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True reference values (TRV) should ultimately be determined in blood from inactive, unstimulated rats but in practice, acceptable reference values (ARV) may be established using blood from decapitated or anesthetized animals if one is cognizant of variations associated with blood sampling procedures. Data reported here illustrate some variations in serum biochemical values following decapitation or anesthesia. Decapitation does not provide serum in which ARV for sodium, potassium or lactate dehydrogenase can be found but ARV can be determined for glucose, insulin and several other parameters. It is suggested that both TRV and ARV for serum electrolytes be determined using serum from cannulated rats. All three anesthetics raised glucose levels and ether and halothane increased alkaline phosphatase activity. Both halothane and Innovar-VetR decreased insulin:glucose ratios suggesting inhibition of insulin release from the pancreas. Innovar-VetR also produced hypoxia due to severe respiratory depression and bradycardia as well as hyperuricemia, hyperglycemia and hyperphosphatemia. Techniques most likely to provide ARV should be of the shortest possible duration, afford least respiratory and cardiovascular suppression and minimize stimulation of the sympathetic nervous system.

The halothane-diethyl ether azeotrope was evaluated in dogs as the anesthetic agent for deep surface hypothermia with total circulatory arrest for open-heart operation. All 10 animals given azeotrope in 100% oxygen (O2) experienced atrial arrhythmias during cooling, and 1 had ventricular fibrillation prior to the completion of cooling at 18 degrees to 20 degrees C. After only 30 minutes' arrest, 8 of the 10 dogs had postoperative motor disturbances. Administering the azeotrope in 95% O2 and 5% carbon dioxide (CO2) yielded markedly improved results characterized by a rapid, smooth cooling course, easy resuscitation following circulatory arrest, and rapid rewarming, and 3 out of 10 dogs experienced mild motor disturbance after 60 minutes of circulatory arrest. This method, when compared with our standard method of ether in 100% O2, resulted in reduced blood lactates and a striking improvement in clinical status on the first postoperative morning. In limited clinical trials, infants undergoing repair of congenital cardiac defects have done well and responded as expected based on the laboratory experience. Since the results with the azeotrope in 95% O2 and 5% CO2 were at least as good as, and in several instances better than, those with the standard method employing either, the nonexplosive characteristic of the azeotrope warrants continued evaluation of this agent.

The performances of an Oxford miniature vaporizer (OMV) and a Fluotec Mark III vaporizer filled with an azeotropic mixture of halothane and diethyl ether were studied. Gas concentrations were estimated using an EMMA gas analyser and a MIRAN spectrophotometer. Calibration tables for both vaporizers were derived. In a small clinical series with air as the carrier gas, to which a small amount of oxygen was added, the azeotrope was found to be a satisfactory anaesthetic agent, giving a short awakening time and an almost pain-free postoperative course.

Thirty adult mongrel dogs were divided into 3 equal groups and studied to define the optimal PCO2 level with azeotrope (halothane-diethyl ether) anesthesia under surface hypothermia (Groups I, II and III = F1CO2 0%, 5% and 10%, respectively). All animals were cooled to 18-20 degrees C and were subjected to 30 (Group I) or 60 minutes (Groups II and III) of total circulatory arrest. Group I animals had frequent arrhythmic episodes during cooling and postoperative motor disturbances occurred in 80% despite only 30 minutes of circulatory arrest. By contrast Group II animals were less arrhythmic during cooling; were easily resuscitated following 60 minutes of arrest and only 30% developed moderate reversible motor disturbances postoperatively. Hemodynamics were similar between Groups II and III during cooling but resuscitation using an F1CO2 of 10% (Group III) was extremely difficult and required massive cardiotonic support throughout rewarming. Furthermore, two dogs in Group III died within the first two postoperative days. However, none of the 8 survivors displayed neurological abnormalities. On balance, a ventilatory regimen utilizing 5% CO2 during surface-induced hypothermia under azeotrope anesthesia resulted in optimum intraoperative management and a satisfactory postoperative course and although some CNS disturbance (high-stepping gait) was noted, all animals recovered completely.

Arterial blood lactate, pyruvate, and excess lactate (XL) were measured and calculated in 33 patients aged 7 months to 6 years over a period of 2 hours during repair of harelip or cleft palate. When the anesthetic was diethyl ether, lactate and pyruvate levels rose significantly 60 minutes after induction of anesthesia but did not rise thereafter. Excess lactate appeared 60 minutes after induction of ether anesthesia, but it, too, showed no further increase. When the anesthetic was halothane there was no significant change in lactate, pyruvate, or XL. Changes with ether were not age-related, nor could they be correlated with changes in rectal or skin temperature. The responses of lactate, pyruvate and XL to ether anesthesia in the present study were not significantly different from those found by others in adults.

We have investigated by means of electron spin resonance (ESR) spectroscopy the influence of three inhalation anesthetics, i.e. halothane, chloroform and diethyl ether, on the interfacial and hydrophobic region as well of 38 mol% cholesterol containing DPPC unilamellar vesicles. The study has been carried out in the temperature range 25-45 degrees C. The variation of the order parameter, S, vs temperature of the lipid phase indicates that with this content of cholesterol the characteristic gel----liquid crystalline main phase transition of DPPC, normally occurring at Tt approximately 41 degrees C, disappears. When halothane and chloroform are added to the vesicles suspension up to [DPPC]/[anesthetic] molar ratio of 1:1 the main phase transition, as detected with the stearic acid spin label I (12,3), reappears again and it results down shifted at Tt approximately 35 and 39 degrees C, respectively. In presence of diethyl ether, instead, the main phase transition is not observable also at the highest concentration of anesthetic used. Moreover, halothane and chloroform affect similarly the hydrophobic core of cholesterol + DPPC vesicles which, in turn, results to be different from the action exerted by diethyl ether in the same region. The ESR findings are discussed in terms of competitive effects shown by cholesterol and inhalation anesthetics. Moreover, the interfacial region of CHOL + DPPC vesicles results to be the target of anesthetics.

A comparative quantitative investigation on the level of 11-oxycorticosteroids (11-OCS) in the peripheral blood and on morphological changes in the lymphoid tissue has been performed on intact and adrenalectomized rats after 3 hours' ether and halothane anesthesia. Three hours after the ether anesthesia, the level of 11-OCS increases more than twice, halothane is not a stress-producing anesthesia. After the ether anesthesia and essential devastation of the lymphoid tissue occurs, resulted from degeneration and a decreasing proliferative activity of the cells. In the adrenalectomized animals, both after halothane and either anesthesia, there are no essential morphological changes. Thus, certain significant differences between hormonal and morphological changes after either the halothane anesthesia have been revealed, as well as the role of the adrenal cortex in this activity.

The end results of therapy of 346 patients with lung tumors, treated with surgery alone, are compared, depending on the type of general anesthetic agent used. Anesthesia was induced with ether in 220 patients, halothane in 103, and neuroleptanalgesia in 23 cases. All the anesthetic agents were administered in a mixture with nitrous oxide. The basic characteristics of patients, who were divided on the basis of anesthetic agent, were identical. The results show that type of anesthesia during surgical treatment for lung tumor has an effect on the end results of therapy, and the best prognosis is ensured when halothane is used. Further analysis established that the end results of surgery with halothane anesthesia are improved, when partial resection rather than radical pneumonectomy is performed, at stage 2 of malignant disease and when metastases into regional lymph nodes are absent. Such improvement may be explained by stimulation of the hypothalamo-pituitary-adrenal system as well as a relatively lower degree of immunosuppression and development of conditions more adverse for implantation of circulating tumor cells than in the case of ether or neuroleptanalgetic anesthesia.

The end results of therapy of 1,358 breast cancer patients were studied. Anaesthesia was performed by ether-nitrogen-oxygen (554 cases) or halothane-nitrogen-oxygen (804 cases) mixture with addition of oxygen. The method of Holstead was employed in all cases. A comparison of groups of patients on the basis of such parameters as the anaesthetic used, age and degree of tumour progression (according to the TNM classification and results of post-operative histological assays) showed them to be identical. The study showed that the type of anaesthesia influenced the end results of therapy of cancer patients: the survival rates of patients receiving halothane anaesthesia were much higher than those of the ether-anaesthetized patients. The differences were most pronounced among patients who received pre-operative radiation therapy and post-operative chemotherapy as well as in cases of metastasis spread into regional lymph nodes. The mechanism of the effect of the anaesthetic on the survival rates of cancer patients may be explained on the basis of the data available on the varying influences of anaesthetics on the pituitary-adrenal cortec system and carcinemia development during operation as well as the role of immunity in tumour cell implantation and growth of metastases.

Alterations in the course of and histopathologic response to influenza viral infections by halothane, enflurane, and diethyl ether anesthesia were evaluated in ferrets. There were no significant differences in the incidence and duration of lethargy, pyrexia, rhinorrhea, or sneezing in infected animals given one of the three anesthetic agents under investigation, compared with those receiving no anesthesia. There were no differences in lung pathology in infected animals given one of the three anesthetic agents, or no anesthesia, though histopathologic changes in the nasal turbinates were significantly greater in ferrets given enflurane. This study suggests that general anesthesia administered to ferrets infected with influenza virus carries minimal morbidity, although enflurane anesthesia was found to produce greater histopathologic changes than the other agents.

Effects of the use of 5% CO(2) and surface-rewarming or perfusion- rewarming on safe total circulatory occlusion time, blood gases and carbohydrate metabolism were studied in 25 dogs subjected to surface hypothermia (18 C) and 30 minutes of circulatory occlusion under halothane or ether anesthesia. Under halothane anesthesia, all animals with 100% 0(2) developed motor disorders while one of five surface-rewarmed dogs and none of the perfusion-rewarmed dogs developed motor disorders with 5% CO(2). Under ether anesthesia, all were normal with either 100% 0(2) or when 5% CO(2) was added. Ventricular fibrillation occurred in one dog at 21C under halothane anesthesia with 5% CO(2). Blood lactate levels remained low through hypothermic procedures when 5% CO(2) was used. Perfusion rewarming had little effect on lactate levels. The use of 100% 0(2) resulted in slightly higher lactate levels, especially in the ether anesthetized group, but these levels still remained within the upper limit of the normal range. Significant differences in lactate levels between halothane and ether anesthesia suggest different mechanisms of tissue circulation and metabolism during hypothermia. Halothane anesthesia can be useful with the use of CO(2) for surface hypothermia with 30 minutes circulatory occlusion but is still inferior to ether.

The examination of 46 patients with pheochromocytoma has shown all the patients to have cardiac insufficiency before operation. This finding shows the necessity of preoperative preparation of the myocardium. The standard administration of beta-adrenoblocking agents without controlling the parameters of central hemodynamics can cause insufficiency of the minute volume of blood circulation. The authors failed to reveal advantages of any kind of general anesthesia. They consider that all the efforts in the course of anesthesiologic measures should be directed to the correction of hemodynamics.