Role of Cerebrospinal Fluid [H+] in Ventilatory Deacclimatization from Chronic Hypoxia

Once ventilatory acclimatization begins in sea level residents sojourning at high altitude, abrupt restoration of normal oxygen tensions will not restore ventilation to normal. We have investigated the role of cerebrospinal fluid (CSF) [H(+)] in this sustained hyperventilation by measuring CSF acid-base status in seven men (lumbar) and five ponies (cisternal) in normoxia, first at sea level and then periodically over 13-24 h of "deacclimatization" after 3-5 d in hypoxia (P(B) = 440 mm Hg). After 1 h deacclimatization, hyperventilation continued at a level only slightly less than that obtained in chronic hypoxia (+1-2 mm Hg Pa(CO2)), whereas CSF pH was either equal (in man) or alkaline (in pony, +0.02, P < 0.01) to sea level values. Between 1 and 12-13 h deacclimatization in all humans and ponies Va fell progressively (Pa(CO2) increased 4-7 mm Hg) and CSF pH became increasingly more acid (-0.02 to -0.05, P < 0.01). Between 12 and 24 h of normoxic deacclimatization in ponies, Pa(CO2) rose further toward normal, coincident with an increasing acidity in CSF (-0.02 pH). Similar negative correlations were found between changes in arterial pH and Va throughout normoxic deacclimatization. We conclude that [H(+)] in the lumbar or cisternal CSF is not the mediator of the continued hyperventilation and its gradual dissipation with time during normoxic deacclimatization from chronic hypoxia. These negative relationships of Va to CSF [H(+)] in normoxia are analogous to those previously shown during acclimatization to hypoxia.     

低氧训练与低氧大鼠心肌细胞凋亡及凋亡因子的表达

背景：低氧训练时,机体既要承受运动负荷,同时处于外界的低氧环境,此时,心组织将如何适应其变化？其机制研究国内外较少。目的：观察低氧与低氧训练对大鼠心肌细胞凋亡及Bax及Bcl-2表达的影响。方法：SD大鼠共60只随机分为6组,常氧组、低氧8h组、低氧12h组、常氧训练组、低氧8h训练组和低氧12h训练组,每组10只。后3组大鼠每天在坡度为0的动物跑台上以25m／min的速度训练1h。训练完后,将低氧8h组、低氧8h训练组和低氧12h组、低氧12h训练组放入氧体积分数为12．5％（相当于海拔4000m）的低氧舱内8h和12h。实验期为4周,5d／周。最后1次实验结束后24h,大鼠均实施速眠新II腹腔麻醉后取材,采用苏木精-伊红染色、原位末端脱氧核糖核苷酸转移酶介导的dUTP缺口末端标记法及蛋白免疫组织化学法检测各组大鼠心肌细胞凋亡和Bcl-2、Bax蛋白表达。结果与结论：①与常氧组相比,低氧12h组、常氧训练组、低氧训练组心肌细胞凋亡指数均显著增加（P〈0．05）;低氧12h训练组心肌细胞凋亡指数显著多于常氧训练组和低氧8h训练组（P〈0．05）。②与常氧组比较,其他各组Bcl-2、Bax、Bcl-2／Bax均显著性增高（P〈0．05）：常氧训练组Bcl-2、Bax、Bcl-2／Bax表达显著高于低氧8h组,显著低于低氧12h训练组（P〈0．05）;低氧12h训练组Bcl-2、Bax、Bcl-2／Bax表达比低氧12h组、低氧8h训练组显著增加（P〈0．05）。提示低氧、低氧训练可诱导大鼠心肌细胞Bcl-2、Bax蛋白表达,运动时低氧刺激与细胞凋亡率、凋亡指数及病理损伤有关,其中以低氧12h后运动训练组最明显,心肌细胞的凋亡调控与Bcl-2和Bax相关。     

The effect of verapamil and inspired CO2 on the bronchoconstriction provoked by hyperventilation in normal humans

Two groups of eight normal subjects were investigated in separate studies to demonstrate the effects of changes in end-tidal PCO2, and of pretreatment with the calcium antagonist drug verapamil, on bronchoconstriction provoked by voluntary hyperventilation. Total respiratory resistance (Ros) was measured by the forced oscillation technique before and after 90 s voluntary hyperventilation. End-tidal PCO2 during hyperventilation was varied by altering inspired CO2 concentration. When end-tidal PCO2 fell during hyperventilation, there was a rise in Ros. This did not occur if end-tidal PCO2 was controlled at a normal resting level during hyperventilation. Specific conductance (sGaw) was measured before and after 90 s voluntary hyperventilation of air. Subjects were treated with oral verapamil or placebo for 2 1/2 days and the effect of hyperventilation on sGaw was reassessed. Verapamil reduced significantly the fall in sGaw caused by hyperventilation. Placebo had no effect. In normal humans, bronchoconstriction provoked by hyperventilating air at ambient temperature and humidity is mediated by the fall in PCO2, and is also reduced by verapamil.     

Low-dose ritonavir moderately enhances nelfinavir exposure

BACKGROUND: The protease inhibitor ritonavir is increasingly administered at subtherapeutic doses in highly active antiretroviral treatment, to utilize its potential for drug interactions and to enhance the plasma concentrations of other concomitantly prescribed protease inhibitors. The addition of low doses of ritonavir to nelfinavir was investigated to describe the extent of pharmacokinetic interaction. METHODS: In this randomized, open-label, one-sequence crossover study, nelfinavir 1250 mg twice a day was dosed for 17 days, followed by 14 days of nelfinavir 1250 mg twice a day plus low doses of ritonavir of either 100 mg or 200 mg orally. Twenty-four healthy volunteers were evaluated for pharmacokinetics of nelfinavir, its metabolite M8, and ritonavir. Plasma concentrations were measured up to 12 hours after morning and evening dosing, respectively, on days 14 and 31. RESULTS: Ritonavir increased the area under the plasma concentration-time curve (AUC) of nelfinavir by 20% (P =.024) and 39% (P =.001) after morning and evening administration, respectively. The AUC of nelfinavir metabolite M8 was increased by 74% and 86% after morning and evening dosing (P <.001 for both). CONCLUSION: During ritonavir combination therapy a clear although minor drug effect on nelfinavir pharmacokinetics was demonstrated but no dose effect was shown.     

Investigating the claims of Konstantin Buteyko, M.D., Ph.D.: the relationship of breath holding time to end tidal CO2 and other proposed measures of dysfunctional breathing

OBJECTIVES: Konstantin Buteyko, M.D., Ph.D., claimed that breath holding time (BHT) can be used to detect chronic hyperventilation and that BHT predicts alveolar CO(2) (Pa(CO(2))) according to his patented mathematical formula. The Buteyko Breathing Technique (BBT) is believed to correct chronic hyperventilation as evidenced by increased BHT. In this study, we test Buteyko's claims and explore the relationship between BHT and end-tidal carbon dioxide (ETCO(2)) as well as measures of dysfunctional breathing (DB) including the Nijmegen questionnaire, the Self Evaluation of Breathing Questionnaire, and thoracic dominant breathing pattern. SUBJECTS: Eighty-three (83) adults healthy or suspected of having dysfunctional breathing, 29 with abnormal spirometry readings, 54 with normal spirometry. OUTCOME MEASURES: BHT, performed according to BBT protocols, was measured along with ETCO(2) and other measures of DB including the Nijmegen questionnaire, and manual assessment of respiratory motion, a palpatory technique for measuring thoraco-abdominal balance during breathing. Correlations between measures of DB were made in the whole sample and also in subgroups with normal or abnormal spirometry. DB measures were compared in normal and abnormal spirometry groups. RESULTS: The results revealed a negative correlation between BHT and ETCO(2) (r= -0.241, p<0.05), directly opposite to Buteyko's claims. BHT was significantly shorter in people with abnormal spirometry (FEV(1) or FVC<15% below predicted), with no difference in ETCO(2) levels between the abnormal and normal spirometry groups. In the abnormal spirometry group, lower BHT was found to correlate with a thoracic dominant breathing pattern. (r= -0.408, p<0.028). CONCLUSIONS: Although BHT does not predict resting ETCO(2), it does correlate with breathing pattern in subjects with abnormal spirometry. It is proposed that altered breathing pattern could contribute to breathing symptoms such as dyspnea and that breathing therapies such as BBT might influence symptoms by improving the efficiency of the biomechanics of breathing.     

Cerebrovascular response to acute hypocapnic and eucapnic hypoxia in normal man

Alterations in human cerebral blood flow and related blood constituents were studied during exposure to acute hypoxia. Observations were made during serial inhalation of decreasing O(2) concentrations with and without maintenance of normocarbia, during 8 min inhalation of 10% O(2), and after hyperventilation at an arterial P(O2) of about 40 mm Hg. In the range of hypoxemia studied, from normal down to arterial P(O2) of about 40 mm Hg, the magnitude of the cerebral vasodilator response to hypoxia appeared to be largely dependent upon the coexisting arterial CO(2) tension. The mean slope of the increase in cerebral blood flow with decreasing arterial O(2) tension rose more quickly (P < 0.05) when eucapnia was maintained when compared with the slope derived under similar hypoxic conditions without maintenance of eucapnia. When 12 subjects inhaled 10% oxygen, cerebral blood flow rose to more than 135% of control in four whose mean decrease in arterial CO(2) tension was - 2.0 mm Hg. The remaining eight had flows ranging from 97 to 120% of control, and their mean decrease in CO(2) tension was - 5.1 mm Hg. When mean arterial P(O2) was 37 mm Hg, hyperventilation was carried out in 10 subjects. Arterial P(O2) increased insignificantly, arterial P(CO2) declined from 34 to 27 mm Hg (P < 0.05), and cerebral blood flow which had been 143% of control decreased to 109%, a figure not significantly different from control.These data demonstrate the powerful counterbalancing constrictor effects of modest reductions in CO(2) tension on the vasodilator influence of hypoxia represented by arterial P(O2) reductions to about 40 mm Hg. Indeed, mild hyperventilation completely overcame the vasodilator effect provided by an arterial O(2) tension as low as 40 mm Hg. The effects of hypoxia on the control of the cerebral circulation must be analyzed in terms of the effects of any associated changes in CO(2) tension.     

Ventilatory Acclimatization to Moderate Hypoxemia in Man: THE ROLE OF SPINAL FLUID [H+]

This study has assessed the regulation of arterial blood and cerebrospinal fluid (CSF) pH and thereby their contribution to the control of breathing in normal man during various stages of ventilatory acclimatization to 3,100 m altitude. CSF acid-base status was determined: (a) from measurements of lumbar spinal fluid during steady-state conditions of chronic normoxia (250 m altitude) and at + 8 h and + 3-4 wk of hypobaric hypoxia; and (b) from changes in cerebral venous P(CO2) at + 1 h hypoxic exposure. After 3-4 wk at 3,100 m, CSF [H(+)] remained significantly alkaline to values obtained in either chronic normoxia or with 1 h hypoxic exposure and was compensated to the same extent ( approximately 66%) as was arterial blood [H(+)]. Ventilatory acclimatization to 3,100 m bore no positive relationship to accompanying changes in arterial P(O2) and pH and CSF pH: (a) CSF pH either increased or remained constant at 8 h and at 3-4 wk hypoxic exposure, respectively, coincident with significant, progressive reductions in Pa(CO2); (b) arterial P(O2) and pH increased progressively with time of exposure; and (c) in the steady-state of acclimatization to 3,100 m the combination of chemical stimuli present, i.e. Pa(O2) = 60 mm Hg, pHa and pH(CSF) = + 0.03-0.04 > control, was insufficient to produce the observed hyperventilation (Pa(CO2) = 32 mm Hg). It was postulated that ventilatory acclimatization to 3,100 m altitude was mediated by factors other than CSF [H(+)] and that the combination of chronic hypoxemia and hypocapnia of moderate degrees provided no mechanisms for the specific regulation of CSF [H(CO3) (-)] and hence for homeostasis of CSF [H(+)].     

Unilateral high-altitude pulmonary edema (HAPE): a case report and discussion of pathophysiology

High-altitude pulmonary edema (HAPE), a potentially life-threatening altitude adaptation disorder, is considered to be caused by an exaggerated increase in pulmonary blood pressure and a non-cardiogenic rise in pulmonary vascular permeability subsequent to alveolar hypoxia. A 40-year-old male mountaineer was affected by an advanced stage of HAPE at high altitude (Monte Rosa plateau, 4000 m). The symptoms abated immediately after the patient descended from the altitude. However, six hours after the symptoms had resolved, radiographic signs of pulmonary edema, confined to the right lung, were seen. This rarely described unilateral radiological pattern of HAPE resolved completely within two days. We suggest that aspiration events of nasal secretion, the right sleeping position at night and an elevated right diaphragm reduced the patient's compensatory hyperventilation capacity of the right lung. The resulting increased alveolar hypoxia in the right lung was responsible for unilateral edema. The pathophysiological mechanism underlying unilateral HAPE is discussed.     

Diurnal variability in orthostatic tachycardia: implications for the postural tachycardia syndrome

Patients with POTS (postural tachycardia syndrome) have excessive orthostatic tachycardia (>30 beats/min) when standing from a supine position. HR (heart rate) and BP (blood pressure) are known to exhibit diurnal variability, but the role of diurnal variability in orthostatic changes of HR and BP is not known. In the present study, we tested the hypothesis that there is diurnal variation of orthostatic HR and BP in patients with POTS and healthy controls. Patients with POTS (n=54) and healthy volunteers (n=26) were admitted to the Clinical Research Center. Supine and standing (5 min) HR and BP were obtained in the evening on the day of admission and in the following morning. Overall, standing HR was significantly higher in the morning (102±3 beats/min) than in the evening (93±2 beats/min; P<0.001). Standing HR was higher in the morning in both POTS patients (108±4 beats/min in the morning compared with 100±3 beats/min in the evening; P=0.012) and controls (89±3 beats/min in the morning compared with 80±2 beats/min in the evening; P=0.005) when analysed separately. There was no diurnal variability in orthostatic BP in POTS. A greater number of subjects met the POTS HR criterion in the morning compared with the evening (P=0.008). There was significant diurnal variability in orthostatic tachycardia, with a great orthostatic tachycardia in the morning compared with the evening in both patients with POTS and healthy subjects. Given the importance of orthostatic tachycardia in diagnosing POTS, this diurnal variability should be considered in the clinic as it may affect the diagnosis of POTS.     

Reduction of the inhibitory effect of ketoconazole on budesonide pharmacokinetics by separation of their time of administration

BACKGROUND: Budesonide is a glucocorticosteroid used in the treatment of, for example, inflammatory bowel diseases, with a recommended once-daily morning dosing regimen. Ketoconazole is a potent inhibitor of the cytochrome P450 3A (CYP3A) activities and known to inhibit the elimination of drugs metabolized by CYP3A, including budesonide. It is of therapeutic interest to know whether the influence of ketoconazole can be reduced by administration on an occasion different in time to CYP3A substrates. METHODS: Eight healthy men completed this randomized, open crossover study that comprised three different periods. In period 1, a single oral dose of 3 mg budesonide was given in the morning. In period 2, a 200-mg ketoconazole tablet was administered once daily in the morning on 4 consecutive days. On the fourth day, 3 mg budesonide was administered at the same time as the ketoconazole. In period 3, 200 mg ketoconazole was administered once daily in the evening on 4 consecutive days. On the fourth day, 3 mg budesonide was administered 12 hours before the ketoconazole. One-week washout periods separated the budesonide administrations. RESULTS: The mean area under the plasma drug concentration-time curve [AUC(0-24)] for budesonide was increased by 6.5 times when it was given simultaneously with ketoconazole. When the administrations of the two drugs were separated by 12 hours, the mean AUC(0-24) for budesonide was increased by only 3.8 times. CONCLUSION: This study shows that the capability of ketoconazole to inhibit the elimination of budesonide is significantly reduced (by 50%) by a 12-hour separation of the administration times.     

Investigation of the therapeutic use of proton pump inhibitor (PPI) by measurement of 24 hour the intra-gastric pH]

The intragastric acidic condition were examined over 24 hours in 13 healthy volunteers to compare the inhibitory effect of PPI and of H2-antagonist on the acid secretion. Both PPI 15 mg and PPI 20 mg showed a stronger action on the acid inhibition than H2-antagonists. The morning PPI (20 mg) administration inhibited the acid secretion from noon the first day, and showed an even stronger effect on the fourth day (total PPI 80 mg). Evening PPI administration showed poorer effects than the morning. However, of this was due to a difference in the inhibitory effect in the daytime. The evening PPI administration showed effective acid inhibition at night, and nocturnal intra-gastric pH inversion appeared. It is suggested that the evening PPI administration is more suitable both the ulcer-healing and food digestion in the curative stage.     

Influence of a circadian-stage-dependent dosing schedule on the pharmacokinetics of isepamicin in humans

These experiments were conducted in order to determine the influence of the time of day of drug administration on the pharmacokinetics of isepamicin. Six healthy volunteers were given 400 mg isepamicin IM, on 2 separate occasions, either in the morning (8 AM) or in the evening (8 PM). Within-subject differences in the pharmacokinetic parameters between the morning and evening dosing regimens were evaluated. The plasma concentrations of isepamicin were not significantly different between the morning and evening trials, but significant time-dependent changes were found with a lower elimination rate constant and a longer elimination half-life in patients administered isepamicin at night. Our finding suggests that isepamicin may have the same clinical effects irrespective of whether dosing takes place in the morning or in the evening, but its clearance tends to be depressed when taken in the evening. Therefore, morning therapy is desirable because of possible interference from aminoglycoside toxicity.     

The effects of abnormal sympathetic nervous function upon the ventilatory response to hypoxia

THE VENTILATORY RESPONSE TO HYPOXIA WAS STUDIED IN TWO GROUPS OF SUBJECTS WITH ABNORMAL SYMPATHETIC NERVOUS CONTROL: (a) human subjects with familial dysautonomia (Riley-Day syndrome), and (b) unanesthetized goats treated with an alpha-adrenergic blocking agent (phenoxybenzamine). The ventilatory response to hypoxia was evaluated in two ways: (a) from the slope of the relationship between ventilation and alveolar P(Co2) ([unk]V(E)-P(ACo2) slope) during the rebreathing of hypoxic and hyperoxic gases, and (b) from the change in ventilation produced when hypoxia was abruptly relieved.The ventilatory and circulatory responses of the unanesthetized, phenoxybenzamine-treated goats were qualitatively similar to those of dysautonomic patients. In contrast to the sustained stimulation of ventilation produced by hypoxia in normal subjects, hypoxia either did not change, or decreased, the [unk]V(E)-P(ACo2) slope of dysautonomic patients and phenoxybenzamine-treated goats; CO(2)-free hypoxia produced a fleeting hyperventilation, which was followed by apnea when hypoxia was abruptly relieved. Unlike normal subjects, the dysautonomic patients and phenoxybenzamine-treated goats became hypotensive while hypoxic.The results indicate that peripheral chemoreceptor reflex responses to hypoxia are preserved in subjects in whom sympathetic nervous responses are impaired. However, the central nervous depression of ventilation by hypoxia is enhanced simultaneously. The inordinate central depression is attributed to the inability of the dysautonomic subjects and goats to maintain systemic blood pressure and, consequently, cerebral blood flow during hypoxia, thereby aggrevating central nervous hypoxia.     

急性低氧及不同强度急性常氧运动与高住低练大鼠腓肠肌血管内皮细胞生长因子的表达

背景:通过运动和,或低氧来增加机体对低氧的应激程度和时间,可提高机体对运动和,或低氧的适应水平,但目前对急性运动和,或低氧对骨骼肌血管内皮生长因子表达的影响所知甚少.目的:观察急性运动和,或低氧对大鼠腓肠肌血管内皮生长因子表达的影响.设计、时间及地点:随机对照动物实验,于2005-09/2006-09在江苏省人民医院临床实验研究室完成.对象:选用健康雄性SD大鼠108只,随机分为6组:即常氧安静组、急性常氧高强度组、急性常氧中强度组、低氧安静组、急性低练高住高强度组和急性低练高住中强度组,每组18只.段氏PT型鼠跑台为杭州产.实验方法:急性常氧运动模型:运动前48 h进行适应活动.高强度运动:运动50 m/min×1.5 min休2 min.中强度运动:运动30 m/min×30 min.低氧模型:采用低氧仪产生低氧气分压的混合气体,低氧3 d,22 h/d,氧气12.8%,温度22℃,湿度55%.急性低练高住模型:在急性高、中强度运动后实施上述低氧计划.于各组处理后即刻、2,4 h分别处死大鼠4只取大鼠腓肠肌.主要观察指标:用Western-blot法测定大鼠腓肠肌血管内皮生长因子表达.结果:低氧和急性常氧运动增强了血管内皮生长因子表达,运动后低氧削弱了运动诱导的血管内皮生长因子表达,长时间中等强度的运动诱导更多的血管内皮生长因子表达.急性运动和,或低氧后即刻、2 h血管内皮生长因子表达最多,其恢复速度由快向慢排序为:低氧或低练高住、常氧运动.结论:急性运动和,或低氧诱导的大鼠骨骼肌血管内皮生长因子的表达属早期速发效应,且存在强度阈值,其恢复速度与表达的幅度成反比,低练高住可能能增强骨骼肌对运动的适应.     

Effect of ligustrazine on pulmonary vascular changes induced by chronic hypoxia in rats

1. Acute and chronic effects on the pulmonary circulation of ligustrazine, a chemically identified and synthesized principle of a Chinese herb, were studied in rats. It dilated lung vessels and reversed hypoxic pulmonary vasoconstriction. 2. In rats kept 2 weeks in 10% O2 in a normobaric chamber and simultaneously treated with ligustrazine, right ventricular hypertrophy and muscularization of pulmonary arterioles were attenuated compared with saline-treated rats. Pulmonary artery pressure, measured in isolated lungs perfused at a constant flow rate, was also less in ligustrazine-treated rats. 3. In isolated blood-perfused lungs of chronically hypoxic and control rats, the relation between pressure and flow was measured during normoxia (ventilation with air plus 5% CO2), hypoxia (2% O2 plus 5% CO2) and after ligustrazine during continued hypoxia. Alveolar pressure was always greater than left atrial pressure; thus flow was determined by the pulmonary artery minus alveolar pressure difference. 4. Pressure/flow lines were measured during normoxia in four groups of rats: (1) control, saline-treated; (2) control, ligustrazine-treated; (3) chronically hypoxic, saline-treated; (4) chronically hypoxic, ligustrazine-treated. Both chronically hypoxic groups had steeper lines (higher resistance) than the control groups, which were similar in all respects. However, in chronically hypoxic rats, the extrapolated intercept of the line on the pressure axis, probably attributable to small newly muscularized arterioles in a state of tone, was much increased in the saline-treated group but did not differ from controls in the ligustrazine-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomized, double-blind, multi-site, crossover, placebo-controlled equivalence study of morning versus evening once-daily sustained-release morphine sulfate in people with pain from advanced cancer

Diurnal variation in pain perception is recognized. The question of whether opioid prescribing should be adjusted to account for diurnal variation can be tested with the advent of once-daily sustained-release morphine. The study recruited 45 people with opioid-responsive pain on stable doses of analgesics and advanced cancer from five regional palliative care programs in Australia. Each participant took one placebo and a 24-hourly dose of sustained-release morphine daily, 12 hours apart-active dose in the morning for one week and in the evening for the other week. The order of the weeks was randomized in a double-blind manner. The primary outcome from the last two days (steady state) on both arms was averaged four-hourly pain scores while awake on a 100 mm visual analogue scale (VAS). Secondary outcomes included VAS and categorical scales for other pain parameters, quality of sleep, nausea, vomiting, constipation, confusion, and somnolence. Twenty-six of 42 participants completed the study and provided adequate power for analysis. Mean VAS was 16 mm for morning dosing and 14 mm for evening dosing (P=0.76, difference of adjusted means 2 mm, 95% confidence interval: -2, 6). No differences were found in pain control, pain during the day, pain disturbing sleep, or with breakthrough medication use. This study suggests that any difference between morning and evening dosing of once-daily sustained-release morphine in people with significant opioid-responsive pain and advanced cancer is small and unlikely to be clinically significant for most people.     

Effect of exercise on morning stiffness and mobility in patients with rheumatoid arthritis

The effects of evening exercises on arthrographic measures of elastic stiffness, subjective ratings of stiffness, and graphic goniometric measures of mobility were examined in 30 patients with rheumatoid arthritis. Measures were obtained on 2 consecutive mornings, one of which was randomly determined to be preceded by evening exercise. Each morning, elastic stiffness and mobility were measured before and after morning exercise. After the final measurements of elastic stiffness and mobility on the second day, patients compared stiffness on the 2 days. Elastic stiffness and subjective ratings of stiffness were less and mobility was greater when evening exercises were performed (p less than 0.001). The relationships between elastic stiffness and subjective ratings of stiffness indicated that the effect of evening exercise was perceived as greater when elastic stiffness was greater, and 21 patients reported less stiffness with evening exercise (p less than .05).     

Digitalis toxicity during acute hypoxia in intact conscious dogs.

Intact, conscious dogs were studied under normal and hypobaric conditions to assess the influence of acute hypoxia on the ability of the animals to tolerate ouabain. Animals were made acutely hypoxic by exposure to hypobaric conditions in a chamber maintained at 446 mm Hg. The ability of the dogs to tolerate ouabain was determined by administering intravenously 7.5 mug/kg of the drug as a loading dose followed by infusion at a rate of 3.0 mug/kg/min to an end point consisting of the development of ventricular or atrioventricular junctional tachycardia. Eight dogs, each acting as its own control, were studied under normoxic and acutely hypoxic conditions. During hypoxia, mean arteriol pO2 decreased to 39 plus or minus 1 (S.E.) mm Hg from 80 plus or minus 1 mm Hg at sea level (P less than .001). The cumulative toxic dose of ouabain was modestly but significantly less (P less than .05) during acute hypoxia (71.7 plus or minus 4.3 mug/kg) compared with normoxic (79.2 plus or minus 4.1 mug/kg) conditions. In these experiments a marked hyperventilation response to ouabain was observed just before onset of toxicity which resulted in a pronounced rise in mean arterial pH (normoxia: 7.39 plus or minus 0.01 to 7.72 plus or minus 0.01; hypoxia: 7.48 plus or minus 0.01 to 7.71 plus or minus 0.04) and fall in pCO2 (normoxia: 41 plus or minus 1 to 14 plus or minus 1 mm Hg; hopoxia: 34 plus or minus 1 to 16 plus or minus 2 mm Hg). Ouabain-induced increases in systemic arterial pressure were comparable in normal and acutely hypoxic animals. Thus, acute hypoxia in unanesthetized dogs exposed to hypobaric conditions results in a decrease of only 10% in the ouabain dose required to produce cardiac arrhythmias, and toxic doses of ouabain produce a striking respiratory alkalosis.     

Patients' satisfaction with the staff function in an emergency department.

Patients' satisfaction with the functional capacity and attitude of the permanent staff working in the morning hours in the emergency department (ED) of a community hospital was compared with that of the staff working during the evening and night shifts. A total of 285 patients given care in the ED were interviewed according to a 'satisfaction' questionnaire regarding the function and attitude of the ED staff during the morning and evening/night shifts. The mean waiting time until a doctor was seen during the morning shift was 25 +/- 17 minutes for non-hospitalized patients and 25 +/- 8 minutes for the hospitalized ones, whereas during the evening and night hours the waiting times were 22 +/- 17 minutes and 19 +/- 13 minutes respectively. The number of laboratory examinations performed during the evening and night shifts markedly exceeded that carried out during the morning. The mean staying time in the ED for both non-hospitalized and hospitalized patients during the morning was by 23% shorter than that during the evening and night shifts. The patients expressed their overall satisfaction with the ED staff in both shifts with high evaluation marks. It is concluded that the survey indicates that the permanent ED staff during the morning hours are more efficient compared with those working during the evening and night shifts.     

缺氧心肌细胞线粒体膜电位及细胞凋亡与纳洛酮的保护效应

背景:研究证明缺血/再灌注损伤可诱导心肌细胞凋亡,再灌注后线粒体膜电位的丧失是细胞凋亡发生的必然途径。如果能保护线粒体膜电位则可能减少细胞凋亡。目的:观察纳洛酮对乳鼠心室肌细胞缺氧/复氧后线粒体膜电位及细胞凋亡的影响,研究其对缺氧心肌细胞的保护效应。设计:观察对比实验。单位:解放军总医院心内科。材料:心肌细胞凋亡检测实验于2004-12在解放军总医院病理生理实验室完成。选用新生乳鼠10只;心肌细胞腺粒体膜电位检测实验于2006-03在同一实验室完成,选用新生乳鼠20只。实验动物均由解放军总医院动物中心提供。盐酸纳洛酮注射液(0.4g/L),北京四环药厂产品,批号0206272;最低必需培养液(Dulbecco,DEME),Gibco公司;平衡盐溶液(PBS)、小牛血清,SIGMA公司。方法:将当日生乳鼠,局部碘酒酒精消毒后胸骨正中开胸,取心尖前1/3心室肌进行细胞培养。培养4d后选择细胞生长情况良好的培养瓶(细胞数>106/瓶)分为3组:对照组(正常培养)、缺氧组(缺氧/复氧)、纳洛酮组(缺氧/复氧加纳洛酮干预)。其中,对照组3瓶细胞,缺氧组和纳洛酮组各15瓶细胞。缺氧组和纳洛酮组又根据缺氧、复氧时间不同分为3个时间点:缺氧2h/复氧0h;缺氧2h/复氧2h;缺氧2h/复氧4h,每个时间点5瓶细胞。缺氧组:换预先充过体积分数0.95N2 体积分数0.05的CO2气体的体积分数0.01小牛血清DEME培养液,培养瓶内也用体积分数0.95N2 体积分数0.05的CO2气体充入置换其中的空气,密封后37℃孵育;达规定时间后换正常条件下(体积分数0.95空气 体积分数0.05的CO2)孵育。纳洛酮组:缺氧/复氧处理同上,同时加入盐酸纳洛酮,使培养液中药物终浓度达5μmol/L(加药容积≤总培养液的0.5%)。对照组不进行缺氧/复氧及用药处理,滴等量生理盐水,作为各组的缺氧0h/复氧0h时间点。干预后,以荧光染色-流式细胞仪检测缺氧/复氧后不同时间心肌细胞的线粒体膜电位变化及凋亡情况。主要观察指标:①缺氧组与纳洛酮组各时间点线粒体膜电位变化情况;②各组在缺氧2h/复氧4h细胞存活、凋亡、坏死水平比较。结果:①缺氧后,缺氧组、纳络酮组细胞的线粒体膜电位均下降。各时间点纳络酮组细胞线粒体膜电位均高于缺氧组(P<0.01)。线粒体膜电位的大幅度下降不是发生在细胞缺氧期,而是复氧期。②缺氧2h/复氧4h,缺氧组细胞的凋亡、坏死比率分别为(9.88±0.98)%和(5.10±0.29)%,明显高于纳络酮组[(2.41±0.52)%和(3.56±0.56)%,P<0.01]。缺氧组内细胞凋亡发生率明显高于坏死发生率(P<0.05)。结论:早期应用纳洛酮可明显减轻和延缓心室肌细胞缺氧/复氧后线粒体膜电位的下降并减少细胞凋亡和坏死的发生。