Cent Oxygen Research Articles

Tracheal constriction by morphine and by fentanyl in man.

The effects of morphine and fentanyl on tracheal smooth muscle tone were studied in 38 patients during induction of anesthesia. Endotracheal tube cuff pressure was used to measure tracheal tone. Anesthesia was maintained with nitrous oxide, 70 per cent in oxygen, and pancuronium and ventilation was controlled with a respirator. Morphine, 0.5 mg/kg, produced a biphasic response, initially causing tracheal dilatation and then tracheal constriction. Ten minutes after morphine injection, cuff pressure increased to significantly (21 +/- 8 per cent) above control. Morphine-induced tracheal constriction could be completely blocked by the prior administration of atropine, 0.5 mg. Fentanyl, 0.006 mg/kg, also produced significant tracheal constriction, cuff pressures increasing to 44 +/- 11 per cent above control at 10 min. Fentanyl-induced tracheal constriction could be blocked by pretreatment with droperidol, 0.25 mg/kg. At equianalgesic doses, morphine and fentanyl produced similar tracheal constriction.

A simple technique for the utilization of postmortem tracheal and bronchial tissues for ultrastructural studies

Human tracheal and bronchial tissues were taken from autopsy cases within five hours of death. The tissue was placed in a modified Krebs-Henseleit solution at either 37° C. or 7° C. A combination of 95 per cent oxygen and 5 per cent carbon dioxide was bubbled through the Krebs-Henseleit solution. Two hours after equilibration of the tissue in the bath at 37° C. an electrical field stimulation was applied to the tissue and, if the tissue was physiologically active, it was utilized for further studies. At the termination of these studies the tissue was processed for electron microscopy. Control tissue was taken directly from the same area as the test tissue and was processed for electron microscopy without immersion in the Krebs-Henseleit solution. The tissue, after immersion in the Krebs-Henseleit solution for at least three hours, showed evidence of substantial recovery from the period of anoxia.

CEREBRAL BLOOD FLOW AND METABOLISM DURING MORPHINE-NITROUS OXIDE ANESTHESIA IN MAN

JOBES, D. R.; KENNELL, E. M.; BUSH, G. L.; MULL, T. D.; LECKY, J. H.; BEHAR, M. G.; WOLLMAN, H. Author Information

Severe fat embolism: a review of 24 cases.

Twenty-four patients suffering from fat embolism syndrome, severe enough to warrant transfer to an artificial ventilation unit, are reviewed. All developed the condition following trauma. Five patients were managed with oxygen therapy and sedation, but the other 19 needed intubation and ventilation to achieve adequate arterial oxygenation. In spite of intensive supportive therapy, 6 patients (who had all required ventilation) died, one due to heparin therapy, the others from progression of the syndrome. A poor prognosis seemed to be associated with young age, a rapidly progressive condition and a continued need for 100 per cent oxygen after institution of artificial ventilation. There seemed to be no relationship between outcome and severity of injury, type of surgical management and time of onset after injury. The clinical features of these patients are discussed with reference to the many unanswered questions that surround this condition.

Alveolar hypoventilation syndrome: Studies of ventilatory control in patients selected for diaphragm pacing

The syndrome of nocturnal hypoventilation and/or apnea without major intrinsic lung disease is of greater surgical interest since the introduction of therapeutic diaphragm pacing. Of our 29 patients successfully managed by diaphragm pacing, we describe 17 in whom detailed studies of the ventilatory responses to hypoxia are available. The diagnosis was established by the following criteria: (1) an increase in arterial carbon dioxide tension (PaCO 2) (> 45 mm Hg) and a depression in the arterial oxygen tension (PaO 2) (< 75 mm Hg) at least during sleep; (2) respiratory arrests and/or apneic episodes during sleep; (3) near normal tests of ventilatory capacity; and (4) diminished ventilatory response to carbon dioxide breathing. New information on the ventilatory responses to hypoxia was obtained by a nonsteady state closed-circuit rebreathing method. The following were compared: (1) hypoxia with carbon dioxide variably absorbed so as to maintain base line PaCO 2 (“normo”-capnic hypoxia); (2) 50 per cent oxygen with carbon dioxide accumulation (hypercapnia hyperoxia); and (3) carbon dioxide accumulation in room air (hypercapnic hypoxia). The data indicate (1) 15 patients showed no measurable ventilatory response to “normo”-capnic hypoxia and two patients showed blunted responses; (2) seven patients showed no ventilatory responses to carbon dioxide whereas 10 patients showed suboptimal increases; (3) combined hypoxia and hypercapnia caused a suboptimal ventilatory response in four patients. These same four patients showed blunted as opposed to absent ventilatory responses to carbon dioxide. (4) Five patients showed no ventilatory responses to all combinations. These 17 patients together with three others not so extensively studied have been managed by nocturnal diaphragm pacing for periods of four months to nearly eight years. We conclude (1) ablation or severe blunting of the ventilatory responses to hypoxia is a frequent and previously underestimated component of this disorder; and (2) diaphragm pacing is an appropriate form of therapy.

DIAZEPAM-KETAMINE ANAESTHESIA FOR OPEN HEART SURGERY

Two hundred open-heart cases were anaesthetized with a diazepam-ketamine combination. The results were excellent. A “Micro-Mini” drip technique insured low, even, but adequate dose levels of ketamine and less drug was used. Induction and maintenance are simple and smooth. Effects on the cardiovascular system and respiratory system are minimal. The margin of safety is wide and 100 per cent oxygen can be used whenever needed.

Hypoxemia of cirrhosis: Detection of abnormal small pulmonary vascular channels by a quantitative radionuclide method

Abnormal pulmonary perfusion pathways found at autopsy in patients with hepatic cirrhosis have been suggested as a major cause of hypoxemia in cirrhosis. However, these abnormal vascular channels have been difficult to document during life. In the present study, the pathophysiology of hypoxemia (arterial oxygen tension [PaO 2] 48.5 to 68 mm Hg) in three patients with hepatic cirrhosis was investigated utilizing conventional cardiopulmonary tests and a special radionuclide technic for the detection of shunting through small dilated pulmonary vessels. Pulmonary function tests revealed normal spirometry and lung volumes; normal closing volume and single-breath nitrogen washout; abnormal diffusing capacity (41 to 68 per cent of predicted); increased venous admixture on 100 per cent oxygen (O 2) (8.1 to 29 per cent); and a decrease in PaO 2 after change from the supine to the sitting position and after exercise. Cardiac catheterization revealed normal pulmonary arterial pressures at rest and during exercise, increased cardiac outputs and no intracardiac shunts. Chest roentgenograms and pulmonary angiograms were within normal limits. Utilizing a quantitative radionuclide technic, 10 per cent, 46 per cent and 70.5 per cent of intravenously injected technetium 99m-macroaggregated albumin ( 99mTc-MAA) particles traversed the pulmonary vasculature and lodged in endorgan systemic capillary beds in the three patients with cirrhosis compared with ⩽6 per cent in eight control subjects. The results of the quantitative radionuclide study document the presence of dilated pulmonary capillaries and/or arteriovenous communications which are too small to be detected angiographically. These abnormal vascular channels can account for the observed hypoxemia primarily on the basis of diffusion/perfusion imbalance and to a lesser extent by true shunting. A similar mechanism may be responsible for the hypoxemia commonly found in other patients with cirrhosis.

Hypertensive pulmonary vascular disease in children. Detection by radioactive nitrogen (13N) inhalation and injection.

Regional lung function has been studied in 16 children with intracardiac shunts and a variety of associated cardiac anomalies using radioactive nitrogen (13N) and a gamma camera-computer system. The distribution and washout of inhaled 13N were usually normal. The distribution of intravenously injected 13N was often abnormal and could be related to local anatomy. The most important finding was delayed clearance by ventilation of intravenously injected 13N in children with an abnormally raised pulmonary/systemic vascular resistance ratio (Rp/Rs) at cardiac catheterisation. The regional localisation of this ventilation-perfusion imbalance could be related in several children to the probable distribution of hypertensive pulmonary vascular disease, predicted either from local anatomy shown at cardiac catheterisation or from the abnormal distribution of pulmonary perfusion. Abnormalities present on breathing air may be partially reversed on breathing 100 per cent oxygen.

Cerebral blood flow and metabolism during morphine--nitrous oxide anesthesia in man.

The effects of two levels of morphine-nitrous oxide anesthesia on cerebral blood flow (CBF) and cerebral metabolism (CMRO2) were measured in healthy male volunteers. CBF and metabolic measurements were made in the awake control state, after morphine, 1 mg/kg, with 70 per cent nitrous oxide and 30 per cent oxygen, and at a total dose of 3 mg/kg morphine with the same concentrations of nitrous oxide and oxygen. Ventilation was controlled and carbon dioxide added to inspired gas to maintain PaCO2 constant at 40 torr. CBF was 48.2 +/- 4.4 (SEM) ml/100 g/min during the control phase; 45.7 +/- 6.4 ml/100 g/min after 1 mg/kg morphine, and 44.3 +/- 4.9 ml/100 g/min after 3 mg/kg morphine. The latter values are not significantly different from control. Cerebral metabolic rates for oxygen, glucose, and lactate were normal in the control phase and did not change significantly when morphine was present at either level. It is concluded that morphine-nitrous oxide anesthesia produces no alteration of cerebral blood flow or metabolism in normal man at the two dose levels studies.

KETAMINE FOR PEDIATRIC CARDIAC ANESTHESIA

Eighty-five patients ranging from 12 h to 7 years of age were included in this study. In the first group 35 cases received ketamine, gallamine and oxygen for surgery on the great vessels. Ketamine provided satisfactory analgesia and amnesia. Heart rate did not change significantly. Gallamine gave additional safety in the prevention of bradycardia. One hundred per cent oxygen increased oxygen saturation and made more oxygen available for the tissues. The combination secured favorable conditions even in cases of sevre right to left shunt. Seven patients developed some degree of bradycardia, requiring treatment. All but one responded to epinephrime infusion. The one who did not improve died on the table. There were 6 additional deaths during the first 48 postoperative hours. Fifty infants and children received pentobarbital and morphine premedication and ketamine, pancuronium, nitrous-oxide oxygen anesthesia for open heart surgery. Cardiovascular stability with good operating conditions characterized the course of anesthesia. The increase in systolic and diastolic blood pressures and heart rate was small after induction. Further changes in these parameters during anesthesia were statistically insignificant. Perfusion pressure during cardio-pulmonary bypass was well maintained. The addition of 50 per cent nitrous oxide to inhaled oxygen significantly potentiated the duration of hypnosis and analgesia proved by ketamine. Mechanical ventilation was facilitated in both groups by the analgesia extending well into the postoperative period. There were 6 deaths in the first 48 postoperative hours in this group. The state of consciousness at the end of anesthesia and postoperative conditions of all 85 patients were comparable with that found with other agents. The techniques described provided suitable alternatives to the anesthetic management pediatric cardiac surgery.

Alteration by halothane of glucose and glycogen metabolism in rat skeletal muscle.

Exposure of resting rat diaphragm for one hour in vitro to halothane (1-1.5, 2-2.5 and 4-4.5 per cent in oxygen) produced significant alterations of intracellular glucose disposition. Glycolysis (as measured by lactate production) increased, while glycogen formation was inhibited in a dose-related fashion. Net glucose uptake was unaffected by the anesthetic except during exposure to 4-4.5 per cent halothane, when 14 per cent depression of uptake was found. Total glycogen content decreased, due mainly to the inhibition of glycogen synthesis and to some extent to a stimulation of glycogenolysis. The anesthetic did not interfere with the effect of insulin on glucose uptake or the intracellular disposition of glucose. Creatine phosphate concentrations decreased following exposure of diaphragm to 1-1.5, 2-2.5 and 4-4.5 per cent halothane, while the adenosine triphosphate concentration declined after exposure to 4-4.5 per cent only. Although the mechanism(s) whereby halothane alters glucose and glycogen metabolism are unknown, it is possible that the anesthetic acts primarily by affecting membranes containing enzymes involved in the metabolism of glycogen.

COMPARISON OF THE INOTROPIC ACTION OF MORPHINE AND KETAMINE STUDIED IN CANINE CARDIAC MUSCLE

This study compares the inotropic action of morphine sulfate and ketamine hydrochloride on isolated canine right ventricular trabeculae. The heart was removed from 19 mongrel puppies weighing 5 to 9 kilograms and placed in Krebs-Ringer bicarbonate solution. The bathing solution contained 1.3 mM. of Ca2+ and was bubbled with a gas mixture of 95 per cent oxygen and 5 per cent carbon dioxide. At Lmax (i.e., the peak of isometric force-length curve) morphine even in large concentrations (up to 1 mg. per milliter) produced no significant direct inotropic effect. At the lower concentrations tested there was a minor but not significant increase in contractile performance, whereas at the highest concentration used there was a minor but not significant depression in contractility. In these same muscles lower concentrations of ketamine had a significant positive inotropic action, but a concentration of 200 mug per milliliter, which is approximately equimolecular to 1 mg. per milliliter of morphine sulfate, caused a profound depression in contractile performance. In the presence of a beta-blocking agent and in reserpine-pretreated muscles, low concentrations of ketamine, which had only a positive inotropic action in the normal muscles, now caused depression of contractile performance. The positive inotropic action of ketamine is thus indirect and mediated via adrenergic influences. At each concentration studied the direct inotropic action of ketamine was exclusively negative. Because of this bimodal inotropic action seen when adrenergic mechanisms are intact, we conclude that caution must be exercised when ketamine is given to patients previously treated or still under the influence of drugs having adrenolytic properties. Caution is also necessary when ketamine is used in patients having diminished cardiac adrenergic reserves as in congestive heart failure.

Coronary vascular resistance during halothane anesthesia.

To study the effect of halothane on the coronary circulation, the circumflex diastolic coronary vascular resistance was measured in the working heart and total mean coronary resistance (TCR) in the isolated nonworking heart of the dog during administration of 100 per cent oxygen and during administration of 2--3 per cent halothane in oxygen. In the working heart, when the diastolic aortic pressure was kept at a nearly control level, halothane induced decreases of 12 per cent in circumflex diastolic coronary vascular resistance and 18 per cent in left ventricular arteriovenous oxygen content difference and no significant change in diastolic coronary blood flow. This effect occurred in spite of the absence of any significant change of myocardial oxygen consumption. In the nonworking beating, arrested or fibrillating heart, halothane induced a decrease of 24 per cent in total mean coronary resistance. Since the decrease in circumflex diastolic coronary vascular resistance in the working heart connot be attributed to myocardial hypoxia and since the results in the isolated nonworking heart eliminate the influences of mechanical and neurohumoral factors on coronary resistance, it is concluded that the observed decrease in resistance is probably due to vasodilation produced by a direct action of halothane on the coronary vessels. This effect was not modified by beta-adrenergic blockade.

The role of oxygen therapy in the healing of experimental skin wounds and colonic anastomosis.

A number of experimental studies have indicated that wound healing is adversely affected by hypoxia, and it has been suggested that healing can be improved by increasing inspired oxygen tensions. However, this hypothesis is based on observations on simulated wounds or tissue implants in experimental animals, and the clinical relevance of these observations is uncertain. The effects of oxygen therapy on the healing of skin wounds and colonic anastomoses were examined in rats. Sutured skin incisions and normal and ischaemic colonic anastomoses were studied in control animals breathing air and in test animals breathing 50 per cent oxygen. Wound healing was assessed by measurements of wound breaking strength, colonic bursting wall tension and wound collagen after 7 days' treatment with oxygen. There was no significant difference in the measurements in skin wounds or colonic anastomoses in test and control animals, and there was a similar incidence of anastomotic dehiscence in the ischaemic colon of test animals and controls. Oxygen therapy had no apparent effect on wound healing in this study, and it was concluded that further studies are required to determine whether or not there is a rational basis for the clinical use of oxygen therapy to help wound healing.

THE EFFECTS OF DOPAMINE AND ISOPROTERENOL ON THE PULMONARY CIRCULATION

Dopamine and isoproterenol, although used primarily for their inotropic effects, are also potent vasoactive substances. To determine their effects on the pulmonary circulation, we cannulated the left lower lobe bronchus in 20 dogs to permit ventilation with either air or a mixture of 95 per cent nitrogen and 5 per cent carbon dioxide; systemic oxygenation was maintained by ventilating the right lung with 95 per cent oxygen. The lobe was perfused at a controlled flow rate and left atrial pressure was held constant. Hypoxic ventilation increased the lobar vascular resistance by 52 per cent (p

Study of the pulmonary circulation in a canine asthma model.

Measurements of respiratory mechanics, gas exchange, and pulmonary hemodynamics were made before and serially for 2 hours after inhalation challenge with Ascaris suum extract in dogs with natural sensitivity to this antigen. Nine of 14 dogs randomly exposed to an inspired oxygen fraction of 0.21 or 0.60 to 0.70, responded to the challenge with bronchospasm reflected by a transient decrease of mean specific respiratory system conductance to 50 per cent of baseline after 5 to 15 min. This was accompanied by a decrease in alveolar ventilation in all and acidosis in some animals. No changes were observed in transmural pulmonary arterial pressure, cardiac output, pulmonary vascular resistance, and pulmonary blood volume in all 9 dogs who responded with bronchospasm, whether or not arterial hypoxemia was allowed to develop. In contrast, a significant increase in pulmonary vascular resistance occurred in control dogs in whom comparable degrees of arterial hypoxemia were produced by 10 per cent oxygen breathing or mechanical bronchial obstruction by placing beads in lobar and segmental airways. No changes in any parameter measured occurred in the 5 dogs who did not develop bronchospasm after antigen challenge. The results indicated that moderately severe, antigen-induced bronchospasm in anesthetized dogs has no effect on the pulmonary circulation even when associated with arterial hypoxemia. Because nonuniformity of alveolar hypoxia allowing redistribution of blood flow is probably not responsible for this failure to develop increases in pulmonary vascular resistance in induced asthma, it is suggested that the elaboration of chemical mediators may have interfered with the hypoxic pulmonary vasoconstrictor response.

乱流拡散火炎の特性について 燃料に都市ガスを用いた場合

As a combustion system in ships, turbulent diffusion flames are widely used. Yet such a combustion system involves various problems to be solved. One of them is that some ill effects are caused by the lowered quality of fuels, and another is how to burn such a fuel as is mixed with various noncombustible ingredients such as waste oil.We, therefore, in order to make basic explications about these problems above, made various experiments, using town gas as fuel, under the condition that overall equivalence ratio (φ) is less than the stoichiometric equivalence ratio.To sum up the results of our experiments, the most important points are as follows:(1) The temperature of the flame reaches its maximum value in the central regions 5cm-25cm from the nozzle tip, while it lowers as the distance from the nozzle tip becomes greater.(2) In regard to the gas analysing results of the axial distance, CO, H2 and unburnt hydrocarbon reach their peak value in the neighbourhood of the nozzle, but they become less in the rear-flow, and the combustion efficiency increases at the same time.(3) Because the overall equivalence ratio is made by changing the quantity of the combustion air, the diffusible width of flame is affected nice distinction to be entrainment of air transfer across the flame surface.It can be said that the experimental flames used in our experiments are not the pure diffusion flames, because we used town gas containing about 3.5 per cent oxygen.

Differences in Survival of Mouse Colon Crypts after Whole- or Partial-body Irradiation

The survival of mouse colon crypts after X-irradiation has been studied by the microcolony technique. The Do for crypt survival was 266 rad after whole-body irradiation in air, but when the colon alone was irradiated, the Do was 340 rad. In mice which were breathing 95 per cent oxygen, the Do values were 238 rad for whole-body and 302 rad for colon irradiation. The survival curves were all extrapolated to the same number, and the DQ was also increased with colon irradiation. There was, therefore an enhancement of colon crypt survival of about 27 per cent by local as opposed to whole-body irradiation. These results might be explained by a circulating repair promoter or by the production of a toxin after whole-body irradiation.

Antidiuretic hormone levels during cardiopulmonary bypass

The effect of CPB on plasma ADH levels, urine flow, and urine osmolality was studied in nine patients. All patients received morphine, 1 mg. per kilogram, and 50 per cent nitrous oxide-50 per cent oxygen for anesthesia. CPB utilized a Travenol disposable bubble oxygenator and the prime consisted of 3 L. of Ringer's lactate. Measurements were made prior to induction of anesthesia , at 30 minutes following surgical incision, and at 15, 30, and 45 minutes during CPB. There were no statistically significant changes in mean arterial BP, cardiac index, serum sodium, or serum osmolality in any period. Urine flow increased from 0.99 +/- 0.3 ml. per minute to a high of 6.13 +/- 2.0 ml. per minute at 30 minute at 30 minutes on CPB (P less than 0.02). Urine osmolality declined from a control value of 691 +/- 142 mOsm. per kilogram to a low of 425 +/- 48 mOsm. per kilogram at 45 minutes on CPB (p less than 0.05). ADH levels rose from a control value of 4.3 +/- 1.5 to 13.0 +/- 3.3 pg. per milliliter with surgical stimulatiion (p less than 0.05). During CPB the ADH levels rose to a peak of 23.7 +/- 3.6 pg. per milliliter at 30 minutes (p less than 0.01) and were declining at 45 minutes. These data suggest that the stress of CPB results in an outpouring of ADH (or vasopressin) to function as a pressor to produce an increase in peripheral resistance. The ADH concentrations far exceed those required for normal physiologic control of water excretion and the urineflow will thus vary more with the hemodynamic changes than with the ADH levels.

Alterations of normal left ventricular performance by general anesthesia.

Serial invasive and noninvasive (systolic time interval) measurements of left ventricular performance were obtained in six healthy volunteers during general anesthesia employing the following sequence: thiopental induction, succinylcholine (prior to endotracheal intubation), and halothane--100 per cent oxygen at 1.25 and 1.75 MAC. Heart rate (HR), mean pulmonary arterial "wedge" pressure (PAW) and mean systemic arterial pressure (MAP) were measured continuously; cardiac index and systolic time intervals (STI's) were measured during each intervention. At both levels of halothane, MAP and stroke work index decreased (both P less than 0.02), while HR and systemic vascular resistance did not change. At 1.25 MAC halothane PAW was unchanged, but at 1.75 MAC PAW increased from 8 +/- 4 (SD) to 11 +/- 5 torr (P less than 0.02). Preload was altered at 1.25 MAC by administration of 600-1,000 ml lactated Ringer's solution; PAW increased from 9 +/- 4 to 17 +/- 3 torr (P less than 0.01). At 1.75 MAC halothane, volume expansion increased PAW in a similar manner, but the resultant ventricular function curve was depressed compared with 1.25 MAC halothane. In additon, at each level of halothane anesthesia, the ventricular function curve was depressed compared with results obtained in awake normal subjects. Afterload was altered at 1.25 MAC halothane by infusion of phenylephrine sufficient to raise MAP by 30 per cent. This intervention resulted in a greater depression of cardiac performance than that observed at 1.75 MAC halothane alone. Although alterations in STI's were directionally similar to changes observed in invasive hemodynamic measurements, STI's were sensitive to acute alternations in loading conditions. It is concluded that the levels of halothane commonly employed for general anesthesia significantly depress left ventricular performance in normal subjects, as evidenced by abnormal responses to alterations in preload and afterload, and that STI's should not be employed for routine measurement of left ventricular performance during anesthesia unless both the afterload and the preload on the myocardium are known.