Sialic acid or troponin T to detect perioperative myocardial damage in patients undergoing elective coronary artery bypass grafting.

Sialic acid (SA), a family of acetylated derivatives of neuraminic acid, is elevated in patients with coronary heart disease. Cardiac troponin T (cTnT), myoglobin (Mb), and creatine kinase-MB (CK-MB) are specific markers of myocardial injury and are, at present, widely used to detect perioperative myocardial damage during coronary artery bypass grafting (CABG) surgery. The present study investigated the net myocardial release of SA and the cardiac markers (cTnT, Mb, CK-MB) during reperfusion after hypothermic cardioplegic cardiac arrest in 25 patients undergoing elective CABG. Additional paired arterial, central venous, and coronary sinus blood samples were obtained after atrial cannulation before aortic cross-clamping (preischemic sample) and at 1 and 10 min after aortic declamping (reperfusion samples). There were no increase in the SA, cTnT, Mb and CK-MB concentrations before aortic cross-clamping, but there was considerable release of these markers within 10 min after aortic declamping: cTnT release was significantly higher compared with baseline values before aortic cross-clamping. In contrast to SA, Mb, and CK-MB, the difference between baseline and release values for cTnT at 1 min after aortic declamping was not significant. The rate of increase for SA was significantly higher than for Mb, CK-MB and cTnT. SA is a unique and novel marker that could be particularly useful in assessing myocardial cell damage in patients undergoing cardiac surgery.     

Reduced expression of systemic proinflammatory cytokines after off-pump versus conventional coronary artery bypass grafting

BACKGROUND: Both cardiopulmonary bypass (CPB) and operative trauma are associated with increased expression of proinflammatory cytokines. We assessed the relative contribution of CPB on activation of various proinflammatory cytokines in patients undergoing coronary revascularization by comparing them with patients receiving coronary artery bypass grafts using off-pump (OPCAB) techniques. METHODS: Twenty-six patients were assigned to either the OPCAB procedure using a suction device and regular sternotomy (n = 13) or were treated conventionally using extracorporeal circulation, blood cardioplegia and hypothermic arrest (29-31 degrees C; n = 13). C-reactive protein and systemic levels of TNF-alpha, TNF specific receptors Rp1 and Rp2, Interleukin-6 (IL-6) and soluble IL-2 receptors (sIL-2r) were assayed by ELISA or EIA. To account for systemic nitric oxide production, total nitrate/nitrite (NOx) was measured using the Griess reaction. RESULTS: Coronary revascularization with CPB was associated with a significant expression increase in the TNF-system and sIL-2r when compared to the OPCAB patients. Although IL-6 expression did not differ between both groups, C-reactive protein levels were significantly lower in the OPCAB group. Moreover, systemic NOx levels as the stable end-product of nitric oxide were lower in the OPCAB group. CONCLUSIONS: The data of the present study indicate that, despite comparable surgical trauma, the OPCAB revascularization procedure without the use of CPB and cardioplegic arrest significantly reduces the systemic inflammatory response syndrome and early catecholamine requirement. This may contribute to improved organ function, subsequently resulting in improved postoperative recovery from surgical revascularization procedures, particularly in critically ill patients.     

Acute cardiac inflammatory responses to postischemic reperfusion during cardiopulmonary bypass.

OBJECTIVES: The investigation centers on whether there is a reperfusion-induced specific cardiac inflammatory reaction after bypass surgery. BACKGROUND: Cardiopulmonary bypass (CPB) leads to systemic inflammation. Additionally, cardiac inflammation due to reperfusion could occur. Knowledge about nature and time course of this reaction might help to develop cardioprotective interventions. METHODS: In 12 patients receiving coronary bypass grafts, arterial and coronary venous blood was obtained before onset of CPB, and 1, 5, 10, 25, 35 and 75 min after cardiac reperfusion. Plasma levels of IL6 and IL8 were measured by immunoassay. CD11b, CD41, and CD62 on blood cells were quantified by flow cytometry. Measurement of CD41, a platelet marker, on neutrophils and monocytes allowed detection of leukocyte-platelet microaggregates. RESULTS: Transcardiac veno-arterial difference of IL6 rose in the 10th and 25th min of reperfusion (from 0 to 7 pg/ml; p < 0.05), and after 75 min (15 pg/ml). IL8 did not change. CD11b on neutrophils (PMN) decreased transcardially to 95, 88 and 82% of the initial level in the 5th, 10th, and 75th min, respectively, suggesting sequestration of activated neutrophils. CD62 on platelets rose about 30% in the 75th min. Initially, leukocyte-platelet microaggregates were formed during coronary passage (+31% of the arterial level for PMN, +23% for monocytes). During reperfusion, coaggregates were retained (PMN: -1% and -7% in the 5th and 10th min, monocytes: -22%, -13% and -12% in the 1st, 5th and 10th min. CONCLUSIONS: During early reperfusion after aortic declamping, the coronary bed is already a source of proinflammatory stimuli and target for activated leukocytes, partly in conjunction with platelets. Mitigation of these phenomena might help to improve cardiac function after CPB especially in patients at risk.     

Controlled oxygen reperfusion protects the lung against early ischemia-reperfusion injury in cardiopulmonary bypasses by downregulating high mobility group box 1

Restricting oxygen delivery during the reperfusion phase of cardiopulmonary bypass (CPB) protects the heart, but effects on lung ischemia reperfusion (IR) in CPB are unknown. We examined whether extracellular high mobility group box 1 (HMGB1) mediated inflammation during early lung IR injury in CPB. Fourteen healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest, followed by 90 minutes reperfusion. Following surgery, the animals were randomized into control (n = 7) or test (n = 7) groups. Control animals received a constant level of 80% FiO(2) during the entire procedure, and the test group received a gradual increase in FiO(2) during the first 25 minutes of reperfusion. In the test group, the FiO(2) was initiated at 40% and increased by 10% every 5 minutes, to 80%. Histology, lung injury variables, HMGB1 expression, and inflammatory responses were assessed at baseline (T1) and at 25 minutes (T2) and 90 minutes (T3) after starting reperfusion. Treatment with controlled oxygen significantly suppressed lung pathologies, lung injury variables, and inflammatory responses (all P < .001). After lung IR injury, HMGB1 mRNA and protein expressions were significantly decreased in the controlled oxygen group (all P < .001). Controlled oxygen reperfusion is protective in the early stages of lung IR injury in a canine CPB model, and this protection is linked to HMGB1 downregulation.     

Effect of cardiopulmonary bypass on cytokine network and myocardial cytokine production

BACKGROUND: In addition to the well-investigated proinflammatory cytokine expression, there is an ever increasing interest in the field of anti-inflammatory response to cardiopulmonary bypass (CPB). Evidence suggests that myocardium serves as an important source of cytokines during reperfusion and application of CPB. The effect of coronary artery bypass graft (CABG) without CPB on myocardial cytokine production has not as yet been investigated. HYPOTHESIS: Cardiopulmonary bypass can cause long-term disturbance in pro- and anti-inflammatory cytokine balance, which may impede a patient's recovery following surgery. Therefore, the effect of CPB on the balance of the pro-/anti-inflammatory cytokines network and myocardial cytokine outflow was assessed throughout a longer period after surgery. METHODS: Twenty patients were scheduled for CABG with CPB and 10 had off-pump surgery. Blood samples were taken before, during, and over the first week following surgery. Coronary sinus blood samples were collected during surgery. The ratio of pro- and anti-inflammatory cytokines was calculated and the cytokine concentration of peripheral and coronary sinus blood were compared in both groups. RESULTS: Pro-/anti-inflammatory cytokine ratio decreased early after CPB followed by a delayed and marked increase. A more balanced ratio was present following off-pump surgery. Coronary sinus levels of certain cytokines exceeded the concentration of systemic blood in the course of CPB but not during off-pump operation. CONCLUSION: Patients show pro-inflammatory predominant cytokine balance at a later stage after CPB in contrast to those without CPB. The heart produces a remarkable amount of cytokines only in the course of surgery with CPB.     

Cardioprotective effects of lowering oxygen tension after aortic unclamping on cardiopulmonary bypass during coronary artery bypass grafting.

The effect on myocardial reperfusion injury of reducing oxygen tension during reperfusion on cardiopulmonary bypass (CPB) in coronary artery bypass grafting (CABG) was examined at the same time as the influence of diltiazem during CPB was evaluated. A prospective, randomized trial evaluated the hemodynamic and myocardial metabolic recovery in 3 groups of patients undergoing elective CABG; subjects were randomly allocated on the basis of oxygen tension during reperfusion after aortic unclamping: group 1 (n=10) hyperoxic reperfusion (oxygen tension [PO2]=450-550 mmHg); group 2 (n=10): hyperoxic reperfusion and subsequent continuous infusion of diltiazem (0.5 microg/kg); group 3 (n=10): lowering reperfusate PO2 (PO2=200-250 mmHg). Hemodynamic and myocardial metabolic measurements were taken at 6 preset times: before starting the surgical procedure and at 30 min and 3, 9, 21, and 45 h after discontinuation of CPB. The cardiac index in the lowering reperfusate PO2 group was higher than that of the hyperoxic reperfusion groups at 30 min and 3 h after CPB, and malondialdehyde and troponin-T were significantly lower at 30 min and 3 h, respectively. In comparison with the hyperoxic + diltiazem group, the hemodynamic and myocardial recovery in the lowering reperfusate PO2 group was improved for about 3 h after CPB. Reduced oxygen tension during reperfusion after aortic unclamping on CPB is more effective against myocardial injury than a calcium antagonist in the short term. It is a convenient and safe management technique that can reduce morbidity and mortality, especially in the severely compromised heart.     

成人瓣膜手术体外循环中应用不同利尿剂对电解质的影响

目的:观察托拉塞米与呋噻米用于成人瓣膜手术体外循环(cardiopulmonary bypass,CPB)中对电解质的影响。方法:随机选取择期CPB下行瓣膜置换术患者60例,分为托拉塞米组(A组)30例,呋噻米组(B组)30例,分别在CPB前、升主动脉阻断后15min、升主动脉开放15min、CPB停机时和术后2h抽取静脉血进行血气分析,记录K+、Na+、Mg++及Ca++离子浓度。同时记录2组患者转机中尿量及自动复跳率。结果:2组患者转机前、阻断升主动脉后15minK+、Na+、Mg++及Ca++离子浓度差异无统计学意义(P>0.05);A组患者开放升主动脉后15min血K+明显高于B组,差异有显著性统计学意义(P<0.01),Mg++、Ca++差异无统计学意义(P>0.05);停机时及术后2h,2组患者血K+、Na+、Mg++及Ca++差异无统计学意义(P>0.05)。2组患者转中尿量及自动复跳率差异无统计学意义。结论:托拉塞米可以用作CPB下瓣膜置换术的利尿剂,但要注意防止复跳时的高钾。     

冠状动脉搭桥体外循环手术中心肌缺血缺氧性损伤的临床观察

目的以心肌肌钙蛋白(IcTnI)和冠状静脉窦血液氧合参数作为评判指标,观察体外循环(CPB)下接受冠状动脉旁路移植手术患者心肌缺血缺氧性损伤的状况。方法选取择期进行冠状动脉旁路移植手术(CABG)的患者12例,分别于CPB前,主动脉开放后0min、0.5min、1min,1.5min、3min和5min经冠状静脉窦取血,测定血清cTnI浓度,冠状静脉窦血流量和血气值,计算心肌氧输送量、氧耗量及其比值以反映心肌氧代谢状况。结果主动脉开放后,冠状静脉窦内cTnI浓度明显升高(P<0.05),而冠状静脉窦血氧分压和氧饱和度均较高,氧耗量较低(P<0.05),心肌氧输送量/氧耗量比值较高;随着心跳恢复,心肌氧耗增加明显,表现心肌氧输送量/氧耗量比值降低(P<0.01)。结论主动脉阻断期间心肌有一定程度的缺血缺氧性损伤和酸中毒;主动脉开放心跳恢复后,心肌供氧和耗氧状况一般能较快趋于正常,但需注意心肌氧供/氧耗的变化。     

Effects of single administration of a phosphodiesterase III inhibitor during cardiopulmonary bypass: comparison of milrinone and amrinone.

The effects of phosphodiesterase III (PDE III) inhibitors administered after aortic declamping during cardiopulmonary bypass (CPB) for open heart surgery were investigated. Ten patients (group M) were administered milrinone (50 microg/kg) after aortic declamping during CPB, 10 patients were administered amrinone (1 mg/kg) at the same time during their surgery (group A), and 10 patients served as controls with no drug administered (group C). Soon after bolus infusion of the PDE III inhibitor, perfusion pressure dropped significantly in groups M and A. However, after release of CPB and at the end of surgery, there was no difference in aortic pressure between the 3 groups. There were also no differences between the groups in heart rate, pulmonary artery pressure, and pulmonary capillary wedge pressure. After weaning from CPB, the cardiac index was high and systemic vascular resistance index was low in groups M and A. There were no significant differences in the need for additional catecholamines and time for rewarming between groups. No adverse reactions were observed. A single administration of a PDE III inhibitor during CPB was useful for post-CPB management of patients undergoing open heart surgery. Amrinone reduced perfusion pressures more than milrinone, but cardiac indices and aortic pressures after weaning from CPB showed no differences between group M and group A patients.     

不同剂量盐酸戊乙奎醚对体外循环冠脉搭桥手术患者心肌保护作用

目的 比较两种不同剂量盐酸戊乙奎醚对体外循环下行冠脉搭桥手术患者心肌保护作用.方法 2011年5月至2013年5月择期行冠脉搭桥手术患者75例,随机分成3组：对照组（25例）,给予等量生理盐水;小剂量组（25例）,戊乙奎醚 0.05 mg/kg;大剂量组（25例）,戊乙奎醚0.1 mg/kg.比较三组冠脉搭桥手术患者不同时间点的心肌肌钙蛋白I（cTnI）、肌酸磷酸激酶同工酶MB（CK-MB）、肌酸激酶（CK）、谷草转氨酶（AST）、α-羟丁酸脱氢酶（α-HBDH）、乳酸脱氢酶（LDH）浓度的变化.结果 三组患者cTnI、CK-MB、CK、AST、α-HBDH、LDH浓度,主动脉开放后1 h（T1）及主动脉开放后24 h（T2）与麻醉诱导前（T0）相比明显升高,差异均有统计学意义（P〈0.05）;T1、T2时间点组间比较,戊乙奎醚大、小剂量组低于对照组,差异有统计学意义（P〈0.05）,戊乙奎醚大剂量组与小剂量组相比差异无统计学意义（P＆gt;0.05）.结论 盐酸戊乙奎醚对体外循环冠脉搭桥手术患者具有心肌保护作用,安全性好,值得临床推广和应用,剂量上大剂量组并不优于小剂量组.     

异丙酚对婴幼儿体外循环心脏手术血细胞因子、心肌NF—κB、ICAM-1表达的影响

目的：观察异丙酚对婴幼儿体外循环心脏手术血细胞因子、心肌核转录因子（NF）-κB）和细胞间粘附分子（ICAM）-1表达的影响并试图说明其临床意义。方法：20例年龄1～9岁的先天性心脏病体外循环下行房、室间隔缺损矫正术的患儿,随机分为对照组（Ⅰ组,10例）和异丙酚麻醉组（Ⅱ组．10例）。麻醉诱导：咪唑安定,芬太尼,泮库溴铵。麻醉维持：Ⅰ组,吸入0．25％～2％安氟醚,Ⅱ组,持续输注异丙酚15～20mg／kg·h。两组分别于全麻诱导气管插管和动静脉穿刺完成后稳定10min（T0）,体外循环前（T1）、主动脉阻断25min（T2）、主动脉开放后30min（T3）、停止体外循环2h（T4）采集血液标本检测肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6。右房插管和缺血再灌注30min取右房心耳组织标本,观察NF-κB和ICAM-1的表达。结果：两组患儿TNF—α在术中和术后无显著差异,IL-6于术中和术后均升高,且Ⅰ组的明显高于Ⅱ组（P〈0．05）。再灌注30min后Ⅰ组心肌组织NF—κB和ICAM-1的表达明显高于Ⅱ组（P〈0．05）。结论：婴幼儿体外循环心脏手术期间,全身炎症反应被激活,心肌细胞NF—κB和ICAM—1过度表达;异丙酚能减轻其炎症反应,抑制心肌NF-κB和ICAM-1的表达。     

Progressive loss of myocardial contractile function despite unimpaired coronary blood flow after cardiac surgery

Objective Mild to moderate transient contractile dysfunction is frequently observed after cardiac surgery on cardiopulmonary bypass (CPB) but may also lead to low–cardiac–output (LCO) failure especially in patients with unstable angina, and is often referred to represent myocardial stunning. Whether time course of contractile dysfunction after cardiac surgery is similar to that of myocardial stunning was investigated in pigs. Methods After baseline measurements of systemic hemodynamics (micromanometry), myocardial contractile function (sonomicrometry), cardiac output and coronary flow (ultrasonic probe), CPB was instituted. Control animals (n = 7) were weaned after 3 h from CPB. In LCO animals (n = 8), global ischemia was induced for 10 min by aortic crossclamping, followed by 1 h of cardioplegic cardiac arrest. After declamping and reperfusion, CPB was terminated after a total of 3 h. Measurements were repeated at 15 min, 4 h and 8 h after CPB. Systemic TNF–plasma concentrations were measured (ELISA) and left ventricular biopsies were analyzed with respect to myocardial TNF (immunohistochemistry) and irreversible cellular damage (light/electron microscopy). Results Contractile function decreased in LCO (75 ± 12%) and control (83 ± 17%) at 15 min compared to baseline (p < 0.05). Thereafter, contractile function remained unchanged in control, but progressively decreased in LCO (52 ± 12% at 4 h; 36 ± 5% at 8 h; p < 0.05). Coronary flow remained unchanged in both groups. Cardiac output progressively decreased to 2.8 ± 0.9 l/min at 8 h in the LCO group compared to baseline (5.9 ± 1.1 l/min, p < 0.05) and control (5.7 ± 1.4 l/min, p < 0.05). There was no evidence for myocardial infarction. TNF–plasma concentrations and myocardial TNF–staining were increased at 8 h after CPB in the LCO group compared to baseline and control (p < 0.05). Conclusions The progressive pattern of myocardial dysfunction apart from ongoing ischemia after cardiac surgery suggested underlying mechanisms at least partially different from those of myocardial stunning.     

Cytokine responses in low-risk coronary artery bypass surgery

Inflammatory cytokines have been implicated in myocardial function, severe congestive heart failure and sepsis. The present study tested the hypothesis that cytokine levels are elevated after low-risk coronary artery bypass surgery (CABG), and that they may be associated with postoperative cardiac dysfunction. Twenty male patients undergoing elective CABG in cardiopulmonary bypass (CPB) were studied. Plasma levels of tumor necrosis factor- (TNF-), interleukin (IL)-6, IL-8, and IL-10 were measured before anesthesia induction, 5 minutes after, and 1, 4, and 20 hours after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were measured postoperatively. Hemodynamic data were also recorded. Myocardial ischemia was followed by an increase in the plasma levels of IL-6, IL-8, and IL-10. The duration of IL-6 response lasted throughout the postoperative period studied. Plasma cytokine levels at 1 hour after reperfusion correlated with the maximum CK-MB value (IL-6, r=0.587, p<0.01; IL-8, r=0.460, p<0.05; IL-10, r=0.570, p<0.05). Higher plasma IL-6 and IL-8 levels after reperfusion tended to be linked with lower cardiac index. The present results confirm that the levels of inflammatory cytokines IL-6, IL-8, and IL-10 are elevated after CABG. Increased systemic pro-inflammatory cytokine levels were partially associated with postoperative myocardial dysfunction.     

Activated protein C in the cardioplegic solution on a porcine model of coronary ischemia-reperfusion has deleterious hemodynamic effects

Summary Purpose: In reperfusion injury activation of coagulation and inflammation contribute to organ dysfunction. Activated protein C (APC) exhibits anticoagulant and anti-inflammatory properties in models of reperfusion injury. We hypothesized that APC could be cardioprotective after ischemia and cardiopulmonary bypass (CPB). Methods: 20 pigs, undergoing 120 min of CPB and aortic cross-clamping, were randomized to receive 1 mg of human APC or placebo to the last cardioplegic solution given 15 min before declamping to the systemic circulation. After aortic declamping the heart was supported by continuing CPB for 30 min followed by 30 min surveillance. Thrombin-antithrombin complexes, neutrophil L-selectin expression in blood and myeloperoxidase activity (MPO) of myocardial biopsies were measured. Results: There was no indication of APC-induced increased bleeding. Thrombin levels were significantly lower in the APC group than in the placebo group and so were the rates of thrombin formation during the first 3 min of reperfusion and between 10 and 30 min after declamping. There were no differences in MPO or in the proportion of L-selectin (+) to L-selectin (−) neutrophils between groups. Significant systolic hypotension in the APC group was observed at 30 and 45 min compared with the placebo group which associated with the increased mortality observed in the APC group (p = 0.019). Conclusions: Human APC in cardioplegic solution during CPB in pigs, decreased reperfusion induced thrombin formation with no associated bleeding. No anti-inflammatory effects of human APC were seen. However, in this setting, APC caused hemodynamic deterioration. The observed phenomenon could be explained by systolic hypotension potentially produced by the release of vasoactive substances generated by the APC activation of PARs in the endothelium.     

黄芪注射液在心内直视手术体外循环中的心肌保护作用

目的探讨心内直视手术中黄芪注射液对心肌的保护作用。方法选取心内直视手术的患者90例,分为3组：围手术期组在围手术期给予黄芪注射液,手术体外循环时给予黄芪注射液预充,体外循环过程中再次给药;体外循环组只是在体外循环预充及过程中给予黄芪注射液;对照组不给药。三组患者分别在麻醉前、主动脉开放和术后检测不同时期血清肌酸激酶同工酶（CK—MB）及血清肌钙蛋白T（eTnT）;在手术前、后比较心电图ST段抬高或压低。结果围手术期组和体外循环组CK—MB、cTnT水平及心电图ST段变化程度较对照组低（P〈0．05）。围手术期组CK—MB、cTnT水平及心电图ST段变化程度较体外循环组低（P〈0．05）。结论在心内直视手术中,黄芪注射液可明显改善心脏能量供应,有效减少心肌细胞损伤,对心肌起到明显保护作用,围手术期使用效果更佳。     

缺血预处理对体外循环中左心功能的恢复及心肌细胞膜流动性变化的影响

目的:观察缺血预处理(IPC)对体外循环(CPB)中心肌细胞膜流动性变化及心功能恢复的影响,评价IPC的心肌保护作用。方法:将72只健康家猫随机分为3组:单纯并行循环(CPB)组、缺血再灌注(IR)组和IPC组。监测CPB中猫左心室内压峰值(LVSP)、左心室等容收缩期压力升高最大速率(dp/dtmax)、左心室舒张期压力下降最大速率(dp/dtmin)等左心功能指标,并应用荧光偏振法测定心肌细胞膜的微黏度(η),以η的倒数表示心肌细胞膜脂流动性。结果:CPB组体外循环过程中左心功能各指标和心肌细胞膜微黏度均无明显变化;IR组主动脉阻断(ACC)期间η明显上升且于再灌注期间进一步升高,IPC组ACC期间η无明显变化,再灌注期间虽有所升高但明显低于IR组;心功能恢复阶段IPC组猫心LVSP、dp/dtmax和dp/dtmin均明显高于IR组。结论:IPC能够有效维持CPB中缺血再灌注心肌细胞膜脂的流动性,同时可改善左心功能的恢复。     

Exogenous high-mobility group box 1 protein induces myocardial regeneration after infarction via enhanced cardiac C-kit+ cell proliferation and differentiation

High-mobility group box 1 protein (HMGB1) is a chromatin protein that is released by inflammatory and necrotic cells. Extracellular HMGB1 signals tissue damage, stimulates the secretion of proinflammatory cytokines and chemokines, and modulates stem cell function. The present study examined exogenous HMGB1 effect on mouse left-ventricular function and myocyte regeneration after infarction. Myocardial infarction was induced in C57BL/6 mice by permanent coronary artery ligation. After 4 hours animals were reoperated and 200 ng of purified HMGB1 was administered in the peri-infarcted left ventricle. This intervention resulted in the formation of new myocytes within the infarcted portion of the wall. The regenerative process involved the proliferation and differentiation of endogenous cardiac c-kit+ progenitor cells. Circulating c-kit+ cells did not significantly contribute to HMGB1-mediated cardiac regeneration. Echocardiographic and hemodynamic parameters at 1, 2, and 4 weeks demonstrated a significant recovery of cardiac performance in HMGB1-treated mice. These effects were not observed in infarcted hearts treated either with the unrelated protein glutathione S-transferase or a truncated form of HMGB1. Thus, HMGB1 appears to be a potent inducer of myocardial regeneration following myocardial infarction.     

Continuous tepid blood cardioplegia can preserve coronary endothelium and ameliorate the occurrence of cardiomyocyte apoptosis

OBJECTIVE: In modern cardiac surgery, crystalloid or blood cardioplegic solutions have been used widely for myocardial protection; however, ischemia does occur during protection with intermittent infusion of cold crystalloid or blood cardioplegic solutions. The present study was designed to evaluate the effect of different cardioplegic methods on myocardial apoptosis and coronary endothelial injury after global ischemia, cardiopulmonary bypass (CPB), and reperfusion in anesthetized open-chest dogs. METHODS: The dogs were classified into five groups to identify the injury of myocardium and coronary endothelium: group 1, normothermic CPB without cardiac arrest; group 2, hypothermic CPB with continuous tepid blood cardioplegia, and with cardiac arrest; group 3, hypothermic CPB with intermittent cold blood cardioplegia, and with cardiac arrest; group 4, hypothermic CPB with intermittent cold crystalloid cardioplegia, and with cardiac arrest; and group 5, sham-operated control group. During CPB, cardiac arrest was achieved with different cardioplegia solutions for 60 min, followed by reperfusion for 4 h before the myocardium and coronary arteries were harvested. Coronary arteries were harvested immediately and analyzed by scanning electron microscopy. Cardiomyocytic apoptosis was detected using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling, Western blot, and DNA ladder methods. RESULTS: Regardless of the detection method used, significantly higher percentages of apoptotic cardiomyocytes were found in group 3 and group 4 than in other groups. Expression of caspase-3 correlated with increased apoptosis. Scanning electron microscopy revealed severe endothelial injury of coronary arteries in group 3 and group 4. CONCLUSION: These results point to an important explanation for the difference in cardiac recovery after hypothermic ischemia and arrest with various cardioplegic solutions.     

丹参酮Ⅱ-A磺酸钠注射液在体外循环中对心肌缺血/再灌注损伤保护作用的研究

目的研究丹参酮Ⅱ-A磺酸钠注射液在体外循环中对心肌缺血／再灌损伤的保护作用。方法随机选取20例行心脏直视手术的患者,分为对照组和丹参酮Ⅱ-A磺酸钠注射液组。丹参酮Ⅱ-A磺酸钠组于转机前给予丹参酮Ⅱ-A磺酸钠注射液2mg／kg。分别于主动脉插管后（T1）、开放主动脉前1-3min（T2）、主动脉开放后30min（T3）、主动脉开放后120min（T4）,主动脉开放后720min（B）共5个时间点进行抽血,测定血清中超氧化物歧化酶（SOD）、丙二醛（MDA）含量;记录主动脉开放至心脏复跳所需时间,心律失常（室速／室颤）的发生率和持续时间。血清中超氧化物歧化酶、丙二醛采用分光光度法测定。结果两组患者围术期血清SOD浓度变化比较：对照组各时间点SOD的变化差异无统计学意义（P〉0．05）,丹参酮Ⅱ-A磺酸钠组SOD浓度逐渐上升,在T4时间点达最高值（P〈0．05）,T5时间点下降;组间比较,丹参酮Ⅱ-A磺酸钠组在T4时间点较对照组高（P〈0．05）。两组患者血清MDA浓度变化比较：对照组MDA浓度随时间点的推进逐步增高,于T4达最高值（P〈0．05）,丹参酮Ⅱ-A磺酸钠组MDA浓度也逐渐升高,在T4时间点达高峰,B时间点下降,两时间点与T1比较差异有统计学意义（P〈0．05）,组间比较,T4、L时间点差异有统计学意义（P〈0．05）,丹参酮Ⅱ-A磺酸钠组比对照组MDA的上升幅度小。两组患者心律失常的发生情况比较：对照组共出现室颤2例,占20％,室速1例,占10％,丹参酮Ⅱ-A磺酸钠组出现室颤1例,无室速发生;对照组室速室颤持续时间3min,电击除颤后转为窦性心律,丹参酮Ⅱ-A磺酸钠组室颤后36s自动转为窦性心律。主动脉开放至心脏复跳所需时间：对照组所需时间较丹参酮Ⅱ-A磺酸钠组明显较长,差异有统计学意义（P〈0．05）。结论在体外循环心脏直视手术中,临床剂量的丹参酮Ⅱ-A磺酸钠注射液能使患者血清中的SOD浓度升高,有效降低MDA的浓度,缩短主动脉开放至心脏复跳所需时间,减少心律失常的发生率并缩短其时间,提示丹参酮Ⅱ-A磺酸钠注射液对心肌缺血／再灌注损伤有保护作用。     

Peri-operative myocardial tissue injury and the release of inflammatory mediators in coronary artery bypass graft patients

OBJECTIVE: This study was conducted to evaluate to what extent the ischemia-reperfusion injury resulting from the cardiopulmonary bypass (CPB) and aortic cross-clamping procedures during coronary artery bypass grafting (CABG) contributes to the systemic inflammatory response generally found in these patients. METHODS: Serum levels of enzymes (CK and CK-MB) and non-enzymatic proteins (FABP and myoglobin) as markers of myocardial tissue injury, bactericidal permeability increasing protein (BPI) as an indicator of neutrophil activation, interleukin-6 (IL-6) as inducer of the acute phase response and lipopolysaccharide binding protein (LBP) as parameter of the acute phase response were measured in 15 low-risk CABG patients with cardiopulmonary bypass (CPB), and 17 low-risk CABG patients without CPB. RESULTS: Already 0.5 h after reperfusion significantly increased plasma levels of all markers of myocardial tissue injury were noted in patients having surgery with CPB, but not in non-CPB patients. No significant differences were found between both groups for BPI and IL-6 levels in the early reperfusion period. BPI and IL-6 levels were higher in the non-CPB group on the first post-operative day (P < 0.05). However, no correlations were found for any marker of peri-operative tissue damage with either early neutrophil activation, or acute phase reactants. CONCLUSIONS: Perioperative myocardial injury resulting from CPB and aortic cross-clamping in low-risk CABG patients does not contribute to the release of inflammatory mediators in these patients.