High Arterial Oxygen Tension Research Articles

The association of arterial partial oxygen pressure with mortality in critically ill sepsis patients: a nationwide observational cohort study

BackgroundAlthough several trials were conducted to optimize the oxygenation range in intensive care unit (ICU) patients, no studies have yet reached a universal recommendation on the optimal a partial pressure of oxygen in arterial blood (PaO2) range in patients with sepsis. Our aim was to evaluate whether a relatively high arterial oxygen tension is associated with longer survival in sepsis patients compared with conservative arterial oxygen tension.MethodsFrom the Korean Sepsis Alliance nationwide registry, patients treated with liberal PaO2 (PaO2 ≥ 80 mm Hg) were 1:1 matched with those treated with conservative PaO2 (PaO2 < 80 mm Hg) over the first three days after ICU admission according to the propensity score. The primary outcome was 28-day mortality.ResultsThe median values of PaO2 over the first three ICU days in 1211 liberal and 1211 conservative PaO2 groups were, respectively, 107.2 (92.0–134.0) and 84.4 (71.2–112.0) in day 1110.0 (93.4–132.0) and 80.0 (71.0–100.0) in day 2, and 106.0 (91.9–127.4) and 78.0 (69.0–94.5) in day 3 (all p-values < 0.001). The liberal PaO2 group showed a lower likelihood of death at day 28 (14.9%; hazard ratio [HR], 0.79; 95% confidence interval [CI] 0.65–0.96; p-value = 0.017). ICU (HR, 0.80; 95% CI 0.67–0.96; p-value = 0.019) and hospital mortalities (HR, 0.84; 95% CI 0.73–0.97; p-value = 0.020) were lower in the liberal PaO2 group. On ICU days 2 (p-value = 0.007) and 3 (p-value < 0.001), but not ICU day 1, hyperoxia was associated with better prognosis compared with conservative oxygenation., with the lowest 28-day mortality, especially at PaO2 of around 100 mm Hg.ConclusionsIn critically ill patients with sepsis, higher PaO2 (≥ 80 mm Hg) during the first three ICU days was associated with a lower 28-day mortality compared with conservative PaO2.

Apneustic anesthesia ventilation improves pulmonary function in anesthetized bottlenose dolphins (Tursiops truncatus).

Use of mechanical ventilation during general anesthesia is a necessary practice in the anesthetization of small cetaceans as spontaneous ventilation fails to provide adequate gas exchange. Currently available methods of ventilation do not account for the intermittent breathing strategy of representative species within this infraorder of fully aquatic mammals and may have a significant effect on cardiac and respiratory physiology. To understand the impact of mechanical ventilation on cardiopulmonary function in one small species of cetacean, the bottlenose dolphin (Tursiops truncatus), we compared controlled mechanical ventilation (CMV) to a novel ventilation method known as apneustic anesthesia ventilation (AAV). AAV simulates the normal inspiratory breath-hold pattern of dolphins. Ten anesthetic procedures (dental procedure, n = 9; bronchoscopy, n = 2) were performed on nine dolphins (age range: 10-42 years; mean = 32 years; median = 37 years; female = 3, 40%; male = 6, 60%). In a cross-over study design, dolphins were instrumented and randomly assigned to AAV or CMV as the initial mode of ventilation, then switched to the alternate mode. Baseline cardiopulmonary data were collected and again after 30 min on each mode of ventilation. Cardiac index, stroke volume index, systemic vascular resistance, alveolar dead space, alveolar-arterial oxygen tension gradient, arterial oxygen content, oxygen delivery index, and dynamic respiratory system compliance index were calculated at each of the four time points. During AAV, dolphins had higher arterial oxygen tension, higher mean airway pressure, reduced alveolar dead space ventilation and lower alveolar-arterial oxygen difference. Cardiovascular performance was not statistically different between the two modes. Our study suggests AAV, which more closely resembles the conscious intermittent respiratory pattern phenotype of dolphins, improves ventilation and pulmonary function in the anesthetized dolphin. Future studies should evaluate the cardiopulmonary effects of neutral buoyancy and cardiopulmonary sparing drug protocols to reduce the need for hemodynamic support of current protocols.

Impact of hyperoxia and phenylephrine on cerebral oxygenation: An experimental clinical study.

Oxygen supply to the brain is of special importance during intracranial surgery because it may be compromised by intracranial pathology. A high arterial blood pressure (mean arterial pressure above 80 mmHg) and a high arterial oxygen tension (PaO2 above 12 kPa) is therefore often targeted in these patients, when for example intracranial pressure is increased or when a mass effect on brain tissue from a tumour is present, and it is pursued by administering vasopressors such as phenylephrine and by increasing inspiratory oxygen fraction (FiO2 ). However, whether these interventions increase cerebral oxygenation remains uncertain. We aimed to investigate the effect of hyperoxia and phenylephrine on brain tissue oxygen tension (PbtO2 ) in patients undergoing craniotomy. In this experimental study, we included 17 adult patients scheduled for elective craniotomy. After securing a stable baseline of the oxygen probe, PbtO2 was measured in white matter peripherally in the surgical field during general anaesthesia. Primary comparisons were PbtO2 before versus after an increase in FiO2 from 0.30 to 0.80 as well as before versus after a bolus dose of phenylephrine (0.1-0.2mg depending on patient haemodynamics). Data were analysed with the Wilcoxon signed rank test. We obtained complete data sets in 11 patients undergoing the FiO2 increase and six patients receiving the phenylephrine bolus. PbtO2 was 22 (median; 5%-95% range, 4.6-54) mmHg during 30% oxygen, 68 (8.4-99) mmHg during 80% oxygen (p=.004 compared to 30% oxygen), 21 (4.5-81) mmHg before phenylephrine, and 19 (4.2-56) mmHg after phenylephrine (p=.56 compared to before phenylephrine). In patients undergoing craniotomy under general anaesthesia, brain tissue oxygen tension increased with a high inspiratory oxygen fraction but remained unchanged after a bolus dose of phenylephrine.

Conservative Oxygen Therapy during Mechanical Ventilation in the ICU

BackgroundPatients who are undergoing mechanical ventilation in the intensive care unit (ICU) often receive a high fraction of inspired oxygen (Fio2) and have a high arterial oxygen tension. The conservative use of oxygen may reduce oxygen exposure, diminish lung and systemic oxidative injury, and thereby increase the number of ventilator-free days (days alive and free from mechanical ventilation).MethodsWe randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy. In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo2) was 90%. In the conservative-oxygen group, the upper limit of the Spo2 alarm was set to sound when the level reached 97%, and the Fio2 was decreased to 0.21 if the Spo2 was above the acceptable lower limit. In the usual-oxygen group, there were no specific measures limiting the Fio2 or the Spo2. The primary outcome was the number of ventilator-free days from randomization until day 28.ResultsThe number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usual-oxygen group, with a median duration of 21.3 days (interquartile range, 0 to 26.3) and 22.1 days (interquartile range, 0 to 26.2), respectively, for an absolute difference of −0.3 days (95% confidence interval [CI], −2.1 to 1.6; P=0.80). The conservative-oxygen group spent more time in the ICU with an Fio2 of 0.21 than the usual-oxygen group, with a median duration of 29 hours (interquartile range, 5 to 78) and 1 hour (interquartile range, 0 to 17), respectively (absolute difference, 28 hours; 95% CI, 22 to 34); the conservative-oxygen group spent less time with an Spo2 exceeding 96%, with a duration of 27 hours (interquartile range, 11 to 63.5) and 49 hours (interquartile range, 22 to 112), respectively (absolute difference, 22 hours; 95% CI, 14 to 30). At 180 days, mortality was 35.7% in the conservative-oxygen group and 34.5% in the usual-oxygen group, for an unadjusted odds ratio of 1.05 (95% CI, 0.81 to 1.37).ConclusionsIn adults undergoing mechanical ventilation in the ICU, the use of conservative oxygen therapy, as compared with usual oxygen therapy, did not significantly affect the number of ventilator-free days. (Funded by the Health Research Council of New Zealand; ICU-ROX Australian and New Zealand Clinical Trials Registry number, ACTRN12615000957594.)

Pitfalls in haemodynamic monitoring in the postoperative and critical care setting.

Haemodynamic monitoring is a vital part of daily practice in anaesthesia and intensive care. Although there is evidence to suggest that goal-directed therapy may improve outcomes in the perioperative period, which haemodynamic targets we should aim at to optimise patient outcomes remain elusive and controversial. This review highlights the pitfalls in commonly used haemodynamic targets, including arterial blood pressure, central venous pressure, cardiac output, central venous oxygen saturation and dynamic haemodynamic indices. Evidence suggests that autoregulation in regional organ circulation may change either due to chronic hypertension or different disease processes such as traumatic brain injury, cerebrovascular ischaemia or haemorrhage; this will influence the preferred blood pressure target. Central venous pressure can be influenced by multiple pathophysiological factors and, unless central venous pressure is very low, it is rarely useful as a predictor for fluid responsiveness. Central venous oxygen saturation can be easily increased by a high arterial oxygen tension, making it useless as a surrogate marker of good cardiac output or systemic oxygen delivery in the presence of hyperoxaemia. Many dynamic haemodynamic indices have been reported to predict fluid responsiveness, but they all have their own limitations. There is also insufficient evidence to support that giving fluid until the patient is no longer fluid responsive can improve patient-centred outcomes. With the exception in the context of preventing contrast-induced nephropathy, large randomised controlled studies suggest that excessive fluid treatment may prolong duration of mechanical ventilation without preventing acute kidney injury in the critically ill.

Association Between High Arterial Oxygen Tension and Long-Term Survival After Spontaneous Intracerebral Hemorrhage.

To determine the relation between high arterial oxygen tension levels (PaO2) and long-term mortality in patients with spontaneous intracerebral hemorrhage treated in the ICU. National observational multicenter cohort study. Twenty-one ICUs in Finland. A total of 3,033 adult patients. None. Patients were divided into high (> 150 mm Hg), intermediate (97.5-150 mm Hg), and low (< 97.5 mm Hg) PaO2 groups based on the lowest measured PaO2/FIO2 ratio during the first 24 hours after ICU admission: 63% (n = 1,923) were in the low group, 29% (n = 892) were in the intermediate group, and 7% (n = 218) were in the high group; 80% were mechanically ventilated. The primary outcome was 6-month mortality, which occurred in 49% of patients and was significantly more frequent in the high PaO2 group than in the intermediate and low PaO2 groups (61% vs 52% and 46%, respectively, p < 0.001). In univariate analysis, patients in the high PaO2 group had a significantly increased risk of 6-month mortality compared with the low PaO2 group (odds ratio, 1.82; 95% CIs, 1.36-2.42; p < 0.001), but this statistically significant relation was lost after adjusting for markers of severity of illness in a logistic mixed-effects regression model (odds ratio, 1.10; 95% CI, 0.76-1.60; p = 0.598). No significant relation between PaO2 levels and long-term mortality was found. The clinical role of hyperoxemia in patients with intracerebral hemorrhage treated in the ICU remains controversial and warrants further studies.

Association between high arterial oxygen tension and long-term survival after intracerebral hemorrhage

Liberal use of oxygen after brain insults remains controversial [1,2]. We studied whether high arterial oxygen tension (PaO2) is associated with decreased long-term survival in patients with spontaneous intracerebral hemorrhage (ICH) treated in the ICU.

Mechanism of Benefit of Head-up Preoxygenation in Obese Patients

Mount Sinai School of Medicine, New York, New York. david.wax@mssm.eduI read with interest the study report in the June 2005 issue of Anesthesiology by Dixon et al. 1regarding the benefits of head-up preoxygenation in obese patients. Although I do not dispute the basic findings of the study or the benefit of head-up position in obese patients, I question the conclusions drawn in the abstract and discussion.Although there was a strong correlation between oxygen tension and time to desaturation, it cannot be concluded that the higher arterial oxygen tension (Pao2) itself was protective. The oxygen content of blood in the form of dissolved oxygen under nonhyperbaric pressure conditions is minimal. At the preinduction Pao2achieved after 3 min of preoxygenation in both supine and head-up subjects, hemoglobin would be expected to be 100% saturated, providing maximal blood oxygen content in both study groups. The additional time to desaturation afforded by the small increase in dissolved oxygen reserve in the head-up group is unlikely to have been significant. More likely, the benefit of head-up positioning in delaying desaturation (as well as increasing Pao2) is a result of factors of pulmonary mechanics mentioned in the study background as they relate to oxygen reserve.Also for this reason, changing the patient’s position from head-up to supine at induction as suggested possible to ease intubation may partially or completely negate the benefits of the head-up preoxygenation despite the increased preinduction Pao2. This repositioning maneuver might be useful in a follow-up study to test this hypothesis.Mount Sinai School of Medicine, New York, New York. david.wax@mssm.edu

Leukotrienes in Acute Lung Injury

Leukotrienes in Acute Lung Injury

Vitamin C prevents hyperoxia-mediated vasoconstriction and impairment of endothelium-dependent vasodilation.

High arterial blood oxygen tension increases vascular resistance, possibly related to an interaction between reactive oxygen species and endothelium-derived vasoactive factors. Vitamin C is a potent antioxidant capable of reversing endothelial dysfunction due to increased oxidant stress. We tested the hypotheses that hyperoxic vasoconstriction would be prevented by vitamin C, and that acetylcholine-mediated vasodilation would be blunted by hyperoxia and restored by vitamin C. Venous occlusion strain gauge plethysmography was used to measure forearm blood flow (FBF) in 11 healthy subjects and 15 congestive heart failure (CHF) patients, a population characterized by endothelial dysfunction and oxidative stress. The effect of hyperoxia on FBF and derived forearm vascular resistance (FVR) at rest and in response to intra-arterial acetylcholine was recorded. In both healthy subjects and CHF patients, hyperoxia-mediated increases in basal FVR were prevented by the coinfusion of vitamin C. In healthy subjects, hyperoxia impaired the acetylcholine-mediated increase in FBF, an effect also prevented by vitamin C. In contrast, hyperoxia had no effect on verapamil-mediated increases in FBF. In CHF patients, hyperoxia did not affect FBF responses to acetylcholine or verapamil. The addition of vitamin C during hyperoxia augmented FBF responses to acetylcholine. These results suggest that hyperoxic vasoconstriction is mediated by oxidative stress. Moreover, hyperoxia impairs acetylcholine-mediated vasodilation in the setting of intact endothelial function. These effects of hyperoxia are prevented by vitamin C, providing evidence that hyperoxia-derived free radicals impair the activity of endothelium-derived vasoactive factors.

Long-term survival after thoracoscopic lung volume reduction: a multiinstitutional review

Background. It has been suggested that bilateral thoracoscopic lung volume reduction (BTLVR) yields significantly better long-term survival than unilateral thoracoscopic lung volume reduction (UTLVR).Methods. All perioperative data were collected at the time of the procedure. Follow-up data were obtained during office visits or by telephone.Results. A total of 673 patients underwent thoracoscopic LVR: 343 had either simultaneous or staged BTLVR and 330, UTLVR. As of July 1998, follow-up was available on 667 (99%) of the 673 patients with a mean follow-up of 24.3 months. The patients in the BTLVR group were significantly younger (62.6 ± 8.0 years versus 65.4 ± 8.1 years; p < 0.0001), had a higher preoperative arterial oxygen tension (69.7 ± 12 mm Hg versus 65.3 ± 11 mm Hg; p < 0.0001), and had a superior preoperative 6-minute walk performance (279.9 ± 93.6 m [933 ± 312 feet] versus 244.5 ± 101.4 m [815 ± 338 feet] p < 0.0001). There was no difference in the operative mortality rate between the two groups (UTLVR, 5.1%, and BTLVR, 7%). Actuarial survival rates for the UTLVR group at 1 year, 2 years, and 3 years were 86%, 75%, and 69%, respectively versus 90%, 81%, and 74%, respectively, for the BTLVR group (p = not significant).Conclusions. Contrary to previous reports, survival after BTLVR was not superior to that after UTLVR even though the former group appeared to have a lower risk preoperatively because of younger age, higher arterial oxygen tension, more advantageous anatomy, and better functional status. Despite thoracoscopic LVR, the actuarial mortality rate approached 30% at 3 years, and this calls into question whether this procedure offers any survival advantage to patients with end-stage emphysema.

Mechanisms of coronary vasoconstriction induced by high arterial oxygen tension.

In isolated rabbit hearts perfused with suspension of red blood cells, we investigated the role of the endothelium and of several substances in the coronary vasoconstriction induced by a high arterial blood oxygen tension (PaO2). Red blood cells in Krebs-Henseleit buffer were oxygenated to obtain control and high-PaO2 perfusates. Arterial oxygen content was kept constant in both perfusates by reducing hemoglobin concentration in the high-PaO2 perfusate. Coronary blood flow was kept constant so that oxygen supply would not vary with the rise in PaO2. Increases in perfusion pressure therefore reflected increased coronary resistance. The high PaO2-induced coronary vasoconstriction was not affected by administration of indomethacin, nordihydroguaiaretic acid, NG-nitro-L-arginine, or superoxide dismutase and catalase but was abolished after endothelium damage or by cromakalim. These results demonstrate that 1) the endothelium contributes to the high PaO2-induced coronary vasoconstriction; 2) this effect is independent of cyclooxygenase or lipoxygenase products, nitric oxide, or free radicals; and 3) the closure of ATP-sensitive K+ channels mediates this vasoconstriction.

Controlled reperfusion of cardiac grafts from non-heart-beating donors

Hearts harvested from non-heart-beating donors sustain severe injury during procurement and implantation, mandating interventions to preserve their function. We tested the hypothesis that limiting oxygen delivery during initial reperfusion of such hearts would reduce free-radical injury. Rabbits sustained hypoxic arrest after ventilatory withdrawal, followed by 20 minutes of in vivo ischemia. Hearts were excised and reperfused with blood under conditions of high arterial oxygen tension (PaO2) (approximately 400 mm Hg), low PaO2 (approximately 60 to 70 mm Hg), high pressure (80 mm Hg), and low pressure (40 mm Hg), with or without free-radical scavenger infusion. Non-heart-beating donor groups were defined by the initial reperfusion conditions: high PaO2/ high pressure (n = 8), low PaO2/high pressure (n = 7), high PaO2/low pressure (n = 8), low PaO2/low pressure (n = 7), and high PaO2/high pressure/free-radical scavenger infusion (n = 7). After 45 minutes of reperfusion, low PaO2/ high pressure and high PaO2/low pressure had a significantly higher left ventricular developed pressure (63.6 +/- 5.6 and 63.1 +/- 5.6 mm Hg, respectively) than high PaO2/high pressure (40.9 +/- 4.5 mm Hg; p < 0.0000001 versus both). However, high PaO2/high pressure/free-radical scavenger infusion displayed only a trend toward improved ventricular recovery compared with high PaO2/ high pressure. Initially reperfusing nonbeating cardiac grafts at low PaO2 or low pressure improves recovery, but may involve mechanisms other than decreased free-radical injury.

Amplification by phenylephrine and serotonin of coronary vasoconstriction induced by a high arterial blood oxygen tension

The aim was to investigate the effect on the coronary network of the interaction between high arterial blood oxygen tension (PaO2) and stimulation by the alpha adrenergic agonist phenylephrine or by serotonin in an isolated, blood perfused rabbit heart preparation. Fresh pig erythrocytes in Krebs-Henseleit buffer were oxygenated to reach normal PaO2 [19.4(SEM 0.7) kPa] or high PaO2 [53.2(5.5) kPa]. Blood oxygen content was kept constant despite the higher PaO2, by slightly reducing the haemoglobin concentration from 9.3(0.2) to 8.8(0.2) g.100 ml-1 (p < 0.01). Coronary blood flow was kept constant throughout the study, so that the oxygen supply would not vary with the rise in PaO2. Increases in coronary resistance were therefore reflected by increased perfusion pressure. Switching from normal to high PaO2 induced coronary vasoconstriction, reflected by enhanced perfusion pressure of +21(5)%. After pretreatment with the alpha adrenergic agonist phenylephrine, perfusion of a high PaO2 solution increased coronary resistance by +35(7)% (p < 0.05), a value significantly higher than that found without phenylephrine. Oxygen consumption and myocardial performance did not vary throughout the study. To determine whether this amplification of the response was specifically due to alpha agonist stimulation or could be observed with other vasoactive agents, we applied the same protocol using serotonin instead of phenylephrine. Here again, coronary vasoconstriction rose in response to high PaO2 after serotonin infusion [+25(5)% versus +59(10)%]. The response of the coronary network to high PaO2 is amplified by pretreatment with the alpha adrenergic agonist phenylephrine or with serotonin, regardless of any changes in metabolic status.

Highdose inhaled steroid therapy and the cortisol stress response to acute severe asthma

Systemic absorption of inhaled corticosteroids taken in high doses (> or = 1500 micrograms beclomethasone dipropionate or budesonide daily), may cause suppression of the hypothalamo-pituitary-adrenal axis. Patients taking long-term high dose inhaled steroid therapy might therefore be at risk of adrenal crisis at times of stress. Plasma cortisol levels were measured in 24 adults with severe acute asthma who had not received treatment with systemic corticosteroids prior to hospital attendance. Seven were not taking inhaled steroids, four were taking 600-1200 micrograms and 13 were taking 1500-2400 micrograms beclomethasone dipropionate or budesonide daily. Plasma cortisol levels in these 13 (median 594 nmol l-1, interquartile range 399-620 nmol l-1) were similar to levels in those taking lower dose/no inhaled steroids (median 512 nmol l-1, interquartile range 287-1050 nmol l-1): there was no relationship between inhaled steroid dose and cortisol level. Nine of the 24 patients failed to achieve plasma cortisol values > 500 nmol l-1 (the normal response to an insulin stress test). When compared with the remaining 15, they had less severe asthma as indicated by higher arterial oxygen tension (P < 0.01) and peak expiratory flow (P < 0.03). Patients taking long-term high dose inhaled corticosteroids appear to be able to mount an appropriate adrenocortical response to the stress of severe acute asthma.

Effects of high arterial oxygen tension on function, blood flow distribution, and metabolism in ischemic myocardium.

Although oxygen inhalation therapy has long been used in the treatment of acute myocardial ischemia, experimental evidence that increased arterial PO2 has any beneficial effect in the absence of hypoxemia is equivocal. In this study, we used a swine model of subendocardial myocardial ischemia to determine the effects of arterial hyperoxia on regional myocardial contractile function (sonomicrometry), myocardial blood flow distribution (microspheres), and regional myocardial glycolytic metabolism (carbon isotope-labeled substrates). In 10 domestic swine, the left anterior descending coronary artery was cannulated and flow to this artery was strictly controlled via a roller pump in the perfusion circuit. Arterial PO2 was controlled by manipulating inspired oxygen concentration (FIO2). Low-flow myocardial ischemia was induced by reducing pump flow to 50% of the control value, which diminished regional endocardial systolic shortening to 30-50% of normal. After a 15-minute period of flow stability, each animal was exposed in randomized order to two additional 15-minute experimental periods: coronary normoxia (PO2 = 90-110 mm Hg) and coronary hyperoxia (PO2 greater than 400 mm Hg). At each level of oxygenation, we measured regional myocardial function, regional myocardial blood flow and metabolism, and hemodynamic indexes of myocardial oxygen demand. Myocardial ischemia during normoxia reduced systolic shortening to 10.9 +/- 5.3% in the ischemic zone. Hyperoxia increased ischemic zone systolic shortening substantially to 15.2 +/- 4.6%. During myocardial ischemia, endocardial blood flow was decreased to 0.26 +/- 0.06 ml.g-1.min-1 in the ischemic zone. During hyperoxia, endocardial blood flow rose to 0.34 +/- 0.10 ml.g-1.m-1. The endocardial: epicardial flow ratio was 0.45 +/- 0.18 in the initial ischemia period and rose to 0.61 +/- 0.23 in the hyperoxic period. Myocardial ischemia increased regional uptake of glucose, conversion of glucose to released lactate, and net myocardial lactate release. In the ischemic myocardium, coronary hyperoxia decreased both chemically measured lactate production and isotopically measured lactate release and decreased glucose extraction and the conversion of glucose to lactate. These data demonstrate for the first time that increasing arterial PO2 to high levels during acute low-flow myocardial ischemia improves both function and flow distribution in the ischemic myocardium and decreases glycolytic metabolism in the ischemic zone. The degree of improvement in contractile function (5% absolute increase in systolic shortening or 25% change normalized to preischemic values) is consistent with the observed increase in subendocardial blood flow.

COMPARISON OF THE EFFECTS OF HIGH FREQUENCY OSCILLATION AND CONTROLLED MECHANICAL VENTILATION ON HYALINE MEMBRANE FORMATION IN A RABBIT MODEL OF THE NEONATAL RESPIRATORY DISTRESS SYNDROME

Saline lavage of the lungs of eight anaesthetized New Zealand White rabbits was performed to produce a surfactant-depletion model of the neonatal respiratory distress syndrome. A characteristic change in the shape of the pressure-volume curve occurred, with the appearance of an inflection point on the inspiratory limb. The animals were treated with high frequency oscillation (HFO) at 15 Hz and the results compared with those of a previously studied group of eight similar rabbits treated with controlled mechanical ventilation (CMV) with end-expiratory pressure equal to the pressure at the inflection point, but with the same mean airway pressure of 15 mm Hg. The animals treated with HFO had significantly higher arterial oxygen tensions and end-expiratory lung volumes than those treated with CMV, but there was no significant difference between hyaline membrane scores. Although there was no significant difference in mean survival times, five of the HFO treated animals showed reversion of the shape of their pressure-volume curves towards the prelavage configuration, suggesting a recovery of surfactant function.

Delineation of myocardial ischemia in an isolated blood-perfused rabbit heart preparation

Isolated perfused heart preparations provide controlled conditions for the study of myocardial respiration and metabolism. Most studies utilize a hemoglobin-free perfusate which requires high arterial oxygen tension and high coronary perfusion rate. A blood-perfused rabbit heart preparation using an "assist" rabbit to maintain blood homeostasis has been developed which is suitable for respiratory, metabolic, and spectroscopic studies of myocardial function under controlled conditions. Fluorescence emission of reduced nicotinamide adenine dinucleotide (NADH) from the surface of blood-perfused rabbit heart was photographed to delineate areas of myocardial ischemia detectable as NADH fluorescence from reduced mitochondria. Blood reperfusion of ischemic myocardium resulted in disappearance of NADH fluorescence. Reocclusion of the coronary artery resulted in the same pattern and amplitude of NADH fluorescence.

Apnea testing in the diagnosis of brain death. Clinical and physiological observations.

The absence of spontaneous respiration is a crucial determinant in the diagnosis of brain death, but standardized criteria for apnea testing have not been established. Guidelines are proposed based on the results of 51 apnea tests and associated physiological measurements. In patients who fulfilled all other conventional criteria for brain death, three exhibited non-repetitive back arching and shoulder shrugging when CO2 pressures reached 41 to 51 mm Hg during apnea testing. These respiratory-like movements were ineffective for ventilation and were not reproducible on the following day at the same of higher pCO2. The nature of these movements, evoked potential testing, and autopsy results suggest that they were not triggered by normal medullary centers, and that these patients were, in fact, brain-dead. In four other patients with severe brain damage sparing only the medulla, normal spontaneous ventilation resumed at CO2 pressures of 30 to 39 mm Hg (mean 34 mm Hg). High arterial oxygen tension raised this apnea point slightly, but spontaneous breathing always began at CO2 pressures lower than 40 mm Hg. This level is therefore adequate to stimulate medullary respiration in patients with severe brain damage who are not brain-dead. In brain-dead patients, pCO2 rises slowly during apnea (2.58 +/- 0.85 mm Hg/min), in part because CO2 production is diminished (1.8 +/- 0.23 ml/min/kg). These data allow estimation of a desired length of an apnea test and standardized interpretation of results.

Myocardial contractile force at high coronary arterial oxygen tension in dogs.

In 34 mongrel dogs, the left anterior descending coronary artery was perfused with the dog's own femoral arterial blood at a constant flow rate and the myocardial contractile force was measured using a myocardial strain gauge arch. When the femoral arterial blood was oxygenated (pO2 61.7 kPa (463 mmHg)) using an artificial lung, so that the perfused myocardium became hyperoxic, the myocardial contractile force was increased by 11.1 +/- 2.3%. When the perfusion rate was reduced by approximately 20%, there was a smaller increase in myocardial contractile force, 8.0 +/- 2.3%. If, in addition, oxygen inhalation was performed the myocardial contractile force decreased by 4.1 +/- 2.1%. In 10 mongrel dogs, the carotid arteries were perfused at a constant flow rate with femoral arterial blood from a donor dog. Oxygen inhalation by the donor dog caused a reduction in the myocardial contractile force of the experimental dog of 5.9 +/- 1.6%. It is suggested that oxygen has a direct effect in increasing myocardial contractile force. This increase is counteracted by oxygen-induced coronary vasoconstriction in some part and by a neurohumoral effect or suppression of chemoreceptor activity.