluate the clinical, cerebrospinal fluid (CSF), and histopathologic effects of epidural ketorolac. STUDY DESIGN: Blinded, randomized, placebo controlled study. ANIMALS: Twenty-two adult mixed breed dogs with 16 treatment and 6 control dogs, weighing 14.4 to 29.8 kg. METHODS: Dogs were anesthetized and epidural catheters were placed at the lumbosacral space. Catheter placement was evaluated fluoroscopically. Ketorolac (0.4 mg/kg) or placebo (5% ethanol) was administered epidurally over a 52-hour period, with 5 injections given at 12-hour intervals. At 1, 2, 4, or 8 hours after the first and last injection of ketorolac, dogs were anesthetized and CSF was obtained. Control dogs had CSF sampled 1 hour after the first and last ethanol injection. Neurologic function and pain responses were evaluated before and during the study. Selected dogs were then killed and necropsies performed. RESULTS: None of the dogs exhibited any clinical or neurologic abnormalities during the study. No statistical difference was noted in pain response or CSF analysis between treatment and control dogs. Gross necropsy revealed gastrointestinal ulceration of varying degrees in all treatment dogs. Histopathologic analysis of the spinal cord and meninges revealed minimal focal leptomeningeal phlebitis in 2 of 8 treatment dogs and minor subdural inflammation in 1 control dog. No changes to the neural structures were noted in any dogs. CONCLUSIONS: Epidural administration of ketorolac did not cause clinical signs, alteration in CSF values, or pathologic changes to the spinal cord when used for short duration. Gastrointestinal ulceration was common when ketorolac was administered epidurally at 0.4 mg/kg every 12 hours for 5 treatments. CLINICAL RELEVANCE: This study documented the neurologic safety of epidural ketorolac in dogs before an efficacy trial can be performed. Gastrointestinal ulceration may limit use to short duration or a single injection.

Fluid therapy and newer blood products.

A fluid therapy plan for a patient is developed prior to surgery and is designed to meet each patient's needs. The volume and type of fluid are dependent on the patient's physical status; the acid-base, fluid, and electrolyte status; the surgical procedure; and the expected losses occurring during the procedure. No one fluid regimen is ideal for all patients. All fluid regimens must be continually re-evaluated. A brief minor surgical procedure in a healthy surgical candidate requires little or no fluid administration. In cases of more extensive surgical procedures involving invasion of the abdomen or chest as well as in cases with trauma and major blood loss, much more volume and a specific balanced replacement fluid are required. Depending on the severity of the surgical case, administration rates of 5 to 15 mL/kg/h or greater of crystalloid may be required to maintain perfusion. These rates are merely guidelines, and resuscitation should continue until the desired end point is reached. Balanced replacement fluids may be used to replace blood loss at a ratio of 3:1 and are added to maintenance and replacement requirements. Blood loss of 20% to 25% of the calculated blood volume or hematocrit values less than 20% are indications for colloids or blood replacement at a ratio of 1:1. The optimal fluid therapy regimen for a patient may involve a combination of crystalloids as well as natural and synthetic colloids, using each type of fluid to obtain and maintain perfusion and oxygenation to the tissues.

Prolonged anesthetic recovery.

Failure to awaken, delayed awakening, and blunted responsiveness following anesthesia constitute a continuum which must be recognized, diagnosed accurately, and responded to appropriately. One must determine whether it is a normal recovery for this animal or a pathological delay. A delayed recovery results in continued depression of many organ systems. The possible etiologic factors, some obvious, others quite obscure, must be considered quickly to provide the patient with the best possible care. Diminished responsiveness is usually the result of a complex interaction between multiple factors. A systematic approach to treatment first begins by ensuring cardiac output, oxygenation, ventilation, and supportive care in all patients. Then consider the potential causes for prolonged recovery and either rule them out or treat them. First consider the potential causes for central nervous system depression. Several commonly encountered medical conditions enhance sensitivity to or decrease the elimination of anesthetic and sedative agents. The astute clinician will be aware of the medical condition and its impact on anesthetic drug effect and elimination to avoid prolonged recoveries.

Effects of Pasteurella haemolytica leukotoxin and lipopolysaccharide on histamine, prostanoid, and leukotriene release by bovine lung parenchyma in vitro.

OBJECTIVE: To identify the effect of Pasteurella haemolytica lipopolysaccharide (LPS) and leukotoxin (LKT) on spontaneous and calcium ionophore-induced histamine and inflammatory mediator release from isolated bovine lung parenchyma. SAMPLE POPULATION: Lungs from 8 healthy cattle. PROCEDURE: Isolated bovine lung parenchyma was incubated in vitro for 2 hours with LKT or LPS, and spontaneous and induced release of inflammatory mediators was determined. RESULTS: LKT and LPS increased spontaneous release of histamine and leukotriene B4. In addition, incubation with LPS increased spontaneous release of prostaglandin E2. Moreover, a differential effect of the 2 toxins on calcium ionophore-induced inflammatory mediator release was observed. LKT specifically primed isolated lung parenchyma to release leukotriene B4 and thromboxane B2 in response to calcium ionophore, whereas LPS did not alter the profile of prostanoids released by bovine lung tissue exposed to calcium ionophore. CONCLUSIONS: Pasteurella haemolytica toxins have a direct effect on bovine lung parenchyma, causing release of inflammatory mediators, which contribute to response to infection. Furthermore, bacterial toxins (LKT in this study) may sensitize tissues to the effects of other irritant stimuli, amplifying the inflammatory response.

A comparison of epidural saline, morphine, and bupivacaine for pain relief after abdominal surgery in goats.

The purpose of this study was to determine the analgesic efficacy of bupivacaine, morphine, or saline (control) when injected epidurally into the lumbosacral epidural space in goats after abdominal surgery. Goats received either bupivacaine (0.5%; 1.5 mg/kg in 0.9% sodium chloride solution), 0.9% sodium chloride solution (0.2 mL/kg), or preservative-free morphine (0.1 mg/kg). Total volume injected into the epidural space was 0.2 mL/kg for all groups. The variables evaluated were times to extubation, sternal recumbency, standing, and eating; heart and respiratory rates; and pain score. Only two of the goats in the bupivacaine group were able to stand on their hindlimbs before 6 hours. Time to eating was shorter for the saline group when compared with the bupivacaine group. Heart rate over all time in the saline group (137 +/- 4 beats/min, mean +/- SEM) was higher than the morphine (125 +/- 3 beats/min) and bupivacaine groups (121 +/- 3 beats/min). Respiratory rate over all time was increased in the saline group (26 +/- 1 breaths/min) compared with the bupivacaine (24 +/- 1 breaths/min) or morphine (24 +/- 1 breaths/min) groups. At 50 minutes, the pain score for the saline group was higher than the morphine group. Pain score over all time in the saline group (1.5 +/- 0.10) was higher than the morphine (1.2 +/- 0.07) and bupivacaine (1.2 +/- 0.04) groups. One goat in the saline group required two intravenous injections of flunixin meglumine for pain.

Effects of alpha 2-adrenergic receptor agonist and antagonist drugs on cholinergic contraction in bovine tracheal smooth muscle in vitro.

Effects of alpha 2-adrenergic receptor stimulation on the cholinergic contractile response of bovine tracheal smooth muscle were studied. To determine the presence and function of alpha2-adrenergic receptors on cholinergic nerves innervating bovine tracheal muscle, effects of 2 alpha 2-adrenoceptor agonists and an antagonist were determined. Muscular contractions were elicited by either electrical field stimulation (EFS) or exogenous acetylcholine (ACH). The contractile response to EFS and exogenous ACH was examined for each tissue. Electrical field stimulation of bovine tracheal smooth muscle caused contractions that were completely abolished by atropine, indicating that predominant excitatory innervation of bovine trachea is cholinergic. The alpha 2 adrenoreceptor agonists clonidine and medetomidine (10(-6) M to 10 (-4) M) concentration-dependently inhibited the contractile response to EFS but not the response to exogenous ACH. Contractions induced by EFS were significantly (P < 0.05) inhibited in clonidine (10(-4) M) - treated tissues at low frequencies (0.01 to 10 Hz), whereas medetomidine (10(-5) M, 10(-4) M) inhibitory effects of the alpha 2-adrenoreceptor agonists clonidine and medetomidine were attenuated by the a2-adrenoreceptor antagonist tolazoline. The alpha 2-agonists used in this study appear to cause prejunctional inhibition of cholinergic nerves, because the smooth muscle contractions elicited by EFS, but not exogenous ACH, were inhibited, compared with controls.

Substance P and calcitonin gene-related peptide-like immunoreactive nerve fibers in lungs from adult equids.

Distribution of pulmonary nerves immunoreactive for either substance P or calcitonin gene-related peptide was determined, using immunohistochemical methods on healthy lungs from adult equids. The overall patterns of distribution of substance P and calcitonin gene-related peptide-like immunoreactivity were similar. Distribution of immunoreactive nerves was not uniform throughout the lungs; nerve fibers immunoreactive for these peptides were more frequently observed near the hilus of the lung than in the caudal lobes or in the periphery of the lung. Nerve fibers immunoreactive for substance P or calcitonin gene-related peptide were most abundant in the lamina propria of the trachea and larger airways, particularly within and directly below the airway epithelium; they were also frequently associated with bronchial and pulmonary vessels. Presence of nerve fibers immunoreactive for substance P and calcitonin gene-related peptide in peribronchial neural ganglia indicated that these sensory nerves may modulate parasympathetic regulation of pulmonary function. Nerve fibers immunoreactive for substance P and calcitonin gene-related peptide were, therefore, well placed to detect inhaled agents and to contribute to the pulmonary response to irritants and pathogens.

Adrenergic and peptidergic innervation of the trachealis muscle in the normal horse: a preliminary report.

The tone of respiratory smooth muscle is largely determined by the input from autonomic nerves. The distribution of adrenergic and selected nonadrenergic, non-cholinergic (NANC) nerves in the normal equine trachealis muscle was investigated using immunohistochemistry. The smooth muscle of the trachealis was found to contain numerous nerves immunoreactive for an enzymatic marker of adrenergic nerves, as well as many nerves immunoreactive for a putative NANC neurotransmitter, peptide histidine isoleucine, a potent bronchodilator. The tissue surrounding the respiratory smooth muscle contained numerous nerves immunoreactive for the neuropeptides substance P and calcitonin gene-related peptide, which can cause marked vasodilation and bronchoconstriction. The complex innervation of the equine trachea should be kept in mind when interpreting the results of physiological experiments.

Airborne dust and aeroallergen concentration in a horse stable under two different management systems.

Airborne dust concentration (ADC) was measured in 2 different horse management systems using an Andersen cascade impactor in the box-stall, and a personal Marple cascade impactor attached to the halter to measure ADC in the breathing zone. The levels of aeroallergens implicated in chronic obstructive pulmonary disease were measured by radioallergosorbent-inhibition immunoassay. A conventional management system (System C) utilising hay feed and straw bedding, and a recommended environment (System R) utilising wood shaving bedding and a complete pelleted diet were studied. In the stall, total and respirable ADC (geometric mean) were significantly higher in System C (2.55 mg/m3; 0.44 mg/m3, respectively) than in System R (0.70 mg/m3; 0.20 mg/m3, respectively). In System C, the total and respirable ADC in the breathing zone (17.51 mg/m3; 9.28 mg/m3) were much higher than in the stall, but values in both regions were similar in System R (0.52 mg/m3; 0.30 mg/m3). Major aeroallergens were significantly higher in System C than in System R: Micropolyspora faeni (1423 ng/m3 and 705 ng/m3), Aspergillus fumigatus (1823 ng/m3 and 748 ng/m3), and mite allergens (1420 ng/m3 and 761 ng/m3). Measurement of ADC with personal samplers indicates that the very high inhalation challenge in the breathing zone is not reflected in measurements of stall air quality. When compared with System C, System R produced only 3% of the respirable dust burden in the breathing zone and a decreased aeroallergen challenge.

Distribution of dopamine beta-hydroxylase and neuropeptide Y-immunoreactive nerves in healthy equine lungs.

Immunohistochemical methods were used to determine the distribution of pulmonary nerves containing either an enzymatic marker of adrenergic nerves, dopamine beta hydroxylase, or the putative neurotransmitter neuropeptide Y in 7 equids with healthy lungs. Nerves immunoreactive for these substances were found on airway smooth muscle in nearly all the samples of healthy equine lung examined. These nerves were generally more numerous in the larger airways but could be detected even in noncartilaginous bronchioles. Pulmonary and bronchial vessels also contained numerous immunoreactive nerves. On the basis of these findings, we suggest that dopamine beta-hydroxylase- and neuropeptide Y-immunoreactive nerves may be involved in the regulation of airway and vascular diameter in equids.

Flunixin meglumine blocks frusemide-induced bronchodilation in horses with chronic obstructive pulmonary disease.

Six horses that developed acute airway obstruction (heaves) when housed in a barn and fed poor-quality hay were studied. Airway obstruction was verified by a maximal change in pleural pressure during tidal breathing (delta Pplmax) of at least 15 cmH2O. Frusemide (1.0 mg/kg bwt) or an equivalent volume of vehicle was then administered intravenously (iv) and lung function was measured 15, 30, 60, 120, 180, 240 and 300 mins after drug administration. The effect of frusemide on lung function was also studied after treatment of horses with the cyclooxygenase inhibitor flunixin meglumine (1.1 mg/kg every 8 h for 2 days before the experiment). Frusemide significantly reduced the delta Pplmax beginning 15 mins after drug administration. This effect persisted for 5 h. The reduction in delta Pplmax was due partly to an increase in dynamic compliance and partly to a decrease in pulmonary resistance. Tidal volume and respiratory frequency were unaffected by frusemide. Vehicle had no effect on lung function. Flunixin meglumine abolished the effect of frusemide on airway calibre but did not prevent diuresis. These results indicate that the effect of frusemide on airways of horses with heaves persists for at least 5 h, is mediated through prostanoids, and is not a result of diuresis.

Exogenous but not endogenous PGE2 modulates pony tracheal smooth muscle contractions.

The modulatory role of prostaglandin E2 (PGE2) was examined in pony tracheal smooth muscle strips. Although exogenous PGE2 inhibited the contractile response to both electrical field stimulation (EFS) and acetylcholine (ACh) in a dose-dependent manner, the concentration required to inhibit the response to EFS (10 nM) was less than that required to inhibit the response to ACh (0.1 microM). Cyclooxygenase inhibition with aspirin or meclofenamate had no effect on either the response to EFS or to ACh even though PGE2 production was inhibited. Our results demonstrate that in ponies as in other species, exogenous PGE2 can inhibit the airway smooth muscle's response to EFS and ACh. However, the failure of cyclooxygenase inhibition to alter the response to EFS and ACh suggests that endogenous prostanoids do not exert a significant modulatory effect on pony tracheal smooth muscle in vitro.

Effects of xylazine on airway function in ponies with recurrent airway obstruction.

The effect of IV administration of the alpha 2-adrenoceptor agonist xylazine hydrochloride (0.5 mg/kg of body weight) was examined in ponies with recurrent obstructive pulmonary disease, commonly called heaves. Six ponies with the disease (principals) were studied during clinical remission and during an acute attack of airway obstruction precipitated by stabling and feeding of dusty hay. Six control ponies were also studied. In principal ponies with airway obstruction, xylazine administration significantly (P < 0.05) decreased pulmonary resistance and increased dynamic compliance, but did not affect PaO2 or PaCO2. The alpha 2-antagonist yohimbine blocked the pulmonary effects of xylazine. Administration of saline solution was without effect in both groups of ponies at all periods and xylazine did not have effect in controls or in principals in clinical remission.

Decreased airway mucosal prostaglandin E2 production during airway obstruction in an animal model of asthma.

Heaves is a respiratory disorder of horses and ponies characterized by bouts of acute airway obstruction and airway hyperresponsiveness. We measured prostaglandin E2 (PGE2) and 15-hydroxyeicosatetraenoic acid (15-HETE) production in vitro in tracheal epithelium obtained from six affected horses at the time of acute airway obstruction as compared with six matched control horses. Strips of epithelium and subepithelial tissue were prepared and stimulated with A23187, histamine, and bradykinin. The PGE2 and 15-HETE in media from strips was quantitated by radioimmunoassay. 15-HETE above the limits of accurate detection was found in epithelial strips of only two principal animals and in none of the control horses, and the amount of 15-HETE was not increased when strips were stimulated. Epithelial strips from affected horses tended to produce less PGE2 than did strips from control horses, and there was a significant correlation between epithelial PGE2 production and the time taken for affected animals to develop airway obstruction. Subepithelial tissue strips from control horses produced significantly more PGE2 in response to A23187 and bradykinin than did strips from affected horses. We conclude that equine tracheal epithelium is not a significant source of 15-HETE. Airway mucosal PGE2 production is reduced in horses with heaves, which suggests that a relative decrease in this bronchorelaxant substance may be a factor in the pathogenesis of this model of asthma.

Increased pulmonary production of immunoreactive 15-hydroxyeicosatetraenoic acid in an animal model of asthma.

Airway obstruction and hyperreactivity are characteristics of human asthma and of "heaves," a naturally occurring respiratory disorder of horses and ponies. We measured pulmonary function and plasma immunoreactive 15-hydroxyeicosatetraenoic acid (i15-HETE) concentrations in simultaneously collected carotid artery and right ventricle blood samples in five affected ponies and their age- and gender-matched control ponies. Measurements and sampling were performed before (Period A), during (Period B), and following recovery from (Period C) acute airway obstruction precipitated by housing ponies in a barn and exposing them to hay dust. Pulmonary resistance increased significantly, and dynamic compliance and PaO2 decreased significantly in affected ponies at Period B. Plasma i15-HETE concentrations were greater in carotid artery samples compared with right ventricle samples in affected ponies at each measurement period, suggesting that the lung was a source of i15-HETE. Carotid artery i15-HETE concentrations were significantly greater in affected ponies than in control ponies and increased at Period B. There was a significant negative correlation between changes in plasma i15-HETE and changes in dynamic compliance between measurement Periods A and B. We conclude that the lung is a source of i15-HETE in ponies with heaves, that these ponies produce greater quantities of i15-HETE than control ponies, and that exposing affected ponies to a barn environment produces acute airway obstruction and increased plasma concentrations of i15-HETE.

In vitro responses of distal airways in horses with recurrent airway obstruction.

Distal airway segments (ID, 3 to 4 mm; length, 5 mm) from 2 groups of horses were isolated and suspended in tissue baths filled with Krebs solution, aerated with 5% CO2 in oxygen and maintained at 37 degrees C. Responses to exogenous acetylcholine, isoproterenol, or electrical field stimulation were compared. Control horses (n = 30) had no history of recurrent airway obstruction, whereas principal horses (n = 15) had recurrent airway obstruction and were studied during an acute episode of airway obstruction. Although the distal airways contracted in response to the cumulative half-logarithmic addition of acetylcholine (10(-10) M to 10(-3) M) in both groups, bronchi obtained from principals were less sensitive to acetylcholine than were bronchi obtained from controls. Tetdrodotoxin-sensitive electrical field stimulation-induced contractions were observed in both groups of airways, but the tension achieved in principal bronchi was less than in controls. All electrical field stimulation-induced contractions were abolished by atropine, indicating that the only excitatory innervation of equine distal airway is through the parasympathetic system. To examine the effect of isoproterenol and determine inhibitory innervation, bronchi were precontracted with histamine. Electrical field stimulation did not cause relaxation of precontracted bronchi in either group, thus indicating that distal airways lack inhibitory innervation. Isoproterenol caused similar, dose-dependent relaxation in both groups.

In vitro responses of airway smooth muscle from horses with recurrent airway obstruction.

The in vitro contractile and relaxant responses of tracheal smooth muscle strips (TSM) and third-generation bronchi (3B) of control horses and horses with recurrent obstructive disease (heaves) were compared. Acetylcholine (ACH) sensitivity of the diseased tissues was less than that of tissues from control horses, especially at the level of the third generation (EC50 controls 15 +/- 11 microM vs 81 +/- 17 microM for heaveys). Despite tracheal and bronchial hyporesponsiveness to ACH, these tissues from heavey horses were hyperresponsive to EFS. The inhibitory effect of isoproterenol and electrical field stimulation (EFS) was examined in histamine-precontracted airways pretreated with atropine (1 microM), indomethacin (3 microM), and phentolamine (1 microM). Precontracted tissues of both groups at both levels of airway demonstrated similar concentration-dependent relaxation in response to cumulative doses of isoproterenol (0.1 nM to 0.1 mM). EFS of precontracted tissues caused 80-90% relaxation in the TSM in both groups and 21% relaxation in 3B of the control group. Electrical field stimulation relaxation of precontracted tissues was not seen in the diseased 3B, suggesting a lack of inhibitory innervation. EFS of similarly precontracted tissues plus propranolol (1 microM) resulted in only 46% relaxation in the TSM of both groups but did not reduce the EFS relaxation of control 3B, suggesting the presence of both sympathetic and nonadrenergic noncholinergic nerves (NANC) in the trachea but only NANC in the 3B.

Effects of furosemide on ponies with recurrent airway obstruction.

The effect of aerosol and intravenous administrations of furosemide was examined in ponies with recurrent obstructive pulmonary disease, commonly called 'heaves'. This recurrent airway disease bears many similarities to human asthma. Six ponies with the disease (principal animals) were studied during clinical remission and during an acute attack of airway obstruction precipitated by stabling and feeding dusty hay. Six control animals were also studied. Furosemide (1.0 mg/kg) or vehicle was administered by aerosol in the first study, and intravenously in a second study. In principal ponies with airway obstruction, furosemide administration significantly decreased pulmonary resistance and increased dynamic compliance, but had no effect on PaO2 or PaCO2. The time course and magnitude of lung function changes were similar following aerosol or intravenous drug administration. Vehicle was without effect in both groups of animals at all time periods and furosemide had no effect in controls or in principals in clinical remission.