异丙酚对大鼠肺动脉压及缺氧性肺血管收缩反应的影响

目的:观察不同剂量异丙酚对肺动脉压及缺氧性肺血管收缩反应(HPV)的影响。方法:采用离体大鼠全血灌注肺模型。结果:空气 4％CO_2通气条件下肺动脉压为1.78±0.24kPa,分别给予异丙酚4mg/kg、6mg/kg、8mg/kg,MPAP分别下降至1.53±0.25kPa、1.40±0.23kPa、1.38±0.24kPa,与给药前相比MPAP明显降低,6mg/kg和8mg/kg异丙酚降压作用明显强于4mg/kg。吸入气为混合气(3％O_2 4％CO_2 93％N_2)情况下肺动脉压从1.60±0.23kPa上升至2.38±0.31kPa。分别给予异丙酚4mg/kg、6mg/kg、8mg/kg。MPAP分别降至2.01±O.35kPa、1.85±0.37kPa、1.83±O.41kPa,抑制缺氧性肺动脉升压反应分别为47％、67％、71％。且6mg/kg和8mg/kg与4mg/kg相比抑制程度有显著差异。结论:异丙酚可降低肺动脉压及抑制缺氧性肺血管收缩反应,且与剂量有关。     

通气侧肺吸入伊洛前列素对肺动脉压和缺氧性肺血管收缩的影响

目的 探讨雾化吸入伊洛前列素对大鼠单肺通气(one-lung ventilation,OLV)期间肺动脉压和缺氧性肺血管收缩(hypoxic pulmonary vasoconstriction,HPV)的影响。方法 雄性SD大鼠30只,随机分为A、B、C三组,每组10只。原位离体肺灌注模型建立后,调整气管导管深度致左侧肺OLV,FiO_2为100%,打开连接于呼吸回路的雾化器,A组吸入生理盐水,B组吸入伊洛前列素0.05μg·kg-1·min-1,C组吸入伊洛前列素0.1μg·kg~(-1)·min~(-1),记录灌注10min(T_1)、雾化吸入10min(T_2)和OLV 1h(T_3)的平均肺动脉压(MPAP)及左心房引流液氧分压(PaO_2)。通过测量T_1、T_2和T_3时的左心房引流液PaO_2计算氧合指数(oxygenation index,OI)。实验结束分别取双侧肺组织进行电镜检查。结果 与T_1时比较,T_2、T_3时三组MPAP明显升高(P0.05);T_2、T_3时B、C组MPAP明显低于A组(P0.05),且C组MPAP明显低于B组(P0.05)。与T_1时比较,T_2、T_3时三组OI明显降低(P0.05);T_2、T_3时C组OI明显高于B组(P0.05)。相对于B、C组通气侧,A组通气侧与A、B、C组非通气侧Ⅱ型肺泡上皮细胞核膜外突内陷,部分板层小体排空。结论 在大鼠原位肺灌注模型中,单肺通气期间雾化吸入伊洛前列素能明显降低平均肺动脉压,减少肺内分流并增加氧合。     

一氧化碳合成酶抑制剂对缺氧性肺血管收缩反应的影响

目的 观察内皮及内源性一氧化碳（CO）合成酶抑制剂（血红素氧化酶抑制剂ZnppIX)对大鼠缺氧性肺血管收缩反应的影响，探讨内源性CO在缺氧性肺血管收缩反应中的作用。方法 制备Wistar大鼠动脉环，观察内皮与缺氧性肺血管收缩反应的关系；并以一氧化氮合成酶抑制剂L－NAME为对照，观察ZnppIX对缺氧性肺血管收缩反应的影响。结果 缺氧可使去氧肾上腺素顶收缩的肺动脉环出现明显的收缩反应，去除内皮或血管环用L－NAME孵育后，缺氧性肺血管收缩反应受抑，而用ZnppIX及L－NAME共同孵育后，缺氧性肺血管收缩反应明显抑制或消除，与L－NAME组相比有显著性差异（P＜0．01）。L－NAME组的缺氧张力变化率与未孵育前相比也有显著性差异（P＜0．01）。结论 缺氧性肺血管收缩反应是内皮依赖性的，ZnppIX可抑制大鼠氧性肺血管收缩反应，内源性CO与NO一样参与了缺氧性血管收缩反应。     

产前缺氧性适应动物模型制备

目的：通过对临产前孕鼠行不同程度的缺氧，找出产前缺氧性适应最合适的缺氧浓度。从而建立产前缺氧性适应动物模型。方法：将孚2天的临产前孕鼠随机分为7组，每只孕鼠两次放入自制的缺氧性适应密封仓中，氧浓度分别降至18％（Ⅱ组），17％（Ⅲ组），16％（Ⅳ组），15％（Ⅴ组），14％（Ⅵ组0，13％（Ⅶ组），两次乏氧间隔5分钟，对照组（Ⅰ组）氧浓度21％，Ⅰ－Ⅶ组孕鼠的缺氧适应时间分别为：第一次10min,5min,7.5min,9.83min,11.5min,13.17min,14min,第二次10min,9.33min,11min,15.17min,13.33min,17min,18min。比较各组娩出的新生鼠耐缺氧时间，并应用尼氏染色和透射电镜对各组新生鼠脑组织进行观察，找出最合适的缺氧浓度。结果：Ⅰ－Ⅴ组娩出的均为正常新生鼠，Ⅵ组娩出的55只新生大鼠，皮肤颜色青紫，运动减少10只（18％），部分新生鼠脑组织正常神经细胞数量减少，部分细胞肿胀，线粒全扩张，可见凋亡细胞，Ⅶ组娩出的52只新生大鼠中，死亡11只（21％），14只皮肤青紫，肢体运动减少（27％），部分新生鼠脑组织病理学检查异常。Ⅳ，Ⅴ，Ⅵ，组新生鼠乏氧时间较对照组明显延工，Ⅳ组，Ⅴ组两组间新生鼠乏氧时间有统计学差异。结论：2次使孕鼠缺氧（无CO2蓄积），氧浓度15％，中间吸入新鲜空气5分钟是产前缺氧性适应合适的动物模型。     

15-羟廿碳四烯酸对大鼠缺氧性肺动脉环的作用

目的 研究15-羟廿碳四烯酸(15-HETE)对缺氧(FiO2 10％)大鼠第三级肺动脉环的作用,以探讨15-HETE在大鼠缺氧性肺血管收缩(HPV)中的作用,为肺动脉高压及其并发症的手术麻醉采取相应的治疗措施,以减少低氧血症的发生。方法 16只健康Wistar大鼠随机分为两组(n=8):A组为对照组,吸大气,其吸入氧浓度(FiO2)为21％;B组为缺氧组,即将大鼠置于FiO2为10％的缺氧箱中。9d后将大鼠处死,游离直径为0.5-1.0 mm肺动脉(PA)剪成3mm长的血管环,血管环在37℃的KH液中平衡40min。KH液中15-HETE的浓度逐渐从10-8增至10-6mol·L-1,分别加入不同K 通道阻断剂后,再加入15-HETE。肺动脉环收缩张力信号通过Medlab-U-4CS生物信号采集处理系统的四通道接头传输到计算机相应处理软件上进行数据记录和分析,并根据血管张力的变化绘制浓度反应曲线;分别计算出收缩率。结果 15-HETE以浓度依赖方式(10-8-10-6mol·L-1)使游离肺动脉环张力明显增加(P<0.05),其在B组中作用更为明显。2mmol·L-1 4-AP、2mmol·L-1 4-AP 10-6mol·L-115-HETE使肺动脉环张力显著性增高(P<0.05),二组间比较,差异无显著性(P>0.05);10-2mol·L-1TEA、10-6mol·L-1GLYB,对血管环张力无明显影响(P>0.05);10-2mol·L-1 TEA 10-6mol·L-115-HETE和10-6mol·L-1 GLYB 10-6     

外源性一氧化碳改善供体肺功能的实验研究

目的观察一氧化碳(CO)对长时间低温保存的供体肺的保护作用。方法建立大鼠肺移植离体肺灌注实验模型:SD大鼠24只随机分为空白对照组、实验组(CO组),每组6对作为肺移植的供体鼠和受体鼠。对照组大鼠供肺移植全程吸入100%氧气直至再灌注后1h;CO组移植全程吸入500×10-6CO和O2的混合气,并且供体肺在冷保存的12h内肺内仍充盈着CO和O2的混合气,余同对照组。于供体肺循环灌注l,20,40,60min测定供肺氧合后动脉血氧分压(PaO2)、平均肺动脉压、气道峰压;灌注结束后测定肺组织湿干比、丙二醛(MDA)含量、髓过氧化物酶(MPO)活性、白细胞介素8(IL-8)的含量。结果作为受体的12只(每组6只)进入结果分析:①CO组供体肺的PaO2在再灌注20、40、60min明显高于对照组,平均动脉压、气道峰压分别在再灌注20、40、60min和40、60min明显低于对照组(P<0.05);②与空白对照组比较,CO组供体肺再灌注后湿干比、MDA、MPO、IL-8含量均明显降低(P<0.05)。结论在肺移植的全程吸入低剂量CO可以减轻供肺的缺血再灌注损伤,改善供肺功能。     

脑死亡供体鼠吸入一氧化碳对受体鼠移植肺损伤的影响

目的 评价脑死亡供体鼠吸入一氧化碳(CO)对受体鼠移植肺损伤的影响.方法 雄性Wistar大鼠24只,体重250～300 g,随机分为3组(n=8),接受非脑死亡供体肺组(NBD组)供体鼠颅内置入Fogarty导管,但不诱导脑死亡,观察2.5 h;接受吸入氧气的脑死亡供体肺组(BDO2组)供体鼠确认脑死亡后吸入40%氧气2 h;接受吸入CO的脑死亡供体肺组(BDCO组)供体鼠确认脑死亡后吸入40%氧气和0.025%CO混合气2 h.处理结束后取供体左肺,进行原位异体肺移植,受体鼠每30 min进行一次动脉血气分析.肺移植成功后2 h处死受体鼠,采集右股动脉血样,采用嘌呤氧化酶法测定血浆超氧化物歧化酶(SOD)活性;采用硫代巴比妥酸法测定丙二醛(MDA)浓度;采用ELISA法测定血浆白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α和IL-10浓度.计算移植肺组织湿/干重比(W/D);测定移植肺组织髓过氧化物酶(MPO)活性,并进行移植肺组织损伤评分.结果 与C组比较,BDO2组和BDCO组PaO2/FiO2、BE、pH值和血浆SOD活性、IL-10浓度降低,移植肺组织W/D、MPO活性、损伤评分和血浆MDA、IL-6、TNF-α浓度升高(P<0.05);与BD02组比较,BDCO组PaO2/FiO2、BE、pH值和血浆SOD活性、IL-10浓度升高,移植肺组织W/D、MPO活性、损伤评分和血浆MDA、IL-6、TNF-α浓度降低(P<0.05).结论 脑死亡供体鼠吸入CO 2 h可减轻受体鼠移植肺损伤,其机制可能是吸入CO提高了移植肺的抗氧化能力,减轻了移植后局部和全身炎性反应.     

星状神经节阻滞对缺氧性肺动脉高压兔的血管内皮一氧化氮合酶及肺动脉压的影响

目的 观察星状神经节阻滞对缺氧性肺动脉高压兔的血管内皮一氧化氮合酶(eNOS)及肺平均动脉压(PMAP)的影响。方法 健康成年日本大耳白家兔在无菌操作下暴露左侧星状神经节，置入并固定硬膜外导管，使其一端开口位于星状神经节附近，另一端自颈背部穿出。置管一周后，选择恢复健康兔24只随机分为四组(每组均为6只)，分别为正常对照组(N)、单纯星状神经节阻滞组(G)、单纯缺氧组(H)、缺氧 星状神经节阻滞组(HG)。用直接测压法测平均肺动脉压(MPAP)、用免疫组化染色方法观察肺血管内皮eNOS含量的变化。结果 与N组比较：G组PMAP无明显变化，H组、HG组PMAP显著升高(P＜0．05)，H组、G组、HG组eNOS表达显著增多(P＜0．05)。与HG组比较，H组PMAP显著下降(P＜0．05)，eNOS表达显著增多(P＜0．05)。结论 星状神经节阻滞后，可降低缺氧性肺动脉高压兔的MPAP，其机制与星状神经节节后纤维分泌eNOS有关，星状神经节阻滞有可能成为缺氧性肺动脉高压的一种治疗方法。     

环氧二十碳三烯酸、5-羟色胺与缝隙连接蛋白在慢性缺氧性肺动脉高压形成中的作用

目的 探讨环氧二十碳三烯酸(EET)、五羟色胺(5-HT)、缝隙连接蛋白40(Cx40)和43(Cx43)在慢性缺氧性肺血管收缩所致肺动脉高压中的作用。方法 选择SPF级BALB/c小鼠40只,8周龄,体重25～29 g。实验一：采用随机数字表法将小鼠分为两组：对照组(O组,n=8)和慢性缺氧模型组(H组,n=32)。所有小鼠正常饮食,O组在正常环境喂养4周,H组予低氧舱(每天吸入10%氧气10 h)喂养4周后,监测MAP和平均肺动脉压(mPAP)。随后处死小鼠,取心肺组织称量并计算右心室肥厚指数。实验二：O组和H组于显微操作下用胶原酶消化法分离远端肺小动脉血管,采用荧光免疫组化法鉴定肺动脉内皮细胞(PAEC)和肺动脉平滑肌细胞(PASMC)。采用随机数字表法将H组分离得PAEC和PASMC进一步分为三组：缺氧+si-Cx40组(H40组)、缺氧+si-Cx43组(H43组)和缺氧+无义siRNA组(HN组),H40组和H43组PAEC和PASMC分别接受Cx40基因和Cx43基因的特异性siRNA脂质体siPORTNeoFX转染,HN组接受无义siRNA转染。所有细胞在10%氧气条件...     

吸入一氧化碳对大鼠脑死亡致肺损伤的影响

目的 评价吸入一氧化碳(CO)对大鼠脑死亡致肺损伤的影响.方法 成年雄性Wistar 大鼠24只,随机分为3组(n=8),假手术组(SH组)颅内置入Fogarty管,但不诱导脑死亡,吸入40%氧气,持续150 min;脑死亡组(BD组)膨胀Fogarty球囊,确认脑死亡后吸入40%氧气,持续120 min;脑死亡+CO组(BDCO组)膨胀Fogarty球囊,确认脑死亡后吸人40%氧气+0.025%CO混合气,持续120 min.于麻醉前、确认脑死亡即刻、吸入CO 30、60、90、120 min时行动脉血气分析;于吸人CO 120 min时.检测血浆白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)和IL-10的浓度;计算肺湿干重比(W/D);检测肺组织髓过氧化物酶(MPO)活性,行肺组织损伤评分.结果 与SH组比较,BD组和BDCO组脑死亡后PaO2/FiO:、BE和pH值下降,血浆IL-6、TNF-α和IL-10的浓度和肺组织损伤评分升高,BD组肺W/D、MPO活性升高(P<0.05);与BD组比较,BDCO组脑死亡后PaO2/FiO2、BE、pH值和血浆IL-10浓度升高,肺组织MPO活性、血浆IL-6、TNF-α的浓度和肺组织损伤评分降低(P<0.05).结论 吸入CO可减轻大鼠脑死亡诱发的肺损伤,其机制可能与CO降低肺组织局部和全身炎性反应有关.     

Appropriate blood flow for arterio-portal shunt in acute hypoxic liver failure.

Hepatic arterial interruption inevitably leads to fatal liver hypoxia when all the collateral arteries to the liver have been eradicated. To prevent such hypoxia, we aimed to determine the appropriate flow of arterial blood in the arterio-portal shunt (APS). After division of all the arteries to the liver, we created three types of APSs between the common hepatic artery (CHA) and the portal vein in dogs, using catheters which were adjusted to pass blood flows of approximately half (group I), equal to (group II) and twice (group III) the CHA blood flow before shunting, except in the control (no-shunt) group. Postoperatively, at 1 and 48 h, we examined the hemodynamics of the liver biochemically and pathologically. After shunting, portal blood flow and oxygen saturation markedly increased, whereas portal venous pressure did not rise significantly. The serum alanine aminotransferase level was significantly higher in the no-shunt group and group I than in group II. Only in group II was the preoperative energy charge maintained, and light- and electron-microscopic examinations revealed no degeneration of the hepatocytes. APS blood flow similar to the original CHA (as in group II) is most appropriate for preventing liver hypoxia.     

重症急性高原病缺氧性胃肠功能障碍患者的护理

对281例重症急性高原病缺氧性胃肠功能障碍患者在对症治疗的同时,实施给氧、病情观察、饮食护理、用药护理及心理护理等。结果患者住院1～23d,治愈243例,自动出院1例,转平原治疗35例,死亡2例。提出对于高原病缺氧性胃肠功能障碍在治疗过程中有针对性地加强重要器官的护理及功能保护,是促进患者康复的关键。     

Nursing care of patients with severe acute mountain sickness induced hypoxic gastrointestinal dysfunction

对281例重症急性高原病缺氧性胃肠功能障碍患者在对症治疗的同时,实施给氧、病情观察、饮食护理、用药护理及心理护理等.结果 患者住院1～23 d,治愈243例,自动出院1例,转平原治疗35例,死亡2例.提出对于高原病缺氧性胃肠功能障碍在治疗过程中有针对性地加强重要器官的护理及功能保护,是促进患者康复的关键.     

Reduced oxygen tension during cardiopulmonary bypass limits myocardial damage in acute hypoxic immature piglet hearts

Objectives.

Cardiopulmonary bypass (CPB) is usually instituted in a hyperoxic fashion (oxygen tension (pO₂) 300–500 mmHg), which may expose cyanotic infants to potential reoxygenation damage. Oxygen free radicals play an important role in this injury. The rate of production of this highly reactive toxic oxygen species is dependent on the oxygen level during reoxygenation. This study tested the hypothesis that reduction of the oxygen in the bypass prime and in blood cardioplegia (BCP) to normoxic levels can reduce reoxygenation injury and will result in improved contractility.

Methods.

We operated on 19 Duroc-Yorkshire piglets (2–3 weeks, 3–5 kg). Five underwent 30 min of BCP arrest during 1 h of CPB without hypoxia (control). Fourteen underwent 120 min of hypoxia (arterial pO₂ 20–30 mmHg) on ventilator before reoxygenation on CPB. Reflecting the clinical routine procedure, nine of them were reoxygenated on CPB for 5 min with high pO₂ (350–450 mmHg) followed by 30 min of BCP arrest (high pO₂) and 25 min of reoxygenation/reperfusion on CPB with high pO₂ levels (NoRx). Five others were put on CPB with pO₂ reduced to normoxic levels (pO₂ 100 mmHg) in CPB and BCP (Rx). Functional and biochemical measurements were made before hypoxia, as well as during and after reoxygenation.

Results.

In contrast to controls, NoRx resulted in a 40% decrease in antioxidant reserve capacity (P<0.01) at 4 mM t-butyl hydroperoxide (t-BHP), a 1212% increase in moycardial conjugated diene production during BCP induction (P<0.0003), a 1000% during reperfusion (P<0.002), a 36.1% and a 37.0% increase in coronary sinus blood conjugated dienes at 35 min (P<0.05) and 60 min (P<0.05) of reoxygenation. These biochemical changes were accompanied by a 79% reduction of left ventricular contractility (P<0.0003). Conversely, Rx led to an improvement in antioxidant reserve capacity (939±212 vs 1342±177 nmol/g protein; P<0.003), less conjugated diene production during BCP induction (15.5±6.1 vs 42.1±8.8 A₂₃₃nm/min per 100 g; P<0.003) and reperfusion (1.8±3.9 vs 22.0±5.5 A₂₃₃nm/min per 100 g; P<0.005), and to a significantly improved post bypass LV contractility (58±25 vs 21±5; P<0.0003).

Conclusions.

These data document that hypoxemic/reoxygenation injury occurs in acute hypoxic immature piglet hearts when reoxygenated on CPB with hyperoxic pO₂ (normal clinical practice). By lowering the antioxidant reserve capacity, hypoxemia seems to render the developing heart susceptible to reoxygenation damage, which occurs with the reintroduction of molecular oxygen, and is associated with free radical production, subsequent lipid peroxidation, and depressed post bypass LV function. Reduction of pO₂ during the initial reoxygenation period and during BCP arrest to normoxic levels resulted in a significant reduction of this oxygen-related damage and in much improved myocardial performance.     

A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy

Background

Current definitions of acute kidney injury (AKI) are not sufficiently sensitive to identify all newborns with AKI during the first week of life.

Methods

To determine whether the rate of decline of serum creatinine (SCr) during the first week of life can be used to identify newborns with AKI, we reviewed the medical records of 106 term neonates at risk of AKI who were treated with hypothermia for hypoxic ischemic encephalopathy (HIE).

Results

Of the newborns enrolled in the study, 69 % showed a normal rate of decline of SCr to?≥50 % and/or reached SCr levels of?≤0.6 mg/dl before the 7th day of life, and therefore had an excellent clinical outcome (control group). Thirteen newborns with HIE (12 %) developed AKI according to an established neonatal definition (AKI–KIDGO group), and an additional 20 newborns (19 %) showed a rate of decline of SCr of <33, <40, and <46 % from birth to days 3, 5, or 7 of life, respectively (delayed rise in estimated SCr clearance group). Compared to the control group, newborns in the other two groups required more days of mechanical ventilation and vasopressor drugs and had higher gentamicin levels, more fluid overload, lower urinary epidermal growth factor levels, and a prolonged length of stay.

Conclusions

The rate of decline of SCr provides a sensitive approach to identify term newborns with AKI during the first week of life.

     

急性低氧和低氧习服影响HepG2细胞内红细胞生成素基因的表达

目的　观察急性低氧和低氧习服影响人HepG2细胞内红细胞生成素 (EPO) ,低氧诱导因子 1α(HIF 1α)和肝细胞核因子 4(HNF 4)基因表达。方法　HepG2细胞在 1%O2 下培养 2 4h后 ,2 1%O2 下培养 2 4h ,以此为 1个周期 ,连续低氧训练 6个周期 ,细胞达到低氧习服状态后 ,用Northern杂交方法检测EPO、HIF 1α和HNF 4基因表达。结果　HepG2细胞在急性低氧条件下培养48h后 ,胞内EPO、HIF 1α和HNF 4基因表达升高 ,mRNA含量分别升至常氧对照细胞的 4.3、2 .3、1.2倍 ;在低氧训练过程中 ,HepG2细胞内EPO、HIF 1α和HNF 4基因的mRNA含量逐渐下降 ;细胞达到低氧习服后 ,再急性低氧 48h ,EPO基因表达水平接近常氧对照组 ,HIF 1α和HNF 4的mRNA含量分别为常氧对照组的 81.4%和 12 2 .4%。结论　HepG2细胞达到低氧习服后 ,急性低氧对EPO基因表达的诱导作用减弱甚至受到抑制。与HNF 4相比 ,HIF 1α在急性低氧或低氧习服影响EPO基因表达中起着更为重要的作用。     

Inhaled nitric oxide for acute hypoxic respiratory failure in children and adults: a meta-analysis

We systematically reviewed randomized controlled trials examining inhaled nitric oxide (INO) for the treatment of acute respiratory distress syndrome or acute lung injury in children and adults. Qualitative assessments of identified trials were made, and metaanalyses were performed according to Cochrane methodology. Five randomized controlled trials (n = 535) met entry criteria. One study demonstrated significant improvement in oxygenation in the first 4 days of treatment, with no difference after this. There was no difference in ventilator-free days between treatment and placebo groups, and no specific dose of INO was more advantageous than any other. INO had no effect on mortality in trials without crossover of treatment failures to open-label INO (relative risk, 0.98; 95% confidence interval, 0.66-1.44). Other clinical indicators of effectiveness, such as duration of hospital and intensive care stay, were inconsistently reported. Lack of data prevented assessment of all outcomes. If further trials assessing INO in acute respiratory distress syndrome or acute lung injury are to proceed, they should be stratified for primary etiology, incorporate other modalities that may affect outcome, and evaluate clinically relevant outcomes before any benefit of INO can be excluded.     

The acute hypoxic ventilatory response under halothane,isoflurane, and sevoflurane anaesthesia in rats*

The relative order of potency of anaesthetic agents on the hypoxic ventilatory response has been tested in humans, but animal data are sparse. We examined the effects of 1.4, 1.6, 1.8, and 2.0 MAC halothane, isoflurane, and sevoflurane on phrenic nerve activity in euoxia (baseline) and during acute normocapnic hypoxia (inspired oxygen fraction 0.09) in adult male Sprague‐Dawley rats. With halothane, all animals became apnoeic even in euoxia, and the hypoxic response was completely abolished at all anaesthetic levels. With isoflurane, 5 of 14 animals exhibited phrenic nerve activity in euoxia at 1.4 MAC and demonstrated a hypoxic response (302% of baseline activity), but all became apnoeic and lost the hypoxic response at higher doses. With sevoflurane, phrenic nerve activity and a hypoxic response was preserved in at least some animals at all doses (i.e. even the highest dose of 2.0 MAC). Similar to the rank order of potency previously observed in humans, the relative order of potency of depression of the hypoxic ventilatory response in rats was halothane (most depressive) > isoflurane > sevoflurane (p = 0.01 for differences between agents).     

Mechanisms of succinylcholine-induced arrhythmias in hypoxic or hypoxic:hypercarbic dogs

To evaluate the effects of succinylcholine on cardiac arrhythmias and serum levels of potassium and catecholamines, dogs with hypoxia alone and with hypoxia and hypercarbia were studied during anesthesia with halothane or enflurane. After the injection of succinylcholine (0.3 mg/kg), cardiac arrhythmias occurred in all halothane:hypoxia dogs and in 70% of dogs given halothane during hypoxia:hypercarbia. No dogs given enflurane anesthesia developed arrhythmias. Serum potassium levels increased significantly 3 and 5 min after succinylcholine in all groups. Serum epinephrine levels increased in the halothane-hypoxia:hypercarbia and enflurane:hypoxia groups and, after the injection of succinylcholine, epinephrine levels increased further in dogs in the halothane:control, halothane:hypoxia, halothane-hypoxia:hypercarbia, enflurane:hypoxia, and enflurane-hypoxia:hypercarbia groups. Norepinephrine levels increased with enflurane-hypoxia:hypercarbia and after the succinylcholine in the halothane:hypoxia, halothane-hypoxia:hypercarbia, and enflurane-hypoxia:hypercarbia groups. The results suggest that succinylcholine induces arrhythmias by sympathetic stimulation and that halothane sensitizes the myocardium to arrhythmias at the same levels of serum catecholamines and potassium in the presence of hypoxia or hypoxia:hypercarbia more than does enflurane.