Redistribution of pulmonary blood flow during hypoxic exercise.

Pulmonary blood flow (PBF) distribution was studied at rest and during exercise in rats acclimatized to chronic hypoxia (barometric pressure [PB] 370 Torr for 3 weeks, A rats) and non-acclimatized (NA) littermates. Both A and NA rats exercised in hypoxia (inspired O2 pressure [PIO2] approximately 70 Torr) or in normoxia (PlO2 approximately 145 Torr). PBF distribution was determined using fluorescent-labeled microspheres injected into the right atrium. The lungs were cut into 28 samples to determine relative scatter of specific PBF ([sample fluorescence intensity/sample dry weight)/(total lung fluorescence intensity/total lung dry weight]). Exercise produced redistribution of PBF both in NA and A rats, and this effect was larger in hypoxia than in normoxia, with minimal redistribution occurring during normoxic exercise in NA rats. The pattern of distribution varies considerably among individual animals. As a result of distribution, the previous high flow areas would be overperfused during hypoxic exercise in some rats. The results support the concept that hypoxic pulmonary vasoconstriction is not uniform and suggest that the combination of hypoxia and exercise may lead to overperfusion and capillary leak in some individuals.

[Early replacement of intravenous aminophylline administration with oral theophylline in treating acute exacerbation of asthma].

Intravenous (i.v.) administration of aminophylline has been used to relieve acute exacerbation of bronchial asthma for almost a century. Despite confidence in its effectiveness, controversy has arisen about its efficacy. We currently use aminophylline in the routine treatment of asthma since the drug is essentially useful. Continuous aminophylline infusion tends to be used rather haphazardly in hospital wards, and the criteria for termination of an infusion have not been clarified. We therefore attempted to determine: 1) whether continuous aminophylline infusion is actually beneficial, 2) whether the TDM (treatment drug monitoring) system can be used to establish a protocol for prescribed dosing after an early switch from i.v. to oral administration, and 3) whether adherence to the protocol would contribute to decreases in the duration of hospitalization and in medical expenses. Seventeen patients with acutely exacerbated asthma were enrolled in this study. Nine patients were prescribed oral theophylline on the second hospital day (p.o. group), while eight received continuous i.v. aminophylline (i.v. group). The serum theophylline concentrations were maintained in the therapeutic range in both groups. Peak flow, symptom scores, and QOL scores showed significant improvements in the p.o. group on the third hospital day. It might therefore be possible, by using the TDM system, to set the dosage of theophylline so that hospitalization is shortened.

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.

[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.

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.

Increasing maximal heart rate increases maximal O2 uptake in rats acclimatized to simulated altitude.

Maximal exercise heart rate (HRmax) is reduced after acclimatization to hypobaric hypoxia. The low HRmax contributes to reduce maximal cardiac output (Qmax) and may limit maximal O2 uptake (VO2max). The objective of these experiments was to test the hypothesis that the reduction in Qmax after acclimatization to hypoxia, due, in part, to the low HRmax, limits VO2max. If this hypothesis is correct, an increase in Qmax would result in a proportionate increase in VO2max. Rats acclimatized to hypobaric hypoxia [inspired PO2 (PIO2) = 69.8 +/- 3 Torr for 3 wk] exercised on a treadmill in hypoxic (PIO2 = 71.7 +/- 1.1 Torr) or normoxic conditions (PIO2 = 142.1 +/- 1.1 Torr). Each rat ran twice: in one bout the rat was allowed to reach its spontaneous HRmax, which was 505 +/- 7 and 501 +/- 5 beats/min in hypoxic and normoxic exercise, respectively; in the other exercise bout, HRmax was increased by 20% to the preacclimatization value of 600 beats/min by atrial pacing. This resulted in an approximately 10% increase in Qmax, since the increase in HRmax was offset by a 10% decrease in stroke volume, probably due to shortening of diastolic filling time. The increase in Qmax was accompanied by a proportionate increase in maximal rate of convective O2 delivery (Qmax x arterial O2 content), maximal work rate, and VO2max in hypoxic and normoxic exercise. The data show that increasing HRmax to preacclimatization levels increases VO2max, supporting the hypothesis that the low HRmax tends to limit VO2max after acclimatization to hypoxia.

Role of beta-adrenergic and cholinergic systems in acclimatization to hypoxia in the rat.

To role of beta-adrenergic and muscarinic cholinergic systems on maximal treadmill exercise performance and systemic O2 transport during hypoxic exercise (PIO2 approximately 70 Torr) was studied in rats acclimatized to hypobaric hypoxia (PIO2 approximately 70 Torr for 3 weeks, A rats) and in non-acclimatized littermates (NA rats). Untreated A rats had lower resting (fH) and maximal heart rate (fHmax) and cardiac output (Q), and higher maximal O2 uptake (VO2max) than NA. The only effect of cholinergic receptor blockade with atropine (Atp) was an increase in pre-exercise fH to comparable levels in A and in NA. beta 1-adrenergic receptor blockade with atenolol (Aten) lowered pre-exercise fH and (fHmax) to comparable values in A and in NA rats. However, since both pre-exercise fH and fHmax were lower in untreated A, the effect of Aten was relatively smaller in A. Aten reduced maximal exercise cardiac output (Qmax) in NA; however, tissue O2 extraction increased such that VO2max was not affected. Aten did not influence Qmax or any other parameter of systemic O2 transport in A. In conclusion the increased cholinergic tone may be responsible for the lower resting fH but not the lower fHmax of A; the integrity of the beta-adrenergic system is not necessary to attain VO2max in hypoxia either in A or in NA; the decreased response to beta-adrenergic stimulation in A limits the efficacy of this system on the mechanisms of systemic O2 transport and reduces the effect of its blockade on these mechanisms.

Chronic hypoxia decreases heterogeneity of pulmonary blood flow distribution in rats.

Pulmonary blood flow (PBF) distribution was studied in 15 chronically hypoxic rats (3 weeks, 10% O2 in N2) breathing 10% O2 (chronic hypoxia, CHx) and after 30 min of breathing air (acute normoxia, ANx). Controls were 15 normoxic littermates (normoxia, Nx) breathing air. Nonradioactive microspheres were infused into the inferior vena cava in the conscious resting state. The lungs were cut into 28 samples, and relative scatter of specific PBF was calculated as (sample activity/sample dry weight)/(total activity/total lung dry weight). In Nx, PBF had a small but significant preferential distribution to the hilar, central regions, with lower blood flow to the peripheral regions (central-to-peripheral pattern). In CHx, however, there was no significant difference between blood flows to the central, middle and peripheral regions of the lung. ANx resulted in no change in PBF distribution. The results indicate that CHx attenuates the central-to-peripheral gradient of PBF distribution, probably due to vascular structural remodeling developed in CHx.

Role of vasoconstrictors in the systemic hypertension of rats acclimatized to hypoxia.

Exposure to hypoxia (2-5 wk) results in systemic hypertension in rats and in humans. The possible mechanism(s) was investigated in rats acclimatized for 3 wk to barometric pressure of approximately 370 Torr (A) and in nonacclimatized littermates (NA) by administration of alpha-adrenergic [phentolamine (PHLM)], angiotensin II (ANG II), and arginine vasopressin (AVP V1) receptor antagonists. Both A and NA rats were studied in hypoxia (inspiratory O2 fraction = 0.10). Baseline mean arterial blood pressure (MABP) was higher in A than in NA rats: 126 +/- 4 vs. 101 +/- 2 mmHg (P < 0.05). Neither ANG II nor AVP V1 receptor antagonist influenced baseline MABP; however, both contributed to MABP recovery after PHLM. After simultaneous blockade of ANG II and AVP V1, PHLM lowered MABP by 65 +/- 2 and 45 +/- 3 mmHg in A and NA rats, respectively (P < 0.05). After combined blockade of the three systems, the smooth muscle relaxant sodium nitroprusside did not further modify MABP, which remained higher in A rats. It is concluded that 1) the hypertension in A rats is partly due to a higher alpha-adrenergic tone, 2) neither ANG II nor AVP contributes to the hypertension, but ANG II and AVP participate in MABP control after PHLM, 3) no other vasoconstrictor agents operate in either group, and 4) the higher MABP in A rats after sodium nitroprusside may reflect additional hypertensive mechanisms.

Pulmonary blood flow distribution during acute hypoxia in conscious resting rats.

The effect of hypoxia on pulmonary blood flow (PBF) distribution were studied in 11 conscious resting rats. Microspheres were infused into the inferior vena cava during normoxia (Nx), acute normobaric hypoxia (AHx, 10% O2, 30 min), and 30 min after removal of hypoxia (post-hypoxia, PHx). The lungs were cut into 28 samples, and relative scatter of specific PBF was calculated as (sample activity/sample dry weight)/(total activity/total lung dry weight). Changes in pulmonary arterial pressure (PAP) during AHx were determined in five additional rats. During Nx, PBF was distributed preferentially to the hilar, central regions, rather than to the periphery. AHx resulted in a decrease in PaO2 from 85.1 +/- 0.9 to 37.8 +/- 1.2 Torr (mean +/- SE). Mean PAP increased significantly from 14.9 +/- 0.6 in Nx to 21.2 +/- 1.0 Torr in AHx (mean +/- SE). However, PBF distribution remained unchanged. PHx restored arterial blood gases and PAP to control levels without changing PBF distribution. The results indicate that conscious resting rats do not demonstrate changes in PBF distribution during AHx.

[Efficacy and assessment of patient education as related to morbidity from asthma].

Asthmatic patients are sometimes ignorant of their treatment and of the pathophysiology of their disease. In such patients, anxiety about the disease may worsen their condition. We studied the effects of an educational program for bronchial asthma. In 45 patients, the Severity of Asthma Scores before and after the program were measured. Sixty percent of the patients were assessed as "improved". On self-administered questionnaires concerned with asthma, most of the patients indicated that the program significantly improved their condition, reduced apprehension about the disease, and increased their trust in the hospital. In 24 patients, three psychological tests were done. Results of the comprehensive asthma inventory indicated that the program was useful for dependent and self-disciplined patients, but was not useful for resigned and depressed patients. The Y-G test showed that most of the patients who were helped by the program were introverted. Results of the Edwards Personal Preference Schedule revealed a difference in desire between the group that benefitted from the program and the group that did not. These results suggest that each group had a certain inclination toward psychogenic symptoms. Therefore, psychological tests are useful for predicting the effects of education. In conclusion, educational programs for patients with bronchial asthma may affect morbidity from asthma. Possible mechanisms include relief of anxiety about the disease and improvement in the patient's compliance with prescribed therapy.

Distribution of pulmonary blood flow in conscious resting rats.

The pattern of pulmonary blood flow (PBF) distribution was determined in the rat, in which lung gravitational forces are minimal. Microspheres were infused into the inferior vena cava of 15 conscious, and 5 anesthetized rats. Relative scatter of specific PBF [(sample activity/sample weight)/(total activity/total weight)] in 28 lung samples was calculated. In 5 of the conscious rats, consecutive determinations were made 30 min apart. In 5 anesthetized rats, PBF was determined in prone and supine positions. Relative scatter of specific PBF varied from 0.84 to 1.12, with PBF being distributed preferentially to the hilar, central regions. There was a high correlation between consecutive measurements: y = 0.88 x +0.11 (n = 140, r = 0.92). By changing from prone to supine position, PBF to the topmost regions increased, and that to the lowermost regions decreased, by only 3 percent. The results indicate that in the conscious resting rat, PBF has a small but significant preferential distribution to the hilar, central regions, with lower blood flow to the peripheral regions of the lung.

Pulmonary gas exchange during hypoxic exercise in the rat.

Pulmonary gas exchange and O2 transport were studied at rest and during maximal treadmill exercise in rats in acute hypoxia (PIO2 approximately 71 Torr), and in littermates acclimatized to PB = 380 Torr (PIO2 approximately 71 Torr) for 3 weeks (chronic hypoxia). To obtain valid estimates of blood gas partial pressures, particularly during exercise, the temperature coefficients of blood pH, PO2 and PCO2 were determined (Appendix). In both acute and chronic hypoxia, the following changes were observed: alveolar and arterial PO2 increased considerably, but the difference, A-aPO2, did not change significantly; arterial O2 concentration (CaO2) decreased, and apparent pulmonary diffusing capacity for O2, Dapp, increased. The increase in Dapp, together with hyperventilation, may prevent further drop in CaO2 due to a large rightward shift in the blood-O2 equilibrium curve caused by lactic acidosis in conjunction with a large Bohr coefficient characteristic of this species. Comparison with corresponding results obtained in man reveals that during hypoxic exercise, the rat shows a larger increase in PAO2, an increase, instead of a decrease, in PaO2, and a larger increase in Dapp.

[Successful treatment of diaphragm pacing-induced obstructive sleep apnea syndrome with nasal CPAP].

We report a 71-year-old female patient with primary alveolar hypoventilation syndrome who received diaphragm pacing (DP) and developed obstructive sleep apnea syndrome (OSAS). Application of nCPAP markedly improved her nocturnal hypoxemia. The monitored polygrams before and after the application strongly suggested that the main mechanism of OSAS was an imbalance of activity between upper airway dilator muscles and pump muscles. Moreover, paradoxical movement of the rib cage is not necessarily due to upper airway obstruction. Monitoring of tidal volume and arterial oxygen saturation is essential for the diagnosis of DP-induced OSAS.