Dexmedetomidine and regulation of splenic sympathetic nerve discharge in aged F344 rats.

Sedatives influence the immune system and centrally-acting alpha2-adrenergic receptor agonists, including Dexmedetomidine (Dex), modulate sympathetic nerve discharge (SND). Because sedatives are used under medical conditions that include elderly patients, and because advancing age attenuates SND responsivity to various interventions, we tested the hypothesis that splenic sympathoinhibitory responses to Dex would be attenuated in aged compared with young Fischer 344 rats. Dex-mediated reductions in splenic SND were similar in aged and young baroreceptor-intact and -denervated rats, indicating that SND changes to Dex administration occur in an age-independent manner. These findings provide new information regarding interactions between alpha2-adrenergic agonists, advanced age, and SND regulation.

Pulmonary blood flow distribution in standing horses is not dominated by gravity.

Recent studies using microspheres in dogs, pigs and goats have demonstrated considerable heterogeneity of pulmonary perfusion within isogravitational planes. These studies demonstrate a minimal role of gravity in determining pulmonary blood flow distribution. To test whether a gravitational gradient would be more apparent in an animal with large vertical lung height, we measured perfusion heterogeneity in horses (vertical lung height = approximately 55 cm). Four unanesthetized Thoroughbred geldings (422-500 kg) were studied awake in the standing position with fluorescent microspheres injected into a central vein. Between 1,621 and 2,503 pieces (1.3 cm3 in volume) were obtained from the lungs of each horse with spatial coordinates, and blood flow was determined for each piece. The coefficient of variation of blood flow throughout the lungs ranged between 22 and 57% among the horses. Considerable heterogeneity was seen in each isogravitational plane. The relationship between blood flow and vertical height up the lung was characterized by the slope and correlation coefficient of a least squares regression analysis. The slopes within each horse ranged from -0.052 to +0.021 relative flow units/cm height up the lung, and the correlation coefficients varied from 0.12 to 0.75. A positive slope, indicating that flow increased with vertical distance up the lung (opposite to gravity), was observed in three of the four horses. In addition, blood flow was uniformly low in three of the four horses in the most cranial portions of the lungs. We conclude that in lungs of resting unanesthetized horses, animals with a large lung height, there is no consistent vertical gradient to pulmonary blood flow and there is a considerable degree of perfusion heterogeneity, indicating that gravity alone does not play the major role in determining blood flow distribution.

Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses.

We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.

Effects of restraint and isolation stress and epidural blockade on endocrine and blood metabolite status, muscle glycogen metabolism, and incidence of dark-cutting longissimus muscle of sheep.

Crossbred lambs (47.3 kg BW) were used to study the effects of restraint and isolation stress on endocrine status and blood metabolites, antemortem glycogenolysis, and incidence of the dark-cutting condition (DCC) in the longissimus muscle (LM) and to determine the role of muscle contraction in the formation of the DCC in sheep. Lambs were assigned randomly to three treatments: unstressed controls (C); a single 6-h period of restraint and isolation stress (RIS); and a single 6-h period of RIS following epidural blockade (RISEB) with lidocaine. Blood was collected immediately before lambs were subjected to RIS and RISEB and at 12-min intervals during the 6-h period. Serum concentrations of glucose, lactate, and insulin were higher (P < .01) in RIS and RISEB lambs than in C lambs. Serum free fatty acid concentrations were higher (P < .01) in stressed lambs only during the first 4 h of stress. Plasma epinephrine and cortisol concentrations also were higher (P < .01) in RIS and RISEB lambs than in C lambs. Lambs were slaughtered within 30 min after completion of stress. Immediately after stunning and at .75, 3, 6, 12, and 24 h postmortem, samples were removed from the LM in the hindsaddle and foresaddle for glycogen, lactate, and pH determinations. Muscle pH was elevated (P < .01) by RIS and RISEB; ultimate pH exceeded 6.0. The LM from carcasses of RIS and RISEB lambs had lower (P < .01) glycogen and lactate concentrations in both regions than the LM of C lambs. Subjecting sheep to a single 6-h period of RIS was an effective animal model to induce the DCC. Failure of the epidural blockade to inhibit antemortem glycogen metabolism and formation of the DCC indicates that muscle contraction was not requisite to those processes in sheep.

Cardiopulmonary effects of desflurane in cats.

OBJECTIVE: To evaluate the cardiopulmonary effects of 2 anesthetic planes of desflurane (DES) during spontaneous ventilation (SV) and controlled ventilation (CV) in cats. DESIGN: Repeated Latin square. ANIMALS: Eight healthy adult cats. PROCEDURE: Each cat received 1.3 times the minimum alveolar concentration (MAC) of DES and 1.7 MAC of DES in oxygen during CV and SV. The data were analyzed as a repeated measures design. Heart rate, cardiac output, arterial blood pressure, pulmonary artery pressure, respiratory rate, PaO2, PaCO2, pHa, PCV, and serum total protein concentration were measured during each treatment. Stroke volume, cardiac index, total peripheral resistance, and oxygen consumption were calculated. RESULTS: Cardiac index and stroke volume were not different between 1.3 and 1.7 MAC of DES, but CV decreased cardiac index and stroke volume (P < 0.05). Systolic arterial pressure was decreased during 1.7 MAC of DES and during CV. Mean arterial blood pressure was decreased at 1.7 MAC during CV, but not SV. The PaCO2 was higher at 1.7 MAC than at 1.3 MAC during SV. Spontaneously ventilating cats at 1.7 MAC had higher pulmonary artery pressures than other treatments. The PCV was decreased during CV. CONCLUSION: 1.7 MAC of DES causes decreased systolic and mean arterial pressures and marked hypercapnia, but cardiac index is not affected. The hypercapnia is probably responsible for the increased pulmonary artery pressures in the spontaneously ventilating cats during 1.7 MAC. Hypercapnia can be corrected by CV but this reduces cardiac output.

Effect of anticholinergic preanesthetic medicaments on the requirements of halothane for anesthesia in the cat.

To study the effects of anticholinergics on anesthetic requirements, minimal alveolar concentrations (MAC) for halothane in the cat were measured before and after IM administration of an anticholinergic (atropine sulfate [0.045 mg/kg], glycopyrrolate [0.011 mg/kg], or scopolamine hydrobromide [0.02 mg/kg]) or a physiologic saline control. The study was performed in 8 adult cats, using a randomized-block experimental design. There was no significant difference between the mean MAC obtained before and after administration of any of the test drugs or vs the control values. The mean MAC of halothane in cats was 0.985% atmosphere.

Serum lipid and lipoprotein changes in ponies with experimentally induced liver disease.

Alterations in serum lipid and lipoprotein concentrations in ponies with experimentally induced liver disease were investigated. Hepatocellular damage was induced, using a nonlethal dose of carbon tetrachloride. In a separate group of ponies, obstructive jaundice was induced by surgical ligation of the common bile duct. Over a 6-day period, blood samples were obtained from ponies after treatment with carbon tetrachloride and for 12 days in ponies subjected to surgery. Serum cholesterol and triglyceride concentrations were unaffected in both groups of ponies, except for significantly (P less than 0.01) high triglyceride concentration in ponies of the ligated group during the second postsurgical week. This increase was most likely attributable to anorexia observed during that period. Hyperbilirubinemia was observed early in ponies of the ligated group; most of the bilirubin was of the conjugated type. Using electrophoretic and ultracentrifugal methods, serum lipoprotein alterations were detected only in ponies of the ligated group. Increases of very low-density and low-density lipoprotein cholesterol concentrations and decrease in high-density lipoprotein cholesterol concentration were found. Although no changes were seen in total serum cholesterol concentration, a redistribution of lipoprotein cholesterol was observed in ponies of the ligated group. Similar alterations in lipoprotein distribution have been found in dogs, rats, and human beings with obstructive jaundice and cholestasis. The association between serum lecithin:cholesterol acyl transferase activities and these lipoprotein alterations remains to be elucidated.

Postoperative epidural analgesia.

Administration of epidural opioids is a technique that is currently being used by many veterinary anesthesiologists and surgeons to provide postoperative analgesia. The duration of analgesia is prolonged and the degree of sedation is much less than that which occurs with parenterally administered opioids and the risks appears to be minimal.

Alleviation of postanesthetic hypoxemia in the horse.

This study was designed to investigate the effect of the nasotracheal insufflation of oxygen at a flow rate of 15 L/min on the arterial partial pressure of oxygen during the recovery period following inhalation anesthesia in the horse. It has been stated that this is a suitable flow rate to prevent postoperative hypoxemia but without any experimental evidence to support those statements. Horses being used for the study of healing of cartilage were anesthetized on two separate occasions. Following one period of anesthesia they were allowed to recover breathing room air, and following the other period of anesthesia oxygen was insufflated into the trachea at 15 L/min throughout the recovery period. This permitted each horse to act as its own control and allowed statistical analysis using Student's t-test for paired samples.The insufflated horses had a higher arterial partial pressure of oxygen during the recovery period than did the noninsufflated horses (p < 0.05).

Dexmedetomidine and regulation of splenic sympathetic nerve discharge.

Recent lines of inquiry indicate that sedatives can influence the immune system, leading to the concept of sedative-induced immunomodulation. It has been hypothesized that sedatives may alter immune responses by modulating the sympathetic nervous system, however, little information is known regarding the effects of sedatives on regulation of splenic sympathetic nerve discharge (SND), a significant omission based on the functional role that changes in splenic SND exert on splenic cytokine gene expression. The present investigation determined the effect of systemic Dexmedetomidine (Dex) administration on the level of directly-recorded splenic SND and tested the hypothesis that the intravenous administration of Dex would inhibit splenic SND in anesthetized rats. The present results demonstrate for the first time that intravenous Dex administration significantly reduces splenic sympathetic nerve outflow in baroreceptor-intact and sinoaortic-denervated rats, indicating that Dex administration alters the central regulation of splenic SND. The present results provide new information regarding the effect of a centrally-acting alpha2-adrenergic agonist on the level of sympathetic nerve outflow to a secondary lymphoid organ that plays a critical role in peripheral immune responses.

The minimum alveolar concentration of desflurane in cats.

Eight adult cats, 4 male and 4 female, (3.5 +/- 0.9 [SD] kg) were used to determine the minimum alveolar concentration (MAC) of desflurane. Desflurane (DES) anesthesia was induced in a 20 L chamber with an oxygen inflow of 10 L/min and the DES vaporizer set at 18%. After 3.5 +/- 0.5 min, the cats were removed from the chamber and anesthesia was maintained via mask (14% DES, 3L/min O2) until successful intubation. Anesthesia was maintained with DES in oxygen at a flow of at least 200 mL/kg/min through a nonrebreathing circuit. The time from the start of induction to completion of intubation was 6.2 +/- 1.1 min. Esophageal temperature was maintained between 37.8 degrees C and 38.6 degrees C. Hand-collected end-tidal gas samples were obtained from a catheter positioned inside the lumen of the endotracheal tube. Inspired and end-tidal DES concentrations were measured with a Biochem 8100 anesthetic agent monitor that was calibrated with known gas standards and modified to accept hand-collected samples. A constant alveolar concentration of DES was maintained for at least 15 minutes, then a clamp was applied to the tail and the cat observed for gross purposeful movement. The end-tidal DES was then increased (if a positive response) or decreased (if a negative response) by 20% and the test repeated after 15 minutes of constant conditions. The final iteration was 10%. The MAC of DES in these cats was 9.79 +/- 0.70 vol %. The FA/FI ratio for desflurane was always greater than 0.97.

Modification of a nonrebreathing circuit adapter to prevent barotrauma in anesthetized patients.

Barotrauma, pneumothorax, and pneumomediastinum occurred in two anesthetized cats in which the waste gas outlet of a nonrebreathing circuit was occluded. To prevent any similar cases of barotrauma, we have modified our nonrebreathing circuit adapters by inserting a 15 cm H2O PEEP valve into the gas pathway of the nonrebreathing circuit adapter. This PEEP valve prevents the circuit and airway pressures from exceeding 15 cm H2O if the pop-off valve of the nonrebreathing circuit adapter is inadvertently left closed.

Effect of two anaesthetic regimens on airway nitric oxide production in horses.

There is evidence that halothane inhibits nitric oxide synthase in vitro, but the effect of intravenous anaesthetic agents is less clear. This study was undertaken to compare the rate of exhaled nitric oxide production (VNO) in spontaneously breathing horses anaesthetized with halothane or an intravenous regimen. Seven adult horses were studied twice in random order. After premedication with romifidine 100 microg kg(-1), anaesthesia was induced with ketamine 2.2 mg kg(-1) and maintained with halothane in oxygen (HA) or by an intravenous infusion of ketamine, guaiphenesin and romifidine (IV). Inhaled and exhaled nitric oxide (NO) concentrations, respiratory minute ventilation (VE), pulmonary artery pressure (PPA), fractional inspired oxygen concentration (FIO2), end-tidal carbon dioxide concentration (E'CO2), cardiac output (Q) and partial pressures of oxygen and carbon dioxide in arterial blood (PaO2, PaCO2) were measured. Exhaled nitric oxide production rate was significantly lower (40 min, P<0.01; 60 min, P<0.02) during HA [40 min, 1.4 (SD 1.4) pmol l(-1) kg(-1) min(-1); 60 min, 0.7 (0.7) pmol l(-1) kg(-1) min(-1)] than during IV [40 min, 9.3 (9.9) pmol l(-1) kg(-1) min(-1); 60 min, 12.5 (13.3) pmol l(-1) kg(-1) min(-1)). Mean pulmonary artery pressure was significantly higher (40 min, P<0.01; 60 min, P<0.001) during HA [40 min, 5.9 (1.1) kPa; 60 min, 5.9 (0.9) kPa] compared with IV (40 min, 4.4 (0.4) kPa; 60 min, 4.4 (0.5) kPa]. NO is reduced in the exhalate of horses anaesthetized with halothane compared with an intravenous regimen. It is suggested that increased mean pulmonary artery pressure during halothane anaesthesia may be linked to the differences in NO production.

Cardiovascular effects of 1.0, 1.5, and 2.0 minimum alveolar concentrations of isoflurane in experimentally induced hypothyroidism in dogs.

This study was performed to determine the cardiovascular responses to isoflurane in euthyroid and hypothyroid dogs. Four healthy mixed-breed dogs were studied prior to thyroidectomy (PRE), 6 months after thyroidectomy (HYP), and after 2 months of oral supplementation with 1-thyroxine (SUP). Heart rate (HR), cardiac output (Q), stroke volume (SV), systolic, diastolic, mean arterial blood pressure (SAP, DAP, MAP), and total peripheral resistance (TPR) were determined in awake dogs and in the same dogs when end-tidal isoflurane concentration were 1.28%, 1.92%, and 2.56%. Ventilation was controlled in anesthetized dogs and PACO2 maintained between 38 to 42 mm Hg. Isoflurane caused significant (P < .05) dose-dependent reduction in Q, SV, SAP, DAP, and MAP in the PRE, HYP, and SUP dogs. Cardiac output was lower in the HYP dogs than in the PRE or SUP dogs during awake measurement. TPR was increased in the awake HYP dogs compared with the PRE or SUP dogs. During anesthesia, HYP dogs tended to have lower Q, SV, SAP, and MAP PRE or SUP groups, but the only significant reduction was SAP during 1.5 MAC. The cardiovascular responses to isoflurane in hypothyroid dogs are similar to euthyroid animals with a dose-dependent depression in Q, SV, and arterial pressure.

Effects of inhaled nitric oxide 10 ppm in spontaneously breathing horses anaesthetized with halothane.

Inhaled nitric oxide, a selective pulmonary vasodilator, is known to improve arterial oxygenation after cardiopulmonary bypass and during acute respiratory distress syndrome in humans. During general anaesthesia with spontaneous ventilation, healthy adult horses develop large alveolar-arterial oxygen tension differences. In this study, we have determined the effects of inhaled nitric oxide (10 parts per million (ppm)) on venous admixture and pulmonary haemodynamics in horses anaesthetized with halothane. Seven adult horses were studied twice in random sequence. After premedication with romifidine 100 micrograms kg-1, anaesthesia was induced with ketamine 2.2 mg kg-1 and maintained with 1.1 MAC (0.95%) of halothane in oxygen. Horses breathed spontaneously. After 65 min, each horse had nitric oxide 10 ppm added to the inspired gas for 20 min (procedure HA + NO) or anaesthesia was continued with halothane in oxygen (procedure HA). Cardiac output, minute ventilation, arterial and mixed venous oxygen and carbon dioxide tensions, and mean pulmonary and carotid arterial pressures were measured for 100 min. Shunt fraction and pulmonary and systemic vascular resistances were calculated. Shunt fraction (SF) and mean pulmonary artery pressure (PPA mean) were not different between the two groups after 65 min of general anaesthesia (HA: SF 0.20 (SD 0.06), PPA mean 45 (8) mm Hg; HA + NO: SF 0.21 (0.04), PPA mean 44 (7) mm Hg) or after 85 min (HA: SF 0.22 (0.07), PPA mean 45 (8) mm Hg; HA + NO: SF 0.20 (0.03), PPA mean 43 (7) mm Hg). There were no significant effects of time or nitric oxide inhalation on any other variable. There was a significant correlation (r = 0.80, P < 0.05) between calculated shunt fraction 65 min after induction of anaesthesia and body weight.