Prevention of Remote Organ Injury in Cardiopulmonary Bypass: The Impact of Flow Generation Technique

Abstract: The purpose of this study was to investigate the effects of 3 different types of flow generation for cardiopulmonary bypass on gastrointestinal permeability and on neutrophil expression of CD11b, a surface marker of neutrophil activation. Fourteen patients undergoing elective coronary revascularization were selected randomly to receive 1 of the 3 flow generation techniques (roller, pulsatile, or centrifugal). Intestinal permeability was assessed by the fraction of an oral dose of ⁵¹chromium-ethylenedi-aminetetraacetate (⁵¹Cr-EDTA) recovered in the urine over 24 h. Neutrophil activation was determined by expression of CD11b markers at 6 time points. Overall, the 14 patients showed significant increases in intestinal permeability. It was not possible to demonstrate statistically significant differences among the flow generation groups: however, when compared to both roller pump groups, the centrifugal pump group showed a 3.2% reduction in intestinal permeability. There was no change in the expression of CD11b receptors throughout the time points, nor was there a relationship of CD11b markers to the flow generation technique.     

The Renin-Angiotensin-Aldosterone System and Hematologic Changes During Pulsatile and Nonpulsatile Cardiopulmonary Bypass

Abstract: The effects of pulsatile and nonpulsatile cardiopulmonary bypass using a roller pump on levels of vasoactive hormones and hematologic changes were studied in 32 patients subjected to elective primary coronary artery bypass graft surgery. Seventeen patients had nonpulsatile perfusion (nonpulsatile group) and 15 patients had pulsatile perfusion (pulsatile group) during the period of cardiac arrest. Vasoactive hormones (plasma renin, angiotensin II, aldosterone, epinephrine, and norepinephrine) were measured in these patients. In order to clarify hematologic changes, plasma free hemoglobin, number of platelets, platelet factor 4, and β -thromboglobulin were measured. There were no significant differences between the pulsatile and nonpulsatile groups with regard to vasoactive hormones and damage of platelets. In the pulsatile group, however, the rise of plasma free hemoglobin levels was significantly higher than that in the nonpulsatile group during and after cardiopulmonary bypass. We did not see the benefit of pulsatile perfusion using a roller pump on vasoactive hormones. Evidence of increased hemolysis with pulsatile flow was demonstrated in our cases.     

Pulse Conductance and Flow‐induced Hemolysis During Pulsatile Cardiopulmonary Bypass

In this study, the hypothesis was tested that a low‐resistant, high‐compliant oxygenator provides better pulse conductance and less hemolysis than a high‐resistant, low‐compliant oxygenator during pulsatile cardiopulmonary bypass. Forty adults undergoing coronary artery bypass surgery were randomly divided into two groups using either an oxygenator with a relatively low hydraulic resistance (Quadrox BE‐HMO 2000, Maquet Cardiopulmonary AG, Hirrlingen, Germany) or with a relatively high hydraulic resistance (Capiox SX18, Terumo Cardiovascular Systems, Tokyo, Japan). The phase shift between the flow signals measured at the inlet and outlet of the oxygenator was used to assess compliance. Pulse conductance in terms of pressure attenuation was calculated by dividing the outlet pulse pressure of the oxygenator by the inlet pulse pressure. A normalized index was used to assess hemolysis. The phase shifts in time of the flow pulses were 36 ± 6 ms in the low‐resistant (high‐compliant) oxygenator, and 14 ± 2 ms in the high‐resistant (low‐compliant) oxygenator group (P < 0.001). The low‐resistant, high‐compliant oxygenator provided 27% better pulse conductance compared with the high‐resistant, low‐compliant oxygenator (0.84 ± 0.02 and 0.66 ± 0.01, respectively, P < 0.001). Inlet pulse pressures were significantly higher (29%) in the high‐resistant, low‐compliant (Capiox) group than in the low‐resistant, high‐compliant (Quadrox) group (838 ± 38 mm Hg and 648 ± 25 mm Hg respectively, P < 0.001), but no significant difference in hemolysis was found. A low‐resistant, high‐compliant oxygenator provides better pulse conduction than a high‐resistant, low‐compliant oxygenator. However, the study data could not confirm the association of high pressures with increased hemolysis.     

体外循环中搏动和非搏动灌注对皮肤微循环自律运动的影响

关于体外循环期间应用搏动灌注的优点，一直有很大的争议。本实验旨在观察体外循环中搏动灌注和非搏动灌注对皮肤微循环自律运动和氧代谢的影响。观察对象是１５例心脏瓣膜病人。当病人温度平稳时，分别以２．４Ｌ·ｍｉｎ~（－１）／ｍ~２的流量进行搏动灌注和非搏动灌注。搏动灌注的参数为：基线３０％～４０％、脉宽４０％～５０％、脉冲频率６０次／ｍｉｎ。结果表明：搏动灌注和非搏动灌注对皮肤微循环血流量、微循环自律性运动频率、氧代谢的影响不明显。我们对这一现象进行了分析。并认为搏动灌注在临床应用中，由于多种因素的影响，其优越性难以体现。     

Cytokine and Endothelial Damage in Pulsatile and Nonpulsatile Cardiopulmonary Bypass

Recently, several types of centrifugal pumps have been widely used as the main pumps for cardiopulmonary bypass (CPB). However, according to the results of our experimental studies, after cardiogenic shock, pulsatile flow was effective in maintaining the functions and microcirculations of end organs, especially those of the liver and kidney. To estimate the effectiveness of pulsatility during CPB, cytokine and endothelin and other metabolic parameters were measured in clinical pulsatile and nonpulsatile CPB cases. From March to May 1997, CPB was performed in 18 elective cases (14 ischemic and 4 valvular disease). In 9 cases, pulsatile perfusion was achieved by the Jostra HL20, which is a newly developed CPB pump (Group P). A nonpulsatile centrifugal pump was used in 9 patients (Group NP). In both groups, as chemical and metabolic mediators, interleukin-8 (IL-8), endothelin-1 (ET-1), and plasma free hemoglobin were measured before and during CPB, and 0.5, 3, 6, 9, 18 h after weaning from CPB. This pulsatile CPB pump could be very simply and easily controlled and could easily produce pulsatile flow. There were no significant differences in CPB time (CPBT), aortic cross clamp time (ACCT), mean aortic pressure, or pump flow during CPB between the both groups. The ET-1 level of Group P was significantly (p < 0.05) lower than that of Group NP 9 h after CPB weaning. The IL-8 level of Group P also showed a lower value than that of Group NP. As for plasma free hemoglobin, there were no significant differences between the groups. These results suggested that even in conventional CPB, pulsatility was effective to reduce endothelial damage and suppress cytokine activation. It may play a important role in maintaining the functions and microcirculations of end organs during CPB.     

Plasma Vasopressin Levels and Urinary Sodium Excretion during Cardiopulmonary Bypass with and without Pulsatile Flow

The use of pulsatile perfusion during bypass should create a more physiological milieu and thus attenuate the vasopressin stress response. To determine this, 20 patients scheduled for elective coronary artery bypass operation were studied in two groups. Group 1 had standard nonpulsatile perfusion, and in Group 2 a pulsatile pump was used. Measurements were made before and after anesthesia, after surgical incision, and at 15 and 30 minutes during and after cardiopulmonary bypass.In both groups, vasopressin levels were significantly elevated after sternotomy (4.5 ± 1.5 to 37 ± 10 pg/ml in Group 1 and 3.1 ± 1.2 to 33 ± 9 pg/ml in Group 2, p < 0.05) and during bypass (198 ± 19 pg/ml in Group 1 and 113 ± 16 pg/ml in Group 2) but were higher in Group 1 (p < 0.05). With comparable perfusion pressures in both groups, Group 2 required higher flow (4.5 ± 0.2 versus 3.5 ± 0.3 L/min, p < 0.05) and had lower resistance (1,351 ± 182 versus 1,841 ± 229 dynes sec cm^-5, p < 0.05) and higher urine Na⁺ (123 ± 5 versus 101 ± 8 mEq/L, p < 0.05). These data demonstrate that pulsatile flow can significantly attenuate the vasopressin stress response to bypass. Since vasopressin, at these concentrations, is a potent vasoconstrictor and is capable of producing a Na⁺ diuresis, this may partially explain the higher flow requirements and the decrease in Na⁺ excretion.     

Pulsatile Versus Nonpulsatile Flow: No Difference in Cerebral Blood Flow or Metabolism during Normothermic Cardiopulmonary Bypass in Rabbits

Background: Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees Celsius.

Methods: In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees Celsius for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees Celsius. At 30 and 60 min of CPB, physiologic measurements were made as before.

Results: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 plus/minus 6 vs. 77 plus/minus 9 ml *symbol* 100 g sup -1 *symbol* min1, respectively (median plus/minus quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 plus/minus 0.5 vs. 4.1 plus/minus 0.6 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min1, respectively) and decreased slightly (0.4 plus/minus 0.4 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min1) between measurements.     

Determination of Pump Flow Rate During Cardiopulmonary Bypass in Obese Patients Avoiding Hemodilution

Abstract   Background and Aim: During cardiopulmonary bypass the pump flow is usually set on 2.4 L/min/m² of body surface area (BSA) to guarantee adequate tissue perfusion without differences for patient constitutional type. The present study attempts to evaluate the adequacy of pump flow rate in obese patients, considering the ideal weight instead of the real one, avoiding the overflow side effects and hemodilution. Methods: Obese patients with body mass index (BMI) > 30 presented for cardiac surgery were randomized in two groups: in one the cardiopulmonary bypass was led traditionally, in the other, pump flow rate was calculated on ideal BMI of 25. Results: Demographics, preoperative tests, and monitoring data were registered. Mortality at hospital discharge and 30 days after were analyzed. The pump flow rate between the groups was different (4.46 vs. 4.87; p = 0.004); there were no differences in organ perfusion (SvO₂; diuresis) and mortality, but the study group presented fewer complications and blood transfusions. Conclusions: The BSA is widely used as the biometric unit to normalize physiologic parameters included pump flow rate, but it is disputable if this practice is correct also in obese patients. The study group, in which pump flow rate was set on ideal BSA, presented no difference in diuresis and mixed venous saturation but fewer complications and fewer perioperative blood transfusions.     

Effect of Synchronous and Asynchronous Pulsatile Flow During Left, Right, and Biventricular Bypass

Ventricular assist devices augment flow from the left atrium to the aorta and/or from the right atrium to the pulmonary artery. Most devices are used in the asynchronous full-to-empty mode (asynchronous) but may also be used in a synchronous counterpulsation mode (synchronous). This study determines the optimal assist modes to reduce myocardial oxygen consumption (MVO2) and metabolism. Twelve pigs were instrumented with carotid artery and Baim coronary sinus catheters for determination of MVO2 and myocardial lactate production (LACT). Six were implanted with a Pierce-Donachy left ventricular assist device (LVAD) and 6 with both right and left ventricular assist devices (BIVAD). Two periods each of control, synchronous, and asynchronous bypass were instituted, the midanterior descending coronary artery (LAD) was ligated, and the sequence was repeated. After each period, MVO2 and LACT were determined and myocardial biopsy specimens were obtained for tissue, lactate, and ATP assay. Following LAD ligation, biopsy specimens were obtained from both the infarct and noninfarct zones of the heart. MVO2 decreased (p < 0.05) in the asynchronous BIVAD mode compared with control. MVO2 was unchanged in synchronous BIVAD or either LVAD mode. Tissue ATP and tissue lactate were unaffected by any mode of bypass. Only BIVAD in the asynchronous mode reduced MVO2. When ventricular assist devices are utilized to aid recovery of the natural heart, two devices should always be inserted to allow biventricular assist. Synchronous counterpulsation offers no advantage.     

幼猪深低温体外循环最适区域性脑灌注流量的实验研究

目的探索幼猪在深低温体外循环中的最适区域性脑灌注（RCP）流量,为先天性心脏病（先心病）小儿患者术中脑保护策略提供理论基础。方法20只健康幼猪,年龄23．7±2．1d,体重6．4±0．6kg,采用随机数字表法分为4组,每组各5例。对照组为单纯深低温停循环（DHCA组）;实验组按不同RCP流量分为3组：RCP25组,流量为25．9±3．0ml（kg·min）;RCP50组,流量为49．7士1．8ml／（kg·rain）;RCP80组,流量为79．5±0．9ml／（kg·min）;通过检测血浆中建立CPB前（T1）、DHCA或RCP前（T2）、RCP结束后10min（T3）、停机前（T4）、CPB结束后1h（Ts）以及2h（T5）6个时间点检测血浆中的S-100β蛋白、神经元特异性烯醇化酶（NSE）的浓度、脑氧摄取率（CEOz）及大脑皮质半胱天冬氨酸酶3（caspase3）的含量,评估不同RCP流量的脑保护效果。结果各组幼猪血浆中S-100β蛋白和NSE的浓度于T4时明显升高,并于T5时达到高峰（P〈0．05）;RCP50组血浆中S-100β蛋白和NSE的浓度从T4时开始明显低于DHCA组和RCP80组（P〈O．05）,与RCP2。组相比,其差异无统计学意义（P〉0．05）。各组CEO2在T1时差异无统计学意义（P〉0．05）,在T2时明显降低（P％0．05）。DHCA组、RCPzs组和RCP50组的CEO2在T3时开始升高,RCP20组在T3时稍微下降,但其差异无统计学意义（P〉0．05）;从T4开始,RCP25组和RCPj。组的CEO。与DHcA组和RCP80组更接近于基础值（T1）（P〈0．05）。大脑皮质中caspase3的含量在3种不同流量的RCP组明显低于DHCA组（F=23．54,P〈0．01）,其中RCP25组及RCP5。组明显低于RCP80组（F=23．54,P〈0．01）,而RCP2s组与RCP50组的caspase3含量差异无统计学意义（P〉0．05）。结论在我们建立的幼猪深低温体外循环模型中,RCP最适灌注流量为25～50ml／（kg·rain）,并且趋向于50ml／（kg·rain）。     

体外循环期间血浆D-二聚体的变化

观察心内直视手术病人体外循环（ＣＰＢ）前后血浆Ｄ－二聚体（Ｄ－Ｄ）的变化，了解其临床意义，应用国产单克隆抗体、ＥＬＩＳＡ法对４５例ＣＰＢ病人分别在全身肝素化后、转流８分钟和转流结束１０分钟时检测Ｄ－Ｄ、ＨＣＴ、ＡＣＴ。结果：ＣＰＢ中和ＣＰＢ后Ｄ－Ｄ明显升高，显示继发性纤溶活性增强，并与转流时间成正比（Ｐ＜０．０１），故应尽可能缩短ＣＰＢ时间。Ｄ－Ｄ检测可做为ＣＰＢ导致的ＤＩＣ与术后外科性出血的鉴别诊断方法之一。     

体外循环中血浆内皮素的变化

观察体外循环心内直视手术病人不同时间（术前１天、术中不同时点，术后１、３、７天）血浆内皮素水平。结果表明，体外循环开始后血浆内皮素持续升高至术前２倍，直至体外循环结束。提示内皮素是心脏手术病人一个新的加压指标，术中选用保护剂可能有益。     

Biocompatibility of Heparin-Coated Membrane Oxygenator During Cardiopulmonary Bypass

Abstract: The biocompatibility of the cardiopulmonary bypass (CPB) circuit, in which an oxygenator is solely heparinized, was assessed by systemic inflammatory reactions as an indicator during CPB. Fourteen patients, 11 males and 3 females, underwent coronary artery bypass surgery and were randomly divided into 2 groups of 7 patients each. For the heparin–coated oxygenator group (Group H), a heparin–coated membrane oxygenator was used in the CPB circuit, and in the control (Group C) an uncoated membrane oxygenator was employed. Systemic inflammatory reactions, such as platelet activation, prostaglandin production, complement activation, and activated granulocyte released substance, were measured prior to, during, and 6 h after CPB. The number of platelets decreased after protamine administration in both groups (14. 5 ±4. 7 times 10⁴/μl in Group H and 13. 8 ± 8. 7 times 10⁴/μd in Group C) and returned to baseline levels in Group H while it remained decreased in Group C at 6 h after CPB. The platelet factor 4 level was significantly lower in Group H (181 ± 40 ng/ml) than in Group C (297 ±131 ng/ml) after protamine administration. Thromboxane–B₂ (TXB₂) rose during CPB in both groups; however, there were significantly different levels of TXB₂ between the 2 groups at 60 min after CPB (293±258 pg/ml in Group H versus 408 ± 120 pg/ml in Group C) and after protamine administration (259 ± 122 pg/ml in Group H versus 709 ± 418 pg/ml in Group C). Plasma concentrations of granulocyte elastase were significantly lower in Group H at 30, 60 and 90 min, immediately after, and post–CPB than those of Group C. Although the oxygenator was solely heparinized in the CPB circuit, it was sufficiently effective to reduce inflammatory reactions during coronary artery bypass operation, and the heparin–coated surface seems to be more endothelium–like.     

白细胞滤器在体外循环中的应用进展

白细胞激活、黏附、释放是导致体外循环(CPB)后发生各种并发症的重要原因之一,因此使用白细胞滤器能减少心、肺、脑等器官功能障碍。而目前使用的白细胞滤器的设计和滤膜的生物相容性等仍存在一些问题尚待改进。由于CPB后白细胞对机体的损伤起主导作用,因此,白细胞滤器研究成熟后可成为预防、治疗CPB导致的非感染性炎性反应的重要方法,而广泛应用于临床。