Exogenously administered vasopressors (sympathomimetics) were evaluated in halothane-anesthetized dogs to determine the effects of these drugs on cardiovascular function before and after hemorrhage. Six dogs were anesthetized with thiamylal sodium (20 mg/kg of body weight) and halothane (1.25 minimal alveolar concentration) in 100% oxygen. After instrumentation, cardiac output, systemic arterial blood pressure (SAP), heart rate (HR), left ventricular pressure, pulmonary arterial pressure, and an index of cardiac contractility (dP/dT) were measured. Stroke volume, cardiac index (CI), stroke index (SI), rate-pressure product, and systemic vascular resistance (SVR) were calculated. Epinephrine (0.1, 0.3, and 0.5 micrograms/kg/min [low, medium, and high doses, respectively]) and dobutamine (1, 5, and 10 micrograms/kg/min [low, medium, and high doses, respectively]) were infused. Methoxamine was given in a bolus of 0.22 mg/kg, IV. All measurements were taken at 2.5 minutes after infusion, and were repeated after removal of 40% of the estimated blood volume. Dobutamine administered at the low dose before hemorrhage increased SAP and dP/dT. At the high and medium dose, dobutamine significantly increased CI, dP/dT, and SAP with no significant change in HR or SVR. The medium dose of epinephrine was the most effective dose of epinephrine at increasing key variables (CI, SI, dP/dT). The response of CI and SI to this dose was not significantly different from the changes seen with high-dose administration of dobutamine. The dP/dT was significantly lower with epinephrine than with dobutamine, and SVR and HR were unchanged with epinephrine, except at the low dose, which decreased SVR. Methoxamine significantly decreased CI, SVR, and HR, whereas SVR and SAP were increased significantly. After hemorrhage, the only variables that had a significant change in the absolute magnitude of the response to a drug, relative to the response before hemorrhage, were a significantly reduced ability of dobutamine and methoxamine to increase SAP, and a significantly decreased ability of methoxamine to decrease CI. We concluded that dobutamine and epinephrine provide beneficial short-term support of the cardiovascular system in the halothane-anesthetized dog during acute hypovolemia.

Baroreflex sensitivity (BS) was used to quantitatively assess the effects of halothane and isoflurane on the heart rate/arterial pressure relationship during steady-state (10 minutes) and dynamic pressure changes in adult horses. Arterial pressure was decreased in response to nitroglycerin or sodium nitroprusside and increased in response to phenylephrine HCl. Mean (+/- SEM) BS in awake horses was 28.9 +/- 2.6 and 13.2 +/- 2.0 ms/mm of Hg during steady-state decreases and increases in systolic arterial pressure (SAP), respectively. Halothane and isoflurane either significantly (P < 0.05) decreased or eliminated BS during steady-state decreases in SAP, with no significant differences detected between anesthetic agents. During steady-state decreases in SAP, significant (P < 0.05) correlation between R-R interval and arterial pressure was not observed for 6 of 10 and 4 of 11 halothane and isoflurane anesthesia periods, respectively. Halothane significantly (P < 0.05) decreased BS during steady-state increases in SAP to 7.9 +/- 0.6 and 6.5 +/- 1.1 ms/mm of Hg during low and high minimal alveolar concentration (MAC) multiples, respectively. Isoflurane decreased BS during steady-state increases in SAP to 9.6 +/- 1.5 and 6.6 +/- 1.1 ms/mm of Hg during low and high MAC anesthesia, respectively, with high MAC of isoflurane decreasing BS significantly (P < 0.05), compared with awake and low MAC values. Plasma catecholamine (epinephrine and norepinephrine) concentrations increased significantly (P < 0.05), compared with baseline values during steady-state vasodilator infusions in halothane- and isoflurane-anesthetized horses. Steady-state infusions of phenylephrine in anesthetized horses resulted in arrhythmia development, with premature atrial and ventricular complexes seen in halothane-anesthetized horses and increased heart rate and atrial premature complexes seen less frequently in isoflurane-anesthetized horses. Dynamic BS was 25.0 +/- 4.5 and 20.1 +/- 2.8 ms/mm of Hg for decreasing and increasing SAP, respectively, in awake horses. The R-R interval and SAP were linearly correlated during dynamic decreases in SAP in 7 of 9 halothane and 8 of 10 isoflurane anesthesia periods. Baroreflex sensitivity decreased to 15.0 +/- 6.8 and 13.3 +/- 3.5 ms/mm of Hg during anesthesia with low MAC of halothane and isoflurane, respectively. High MAC of halothane and isoflurane significantly (P < 0.05) decreased BS during dynamic decreases in SAP in 7.8 +/- 1.8 and 7.2 +/- 1.3 ms/mm of Hg, respectively. There were no significant differences in BS depression between halothane and isoflurane.

Atracurium (0.4 mg/ml in isotonic NaCl solution) was administered by IV infusion to 7 healthy adult horses for 2 hours. Over the 2-hour period, a 95 to 99% reduction of train-of-four hoof-twitch response was maintained by 0.17 +/- 0.01 mg of atracurium/kg of body weight/h, for a total of 161 +/- 6 mg of atracurium (mean +/- SEM) for horses 1 to 4, 6, and 7. Horse 5, a mare in estrus, required 0.49 mg of atracurium/kg/h to maintain comparable relaxation. Hoof-twitch recovery time from 10 to 75% of baseline strength was 19.8 +/- 2.5 minutes for all horses. The 10 to 75% recovery time for horse 5 was 18 minutes. Recovery time from discontinuation of halothane until standing was 86 +/- 14 minutes (range, 55 to 165 minutes). Horse 5 had a 165-minute recovery. Regarding recovery from anesthesia, 3 recoveries were rated as excellent, 1 recovery good, and 2 recoveries as fair. Horse 5 laid quietly until she stood with 1 strong, smooth effort.

Hemodynamic effects of spontaneous ventilation, intermittent positive-pressure ventilation (IPPV), and high-frequency oscillatory ventilation (HFOV) were compared in 6 dogs during halothane anesthesia. Anesthesia was induced with IV thiamylal Na and was maintained with halothane (end-tidal concentration, 1.09%). During placement of catheters, dogs breathed spontaneously through a conventional semiclosed anesthesia circuit. Data were collected, and dogs were mechanically ventilated, using IPPV or HFOV in random order. Ventilation was adjusted to maintain PaCO2 between 38 and 43 mm of Hg during IPPV and HFOV. Cardiac index, aortic blood pressure, and maximum rate of increase of left ventricular pressure were significantly (P less than 0.05) less during HFOV than during spontaneous ventilation, whereas right atrial and pulmonary artery pressure were significantly greater during HFOV than during spontaneous ventilation. During IPPV, only the maximum rate of increase of left ventricular pressure was significantly less than that during spontaneous ventilation.

The arrhythmogenic dose of epinephrine (ADE) was determined in heartworm-infected and noninfected (control) dogs during thiamylal-induced and halothane-maintained anesthesia to assess the myocardial sensitization. The ADE in heartworm-infected dogs (2.42 +/- 0.26 micrograms/kg of body weight) was significantly lower than that for the controls (3.36 +/- 0.29 micrograms/kg). After 2 weeks, ADE was determined again in these dogs after atropine treatment. Atropine treatment lowered the ADE to 1.76 +/- 0.33 micrograms/kg and 1.77 +/- 0.19 micrograma/kg in heartworm-positive and negative dogs, respectively. After 2 weeks more the ADE was determined after administration of prazosin, an alpha 1-antagonist. Only 2 of 6 controls and 3 of 6 heartworm-positive dogs had arrhythmias after a threefold increase of ADE. The mean ADE in the dogs that responded to treatment were 7.4 micrograms/kg and 7.2 micrograms/kg for heart worm-positive and negative dogs, respectively. The findings of this study indicated that ADE in heartworm-infected dogs were lower than those in the control dogs, which makes the heartworm-infected dogs more vulnerable to arrhythmia during anesthesia. Atropine did not protect the dogs of either group. However, prazosin protected the dogs of both groups by significantly increasing the threshold of the ADE. On the basis of our findings, to reduce the risk of arrhythmia, we suggest that routine screening of dogs for heartworm infection be done before anesthetics are used.

The cardiopulmonary effects of 2 planes of halothane anesthesia (halothane end-tidal concentrations of 1.78% [light anesthesia] and 2.75% [deep anesthesia]) and 2 ventilatory modes (spontaneous ventilation [SV] or mechanically controlled ventilation [CV]) were studied in 8 cats. Anesthesia was induced and maintained with halothane in O2 only, and each cat was administered each treatment according to a Latin square design. Cardiac output, arterial blood pressure, pulmonary arterial pressure, heart rate, respiratory frequency, and PaO2, PaCO2, and pH were measured during each treatment. Stroke volume, cardiac index, and total peripheral resistance were calculated. A probability value of less than 5% was accepted as significant. In the cats, cardiac output, cardiac index, and stroke volume were reduced by deep anesthesia and CV, although only the reduction attributable to CV was significant. Systemic arterial pressure was significantly reduced by use of deep anesthesia and CV. Respiratory frequency was significantly lower during CV than during SV. Arterial P(O2) was significantly decreased at the deeper plane of anesthesia, compared with the lighter plane. At the deeper plane of anesthesia, arterial P(CO2) and pulmonary arterial pressure were significantly lower during CV than during SV. The deeper plane of halothane anesthesia depressed cardiopulmonary function in these cats, resulting in hypotension and considerable hypercapnia. Compared with SV, CV significantly reduced circulatory variables and should be used with care in cats. Arterial blood pressure was judged to be more useful for assessing anesthetic depth than was heart rate or respiratory frequency.

The effects of butorphanol tartrate on arterial pressure, jejunal blood flow, vascular resistance, oxygen extraction, and oxygen uptake were determined in 10 anesthetized ponies ventilated with a mixture of halothane and 100% oxygen, using isolated autoperfused jejunal segments. Physiologic saline solution or butorphanol tartrate (0.2 mg/kg of body weight) was administered as a single bolus into the left jugular vein. By 2 minutes, butorphanol decreased arterial blood pressure and intestinal blood flow, and increased intestinal oxygen extraction. However, intestinal vascular resistance and oxygen uptake were unaffected. Results of this study indicate that butorphanol tartrate induces a hypotension that secondarily decreases intestinal blood flow, but intestinal vascular resistance and metabolism are not adversely affected. We conclude that butorphanol tartrate does not compromise intestinal viability in halothane-anesthetized ponies and, therefore, may be a good analgesic choice for the equid destined for abdominal surgery.

Wick catheters were used to measure intracompartmental pressures of the extensor carpi radialis muscles and long heads of the triceps brachii muscles of 7 horses maintained under halothane anesthesia during controlled ventilation. Horses were positioned in left lateral recumbency on a water bed for 4 hours. Using a crossover design, 6 of the 7 horses were subjected to normotensive and hypotensive anesthesia on separate occasions. Hypotension was achieved by increasing the inspired halothane concentration. Hematologic and biochemical measurements were determined at designated intervals before, during and for 7 days after each anesthetic episode. Under hypotensive conditions, 2 horses developed severe, generalized myositis and were euthanatized. Three of the 5 other horses developed swelling of the downside masseter muscle, 4 demonstrated mild extensor deficits of the downside forelimb, and 1 had a severe extensor deficit of the uppermost hind limb. As a group, the hypotensive horses had markedly increased activities of serum enzymes (creatine kinase, aspartate transaminase, and blood lactate) and abnormalities in calcium-phosphorus homeostasis. Lameness or enzyme alterations were not observed in normotensive horses. Altough the intracompartmental pressure values were markedly increased in the muscle bellies of the compressed limbs of all horses, there was a statistically significant difference in intracompartmental pressures between the downside or compressed muscle compartments of the extensor carpi radialis of hypotensive and normotensive horses. High concentrations of halothane may predispose anesthetized horses to postanesthetic myositis, even when protective padding is used. Intracompartmental muscle pressure, as measured by the wick catheter, may not be a reliable predictor of equine postanesthetic lameness.

We tested the hypothesis that lymphocytes from swine with susceptibility to malignant hyperthermia (MH) had increased sensitivity to the membrane-perturbing effects of halothane that increase cytoplasmic calcium. Cytoplasmic concentration of ionized calcium in lymphocytes isolated from blood was determined in the presence and absence of halothane for 10 Pietrain X Poland China swine that were susceptible to MH and 20 Yorkshire swine that were resistant to MH. Calcium was determined by dual-emission spectrofluorometry and by measuring the ratio of free to calcium-bound form of the fluorescent calcium dye Indo-1. Mean values for calcium concentrations in lymphocytes from MH-susceptible (MHS) swine were 80% less than control values (40.5 +/- 38.8 and 185.3 +/- 91.6 nmol/L; P less than 0.01). Untreated lymphocytes from MHS swine accumulated calcium at half the rate observed for controls. Exposure to 1 mmol/L halothane resulted in a 3-fold increase of free calcium concentration to 127.9 +/- 81.9 nmol/L in the lymphocytes of MHS swine, but had no significant effect on lymphocytes from control swine (225.0 +/- 91.4; P less than 0.01). Exposure to 2 mmol/L halothane resulted in a 6-fold increase of free calcium concentration to 255.9 +/- 91.4 nmol/L in lymphocytes from MHS swine and a 63% increase in lymphocytes from controls (303.8 +/- 116). The rate of halothane-induced increase in cytosolic calcium was 13 times greater in lymphocytes from MHS swine, compared with controls. These data indicated that the molecular defect that results in halothane-hypersensitivity and is characteristic of muscle of MHS swine also occurs in lymphocytes from MHS swine.