婴儿法洛四联症体外循环管理探讨

目的 探讨婴儿法洛四联症体外循环(CPB)管理方法。方法 回顾我院自1997年7月开展婴儿法洛四联症心脏手术至2001年9月共28例的CPB情况,包括血液稀释、灌注方式、心脑肺保护等。结果 CPB时间50～406min,平均(112±66)min,主动脉阻断时间31～94min,平均(55±16)min。主动脉开放后28例心脏均自动复跳,自动复跳率100％。26例在多巴胺、肾上腺素支持下撤离CPB,2例经长时间辅助不能脱离CPB。12例采用深低温低流量CPB。CPB中尿量0～450mL,平均(69±25)mL。7例采用超滤的患儿超出液体120～500mL,平均(247±105)mL。停机及术毕HCT分别为0.27和0.33。术后主要并发症为低心排综合征(9)、神经系统损伤(5)、呼衰(3)。结论 婴儿TOF手术的CPB管理是手术成功的一个重要的方面,我们认为:应采用适中的血液稀释和胶体液预充、选择与外科手术相配合的灌注方式、注重术中心脑肺保护。     

Changes in regional cerebral blood flow under hypothermic selective cerebral perfusion

OBJECTIVE: Currently the most frequently used perfusion technique during aortic arch surgery to prevent cerebral damage is hypothermic selective cerebral perfusion (SCP). Changes in cerebral blood flow (CBF) are known to occur during these procedures. We investigated regional changes of CBF under conditions of SCP in a porcine model. METHODS: In this blinded study, twenty-three juvenile pigs (20 - 22 kg) were randomized after cooling to 20 degrees C on CPB. Group I (n = 12) underwent SCP for 90 minutes, while group II (n = 11) underwent total body perfusion. Fluorescent microspheres were injected at seven time-points to calculate total and regional CBF. Hemodynamics, intracranial pressure (ICP), cerebrovascular resistance (CVR) and oxygen consumption were assessed. Tissue samples from the neocortex, cerebellum, hippocampus and brain stem were taken for a microsphere count. RESULTS: CBF decreased significantly (p = 0.0001) during cooling, but remained at significantly higher levels with SCP than with CPB throughout perfusion (p < 0.0001) and recovery (p < 0.0001). These findings were similar among all regions of the brain, certainly at different levels. Neocortex CBF decreased 50%, whereas brain stem and hippocampus CBF decreased by only 25 % during total body perfusion. All four regions showed 10 - 20% less CBF in the post-CPB period. CBF during SCP did not fall by more than 20% in any analysed region. The hippocampus turned out to have the lowest CBF, while the neocortex showed the highest CBF. CONCLUSION: SCP improves CBF in all regions of the brain. Our study characterizes the brain specific hierarchy of blood flow during SCP and total body perfusion. These dynamics are highly relevant for clinical strategies of perfusion.     

Influence of cardiopulmonary bypass temperature on circulatory pathophysiology and clinical outcomes

This study was designed to investigate the effects of cardiopulmonary bypass (CPB) perfusion temperature. Forty-four patients who had undergone elective coronary bypass surgery were randomly divided into 2 groups (22 patients each) according to their perfusion temperature (N group=36 degrees C; L group=30 degrees C). The concentrations of endogenous catecholamines, complements, elastase, serotonin, arachidonic acid metabolites and endothelin underwent various changes throughout the CPB but did not exhibit any statistical differences in either group. None of the substances measured correlated with systemic vascular resistance at any time. The temperature of the perfusion appears to be a major determinant of vascular tone. The postoperative PO2 was better, and postoperative pulmonary vascular resistance lower in the N group (p<0.05), most likely because of a much larger water balance during hypothermic CPB (p<0.01). The postoperative blood loss was statistically less in the N group (p<0.05). Although apparent brain damage, evidenced by the leakage of creatine kinase-BB, was not seen, the jugular bulb venous hemoglobin saturation levels (<50% in 27% of the N group, p<0.05) and higher lactate levels suggested that normothermic perfusion was relatively disadvantageous. It is concluded that normothermic CPB was relatively safe and advantageous with regard to hemostasis and pulmonary function.     

Cardiopulmonary bypass induced microcirculatory injury of the small bowel in rats

AIM： To investigate microvascular injury quantitatively in the small bowel with respect to cardiopulmonary bypass （CPB） and related mechanisms. METHODS： In 10 male SD rats, normothermic CPB was established and continued with a flow rate of 100-150 mL/kg per minute for 60 min, while another 10 sham-operated animals served as controls. An approximate 10-cm loop of the terminal ileum was exteriorized for observation by means of intravital fluorescence microscopy. The small bowel microcirculatory network including arterioles, capillaries, and collecting venules was observed prior to CPB, CPB 30 min, CPB 60 min, post-CPB 60 min and post-CPB 120 rain. The intestinal capillary perfusion, microvascular permeability and leukocyte adherence were also measured. RESULTS： The systemic hemodynamics remained stable throughout the experiment in both groups. In CPB animals, significant arteriolar vasoconstriction, blood velocity reduction and functional capillary density diminution were found. As concomitances, exaggerated albumin extravasation and increased leukocyte accumulation were also noted. These changes were more pronounced and there were no signs of restitution at the end of the observation period. CONCLUSION： CPB induces significant microcirculatory injury of the small bowel in rats. The major underlying mechanisms are blood flow redistribution and generalized inflammatory response associated with CPB.     

Coagulation activation and organ dysfunction following cardiac surgery

STUDY OBJECTIVES: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with major inflammatory triggers that cause marked activation of the microcirculation. This inflammatory response is associated with significant organ dysfunction. How this response causes organ dysfunction is not well understood; consequently, few interventions exist to prevent or treat it. In other acute inflammatory conditions, such as sepsis, increased coagulation activation in the microcirculation may be a cause of organ injury. We documented the association between coagulation activation and organ dysfunction to investigate whether coagulation activation also plays a role in organ injury following cardiac surgery with CPB. DESIGN: Prospective study of 30 patients undergoing cardiac surgery with CPB. Prothrombin fragment (PTF) 1 + 2 and plasminogen activator inhibitor (PAI) activity were measured, and levels correlated with postoperative measures of organ function including the left-ventricular stroke work index, the Pao(2)/fraction of inspired oxygen (Fio(2)) ratio, and creatinine levels. RESULTS: PTF levels increased eightfold (p < 0.05), and PAI activity increased threefold (p < 0.05) over the first 4 h after CPB. PTF levels were correlated with deteriorations in the left-ventricular stroke work index (p = 0.04), the Pao(2)/Fio(2) ratio (p = 0.02), and creatinine levels (p = 0.02). CONCLUSIONS: Levels of coagulation activation are associated with markers of postoperative organ dysfunction. Additional studies are warranted to investigate whether strategies that limit coagulation activation are associated with reductions in postoperative organ dysfunction.     

Perfusate Oncotic Pressure During Cardiopulmonary Bypass

Abstract. Current practice with respect to the use of a dilutional prime for cardiopulmonary bypass (CPB) varies widely, and the safe lower limit of perfusate protein content has not been defined. We studied this question in 75 rabbits subjected to a 1-hour CPB with a perfusate colloid osmotic pressure (COP) ranging from 26 to 4 mm Hg. Metabolic acidosis was inversely related to COP; acid-base equilibrium is thus best maintained with a high perfusate protein content. Tissue edema rapidly increased at COP levels below 16 mm Hg, i.e. with a protein level less than 4.2 g%. Urinary excretion during CPB was antagonized by the COP, the reason being that glomerular filtration rate was proportional to the difference between perfusion pressure and COP. The safety margin for renal function during CPB thus widens with a decreasing perfusate protein content. We conclude that the optimum levels of perfuste oncotic pressure and protein content during experimental cardiopulmonary bypass are 16 mm Hg and 4.2 g%.     

Oxygen consumption during cardiovascular surgery conducted under extra-corporeal circulation

Whole-body oxygen consumption (VO2) is universally considered both a measure of the metabolic activity of the body and an indicator of the adequacy of tissue perfusion during cardiopulmonary bypass as well. There is little agreement in the literature about the main determinants of oxygen consumption during CPB, except for the role of temperature in reducing the metabolic activity of the body. Many studies, which have been performed both on animals and in humans, have reached some contradictory conclusions about the role of delivery and perfusion flow rates, of haemodynamic variables, of the acid-base status, and of drugs influencing the variations of oxygen consumption during CPB. Aim of this paper is to review the evidences in literature about the determinants of whole-body oxygen consumption during cardiopulmonary bypass in man.     

Higher hematocrit improves liver blood flow and metabolism during cardiopulmonary bypass in piglets

OBJECTIVES: Hemodilution has been applied conventionally during cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) to counteract the increase in viscosity and deleterious rheological effects caused by hypothermia. However, liver dysfunction after low-flow bypass and DHCA is common, and little is known about the effects of hematocrit (Hct). The purpose of the present study is to evaluate the impact of two hemodilution priming protocols used clinically on liver perfusion and metabolism. MATERIALS AND METHODS: Ten piglets were randomized into 2 groups. One group (n = 5) had a crystalloid prime resulting in an Hct of about 15 % (low hematocrit; group L), the other (n = 5) a total-blood prime (Hct = 25 %; high hematocrit; group H). All animals underwent 70 min cooling at full flow (150 ml/kg/min), 30 min of low flow (50 ml/kg/min) at 15 degrees C followed by 45 min of DHCA and 75 min of rewarming at full flow. Liver blood flow (LBF) was assessed at the beginning of CPB at 34 degrees C, at the end of cooling at 15 degrees C, at the end of low flow, 5 min after the start of warming, and at the end of rewarming at 34 degrees C by injections of radioactive microspheres. Liver function was evaluated at the same time using the MEGX test, which measures the metabolism of lidocaine. RESULTS: LBF was insignificantly reduced during cooling, decreased during low flow (p = 0.001), and increased again after DHCA with the highest flow at the end of rewarming. LBF tended to be lower at all times in group L (p = 0.096). The liver lidocaine metabolic rate did not significantly decrease during cooling and low flow, but was increased at the end of rewarming (p = 0.01); the metabolism was higher in group H (p = 0.025). Multiregression analysis revealed liver blood flow (p = 0.003) and hematocrit (p < 0.001) as independent determinants of the liver lidocaine metabolism; arterial blood pressure and temperature did not have significant influence in this model. CONCLUSION: Hemodilution results in a tendency towards reduced liver blood flow during CPB; much worse is the resulting impaired liver metabolism, independent of reduced blood flow and pressure. Avoidance of low hematocrit during CPB may be a useful adjunct to preserve liver function in patients undergoing cardiac surgery with long duration CPB and DHCA.     

主动脉弓部手术中单侧大脑灌注血流变化与神经系统并发症关系的分析

目的:通过经颅多普勒超声(TCD)监测主动脉弓部手术中大脑中动脉(MCA)的血流,评估选择性脑灌注(SCP)期间血流变化与术后神经系统并发症的关系。方法:自2010年9月至2011年1月,共有23例符合研究标准的主动脉夹层病例入选。术中均采用深低温停循环(DHCA)和单侧脑灌注的方法,通过TCD连续记录,从麻醉完成至体外循环结束这一过程中MCA血流改变,选取6个时间点进行比较。以非灌注侧流量下降比例分为4组(<10%,10%～20%,20%～30%,>30%),观察每组术后神经系统并发症的情况和术后早期死亡的情况。结果:本组患者在全流量体外循环期间,双侧MCA血流速度差异无统计学意义(P=0.565)。SCP期间,灌注侧(右侧)MCA血流较SCP之前相比,流速为基本无变化;非灌注侧(左侧)较SCP之前显著下降,主动脉开放后基本恢复至转机前水平。术后短暂神经系统损害发生率13.0%(3/23例),3例患者中,流量下降20%～30%组中1例(12.5%),>30%组中2例(50%)。无早期死亡和永久神经系统损伤。结论:选择性脑灌注可以满足主动脉弓部手术脑部供血;半侧脑灌注期间,灌注侧血流基本无变化,非灌注侧血流下降。安全阈值可能是30%,即下降30%之内是安全的。     

Cerebral microcirculatory changes in rat with a cardiopulmonary bypass using fluorescence videomicroscopy

Cerebral microcirculatory changes in rat with a cardiopulmonary bypass (CPB) at normothermia was investigated in relation to cerebrovascular disorders caused by surgical operation with CPB. The mean arterial pressure was changed from 50 to 200 mmHg by changing the pump flow-rate. A non-pulsatile flow model was developed by stopping the cardiac beat using a fibrillator. The pial microcirculation was visualized using fluorescence-labeled red cells and dextran, and was directly observed under a fluorescence videomicroscope during CPB. Based on the recorded videoimages, the arteriolar diameter and red cell velocity were measured, in which single arterioles with approximately 40 microm diameter were selected among the pial arterioles. It was shown that when the arterial pressure was changed: (1) arteriolar vasodilation or constriction appeared during pulsatile flow but it disappeared during non-pulsatile flow, and (2) the arteriolar red cell velocity increased or decreased linearly during non-pulsatile flow as well as pulsatile flow. The flow-rate was almost constant at a large range of the mean arterial pressure from 60 to 160 mmHg during pulsatile flow (autoregulation), but it increased or decreased during non-pulsatile flow with an increase or decrease in mean arterial pressure, respectively. It was suggested that pulsativity might be responsible for cerebral autoregulation.     

上腔静脉逆行灌注救治体外循环期间动脉大量气栓(附7例报告)

本文报告７例心脏直视手术体外循环期间动脉大量气栓,经上腔静脉逆行灌注等抢救,４例存活。随防１～６年,３例无永久性中枢神经系统损害。采用的逆灌压力４．０～８．０ｋＰａ,略高于以往文献报道。作者认为：上腔静脉逆行灌注能排除脑血管内气体,再经右心房逆行灌注可排除冠状血管内气体。这对解除或减轻中枢神经系统和心肌损伤、防止严重低心排综合征的发生、增加心脑复苏机会十分重要。应在气栓发生后即刻采用。高压氧可促进脑气栓吸收,增加脑组织氧供,改善脑损伤后遗症。应在病人循环功能稳定后及早进行。     

Pressure-flow characteristics of the coronary collateral circulation during cardiopulmonary bypass. Effects of ventricualr fibrillation

Even though ventricular fibrillation is used frequently during cardiopulmonary bypass (CPB), the effects of fibrillation on myocardial regions supplied by collateral vessels have not been determined. To study these effects, nine dogs with left ventricles (ameroid model) consisting of a region of myocardium supplied by collateral vessels (CR) and a region supplied by normal coronary arteries (NR) were subjected to normothermic CPB at two perfusion pressures. In both the empty beating heart (EBH) and empty fibrillating heart (EFH) regional myocardial flow was determined by tracer microspheres. Retrograde coronary pressure was measured via cannulation of the circumflex artery distal to the ameroid induced occlusion. When perfusion pressure was maintained at 80 mm Hg, retrograde coronary pressure was similar in the EBH (46 +/- 4 mm Hg) and in the EFH (48 +/- 3 mm Hg). During fibrillation subendocardial flow in the CR was unchanged, while flow in the NR increased (P less than 0.02). In addition, the endo/epi was greater in the NR than in the CR (P less than 0.01), a difference which did not exist in the EBH. The flow response to fibrillation in the CR could be produced in the NR by reducing the perfusion pressure to 50 mm Hg. These data suggest that during CPB, fibrillation exaggerates existing subendocardial perfusion deficits in collateral regions and the impaired flow response appears to be related to a low regional intravascular pressure.     

Stanford A型主动脉夹层手术中的体外循环管理

目的:总结我院165例Stanford A型主动脉夹层手术体外循环管理经验。方法:收集165例Stan-ford A型主动脉夹层患者,实施Wheat、David、Bentall及全弓置换和支架象鼻术等术式。根据术式分别采用常规中低温体外循环,深低温停循环(DHCA)加选择性顺行性脑灌注(SACP)等体外循环灌注方法。其中,主动脉全弓置换术均行右锁骨下动脉与右心房插管建立体外循环,在DHCA加SACP下完成主动脉远端支架植入及弓部血管吻合,期间脑灌注流量5～10ml.kg-1.min-1。术中采用单泵双管及单侧选择性脑灌注、α+pH稳态和高氧血气管理及超滤等技术。结果:体外循环转流时间(197.3±28.3)min、深低温停循环时间(25.3±3.8)min、SACP时间(45.2±7.7)min、心肌阻断时间(86.1±10.8)min。重症监护室时间72～516(181.31)h。院内死亡17例(死亡率11.25%),余134例均痊愈出院,出院时心功能NYHAⅠ～Ⅱ级。结论:正确选择体外循环方法及良好的体外循环管理是Stanford A型主动脉夹层手术成功的保障。主动脉全弓替换术中采用单泵双管及单侧选择性脑灌注、α+pH稳态和高氧血气管理及超滤等技术切实可行,临床预后满意。     

Thermodiffusion for continuous quantification of hepatic microcirculation--validation and potential in liver transplantation.

Hepatic microcirculation is a main determinant of reperfusion injury and graft quality in liver transplantation. Methods available for the quantification of hepatic microcirculation are indirect, are invasive, or preclude postoperative application. The aim of this study was the validation of thermodiffusion in a new modification allowing long-term use in the clinical setting. In six pigs Doppler flowmeters were positioned around the hepatic artery and portal vein for the measurement of total liver blood flow. Liver perfusion was quantified by thermodiffusion and compared to H(2) clearance as an established technique under baseline conditions, during different degrees of portal venous obstruction and during occlusion of the hepatic artery. Thermodiffusion measurements were recorded for five days postoperatively followed by histological evaluation of the hepatic puncture site. Perfusion data obtained by thermodiffusion were significantly correlated to H(2) clearance (r = 0.94, P < 0. 001) and to liver blood flow (r = 0.9, P < 0.05). The agreement between thermodiffusion and H(2) clearance was excellent (mean difference -2.1 ml/100 g/min; limits of agreement -12.5 and 8.3 ml/100 g/min). Occlusion of the portal vein or hepatic artery was immediately detected by thermodiffusion, indicating a decrease of perfusion by 64 +/- 7% or 27 +/- 5% of baseline, respectively. Perfusion values at baseline and during vascular occlusion were reproducible during the entire observation period. Histological changes of the liver tissue adjacent to the thermodiffusion probes were minute and did not influence long-term measurements. In vivo validation proved that enhanced thermodiffusion is a minimally invasive technique for the continuous, real-time quantification of hepatic microcirculation. Changes in liver perfusion can be safely detected over several days postoperatively. The implication for liver transplantation has led to the clinical application of thermodiffusion.     

Non-invasive monitoring of brain oxygen metabolism during cardiopulmonary bypass by near-infrared spectrophotometry

A new portable high performance apparatus for near-infrared (NIR) laser spectrophotometry was developed to monitor the oxygenation state of the human brain. Three different wavelengths of the NIR laser beam were used, 780, 805 and 830 nm, to illuminate the head through a fiber optic bundle. The amount of light reflected by or transmitted from the tissue was detected by a photomultiplier or photodiode. Equations as explained here, were used to calculate the oxy and deoxy Hb content and blood volume changes non-invasively. The equations were verified in vivo with the rat head in order to confirm the reliability and acceptability of our methodology. NIR monitoring was applied to 15 cases of cardiopulmonary bypass (CPB) in reflectance mode. The results demonstrated that using current CPB technique, cerebral oxygenation levels during bypass were maintained within the physiological range and changes in brain blood volume corresponded well to the pump flow balance. That is, the brain oxygenation level was maintained roughly constant at a mean perfusion pressure of over 60 mmHg during CPB, whereas below 50 mmHg, apparent decremental changes in oxy Hb content were observed. These findings led us to conclude that non-invasive monitoring of cerebral oxygenation using NIR light can provide valuable bedside data about tissue metabolism and allow for the proper management of critical patients.     

37例心脏移植的体外循环管理经验

目的:总结37例原位心脏移植体外循环管理经验。方法:37名患者进行了同种异体心脏移植手术,术前心脏超声检查EF值平均(24.52±4.79)%;采用中度低温、轻中度血液稀释、中高流量体外循环灌注。术中监测血气和电解质,常规使用超滤技术和白蛋白。供心保护采用HTK心肌保护液,经主动脉根部灌注冷HTK心脏停搏液,快速取下心脏,并放置于冷HTK液中低温保存。结果:供心热缺血时间(7.7±1.7)min,冷缺血时间(194.52±121.57)min,体外循环时间(110.87±29.83)min。主动脉阻断时间为(47.83±8.91)min,平均动脉压55～85mmHg。37例患者均顺利脱离体外循环机。结论:良好的供心保护,体外循环过程中保持平均动脉压在60～80mmHg及晶胶比在0.45～0.60,血气和电解质的动态监测以及超滤和白蛋白的应用是心脏移植体外循环管理的关键。     

Reduction of platelet thrombi and emboli by L-arginine during cardiopulmonary bypass in a pig model

We wanted to test the hypothesis that NO generation by L-arginine (LA) infusion will be beneficial in increasing blood flow to all organs to counteract the process of global ischemia during cardiopulmonary bypass (CPB) and to reduce platelet emboli by platelet inhibition. The effect of LA infusion on NO formation, vasodilation, and reduction of thromboembolic burden in organs and tissues after CPB was quantified with In-111-labeled autologous platelets in two major groups: 180 minutes CPB (CPB) and 90 minutes CPB plus 90 minutes reperfusion (RP). Platelets labeled with In-111 tropolone (650–780 Ci) were administered 24 hours before CPB and LA infusion (bolus, 10 mg/kg and infusion at 2 mg/kg/min, 21 pigs for 180 minutes CPB) in 8 groups of 30 Yorkshire pigs (30–35 kg, 6 pigs; LA 2 mg/kg/min, 3 pigs; sham-thoracotomy control, 6 pigs; unoperated control, 6 pigs). Two groups of 9 pigs (control CPB, 6 pigs; LA 2 mg/ kg/min, 3 pigs) underwent 90 minutes of CPB and 90 minutes of reperfusion. All pigs were heparinized (ACT >400 seconds); CPB was instituted with a roller pump, an oxygenator (OX: Bentley Univox, 1.8 m²), and an arterial filter (AF: 0.25 m², Bentley) at a blood flow of 2.5–3.5 1/min. Radioactive thrombi in OX and AF and emboli in viscera, brain, and connective tissues were imaged with a gamma camera and were finally measured with an ion chamber and a gamma counter. The percent of injected platelets (mean ± SD) in the organs and tissues of all pigs was calculated. Cerebral emboli were mapped in 25 regions of both hemispheres of pig brain. Flow cytometry with antibodies to CD61 (GPIIIa) and CD62P (GMP-140: control) of porcine platelets was carried out with blood samples taken before, during, and after CPB. Coronary bypass with LA infusion decreased the amount of adherent thrombi in OX and AF (p < 0.07). The embolic burden in brain and lung also decreased. Regional cerebral mapping of In-111 platelets showed reduced emboli in almost all regions, including the medulla, hippocampus, and posterior cerebral cortex in both LA-treated groups. Flow cytometry of blood samples demonstrated the shift of equilibria from single platelet to platelet-aggregate-microparticle during CPB and steady-state level after the first 5–10 minutes of initiation of CPB. The L-arginine infusion reduced thrombi and emboli during CPB in the pig model.     

Organ blood flow and somatosensory-evoked potentials during and after cardiopulmonary resuscitation with epinephrine or phenylephrine

Pure alpha-adrenergic agonists, such as phenylephrine, and mixed alpha- and beta-adrenergic agonists, such as epinephrine, raise perfusion pressure for heart and brain during cardiopulmonary resuscitation (CPR). However, with the high doses used during CPR, these drugs may directly affect vascular smooth muscle and metabolism in brain and heart. We determined whether at equivalent perfusion pressure, continuous infusion of phenylephrine (20 micrograms/kg/min) or epinephrine (4 micrograms/kg/min) leads to equal organ blood flow, cerebral O2 uptake, and cerebral electrophysiologic function. During 20 minutes of CPR initiated immediately upon ventricular fibrillation in anesthetized dogs, left ventricular blood flow was similar with epinephrine (45 +/- 9 ml/min/100 g) or phenylephrine (47 +/- 8 ml/min/100 g) infusion. The ratio of subendocardial to subepicardial blood flow fell equivalently during CPR with either epinephrine (1.23 +/- 0.06 to 0.70 +/- 0.05) or phenylephrine (1.32 +/- 0.07 to 0.77 +/- 0.05) administration. At similar levels of cerebral perfusion pressure (44 +/- 3 mm Hg), similar levels of cerebral blood flow were measured in both groups (27 +/- 3 ml/min/100 g). Cerebral O2 uptake was maintained at prearrest levels in both groups. Somatosensory-evoked potential amplitude was modestly reduced during CPR, but it promptly recovered after defibrillation. During CPR and at 2 hours after resuscitation, there were no differences between drug groups in the level of regional cerebral or coronary blood flow, cerebral O2 uptake, or evoked potentials. Therefore, with minimal delay in the onset of CPR and with equipotent pressor doses of phenylephrine and epinephrine, we found no evidence that one agent provides superior coronary or cerebral blood flow or that epinephrine by virtue of its beta-adrenergic properties adversely stimulates cerebral metabolism at a critical time that would impair brain electrophysiologic function. Moreover, epinephrine did not preferentially impair subendocardial blood flow as might be expected if it enhanced the strength of fibrillatory contractions.     

Pharmacology and biological efficacy of a recombinant, humanized, single-chain antibody C5 complement inhibitor in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response that causes substantial clinical morbidity. Activation of complement during CPB contributes significantly to this inflammatory process. We examined the capability of a novel therapeutic complement inhibitor to prevent pathological complement activation and tissue injury in patients undergoing CPB. METHODS AND RESULTS: A humanized, recombinant, single-chain antibody specific for human C5, h5G1.1-scFv, was intravenously administered in 1 of 4 doses ranging from 0.2 to 2.0 mg/kg before CPB. h5G1.1-scFv was found to be safe and well tolerated. Pharmacokinetic analysis revealed a sustained half-life from 7.0 to 14.5 hours. Pharmacodynamic analysis demonstrated significant dose-dependent inhibition of complement hemolytic activity for up to 14 hours at 2 mg/kg. The generation of proinflammatory complement byproducts (sC5b-9) was effectively inhibited in a dose-dependent fashion. Leukocyte activation, as measured by surface expression of CD11b, was reduced (P<0.05) in patients who received 1 and 2 mg/kg. There was a 40% reduction in myocardial injury (creatine kinase-MB release, P=0.05) in patients who received 2 mg/kg. Sequential Mini-Mental State Examinations (MMSE) demonstrated an 80% reduction in new cognitive deficits (P<0.05) in patients treated with 2 mg/kg. Finally, there was a 1-U reduction in postoperative blood loss (P<0. 05) in patients who received 1 or 2 mg/kg. CONCLUSIONS: A single-chain antibody specific for human C5 is a safe and effective inhibitor of pathological complement activation in patients undergoing CPB. In addition to significantly reducing sC5b-9 formation and leukocyte CD11b expression, C5 inhibition significantly attenuates postoperative myocardial injury, cognitive deficits, and blood loss. These data suggest that C5 inhibition may represent a novel therapeutic strategy for preventing complement-mediated inflammation and tissue injury.     

长时间阻断主动脉的心肌保护与辅助循环脱机指征

长时间的心肌缺血是影响心肌保护的重要因素，也是不能脱离体外循环的常见原因之一。本文报告了４１例长时间阻断主动脉的心肌保护方法与辅助循环脱机指征，其中主动脉阻断时间（ＡＣＣＴ）＞１２０分３２例，ＡＣＣＴ＞１８０分９例；主动脉根部间断顺行灌注停搏液１４例；顺行灌注联合间断逆行灌注含血停搏液２０例；顺行灌注联合持续逆行灌注７例；主动脉开放前控制性热血再灌注１４例；结果显示：顺行灌注联合持续逆行灌注对心肌保护效果最佳，它可使主动脉阻断的安全时限达４小时左右。本文还就辅助循环方法与脱机指征进行讨论。作者主张根据左房压和平均动脉压的动态变化，调解辅助循环流量是脱机的可靠方法。