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Biomedical subjects

E P Steffey

Publications and source records attributed to E P Steffey.

At least 19 recordsLinked to original sources

Actions of isoflurane and halothane in pregnant mares.

Eighteen healthy, pregnant mares scheduled for laparotomy and uterine manipulation were randomly allotted to 2 equal groups. After IV administration of xylazine hydrochloride and thiamylal sodium, general anesthesia was maintained with halothane (HALO) or isoflurane (ISO) in oxygen. Results of cardiovascular measurements were similar with both inhalant anesthetics; mean arterial blood pressure was 79 and 82 mm of Hg with HALO and ISO, respectively. Respiratory rate decreased most with ISO (mean frequency was 4 and 9 breaths/min with ISO and HALO, respectively). Partial pressure of arterial CO2 was increased similarly with HALO and ISO. Partial pressure of arterial O2 varied greatly among mares and decreased with duration of use of both anesthetics. Recovery time from anesthesia was significantly (P < 0.05) shorter after use of ISO vs HALO. Minor superficial injuries were associated with recovery from both anesthetics (in 5 mares with ISO and in 1 mare with HALO). Physical signs of postanesthetic myopathy or vital-organ dysfunction were not associated with either agent.

Anesthesia, Inhalation

Other new and potentially useful inhalational anesthetics.

Sevoflurane and desflurane are volatile inhaled anesthetics that are currently being investigated as possible improvements for the anesthetic management of human patients. Information to date suggests these agents have several advantages over existing clinical agents. For example, the blood/gas partition coefficient for both agents is lower than that of other halogenated anesthetics. Consistent with this physical characteristic is a more rapid induction of and emergence from anesthesia. Both cause a dose-related depression of cardiopulmonary function, which is comparable to isoflurane. Results of studies to date favor desflurane over sevoflurane because it is less soluble in blood, is stable in soda lime, is biodegraded the least of any volatile anesthetic, and is not toxic.

Anesthesia, Inhalation

Pulmonary blood flow distribution in anesthetized ponies.

Results of recent investigations in humans and dogs indicate that gravity-independent factors may be important in determining the distribution of pulmonary blood flow. To further evaluate the role of gravity-independent factors, pulmonary blood flow distribution was examined using 15-microns radionuclide-labeled microspheres in five prone ponies over 5 h of pentobarbital sodium anesthesia. The ponies were killed, and the lungs were excised and dried by air inflation (pressure 45 cmH2O). The dry lungs were cut into transverse slices 1-2 cm thick along the dorsal-ventral axis, parallel to gravity. Radioactivity of pieces cut from alternate slices was measured with a gamma well counter. The main finding was a preferential distribution of pulmonary blood flow to dorsal-caudal regions and higher flow in the center of each lung slice when compared with the slice periphery. Flow was lowest in cranial and ventral areas. Differences of +/- 2 SD were observed between core and peripheral blood flow. No medial-lateral differences were found. Pulmonary blood flow distribution did not change over 5 h of anesthesia, and the basic flow pattern was not different in the left vs. right lung. These results suggest that in the intact prone mechanically ventilated pony (inspired O2 fraction greater than or equal to 0.95) factors other than gravity are primary determinants of pulmonary blood flow.

Anesthesia

Hemodynamic and respiratory responses to variable arterial partial pressure of oxygen in halothane-anesthetized horses during spontaneous and controlled ventilation.

Cardiovascular and respiratory responses to variable PaO2 were measured in 6 horses anesthetized only with halothane during spontaneous (SV) and controlled (CV) ventilation. The minimal alveolar concentration (MAC) for halothane in oxygen was determined in each spontaneously breathing horse prior to establishing PaO2 study conditions--mean +/- SEM, 0.95 +/- 0.03 vol%. The PaO2 conditions of > 250, 120, 80, and 50 mm of Hg were studied in each horse anesthetized at 1.2 MAC of halothane and positioned in left lateral recumbency. In response to a decrease in PaO2, total peripheral resistance and systolic and diastolic arterial blood pressure decreased (P < 0.05) during SV. Cardiac output tended to increase because heart rate increased (P < 0.05) during these same conditions. During CV, cardiovascular function was usually less than it was at comparable PaO2 during SV (P < 0.05). Heart rate, cardiac output, and left ventricular work increased (P < 0.05) in response to a decrease in PaO2, whereas total peripheral resistance decreased (P < 0.05). During SV, cardiac output and stroke volume increased and arterial blood pressure and total peripheral resistance decreased with duration of anesthesia at PaO2 > 250 mm of Hg. During SV, minute expired volume increased (P < 0.05) because respiratory frequency tended to increase as PaO2 decreased. Decrease in PaCO2 (P < 0.05) also accompanied these respiratory changes. Although oxygen utilization was nearly constant over all treatment periods, oxygen delivery decreased (P < 0.05) with decrease in PaO2, and was less (P < 0.05) during CV, compared with SV, for comparable PaO2 values.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia

Unilateral hypoxic pulmonary vasoconstriction in the dog, pony and miniature swine.

The hypoxic pulmonary vasoconstrictor response to unilateral hypoxia was analyzed in pentobarbital anesthetized dogs (n = 5), miniature swine (n = 5), and ponies (n = 5). The left and right lungs (LL, RL) were separately ventilated with the LL exposed to inspired oxygen concentrations (CIO2) of 100%, 12%, 8% or 4%, while the RL always received a CIO2 = 100%. Pulmonary blood flow distribution was measured using 15 microns radioactive microspheres. LL PAO2, and percent pulmonary blood flow diversion (%FD) were calculated at each CIO2. At CIO2 of 4% there were significant differences (P greater than or equal to 0.05) between the %FD responses of each species (mean +/- S.E.): the %FDswine (95.1 +/- 1.3) greater than %FDpony (76.0 +/- 4.6) greater than %FDdog (50.1 +/- 9.4). For all species, the %FD was inversely related to the level of regional hypoxia, but there were marked species differences in the magnitude and sensitivity of hypoxic pulmonary vasoconstriction with the swine being the strongest responder, the pony intermediate, and the dog the weakest responder.

Animals

Clinical investigations of halothane and isoflurane for induction and maintenance of foal anesthesia.

Fifty-eight foals were divided into two groups for study of aspects of the clinical anesthetic management of foals and to characterize effects of halothane (n = 30) and isoflurane (n = 28) in foals. There were no significant differences (P greater than 0.05) in the demographics of the two groups. Results of hemograms and biochemical analysis of venous blood samples before and after anesthesia were either not influenced or only mildly (clinically unimportant) affected by either agent. Like adult horses, foals have an increased PaCO2 when anesthetized with inhaled anesthetics. We could detect no difference in the magnitude of increase in PaCO2 with either anesthetic. Anesthetic induction and recovery was most rapid with isoflurane. The quality of induction and recovery was similarly acceptable with either agent. Heart rate during isoflurane was not significantly different from conscious conditions but during halothane, heart rate was significantly less than control except at 91-120 min when statistical significance was not detected. These results support the clinical impression that foals can be safely and reliably anesthetized with either agent.

Anesthesia, Inhalation

Cardiovascular, respiratory, and analgesic effects of fentanyl in unanesthetized rhesus monkeys.

To determine the suitability of the rhesus monkey as a model for investigation of opioids, we examined the analgesic, respiratory, and cardiovascular effects of fentanyl in six adult male rhesus monkeys. Fentanyl was administered in sequential bolus injections of 2, 4, 16, 64, and 128 micrograms/kg, with 10 min between each dose. Arterial plasma fentanyl concentrations and blood gas tensions were measured 3 and 9 min after each dose and 1, 2, 5, 20, 60, and 120 min after the final dose. At the same time periods, mean systemic arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures, cardiac output, heart rate, and respiratory rate were measured. Analgesia was quantified as the time required for tail withdrawal from a standardized noxious stimulus. Tail latency response time increased significantly after the 4-microgram/kg dose (plasma fentanyl concentration = 2.7 +/- 0.9 ng/mL). Maximum tail latency response time was attained after the 64-micrograms/kg dose (43.4 +/- 26.0 ng/mL). Respiratory rate decreased significantly after the 2-microgram/kg dose, and PaCO2 increased significantly after the 4-microgram/kg dose. All animals became apneic, requiring tracheal intubation and controlled ventilation, after the 64-micrograms/kg dose. Also, mean arterial pressure and cardiac output decreased significantly after the 64-micrograms/kg dose. There were no other significant cardiovascular changes. Peak plasma fentanyl concentration after the 128-micrograms/kg dose was 117.0 +/- 49.6 ng/mL. It appears that plasma concentrations of approximately 40 ng/mL are sufficient to reach the full cardiovascular, respiratory, and analgesic effects of fentanyl in the rhesus monkey. Significant respiratory and analgesic effects are evident at concentrations as low as 3 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia

Effects of five hours of constant 1.2 MAC halothane in sternally recumbent, spontaneously breathing horses.

Circulatory and respiratory effects of five h of constant 1.06 per cent alveolar halothane in oxygen were identified in eight healthy horses, which breathed spontaneously, were otherwise unmedicated and positioned in sternal recumbency. Only a few important significant (P less than 0.05) changes occurred with time. Total peripheral resistance was about 15 per cent lower after two hours of constant dose halothane than after 30 mins of constant dose (P less than 0.05) and accounted for the significant 10 per cent reduction in mean carotid arterial blood pressure. By 5 h, the reduction in resistance and arterial blood pressure was 20 and 25 per cent respectively. Heart rate increased progressively with time and the increase became significant at 5 h (15 per cent increase). However, the heart rate change was not large enough to alter cardiac output. There were no major time-related changes in PaO2 or PaCO2. Three of four horses recovered from anaesthesia had markedly elevated serum creatine kinase levels and clinical signs of severe post anaesthetic myopathy.

Acid-Base Equilibrium

Effect of body posture on cardiopulmonary function in horses during five hours of constant-dose halothane anesthesia.

Cardiovascular and respiratory functions were serially characterized in 7 healthy, spontaneously breathing, adult horses (from which food had been withheld) during 5 hours of constant 1.06% alveolar halothane (end-expired halothane concentration of 1.06%; equivalent to 1.2 times the minimal alveolar anesthetic concentration for horses). To enable comparison of temporal results in relation to 2 body postures, horses were studied in lateral recumbency (LR) and dorsal recumbency (DR) on separate occasions. Temporal changes in results of measures of circulation previously reported from this laboratory for horses in LR were confirmed (ie, a time-related increase in systemic arterial blood pressure, cardiac output, stroke volume, and PCV). During DR, systemic arterial blood pressure was initially significantly (P less than 0.05) greater and pulmonary artery pressure less than results at comparable periods during LR. Differences ceased to exist with duration of anesthesia. Except for a greater heart rate at hour 5 of DR, no other significant differences in circulation were found between LR and DR. In general, except for PaO2, measures of ventilation did not change with time in either LR or DR. The PaO2 was significantly greater during LR, compared with DR, but the average did not change significantly with time in either body posture.

Administration, Inhalation

Effect of high PaCO2 and time on cerebrospinal fluid and intraocular pressure in halothane-anesthetized horses.

The effects of different arterial carbon dioxide tensions (PaCO2) on cerebrospinal fluid pressure (CSFP) and intraocular pressure (IOP) were studied in 6 male halothane-anesthetized horses positioned in left lateral recumbency. Steady-state anesthetic conditions (1.06% end-tidal halothane concentration) commenced 60 minutes following anesthetic induction with only halothane in oxygen. During atracurium neuromuscular blockade, horses were ventilated, and respiratory rate and peak inspiratory airway pressure were maintained within narrow limits. The CSFP and IOP were measured at 3 different levels of PaCO2 (approx 40, 60, and 80 mm of Hg). The PaCO2 sequence in each horse was determined from a type of switchback design with the initial PaCO2 (period 1), established 30 minutes after the commencement of steady-state anesthesia, being repeated in the middle (period 3) and again at the end (period 5) of the experiment. Measurements taken from the middle 3 periods (2, 3, and 4) would form a Latin square design replicated twice. The interval between each period was approximately 45 minutes. Data from periods 2, 3, and 4 indicated that CSFP (P less than 0.05) and mean systemic arterial pressure increased significantly (P less than 0.05) with high PaCO2. Mean central venous pressure, heart rate, and IOP did not change significantly during these same conditions. Measurements taken during periods 1, 3, and 5 were compared to assess the time-related responses to anesthesia and showed a significant increase in CSFP, a significant decrease in mean central venous pressure, and a small (but not statistically significant) increase in mean systemic arterial pressure.

Animals

Laryngotracheal lesions following routine orotracheal intubation in the horse.

Sequelae of routine orotracheal intubation under clinical conditions were characterised in 38 healthy horses presented at three veterinary medical teaching hospitals. Four of these were necropsied and their tissues studied histologically. To minimise variation, 30 mm id cuffed silicone endotracheal tubes or Cole cuffless tubes were used in all patients. Fibreoptic endoscopic examination of upper respiratory and tracheal areas was accomplished pre-intubation, immediately post extubation and after 24 h. Endoscopy revealed that intubation was associated with laryngeal and/or tracheal lesions in all horses. Observations included abundant tracheal mucus, epithelial ecchymoses, basement membrane haemorrhage and mucus covered diphtheritic membrane plaques. Histological examination of lesions from the upper respiratory system of the four necropsied horses confirmed that the damage was comparable to that associated with tracheal intubation and reported in other species.

Animals

High frequency jet ventilation in horses: an experimental study.

High frequency jet ventilation (HFJV) is a recently developed mode of ventilation that delivers small tidal volumes at frequencies greater than 60 cycles per min via an injection catheter to the animal's airway. The construction of a high frequency jet ventilator suitable for use in adult horses is described. The effectiveness of this ventilator in maintaining normal arterial blood-gas tension was evaluated in five healthy adult horses. The horses were anaesthetised with intravenous acetylpromazine, guaifenesin, and thiamylal, positioned in lateral recumbency and baseline measurements were made during spontaneous ventilation. The horses were then paralysed with succinylcholine and ventilated for at least 20 mins with HFJV. Air was delivered from the ventilator to the animal by a polyethylene tube. The tip of this tube remained within and approximately 30 cm from the cuffed end of a standard 30 mm internal diameter large animal orotracheal tube. Frequency of flow interruption was 3 Hz with a constant source pressure of 275 kPa and an inspiratory to expiratory ratio of approximately 1:2.6. Gas delivery to the horse, as estimated with a resonator system was approximately 2 litres/breath. During HFJV, arterial carbon dioxide tension was significantly reduced and arterial oxygen tension significantly increased above measurements made when the horses were spontaneously breathing air.

Animals

Hematologic and serum biochemical alterations associated with multiple halothane anesthesia exposures and minor surgical trauma in horses.

Five horses were anesthetized similarly by use of xylazine, guaifenesin, thiamylal sodium, and halothane in oxygen on 3 consecutive days, and minor surgical procedures were performed. For 1 to 10 days after the last anesthetic exposure, clinical, hematologic, and serum biochemical features were monitored, and after necropsy, histologic examination of major organ tissues was performed. Predominant hematologic changes from base-line values included leukocytosis (maximal at 27 hours, 10,500 +/- 1,750 cells/microliter), neutrophilia (maximal at 51 hours, 7,485 +/- 1,719 cells/microliter), and lymphopenia (minimal at 51 hours, 1,636 +/- 564 cells/microliter). Alterations observed in other clinicopathologic features were minor and indicative of mild renal disturbance and nonspecific cellular necrosis. Histopathologic lesions in the liver were mild.

Anesthesia, General

Effects of halothane anesthesia on the clearance of gentamicin sulfate in horses.

Inhalation anesthetics decrease the clearance of some drugs that are eliminated by renal excretion. The purpose of the study reported here was to investigate the effects of halothane anesthesia on the pharmacokinetics and urinary excretion of gentamicin sulfate, using the horse as a model. Using a crossover design, pharmacokinetic values after a single IV dose of gentamicin (4 mg/kg) were compared in halothane-anesthetized and unanesthetized horses. Compared with unanesthetized horses, the anesthetized horses had significant decreases in total body clearance (P less than 0.01) and apparent volume of distribution (P less than 0.05), and a significant increase in half-life (P less than 0.05) of gentamicin.

Anesthesia, Inhalation

Effects of simultaneous viewing and vaporization of plaques using the steerable, laser-heated metal cap in the atherosclerotic monkey model.

A steerable, fiberoptic catheter coupled to a laser light guide tipped with a metal cap was used. Four monkeys fed an atherogenic diet for 7-8 years were angiographed and were found to have extensive mural plaque in the iliac arteries. Plaque sites in these monkeys were vaporized using the laser-heated metal cap. Energies of 1.5-9 Joules were employed. Application of the energy was tangential of perpendicular to the plaque. Lased sites were examined histologically at 24 hr or at 3 months after treatment. No effect was seen at 1.5 Joules. Three to six Joules tangentially produced a superficial lesion that extended into the tunica intima. Six Joules perpendicularly produced a burn into the tunica adventitia, with damage to the vasavasorum. Nine Joules tangentially produced a burn into the tunica media. Three months after treatment, this lased site showed no stenosis or aneurysm formation.

Animals

Cardiopulmonary function during 5 hours of constant-dose isoflurane in laterally recumbent, spontaneously breathing horses.

Hemodynamic and respiratory effects of 5 h of unvarying 1.57%, end-tidal (1.2 MAC) isoflurane in O2 anesthesia were characterized in ten left laterally recumbent horses. Compared to base line values at 30 min of constant dose isoflurane, cardiac output, hematocrit, total plasma solids, PaCO2, and peak inspired gas flow progressively and significantly (P less than 0.05) increased over the course of study. Arterial blood pressure increased (P less than 0.05) during the first 2 h of constant dose of isoflurane then decreased and remained near base line values. Inspiratory time progressively decreased with time of anesthesia. All horses recovered from anesthesia uneventfully within 1 h of termination of isoflurane.

Anesthesia, Inhalation

Arterial blood PO2 and PCO2 in horses during early halothane-oxygen anaesthesia.

Arterial blood was collected from 25 clinically normal horses immediately before and serially throughout the first hour of halothane oxygen anaesthesia. Blood was analysed for oxygen and carbon dioxide partial pressure (PaO2, PaCO2). Measurements of inspired oxygen concentration during anaesthesia permitted direct correlation with blood gases. Horses were divided arbitrarily into two groups based on their age: two to seven years, n = 15; over seven years, n = 10. Average (+/- sd) PaO2 and PaCO2 was 14.1 +/- 1.5 kPa (106 +/- 11 mmHg) and 5.9 +/- 0.6 kPa (44.4 +/- 4.4 mmHg) respectively in conscious, young horses and 14.0 +/- 0.7 and 5.8 +/- 0.5 kPa (105 +/- 5 and 43.3 +/- 3.8 mmHg) respectively in conscious older horses. Arterial oxygen tension decreased to 9.3 +/- 1.0 and 8.5 +/- 1.4 kPa (69.6 +/- 7.8 and 63.7 +/- 10.4 mmHg) in young and older air breathing horses respectively immediately following intravenous anaesthetic induction, recumbency and orotracheal intubation. At this time, PaCO2 was 6.5 +/- 0.5 and 6.0 +/- 0.7 kPa (48.7 +/- 3.5 and 45.1 +/- 4.9 mmHg) respectively. By 30 mins after the start of halothane in oxygen (6 litres/min) anaesthesia PaO2 increased to a maximum in both study groups. Arterial PCO2 increased steadily during anaesthesia and 60 mins after induction PaCO2 was 10.5 +/- 2.4 kPa (78.5 +/- 17.8 mmHg) in the younger horses and 9.2 +/- 1.6 kPa (68.8 +/- 11.8 mmHg) in the older horses. During inhalation anaesthesia PaO2 tended to be greater at comparable time periods in the younger horses despite a slightly greater degree of hypoventilation.

Aging