Acute respiratory failure in multiple sclerosis.

A 23-year-old woman developed acute respiratory failure in the course of multiple sclerosis. The lack of bulbar dysfunction, the presence of quadriplegia, and the bilateral diaphragmatic weakness indicated the presence of spinal cord lesions involving pyramidal tracts bilaterally. Magnetic resonance imaging revealed a cervical demyelinating lesion between C1 and C3.

Regional blood flow in conscious resting rats determined by microsphere distribution.

To determine organ blood flow in the resting state, a box was designed to keep conscious untrained rats minimally disturbed. Blood pressure, heart rate, and organ blood flow, determined by the microsphere distribution and reference sampling technique, were measured in 11 Sprague-Dawley rats. After an acclimation period, 15-microns-diameter microspheres labeled with 113Sn were infused into the ascending aorta, a reference blood sample was withdrawn from the caudal artery, and organ blood flows were computed according to standard procedures. The average values of heart rate (365 beats/min) and blood flow to the brain (45 ml.min-1.100 g-1) and hindlimb muscles (15 ml.min-1.100 g-1) were significantly lower than most values reported earlier, whereas splanchnic blood flow was significantly higher (106 ml.min-1.100 g-1). Blood flow to the soleus muscle, which is considered the most active for postural maintenance, was relatively high (99 ml.min-1.100 g-1). The combination of low skeletal muscle and high visceral blood flows observed in these experiments suggests a low sympathetic tone, which is consistent with the low level of circulating catecholamines also observed in this study. It is hypothesized that the difference between our present and previous results is a lower level of stress, attributable to a more complete acclimation to the experimental environment.

Changes in regional blood flow distribution and oxygen supply during hypoxia in conscious rats.

The effects of acute hypoxia on central hemodynamics, regional blood flow, and regional oxygen supply (blood flow x arterial O2 concentration) were studied in conscious resting rats. Regional blood flow was determined by the radiolabeled microsphere technique. Blood pressure, heart rate; and aortic blood flow increased and total peripheral resistance decreased significantly during hypoxia. Blood flow to brain, respiratory muscles, and liver increased both in absolute value and as a fraction of the aortic blood flow. Fractional blood flow to the gastrointestinal tract, spleen, pancreas, skin, fat, and hindlimb bones decreased during hypoxia; blood flow decreased in absolute values only in stomach and fat. Oxygen supply to brain, respiratory muscles, and liver increased during hypoxia, whereas it decreased in the remaining organs investigated.

Splenic contraction-induced reversible increase in hemoglobin concentration in intermittent hypoxia.

The effect of intermittent hypoxia (IHx) on blood hemoglobin concentration ([Hb]) and the underlying mechanisms were studied in rats exposed to 10% O2, 1 h/day, for up to 5 wk. IHx protocols with longer daily hypoxic exposure show persistent polycythemia; however, it is unknown whether [Hb] increases transiently during hypoxia in protocols without polycythemia. Hypoxia produced a reversible [Hb] increase after 4 days of IHx but not in normoxic controls (NxC) or after shorter period of IHx. Splenectomy abolished the phenomenon. Plasma epinephrine and norepinephrine levels during hypoxia were comparable in IHx and NxC groups, but the epinephrine-induced [Hb] increase was larger in IHx. The alpha1- and alpha2-adrenoreceptor blockade (phentolamine) and alpha2-blockade (yohimbine) abolished the [Hb] increase of IHx rats. Conversely, alpha2-receptor stimulation (oxymetazoline) increased [Hb] during normoxia in IHx but not in NxC. In conclusion, this IHx protocol results in reversible [Hb] increases during hypoxia via splenic contraction mediated by increased alpha2-adrenoreceptor response. This may protect O2 supply during hypoxia without the cardiovascular burden of polycythemia during normoxia.

Acute vs. chronic effects of elevated hemoglobin O(2) affinity on O(2) transport in maximal exercise.

These studies were conducted to compare the effects on systemic O(2) transport of chronically vs. acutely increased Hb O(2) affinity. O(2) transport during maximal normoxic and hypoxic [inspired PO(2) (PI(O(2))) = 70 and 55 Torr, respectively] exercise was studied in rats with Hb O(2) affinity that was increased chronically by sodium cyanate (group 1) or acutely by transfusion with blood obtained from cyanate-treated rats (group 2). Group 3 consisted of normal rats. Hb O(2) half-saturation pressure (P(50); Torr) during maximal exercise was approximately 26 in groups 1 and 2 and approximately 46 in group 3. In normoxia, maximal blood O(2) convection (TO(2 max) = cardiac output x arterial blood O(2) content) was similar in all groups, whereas in hypoxia TO(2 max) was significantly higher in groups 1 and 2 than in group 3. Tissue O(2) extraction (arteriovenous O(2) content/arterial O(2) content) was lowest in group 1, intermediate in group 2, and highest in group 3 (P < 0.05) at all exercise PI(O(2)) values. In normoxia, maximal O(2) utilization (VO(2 max)) paralleled O(2) extraction ratio and was lowest in group 1, intermediate in group 2, and highest in group 3 (P < 0.05). In hypoxia, the lower O(2) extraction ratio values of groups 1 and 2 were offset by their higher TO(2 max); accordingly, their differences in VO(2 max) from group 3 were attenuated or reversed. Tissue O(2) transfer capacity (VO(2 max)/mixed venous PO(2)) was lowest in group 1 and comparable in groups 2 and 3. We conclude that lowering Hb P(50) has opposing effects on TO(2 max) and O(2) extraction ratio, with the relative magnitude of these changes, which varies with PI(O(2)), determining VO(2 max). Although the lower O(2) extraction ratio of groups 2 vs. 3 suggests a decrease in tissue PO(2) diffusion gradient secondary to the low P(50), the lower O(2) extraction ratio of groups 1 vs. 2 suggests additional negative effects of sodium cyanate and/or chronically low Hb P(50) on tissue O(2) transfer.

Effect of chronic sodium cyanate administration on O2 transport and uptake in hypoxic and normoxic exercise.

Systemic O2 transport during maximal exercise at different inspired PO2 (PIO2) values was studied in sodium cyanate-treated (CY) and nontreated (NT) rats. CY rats exhibited increased O2 affinity of Hb (exercise O2 half-saturation pressure of Hb = 27.5 vs. 42.5 Torr), elevated blood Hb concentration, pulmonary hypertension, blunted hypoxic pulmonary vasoconstriction, and normal ventilatory response to exercise. Maximal rate of convective O2 transport was higher and tissue O2 extraction was lower in CY than in NT rats. The relative magnitude of these opposing changes, which determined the net effect of cyanate on maximal O2 uptake (VO2 max), varied at different PIO2: VO2 max (ml. min-1. kg-1) was lower in normoxia (72.8 +/- 1.9 vs. 81. 1 +/- 1.2), the same at 70 Torr PIO2 (55.4 +/- 1.4 vs. 54.1 +/- 1.4), and higher at 55 Torr PIO2 (48 +/- 0.7 vs. 40.4 +/- 1.9) in CY than in NT rats. The beneficial effect of cyanate on VO2 max at 55 Torr PIO2 disappeared when Hb concentration was lowered to normal. It is concluded that the effect of cyanate on VO2 max depends on the relative changes in blood O2 convection and tissue O2 extraction, which vary at different PIO2. Although uptake of O2 by the blood in the lungs is enhanced by cyanate, its release at the tissues is limited, probably because of a reduction in the capillary-to-tissue PO2 diffusion gradient secondary to the increased O2 affinity of Hb.

Application of the fold plication method for unilateral lung volume reduction in pulmonary emphysema.

BACKGROUND: Unilateral lung volume reduction procedures are used to treat pulmonary emphysema. The most significant technical problem with this operation is an air leak from the pulmonary stump. Bovine pericardium has been used to prevent air leaks but is associated with interstitial pneumonia and a high cost. METHODS: The fold plication method was devised to prevent postoperative air leaks to avoid interstitial pneumonia, and to decrease cost. This technique was applied in 20 consecutive patients with emphysema who underwent a unilateral lung volume reduction operation via a thoracoscopic two windows approach. RESULTS: The operative time was approximately 1 hour. There was minimal postoperative bleeding, no persistent air leaks, and no evidence of pneumonia. Pulmonary function improved in all patients. CONCLUSIONS: The unilateral fold plication method is an economical and safe alternative to bovine pericardial patching after lung volume reduction operation to prevent stump air leaks.

Expression of inducible nitric oxide synthase immunoreactivity in rat brain following chronic hypoxia: effect of aminoguanidine.

To clarify the role of inducible nitric oxide synthase (iNOS) in the histopathological changes that occur in the brain after exposure of rats to normobaric hypoxia (10% O2 in N2) for 2 weeks, we examined the localization of iNOS and the effect of aminoguanidine, a relatively selective iNOS inhibitor, on the histological outcome. Animals were divided into a hypoxia group, an aminoguanidine-treated hypoxia group and a normoxic control group. The hypoxia group showed severe ischemic changes and prominent angiogenesis in the CA1 hippocampus and cerebral cortex. Aminoguanidine significantly reduced the ischemic change and angiogenesis in these regions, and also reduced iNOS-immunoreactive cells compared to the hypoxia group. These findings suggest that iNOS activity could play a role in the neuropathological alterations induced by chronic hypoxia.

alpha2-Adrenergic-receptor response in reversible increase in hemoglobin concentration in intermittent hypoxia.

We have previously shown that intermittent hypoxia (IHx, 10% O(2), 60 min/day) leads to an increase in the splenic alpha2-adrenoceptor response and results in a splenic contraction-induced reversible increase in hemoglobin concentration ([Hb]). In the present study, we determined whether IHx of shorter duration (15 min/day (15-min) and 30 min/day (30-min)), produced this phenomenon in rats. A significant increase in [Hb] during hypoxia was observed in both the groups, but its magnitude was larger in the 30-min IHx rats. Even when the cumulative exposure time (time/dayxdays) was shorter, the [Hb] increase was larger in the rats with longer daily hypoxic exposure. The alpha2-adrenoceptor antagonist yohimbine abolished the [Hb] increase of 15- and 30-min IHx. The increase in [Hb] following administration of the alpha2-adrenoceptor agonist oxymetazoline was also higher in 30-min IHx; indicating that the higher [Hb] produced by longer daily hypoxic exposure times is the result of increases in alpha2-adrenergic-receptor response of greater magnitude. In conclusion, IHx for periods as short as 15 and 30 min/day increases the splenic alpha2-adrenoceptor response and its magnitude reaches the maximum value depending on the daily hypoxic exposure time. A reversible increase in [Hb] constitutes a useful mechanism that protects organ oxygen supply during hypoxic episodes of variable duration and intensity.

Curative resection of both primary and second primary lung cancer.

Curative resection of a second primary lung cancer in a patient who survived small-cell lung cancer is reported. Small-cell cancer had been treated with chemotherapy followed by surgical resection 12 years before. The patient developed squamous cell cancer as the second primary tumor and underwent lobectomy with mediastinal node dissection. Patients who undergo two curative pulmonary resections of both primary and second primary lung cancer are extremely rare. The patient is alive 176 months after the initial diagnosis of small-cell lung cancer and 28 months after resection for his second primary lung cancer. Careful follow-up at an interval of 3-6 months beyond 10 years is very important because adequate treatments could lead to longer survival of patients with primary small-cell lung cancer.

Effectiveness of the fold plication method in lung volume reduction surgery.

OBJECT: The fold plication method is a new operative procedure for lung volume reduction surgery whereby the target area is obliterated by plicating the folded tissue using a knifeless stapler, without the use of bovine pericardium. The effectiveness of this new method was evaluated in patients with advanced pulmonary emphysema. PATIENTS AND METHODS: Two weeks before and 6 months after surgery, pulmonary function, static lung compliance, maximal esophageal pressure, maximal inspiratory and expiratory mouth pressures, 6-min walking distance and the Borg scale were determined in twenty consecutive patients who underwent video-assisted thoracoscopic unilateral surgery. RESULTS: There was an increase in forced expiratory volume in one second (31%), forced vital capacity, peak expiratory flow rate and maximal voluntary ventilation, and a decrease in functional residual capacity (-16%) measured by plethysmograph. Static lung compliance decreased, and maximal esophageal pressure, and maximal inspiratory and expiratory mouth pressures increased. The 6-min walking distance increased (20%) and the Borg scale decreased (5.9 to 3.5). CONCLUSION: The results compare favorably with those obtained with other methods. Thus, the fold plication method could be considered an alternative procedure for lung volume reduction surgery.

Reversal of airflow obstruction and improvement in cystic lesions with treatment of HIV associated PCP.

A 54-year-old Japanese male smoker in whom lung function had been normal developed airflow obstruction coincident with the development of human immunodeficiency virus (HIV)-associated Peumocystis carinii pneumonia (PCP). Chest high resolution computed tomography (HRCT) revealed cystic lesions involving the upper lung fields. Both cystic lesions and airflow obstruction improved simultaneously with treatment of PCP and acquired immunodeficiency syndrome (AIDS). Bronchiolar PCP lesions creating a check-valve mechanism may explain these reversible changes.

O2 uptake and CO2 elimination during mechanical ventilation with high frequency oscillation.

This study was intended to elucidate gas exchange in a quasi-steady state during high frequency oscillatory ventilation (HFO) in terms of arterial blood gases, tidal volume(VT) and frequency of oscillation (f). Firstly, experiments were performed on anesthetized, paralyzed and tracheostomized dogs using a piston-type oscillator with a fresh air bias flow. The f values employed in the animal experiments were 10 to 30 Hz, and VT values were 1 to 3 ml/kg of body weight. Changes in PaO2 observed during HFO could be expressed by the equation PaO2 = 125.2-60.3/(VT X f), which closely coincided with the alveolar ventilation equation for O2, i.e., PaO2 = 125-78/, VA, Where P(A-a) O2 and O2 consumption were assumed to be 25 Torr and 90 ml/min, respectively. PaCO2 during HFO deviated from the curve of the alveolar ventilation equation, PaCO2 = constant/, VA at a higher VT x f, and was distributed along the hyperbolic curve of PaCO2 = 1/, VA + 14.7. This suggested that HFO shows a certain limitation in CO2 elimination. Secondly, indicator gas transport through straight tube models for two directions, i.e., wash-in and wash-out, were observed. Wash-in of indicator gases (He, N2 and SF6) in terms of indicator appearance time at the other end of the tube changed as a function of VT x f. The effect of increasing f at a fixed VT on the wash-in was much less than that of increasing VT at a fixed f. The heavier gas (SF6) was washed in faster than the lighter gas (He) although wash-in of each indicator gas was closely related to the function VT x f. Washout in terms of the appearance time of indicators in the opposite direction was, however, strongly dependent on VT, and the effect of increasing f at a fixed VT on wash-out reached a limit beyond a certain f. It was concluded from the present study, that both convective dispersion and augmented diffusion play important roles, although they are not clearly distinguished, as gas transport mechanisms during HFO. The difference between inspiratory and expiratory gas transport modes could be explained by differences in flow profiles, relative important of convective dispersion, and/or time required for gas mixing in the airways.

Effects of inspiratory pressure oscillation on pulmonary gas exchange and circulatory functions in anesthetized, mechanically ventilated dogs.

Anesthetized, mechanically ventilated dogs were used to study the effects of inspiratory pressure oscillation on gas exchange. Respiratory failure was induced in dogs artificially, changing either tidal volume or ventilatory rate. Pressure oscillation of approximately 2 Hz with amplitudes of 2 to 7 cmH2O was applied on the inspiratory phase of mechanical ventilation. PaO2 and PaCO2 were improved consistently by pressure oscillation while minute ventilation was kept fixed. No significant change was observed in AaDO2, cardiac output, heart rate, ECG and both systemic and pulmonary arterial pressures under oscillated ventilation. The oscillated ventilation could be continued for more than 60 minutes without causing any significant change in circulatory function. The ratio of alveolar ventilation to minute ventilation (VA/VE) increased and that of dead space to tidal volume (VD/VT) decreased significantly. The oscillated ventilation while breathing He-O2 and SF6-O2 showed no consistent difference in the effects on gas exchange. It can be concluded that simple pressure oscillation improves gas mixing in the lungs and may be applied to respiratory care. However the mechanism remains to be elucidated.

A computerized standard flow-generator for spirometer calibration.

We analyzed the dynamic characteristics of a newly designed standard flow generator (SFG) to be used for spirometer calibration. The SFG consisted of a computer, large-bore cylinder, and piston driven by a high torque motor. The computer develops numerical equations to simulate a flow-volume pattern with different convexities of the descending limb. The excursion of the piston was processed according to the computer-developed equation. The computer's numerical solutions were compared to those of the SFG and agreement of the values of the peak flow, forced expiratory volume, and flow-volume pattern was satisfactory in repeated trials. Application of an external resistive load (3.5 cm H2O/sec) did not change the flow output. However, there were several minor disagreements due to the dynamic characteristics of the SFG. In an emphysema pattern the ascending limb of the generated flow-volume curve flattened and the descending limb was less convex compared to the preset pattern. When the SFG was generating sinusoidal waves of high frequency (e.g., 10.0 Hz) the flow output was deformed. The newly designed SFG was used to examine the dynamic characteristics of rolling-seal spirometers. There was an overshoot of the peak flow, over-convection, and oscillations of the descending limb in the spirometer output. These deformations were more prominent with the severe emphysema pattern. It is concluded that the SFG can be very useful in the examination and calibration of spirometers.

Paraquat poisoning--a review of four cases.

Paraquat poisoning has been associated with very high mortality. The toxic mechanism is considered to be related to the production of superoxide ions. Review of the literatures reveals that with vigorous treatment recovery from poisoning is not impossible. Clinical experience in four cases of paraquat poisoning and the principles of management of this intoxication are presented.

[Thoracoscopic unilateral fold plication method in lung volume reduction surgery for diffuse pulmonary emphysema].

We have devised a 'Fold Plication Method', which helps ensure safe and simple lung volume reduction surgery (LVRS) for pulmonary emphysema and prevent air leakage from pulmonary stumps, which is most crucial problem, in addition to postoperative interstitial pneumonia that is occasionally caused by the use of the bovine pericardium. We performed LVRS on seven patients with the disease, using this method and the thoracoscopic surgery, which is based on the 'Two Windows Method' we had previously developed. The operation was performed without observable bleeding within approximately one hour for all patients, who then recovered favorably.

[A case of idiopathic tracheal stenosis].

A 44-year-old woman who had been treated for bronchial asthma for 5 years was admitted for further evaluation of progressive dyspnea. Physical examination revealed wheezing originating in the neck. A flow-volume curve suggested upper-airway stenosis. The patient had no history of trauma, endotracheal intubation, granulomatous diseases, or any other severe respiratory tract infections. Chest radiography and laboratory examination showed no abnormalities. Tracheal X-P, computed tomography and magnetic resonance imaging of the neck, and bronchoscopy demonstrated circumferential subglottic tracheal stenosis extending for 40 mm. The diameter of the lumen was 5 mm at its narrowest. The trachea distal to the lesion was normal. Bronchoscopic biopsy revealed thickened tracheal mucosa and submucosa with increased fibrous tissue and chronic inflammatory cell infiltration, suggesting a nonspecific inflammatory process. These findings are compatible with idiopathic tracheal stenosis, which was reported by Bhalla et al. The patient was treated with Nd-YAG laser surgery via a fiberoptic bronchoscope, which resulted in a great improvement in respiration. Regression of the lesion has not occurred in the 40 months since the laser surgery. The majority of patients with this condition have been treated by surgical resection of the stenotic lesion and reconstruction. However, the success of Nd-YAG laser surgery in the present case suggests that this approach would be a satisfactory alternative procedure for treatment of idiopathic tracheal stenosis.

[Platelet activation in obstructive sleep apnea syndrome].

The incidences of cardiovascular and cerebrovascular diseases are reportedly higher in patients with obstructive sleep apnea (OSA) than in OSA-free subjects, though the mechanism remains unknown. Recently, the contribution of activated platelets to a number of pathological conditions such as stroke or ischemic heart disease has been suggested. We hypothesized that the expression of activated platelet markers resulting from OSA might be higher than in healthy subjects. By flow cytometry using monoclonal antibodies, we measured two such markers, PAC-1 and CD 62 P, in OSA patients and healthy subjects. Twelve healthy men (age, 52.7 +/- 12.8 y/o; and body mass index (BMI), 22.2 +/- 16.1 kg/m2; mean +/- S.D.) and 20 male patients with OSA (age, 50 +/- 7.96 y/o; BMI, 28.1 +/- 3.3 kg/m2; apnea hypopnea index (AHI), 38.2 +/- 21.2 times/hr; and lowest SpO2, 75.6 +/- 11.3%) were enrolled in this study. PAC-1 expression was significantly higher in OSA patients (65.1 +/- 17.8%) than in healthy subjects (16.8 +/- 7.4%), as was CD 62 P expression (8.5 +/- 8.8% vs. 0.88 +/- 0.57%). The increase in PAC-1 expression was correlated with AHI and the arousal index. These findings suggest that activated platelet markers could be good indicators for untreated OSA.