Magnus Hägerdal

Minute ventilation and oxygen consumption during labor with epidural analgesia.

Oxygen consumption (VO2) and minute ventilation (VE) were measured between and during uterine contractions in the first stage of labor before and after lumbar epidural analgesia (LEA) in 11 women who served as their own controls. O2 and VE between contractions were essentially unchanged by LEA to a T10 or higher sensory level. Before LEA, both VO2 and VE were increased significantly during contractions by 63% and 74% respectively, whereas following LEA there was no significant increase in O2 or VE during contractionsIn the second stage of labor, O2 and VE were measured in seven patients electing to have no analgesia or sedation and in 10 patients having complete pain relief produced by LEA. Measurements were obtained 5–10 min before delivery. During contractions with pushing, O2 and VE were decreased by 25% and 31%, respectively, in patients having LEA as compared with patients having no analgesia or sedationThese results suggest that the increase in O2 and VE are due primarily to pain associated with uterine contractions and that LEA decreased the work of breathing and the oxygen consumption of the parturient in both the first and second stages of labor

THE EFFECT OF HYPERTHERMIA UPON OXYGEN CONSUMPTION AND UPON ORGANIC PHOSPHATES, GLYCOLYTIC METABOLITES, CITRIC ACID CYCLE INTERMEDIATES AND ASSOCIATED AMINO ACIDS IN RAT CEREBRAL CORTEX

The influence of hyperthermia on cerebral blood flow, cerebral metabolic rate for oxygen and cerebral metabolite levels was studied by increasing body temperature from 37° to 40°C and 42°C in rats under nitrous oxide anaesthesia maintained at constant arterial CO2 tension. The metabolic rate for oxygen increased by 5‐6% per degree centigrade. At 42°C the increase in cerebral blood Row was comparable to that in the metabolic rate. The increased temperatures were not accompanied by changes in organic phosphates (phosphocreatine, ATP, ADP or AMP) or in lactate/pyruvate ratio. There was an increase in the tissue to blood glucose concentration ratio. At steady state, there was an increase in glucose‐6‐phosphate but no other changes in glycolytic metabolites or citric acid cycle intermediates, and the only change in amino acids studied (glutamate, glutamine, aspartate, alanine and GABA) was an increase in glutamate concentration.

The Effect of Nitrous Oxide on Oxygen Consumption and Blood Flow in the Cerebral Cortex of the Rat

The effect of 70% nitrous oxide upon cerebral oxygen consumption (CMRo2) and cerebral blood flow (CBF) was studied in artificially ventilated rats. The control groups consisted of unanaesthetized animals in which a stress‐induced increase in CMRo2 and CBF was prevented by previous adrenalectomy, or by administration of a beta blocker (propranolol). There were no significant differences in CMRo2 between animals ventilated with either N2O or N2. It is concluded that if nitrous oxide depresses cerebral metabolism the depression cannot exceed 10%.

Protective effect of hypothermia in cerebral oxygen deficiency caused by arterial hypoxia.

To study the cerebral protective effects of hypothermia in arterial hypoxia, anesthetized (70 per cent N2O), mechanically ventilated rats were cooled to a body temperature of 27 C. Hypoxia was induced by decreasing the oxygen content in the inspired gas mixture either to 6–7 per cent or to 2.5–3 per cent. This reduced mean PaO2 to about 25 and 11–12 torr, respectively. At PaO2 25 torr, there was no change in cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), or labile tissue metabolites. The absence of signs of cerebral hypoxia could be attributed to an effect of temperature and pH on the hemoglobin–oxygen dissociation curve. Thus, at 27 C with a PaO2 of 25 torr the total oxygen content (TO2) of arterial blood remained >15 ml (100 ml)-1, about three times the value obtained at this PO2 in normothermic rats. At PaO2 11–12 torr, arterial TO2 was reduced to about 5 ml (100 ml)−1. The hypoxia induced no change in CMRO2, a threefold increase in CBF, a moderate lactacidosis in the tissue, and a small decrease in phosphocreatine content, but no change in ATP, ADP, or AMP. These changes are less marked than those occurring at the same arterial TO2 in normothermic rats. It is concluded that hypothermia exerts a pronounced protective effect on the brain in hypoxic hypoxia, and that two mechanisms are involved. First, since hypothermia shifts the oxyhemoglobin-dissociation curve towards the left, and prevents or minimizes a rightward shift due to acidosis, it maintains a high TO2 in arterial blood at a given PaO2. Second, by reducing CMRO2, and thereby presumably also cellular energy requirements, hypothermia exerts a protective effect at the cellular level.

The Effects of Diazepam on Cerebral Blood Flow and Oxygen Consumption in Rats and its Synergistic Interaction with Nitrous Oxide

The effects of diazepam on cerebral blood How (CBF) and cerebral oxygen uptake(CMRo2) was studied using a 133xenon modification of the Kety— Schmidt (1948) technique in paralyzed, artificially ventilated nits with and without simultaneous administration of 70 per cent nitrous oxide. Diazepam was given iv in doses that induced light to heavy sedation or general anesthesia. When given with 70 per cent nitrous oxide, diazepam in sedative and anesthetic doses lowered CBF and CMRo2 to about GO per cent of control. In the absence of nitrous oxide all doses of diazepam caused moderate (20–30 percent) decreases in CBF, but CMRo2 remained unchanged or was only slightly lowered. It is concluded that diazepam interacts with nitrous oxide to produce a reduction in CMRo2 similar to that seen in barbiturate anesthesia, but that alone the drug produces sedation and anesthesia without a comparable decrease in CMRo2.

Protective Effects of Combinations of Hypothermia and Barbiturates in Cerebral Hypoxia in the Rat

The protective effects of phenobarbital and hypothermia in cerebral hypoxia were studied in Wistar rats with unilateral carotid ligation. The animals were exposed to hypoxia (Pao2 25–15 torr) for 25 minutes. Cerebral protection was evaluated by means of effects on cerebral tissue ATP, phosphocreatine (PCr), lactate, and nicotinamide-adenine dinucleotidc (NADH) values. At Pao2 25 torr, cerebral blood flow (CBF) and cerebral oxygen consumption (CMRo2) were decreased by 25 per cent either with phenobarbital, 50 mg/kg, or by hypothermia, 32 C, or decreased by 40–50 per cent with hypothernlia, 27 C, phenobarbital, 150 mg/kg, or the combination of 32 C and phenobarbital, 50 mg/kg. The group given phenobarbital, 50 mg/kg, as well as the normothermic hypoxic control group, had marked metabolic changes, with a 30–50 per cent decrease in PCr and a four- to sixfold increase in lactate levels on the ligated side compared with the hypothermic rats. The hypothermic rats showed almost no metabolic sign of hypoxia. All rats in the group that received phenobarbital, 150 mg/kg, developed cardiac arrhythmias and decreases in blood pressure. No animal in this group survived.At Pao2 15 torr, hypothermia to 32 C alone or combined with phenobarbital, 50 mg/kg, decreased PCr 40–50 per cent and increased lactate values four to fivefold on the ligated side compared with hypothermia to 27 C alone. With the exception of an elevated lactate level on the ligated side, there was no metabolic sign of hypoxia with hypothermia to 27 C.As judged by metabolic criteria, hypothermia offers better cerebral protection from hypoxia than docs a dose of phenobarbital that gives the same decreases in CBF and CMRo2 Hypothermic rats had less severe metabolic acidosis and higher arterial oxygen contents, which may partly explain the greater protective effect.

EFFECT OF HYPOTHERMIA UPON ORGANIC PHOSPHATES, GLYCOLYTIC METABOLITES, CITRIC ACID CYCLE INTERMEDIATES AND ASSOCIATED AMINO ACIDS IN RAT CEREBRAL CORTEX

—The influence of hypothermia upon the metabolism of the brain was studied by reducing body temperature in N2O‐anaesthetized rats to 32, 27 or 22°C, with subsequent measurements of organic phosphates, glycolytic metabolites, citric acid cycle intermediates and associated amino acids. Hypothermia was maintained for either 1 or 2 h and the effect of anaesthesia was evaluated by maintaining unanaesthetized animals at 22°C. Hypothermia had no influence on the cerebral cortical concentrations of ATP, ADP or AMP and there was only a small increase in phosphocreatine. Since the tissue concentrations of glucose and glycogen were reduced, it is concluded that the well known resistance of the hypothermie brain to ischaemia is unrelated to increased energy stores.

Brain metabolism in the critically ill.

A large number of clinical conditions are associated with a transient or permanent disturbance of brain function. Common to all of them is that, in some way, brain metabolism is changed from the normal. These changes cover a vast spectrum, ranging from the subtle alterations of metabolism encountered in mental disease to those underlying death and dissolution of cells in conditions of oxygen lack. This communication is concerned with brain metabolism in the critically ill with emphasis on conditions of hypoglycemia, hypoxia, and ischemia. We begin by briefly recalling the salient features of brain metabolism in the healthy individual. Since clinicians caring for critically ill patients take an interest in factors that may aggravate the primary disease and in measures that may prevent or minimize its final effect on the brain, we will also briefly consider how brain metabolism is influenced by potentially harmful factors (hyperthermia, anxiety and stress, and tissue acidosis due to CO2 retention) as well as by measures that are often instituted to ameliorate the effects of hypoxia and ischemia (hypothermia, administration of anesthetics and sedatives). We refer the reader to selected references with preference to recent articles reviewing previous literature.

Influence of Changes in Arterial PCO2 on Cerebral Blood Flow and Cerebral Energy State during Hypothermia in the Rat

In order to study the relationship between arterial PCO2 and cerebral blood flow (CBF) in hypothermia, the body temperature of artificially ventilated rats was decreased to 22d̀C, and changes in CBF were evaluated from arteriovenous differences in oxygen content (AVDO2) at PaCO2 values of 15, 30, 40 and 60 mm Hg. The results were compared to those obtained at normal body temperature (37d̀C) over the PaCO2 range 15–60 mm Hg. Separate experiments were performed to evaluate CBF and CMRO2 at 22d̀C and a PaCO2 of 15 mm Hg, using an inert gas technique for CBF. The tissue contents of phosphocreatine, ATP, ADP, AMP and lactate were measured in hypothermic animals at Paco2values of 15, 30 and 60 mm Hg.

Effect of High vs. Low Arterial Blood Oxygen Content on CerebralEnergy Metabolite Levels during Hypoxia with

The effects of different levels of arterial blood oxygen content (CaO2) on brain tissue adenosine triphosphate (ATP), phosphocreatine (PCr), lactate, and reduced nicotinamide adenine dinucleotide (NADH) were studied during cerebral hypoxia in normothermic and hypothermic male Wistar rats with unilateral carotid ligation. Animals were exposed to hypoxia (PaO2 19–26 torr) for 25 min, and brain tissue metabolite values measured microfluorometrically were compared with those of normothermic normoxic controls. CaO2 was 4.0 ± 0.2 ml/dl (mean ± SEM) at PaO2 26 torr in normothermic animals. CaO2 was increased to 8.2 ± 0.3 ml/dl at PaO2 26 torr by means of bicarbonate infusion producing a leftward shift of the oxyhemoglobin-dissociation curve in one normothermic hypoxic group. In all normothermic hypoxic groups ATP and PCr decreased and lactate and NADH increased significantly compared with control values. There was no significant difference in brain tissue metabolite values among these groups despite an increase in CaO2 by twofold in one group. Hypothermia (32 C) resulted in CaO2 8.4 ± 0.2 ml/dl at PaO2 26 torr. This was decreased to 4.0 ± 0.2 ml/dl by decreasing PaO2 to 19 torr in another group at the same temperature. ATP and PCr were well preserved in both groups despite the difference in CaO2s. Although the lactate and NADH levels were increased in the hypothermic group with CaO2 4.0 ± 0.2 ml/dl, they were significantly lower than those values in normothermic hypoxic groups. These results indicate that the increase in CaO2 produced by hypothermia is not a major determinant in hypothermic protection during cerebral hypoxia.