犬急性肺损伤早期不同通气策略对气体交换和血管外肺水的影响

目的: 探讨急性肺损伤(ALI)早期应用控制性高浓度氧疗、持续气道内正压(CPAP)和双水平气道内正压(BiPAP)不同通气策略对气体交换和血管外肺水的影响。方法: 24只杂种犬在制作油酸ALI模型成功后(PaO₂/FiO₂≤300 mmHg),保持自主呼吸,随机分为:(1)控制性高浓度氧疗组(n=8);(2)CPAP组(n=8);(3)BiPAP组(n=8)。连续记录并计算正常、ALI早期(阳性对照)和干预后1~4 h内各项气体交换和血流动力学指标。结果: 在氧合指数(PaO₂/FiO₂)的改善上,干预后4 h BiPAP组效果最明显(375.83±81.55, P<0.01),其次是CPAP组(327.17±78.82, P<0.01),氧疗组改善不显著(255.00±49.85, P>0.05)。在肺泡死腔与潮气容积之比值[V_D(alv)/V_T]上,氧疗组进一步增大(P<0.01),CPAP组和BiPAP组显著降低(P<0.01)。3种通气策略均可提高氧输送量(DO₂),BiPAP组效果最明显(P<0.01),其次是CPAP组和氧疗组。氧疗组的氧耗量(VO₂)显著增高,氧摄取率(O₂ER)明显高于CPAP组和BiPAP组(P<0.05, P<0.01)。干预后3组肺泡气-动脉血氧分压差[P_(A-a)O₂]较正常基础值和ALI早期均显著增高(P<0.01),3组间两两比较无显著差异(P>0.05)。在肺内分流比例(Qs/Qt)上,BiPAP组改善最明显(P<0.01),其次是CPAP组(P<0.01),氧疗组效果不显著。3组实验动物的肺动脉楔压(PAWP)和心排指数(CI)保持相对稳定。在平均肺动脉压(MPAP)和肺循环阻力指数(PVRI)上CPAP组和BiPAP组均进一步增高(P<0.05, P<0.01)。3组对血管外肺水指数(ELWI)的改善无显著作用(P>0.05)。结论: 在ALI早期,BiPAP和CPAP对于改善气体交换和组织氧合具有积极作用,其中BiPAP效果更为显著。3种通气策略对血管外肺水的改善无显著作用。     

Inhibition of force and shortening in smooth muscle by vanadate

 We have investigated the effects of vanadate (V_i) on force generation by, and shortening of, chemically skinned smooth muscle preparations from guinea-pig taenia coli at 22°C. A method, using phosphatase inhibitors, was introduced to obtain stable, long-lasting contractions in thiophosphorylated preparations. V_i (10–1000 μM) dose-dependently inhibited active force, to about 20% of its maximum level. At a higher temperature (30°C), the rate of inhibition was faster but the extent of inhibition was less. The rate of contraction following photolytic release of ATP to fibres in rigor was not affected by V_i (30 μM). The maximal shortening velocity (V _max) was inhibited in a similar manner as active force by V_i (30 μM). In conclusion, the results suggest that V_i interacts with a force-generating actomyosin-ADP (AMADP) state reached after phosphate release. The rate of inhibition of smooth muscle contraction was markedly lower than in skeletal muscle, suggesting differences either in properties of the V_i-bound states or, more likely, in the concentration of AMADP states capable of binding V_i. This suggests that the long duty cycle in smooth muscle is not associated with a higher relative population of AMADP states reached immediately after P_i release, but rather by an increase in the population of subsequent force-generating cross-bridge states. The V_i-bound cross-bridges introduce an internal load to shortening, possibly acting in a similar manner as cross-bridge states introduced at low levels of activation. Received: 20 October 1998 / Accepted: 2 February 1999     

低钠灌流时豚鼠心室肌细胞内钾离子活度和膜电位的变化及pH的影响

目的:进一步观察低钠液(低[Na]_o)灌流引起心肌细胞内钾离子活度(aⁱK)及膜电位(V_m)的变化,探讨其变化的机制及相互关系,以及pH的影响。方法:在豚鼠心室肌,应用普通及钾离子选择性微电极技术测定不同浓度低[Na]_o灌流时的V_m和aⁱK。结果:不同浓度的低[Na]_o引起了不同程度的aⁱK下降及V_m增加,并分别在不同的变化水平达到稳定。低[Na]_o可增加心肌细胞的静息电位(RP)和收缩活动,缩短动作电位时程(APD),但不影响动作电位幅度(APA)。在低[Na]_o的pH由7.4降至7.0时,aⁱK的下降减小,而对V_m的增加无影响。结论:aⁱK的下降和V_m的增加与灌流液Na⁺浓度呈良好的线性关系,而每一种低[Na]_o都可以使aⁱK和V_m在变化的水平上达到新的平衡。     

慢性心力衰竭大鼠内皮素系统表达的变化

目的:研究慢性心衰大鼠在心衰早期(冠脉结扎10d)和心衰晚期(冠脉结扎70d)的左心室内皮素受体A(ET_AR)和内皮素受体B(ET_BR)及内皮素前体(PreproET₁)的mRNA表达水平,了解心衰时心肌内皮素系统的变化及其与病程的关系。方法:用逆转录-聚合酶链反应(RT-PCR)检测冠脉结扎心衰模型大鼠的左心室ET_A和ET_B受体及PreproET₁的mRNA表达,以放射免疫技术检测血浆中内皮素(ET₁)和心钠素(ANP)的浓度。结果:冠脉结扎10d后,血浆ET₁、ANP的水平和左心室ET_AR、ET_BR、PreproET₁的mRNA表达水平均明显高于假手术组;冠脉结扎70d后,血浆ET₁和ANP的水平显著高于冠脉结扎10d组和假手术组,ET_A受体mRNA表达水平和假手术组相比无显著性差异,而ET_B受体及PreproET₁mRNA表达水平仍明显高于假手术组,但显著低于冠脉结扎10d组。结论:在慢性心衰的不同阶段,左心室内皮素系统的改变参与机体心脏功能的调节,循环ET₁水平的上升在早期主要是由于PreproET₁的mRNA表达上调所致,在后期则主要与下调的内皮素受体水平有关。     

新型手术机器人系统自主置入胸椎椎弓根螺钉的准确性研究

目的 评估新型手术机器人机器人系统用于置入胸椎椎弓根螺钉的准确性。方法 选取3具成人脊柱标本行CT扫描并三维重建。在术者监视下,机器人遵循术前规划,于各胸椎椎弓根经皮自主置入克氏针,完成开路扩孔、攻丝和经皮置钉。置钉后再行薄层CT扫描,测量螺钉破壁情况评估置钉准确性,螺钉位置准确性的评价基于Gertzbein-Robbins分级标准。比较上胸椎（T₁-T₄）、中胸椎（T₅-T₈）、下胸椎（T₉-T₁₂）螺钉置入准确性的差异。结果 共置入胸椎椎弓根螺钉72枚,螺钉位置临床可接受率（A级或B级）为84.7%。胸椎不同分段间螺钉位置临床可接受率的差异无统计学意义（P＞0.05）,但下胸椎置钉优秀率（A级）更高（P＜0.05）。结论 携带自主动力装置的新型手术机器人系统可准确置入胸椎椎弓根螺钉,置钉准确率与胸椎分段无关。     

原发性肾小球疾病患者花生四烯酸和肿瘤坏死因子α的变化

目的: 探讨原发性肾小球疾病患者体内花生四烯酸(AA)和肿瘤坏死因子α(TNF-α)的变化及对氧化应激的影响。方法: 以经临床和肾活检确诊原发性肾小球疾病患者55例为研究对象,按肾小球滤过率(GFR)分为慢性肾脏病(CKD)1、2期,CKD3、4期和CKD5期3个组,用酶联免疫吸附测定试剂盒(ELISA)测患者血清游离AA、TNF-α、丙二醛(MDA)和高敏C反应蛋白(hs-CRP)浓度。结果: CKD1、2期和3、4期患者之间AA和MDA差异无统计学意义(P>0.05),CKD5期AA明显高于其它各组(P<0.05),而MDA明显低于其它各组(P<0.05)。CKD3、4期和5期之间的TNF-α差异无统计学意义(P>0.05),但都明显低于CKD1、2期(P<0.05)。各组间hs-CRP差异无统计学意义(P>0.05)。MDA与AA呈负相关(r=-0.752,P<0.01),与TNF-α呈正相关(r=0.463,P<0.01),MDA(Y)与AA(X₁)和TNF-α(X₂)的多元线性回归方程为 Y=1 361.723-2.661X₁+9.320X₂(F=52.445, P<0.01)。结论: AA和TNF-α是影响原发性肾小球疾病患者氧化应激的重要因素,AA具有抑制氧化应激的作用,TNF-α具有促进氧化应激作用。     

钾通道对大鼠肺动脉平滑肌细胞[Ca2+]i的调节

目的:探讨在常氧、低氧条件下钾通道对大鼠肺动脉平滑肌细胞(PASMCs)[Ca²⁺]_i的调节。方法:采用钙荧光探针(Fura-2/AM)负载培养的大鼠PASMCs,观察常氧、低氧培养后3种钾通道抑制剂(4AP,TEA、Glib)对PASMCs[Ca²⁺]_i的调节,同时用四唑盐(MTT)比色法比较4AP、TEA、Glib对大鼠PASMCs增殖的影响。结果:(1)常氧状态下,PASMCs[Ca²⁺]_i为(156.91±8.60)nmol/L,低氧时为(294.01±16.81)nmol/L(P＜0.01)。(2)常氧状态下,4AP可引起PASMCs[Ca²⁺]_i升高,达(280.52±23.21)nmol/L(P＜0.01),而TEA、Glib无此作用。(3)低氧时,4AP和TEA都可引起PASMCs[Ca²⁺]_i的升高,分别为(422.41±24.28)nmol/L、(380.84±11.02)nmol/L(P<0.01),Glib无作用。(4)MTT比色法中,常氧和低氧状态下4AP均引起吸光度(A)值升高,分别是0.582±0.062,0.873±0.043(P＜0.01)。TEA仅在低氧时A值升高(0.729±0.041,P＜0.05),而Glib无论常氧还是低氧均无影响。结论:无论常氧还是低氧条件下,电压依赖性钾通道(K_V)对PASMCs[Ca²⁺]_i及其增殖起主要作用。钙激活的钾通道(K_Ca)在常氧条件下对[Ca²⁺]_i不起调节作用,而在低氧下使[Ca²⁺]_i降低,反应性地调节PASMCs增殖。ATP敏感性钾通道(K_ATP)无论在常氧还是低氧情况下对[Ca²⁺]_i的调节不起作用。     

氢氟酸烧伤中毒对兔外周血单个核细胞凋亡与胞内钙浓度的影响

目的: 研究氢氟酸烧伤中毒对兔外周血单个核细胞(PBMC)早期凋亡百分率和胞内游离钙浓度([Ca²⁺]_i)的影响。方法: 用流式细胞仪检测兔烧伤染毒前后外周血单个核细胞的Annexin V变化, 以观察其早期凋亡百分率。用Fluo-3/Am荧光探针观察烧伤染毒前后外周血单个核细胞内Ca²⁺平均荧光强度值的变化, 以观察细胞内[Ca²⁺]_i的变化。 结果: 12只烧伤中毒兔外周血单个核细胞早期凋亡百分率显著增加, 烧伤染毒前后比较P<0.01。而12只烧伤中毒兔中8只染毒后1 h外周血单个核细胞内[Ca²⁺]_i显著降低, 烧伤染毒前后比较P<0.05。其余4只却表现[Ca²⁺]_i染毒前后比较P>0.05。 结论: 本实验氢氟酸烧伤中毒使兔外周血单个核细胞早期凋亡百分率显著增加, 外周血单个核细胞内[Ca²⁺]_i却显著降低。提示氢氟酸烧伤中毒引导的细胞凋亡并非细胞内[Ca²⁺]_i增加所引发。     

间歇性高容量血液滤过对肾替代治疗病人血清莫西沙星药物浓度的影响

目的: 研究间歇性高容量血液滤过(PHVHF)治疗时莫西沙星的血清药物浓度变化,为临床用药提供依据。方法: 8名行PHVHF治疗患者在治疗开始60 min内匀速静滴莫西沙星400 mg,给药后不同时间收集滤器前、后血样和置换液,采用高效液相色谱法(HPLC)测定血清及置换液中莫西沙星浓度。用DAS 2.1.1软件计算药代动力学参数。结果: PHVHF治疗前后血尿素氮(BUN)及肌酐(SCr)、血清钾(K⁺)水平显著下降(P<0.05),血清钠(Na⁺)氯(Cl^-)维持稳定。HPLC分析方法测定血滤患者血清及置换液中莫西沙星浓度,线性关系良好,准确度及精密度高。静滴莫西沙星400 mg后在该患者体内的药代动力学符合开放型二室模型。主要药代参数:峰浓度(C_max)=(4.843±1.854) mg/L,半衰期(T_1/2)=(4.822±2.126) h,达峰时间(T_max)=(1.31±0.59) h,总体分布容积 (V_d)=(82.63±24.69) L,总体清除率(CL_tot)=(14.36±8.43) L/h ,AUC/MIC₉₀在MIC₉₀值分别为0.25 mg/L、0.12 mg/L、0.03 mg/L时均大于100,C_max/ MIC₉₀在MIC₉₀值分别为0.25 mg/L、0.12 mg/L、0.03 mg/L时均大于10。结论: PHVHF治疗可明显改善肾功能,稳定内环境,部分清除血清中莫西沙星,但PHVHF治疗后血清药物浓度仍可达到针对病原菌的有效治疗浓度。     

盐霉素抑制耐格列卫的人慢性粒细胞白血病细胞株K562/Glv增殖并诱导其凋亡

目的: 探讨盐霉素对耐格列卫的人慢性粒细胞白血病细胞株K562/Glv抑制增殖和诱导凋亡的作用及其机制。方法: 采用CCK-8的方法检测盐霉素对K562/Glv细胞生长的抑制作用;流式细胞术检测细胞凋亡、活性氧、细胞内Ca²⁺浓度([Ca²⁺]_i)和线粒体膜电位(ΔΨ_m);比色法检测caspase-3、-8和-9活性;Western blotting 分析细胞色素C、Bcl-2、Bax、β-catenin和磷酸化低密度脂蛋白受体相关蛋白6(p-LRP6)蛋白水平。结果: 盐霉素对K562/Glv细胞生长具有剂量依赖性抑制作用,0.2 μmol/L时细胞增殖抑制率为(36.70±2.31)%,细胞凋亡率为(19.66±2.43)%;0.2 μmol/L盐霉素作用于K562/Glv细胞,ΔΨ_m显著下降,24 h时下降至对照组的(19.8±2.4)%,细胞内活性氧和[Ca²⁺]_i在短期显著升高。Caspase-3、-8和-9活性均显著增加,与对照组比较,差异有统计学意义(P<0.01)。Bcl-2 的表达下调,Bax 的表达明显增加,Bcl-2/Bax 比值显著降低。同时,盐霉素也减少K562/Glv细胞内β-catenin和p-LRP6蛋白水平。结论: 盐霉素不仅通过Bcl-2/Bax途径和线粒体凋亡途径诱导耐格列卫人慢性粒细胞白血病细胞K562/Glv的凋亡,而且通过抑制Wnt信号途径抑制K562/Glv细胞增殖。     

Evaluation of adaptive support ventilation in paralysed patients and in a physical lung model

OBJECTIVE: Evaluation of the respiratory pattern selected by the Adaptive Support Ventilation (ASV) in ventilated patients with acute, chronic respiratory failure and normal lungs and in a physical lung model. DESIGN: We tested ASV both on patients and in a physical lung model, with a normal level of minute ventilation and with minute ventilation increased by 30%. In each patient, respiratory pattern, mechanics and blood gases were recorded. SETTING: General ICU of a University Hospital. RESULTS: In patients with normal lungs, mean values+/-SD were: tidal volume (Vt) 558.1+/-142.4 mL, respiratory rate (RR) 12.6+/-1.3b/min and inspiratory time/total time ratio (Ti/Ttot) 42.4+/-4.1%; in COPD, mean values+/-SD were: Vt 724+/-171 mL, RR 9.2+/-2.7b/min and Ti/Ttot 26.6+/-10.5%; in restrictive ones, mean values+/-SD were: Vt 550.2+/-77.0 mL, RR 15.8+/-2.6b/min, Ti/Ttot 47.5+/-2.5%. In the lung model, at a normal setting, mean values+/-SD were: Vt 523+/-18.5 mL, RR 14+/-0.0b/min, Ti/Ttot 44.0%, in COPD, mean values+/-SD were: Vt 678+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.7%, in restrictive one, mean values+/-SD were: Vt 513+/-12.8 mL, RR 15+/-0.0b/min, Ti/Ttot 48+/-1.5%. In model hyperventilation conditions in a normal setting a Vt of 582+/-16.6 mL, RR 16+/-0.0b/min, Ti/Ttot 48+/-0.0% were selected, in the obstructive setting Vt 883+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.0% and in a restrictive one Vt 545+/-8.4 mL, RR 18+/-0.0b/min, Ti/Ttot 50-0.0%. CONCLUSIONS: In normal patients ASV selected a ventilatory pattern close to the physiological one, in COPD almost a high expiratory time pattern and in restrictive ones a reduced tidal volume pattern. In the model the selection was similar. In the hyperventilation test, ASV chose a balanced increase in both Vt and RR.     

Impact of breathing pattern on work of breathing in healthy subjects and patients with COPD

The impact of the respiratory pattern on respiratory muscle workload represents an unresolved controversy and is important for the treatment of patients with respiratory disorders and respiratory muscle failure. We designed this study to investigate the relationship of respiratory pattern and inspiratory workload. We measured esophageal pressure and inspiratory flow and calculated work of breathing, tidal volume and respiratory rate. Ten healthy subjects and 10 COPD patients participated and performed five different breathing patterns starting from respiratory rate 12 and tidal volume 1l or quiet breathing, respectively. They were instructed to increase respiratory rate by 50 and 100% as well as tidal volume by 50 and 100% while maintaining constant minute-ventilation. In healthy subjects Delta VT was the single best parameter to predict Delta WOB (R=0.958, R(2)=0.918, p<0.0001). The relationships of changes in tidal volume, respiratory rate and rapid shallow breathing index to changes in WOB were linear. In the COPD Delta VT was also the single best parameter to predict changes in work of breathing (R=0.777, R(2)=0.604, p<0.0001), however the relation of respiratory rate and rapid shallow breathing index to work of breathing was exponential (e-function) with lower indices generating higher workload. We conclude that rapid shallow breathing might be a strategy to compensate for burdensome respiratory mechanics. In COPD patients however we observed a critical threshold where any further increases in rapid shallow breathing index will be of no further benefit.     

Delayed ventilatory response to CO2 after carbonic anhydrase inhibition with acetazolamide administration in the anesthetized rat

In order to estimate to what extent the stimulatory action of CO2 on ventilation is mediated by the formation of H+, we studied effects on the temporal profile of ventilatory response to CO2 of carbonic anhydrase (CA) inhibition with acetazolamide in the halothane anesthetized spontaneously breathing rat. Since hydration reaction of CO2 yielding H+ is delayed by CA inhibition, the time courses of changes in tidal volume (VT), respiratory frequency (f), and minute ventilation (VE) in response to a stepwise increase in end-tidal PCO2 (delta PETCO2 15 mmHg) were compared before (control state) and after i.v. injection of acetazolamide (50 mg/kg) in the hyperoxic condition. In the control state, an increase in VT was significantly slower than that in f, and the mean response half-times (T1/2) for the increase in VT, f, and VE were 50.6, 18.1, and 31.0 s, respectively. After acetazolamide administration, responses to CO2, especially f-response and consequently VE-response became much slower, and the T1/2 for VT, f, and VE were 67.9, 55.0, and 63.0 s, respectively. The delay in VT-response was not statistically significant. The magnitude of increase in VE in the steady state hypercapnic stimulation was almost the same before and after acetazolamide administration. The results suggest that a rapid increase in f during CO2 inhalation occurs predominantly through an increase in H+ produced by hydration of CO2 with CA, whereas VT-response may occur without involvement of this process. The different time courses of VT- and f-responses and possible effects of molecular CO2 and/or H+ on the regulatory mechanisms for ventilatory pattern were discussed.     

Comparison between ventilatory and mouth occlusion pressure responses to hypoxia and hypercapnia in healthy sleeping man

Ventilatory and mouth occlusion pressure (P0.1) responses to progressive isocapnic-hypoxia and hyperoxic-hypercapnia were compared in eleven healthy sleeping men during the same night. Hypoxic and hypercapnic responses were determined during wakefulness, non-rapid and rapid-eye-movement sleep. The following parameters were measured: minute ventilation (VE), tidal volume (VT), 'duty cycle' (TI/TT), mean inspiratory flow rate (VT/TI) and P0.1, an index of the neuromuscular inspiratory drive. To allow a direct comparison between the two types of chemostimuli, responses were characterized by the value of the different parameters at 'equivalent' levels of hypoxia and hypercapnia, i.e., at levels which produced the same P0.1 during wakefulness: an oxyhaemoglobin saturation (Sao2) of 94% during the isocapnic-hypoxic tests (PETCO2 = 42.5 +/- 1.2 mmHg) was found to be equivalent to a PETCO2 of 47.4 +/- 3.7 mmHg during hypoxic-hypercapnic tests. For both tests, the arousal levels of the stimulus and of P0.1 were similar in all sleep stages. Sleep did not significantly modify P0.1 or breathing pattern responses to hypoxia (Sao2 = 94%). In contrast, at the 'equivalent' level of hypercapnic stimulation, P0.1 (P less than 0.05) and VE (P less than 0.01) responses were significantly impaired, particularly in REM sleep, with a decrease in VT (P less than 0.01) and VT/TI (P less than 0.05) responses. The results suggest that CO2 intracranial receptor mechanisms are more affected by sleep than the O2 peripheral receptor activity.     

Comparison of respiratory regulation in alcohol and opiate abusers

Opioid drugs and alcohol, both central nervous system depressants, may also have a depressive action on the brain stem centre responsible for breathing control. Disorders of breathing regulation are reflected in respiratory efficiency. The aim of this study was to evaluate the regulation of breathing by measuring the respiratory pattern and occlusion pressure of abusers of opiates and alcohol. There were 180 persons under examination: 84 alcohol abusers (group I), 36 opiates abusers (group II) and 40 healthy persons (control group). Both groups of dependent persons were treated in the Detoxication Unit of the Department of Clinical Toxicology CMUJ. Respiratory regulation was evaluated "on line" by means of synchronous measurements of the respiratory pattern (according to Milic-Emili assumptions) and occlusion pressure P 0.1 (according to Whitlaw assumptions). The central respiratory drive (VT/Tin) and the timing component of the breathing cycle (Tin/Ttot) were simillar in both groups of abusers. In comparison to the control group, in the group of opiates abusers, values of VT/Tin were higher during examination performed after treatment, and values of Tin/Ttot were elevated (in group I--only before treatment; in group II--before and after treatment). Examination of respiratory pattern and occlusion pressure is based on recording spontaneous breathing, which this can be performed even in unconscious patients in very early stage of poisoning.     

Breathing pattern and occlusion pressure during moderate and heavy exercise

We studied changes in breathing pattern and mouth occlusion pressure (P0.1) in 11 healthy subjects performing graded steady-state exercise on a cycle ergometer up to the maximal load sustainable for 4 min. With increasing work intensity both the tidal volume (VT) and end-inspiratory volume relations to inspiratory (TI) and expiratory (TE) durations were linear in the moderate work load range; in the high load range VT and end-inspiratory volume tended to plateau with further decreases in TI and TE. The ratio of TI to total breath duration (TI/Ttot) increased with work intensity. Intraindividual coefficients of variation for VT, breathing frequency (f), mean inspiratory flow (VT/TI), and other respiratory variables decreased with increasing work intensity, indicating that breath-to-breath variations in breathing pattern became smaller as the level of ventilation increased. P0.1 rose with VT/TI as a power function with an exponent averaging 1.5 (range 1.3-1.9), indicating that the ratio P0.1/(VT/TI), an index of respiratory system impedance, increased with VT/TI and work intensity. We conclude that in moderate and heavy exercise the work of inspiration at a given ventilation is reduced because of the increase in TI/Ttot, the impedance of the respiratory system increases with work intensity because of both an increase in f and a flow-dependent rise in airway resistance, and the neuromuscular inspiratory activity is reflexly augmented because of internal flow-resistive loading.     

Respiratory and thermoregulatory responses of rabbits breathing carbon dioxide during heat exposure.

1. Rabbits were clipped and exposed in turn to three environmental conditions: control (C), cold exposure (CE) and water deprivation (WD). Following each type of treatment, the rabbits were exposed to an ambient temperature (Ta) of 35 degrees C for 1 hr. Throughout this period they breathed either normal atmospheric air or 6% CO2 in air. 2.During heat exposure, measurements were made of the respiratory responses and of the O2 consumption (Vo2) of the rabbits. Rectal temperature (Tre) was measured immediately before and again immediately after heat exposure. 3. When subjected to cold exposure or water deprivation the rabbits showed an initial decrease in respiratory frequency (RF) and an initial increase in VT when compared with controls. There was no difference in VE. Rabbits breathing 6% CO2 showed an increase in VT and VE and a decrease in RF when compared with rabbits breathing atmospheric air. In all cases a change in VT or RF was associated with a reciprocal change in the other parameter. 4. The respiratory responses to breathing 6% CO2 were essentially similar in treated and control rabbits, from which it is concluded that neither cold exposure nor water deprivation alter the sensitivity of the medullary respiratory centre to the respiratory drive from the central chemosensors. 5. The increase in Tre during heat exposure was significantly less in rabbits breathing 6% CO2 than in rabbits breathing atmospheric air. However, there was no significant over-all difference in VO2 between rabbits breathing CO2 and those breathing air. From this it is concluded that increased ventilation induced by CO2 causes a greater dissipation of heat than does thermally-induced panting. 6. It is concluded that VT is controlled by the level of blood PCO2 whereas RF is controlled by thermoregulatory requirements. It is further concluded that the reciprocal relationship between VT and RF is regulated in such a way as to maintain VE at the appropriate level for effecting gaseous exchange and evaporative heat loss.     

Effects of naloxone on the control of breathing in children with chronic obstructive pulmonary disease

The effect of naloxone on occlusion pressure (P0.1), the pattern of breathing and the expiratory flows during spontaneous ventilation was studied in 16 children with chronic obstructive pulmonary disease under control conditions, after isotonic saline injection and 5 (N5) and 25 (N25) min after i.v. injection of naloxone (2 micrograms X kg-1). At N5, no change was observed in tidal volume normalized for body weight (VTBW), inspiratory time (TI), respiratory frequency (f), mean inspiratory flow (VTBW/TI) and the ratio of TI and total duration of the respiratory cycle (TI/TT). P0.1 decreased significantly (p less than 0.001) at N5 and returned to control values at N25. The decrease in P0.1 without any change in the breathing pattern suggests that naloxone has an effect on respiratory mechanics. Indeed, at N5, the expiratory flows generated at 25% of VT, measured on the flow-volume curves during spontaneous ventilation, increased significantly when compared to control values. Moreover, the decrease of P0.1 after naloxone was found to be correlated to the reduction of dynamic lung compliance (CLdyn) (p less than 0.02). It is speculated that peripheral airway obstruction, as reflected by the decrease in CLdyn, might be a triggering factor for the release of endorphins. The bronchodilation observed after naloxone could then be due to naloxone's antagonistic effect on endorphin-induced bronchoconstriction.     

Nocturnal nasal intermittent positive pressure ventilation (NIPPV) therapy for chronic respiratory failure: long-term effects

The development of positive pressure ventilation delivered through a nasal or face mask has greatly expanded the use of non-invasive ventilation in patients with chronic respiratory insufficiency, particularly during sleep. Disorders ranging from neurologic and neuromuscular, such as polio and muscular dystrophy, central alveolar hypoventilation, thoracic cage disorders such as kyphoscoliosis, and pulmonary disorders such as COPD, particularly of the blue-bloater type. The relative hypoventilation that is common to each condition is due to varying combinations of an inadequate respiratory drive and an increase in the work of breathing. Previous studies have shown sustained reversal of awake hypercapnia in patients with alveolar hypoventilation syndrome using nocturnal NIPPV. We analysed 10 consecutive patients with chronic respiratory insufficiency due to diverse aetiologies over a period of time using long-term domiciliary nocturnal NIPPV. Awake hypercapnia and hypoxaemia improved in nine patients over time and deteriorated in one patient. There was no significant change in pulmonary function apart from one patient with progressive muscular dystrophy who deteriorated. A considerable reduction in the need for subsequent hospital admission was noted in the group as a whole following institution of NIPPV. We conclude that nocturnal NIPPV improves awake gas exchange in patients with chronic respiratory failure.     

Noninvasive intermittent positive pressure ventilation in treatment of chronic respiratory disease exacerbation

Noninvasive intermittent positive pressure ventilation (NIPPV) via nasal mask became a routine method of treatment of severe exacerbations of chronic respiratory failure. The aim of the study was to apply NIPPV in patients with COPD admitted to hospital due to exacerbation of the disease who on standard treatment developed progressing respiratory acidosis (pH < 7.30). Fourteen COPD patients were treated with NIPPV. Arterial blood gases at the beginning of treatment were: PaO2 41 +/- 9 mmHg, PaCO2 = 87 +/- 17 mmHg, pH = 7.30 +/- 0.05. In 10 patients NIPPV applied quasi continuously resulted in clinical improvement and an amelioration of arterial blood gases. PaO2 rose from 41 +/- 9 mmHg to 56 +/- 12 mmHg, PaCO2 fell from 85 +/- 17 to 57 +/- 9 mmHg and pH rose from 7.30 +/- 0.05 to 7.41 +/- 0.04. In 4 patients NIPPV did not prevent further progression of respiratory acidosis. They were intubated and mechanically ventilated. Three patients survived and were discharged home. One patient died from septic shock. We conclude that NIPPV is an effective method to treat respiratory acidosis developing during exacerbation of severe COPD.