Article

Effects of Elevated Body Temperature on Control of Breathing

Authors:
  • Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia
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Abstract

Effects of Elevated Body Temperature on Control of Breathing Changes in body temperature can be evoked mainly by alterations in the peripheral temperature, or modified by shifts in the central body temperature. Two conditions can lead to abnormal elevation of body temperature: hyperthermia or fever. As regards respiratory system, exposure to heat stress is accompanied by marked alterations in breathing, especially by an increase in ventilation. Ventilation rises due to an increase in central output from hypothalamus or brainstem, an increase in peripheral output via skin temperature receptors, an increase in central or/and peripheral chemoreceptor output or sensitivity and can be also mediated through changes in thermoregulatory mechanisms. This review summarizes results of previous studies as well as of experiments done in our laboratory in order to elucidate the mechanisms included in respiratory changes under heat stress.

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... Another aspect of plausibility is the cross-reliability or co-existence plausibility. Various efforts have been conducted to indicate correlations between different vital signs [9,10,11]. For instance, considering the possible effect of the body temperature on the heart rate value, the probability of an increase in heart rate is high in the case of elevated body temperature [10]. ...
... Several factors influenced the setup of the fuzzy membership functions and the correlation coefficients. Besides the medical publications [8,9,10,11,20], expert's opinions from various physicians, the accuracy of the sensors used, and the medical condition of the patient were considered in configuring the system. To repeat the experiments with other sensors or patients, the setup should be reconfigured again to reflect such personalization. ...
... Another aspect of plausibility is the cross-reliability or co-existence plausibility. Various efforts have been conducted to indicate correlations between different vital signs [9,10,11]. For instance, considering the possible effect of the body temperature on the heart rate value, the probability of an increase in heart rate is high in the case of elevated body temperature [10]. ...
... Several factors influenced the setup of the fuzzy membership functions and the correlation coefficients. Besides the medical publications [8,9,10,11,20], expert's opinions from various physicians, the accuracy of the sensors used, and the medical condition of the patient were considered in configuring the system. To repeat the experiments with other sensors or patients, the setup should be reconfigured again to reflect such personalization. ...
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The time course of the volume threshold curve for the inspiratory off-switch, i.e. the relationship between volume, (Vx) and inspiratory duration (Tj) with intact vagus nerves, was determined in steady conditions at different inspired CO2 concentrations and body temperatures in lightly anesthetized cats by means of ‘ramp’-shaped inflations and deflations of different rise times. With intact vagal feedback the Vx–TT data points could be very well fitted to hyperbolas in all conditions studied. Changes in steady state FACO2 never caused any detectable influence on the volume threshold curves. Changes in body temperatures, in a range below the panting threshold, caused pronounced effects on the volume threshold curve which could best be characterized as a shift of the whole curve along the volume axis to lower values with increased temperature. Thus, at each rate of volume expansion the threshold for inspiratory off-switch was reached earlier the higher the temperature. Also in the absence of vagal volume feed-back Ti became correspondingly shorter with increased temperature which indicates that these temperature effects are mainly of central origin. The mechanisms for the CO2 and temperature effects on tidal volume and inspiratory duration are discussed.
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Respiratory failure caused by meconium aspiration requires combined strategies. We hypothesized that surfactant lung lavage with asymmetric high-frequency jet ventilation (AHFJV) can increase the removal of meconium and improve lung function. During conventional ventilation (CV), a suspension of human meconium (25 mg/ml, 4 ml/kg) was instilled into the tracheal tube of anesthetized rabbits to cause respiratory failure. Animals were then divided into four groups: saline lavage + CV (Sal-CV), surfactant lavage + CV (Surf-CV), saline lavage + HFJV (Sal-HFJV), and surfactant lavage + HFJV (Surf-HFJV). Lung lavage (10 ml/kg in 3 portions) was performed with diluted surfactant (Curosurf, 100 mg of phospholipids/kg) or saline during CV (frequency (f), 30/min; inspiration time (Ti), 50%) or AHFJV (f, 300/min; Ti, 70%). Animals were ventilated for an additional hour with either CV or HFJV (Ti, 50%). Surfactant lavage with both CV and AHFJV removed more meconium than saline lavage. However, the highest removal was found in the Surf-HFJV group vs. all other groups (P < 0.05). The oxygenation index decreased after surfactant lavage in both groups compared to controls (P < 0.001), and more prominently in the Surf-CV group. Elimination of CO2 was significantly higher in the Surf-HFJV group vs. all other groups (P < 0.05). The ventilation efficiency index increased after lavage in both surfactant groups vs. saline controls (P < 0.05). Dynamic lung-thorax compliance gradually increased, and right-to-left pulmonary shunts decreased in both surfactant groups vs. saline controls after lavage (P < 0.05). Combination of surfactant lavage with both CV and AHFJV was beneficial in rabbits with meconium aspiration syndrome. While AHFJV was more effective in the removal of meconium, CV had a more favorable effect on lung function in the postlavage period. Pediatr Pulmonol. 2004; 38:285–291. © 2004 Wiley-Liss, Inc.
Article
The major goal of the current study was to investigate the association between continuous performance tests (CPTs) and the heart rate variability (HRV) of attention deficit hyperactivity disorder (ADHD) children. The HRV, specifically the 0.10-Hz component, may be considered to be a psychophysiological index of effort allocation (motivation): The less effort the subject allocates, the greater the 0.10-Hz component. Results indicated that, compared to controls, ADHD subjects had a greater 0.10-Hz component, which was associated with poor test performance over time. Thus, using a psychophysiological measure, we were able to confirm the clinical concept of ADHD from a motivational perspective.
Article
The intimate connection between the brain and the heart was enunciated by Claude Bernard over 150 years ago. In our neurovisceral integration model we have tried to build on this pioneering work. In the present paper we further elaborate our model. Specifically we review recent neuroanatomical studies that implicate inhibitory GABAergic pathways from the prefrontal cortex to the amygdala and additional inhibitory pathways between the amygdala and the sympathetic and parasympathetic medullary output neurons that modulate heart rate and thus heart rate variability. We propose that the default response to uncertainty is the threat response and may be related to the well known negativity bias. We next review the evidence on the role of vagally mediated heart rate variability (HRV) in the regulation of physiological, affective, and cognitive processes. Low HRV is a risk factor for pathophysiology and psychopathology. Finally we review recent work on the genetics of HRV and suggest that low HRV may be an endophenotype for a broad range of dysfunctions.
Article
The Neurovisceral Integration Model is based on the premise of significant central nervous system–peripheral nervous system interactions. In support of this model we have previously shown that the prefrontal cortex tonically inhibits cardioacceleratory circuits as evidenced by increased heart rate (HR) when the prefrontal cortex is inactivated by injections of sodium amobarbitol (ISA) into the internal carotid artery. In this report we re-examine these data to investigate possible age-related differences in the prefrontal control of HR in humans. Seventy-three patients were divided into three groups based on a tertile split with mean ages of 20, 34, and 47, respectively. There were significant age-related differences in cortical control of HR as evidenced by a significant three way interaction of age (young, middle, old) by side (left versus right) by time (baseline and epochs 1–10 of inactivation) [Roy's Root (10,59) = 0.378, p = 0.028]. Results showed significant HR increases that did not differ between hemispheres in the youngest age group, significant increases in the middle age group that were larger in the right hemisphere than in the left, and significant HR increases in the oldest group in the right hemisphere only. The findings suggest important age-related differences in cortical inhibitory control of HR that appear less lateralized in the youngest group and significantly attenuated in the oldest age group. These results have important implications for the understanding of age-related differences in cognitive, affective, behavioral, and physiological functioning. In addition they support the importance of investigating central nervous system–peripheral nervous system relationships.
Article
Since inflammation and oxidation play a key role in the pathophysiology of neonatal meconium aspiration syndrome, various anti-inflammatory drugs have been tested in the treatment. This study evaluated whether the phosphodiesterase (PDE) 3 inhibitor olprinone can alleviate meconium-induced inflammation and oxidative lung injury. Oxygen-ventilated rabbits intratracheally received 4 ml/kg of meconium (25 mg/ml) or saline. Thirty minutes after meconium/saline instillation, meconium-instilled animals were treated by intravenous olprinone (0.2 mg/kg) or were left without treatment. All animals were oxygen-ventilated for an additional 5 h. A bronchoalveolar lavage (BAL) of the left lungs was performed and differential leukocyte count in the sediment was estimated. The right lungs were used to determine lung edema by wet/dry weight ratio, as well as to detect oxidative damage to the lungs. In the lung tissue homogenate, total antioxidant status (TAS) was determined. In isolated lung mitochondria, the thiol group content, conjugated dienes, thiobarbituric acid-reactive substances (TBARS), dityrosine, lysine-lipid peroxidation products, and activity of cytochrome c oxidase (COX) were estimated. To evaluate the effects of meconium instillation and olprinone treatment on the systemic level, TBARS and TAS were determined in the blood plasma, as well. Meconium instillation increased the relative numbers of neutrophils and eosinophils in the BAL fluid, increased edema formation and concentrations of oxidation markers, and decreased TAS. Treatment with olprinone reduced the numbers of polymorphonuclears in the BAL fluid, decreased the formation of most oxidation markers in the lungs, reduced lung edema and prevented a decrease in TAS in the lung homogenate compared to non-treated animals. In the blood plasma, olprinone decreased TBARS and increased TAS compared to the non-treated group. Conclusion, the selective PDE3 inhibitor olprinone has shown potent antioxidative and anti-inflammatory effects in the meconium-induced oxidative lung injury.
Article
We aimed to study short-term heart rate variability (HRV) as an index of cardiac autonomic control in never-treated major depressive disorder (MDD) adolescent patients using linear and nonlinear analysis. We have examined 20 MDD girls and 20 healthy age-matched girls at the age of 15 to 18yr. The ECG was recorded in three positions: the 1st supine rest, orthostasis, the 2nd supine position. HRV magnitude was quantified by time and frequency-domain analysis (mean RR interval, SDRR, RMSSD, spectral powers in low [LF] and high frequency [HF] bands). In addition to linear measures, HRV complexity was assessed by nonlinear (symbolic dynamics) indices: normalized complexity index (NCI), normalized unpredictability index (NUPI), and pattern classification measures (0V%, 1V%, 2LV%, 2UV%). HRV magnitude (RMSSD, SDRR, LF and HF powers) was significantly decreased in MDD group in a supine rest and after posture change. HRV complexity was significantly reduced (lower NCI) in the standing position. Pattern classification analysis revealed significantly higher 0V% and lower 2LV% in MDD group in supine position and orthostasis. The HRV linear and nonlinear analysis revealed decreased magnitude and complexity of heart rate time series indicating altered neurocardiac regulation in girls with major depression without pharmacotherapy.
Article
The major objective of this review is to evaluate existing information and reach conclusions regarding whether there is interaction between P(CO(2))/H(+) stimulation of carotid (peripheral) and intracranial (central) chemoreceptors. Interaction is defined as a ventilatory response to simultaneous changes in the degree of Pco2/H(+) stimulation of both chemoreceptors that is greater (hyperadditive) or less (hypoadditive) than the sum of the responses when stimulation of each set of chemoreceptors is individually altered. Simple summation of the simultaneous changes in stimuli results in no interaction (i.e., additive interaction). Knowledge of the nature of central/peripheral interaction is crucial for determining the physiological significance of newer models of ventilatory control based on recent neuroanatomic observations of the circuitry of key elements of the ventilatory control system. In this review, we will propose that these two sets of receptors are not functionally separate but rather that they are dependent on one another such that the sensitivity of the medullary chemoreceptors is critically determined by input from the peripheral chemoreceptors and possibly other breathing-related reflex afferents as well. The short format of this minireview demands that we be somewhat selective in developing our ideas. We will briefly discuss the limitations of experiments used to study CO(2)/H(+) sensitivity and interaction to date, traditional views of the relative contributions of peripheral and central chemoreceptors to CO(2)/H(+) sensitivity, the evidence for and against different types of interaction, and the effect of tonic carotid chemoreceptor afferent activity on central control mechanisms.
Article
The multiscale time irreversibility (MTI) involves the lack of consistency in the properties of a time series if one reverses the reading direction along the time. To analyze the RR time series at rest and during aerobic exercise through the MTI, both in healthy people and cardiac patients. The heartbeat signal was recorded beat to beat for 15 min at rest and 15 min while pedalling on a static bicycle in 10 healthy and active men (age 26.5 +/- 3.3 years; height 179.3 +/- 6.6 cm; weight 80.4 +/- 11.8 kg) and 10 cardiac patients (age 61.1 +/- 4.7 years, height 165.3 +/- 5.3 cm; weight 86.9 +/- 11.1 kg). The MTI was calculated through the asymmetry index (AI), defined as the sum of the values of asymmetry obtained for each scale from 1 to 10. The AI decreases significantly in healthy subjects from 0.51 +/- 0.28 at rest to 0.28 +/- 0.24 during exercise (P = 0.01) but not in cardiac patients (-0.2204 +/- 0.5097 at rest and 0.0848 +/- 0.1200 during exercise; P = 0.07). MTI distinguish adequately the four experimental situations because it can be considered as an index of the internal property of the signal in contrast to linear methods which are highly sensitive to external influences over the heart rhythm, particularly sympathetic and parasympathetic stimuli.
Article
Autonomic nervous system (ANS) dysfunction and reduced heart rate variability (HRV) have been reported in a wide variety of psychiatric disorders, but have not been well characterized in bipolar mania. We recorded cardiac activity and assessed HRV in acutely hospitalized manic bipolar (BD) and schizophrenia (SCZ) patients compared to age- and gender-matched healthy comparison (HC) subjects. HRV was assessed using time domain, frequency domain, and nonlinear analyses in 23 manic BD, 14 SCZ, and 23 HC subjects during a 5min rest period. Psychiatric symptoms were assessed by administration of the Brief Psychiatric Rating Scale (BPRS) and the Young Mania Rating Scale (YMRS). Manic BD patients demonstrated a significant reduction in HRV, parasympathetic activity, and cardiac entropy compared to HC subjects, while SCZ patients demonstrated a similar, but non-significant, trend towards lower HRV and entropy. Reduction in parasympathetic tone was significantly correlated with higher YMRS scores and the unusual thought content subscale on the BPRS. Decreased entropy was associated with increased aggression and diminished personal hygiene on the YMRS scale. Cardiac function in manic BD individuals is characterized by decreased HRV, reduced vagal tone, and a decline in heart rate complexity as assessed by linear and nonlinear methods of analysis. Autonomic dysregulation is associated with more severe psychiatric symptoms, suggesting HRV dysfunction in this disorder may be dependent on the phase of the illness.
Article
Power spectral analysis of electrocardiogram (ECG) R-R intervals is useful for the detection of autonomic dysfunction in various clinical disorders. Although both panic disorder (PD) and major depressive disorder (MDD) are known to have effects on the cardiac autonomic nervous system, no previous study has tested this among drug-naïve (i.e. no history of treatment) patients with MDD and PD in the same study. The purpose of this study was to compare cardiac autonomic functions among drug-naïve patients with MDD and PD and those of healthy controls. Subjects were 17 drug-naïve PD patients, 15 drug-naïve MDD patients and 15 normal controls. ECGs were recorded under both supine resting and supine deep-breathing conditions (10-12 breaths/min; 0.17-0.20 Hz). We measured the low-frequency power (LF; 0.05-0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15-0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. As expected, deep breathing induced an increase in HF power and a decrease in the LF/HF ratio in healthy controls. Compared to these controls, however, the MDD group had a lower response to regular deep breathing in LF power and in LF/HF ratio. PD patients showed intermediate results between normal controls and MDD patients. The results indicate that the reactivity to deep breathing revealed diminished cardiac autonomic reactivity in drug-naïve MDD patients.
Article
The polyvagal theory describes an autonomic nervous system that is influenced by the central nervous system, sensitive to afferent influences, characterized by an adaptive reactivity dependent on the phylogeny of the neural circuits, and interactive with source nuclei in the brainstem regulating the striated muscles of the face and head. The theory is dependent on accumulated knowledge describing the phylogenetic transitions in the vertebrate autonomic nervous system. Its specific focus is on the phylogenetic shift between reptiles and mammals that resulted in specific changes to the vagal pathways regulating the heart. As the source nuclei of the primary vagal efferent pathways regulating the heart shifted from the dorsal motor nucleus of the vagus in reptiles to the nucleus ambiguus in mammals, a face-heart connection evolved with emergent properties of a social engagement system that would enable social interactions to regulate visceral state.
Article
The purpose of this paper is to investigate the effect of orthostatic challenge on recurrence plot based complexity measures of heart rate and blood pressure variability (HRV and BPV). HRV and BPV complexities were assessed in 28 healthy subjects over 15 min in the supine and standing positions. The complexity of HRV and BPV was assessed based on recurrence quantification analysis. HRV complexity was reduced along with the HRV magnitude after changing from the supine to the standing position. In contrast, the BPV magnitude increased and BPV complexity decreased upon standing. Recurrence quantification analysis (RQA) of HRV and BPV is sensitive to orthostatic challenge and might therefore be suited to assess changes in autonomic neural outflow to the cardiovascular system.
Article
The vagal (high frequency [HF]) component of heart rate variability (HRV) predicts survival in post-myocardial infarction patients and is considered to reflect vagal antagonism of sympathetic influences. Previous studies of the neural correlates of vagal tone involved mental stress tasks that included cognitive and emotional elements. To differentiate the neural substrates of vagal tone due to emotion, we correlated HF-HRV with measures of regional cerebral blood flow (rCBF) derived from positron emission tomography (PET) and (15)O-water in 12 healthy women during different emotional states. Happiness, sadness, disgust and three neutral conditions were each induced by film clips and recall of personal experiences (12 conditions). Inter-beat intervals derived from electrocardiographic recordings during the 60-second scans were spectrally-analyzed, generating 12 separate measures of HF-HRV in each subject. The six emotion and six neutral conditions were grouped together and contrasted. We observed substantial overlap between emotion-specific rCBF and the correlation between emotion-specific rCBF and HF-HRV, particularly in the medial prefrontal cortex. Emotion-specific rCBF also correlated with HF-HRV in the caudate nucleus, periacqueductal gray and left mid-insula. We also observed that the elements of cognitive control inherent in this experiment (that involved focusing on the target mental state) had definable neural substrates that correlated with HF-HRV and to a large extent differed from the emotion-specific correlates of HF-HRV. No statistically significant asymmetries were observed. Our findings are consistent with the view that the medial visceromotor network is a final common pathway by which emotional and cognitive functions recruit autonomic support.
Article
In cats under pentobarbitone anaesthesia the effects of focal temperature changes of the 'chemoreceptive' areas on the ventral surface of medulla, described by Loeschchke and his associates, were studied with respect to tidal volume, V(T), tidal variation in efferent phrenic activity, Phr(T), and respiratory rate. The cats were either paralysed and ventilated at various constant P(A,CO2) and P(a,O2) levels, or breathing spontaneously. It was confirmed that focal bilateral cooling of the intermediate, 'I(S)', areas caused rapid depression of respiration even at constant artificial ventilation. In normocapnic and normoxic conditions apnoea usually ensued at brain surface temperatures of 20-22°C.
Article
Surface tension is determined with an apparatus which records pressure across the surface of a bubble, expanded in the sample liquid and communicating with ambient air. The disposable sample chamber, with a volume of 20 microliter, communicates with a pulsator and a pressure transducer. The volume displacement of the pulsator's moving piston is hydraulically geared down 1,000 times, which gives the pulsator a stroke volume of 0.43 microliter. When this volume is moving into the sample chamber, it causes the bubble radius to change from a maximum of 0.55 mm, accurately measured through a microscope, to a minimum of 0.4 mm. The pulsator speed is usually 20 rpm, but it can be changed from 0.02 to 80 rpm. From the known pressure gradient across bubble surface, and bubble radius, surface tension is calculated with the law of Laplace.
Article
To evaluate the efficacy of glucocorticoids in the treatment of infants with meconium aspiration syndrome, a double-blind study using hydrocortisone or a lactose placebo was undertaken. Thirty-five infants were included in the study. No significant differences in arterial Po2, Pco2, pH, A-aDo2 gradients, in requirement for assisted ventilation, or in survival were domonstrated between the groups. In control infants, a significant decrease (p less than 0.01) in respiratory distress score was found at 48 to 72 hours of age; in treated infants, it was seen only after 72 hours. The infants in the treated group took a significantly longer (p less than 0.01) period of time to wean to room air than those in the control group (68.9 +/- 9.6 hours vs 36.6 +/- 6.9 hours). On the basis of these observations, hydrocortisone is not recommended for treatment of MAS.
Article
Increased body temperature stimulates hyperventilation in man but little is known about its effects on ventilatory responsiveness to hypoxia. Hence this study examined the effects of hyperthermia on hypoxic ventilatory response (HVR), hypercapnic ventilatory response (HCVR), and oxygen consumption (VO2). Six fasting subjects had these variables measured under basal conditions and at two levels of hyperthermia. Hypoxic ventilatory response was measured as the shape paramater A of the VE/PAO2 curves. Since hyperthermia produces hyperventilation and, therefore, hypocapnia, HVR was measured at the hyperthermic (hypocapnic alveolar CO2 tension (PACO2) and at the basal (normothermic) PACO2. Hypoxic ventilatory response (A) increased when measured at basal PACO2 levels, from 113 +/- 8.8 (S.E.M.) to 189 +/- 21.8 at 0.7 degrees C. and 240 +/- 34.0 at + 1.40 degrees C. (P less than 0.005). HVR measured during hyperthermic hypocapnia also increased at each temperature level but did not reach statistical significance (P = 0.1). Hypercapnic ventilatory response, as measured by the slope S of VE/PACO2 lines, increased significantly at each temperature elevation (P less than 0.025). We conclude that raising body temperature causes a significant augmentation of ventilatory responses to hypoxia (during normothermic PACO2 conditions) and to hypercapnia.
Article
The ventilatory response to hypoxia (PAO2 55 and 45 Torr) at each of four levels of PACO2 was studied in five healthy subjects before and after a rise in rectal temperature of 1.4 degrees C had been induced by means of a heated flying suit. At a given level of chemical drive both ventilation and mean inspiratory flow increased after heating, frequency relatively more than tidal volume. In isoventilation comparisons mean inspiratory flow was identical in normo- and hyperthermia, whereas the durations of inspiration (TI) and expiration (TE) were proportionately shortened. It is suggested that a rise in temperature shortens TI by affecting a central "clock" and that TE changes are secondary to changes in end-inspiratory volume. The euoxic CO2 response in hyperthermia was suggestive of multiplication between CO2 and temperature. Hypoxic sensitivity was significantly increased, indicating a temperature effect on the arterial chemoreceptors. The breathing pattern was in either temperature condition identical in euoxia and in hypoxia.
Article
Excised cat carotid bodies and nerves were placed in a Lucite chamber through which saline flowed at different temperatures. Action potentials were recorded with a suction electrode. Glomus cells were impaled with microelectrodes and identified by ejecting Procion navy blue from the micropipette. Membrane potentials (MP) averaged 20 mV and input resistances (R0), 40 Momega. Cooling induced depolarization and decreased R0. This effect had a reversal potential of about -6 mV. [K+]0 did not affect MP, R0, or cooling effects. Lack of sodium increased MP, R0, and depressed cooling effects. Low chloride had opposite effects. Ca2+ and Mg2+ influenced MP and R0 but had little effects on temperature actions. Ouabain decreased MP and R0. Results indicate that glomus cells are exquisitely sensitive to temperature changes; their MP and R0 increase with high temperatures and decrease when temperature is lowered. These effects are mostly dependent on the external concentration of Cl- and Na+. Glomus cells may be the site of the intense metabolism of this tissue and thus contribute to the generation of chemosensory impulses.
Article
An animal model of meconium aspiration was developed to determine the efficacy of glucocorticoids in its treatment. Rabbit pups were made to aspirate either meconium or saline prior to the onset of respiration. Cortisol was administered in a random, blind fashion. Slight decrease in respiratory rate and less severe histopathologic changes in the lungs were seen in corticosteroid-treated animals. Survival was significantly decreased, without definite cause, in the glucocorticoid-treated animals whether or not they had aspirated meconium. Because of this decreased survival and the relatively insignificant improvement in clinical course and histopathology found with glucocorticoid treatment, we cannot recommend cortisol for the treatment of meconium aspiration.
Article
Surfactant inactivation has been shown to be a significant factor in animal models of lung injury and may also be important in some forms of respiratory failure in full-term newborns. Fourteen full-term newborns with respiratory failure associated with pneumonia (7 patients) and meconium aspiration syndrome (7 patients) were treated with 90 mg/kg of a calf lung surfactant extract, given intratracheally up to every 6 hours for a maximum of four doses. The group mean fraction of inspired oxygen (FI02) before treatment was 0.99 +/- 0.01 SEM, and the mean airway pressure (MAP) was 14.6 +/- 1.0 cm H2O. Patients showed significant improvement in oxygenation after initial surfactant treatment, with the arterial-alveolar oxygenation ratio (a/A ratio) rising from 0.09 +/- 0.01 before surfactant treatment to 0.22 +/- 0.05 by 15 minutes (P = .03) and remaining improved for 6 hours. The oxygenation index, incorporating MAP as well as oxygen variables, also improved significantly from 26.2 +/- 3.1 to 11.2 +/- 1.7 at 15 minutes (P less than .001), with improvement sustained for more than 6 hours. Chest radiographs were blindly scored from 0 (normal) to 5 (severe opacification), and these improved with marginal significance after initial surfactant treatment (from 2.9 +/- 0.2 to 2.5 +/- 0.2, P = .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The pathophysiology of meconium aspiration is marked by lung hyperinflation because of airway obstruction, which is often followed by an acute pneumonitis with classic lung injury characteristics. Surfactant dysfunction may contribute to this latter pulmonary pathophysiology. We sought to determine to what extent meconium itself might contribute to a functional surfactant deficiency. Specimens of newborn infants' first meconium were collected and pooled. Serial dilutions of the meconium were then added to various concentrations of calf lung surfactant extract, a mixture with the surface properties of natural surfactant that is used clinically to treat neonatal respiratory distress syndrome, and the dynamic surface activity of these mixtures was studied with a pulsating bubble surfactometer. At surfactant concentrations of less than or equal to 1.5 mg/ml, even 6500-fold dilutions of meconium-inhibited surface tension lowering ability (10 +/- 2 mN/m vs 1 +/- 0.1 mN/m for controls, p less than 0.05). Moreover, this inhibitory activity resided in both the chloroform-soluble and the aqueous phases of meconium and appeared to be additive in nature. However, at sufficiently high concentrations of surfactant, even large amounts of meconium were unable to affect surface tension lowering properties. Thus meconium inhibits surfactant function in a manner that is dependent on the surfactant concentration, suggesting the possible utility of exogenous surfactant therapy in some cases of meconium aspiration.
Article
During surgery under pentobarbital sodium anesthesia, 20 rats had heat exchange devices implanted into their abdominal cavity. After recovery, 14 rats underwent two sets of trials, one in which body core temperature (Tbc) was lowered to 34.5-35.5 degrees C and another in which Tbc was raised to 40.5-41.5 degrees C. Rats breathed air and hypoxic (15, 11, and 7% O2 in N2) and hypercapnic (2, 4, and 6% CO2 in air) gas mixtures. Respiratory responses were measured using a barometric method and compared with data from the same rats breathing the gas mixtures at normal Tbc (37.5-38.5 degrees C) before surgery. The six remaining rats served as controls (Tbc unchanged). Lowering Tbc increased respiration in air, whereas heating had no effect. Hypothermia and severe hypoxia combined to inhibit respiration when compared with breathing air at lowered Tbc or low O2 at normal Tbc. The CO2 response slope became steeper when Tbc was raised, suggesting an increased CO2 sensitivity. Possible sites for the hypothermia-hypoxia interaction and the hyperthermia-hypercapnia interaction are discussed.