Protective effect of sivelestat sodium (Eraspol) on postoperative lung dysfunction in patients with type A acute aortic dissection: a pilot study

AIM: The authors evaluated the protective effect of sivelestat sodium on postoperative lung dysfunction in patients with type A acute aortic dissection who underwent aortic arch surgery with cardiopulmonary bypass (CPB) under deep hypothermia with circulatory arrest (DHCA). METHODS: Twelve patients with type A acute aortic dissection who underwent aortic arch replacement under CPB with DHCA and were pretreated with or without sivelestat sodium (sivelestat group, N.=7 patients; control group, N.=5 patients) were observed. The ratio of arterial oxygen tension to inspired oxygen fraction (P/F ratio) was measured as a parameter of pulmonary function before and after operation. The number of white blood cells was also counted as an index of inflammatory reaction before and after the operation. RESULTS: The P/F ratio decreased significantly after operation in the control group. However, the P/F ratio was unchanged between before and after operation in the sivelestat group. The number of white blood cells tended to increase after operation in the control group, whereas it decreased significantly after operation in the sivelestat group. CONCLUSION: The present study demonstrated the protective effect of sivelestat sodium on postoperative lung injury in patients with acute type A aortic dissection undergoing aortic arch surgery under CPB with DHCA.     

The amylase-creatinine clearance ratio following cardiopulmonary bypass

The incidence of unexplained pancreatitis in patients dying after cardiac operations has been recorded as 16%, with evidence to implicate ischemia in the pathogenesis of the pancreatitis. Increased amylase--to--creatinine clearance ratios (ACCR), suggesting pancreatic dysfunction, have been reported in patients following nonpulsatile cardiopulmonary bypass (CPB). Pulsatile CPB is increasingly recognized to be a more physiological form of perfusion, particularly with respect to capillary blood flow. In this study the ACCR has been determined before, during, and after cardiac operations performed with both nonpulsatile and pulsatile CPB. Twenty patients undergoing elective cardiac operations were studied. Ten patients had nonpulsatile CPB (nonpulsatile group) and 10 had pulsatile CPB (pulsatile group). The two groups were comparable as regards perioperative variables and perfusion parameters. In both groups the ACCR was estimated preoperatively, on three occasions during the operation, and daily on the first 5 postoperative days. A significant elevation in ACCR was observed in nine of 10 patients in the nonpulsatile group but in only one of 10 patients in the pulsatile group (p less than 0.001). The significant improvement of ACCR stability following pulsatile CPB may indicate that this form of perfusion will reduce the risk of pancreatitis following cardiac operations performed with CPB.     

Clinical benefits of normothermic cardiopulmonary bypass on postoperative systemic metabolism

To evaluate the influence of body temperature during cardiopulmonary bypass (CPB) on postoperative systemic metabolism, 32 patients undergoing elective cardiac surgery were randomly assigned to either hypothermia (n = 16) or normothermia (n=16). Serial hemodynamic parameters and blood samples were obtained after surgery. CPB and operation times were significantly shorter and the platelet reduction ratio during CPB [= (platelets before CPB-platelets after CPB)/platelets before CPB] was significantly lower in normothermic patients than in hypothermic patients. The platelet reduction ratio was dependent on the minimum rectal temperature during CPB, the operation time, and the CPB time. In the early postoperative period, hypothermic patients had abnormally high systemic vascular resistance and a reduced cardiac index compared with the normothermic patients. There were no differences between 2 groups in postoperative hepatic and renal functions, changes in oxygen consumption, arterial-venous PCO₂ or arterial-venous pH gradient. This study suggested a beneficial influence of normothermic CPB on postoperative hemodynamics. Normothermic CPB was not associated with adverse effects on postoperative metabolic recovery.     

Effects of operation on immune response in cancer patients: sequential evaluation of in vitro lymphocyte function.

The effect of operation on in vitro lymphocyte function in 35 cancer patients was studied. Lymphocyte proliferative responses to phytohemagglutinin (PHA), poke-weed mitogen (PWM), and concanavalin A (Con A) were measured by 3H-thymidine incorporation. Sheep red blood cell (SRBC) rosette formation also was quantitated. These tests were performed preoperatively and at 24 hours, one week, and 4 weeks postoperatively. Intra-abdominal and intrathoracic procedures, transfusions, and longer operating times depressed the lymphocyte proliferative response. However, an increased lymphocyte proliferative response was noted in sarcoma patients 24 hours postoperatively, possibly as a result of lowered tumor burden. Several of these changes still were evident 4 weeks after operation. Rosette formation also decreased significantly 24 hours postoperatively in patients who had intrathoracic or intra-abdominal procedures, but returned to preoperative levels after one week. In general, operation appears to cause transient depression of lymphocyte function in some cancer patients. However, lymphocyte function returns to normal by the fourth postoperative week in most patients.     

Coronary artery bypass grafting by warm blood cardioplegia and normothermic cardiopulmonary bypass

Warm blood cardioplegia and normothermic cardiopulmonary bypass (CPB) have been used in coronary artery bypass grafting (CABG). The method of myocardial protection was intermittent combined antegrade and retrograde warm blood cardioplegia with terminal warm blood cardioplegia. We performed elective CABG in 30 patients above the age of 70 years (elderly group). These patients were compared with 30 patients below 70 years who underwent elective CABG (young group). No significant differences were observed about the preoperative data between two groups. No significant differences were obtained in the postoperative cardiac function, cerebral or renal complication between two groups. Warm blood cardioplegia and normothermic CPB were not associated with adverse effects on postoperative recovery in elderly as well as young patients. We may conclude that warm blood cardioplegia with normothermic CPB is a safe procedure for CABG in elderly as well as young patients.     

Changes in lymphocyte subsets, mitogen responsiveness, and interleukin-2 production after cardiac operations

We studied 104 patients after cardiac operations to search for changes in peripheral blood lymphocyte subsets, mitogen responsiveness, and interleukin-2 production. Mononuclear cells obtained from 10 patients with cholecystectomy were examined as control samples. Cultures for phytohemagglutinin and interleukin-2 production were incubated in microtiter plates for 24 hours with cells labeled with tritium thymidine used as target cells. Lymphocyte subsets were measured by using monoclonal antibodies. The results obtained with preoperative blood samples were compared with those from the first, third, and seventh days after operation. In patients having cardiac operations, mitogen responsiveness was low on both the first and the seventh days after operation and interleukin-2 production was markedly depressed (greater than 90% depressed) on the first postoperative day. However, in control samples from patients having cholecystectomy, lymphocyte subsets, mitogen responsiveness, and interleukin-2 production showed no significant changes. Improvement in interleukin-2 production occurred immediately in patients without blood transfusion from random donors and reached normal levels by postoperative day 3. However, interleukin-2 production remained depressed on day 3 in all patients with transfusion from random donors and remained significantly diminished even on day 7 in such patients in New York Heart Association classes III and IV. We conclude that heart operations for which cardiopulmonary bypass is used are associated with depression of cellular immunity, including interleukin-2 production. Furthermore, it appears that both blood transfusion from random donors and the general preoperative condition of the patients contribute to suppression of measures of cell-mediated immunity.     

Clinical efficacy of heparin-bonded bypass circuits related to cytokine responses in children

BACKGROUND: Cardiopulmonary bypass (CPB) induces numerous systemic reactions. This study examined the efficacy of heparin-bonded CPB circuits on inflammatory responses and postoperative status in children. METHODS: Thirty-four infants undergoing elective cardiac surgery were randomly divided into two groups: a heparin-bonded CPB group (n = 17) and a non-heparin-bonded group (n = 17). Plasma levels of the inflammatory cytokines were measured before, during, and after CPB, and postoperative status was determined by examining the respiratory index, blood loss, and the post- and preoperative body weight percent ratio. RESULTS: Significant differences in tumor necrosis factor-alpha, interleukin-6, and interleukin-8 patterns were observed during and after CPB between the two groups (p < 0.01, p < 0.01, p < 0.05, respectively). All cytokines measured were significantly lower in the heparin-bonded group just after CPB (p < 0.05). There were no differences in duration of intubation, intensive care unit or hospital stay, or postoperative blood loss, but the respiratory index 3 hours after CPB and body weight percent ratio 24 and 48 hours after CPB were significantly reduced in the bonded group (p < 0.05, p < 0.01, p < 0.05, respectively). CONCLUSIONS: Our findings suggest that heparin bonding of the bypass circuits affects early postoperative status and reduces cytokine responses in pediatric cardiac surgery.     

戊乙奎醚对心肺转流中患者血浆sTM和vWF水平的影响

目的研究戊乙奎醚(长托宁)对心肺转流(CPB)全身性血管内皮细胞(VEC)急性损伤的保护作用。方法30例择期瓣膜置换手术患者随机分为两组,每组15例。观察组术前肌注戊乙奎醚0.02mg/kg和吗啡0.01mg/kg;东莨菪碱组术前肌注东莨菪碱0.3mg和吗啡0.01mg/kg。分别于术前、CPB前、CPB后30min、停CPB、手术结束、术后1d和3d采血测血浆可溶性血栓调节蛋白(sTM)和血管性假血友病因子(vWF)的变化。结果两组血浆sTM和vWF在CPB后30min至术后1d均显著增高(P<0.01),术后3d恢复到术前水平。观察组患者CPB期间至术后3d的所有指标均低于对照组。结论CPB可导致全身性VEC急性损伤,戊乙奎醚可以显著减轻CPB导致的VEC损伤。     

丙泊酚对心肺转流病人血浆血栓调节蛋白和血管性假血友病因子水平的影响

目的 探讨丙泊酚用于心肺转流(CPB)对全身性血管内皮细胞(VEC)急性损伤的保护作用.方法 30例心脏瓣膜置换术病人随机均分为观察组和对照组,CPB过程中分别持续输注丙泊酚、硝酸甘油维持病人血流动力学的稳定.分别于术前、CPB前、CPB 30 min、停CPB、手术结束、术后1、3 d采血动态监测两组病人血浆可溶性血栓调节蛋白(sTM)和血管性假血友病因子(vWF)的变化.结果 两组病人血浆sTM和vWF在CPB期间和术后1 d均显著增高(P＜0.05或P＜0.01).观察组病人CPB期间至术后3d的所有指标均低于对照组(P＜0.05或P(0.01).观察组的指标术后3 d恢复到术前水平.对照组未能恢复.结论 CPB可导致全身性VEC的急性损伤,丙泊酚可以减轻CPB导致的VEC损伤.     

急性血小板分离回输对体外循环心脏直视手术患者的血液保护效果

目的 评价急性血小板(Plt)分离回输对体外循环(CPB)心脏直视手术患者的血液保护效果.方法 择期拟在CPB下行心脏直视手术患者30例,ASA分级Ⅱ或Ⅲ级,年龄41～63岁,体重52～72 kg.采用随机数字表法,将患者随机分为2组(n=15):对照组(C组)和急性Plt分离组(APP组).APP组在麻醉诱导后行APP,提取富Plt血浆,于CPB结束鱼精蛋白中和肝索后回输,C组不行APP.于麻醉诱导前、术后1、24和48h时记录Hb、Plt、PT、APTT及Fib.记录CPB时间、主动脉阻断时间、术后引流量和输血情况.结果 APP组急性Plt分离处理的全血容量为(1285±185) ml,采集富Plt血浆(192±38) ml,其中Plt计数(817±282)×10/L,占全身血容量Plt总数(21±3)％,Plt分离时间(35±10) min.与C组比较,APP组术后1h时Plt升高,术后24h内引流量、异体红细胞、Plt输注量和异体Ph输注率降低(P＜0.05或0.01),其余指标差异无统计学意义(P＞0.05).结论 急性Plt分离回输对CPB心脏直视手术患者具有血液保护作用.     

Heparin-coated cardiopulmonary bypass circuits reduce blood cell trauma. Experiments in the pig

Blood cell trauma and postoperative bleeding remain important problems in cardiopulmonary bypass (CPB). We compared heparin-coated with non-coated circuits in the pig. Twenty animals were perfused for 2 h at normothermia using membrane oxygenators (Bentley Bos 50). Two groups were studied. In the non-coated group (NC, n = 11) the CPB circuits used were without a heparin coating. This group had systemic heparinization of 400 IU/kg to maintain an ACT (activated clotting time) of over 400 s during CPB. In the coated group (C, n = 9), all surfaces exposed to blood in the CPB circuits were heparin-coated. This group had the heparin dose reduced to 25% (100 IU/kg) without further administration regardless of ACT. During CPB, group C displayed shorter ACT (per definition), higher platelet count, platelet adhesion and lower fibrinolysis and haemolysis (P less than 0.05) as compared to group NC. No thromboembolic events were detected during CPB. Three animals in group NC and 4 animals in group C were weaned from CPB and protaminized. Four hours postoperatively, the leucocyte consumption was two-fold greater and blood loss about four-fold greater in group NC as compared with group C (P less than 0.05). Perfusion with heparin-coated surfaces reduces blood cell trauma. The decreased postoperative blood loss observed in group C is probably explained by the reduced dosages of heparin and protamine.     

Blood concentration of propofol during cardiopulmonary bypass--comparison between arterial and internal jugular venous blood

Twelve adult patients for cardiac surgery were divided into 2 groups, normothermia (6 patients) and mild hypothermia (6 patients), based on their body temperature during cardiopulmonary bypass (CPB). Propofol was continuously administered throughout each operation at a dose of 2 mg.kg-1.h-1. Arterial and internal jugular venous bulb blood samples were drawn simultaneously before CPB, at 5, 30, 60, and 90 minutes after the start of CPB, 30 minutes after the end of CPB, and at the conclusion of the operation, to measure propofol concentrations. In the normothermia group, propofol concentration in the arterial blood decreased significantly 5 minutes after the start of CPB, and then recovered immediately to the pre-CPB value. In the mild hypothermia group, however, no significant change in propofol concentration was observed. In both groups, there was no significant difference in propofol concentration between arterial and internal jugular venous bulb blood throughout the study period. Our results suggest that there are no significant differences between the effect of normothermic and that of mild hypothermic CPB on the pharmacokinetics of propofol in the brain.     

Cardiopulmonary bypass, steroid administration, and surgical injury synergistically impair memory T cell function and antigen presentation

Previous reports showed that cardiac surgery with cardiopulmonary bypass (CPB) impair cell-mediated immunity by using antigen-non-specific responses. This study elucidated the effects of cardiac surgery with CPB on antigen-specific immunity. Twenty patients who underwent elective cardiac surgery using CPB were randomly divided into two groups: group A (n=10) and group B (n=10) with and without steroid administration, respectively. Group C patients underwent off-pump CABG (n=8). Peripheral blood mononuclear cells (PBMCs) were taken before and after surgery. Proliferation responses to pure protein derivative antigen were measured. The effects of CPB and steroid on T cell response and antigen-presentation were assessed by cross-stimulation between the preoperative and the postoperative PBMCs. Antigen-specific T cell responses decreased to about 5% of the preoperative values immediately after surgery with CPB, regardless of steroid administration. The T cell response in group B on POD 7 was significantly higher than that in group A. CPB impaired mainly T cell responses, and steroid administration enhanced impairment of T cell response and antigen-presentation. Open-heart surgery with CPB severely impaired antigen-specific immunity. Steroid administration enhanced the impairment of antigen-presentation as well as T cell function, and retarded the recovery of antigen-specific immunity.     

Triiodothyronine stimulates growth of peripheral blood mononuclear cells in serum-free cultures in uremic patients.

The effect of triiodothyronine (T3) on the responses to mitogens and on the production of prostaglandin E2 and interleukin 2 were studied in serum-free cultures of peripheral blood mononuclear cells (PBMC) in 20 patients undergoing hemodialysis and in 30 control subjects. T3 increased the growth of PMBC induced by phytohemagglutinin and pokeweed mitogen in both groups. PBMC reached growth maximum at 0.5 nM T3 when stimulated by phytohemagglutinin in both groups. At higher concentrations of T3 the effect declined in the control group, but the response of uremic PBMC was constant. The response to T3 of pokeweed mitogen stimulated PBMC was lower in the uremic patients. The production of prostaglandin E2 by PBMC was higher in the uremic patients than in the controls. T3 had no effect on prostaglandin E2 production. Indomethacin alone and in combination with T3 had a stimulatory effect on cell growth in the patient group. T3 had no effect on the release of interleukin 2 by PBMC. An additive effect of interleukin 2 and T3 was observed in cultures stimulated by suboptimal concentrations of the mitogens. In conclusion, the impaired growth of PBMC in serum-free cultures from uremic patients was enhanced, however, not normalized, by external addition of T3, inhibition of prostaglandin E2 synthesis, and addition of interleukin 2.     

非体外循环下冠脉搭桥术的围术期管理

目的：比较非体外循环搭桥术与体外循环搭桥术病人的术中及术后早期恢复情况。方法39例病人接受了非体外循环下冠脉搭桥术,同时期33例病人接受了体外循环冠脉搭桥术。两组均采用中等剂量阿片静脉复合全麻,结果：病人的麻醉时间、手术时间、术后机械通气时间和在监护室的停留时间,非体外循环组明显短于体外循环组（P＜0．01）。围术期平均输血量和血血病人数在1支桥病人中非体外循环组明显少于体外循环组（P＜0．05）。术后房颤发生率和围术期心肌梗死发生率两组间无明显差异,术后脑卒中,低心排及死亡的发生率各组均为0％。结论与外循环搭桥术相比,非体外循环搭桥术缩短了病人的麻醉、手术及在监护室停留时间,加快了病人的恢复、从耐而提高了手术的安全性,并降低了手术费用。     

术前服用阿司匹林对经尿道前列腺切除术出血量的影响

目的：探讨术前服用阿司匹林对经尿道前列腺电切术出血量的影响。方法：回顾分析2002年1月～2008年12月115例行经尿道前列腺切除术的患者。根据术前停服阿司匹林是否≥10天,分为阿司匹林组（31例）和对照组（84例）。使用Mann-Whitney检验比较两组术中和术后出血量、术中每分钟出血量、术中和术后每克切除组织出血量、输血量、膀胱冲洗天数和术后住院天数。结果：两组患者术后出血量、术后每克切除组织出血量、膀胱冲洗天数、术后住院天数均差异有统计学意义（P〈0．05）。两组患者年龄、前列腺体积、切除组织重量和手术时间均差异无统计学意义（P〉0．05）。两组患者术中出血量、术中每克切除组织出血量、术中每分钟出血量和输血量的均差异无统计学意义（P〉O．05）。结论：术前停用阿司匹林〈10天不增加术中出血量、术中每克切除组织出血量、术中每分钟出血量、输血量,增加术后出血量、术后每克切除组织出血量、膀胱冲洗天数和术后住院天数。建议TURP术前至少10天停服阿司匹林。     

The immunomodulating properties of vitamin E in surgery involving artificial circulation

The immunomodulating effect of vitamin E was studied in 21 patients who underwent operation on an open heart. The vitamin was administered in a dose of 40 mg/kg 3.5 hours before the operation for anti-ischemic protection in cardiosurgical operations with extracorporeal circulation. The immune status was evaluated according to the level of phagocytosis, the index of leukocyte migration, the total leukocyte count, the number of immune complexes, and the immunoglobulin level. An immunodepressive effect of extracorporeal circulation was noted. The postoperative phagocytosis values were higher (p less than 0.05) in patients given vitamin E. The postoperative leukocytosis level was lower (p less than 0.01) than in the control group and the leukocyte response to mitogen remained adequate, in contrast to that in the control group. No statistically significant differences in the level of immune complexes and immunoglobulins were obtained. It is concluded that the degree of immunodepression in the postoperative period decreases in patients given vitamin E in the indicated dose before the operation.     

心脏手术围术期红细胞内三磷酸腺苷含量变化

目的对体外循环心脏手术患者术中及术后３天红细胞（ｒｅｄｂｌｏｏｄｃｅｌ，ＲＢＣ）内三磷酸腺苷（ａｄｅｎｏｓｉｎｅｔｒｉｐｈｏｓｐｈａｔｅ，ＡＴＰ）含量进行动态观察。方法１５例心脏手术患者分别于麻醉诱导前、锯胸骨、体外心肺转流建立、主动脉阻断５分钟、转流结束、手术结束、术后第１天、术后第２天和术后第３天９个时间点取动脉血，测定ＲＢＣ内ＡＴＰ含量。结果手术期间ＲＢＣ内ＡＴＰ含量呈升高趋势，于手术结束达最高点，术后３天明显下降。结论麻醉、体外循环及手术对ＲＢＣ能量代谢具有一定影响     

Oversaturation Status of Reticuloendothelial System Following Cardiopulmonary Bypass

Abstract: In the past, it was generally believed that the phagocytic function of the reticuloendothelial system (RES) was depressed after cardiopulmonary bypass (CPB), but several investigators reported differing results. Therefore, this study was performed to determine the effect of CPB on RES function, experimentally and clinically. Six dogs undergoing CPB (CPB group) were compared with an identical number of dogs subjected to thoracotomy without CPB (control group). A lipid emulsion test was performed in all dogs before and after the surgical procedure to measure RES phagocytic function. Any ultrastructural changes in Kupffer cells were observed by electron microscopy. In both groups, the RES phagocytic index showed a significant decline after surgery. However, comparison of the 2 groups revealed that there was a significantly greater decrease in the CPB group (p < 0. 05). Electron microscopy of the Kupffer cells showed that the number of phagosomes, especially those containing deformed erythrocytes, increased after CPB. Twenty patients undergoing cardiac surgery requiring CPB (Group A) and 8 patients undergoing pulmonary resection (Group B) were studied. RES phagocytic function was determined 3 days prior to surgery and 3 days postoperatively using the lipid emulsion test. No significant difference was observed in the preoperative phagocytic indices between the 2 groups. The phagocytic function remained almost unchanged in Group A on the third postoperative day, compared with the preoperative value, but it increased significantly in Group B on the third postoperative day, compared with the preoperative value. The intergroup difference was significant on the third postoperative day (p < 0. 01). These findings suggest that phagocytic activities of RES are not depressed but stimulated by CPB and that the phagocytic ability of RES is saturated by formed microparticles after CPB, such as residual of hemolyzed erythrocytes, protein aggregates, and microbubbles, among others. “Depressed RES phagocytic function” after CPB may not be a proper expression of this situation. It should be considered that the status of RES function after CPB is not functionally depressed but functionally oversaturated.     

Heparin-coated circuits reduce myocardial injury in heart or heart-lung transplantation: a prospective, randomized study.

BACKGROUND: The effects of heparin-coated (HC) circuits have been primarily investigated in routine cardiac operations with limited duration of cardiopulmonary bypass (CPB) and ischemia. Their benefits have not been conclusively proven but could be more significant when CPB and ischemic times are longer, such as during heart transplantation (HTx) or heart-lung transplantation (HLTx). METHODS: In a 22-month period, 29 patients undergoing HTx and HLTx were randomly divided into two groups using HC (Duraflo II, n = 14, 10 HTx and 4 HLTx) or uncoated but identical circuits (NHC group, n = 15, 10 HTx and 5 HLTx). All patients received full systemic heparinization (3 mg/kg) during CPB. Plasma endotoxin, interleukin (IL)-6, IL-8, IL-10, IL-12, and cardiac troponin-I were measured before heparin administration, immediately after aortic cross-clamping, 5, 30, 60, 90, 120 minutes, and 12 and 24 hours after aortic declamping. The intensive care unit (ICU) staff and the laboratory technologists were blinded as to the use of HC circuits. RESULTS: No statistically significant differences between groups were found with respect to all baseline values, duration of CPB and aortic cross-clamping, graft ischemic time, doses of heparin, postoperative blood loss and transfusion, peak lactate and creatine kinase-MB isoenzyme values, duration of mechanical ventilation, or length of ICU stay. One patient in each group died during the hospital stay. Patients in the HC group needed more protamine sulfate after CPB. Although endotoxin levels were similar in the two groups, significantly lower IL-6, IL-8, and IL-10 levels were observed 1 hour after aortic declamping in the HC group. The release of cardiac troponin-I was also significantly reduced in the HC group 12 and 24 hours after reperfusion. CONCLUSIONS: The use of HC circuit limits both pro- and anti-inflammatory responses to CPB. It may also reduce myocardial injury after prolonged duration of CPB and ischemia.