大鼠体外循环模型的建立

目的建立大鼠体外循环实验模型。方法雄性成年SD大鼠10只(450～550g),麻醉后给予气管切开,呼吸机辅助通气,股动脉置管接监护仪实时监测动脉血压并按时采集动脉血标本,股静脉置管用于持续补液和静脉血样采集。经右颈静脉置多孔引流管至右心房行中心静脉引流,血液经特制微型膜肺氧合后,由蠕动泵经右颈动脉实施灌注。本模型采用林格氏液和贺斯进行无血预充,总量为16ml,晶胶比为1∶1,灌注流量100～150ml(kg·min),转流时间60min。结果实验中膜肺氧合满意,血流动力学稳定,所有动物都成功脱机。结论利用大鼠可以建立简单、廉价的体外循环动物模型。本模型适用于研究与体外循环相关的全身炎症反应和多脏器功能损伤的病理生理机制及其防治策略。     

可植入式心室辅助装置动物模型的建立

目的探讨建立可植入式心室辅助装置研究的实验动物模型。方法选取体质量120-180 kg小公牛7只,常规全麻后左侧第4肋间开胸,建立体外循环,体外循环辅助下诱颤后,植入自主研发的国产可植入式心室辅助装置（DIVAD,domestic-made implantable ventricular assist device）,DIVAD机械性能参数接近国际同类产品,泵尺寸29.5mm×72 mm,重量158 g,体外转速可达9000 r/min,流量可达8 L/min,整合流量计,并可通过体外控制器监测控制。DIVAD连接左室及降主动脉,转速3500-8000 r/min左右,行左室辅助。术后撤除体外循环,持续监测动物生命体征及DIVAD运转情况。肝素静滴维持ACT在正常值1.5-2倍之间。结果7只小牛术后全部复跳,均能成功撤离体外循环辅助,最长存活时间超过93 h,最短存活时间0.5 h,平均存活时间20.28 h。结论小牛可以作为DIVAD研究的合适动物模型,其围手术期处理有相应特点,小牛DIVAD实验模型的建立对于进一步研究改进DIVAD有重要作用。     

家庭应用无创机械通气对COPD患者肺功能及医疗费用的影响

目的:在COPD急性发作期无创机械通气治疗已经被临床医生重视并广泛应用于临床治疗.但对于家庭应用无创机械通气治疗缓解期的患者是否获益,目前尚无明确结论.本试验旨在探讨家庭应用无创机械通气对COPD患者生活质量、运动耐量、肺功能及医疗费用的影响.方法:随机观察103例慢性阻塞性肺疾病急性发作合并 Ⅱ型呼吸衰竭患者,于医院应用无创辅助通气治疗缓解后出院.其中39例继续应用无创机械通气治疗(治疗组),其余64停止无创机械通气治疗(对照组),观察6个月,比较家庭应用无创机械通气治疗后生活质量、运动耐量、肺功能变化、血气分析、心率、呼吸频率及急性发作的间隔期、医疗费用状况.结果:治疗组较对照组生活质量、运动耐量明显改善(P＜0.05),肺功能下降明显减慢(P＜0.05),平均医疗费用明显减少(P＜0.05).结论:家庭应用无创机械通气能够延缓COPD患者肺功能下降速度,减少医疗费用近万元,延长急性加重间隔时间6个月以上,减少住院次数,提高生存质量.     

一种新型大鼠心脏移植模型的制作体会

目的采用腹部套管法建立大鼠心脏移植模型,并分析该方法优劣,为器官移植研究提供合适的动物模型。方法SD大鼠60只,参照Baxter的报道进行同种腹部异位心脏移植,成功制作了该模型并总结了经验。结果共实施手术30例,成功27例,成功率90%;移植心存活30 d以上。结论新型的大鼠心脏移植模型简单易行,成功率高,适合用于器官移植研究,值得推广应用。     

大鼠心肌缺血再灌注模型构建的改良

目的改良大鼠心肌缺血再灌注模型的构建方法,增强实用性。方法32只SD雄性大鼠随机分为四组（A组：伪手术组;B组：缺血组;C组：缺血30 min再灌注组;D组：缺血60 min再灌注组）。缺血过程在人工机械通气条件下完成,术前术中监测心电图变化,模型成功72 h后抽血进行心肌酶谱分析,并观察左室压变化。结果造模成功率为91%。B、C、D组各心肌酶含量明显高于A组（P〈0.05）,C、D组低于B组（P〈0.05）。B、C、D组左室压值低于A组（P〈0.05）,C、D组高于B组（P〈0.05）。结论改进后的模型制备方法简便易行,成功率高,评价指标符合临床应用。     

家兔不同人工通气量时的血气分析

家兔是国内生理学实验常用动物。在人工通气维持呼吸的实验中,要求每个实验者在整个实验中都使用血气监测装置,目前还很难办到。多数作者是通过测定呼出气CO_2浓度来调节通气量的。然而对通气量大小的调节各个作者的报告不尽一致。本实验目的是观察部分家兔人工通气呼出气平均CO_2浓度与血气分析值关系,为条件相近的实验者提供调节人工通气的参数作参考。     

机械通气对慢性阻塞性肺疾病患者红血球变化的影响

目的:评价机械通气治疗对慢性阻塞性肺疾病(COPD)患者红血球变化的影响.方法:采用病例报告表,收集我院ICU2004年-2008年收治的67例COPD行机械通气患者的血球分析及血气分析,建立数据库:①测定67例COPD患者机械通气前、通气1天、通气7天后红细胞计数、血红蛋白、红细胞压积以及氧分压值,评估机械通气对COPD患者红血球变化的影响.②根据预后分为生存组和死亡组:比较两组通气前与通气1天、7天后红血球分析变化值.③以65岁为界分为低龄组和高龄组,比较两组通气前与通气1天、7天的红血球分析变化值.结果:①机械通气后红细胞计数、血红蛋白、红细胞压积随时间均明显降低,氧分压明显升高(P<0.05).②生存组和死亡组通气前后红血球分析变化值随时间变化有显著差异.③高龄组和低龄组通气前后红血球分析变化值无明显差异.结论:COPD患者行机械通气治疗后红细胞计数、血红蛋白、红细胞压积随时间增加明显降低,其变化影响预后,应尽早拔除气管插管,缩短有创机械通气时间,缩短ICU和总住院时间,有效改进治疗效果,降低治疗费用,是具有一定临床实用价值的治疗方案.     

MAXIMA膜式氧合器在体外循环中的应用(附260例报告)

在体外循环中应用MAXIMA膜式氧合器260例,术中各项血气分析指标基本正常,术后发生肺部并发症减少。作者认为:体外循环手术中应用膜式氧合器,尤其对危重病人,可减轻体外循环对肺功能的扰乱。同时也是对心脏功能的支持。     

冠状动脉粥样硬化大鼠实验动物模型的改进与评价

目的通过对文献报道的动脉粥样硬化大鼠造模方法的改进,建立一种适合进行心血管疾病研究的冠状动脉粥样硬化Wistar大鼠模型。方法将40只大鼠随机分为对照组与模型组,对照组15只,模型组25只。模型组高脂饲料喂养配合前3个月,每月按15万U/kg每月腹腔注射维生素D3一次,对照组喂养普通饲料,造模时长150 d。实验结束后通过对血管内皮、脂代谢、炎症浸润几个方面对模型大鼠进行考察。结果证实模型组大鼠较对照组血清LDL-C、CHO、TG水平明显升高,HDL-C/LDL-C、NO/ET-1值明显降低;AI值显著增高;血清NO、ET-1、ox-LDL、AngⅡ、sICAM-1表达明显增高;HE染色显示：模型组大鼠冠状动脉出现血栓、内皮破坏、粥样斑块形成,血管壁钙化情况;心肌纤维组织增生,炎细胞浸润,心肌轻度变性;主动脉出现动脉粥样硬化斑块形成,而对照组无病变产生。结论本方法能够提供一种稳定的、复制性好的用于冠状动脉粥样硬化实验研究的大鼠模型。     

氨溴索不同给药方式对机械通气大鼠肺内炎性因子水平及肺组织湿/干比值的影响

目的:探讨不同氨溴索给药方式对大鼠机械通气肺部炎性因子释放及肺组织湿/干比值的影响。方法:将45只健康SD雄性大鼠随机分成静脉组、雾化组和对照组,各15只。对照组:大鼠麻醉后行气管切开插管,并行单纯机械通气4h;静脉组:大鼠麻醉后从尾静脉泵入氨溴索,气管切开插管后行机械通气4h;雾化组:大鼠麻醉后行气管切开插管,通过自制装置氧气驱动雾化吸入氨溴索,并行机械通气4 h。各组机械通气后放血处死大鼠,取肺组织,计算肺湿/干重比(W/D)。收集支气管灌洗液(BALF)并检测TNF-α,IL-1β和IL-6浓度。结果:与对照组比较,静脉组和雾化组大鼠支气管灌洗液中TNF-α,IL-1β和IL-6的浓度明显降低(P0.05),但此两组间无显著性差异(P0.05);与对照组比较,静脉组和雾化组大鼠肺组织W/D比也明显降低(P0.05),但雾化组大鼠肺组织W/D比明显低于静脉组大鼠(P0.05)。结论:氨溴索静脉给予和雾化给予都能显著降低大鼠机械通气时肺内炎性因子水平和肺W/D比,而且雾化给予较静脉给予更能减轻大鼠肺组织的W/D比。     

Pre-emptive and continuous inhaled NO counteracts the cardiopulmonary consequences of extracorporeal circulation in a pig model.

Cardiopulmonary bypass (CPB) activates a systemic inflammatory response characterized clinically by alterations in cardiovascular and pulmonary function. The aim of this study was to measure the cardiopulmonary consequences in sham-operated pigs, and in animals subjected to CPB in the presence or absence of lipopolysaccharide (LPS). We also investigated, if the perioperative administration of inhaled NO exerts significant cardiopulmonary effects in an anaesthetized and mechanically ventilated pig model of extracorporeal circulation. Thirty pigs were randomized into six equal groups (sham; sham+INO; CPB; CPB+INO; CPB+LPS; CPB+LPS+INO) and subjected to anaesthesia with mechanical ventilation for up to 24h. We found that CPB+LPS group has the highest degree of lung injury. We also demonstrated that there was a significant difference on the cardiovascular parameters (heart rate, central venous pressure, stroke volume index, and mean systemic arterial blood pressure) between the CPB groups and the sham groups. The deteriorated lung mechanics was associated with a decrease in active subfraction of surfactant (LA) with time during the procedure (P=0.0003), on which inhaled NO had only an initial beneficial effect. In our model, inhaled NO had no long-term beneficial effect on lung mechanics and surfactant homeostasis despite improving lung haemodynamics, inflammation, and oxygenation. We conclude from this study that the use of pre-emptive and continuous inhaled NO therapy has protective and safe effects against lung ischemia/reperfusion associated with CPB.     

Contribution of cardiogenic oscillations to gas exchange in constant-flow ventilation

The contribution of cardiogenic oscillations to gas exchange during constant-flow ventilation was examined in 11 dogs. With the use of two variations of cardiopulmonary bypass to maintain the systemic and pulmonary circulation, the influence of cardiogenic oscillations was removed by arresting the heart. Cardiac arrest by ventricular fibrillation was associated with a mean decrease in alveolar ventilation of 43% in five dogs on right and left heart bypass. However, successful defibrillation and return of the prearrest level of alveolar ventilation could not be achieved; thus we studied six dogs on left heart bypass. Alveolar ventilation decreased an average of 37% with cardiac arrest, and defibrillation resulted in a return of alveolar ventilation to 81% of the prearrest value. These results are consistent with previous predictions that cardiogenic oscillations are an important mechanism of gas transport during constant-flow ventilation.     

乌司他丁对体外循环法洛四联症患儿围心脏手术期循环和呼吸功能的影响

目的:探讨乌司他丁对体外循环法洛四联症患儿围心脏手术期循环和呼吸功能的影响。方法:选取我院于收治的60例法洛四联症婴幼儿参与研究,并将其随机分为对照组和试验组两组,每组患儿30例。其中试验组患儿在体外循环前以及患儿进行手术后的三天内每天均给予10000U/kg乌司他丁,而对照组患儿则在相应的时间点给予等量的生理盐水。分析比较两组患儿的体外循环时间、心脏停搏时间、手术时间、在监护室治疗的时间以及患儿术后住院时间和患儿肺部感染发生例数等临床病理情况。结果:所有入选患儿均痊愈出院,在两组患儿的手术操作情况和治疗效果对比中,对照组患儿的手术时间、体外循环时间和心脏停搏时间均显著低于试验组患儿,但重症监护时间及术后住院时间则高于试验组患儿;在两组患儿治疗后的循环功能指标比较中,试验组患儿超滤后CVP和血管活性药物均低于对照组患儿而超滤后MAP则显著高于对照组患儿;在两组患儿治疗后的呼吸功能指标的比较中,试验组患儿的动脉血氧分压明显高于对照组患儿以及试验组患儿的术后机械通气时间和肺部感染例数均低于对照组患儿,两组患儿的数据比较差异除手术时间、体外循环时间和心脏停搏时间外均具有统计学意义(均P0.05)。结论:乌司他丁对体外循环法洛四联症患儿围心脏手术期的循环和呼吸功能具有较好的保护作用,值得在临床上加以广泛推广和运用。     

Surgical Placement of Catheters for Long-term Cardiovascular Exercise Testing in Swine

This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early cardiopulmonary dysfunction is difficult to diagnose, particularly in animal models, as cardiopulmonary function is often measured invasively, requiring anesthesia. As many anesthetic agents are cardiodepressive, subtle changes in cardiovascular function may be masked. In contrast, chronic instrumentation allows for measurement of cardiopulmonary function in the awake state, so that measurements can be obtained under quiet resting conditions, without the effects of anesthesia and acute surgical trauma. Furthermore, when animals are properly trained, measurements can also be obtained during graded treadmill exercise.Flow probes are placed around the aorta or pulmonary artery for measurement of cardiac output and around the left anterior descending coronary artery for measurement of coronary blood flow. Fluid-filled catheters are implanted in the aorta, pulmonary artery, left atrium, left ventricle and right ventricle for pressure measurement and blood sampling. In addition, a 20 G catheter is positioned in the anterior interventricular vein to allow coronary venous blood sampling.After a week of recovery, swine are placed on a motor-driven treadmill, the catheters are connected to pressure and flow meters, and swine are subjected to a five-stage progressive exercise protocol, with each stage lasting 3 min. Hemodynamic signals are continuously recorded and blood samples are taken during the last 30 sec of each exercise stage.The major advantage of studying chronically instrumented animals is that it allows serial assessment of cardiopulmonary function, not only at rest but also during physical stress such as exercise. Moreover, cardiopulmonary function can be assessed repeatedly during disease development and during chronic treatment, thereby increasing statistical power and hence limiting the number of animals required for a study.     

Effects of long-term captopril and L-arginine treatment on ventilation and blood pressure in obese male SHHF rats.

We investigated the effects of captopril (Cap) and L-arginine (Arg) on hypertension and cardiopulmonary function. Our hypothesis was that Cap therapy or Arg will improve cardiopulmonary risk factors for hypertension and hypoventilation in the obese spontaneously hypertensive heart failure rat, which is characterized by hypertension, obesity, and disorders of lipid and carbohydrate metabolism. For the first study, one group of rats received Cap in drinking water, and a second group received deionized water (DI). For the second study, rats were further subdivided. Some Cap-treated rats continued on this treatment, and the other half were now given DI to determine whether there would be residual effects of Cap treatment. A subgroup of rats who had received DI was then given Arg, whereas the rest remained on DI. In the first study, Cap-treated rats exhibited decreases in systolic and diastolic blood pressures, frequency of breathing, and minute ventilation, but ventilatory control was maintained. In contrast, blood pressures and relative ventilation to metabolism were higher in the DI-treated group. Removal of Cap increased blood pressure and decreased tidal volume while these rats maintained frequency. Although Arg-treated rats did not exhibit a decrease of blood pressure, ventilation was maintained in this group by preserving tidal volume. Thus Cap and Arg affected ventilation through different mechanisms independent of blood pressure.     

RIGHT AND LEFT VENTRICULAR HEMODYNAMIC INDICES AS PREDICTORS OF THE NEED FOR AND OUTCOME OF POST-CARDIOTOMY MECHANICAL INTRAAORTIC BALLOON PUMP SUPPORT

Preoperative cardiac catheterization data of 21 patients requiring intraaortic balloon pumping (IABP) for weaning from cardiopulmonary bypass were analyzed and compared with similar data in 28 patients who underwent nearly similar operative procedures, but did not require IABP for weaning. Cardiac index (CI) and systemic vascular resistance (SVR) were found to have predictive value for the need of IABP for weaning from cardiopulmonary bypass and differentiated survival from non-survival. Left ventricular end diastolic pressure (LVEDP) was not found to be predictive. Ejection fraction (EF) was significantly lower in those who required IABP than those who did not; EF did not predict the outcome. Pulmonary capillary wedge pressure ([unk]), pulmonary artery pressure ([unk]) and pulmonary vascular resistance (PVR) were predictive of the need for IABP, but not the outcome. Left ventricular minute work index (LVMWI) was significantly lower in those requiring IABP, right ventricular minute work index (RVMWI) was predictive of survival with IABP. Together, LVMWI and RVMWI were predictive of the need for and outcome of IABP following cardiopulmonary bypass. Twenty-seven of 28 control RVMWI's were normal. No patient requiring IABP had depressed RVMWI's preoperatively. Elevated preoperative RVMWI's were associated with 80% survival with postcardiotomy IABP; normal RVMWI's were associated with a 56% survival with post-cardiotomy IABP. Elevated preoperative RVMWI's reflected moderate to maximal right ventricular compensatory capacity in response to depressed left ventricular function. Normal preoperative RVMWI's in the presence of depressed LVMWI's were indicative of decreased right ventricular compensatory capacity in post-cardiotomy IABP-support settings. Right ventricular function is as important as left ventricular function as a prognosticator for the need and outcome of IABP support of the failing post-cardiotomy circulation.     

Phosphodiesterase 4 inhibition attenuates persistent heart and lung injury by neonatal hyperoxia in rats

Phosphodiesterase (PDE) 4 inhibitors are potent anti-inflammatory drugs with antihypertensive properties, and their therapeutic role in bronchopulmonary dysplasia (BPD) is still controversial. We studied the role of PDE4 inhibition with piclamilast on normal lung development and its therapeutic value on pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) in neonatal rats with hyperoxia-induced lung injury, a valuable model for premature infants with severe BPD. The cardiopulmonary effects of piclamilast treatment (5 mg·kg(-1)·day(-1)) were investigated in two models of experimental BPD: 1) daily treatment during continuous exposure to hyperoxia for 10 days; and 2) late treatment and injury-recovery in which pups were exposed to hyperoxia or room air for 9 days, followed by 9 or 42 days of recovery in room air combined with treatment started on day 6 of oxygen exposure until day 18. Prophylactic piclamilast treatment reduced pulmonary fibrin deposition, septum thickness, arteriolar wall thickness, arteriolar vascular smooth muscle cell proliferation and RVH, and prolonged survival. In the late treatment and injury-recovery model, hyperoxia caused persistent aberrant alveolar and vascular development, PH, and RVH. Treatment with piclamilast in both models reduced arteriolar wall thickness, attenuated RVH, and improved right ventricular function in the injury recovery model, but did not restore alveolarization or angiogenesis. Treatment with piclamilast did not show adverse cardiopulmonary effects in room air controls in both models. In conclusion, PDE4 inhibition attenuated and partially reversed PH and RVH, but did not advance alveolar development in neonatal rats with hyperoxic lung injury or affect normal lung and heart development.     

血红蛋白200g/L以上紫绀型先天性心脏病患者手术效果分析

目的:明确血红蛋白200 g/L以上紫绀型先天性心脏病患者的手术效果。方法:选取2009年3月至2012年3月于我中心就诊手术治疗的紫绀型先天性心脏病患者,按血红蛋白计数≥200 g/L和200 g/L分为A组和B组,完善术前检查后进行手术治疗。记录患者手术效果和随访情况;观察比较两组患者手术中情况包括:手术方式、手术时间、体外循环时间、心脏停搏时间、心脏自动复跳情况;记录并比较两组患者手术后恢复情况,包括机械通气时间、监护室滞留时间、手术后24小时内出血量、二次开胸止血例数和血管活性药物评分,以及监护室内肝肾功能异常和肺部并发症发生例数。结果:A组死亡3例(5.2%),23例术后3个月随访效果良好;B组死亡2例(5.8%),12例术后3个月随访效果良好。两组患者手术方式、手术时间、体外循环时间和心脏停搏时间、自动复跳例数均无明显差异(P0.05)。与B组比较,A组患者术后机械通气和监护室滞留时间长,术后24小时出血量多,血管活性药物使用评分高,肝肾功能异常例数和肺部并发症发生例数较多有统计学意义(P0.05),两组间二次开胸止血例数无统计学差异(P0.05)。结论:血红蛋白200 g/L以上紫绀型先天性心脏病患者与其他紫绀型先天性心脏病患者手术效果相似,但手术后恢复慢,并发症较多。     

Function of human intrinsic cardiac neurons in situ

We sought to determine the behavior of intrinsic cardiac neurons in human subjects undergoing cardiac surgery and to correlate their activity with hemodynamics status. A lead II electrocardiogram, pulmonary artery pressure, and systemic arterial pressure were recorded along with extracellular activity generated by right atrial neurons in 10 patients undergoing coronary artery bypass surgery. Identified neurons generated spontaneously activity that was, for the most part, unrelated to the cardiac cycle. Most neurons were activated by gentle mechanical distortion of ventricular epicardial loci. The activity generated by neurons in each patient increased when arterial pressure increased and decreased when arterial pressure fell. Intrinsic cardiac neurons continued to generate activity during cardioplegia and cardiopulmonary bypass, but at reduced levels. Normal neuronal activity was restored postbypass. It is concluded that human intrinsic cardiac neurons generate spontaneous activity and that many receive inputs from ventricular mechanosensory neurites. The latter may account for the fact that their behavior depends, in part, on cardiac dynamics. They are also sensitive to intravenously administered pharmacological agents. These data also indicate that cardiopulmonary bypass and cardioplegia do not induce residual depression of their function.     

Effects of vagus nerve stimulation and vagotomy on systemic and pulmonary inflammation in a two-hit model in rats

Pulmonary inflammation contributes to ventilator-induced lung injury. Sepsis-induced pulmonary inflammation (first hit) may be potentiated by mechanical ventilation (MV, second hit). Electrical stimulation of the vagus nerve has been shown to attenuate inflammation in various animal models through the cholinergic anti-inflammatory pathway. We determined the effects of vagotomy (VGX) and vagus nerve stimulation (VNS) on systemic and pulmonary inflammation in a two-hit model. Male Sprague-Dawley rats were i.v. administered lipopolysaccharide (LPS) and subsequently underwent VGX, VNS or a sham operation. 1 hour following LPS, MV with low (8 mL/kg) or moderate (15 mL/kg) tidal volumes was initiated, or animals were left breathing spontaneously (SP). After 4 hours of MV or SP, rats were sacrificed. Cytokine and blood gas analysis was performed. MV with 15, but not 8 mL/kg, potentiated the LPS-induced pulmonary pro-inflammatory cytokine response (TNF-α, IL-6, KC: p<0.05 compared to LPS-SP), but did not affect systemic inflammation or impair oxygenation. VGX enhanced the LPS-induced pulmonary, but not systemic pro-inflammatory cytokine response in spontaneously breathing, but not in MV animals (TNF-α, IL-6, KC: p<0.05 compared to SHAM), and resulted in decreased pO(2) (p<0.05 compared to sham-operated animals). VNS did not affect any of the studied parameters in both SP and MV animals. In conclusion, MV with moderate tidal volumes potentiates the pulmonary inflammatory response elicited by systemic LPS administration. No beneficial effects of vagus nerve stimulation performed following LPS administration were found. These results questions the clinical applicability of stimulation of the cholinergic anti-inflammatory pathway in systemically inflamed patients admitted to the ICU where MV is initiated.