Severe Metabolic Changes Research Articles

Alterations in Carbohydrate and Lipid Metabolism Induced by a Diet Rich in Coconut Oil and Cholesterol in a Rat Model

Objective: The type of dietary fat as well as the amount of cholesterol occurring in the diet have been associated with several metabolic disorders. Thus, the aim of the present study was to investigate the influence of a hypercholesterolemic diet enriched with coconut oil and cholesterol on carbohydrate and lipid metabolism in a rat model.Methods: Twenty male Wistar rats weighing about 190 g were assigned to two dietary groups. One group received a semipurified control diet and the other was given a diet enriched in coconut oil (25% by weight) and cholesterol (1% by weight) for 26 days.Results: Our results indicated a significant increase in serum total cholesterol (+285%; p<0.001), low-density lipoproteins (+154%; p<0.01), liver cholesterol (+1509%; p<0.001), as well as a significant increase in liver weight (+46%; p<0.001) in those rats fed the hypercholesterolemia-inducing diet as compared to controls. Moreover, a significant decrease in serum high-density lipoproteins (−67%; p<0.001), triacylglycerols levels (−33%; p<0.05), and abdominal fat weight (−39%; p<0.01) were found. The observed alterations in serum lipid and lipoprotein profile resembled a situation of type IIa hyperlipidemia in humans. Measurement of several enzymes concerned with lipid utilization revealed a significant increase in 3-hydroxy-3-methylglutaryl-CoA reductase activity (+68%; p<0.01) in the liver of animals fed the hypercholesterolemic diet, while a significant reduction in plasma lecithin-cholesterol acyltransferase activity (−66%; p<0.001) was found. The situation of hypoglycemia (−18%; p<0.05) was accompanied by lower levels of serum insulin (−45%; p<0.01) and liver glycogen (−30%; p<0.05) in the hypercholesterolemic rats. Furthermore, glucose utilization was altered since lower glucose-6-Pase (−33%; p<0.05) and increased glucokinase (+212%; p<0.001) activities in the liver were found in the rat model of hypercholesterolemia.Conclusion: These results provide new evidence that a diet-induced hypercholesterolemia in rats is associated with several adaptative changes in carbohydrate metabolism. These findings may be of importance not only considering the role of western diets on cholesterogenesis, but also in other metabolic disturbances involving lipid and carbohydrate metabolism.

Pivalate Affects Carnitine Status but Causes No Severe Metabolic Changes in Rat Liver

To investigate the carnitine deficiency induced by pivalate, rats had free access to drinking water with or without pivalate. Consumption of 20 mmol/L pivalate for 1 wk decreased the levels of both free and total carnitine in plasma to ∼20% of levels before treatment. After 4 wk, the concentrations of free carnitine in the liver, heart and muscle of pivalate-treated rats were ∼60–80% of the control, and in the kidney, 26% of the control. Fractional excretion of free carnitine (FEFC) in pivalate-treated rats was measured; however, the treatment for 3 or 8 d did not affect the values relative to those obtained before treatment. Treatment with pivalate for 4 wk did not affect plasma concentrations of glucose, ammonia and free fatty acids (FFA) in the rats; however, the concentration of 3-hydroxybutyrate (3-OHB) was higher, and the FFA/3-OHB ratio was lower than those of controls. In a liver perfusion study, ketogenesis from oleate and gluconeogenesis from lactate and pyruvate in rats treated with pivalate for 4 wk were not different from controls. These results suggest that administration of pivalate did not induce the excessive excretion of free carnitine in urine, and secondary carnitine deficiency induced by intake of 20 mmol/L pivalate for 4 wk did not cause severe metabolic changes in rat liver.

Osmotic diarrhoea and skeletal muscle protein synthesis in vivo.

The pathogenic nature of the wasting seen in diarrhoea is unknown. This study measured protein synthesis in an established model of diarrhoea using lactose for seven days. Comparisons were also made with data obtained from rats fed an identical diet in which lactose was replaced by isocaloric glucose ad libitum (that is, the control diet). To account for diarrhoea induced anorexia, a third group of rats were included, which were fed identical amounts of the control diet as the rats with diarrhoea inducing diet. Comparisons of the diarrhoea induced group with rats fed the control diet ad libitum showed that diarrhoea caused a significant reduction in body weights. Type I and type II muscles showed significant reductions in protein, RNA, and DNA contents, as well as a fall in the derived parameters, RNA/DNA, protein/DNA, and RNA/protein. Fractional rates of protein synthesis (ks) were also reduced. However, synthesis rates of type I and II muscles relative to RNA (kRNA) were unchanged in these muscles in diarrhoea induced rats compared with ad libitum fed controls. In the jejunum there was an increase in the RNA/DNA ratio, and reductions in ks and kRNA. Comparisons were also made between rats with diarrhoea and rats pair fed the control diet. There were no changes in total muscle protein, RNA or DNA contents. This suggests that an important feature of body wasting in diarrhoea is the element of anorexia, which induces severe metabolic changes. The comparison between rats with diarrhoea and the pair fed group showed that histological features of the plantaris were not overtly changed, though diarrhoea caused significant reductions in RNA/DNA, protein/DNA, ks, and kRNA. Similar changes were seen for the soleus; though the reduction in ks failed to attain statistical significance. In the jejunum a comparison of diarrhoea induced rats with pair fed controls, showed increases in the ratios of RNA/DNA and protein/DNA.

Hypoxia increases glucose transport at blood-brain barrier in rats

Prolonged hypoxia causes several adaptive changes in systemic physiology and tissue metabolism. We studied the effects of hypobaric hypoxia on glucose transport at the blood-brain barrier (BBB) in the rat. We found that hypoxia increased the density of brain microvessels seen on immunocytochemical stains using an antibody to the glucose transporting protein GLUT. In addition, we found that hypoxia increased the density of GLUT in isolated cerebral microvessels as determined by specific cytochalasin B binding. The higher GLUT density in isolated cerebral microvessels was evident after 1 wk of hypoxia and was associated with decreased activity of gamma-glutamyltranspeptidase. Consistent with these findings, we also demonstrated that 3 wk of hypobaric hypoxia caused increased unidirectional transport of glucose at the BBB in several brain regions in vivo, as determined by the doubly labeled single-pass indicator-fractionation atrial bolus injection method in anesthetized rats. We conclude that chronic hypobaric hypoxia is associated with increased glucose transport at the BBB.

Influence of age on skeletal muscle glucose transport and glycogen metabolism

Age-related alterations in skeletal muscle carbohydrate metabolism can influence both health and performance. Exercising muscle glycogenolysis is accelerated in old, male rats compared with young animals, perhaps secondary to the age-related reduction in muscle oxidative capacity and blood flow during contractile activity. Muscle oxidative capacity and blood flow during exercise are also reduced in untrained older humans. Endurance training enhances muscle oxidative capacity and promotes muscle glycogen sparing during exercise by young and old rats. Resting muscle glycogen concentration is unchanged in old rats, but considerably reduced in untrained, older humans. Exercise training increases the muscle glycogen levels of older people. The concentration of GLUT-4 glucose transporter protein declines in some muscles of rats during growth and development, but remains stable thereafter. Exercise training can elevate the muscle GLUT-4 protein levels of both young and old humans. On the other hand, exercise training has been shown to increase the GLUT-4 values of adult, but not old rats. After one bout of exercise, muscle sensitivity for insulin-stimulated glucose transport is improved in young and old rats. These findings indicate that several age-related changes in muscle carbohydrate metabolism can be minimized by acute or chronic exercise.

Effect of the peroxisome proliferator LY171883 on triglyceride accumulation in rats fed a fat-free diet

LY171883 is a leukotriene D 4 antagonist that induces peroxisome proliferation in the rodent liver. Like many peroxisome-proliferating agents, it causes transient lipid accumulation and several other changes in hepatic lipid metabolism. The effect of LY171883 on lipid metabolism was studied further in rats maintained on a fat-free diet. Administration of a fat-free diet for 14 days caused a 5.6-fold increase in liver triglycerides associated with a 3.3-fold increase in fatty acid synthetase. Co-administration of 0.1% LY171883 increased liver triglycerides slightly, whereas 0.3% LY171883 prevented the accumulation of triglycerides. Furthermore, treatment with 0.3% LY171883 reversed the fatty liver in rats pretreated with the fat-free diet for 14 days. Fatty acid synthetase activity increased comparably in all treatment groups, indicating that 0.3% LY171883 did not prevent the lipogenic response to a fat-free diet. In rats treated with 0.3% LY171883, peroxisomal β-oxidation increased 9.5-fold, mitochondrial β-oxidation 4.8-fold, carnitine palmitoyltransferase I 1.9-fold, and plasma ketones 3-fold. In the 0.1% dose group the increases in these parameters were smaller. The data indicate that 0.3% LY171883 sufficiently increased mitochondrial and peroxisomal β-oxidation such that fatty acids generated by lipogenesis were preferentially oxidized rather than esterified to triglycerides. In the 0.1% dose group oxidation was only mildly increased, and the excess fatty acids continued to be esterified.

Dietary modification of potential vitamin K supply from enteric bacterial menaquinones in rats

Rats given a low-fibre diet based on boiled white rice developed symptoms of severe vitamin K deficiency within 23 d. Inclusion of autoclaved black-eye beans (Vigna unguiculata) in the diet prevented the bleeding syndrome. To test the hypothesis that deficiency resulted from low phylloquinone intake exacerbated by inadequate production of menaquinones by the enteric bacteria, a follow-up experiment was carried out in which groups of rats were given an all-rice diet, a rice + beans diet or a stock diet. Rats on the all-rice diet had significantly lower faecal concentrations of the main menaquinone-producing bacterial species (Bacteroides fragilis and Bacteroides vulgatus) than animals on either of the other two diets. This coupled with the much lower faecal output on this diet suggests that total menaquinone production was low for the all-rice diet. The alterations in faecal flora were associated with several significant changes in caecal metabolism. Rats given the stock diet had much shorter caecal transit times and a considerably greater proportion of butyric acid in volatile fatty acid end-products than did rats on either of the other two diets.

Persistence of Hypertriglyceridemic Effect of Low-Fat High-Carbohydrate Diets in NIDDM Patients

Although low-fat high-carbohydrate diets are recommended for patients with non-insulin-dependent diabetes mellitus (NIDDM) in an effort to reduce the risk of coronary artery disease (CAD), the results of short-term studies have shown that these diets can lead to changes in carbohydrate and lipid metabolism associated with an increased risk of CAD. This study has extended these earlier observations by determining the metabolic effects of such diets over a longer period in these patients. The comparison diets contained either 40 or 60% of the total calories as carbohydrates, with reciprocal changes in fat content from 40 to 20% consumed in random order for 6 wk in a crossover experimental design. The ratio of polyunsaturated to saturated fat and the total cholesterol intake were held constant in the two diets. Plasma glucose and insulin concentrations were significantly (P less than .001) elevated throughout the day when patients consumed the 60% carbohydrate diet, and 24-h urinary glucose excretion more than doubled (0.8 vs. 1.8 mol/24 h). Fasting plasma total and very-low-density lipoprotein (VLDL) triglyceride (TG) concentrations increased by 30% (P less than .001) after 1 wk on the 60% carbohydrate diet, and the magnitude of carbohydrate-induced hypertriglyceridemia persisted unchanged throughout the 6-wk study period. Total plasma cholesterol concentrations were similar after both diets. However, VLDL cholesterol (VLDL-chol) was significantly increased, whereas both low-density lipoprotein (LDL-) and high-density lipoprotein (HDL-) chol concentrations were significantly decreased after consumption of the 60% carbohydrate diet. Consequently, neither total-chol-to-HDL-chol nor LDL-chol-to-HDL-chol ratios changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Potentiation of the actions of insulin by taurine.

Taurine was found to mediate several changes in myocardial metabolism. In the absence of insulin, only oxygen consumption was significantly elevated by taurine; however, in the presence of 2.5 U/L insulin the amino acid caused the stimulation of glycolysis and glycogenesis, as well as oxygen utilization. These effects of taurine were shown to be dependent on insulin concentration, suggesting a link between the two substances. Measurements of key metabolic intermediates revealed that taurine stimulated glycolysis by enhancing flux through phosphofructokinase. Similarly, it was shown that glycogenesis was promoted because of the increase in glycogen synthase I and decrease in phosphorylase alpha activity. Several possible mechanisms for the observed changes are discussed.

Cerebral Protective Effect of Low-Grade Hypothermia

Male Wistar rats with unilateral carotid ligation were exposed to arterial hypoxia (PaO2 20-23 torr for 20 min) while body temperature was controlled at 37 degrees C, 36 degrees C, or 34 degrees C. Brain cortical concentrations of ATP, phosphocreatine (PCr) and lactate were measured microfluorometrically. Normothermic hypoxic rats had severe metabolic changes with low brain ATP and extremely high brain lactate. When rectal temperature was controlled at 36 degrees C during hypoxia, brain ATP was not different from that observed in normothermic, normoxic rats, and brain lactate was significantly lower than during normothermic hypoxia. At 34 degrees C, brain lactate was even less, but still three times higher than that observed in normothermic normoxic rats. PCr was significantly higher following hypoxia at 34 degrees C than at 37 degrees C. In part, this latter finding may reflect preservation of intracellular pH at 34 degrees C. A decrease of body temperature of 1-3 degrees C can minimize or prevent brain energy failure during hypoxia as well as decrease the magnitude of brain tissue acidosis. Thus, in experiments examining protective effects of therapies during brain hypoxia-ischemia, stringent control of body temperature is necessary. Furthermore, a possible clinical benefit resulting from modest reduction in body temperature in patients with marginal cerebral oxygenation is suggested.

Energy metabolism of Plantago lanceolata, as affected by change in root temperature

The long and short term metabolic effects of a shift in root temperature was investigated in Plantago lanceolata L. with special reference to the role of the cyanide resistant alternative pathway in root respiration. After a 10‐day period of growth at a 13°C root temperature, a decrease in root as well as shoot growth was observed, compared to control plants grown continuously at 21°C. Apart from an increase in shoot soluble and insoluble sugar level, no changes in metabolism were found, neither in root respiration, shoot photosynthesis, nor in root sugar and plant protein level.Decreasing the root temperature from 21 to 13°C gave several clear short term changes in metabolism. Within one hour a decrease in cytochrome chain activity of the roots was found together with an increase in activity of the alternative chain. After 24 h a recovery to the initial level of both chains was observed. An increase in root temperature from 13 to 21°C gave an immediate increase in activity of both respiratory chains that was still present 24 h after the switch.It is concluded that the activity of the alternative respiratory pathway in the root is strongly affected by a sudden temperature change in the root environment. This pathway acts in a way which is described by ‘the energy overflow model'. The presence of the alternative electron transport pathway should be taken into account in determinations of the respiratory Q10. Moreover, the length of time between the temperature change and respiration measurements is an important factor.

Effect of syringomycin and syringotoxin produced by Pseudomonas syringae pv. syringae on structure and function of mitochondria isolated from holcus spot resistant and susceptible maize lines

Syngomycin (SR) and syringotoxin (ST), two toxigenic peptides produced by ecotypic strains of Pseuomonas syringae pv. syringae, caused several changes in oxidative metabolism of mithochodria isolated from etiolated shoots of ACCO maize lines WF9 and B37 which differed in susceptibility to holus spot disease. Evidence was obtained that both toxins, in a concentration range of 6 to 24 μg mg−1 mitochondrial protein, depending on the toxin and on the substrate being oxidized, caused uncoupling of oxidative phosphorylation, stimulation of succinate, malate/glutamate and NADH respiration, stimulation of ATPase activity, inhibition of ATP formation, increased swelling, and a decrease in mitochoondrial membrane potential. Generally the effect induced by ST was greater than that of SR. ST at 6 μg mg−1 protein caused complete uncoupling with all three substrates tested, while SR had the same effect at 12 μg mg−1 protein with NADH and succinate and at 24 μg mg−1 protein with malate/glutamate. This difference between SR and ST was probably due to a difference in specificity for their sites of action. Electron micrographs of B37 mithochodria indicated that SR and ST caused swelling with fragmentation of the inner membrane.The effects of the two toxins on WF9 and B37 mithochondria were the same, although, based on number of lesions and population dynamics of the pathogen in leaf tissues, pathogenicity tests indicated that leaves of WF9 were more susceeptible to P. syringae pv. syringae than those of B37. However, when leaf tissues were treated with SR or ST, B37 was more sensitive to the toxins than WF9. Both toxins caused typical holcus spot symptoms. Based on assays of bacterial populations in leaves, susceptibility of WF9 in contrast to the resistance of B37 to holcus spot was apparently due to the effects of host substrate on the extent and rate of growth of pathogenic bacteria in relation to production of SR.

Metabolic disorders in severe abdominal sepsis: Glutamine deficiency in skeletal muscle

The metabolic profiles of 14 patients with prolonged abdominal sepsis were analysed on the second day after laparotomy. The profiles of survivors were compared with those of non-survivors who died one to five days after the time of evaluation due to uncontrollable multiple organ failure. In the non-surviving patients plasma gluoose and glucagon levels were significantly higher than in surviving patients. The plasma concentrations of phosphoserine, cysteine, valine, phenylalanine, and 3-methylhistidine were found to be significantly increased in non-survivors and their muscle tissue showed significantly decreased concentrations of glutamine, proline and lysine with increases in valine and leucine. A correct classification of non-survivors and survivors could be obtained from the plasma and muscle amino acid concentrations, the highest discriminant power being from muscle glutamine. In severe sepsis metabolic changes correlate with the outcome of the patients, and amino acid metabolism seems to be characterised by low concentrations of muscle glutamine and high levels of the branched chain amino acids possibly indicating an inhibited intracellular glutamine formation in muscle tissue.

Cerebral protective effect of low-grade hypothermia.

Male Wistar rats with unilateral carotid ligation were exposed to arterial hypoxia (PaO2 20-23 torr for 20 min) while body temperature was controlled at 37 degrees C, 36 degrees C, or 34 degrees C. Brain cortical concentrations of ATP, phosphocreatine (PCr) and lactate were measured microfluorometrically. Normothermic hypoxic rats had severe metabolic changes with low brain ATP and extremely high brain lactate. When rectal temperature was controlled at 36 degrees C during hypoxia, brain ATP was not different from that observed in normothermic, normoxic rats, and brain lactate was significantly lower than during normothermic hypoxia. At 34 degrees C, brain lactate was even less, but still three times higher than that observed in normothermic normoxic rats. PCr was significantly higher following hypoxia at 34 degrees C than at 37 degrees C. In part, this latter finding may reflect preservation of intracellular pH at 34 degrees C. A decrease of body temperature of 1-3 degrees C can minimize or prevent brain energy failure during hypoxia as well as decrease the magnitude of brain tissue acidosis. Thus, in experiments examining "cerebral protective effects" of therapies during brain hypoxia-ischemia, stringent control of body temperature is necessary. Furthermore, a possible clinical benefit resulting from modest reduction in body temperature in patients with marginal cerebral oxygenation is suggested.

L-alpha-hydroxycholecalciferol treatment of adults with chronic renal failure.

Five adult patients with chronic renal failure and associated renal osteodystrophy have been treated for 6 months with 1-alpha-hydroxycholecalciferol (1 alpha-OH-D3), a synthetic vitamin D analogue. All 5 patients had severe metabolic bone changes as estimated by bone scintigraphy. Three patients were hypocalcemic, 4 had elevated serum alkaline phosphatases, 5 had elevated serum immunoreactive parathyroid hormone (i-PTH) concentration and 3 had bone pains. During treatment serum calcium increased in all patients (mean 11.4%) and 3 originally hypocalcemic patients became normocalcemic. Serum alkaline phosphatases decreased (mean 27.3%) and became normal in 4 patients, who initially had elevated values. A pronounced decline in the serum concentration of i-PTH (mean 53%) was seen in all patients and 1 patient obtained normal i-PTH levels after 4 months of treatment. The intestinal calcium absorption, which was low initially, even when calcium intake was considered, rose almost threefold (mean 273%) and reached normal values in all cases. The bone mineral content increased in all patients, but the changes were small (mean 4.9%) and insignificant. Finally, bone pain disappeared in 2 patients and improved in 1 of 3 patients exhibiting this symptom. A linear correlation (r = 0.48, p less than 0.001) was found between the dose of 1 alpha-OH-D3 and serum calcium. But in spite of this and the frequent control, all patients developed one episode of hypercalcemia. This disappeared within 48 hours after discontinuing the drug. It is concluded that treatment with 1 alpha-OH-D3 appears to be of therapeutic value in metabolic bone disease associated with chronic renal failure, but frequent control of blood biochemistry seems mandatory.

Spironolactone and testicular cytochrome P-450: decreased testosterone formation in several species and changes in hepatic drug metabolism.

The daily administration of spironolactone caused a 40–90% decrease in the level of microsomal cytochrome P-450 in the testes of rat, guinea pig, rabbit, mouse and dog, but no reduction was detected in the amount of cytochrome b5. The loss of microsomal cytochrome P-450 was concomitant with a similar loss of both the microsomal heme associated with cytochrome P-450 and the activity of the microsomal 17α-hydroxylase. In contrast to its effects on the 17α-hydroxylase, spironolactone administration slightly increased the enzyme activity of the microsomal 17β-dehydrogenase. The extent of the destruction of cytochrome P-450 by spironolactone was dependent upon the dosegiven and upon the duration of the treatment. The decline in androgen formation in the testis resulted in a 30–35% decrease in the activity ofhepatic 3,4-benzpyrene hydroxylase in the rat, but an 80% increase in the guinea pig. The decrease inthe 3,4-benzpyrene hydroxylase activity in the rat could be prevented by the administration ofandrogens, ...

Diagnostic value of stationary potential measurement in head injuries.

Traumatic brain injuries were analysed clinically and experimentally by recording stationary potential(SP) which is a very stable component in the electrical phenomena of the brain. SP value is considered to change positively or negatively only when there are organic lesions, severe metabolic changes of the brain, or epileptic seizures. Clinically, we have measured the SP of 103 head-injured patients. When an organic lesion was located in the cerebral hemisphere, the SP showed various changes according to the location of the lesion. Positive SP changes were usually seen in the cases of mild cortical compression and subcortical lesions. Clinically, these lesions included epidural hematoma, subdural hematoma without contusion, chronic subdural hematoma, simple depressed fracture and intracerebral hematoma without cortical damage. Whereas, almost all of the cortical lesions or extensive brain lesions showed negative changes of SP. They were such as cerebral contusion, intracerebral hematoma with vascular lesion, depressed fracture with cortical damage and traumatic epilepsy. Subsequently, to support these clinical data, experimental cortical compression with clot inserted into subdural and extradural space, subcortical lesion by artificial intracerebral hematoma, cerebral contusion by mechanical destruction were investigated in cats. The experimental results showed the same tendency as the clinical data. In another experimental study, clarification of the possibility of SP change in concussion was attempted.

Inhibition of replication of ribonucleic acid bacteriophage f2 by superinfection with bacteriophage T4.

Superinfection by phage T4 of cells infected by the ribonucleic acid (RNA) phage f2 results in inhibition of further f2 production. Experiments using rifampin show that the exclusion of f2 requires T4 gene function soon after T4 infection. By using a sensitive new peptide-mapping procedure to identify f2 coat protein in infected cells, we show that synthesis of the f2 coat occurs at a reduced level until 4 min after T4 superinfection and then ceases abruptly. Within 4 min after T4 superinfection, there are also several changes in f2 RNA metabolism, all of which require T4 gene function: preexisting f2 replicative intermediate RNA and f2 single-stranded RNA are degraded to small but still acid-precipitable fragments, and most f2-specific RNA is released from polyribosomes. We favor the hypothesis that T4 induces the synthesis of a specific endoribonuclease which degrades f2 RNA and that the inhibition of f2 protein synthesis may be a consequence of this degradation, rather than a direct effect of T4 upon translation.

Oculo-Cerebro-Renal Syndrome

THE OCULO-CEREBRO-RENAL syndrome is a congenital hereditary affectation limited to males. It is characterized by growth retardation, mental deficiency, hypotonia, mild or severe metabolic acidosis, generalized hyperaminoaciduria, proteinuria, rickets, and characteristic eye changes, the most prominent of which are bilateral congenital cataracts and glaucoma. Since the original description of this syndrome by Lowe et al¹in 1952 many other reports have appeared. Recently a disturbance in the metabolism of ornithin has been described in a patient affected with this syndrome.²The term oculocerebro-renal syndrome³and Lowe's syndrome⁴have both been used interchangeably, though the former is preferable. In some published reports a diversity of clinical and metabolic manifestation from the original description has been noted.⁵ The purpose of the present communication is to compile a comprehensive review of clinical and laboratory findings of the syndrome and to add certain as yet undocumented characteristics of the

A simplified method for safe and controllable hypothermia in neurosurgery.

In the Neurosurgical Clinic of the University of Milan moderate hypothermia (28°–30° C.) has been performed, since 1957, in about 100 cases of major intracranial surgery. The applied method consists in blowing a fast current of cool air on the bare body surface of the anaesthetized patient. The airflow is derived from an air conditioner through a wide bore plastic tube at a velocity ranging from 0.5 to 1 m. per second and a temperature of 8° to 12° C. Rewarming of the patient is obtained with warm air (40° to 55° C.) produced in the same way. The average cooling-time for adult patients has been of about 1 to 3 hours; after-drop has been less than 1.5° C. in 90% of the cases; severe cardio-circulatory, respiratory and metabolic changes occurred only occasionally. The following advantages are pointed out:simplicity: the whole procedure can be adequately managed by a single anaesthetist and does not interfere with surgery;safety: the lower limit of temperature can be fixed in advance and constant control of the level of hypothermia can be assured during any time of the surgical procedure;low cost of basic equipment.