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Biomedical subjects

G A Gregory

Publications and source records attributed to G A Gregory.

At least 55 records · Page 3Linked to original sources

Dynamics of respiration during rapid rate mechanical ventilation in anesthetized and paralyzed rabbits.

Infants with respiratory failure are often ventilated at rates exceeding 60 breath X min-1. To obtain insight into the factors controlling the delivery and distribution of tidal volume at these ventilatory rates, we analyzed the inspiratory and expiratory pressure-flow relationships of the respiratory system and its components (lungs, endotracheal tube, and chest wall) in anesthetized, paralyzed rabbits ventilated at 60, 90, and 120 breath X min-1. Inspiratory times were 0.3, 0.2, and 0.1 s. Driving pressure was maintained constant. We expressed the effect of ventilatory rate and flow direction on the pressure-flow relationships as changes in compliance, mean resistance, and inertance. We found a nonlinear pressure-flow relationship in both endotracheal tube and respiratory system. This nonlinearity could be accurately described as a function of gas flow and volume acceleration with similar coefficients for tube and respiratory system. Although the inspiratory and expiratory compliance and the mean inspiratory resistance of the lungs were lower at the higher ventilatory rates, the constant resistive behavior of the endotracheal tube and the constant elastic behavior of the chest wall caused a relatively rate-independent pressure-flow behavior of the respiratory system. The lower inspiratory resistance of the lungs was offset by the higher inspiratory resistance of the endotracheal tube, resulting in the resistance of the respiratory system being independent of the direction of gas flow. The rate-dependency of compliance and inspiratory resistance of the lungs suggests an heterogeneous distribution of inspiratory flow at rapid ventilatory rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Effect of age on the solubility of volatile anesthetics in human tissues.

To determine the effect of age on the solubility of volatile anesthetics in human tissues, the authors measured the solubilities of isoflurane, enflurane, halothane, and methoxyflurane in vitro at 37 degrees C in 35 postmortem human tissue specimens. Specimens were taken from neonates, and young (20-50 yr), middle-aged (50-70 yr), and elderly adults (greater than 70 yr). Brain/gas, heart/gas, and liver/gas partition coefficients for all four anesthetics increased significantly (P less than 0.05) between birth and adulthood, although brain/gas partition coefficients in young adults tended to be higher than those in middle-aged and elderly adults. Heart/gas and liver/gas partition coefficients tended to increase with aging. Muscle/gas partition coefficients for the four anesthetics increased linearly with age. Fat/gas partition coefficients did not change significantly with age. Tissue/blood solubilities for the four anesthetics were of the same order of magnitude for a given tissue and age group. Tissue/blood solubilities for enflurane were 30% lower than those for isoflurane in the same tissue and age group. In summary: the solubility of volatile anesthetics in human tissues increases with age; the lower solubility of anesthetics in neonates partially explains the more rapid increase of alveolar and tissue anesthetic partial pressures in neonates; despite the higher blood solubility of enflurane, its lower tissue solubility may explain a rate of recovery comparable with that of isoflurane.

Adipose Tissue↗

Effects of hypoxic hypoxia on cerebral phosphate metabolites and pH in the anesthetized infant rabbit.

The effects of hypoxic hypoxia on high-energy phosphate metabolites and intracellular pH (pHi) in the brain of the anesthetized infant rabbit were studied in vivo using 31P nuclear magnetic resonance spectroscopy. Five 10- to 16-day-old rabbits were anesthetized with 1.5% halothane. Ventilation was controlled to maintain normocarbia. Inspired O2 fraction was adjusted to produce three states of arterial oxygenation: hyperoxia (PaO2 greater than 250 mm Hg), normoxia (PaO2 approximately 100 mm Hg), and hypoxia (PaO2 25-30 mm Hg). During hypoxia, blood pressure was kept within 20% of control values with a venous infusion of epinephrine. During hyperoxia, the phosphocreatine-to-ATP ratio was 0.86, a value that is 2-2.5 times less than that reported for adults. During normoxia, ATP decreased by 20% and Pi increased by 90% from hyperoxia values. During 60 min of hypoxia, the concentrations of high-energy phosphate metabolites did not change, but intracellular and arterial blood pH (pHa) decreased significantly. When hyperoxia was reestablished, pHi returned to normal and pHa remained low. These results suggest that during periods of hypoxemia, the normotensive infant rabbit maintains intracellular concentrations of cerebral high-energy phosphates better than has been reported for adult animals.

Adenosine Triphosphate↗

Halothane anesthesia reduces pulmonary function in the newborn lamb.

To study the effects of anesthesia on respiratory function of the neonate, the authors investigated the effect of breathing 100% oxygen and of breathing oxygen plus 0.75 MAC halothane on functional residual capacity, lung and airway resistance, expired minute volume, work of breathing, lung compliance, and blood gases and pH in nine 5-8-day-old, 4.6-7.7-kg lambs. Breathing 100% oxygen increased PaO2 but had no effect on PaCO2, minute ventilation, or lung mechanics. Three-fourths MAC halothane depressed minute ventilation 34% +/- 13% (P less than 0.05) and increased PaCO2 50% +/- 5% (P less than 0.05). Lung and airway resistance increased 59% +/- 26% (P less than 0.05); work of breathing decreased (P less than 0.05); and lung compliance was unchanged. Functional residual capacity was reduced 32% +/- 6% (P less than 0.05), which may be due to loss of diaphragm and intercostal muscle function and to an inability to take deep breaths. The authors conclude that 0.75 MAC halothane significantly impairs the pulmonary function of lambs who breathe spontaneously. Similar changes in human infants could account for the hypoxemia and hypercarbia that often are seen during anesthesia.

Airway Resistance↗

The cardiovascular and metabolic effects of halothane in normoxic and hypoxic newborn lambs.

Oxygen consumption, cardiac output, and tissue oxygen delivery were measured in normoxic and hypoxic 1-3-day-old lambs during the following six conditions: 1) (control) paralysis with pancuronium and controlled ventilation with room air; 2) paralysis, controlled ventilation and hypoxia (PaO2 = 30 +/- 3 mmHg, [SD]); 3) paralysis, controlled ventilation with room air and 0.5 MAC halothane; 4) paralysis, controlled ventilation, hypoxia, and 0.5 MAC halothane; 5) paralysis, controlled ventilation with room air, and 1 MAC halothane; and 6) paralysis, controlled ventilation, hypoxia, and 1 MAC halothane. During normoxia, 0.5 and 1 MAC halothane decreased total body oxygen consumption, cardiac output, and arterial blood pressure. One-half MAC halothane had no effect on blood flow to any organ except muscle, whose flow decreased 64%. One MAC halothane decreased blood flow to the brain, heart, kidney, muscle, and gut. Both concentrations of halothane decreased serum catecholamine levels below control values and prevented hypoxia from increasing catecholamine levels. Hypoxia decreased the oxygen consumption about 40% from the immediately previous normoxic value, whether the animals were anesthetized or not. Tissue oxygen delivery followed changes in blood flow. The cardiac output, arterial blood pressure, and heart rate of anesthetized, hypoxic animals were not different from those in the previous normoxic condition. Halothane did not prevent redistribution of blood flow to the heart and brain of hypoxic animals, nor did halothane prevent hypoxic pulmonary vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of enflurane, halothane, and isoflurane for diagnostic and therapeutic procedures in children with malignancies.

The authors performed a randomized, prospective trial comparing enflurane, halothane, and isoflurane (each administered with nitrous oxide) to establish which inhaled anesthetic produced the fewest complications and the most rapid induction of anesthesia for children undergoing general anesthesia for diagnostic procedures as oncology outpatients. Sixty-six children, ranging from 8 months to 18 years, underwent a total of 124 anesthetics. Induction of anesthesia (time from placement of facemask to beginning of skin preparation) was faster with halothane (2.7 +/- 1.0 min, mean +/- SD, n = 46) than with enflurane (3.2 +/- 0.8 min, n = 43) or isoflurane (3.3 +/- 1.2 min, n = 35). Emergence from anesthesia (time from completion of the procedure to spontaneous eye opening) was more rapid with enflurane (4.7 +/- 4.4 min) than with halothane (6.2 +/- 4.5 min) or isoflurane (6.2 +/- 3.9 min). Total time from the start of procedure until discharge was longer with isoflurane (25.1 +/- 6.8 min) than with enflurane (21.5 +/- 8.6 min) or halothane (22.3 +/- 7.6 min). During induction, the incidence of laryngospasm was greatest with isoflurane (23%) and the incidence of excitement least with halothane (13%). During the maintenance of, emergence from, and recovery from anesthesia, coughing occurred most frequently with isoflurane. During the recovery period, headache occurred most frequently with halothane (9%); there were no significant differences in the incidence of nausea, vomiting, hunger, or depressed effect. The authors conclude that the rapid induction and minimal airway-related complications associated with halothane anesthesia make it an excellent anesthetic agent for pediatric patients undergoing short diagnostic procedures.

Adolescent↗

Resistance and inertia of endotracheal tubes used in infants during periodic flow.

To study the effects of a periodic pattern of gas flow on the dynamic behavior of infant endotracheal tubes, we measured the resistance (expressed as a function of gas flow) and inertia of endotracheal tubes of 2.5, 3.0, and 3.5-mm internal diameter under conditions of both periodic and quasisteady gas flow. We examined how resistance and inertia are affected by ventilatory rate, the direction of gas flow through the tube, and the expansion of the airway caliber at the junction of the tube and the trachea. The resistance of the endotracheal tubes was proportional to gas flow for ventilatory rates of 60, 90, and 120 breath/min and for quasisteady flow, indicating turbulence even at low flow rates. The resistance of the tubes was less sensitive to ventilatory rate, direction of flow, and expansion of the airway caliber than that of larger endotracheal tubes, a finding explained by the flow conditions defined by the Womersley and Reynolds numbers in these tubes. All tubes exhibited measureable inertia, as predicted from their small diameter. The resistive and inertial properties of the endotracheal tubes described in this report can be used to evaluate the contribution of the endotracheal tube to the dynamics of breathing in intubated infants.

Humans↗

The effect of a gas leak around the endotracheal tube on the mean tracheal pressure during mechanical ventilation.

Infants requiring mechanical ventilation are usually intubated with uncuffed endotracheal tubes, which permit gas to leak between the tube and the trachea. This gas leak may alter the mean pressure transmitted to the trachea by changing the pattern of airway flow and modifying the resistive behavior of the endotracheal tube. To test this hypothesis, we measured mean tracheal pressure, gas flow through the endotracheal tube, and resistance of the tube in rabbits ventilated with and without a leak. We also studied the effect of the tube size and the pattern of ventilation on these measurements. We found that a leak reduced the mean tracheal pressure by 15 to 21% with respect to the mean proximal airway pressure. This reduction was caused by an increased difference between inspiratory and expiratory flow through the endotracheal tube, and by the mean expiratory resistance of the tube being lower than its mean inspiratory resistance. The rabbits with smaller tubes had lower mean tracheal pressures. A ventilatory pattern of short inspiratory times and high peak pressures was associated with a proportionally greater decrease in mean tracheal pressure caused by the leak. These findings suggest that the mean proximal airway pressure, measured at the ventilator, may overestimate the mean tracheal pressure in the presence of a gas leak around the tube. Furthermore, the decrease in mean tracheal pressure caused by the leak may decrease oxygenation despite a constant mean proximal airway pressure.

Airway Resistance↗

Age and the solubility of volatile anesthetics in ovine tissues.

To determine the effect of age on the solubility of volatile anesthetics in tissues, we measured the blood/gas and tissue/gas partition coefficients of isoflurane, enflurane, halothane, and methoxyflurane in vitro at 37 degrees C in newborn lambs and postpartum adult sheep. The tissue specimens examined were brain, heart, liver, kidney, muscle, and fat. Hematocrit and serum concentrations of albumin, globulin, cholesterol, and triglycerides were measured. The blood/gas partition coefficients, hematocrit, and the serum concentrations of albumin, globulin, cholesterol, and triglycerides in the newborn lambs did not differ from those in the adult sheep. The tissue/blood partition coefficients [the ratio of (tissue/gas)/(blood/gas)] in newborn lambs were 28% [mean value for the four anesthetics] less than those in the adults. The tissue/blood partition coefficients for enflurane and methoxyflurane in newborn tissues were significantly less (P less than 0.05) than those for halothane and isoflurane. We conclude that the blood/gas partition coefficients in sheep do not change significantly with age, and that the time required for equilibration of volatile anesthetics (particularly enflurane and methoxyflurane) in newborn tissues is probably less than in adult sheep.

Aging↗

Age and solubility of volatile anesthetics in blood.

The more rapid rate of rise of alveolar anesthetic partial pressure in children compared with adults may be explained in part by an increasing solubility of volatile anesthetics in blood with age. To investigate this possibility, the authors measured the blood-gas partition coefficients of isoflurane, enflurane, halothane, and methoxyflurane in four groups of fasting subjects: 10 full-term newborns (at delivery), 11 children (3-7 years old), 11 adults (20-40 years old), and 10 elderly adults (75-85 years old). The blood-gas partition coefficients were greatest in adults: isoflurane 1.46, enflurane 2.07, halothane 2.65, and methoxyflurane 16.0; and least in newborns: 1.19, 1.78, 2.14, 13.3, respectively. The blood-gas partition coefficients in children (1.28, 1.78, 2.39, 15.0, respectively), which were intermediate between those in newborns (P less than 0.005) and those in adults (P less than 0.005), were not significantly different from those in elderly adults (1.29, 1.79, 2.41, 15.0, respectively). The blood-gas partition coefficients of both isoflurane and enflurane correlated directly with the serum albumin and triglyceride concentrations; that of halothane correlated directly with the serum cholesterol, albumin, triglyceride, and globulin concentrations; and that of methoxyflurane correlated directly with the serum cholesterol, albumin, and globulin concentrations. The authors conclude that age significantly affects blood-gas partition coefficients, and the lower blood-gas partition coefficients in children explain in part the more rapid rise of alveolar anesthetic partial pressure in this age group.

Adult↗

The effect of paralysis on oxygen consumption in normoxic children after cardiac surgery.

To determine whether paralysis reduces oxygen consumption (V02) after cardiac surgery in infants, the authors measured V02 before and after paralysis in 17 sedated infants who were ventilated mechanically after cardiac surgery. Oxygen consumption was determined as being the difference between oxygen content of inspired and expired gases. The absence or presence of "movement" (breathing or repeated movement of the extremities) before paralysis was noted. For eight infants who did not "move" before paralysis, VO2 was similar before (9.1 +/- 1.2 ml . kg-1 . min-1, mean +/- SD) and after (9.0 +/- 1.5 ml . kg-1 . min-1) paralysis (P = 0.81). However, for nine infants who did "move" before paralysis, VO2 decreased from 9.2 +/- 1.4 ml . kg-1 . min-1 before paralysis to 8.0 +/- 1.4 ml . kg-1 . min-1 after paralysis (P less than 0.05). One infant in each group had an increase in VO2 greater than 10% of the baseline value (i.e., 12% and 14%). In conclusion, if breathing or repeated movement is present before paralysis, paralysis decreases VO2 by 13% in sedated infants after cardiac surgery. If repeated or regular movement is not present before paralysis, paralysis does not decrease VO2. These data suggest that in normoxic patients, muscle paralysis does not significantly alter V02 and therefore should not be used for this purpose.

Anesthesia↗

Functional residual capacity and lung mechanics at different levels of mechanical ventilation.

We assessed the effects of rapid ventilatory rates (60 to 120 breath/min) and high mechanical ventilation pressures (30/5 to 40/10 cm H2O) on lung mechanics and intravascular pressures in 9 paralyzed, sedated rabbits ventilated with a time-cycled, pressure-limited flow generator (Baby bird). Measurements of tidal volume, ventilator line pressure, tracheal pressure, functional residual capacity (FRC), and arterial and venous blood pressures showed that: 68% of the peak pressure developed by the ventilator was transmitted to the trachea at 60 breath/min, 74% at 120 breath/min, and 87% when ventilation pressures were increased to 40/10 cm H2O; when the ventilatory rate and the PEEP were increased, the end-expiratory pressure in the trachea became progressively greater than that indicated on the ventilator pressure gauge; FRC increased when the PEEP and mean tracheal pressure increased; tidal volume and dynamic compliance decreased and minute ventilation increased as ventilatory rate increased; compliance decreased whenever FRC increased, and increased whenever FRC decreased; and there was little effect on mean central venous or arterial pressure. These data indicate that increasing ventilator rates cause gas trapping within the lung. In normal animals, this may interfere with gas exchange and pulmonary blood flow. In abnormal lungs, the gas trapping may increase FRC and improve gas exchange within the lung.

Animals↗

The effect of hypocarbia on the cardiovascular system of puppies.

Respiratory alkalosis (hypocapnia) is used to treat persistent pulmonary hypertension in newborns. With the exception of the brain, there are no data on the effects of hypocapnia on organ blood flow in the neonate. Therefore, we examined the effects of 2 h of hypocapnia on blood pressure, oxygen consumption, cardiac output and organ blood flows in puppies. In six animals (group I), reducing the PaCO2 to 21.8 +/- 1.5 mm Hg (pH 7.62 +/- 0.04) caused an immediate and sustained reduction in cerebral blood flow (40%) and in myocardial blood flow (25%). There were no significant changes in arterial blood pressure, total body oxygen consumption, cardiac output, right and left ventricular rate-pressure product, or blood flow to the gut, liver, muscle, and kidneys. In four control animals (group II)(PaCO2 39.8 +/- 3.0, pH 7.38 +/- 0.04), there were no changes in any of the measured variables (arterial blood pressure, total body oxygen consumption, cardiac output, or blood flow to any organ, including brain and heart) during 2 h of normocarbic ventilation. We did not determine whether the reductions in cerebral and myocardial blood flows were detrimental. We suspect that they were not because the animals did not develop metabolic acidosis and they had normal cardiac outputs, and ventricular rate-pressure products throughout the study.

Acid-Base Equilibrium↗

The effects of tolazoline on the distribution of cardiac output in normoxemic and hypoxemic lambs.

We measured cardiac output and its distribution (microspheres), blood gases and pH, heart rate, and pulmonary and aortic pressures in three groups of 1- to 3-day-old lambs. Group I consisted of six animals who had these measurements made during both control (normoxemic) and hypoxemic (PaO2 25 +/- 3 mm Hg) periods. Hypoxemia increased the pulmonary artery pressure 70% (p less than 0.01). This elevation in pulmonary arterial pressure lasted as long as the animals were hypoxemic (90 min). Hypoxemia had no effect on cardiac output, mean systemic arterial pressure, heart rate, or the rate-pressure product of the left ventricle. Blood flow to the heart increased an average of 228% (p less than 0.05); flow to the brain increased 233% (p less than 0.05); flow to the skin decreased 35% (p less than 0.05) after 60 and 90 min of hypoxemia. Blood flow to the remaining organs was uneffected by hypoxemia. Group II consisted of four animals who were given 1, 5, and 10 mg/kg/h of tolazoline (Priscoline) intravenously while normoxemic. There was no effect on the pulmonary arterial pressures or blood gases and pH. Tolazoline (5 and 10 mg/kg/h) reduced systemic arterial pressures an average of 22% (p less than 0.05). Tolazoline (1 mg/kg/h) reduced blood flow to the spleen 48% and that to the brain by 20% and increased flow to the body 32% (p less than 0.05). Five mg/kg/h of tolazoline decreased renal and brain blood flow 35 and 20%, respectively (p less than 0.05) while that to the body and liver increased 26 and 48% (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hematocrit and the solubility of volatile anesthetics in blood.

To clarify the effect of hematocrit on the solubility of volatile anesthetics in blood, we measured the blood-gas partition coefficients of isoflurane, enflurane, halothane, and methoxyflurane concurrently at 37 degrees C in blood from four adults. We measured the blood-gas partition coefficients in the plasma (hematocrit 0%) and packed red cell fractions (hematocrit 80%), and in four mixtures of these two fractions (hematocrits 10%, 25%, 40%, and 55%). The mixtures were prepared by recombining appropriate amounts of plasma and packed red cells from each adult. As hematocrit increased, the blood-gas partition coefficient of isoflurane decreased linearly (P less than 0.01), whereas that of enflurane increased linearly (P less than 0.05). The partition coefficient for isoflurane in plasma was 20% greater than that in packed red cells, whereas the partition coefficient for enflurane in plasma was 10% less than that in packed cells. The blood-gas partition coefficients of halothane and methoxyflurane did not change significantly between measurements in plasma and packed red cells. We conclude that hematocrit exerts a statistically significant effect on the blood-gas partition coefficient of isoflurane and enflurane.

Adult↗

The minimum anesthetic concentration of isoflurane in children.

The minimum anesthetic concentration (MAC) of isoflurane was determined in five pediatric age groups. MAC was 1.6% in infants 0-1 month of age, 1.87% in those 1-6 months of age, 1.8% in those 6-12 months of age, 1.6% in those 1-3 yr of age, and 1.6% in children 3-5 yr of age. MAC in neonates was less than predicted.

Adult↗

The effect of halothane anaesthesia on the asphyxiated foetal lamb in utero.

In a previous study, we examined the effects of halothane on the normal foetal lamb in utero. The most significant finding was a 33 per cent fall in foetal mean arterial blood pressure (MABP). Cardiac output and placental blood flow were not affected. To determine if the asphyxiated foetus would respond similarly, the following study was performed. Seven pregnant ewes were surgically prepared two days prior to study with maternal and foetal indwelling arterial and venous cannulas. An inflatable occlusion loop was secured around the umbilical cord. On the day of study, a tracheostomy was performed on each ewe. Microspheres were injected into the foetal circulation during the control period. The occlusion loop was inflated to produce foetal asphyxia and microspheres were again injected. The ewe was then anesthetized with halothane; and after 15 minutes, microspheres were injected into the asphyxiated foetus and halothane levels were measured. The asphyxiated foetuses showed a significant rise in MABP, fall in heart rate and fall in cardiac output from control. Blood flow to the brain was significantly increased and flow to the placenta and gut decreased. Exposure of the asphyxiated foetus to halothane resulted in a fall of MABP to control but no significant change in cardiac output or brain blood flow. The mean halothane level in the foetus was 46.0 mg X l-1 or 0.32 vol%. Exposure of the asphyxiated foetus to halothane for 15 minutes does not produce significant further deterioration of the foetal lamb in utero.

Acid-Base Equilibrium↗