Effects of dopexamine on rat cardiorenal functions during lipopolysaccharide-induced experimental sepsis

We aimed to test the protective effect of dopexamine on renal function and systemic haemodynamics in rats with induced sepsis. Female Sprague-Dawley rats were randomized into three equal groups: group 1 (control, received 3% creatinine throughout the experiment); group 2 (sepsis, received 3% creatinine and Escherichia coli lipopolysaccharide [LPS] endotoxin [8 mg/kg per h]); and group 3 (sepsis plus dopexamine, received 3% creatinine, E. coli LPS and dopexamine [1 microgram/kg per min]). Time-adjusted heart rate, systolic, diastolic and mean arterial pressures, urine volume and glomerular filtration rate (from creatinine clearance) were recorded. After bacterial infusion heart rate increased and mean arterial pressure decreased; the fall in mean arterial pressure was less pronounced with dopexamine (group 3) than without (group 2). Dopexamine also induced significant and moderate increases in urine volume and heart rate, respectively. We concluded that dopexamine has some positive inotropic-chronotropic effects and induces favourable responses in renal function.     

Induction of mild hypothermia with infusion of cold (4 degrees C) fluid during ongoing experimental CPR

INTRODUCTION: Therapeutic hypothermia after resuscitation has been shown to improve the outcome regarding neurological state and to reduce mortality. The earlier hypothermia therapy is induced probably the better. We studied the induction of hypothermia with a large volume of intravenous ice-cold fluid after cardiac arrest during ongoing cardiopulmonary resuscitation (CPR). METHODS: Twenty anaesthetised piglets were subjected to 8 min of ventricular fibrillation, followed by CPR. They were randomized into two groups. The hypothermic group was given an infusion of 4 degrees C acetated Ringer's solution 30 ml/kg at an infusion rate of 1.33 ml/kg/min, starting after 1 min of CPR. The control group received the same infusion at room temperature. All pigs received a bolus dose of vasopressin after 3 min of CPR. After 9 min, defibrillatory shocks were applied to achieve restoration of spontaneous circulation (ROSC). Core temperature and haemodynamic variables were measured at baseline and repeatedly until 180 min after ROSC. Cortical cerebral blood flow was measured, using Laser-Doppler flowmetry. RESULTS: All pigs had ROSC, except one animal in the hypothermic group. Only one animal in the hypothermic group died during the observation period. The calculated mean temperature reduction was 1.6+/-0.35 degrees C (S.D.) in the hypothermic group and 1.1+/-0.37 degrees C in the control group (p=0.009). There was no difference in cortical cerebral blood flow and haemodynamic variables. CONCLUSION: Inducing hypothermia with a cold infusion seems to be an effective method that can be started even during ongoing CPR. This method might warrant consideration for induction of early therapeutic hypothermia in cardiac arrest victims.     

Autonomic regulation during mild therapeutic hypothermia in cardiopulmonary resuscitated patients

Objective  

We investigated whether there are differences in autonomic cardiovascular regulation in resuscitated patients undergoing therapeutic hypothermia (TH) in relation to the clinical outcome.     

Correction of perioperative hypothermia decreases experimental sepsis mortality by modulating the inflammatory response

OBJECTIVE: The objective of this study was to investigate if the correction of perioperative hypothermia improves sepsis survival. DESIGN: Mice with anesthesia-induced perioperative hypothermia had sepsis induced by cecal ligation and puncture and were treated with fluid resuscitation and antibiotics. The mice were either warmed (35 degrees C) or kept at room temperature for 1 hr in the immediate postoperative period. SETTING: This study was conducted at a university research laboratory. SUBJECTS: This study included adult, female outbred mice. INTERVENTIONS: Immediately after surgery, mice were randomized to 1 hr of warming or maintained at room temperature. Warming was accomplished by placing the mice in a cage preheated to 35 degrees C. MEASUREMENT AND MAIN RESULTS: The anesthesia-induced hypothermia resolved within 10 hrs, and perioperative warming reestablished normothermia within 1 hr. Restoring normothermia improved sepsis survival from 42% to 60% (p < .02). Warming also significantly corrected the changes in body weight, reflecting improved overall physiological status. To examine the mechanism of this beneficial response, plasma levels of interleukin-6 were assessed. Warming was associated with a decrease in interleukin-6 levels in both those mice that died as well as survivors, reflecting a blunting but not complete inhibition of the inflammatory response. Among surviving mice, warming also significantly increased the peripheral blood cell count, including the neutrophils, an indication that warming augmented innate immunity. CONCLUSIONS: Correction of perioperative hypothermia improves survival after sepsis by appropriately modulating the early inflammatory response.     

EEG should be performed during induced hypothermia

Induced hypothermia has improved neurological outcome after cardiac arrest. Even though anoxic insults to the brain often provoke epileptic activity, it is unclear whether EEG monitoring is necessary in these patients. We report the case of a 53-year-old female who suffered cardiac arrest. During induced hypothermia extensive shivering was managed by sedation and curare. After their discontinuation convulsions appeared and status epilepticus was disclosed on EEG recording, and was treated by thiopental infusion for 10 days. The patient recovered slowly and has now regained independent living (CPC 1). In induced hypothermia several factors including the use of curare, may conceal clinical signs of epileptic activity. We therefore suggest a broader use of EEG in these patients.     

亚低温治疗对实验性脑梗死大鼠心脏功能的影响

背景实施亚低温可能对全身各重要脏器的功能和代谢产生一定影响,这些影响有利还是有弊,需要进一步研究考证.目的在亚低温治疗脑梗死的同时测定心脏的能量储备,心电图,观察其超微结构,从而探讨亚低温对心脏功能的影响.设计随机对照实验.单位武汉大学人民医院神经内科.材料实验在武汉大学人民医院神经内科实验室完成.选择SD大鼠58只,随机分为假手术组10只,脑梗死后常温组(简称常温组)24只,脑梗死后亚低温治疗组(简称亚低温组)24只.方法常温组、亚低温组采用线栓法制作大脑中动脉梗死模型,假手术组仅切开皮肤及结扎血管,不穿线入大脑中动脉.亚低温组动物置于4℃环境中将动物肛温控制在(34±1.0)℃;假手术组、常温组动物置于室温(20℃)环境中.12 h后测定心肌组织的三磷酸腺苷、二磷酸腺苷和磷酸腺苷值及能量储备值,并于电镜下观察心肌超微结构改变.主要观察指标①各组大鼠心肌能量代谢的改变.②各组大鼠心电生理改变.③各组大鼠心肌超微结构.结果58大鼠均进入结果分析.①缺血后12 h时常温组和亚低温组大鼠心肌三磷酸腺苷、二磷酸腺苷、能量储备值均低于假手术组(P＜0.01),但亚低温组的三磷酸腺苷和能量储备值却高于常温组(P＜0.01).②常温组和亚低温组异常心电图发生率差异无显著性意义(P＞0.05);但亚低温组的心率明显低于常温组[(290.92±44.18),(472.20±12.79)次/min,P＜0.01],有3只大鼠的心率低于150次/min.③超微结构显示常温组和亚低温组心肌均有缺血性损伤,但亚低温组的损伤较常温组轻.结论全身亚低温治疗脑梗死时可显著减缓心率,改善心肌的能量储备,减轻脑梗死引起的心肌缺血,不会增加心电图异常的发生率.     

亚低温对心脏外科术后低心排的治疗评价

目的 探讨亚低温对心脏外科术后低心排的治疗价值及其疗效.方法 选择2009年5月至2011年2月本院心脏外科术后应用大剂量血管活性药物及主动脉内球囊反搏术(IABP)治疗仍存在低心排,而给予亚低温治疗的患者12例.监测患者亚低温治疗前后心排血指数(Cl)、混合静脉血氧饱和度(S-vO2)、尿量的变化等.结 果在应用亚低温治疗过程中,将患者膀胱温度降至33～ 35℃以降低组织的氧需求.与治疗前比较,经亚低温治疗后患者CI(ml·s-1·m-2)明显增加(38.34±5.00比30.01±5.00),S-vO2明显升高(0.64±0.07比0.54±0.08),尿量(ml·kg-1·h-1)明显增加(3.0±2.1比1.5±1.1,均P＜0.05);而心率、平均动脉压、动脉血氧分压则无明显改变.结论 亚低温治疗可有效改善心脏外科术后低心排患者循环功能,且操作简单.     

Rewarming of healthy volunteers after induced mild hypothermia: a healthy volunteer study

Objectives: The study compares the efficacy of two active and one passive warming interventions in healthy volunteers with induced mild hypothermia.

Methods: Eight volunteers were studied in a random order crossover design. Each volunteer was studied during re-warming from a core temperature of 35°C with each of: a radiant warmer (Fisher & Paykel); a forced air warmer (Augustine Medical), and a polyester filled blanket, to re-warm.

Results: No significant differences in re-warming rates were observed between the three warming devices. It was found that the subject's endogenous heat production was the major contributor to the re-warming of these volunteers. Metabolic rates of over 350 W were seen during the study.

Conclusions: For patients with mild hypothermia and in whom shivering is not contraindicated our data would indicate that the rate of re-warming would be little different whether a blanket or one of the two active devices were used. In the field, this may provide the caregiver a useful choice.

     

Tracheal temperature for monitoring body temperature during mild hypothermia in pigs

Aim of the study

Out-of-hospital induction of mild therapeutic hypothermia after cardiac arrest needs easy to use and accurate body temperature monitoring. The aim of the study was to evaluate the best temperature probe position on a specially designed tracheal tube, as compared to pulmonary artery temperature (Tpa) during cooling to mild hypothermia in pigs.

Methods

Eight swine (29-38 kg) were anesthetized and intubated with an endotracheal tube with three temperature probes: T1 was attached to the wall of the tube, 1 cm proximal to the cuff-balloon, without contact to the mucosa; T2 and T3 were placed on the cuff-balloon with tight contact to the mucosa, T3 was covered by a small plastic tube to protect the mucosa against mechanical alterations. Body temperature was measured with a pulmonary artery catheter. Pigs were cooled from Tpa 38.5 to 33.0 °C with fast surface and slow endovascular cooling in a crossover design. To assess hysteresis, areas under the curve (AUC) were compared. Data are presented as mean and 95% confidence intervals.

Results

Temperatures were not different either during fast surface (T1-Tpa: 0.1[−0.3 to 0.5] °C, T2-Tpa: 0.2[0.0 to 0.4] °C, T3-Tpa: 0.4[0.1 to 0.7] °C) or slow endovascular (T1-Tpa: −0.3[−0.5 to 0.2] °C, T2-Tpa: −0.1[−0.3 to 0.0] °C, T3-Tpa: −0.1[−0.5 to 0.3] °C) cooling. There was no difference in hysteresis related to the location of the temperature probes. Faster surface cooling correlated with a larger but not significantly different hysteresis between the probes.

Conclusions

Tracheal temperature is an accurate surrogate for body temperature during fast and slow cooling to mild hypothermia in pigs and regardless of the location of the temperature probe on the tube.     

Thermal and cardiovascular changes during three methods of resuscitation from mild hypothermia

The interrelations among core temperatures (cardiac, esophageal, tympanic, rectal), skin temperature, and cardiovascular function (cardiac output, arterial pressure, heart rate, total peripheral resistance) were studied in a conscious subject during entry into mild hypothermia through cold water (10 degrees C) immersion, and during rewarming by three basic procedures: peripheral heat donation (bath); core heat donation (inhalation); and no exogenous heat (spontaneous). Swan-Ganz catheterization of the heart enabled measurement of cardiac temperature as well as cardiac output by the thermal dilution method. During cooling, all sites of core temperature measurement showed similar rates of entry into hypothermia. However, during the rewarming procedures, divergent patterns of temperature change among the four sites occurred. Rectal and tympanic temperatures were not representative of cardiac temperature, but esophageal temperature was, and is therefore most suitable as a criterion for experimental evaluation of the thermal benefit of various core rewarming techniques. During the first 30 min of rewarming, rates of increase in cardiac temperature for bath, inhalation, and spontaneous procedures varied according to the proportions 4:2:1, respectively. No afterdrop of cardiac temperature occurred with the inhalation or spontaneous procedures, but an afterdrop at this site did occur during the first 15 min of bath rewarming as soon as skin temperature was greater than 30 degrees C. This afterdrop coincided with cardiovascular changes including abrupt decreases in arterial pressure and total peripheral resistance, along with increases in heart rate and cardiac output. Such evidence of increased peripheral circulation was not observed with the inhalation and spontaneous methods. The findings relate to experimental evaluation of rewarming techniques and principles for resuscitation of hypothermia victims, especially in the first-aid situation.     

亚低温治疗实验性脑梗死时对心脏的影响

目的　研究全身亚低温治疗实验性脑梗死时对心脏的影响。方法　 5 8只Wistar大鼠分成对照组 (n =10 )、常温组 (n =2 4)和亚低温组 (n =2 4) ,采用线栓法制作大脑中动脉 (MCA)梗死模型。监测ECG ,测定术后 12h心肌高能磷酸化合物 (ATP、ADP、AMP)、能量储备 (EC)值和心肌超微结构改变。结果　缺血后 12h时常温组和亚低温组大鼠心肌ATP、ADP、EC均低于对照组 (P <0 .0 1) ,但亚低温组的ATP和EC却高于常温组 (P <0 .0 1) ;常温组和亚低温组异常ECG发生率无明显差异 (P >0 .0 5 ) ;但亚低温组的心率明显低于常温组 (P <0 .0 1) ,有 3只大鼠的心率低于 15 0次 /min ;超微结构显示常温组和亚低温组心肌均有缺血性损伤 ,但亚低温组的损伤较常温组轻。结论　全身亚低温治疗实验性脑梗死时能改善心肌的能量储备 ,减轻脑梗死引起的心肌缺血 ,不会增加ECG异常的发生率 ,但可显著减缓心率     

亚低温对猪脓毒性休克时心肌的影响

目的 探讨亚低温对猪脓毒性休克时心肌的保护作用.方法 24头贵州小型猪随机(随机数字法)分为休克前亚低温组、休克后亚低温组和常温对照组,每组8头.麻醉后股静脉注入大肠杆菌内毒素制作猪脓毒症模型.制模后各组同时用输液泵以相同速度股静脉持续输入生理盐水,休克前亚低温组用4℃的生理盐水,常温对照组和休克后亚低温组用38℃的生理盐水,休克后亚低温组在动脉收缩压降至基础值的60%,维持1 h后,开始改用4℃的生理盐水.制模前和制模后温度干预6 h、12h时观察各组心脏血流动力学指标、血乳酸、肌钙蛋白I(CTnI)、冠状动脉造影TIMI血流、电镜下心肌超微结构变化.结果 6 h,12 h后,休克前亚低温组各项指标均显著优于休克后亚低温组和常温对照组(P<0.01).6 h后,休克后亚低温组的CTnI、超微结构损伤变化轻于常温对照组(P<0.05),但两组血乳酸、TIMI血流、血流动力学指标变化差异无统计学意义(P>0.05).12 h后,休克后亚低温组各项指标和常温对照组差异无统计学意义(P>0.05).结论 亚低温对猪脓毒症时的心肌有一定的保护作用;猪脓毒性休克发生以前早期使用亚低温对心肌的保护作用和改善心功能较明显;猪脓毒性休克发生以后,亚低温可以延缓心肌损伤的速度,但并不减轻心肌损伤的程度,也不能减少心功能的丧失.     

重型颅脑损伤亚低温治疗中脑氧代谢的变化

背景亚低温对重型颅脑损伤患者的治疗作用已被人们所认识,但其机制尚需进一步证实.目前对于重型颅脑损伤后及亚低温治疗过程中脑组织氧代谢状态的改变,尚未见到相应报道.目的观察重型颅脑损伤患者亚低温治疗过程中的脑氧代谢变化规律,揭示亚低温治疗的作用.设计以患者为观察对象的析因设计.单位天津市环湖医院亚低温治疗中心.对象选择1998-08/2000-01在天津市环湖医院亚低温治疗中心就诊的重型颅脑损伤患者13例.男11例,女2例;年龄18-65岁.脑挫裂伤并硬膜下血肿6例,硬膜外血肿1例,蛛网膜下腔出血4例,弥漫性轴索损伤2例;保守治疗7例,手术清除血肿同时行内/外减压术6例.方法所有患者在亚低温治疗室内应用体温调节毯进行全身降温,同时给予冬眠肌松合剂(生理盐水500 mL+氯丙嗪100 mg+异丙嗪100 mg+卡肌宁400 mg)持续静滴.采用Neurotrend-7TM多参数监测系统持续监测脑组织氧分压、二氧化碳分压、pH值及脑温,比较治疗前后指标的变化.并对患者脑氧代谢与格拉斯哥昏迷量表(总分15分,正常为15分,分数越低意识障碍程度越深)及格拉斯哥预后评分进行相关性分析.主要观察指标持续监测脑组织氧分压、二氧化碳分压、pH值及脑温.结果13例患者均进入结果分析.①脑氧代谢的变化趋势氧分压亚低温后18 h明显高于降温前[(2.23±1.29,1.29±0.57)kPa,t=2.449,P＜0.05].二氧化碳分压亚低温后6 h明显低于降温前[(7.32±0.92,7.75±1.07)kPa,t=2.446,P＜0.05].pH值达低温时明显高于降温前[(7.06±0.15,6.83±0.20),t=5.164,P＜0.05].颅内压达低温时明显低于降温前[(2.03±1.01,2.57±0.93)kPa,t=2.948,P＜0.05].脑灌注压亚低温后6 h明显高于降温前[(9.40±1.80,7.80±1.59)kPa,t=2.365,P＜0.05].②重型颅脑损伤患者脑氧代谢与格拉斯哥预后评分的相关关系二氧化碳分压在低温24 h时的数值与格拉斯哥预后评分呈负相关(r=-0.699,P＜0.05).治疗前后脑氧代谢指标的变化与格拉斯哥预后评分呈正相关.结论脑氧代谢持续监测安全、有效,有利于早期发现重型颅脑损伤后脑组织缺氧及酸中毒.亚低温治疗能有效缓解重型颅脑损伤后的脑组织缺氧及酸中毒,从而改善患者预后.     

重型颅脑损伤亚低温治疗中脑氧代谢的变化

背景：亚低温对重型颅脑损伤患者的治疗作用已被人们所认识,但其机制尚需进一步证实.目前对于重型颅脑损伤后及亚低温治疗过程中脑组织氧代谢状态的改变,尚未见到相应报道.目的：观察重型颅脑损伤患者亚低温治疗过程中的脑氧代谢变化规律,揭示亚低温治疗的作用.设计：以患者为观察对象的析因设计.单位：天津市环湖医院亚低温治疗中心.对象：选择1998-08/2000-01在天津市环湖医院亚低温治疗中心就诊的重型颅脑损伤患者13例.男11例,女2例;年龄18-65岁.脑挫裂伤并硬膜下血肿6例,硬膜外血肿1例,蛛网膜下腔出血4例,弥漫性轴索损伤2例;保守治疗7例,手术清除血肿同时行内/外减压术6例.方法：所有患者在亚低温治疗室内应用体温调节毯进行全身降温,同时给予冬眠肌松合剂（生理盐水500 mL＋氯丙嗪100 mg＋异丙嗪100 mg＋卡肌宁400 mg）持续静滴.采用Neurotrend-7TM多参数监测系统持续监测脑组织氧分压、二氧化碳分压、pH值及脑温,比较治疗前后指标的变化.并对患者脑氧代谢与格拉斯哥昏迷量表（总分15分,正常为15分,分数越低意识障碍程度越深）及格拉斯哥预后评分进行相关性分析.主要观察指标：持续监测脑组织氧分压、二氧化碳分压、pH值及脑温.结果：13例患者均进入结果分析.①脑氧代谢的变化趋势：氧分压亚低温后18 h明显高于降温前[（2.23&;#177;1.29,1.29&;#177;0.57）kPa,t=2.449,P＜0.05].二氧化碳分压亚低温后6 h明显低于降温前[（7.32&;#177;0.92,7.75&;#177;1.07）kPa,t=2.446,P＜0.05].pH值达低温时明显高于降温前[（7.06&;#177;0.15,6.83&;#177;0.20）,t=5.164,P＜0.05].颅内压达低温时明显低于降温前[（2.03&;#177;1.01,2.57&;#177;0.93）kPa,t=2.948,P＜0.05].脑灌注压亚低温后6 h明显高于降温前[（9.40&;#177;1.80,7.80&;#177;1.59）kPa,t=2.365,P＜0.05].②重型颅脑损伤患者脑氧代谢与格拉斯哥预后评分的相关关系：二氧化碳分压在低温24 h时的数值与格拉斯哥预后评分呈负相关（r=-0.699,P＜0.05）.治疗前后脑氧代谢指标的变化与格拉斯哥预后评分呈正相关.结论：脑氧代谢持续监测安全、有效,有利于早期发现重型颅脑损伤后脑组织缺氧及酸中毒.亚低温治疗能有效缓解重型颅脑损伤后的脑组织缺氧及酸中毒,从而改善患者预后.