Does aprotinin reduce lung reperfusion damage after cardiopulmonary bypass?

OBJECTIVE: The role of aprotinin in the prevention of lung reperfusion injury was investigated in the patients undergoing cardio-pulmonary bypass (CPB) for coronary artery bypass grafting (CABG) operations. METHODS: The study was planned randomly and prospectively. Two hundred milliliters of physiological saline solution was added to the prime solution of patients in group I (n=10) whereas, 200 ml aprotinin (Trasylol, Bayer AG) was given to patients in group II (n=10). In order to measure lung tissue malondialdehyde (MDA) levels, glutathion peroxidase (GSH-Px) activity levels and polymorphonuclear leukocytes (PMNs) numbers, lung tissue samples were taken before CPB and 5 min after removing the cross clamp. In addition, alveolo-arterial oxygen difference (AaDO(2)) for tissue oxygenation was calculated by obtaining arterial blood gas samples. RESULTS: MDA levels before CPB increased from 41.72+/-21.00 nmol/g tissue to 66.71+/-13.44 nmol/g tissue in group I and from 43.44+/-5.16 nmol MDA/g tissue to 53.22+/-10.95 nmol MDA/g tissue in group II after cross clamp removal (P=0.001 and P=0.021, respectively). The increase in group II was found to be significantly lower than group I (P=0.048). With the initiation of reperfusion, GSH-Px activity decreased in group I from 3.05+/-0.97 to 2.31+/-0.46 U/mg protein (P=0.015) whereas GSH-Px activity in group II decreased from 3.18+/-1.01 to 2.74+/-0.81 U/mg protein (P=0. 055). This decrease in the group II was less than group I (P=0.049). AaDO(2) significantly increased in the group I and II (P=0.012 and P=0.020, respectively), but elevation in the group I was significant than in the Group II (P=0.049). In histopathological examination, it was observed that neutrophil counts in the lung parenchyma rose significantly following removal of cross clamp in both groups (P=0. 001). The increase in group I was significantly larger than in group II (P=0.050). CONCLUSION: Results represented in our study indicate that addition of aprotinin (2 million units) into the prime solution during CPB can reduce lung reperfusion injury.     

Does sodium nitroprusside reduce lung injury under cardiopulmonary bypass?

Objective: We hypothesized that direct pulmonary arterial infusion of sodium nitroprusside (SNP) would ameliorate lung injury under cardiopulmonary bypass. Methods: Experiments were performed on 12 adult mongrel dogs of both sexes weighing 20–28 kg. The animals were randomly divided into two groups of six animals each. All animals were subjected to total cardiopulmonary bypass (CPB) and moderate hypothermia (28°C core temperature). During total CPB, the aorta was clamped together with the pulmonary artery to prevent any antegrade flow to the lungs. After cardioplegic arrest for 120 min, the animals were rewarmed, weaned from CPB, and their condition stabilized for another 90 min. After the release of the aortic cross-clamp, the dogs received either a 5% glucose solution as a placebo (group I) or SNP (0.5 μg/kg per min) (group II), both infused into the pulmonary arterial line. The infusion was stopped after 60 min. To measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear leukocytes count, lung tissue samples were taken before CPB and after weaning from CPB. In addition, alveolar-arterial oxygen difference (AaDO₂) for tissue oxygenation was calculated by obtaining arterial blood gas samples. Results: Values of MDA before CPB of 42.0±5.3 nmol/g of tissue rose to 67.6±5.7 nmol/g of tissue after weaning from CPB in group I (P=0.028). In group II MDA values also increased from 43.1±4.3 to 52.4±5.7 nmol MDA/g of tissue after weaning from CPB (P=0.046). The MDA increase in group II after CPB was found to be significantly lower than that for group I (P=0.004). The wet-to-dry lung weight ratio in the sodium nitroprusside group was 5.1±0.2, significantly lower than in the control group (6.8±0.4), (P=0.01). AaDO₂ increased significantly in group I (P=0.028). There was no statistically significant difference (P=0.065) between groups I and II. During histopathological examination it was observed that neutrophil counts in the lung parenchyma rose significantly after CPB in both groups. The increase in group I was significantly larger than that in group II (P<0.001). Conclusions: The results represented in our study indicate that pulmonary arterial infusion of sodium nitroprusside during reperfusion can reduce lung injury under cardiopulmonary bypass.     

N-乙酰半胱氨酸对体外循环犬肺组织转化生长因子-β1表达的影响

目的 探讨N-乙酰半胱氨酸(NAC)对体外循环(CPB)犬肺组织转化生长因子-β1(TGF-β1)表达的影响.方法 成年犬24只,雌雄不拘,体重15～16 kg,随机分为3组(n=8):N1组于CPB开始前、N2组于CPB开始后复温前静脉注射NAC 150 mg/kg,持续静脉输注NAC 50 mg/kg;对照组(C组)给予等容量生理盐水.分别于CPB前(T0)、CPB开始30 min(T1)、停机后15、30、60 min(T2-4)时取肺组织,检测TGF-β1表达,测定丙二醛(MDA)含量,光镜下观察病理学结构,于T0、T3及T4时抽取股动脉血行血气分析,计算呼吸指数(RI).结果 与T0时比较,各组于T3,4时RI、余时点肺组织MDA含量升高、TCF-β1表达上调(P＜0.05);与C组比较,N1组和N:组L3,4时RI、各时点肺组织MDA含量降低,N1组各时点、N2组T2-4时TGF-β1表达下调(P＜0.05);与N1组比较,N2组T3,4时RI升高、各时点肺组织TGF-β1表达上调(P＜0.05).N1组和N2组肺部炎性改变较C组明显减轻.结论 NAC通过下调肺组织TGF-β1表达,降低炎性反应,可减轻CPB诱发犬肺损伤的程度,且CPB前给药效果更好.     

Changes in forehead and sole tissue temperature during cardiopulmonary bypass for acquired cardiac disease]

The forehead tissue temperature (FT-T) and the sole tissue temperature (ST-T) were measured and recorded by a deep body thermometer (Terumo Corp.) during open heart surgery. The changes in FT-T and ST-T after cardiopulmonary bypass (CPB) showed two characteristic patterns; the convergence pattern and the dissociation pattern. It is said that the dissociation pattern can notes a poor peripheral circulation. The deverging point of the two patterns was studied in 65 patients with acquired cardiac disease. We divided the patients into two groups taking 3.5 degrees C of the FT-T and ST-T difference (DT) after 2 hour weaning from CPB. The number of the patients in convergence group (group I) was 42, and that in the dissociation group (group II) was 23. The two groups were compared with the DT and the time required for the rise in each temperature from CPB rewarming to CPB weaning. There was no intergroup difference in the DT when the FT-T began to rise upon CPB rewarming. However, the DT was 3.8 +/- 2.3 (mean +/- SD) degrees C in group I and 7.1 +/- 1.8 degrees C in group II when the ST-T began to rise, and 4.2 +/- 2.5 degrees C in group I and 6.9 +/- 1.4 degrees C in group II when the FT-T reached its peak; the figures were significantly lower in group I (P < 0.01). The time required for the rise in ST-T was significantly shorter in group I (14.8 +/- 17.1 min) than in group II (25.8 +/- 14.7 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pneumocyte apoptosis induction during cardiopulmonary bypass: effective prevention by radical scavenging using N-acetylcysteine.

Cardiopulmonary bypass (CPB) and cardioplegic arrest are associated with pulmonary dysfunction. We sought to investigate whether pulmonary ischemia/reperfusion during standard CPB and cardioplegic arrest is associated with reactive oxygen species (ROS)-mediated pulmonary tissue injury and pneumocyte apoptosis induction, and whether ROS scavenging using N-acetylcysteine (NAC) attenuates these alterations. Twelve pigs (41 +/- 8 kg) were randomized to receive either NAC (100 mg/kg prior to CPB; n = 7) or placebo (n = 5) and subjected to CPB and 60 min of cold (4 degrees C) crystalloid cardioplegic arrest. We collected lung biopsies prior to CPB, at 60 min CPB, as well as at 30, 60, and 120 min post CPB. Lung specimens were immunocytochemically stained against nitrotyrosine, 8-isoprostaglandin-F(2)alpha, and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) as indicators for ROS-mediated tissue injury and active caspase-3, an apoptosis signal pathway key enzyme. Oxidative stress markers were judged using a scale from 1 to 4 (low to intensive staining), and caspase-3-positive pneumocytes were counted per view field. In placebo, the number of caspase-3-positive pneumocytes significantly increased over time to reach a maximum at 120 min post CPB (p = .03 vs baseline). NAC significantly prevented caspase-3 activation in pneumocytes (p = .001 vs Placebo). Pneumocyte nitrotyrosine and 8-OH-dG staining significantly increased over time (p = .003) in the placebo group, but decreased in the NAC group (p = .004). In both groups staining for 8-isoprostaglandin-F(2)alpha showed no significant changes. This yields the conclusion that standard CPB and cardioplegic arrest initiate ROS-mediated tissue injury and apoptosis in pneumocytes that can be reduced by NAC. Thus, ROS scavenging using NAC may represent a novel approach to minimize lung injury associated with CPB.     

Does normoxemic cardiopulmonary bypass prevent myocardial reoxygenation injury in cyanotic children?

OBJECTIVE: To evaluate whether the deleterious effect of cardiopulmonary bypass (CPB) can be prevented by controlling PaO(2) in cyanotic children. DESIGN: Prospective, randomized, clinical study. SETTING: Single university hospital. PARTICIPANTS: Pediatric patients undergoing cardiac surgery for repair of congenital heart disease (n = 24). INTERVENTIONS: Patients were randomly allocated into 3 groups. Patients in the acyanotic group (group I, n = 10) had CPB initiated at a fraction of inspired oxygen (F(I)O(2)) of 1.0 (PO(2), 300 to 350 mmHg). Cyanotic patients were subdivided as follows: Group II (n = 7) had CPB initiated at an F(I)O(2) of 1.0, and group III (n = 7) had CPB initiated at an F(I)O(2) of 0.21 (PO(2), 90 to 110 mmHg). A biopsy specimen of right atrial tissue was removed during venous cannulation, and another sample was removed after CPB before aortic cross-clamping. The tissue was incubated in 4 mmol/L of t-butylhydroperoxide, and the malondialdehyde (MDA) level was measured to determine the antioxidant reserve capacity. Blood samples for cytokine levels, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 response to CPB were collected after induction of anesthesia and at the end of CPB before protamine administration. MEASUREMENTS AND MAIN RESULTS: After initiation of CPB, MDA level rose markedly in the cyanotic groups compared with the acyanotic group (210 +/- 118% v 52 +/- 34%, p < 0.05), which indicated the depletion of antioxidants. After initiation of CPB, TNF-alpha and IL-6 levels of the cyanotic groups were higher than for the acyanotic group (168 +/- 77 v 85 +/- 57, p < 0.001; 249 +/- 131 v 52 +/- 40; p < 0.001). When a comparison between the cyanotic groups was performed, group II (initiating CPB at an F(I)O(2) of 1.0) had significantly increased MDA production compared with group III (initiating CPB at an F(I)O(2) of 0.21) (302 +/- 134% v 133 +/- 74%, p < 0.05). Group II had higher TNF-alpha and IL-6 levels than group III (204 +/- 81 v 131 +/- 52, p < 0.001; 308 +/- 147 v 191 +/- 81, p < 0.01). CONCLUSION: Conventional clinical methods of initiating CPB at a hyperoxemic PO(2) may increase the possibility of myocardial reoxygenation injury in cyanotic children. This deleterious effect of reoxygenation can be modified by initiating CPB at a lower level of oxygen concentration. Subsequent long-term studies are needed to determine the best method of decreasing the oxygen concentration of the CPB circuit.     

N-乙酰半胱氨酸对体外循环诱发犬肺损伤的影响

目的 探讨N-乙酰半胱氨酸对体外循环(CPB)诱发犬肺损伤的影响.方法 成年犬36只,雌雄不拘,体重15 ～ 16 kg,采用随机数字表法,将其随机分为2组(n=18):CPB组(C组)和N-乙酰半胱氨酸组(N组).右锁骨下动脉和右心房分别插管,制备CPB模型,N组于CPB前即刻静脉注射N-乙酰半胱氨酸150mg/kg,然后以20 mg·kg-1·h-1速率静脉输注至CPB结束后60 min;C组给予等容量生理盐水.分别于CPB前、CPB结束后30、60 min时采集动脉血样,进行动脉血气分析,计算呼吸指数和氧合指数;然后处死动物,取肺组织,测定MDA含量、SOD活性和转化生长因子-β1( TGF-β1) mRNA表达;光镜和电镜下观察肺组织病理学结果.结果 与C组比较,N组呼吸指数和肺组织MDA含量降低,氧合指数和肺组织SOD活性升高,TGF-β1 mRNA表达下调(P＜0.05或0.01),肺组织病理学损伤程度明显减轻.结论 N-乙酰半胱氨酸可减轻CPB诱发犬肺损伤,其机制与减轻脂质过氧化反应,下调肺组织TGF-β1表达有关.     

Effect of hypothermic hemodilutional cardiopulmonary bypass on plasma sufentanil and catecholamine concentrations in humans

The effect of hypothermic hemodilutional cardiopulmonary bypass (CPB) on plasma sufentanil and catecholamine concentrations was studied in four groups of ten patients each, receiving four different doses of sufentanil. Samples for measurement of sufentanil were obtained before CPB, at 15, 30, and 45 minutes of CPB, during rewarming, immediately after and 15, 60, and 240 minutes after CPB. In addition, in groups III and IV, which received the highest dose of sufentanil, blood samples were also obtained for measurement of plasma levels of epinephrine and norepinephrine. Sufentanil concentration decreased in all groups with the start of CPB (group I, 2.92 +/- 0.2 to 2.04 +/- 0.2; group II, 3.30 +/- 0.3 to 1.51 +/- 0.2; group III, 7.08 +/- 0.7 to 3.45 +/- 0.3; group IV, 10.33 +/- 0.5 to 4.59 +/- 0.5 ng/ml). No further decreases occurred during CPB but increases occurred with rewarming. The first measurement after CPB approached the concentration before CPB (group I, 2.82 +/- 0.3; group II, 2.56 +/- 0.5; group III, 4.42 +/- 0.4; group IV, 6.10 +/- 0.4 ng/ml). Norepinephrine concentrations demonstrated a wide variability with no significant changes. Epinephrine levels increased significantly during rewarming in both groups (group III, 141 +/- 23 to 279 +/- 79 pg/ml; P less than 0.05; group IV, 105 +/- 24 to 267 +/- 68 pg/ml, P less than 0.05). The stability of plasma sufentanil concentrations during CPB suggest that no measurable metabolism or excretion occurred. The increase with rewarming and after CPB suggest significant sequestration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Melatonin attenuates posttransplant lung ischemia-reperfusion injury

BACKGROUND: Melatonin, a pineal hormone, is a free radical scavenger and an antioxidant. The purpose of this study was to assess the protective effect of melatonin on posttransplant lung ischemia-reperfusion injury. METHODS: Rat single-lung transplantation was performed in two (n = 10) experimental groups after 18 hours of cold (4 degrees C) ischemia. Group I animals consisted of the ischemic control group. In group II, donor and recipient animals were treated with intraperitoneal injection of 10 mg/kg melatonin 10 minutes before harvest and reperfusion, respectively. After 2 hours of reperfusion, oxygenation, plasma, and bronchoalveolar lavage nitrite levels were measured. Lung tissue was assessed for thiobarbituric acid reactive substances and myeloperoxidase activity. Peak airway pressure was recorded throughout the reperfusion period. RESULTS: The melatonin-treated group showed significantly better oxygenation (321.8+/-33.8 mm Hg versus 86.1+/-17.4 mm Hg; p < 0.001), reduced lipid peroxidation (0.65+/-0.3 nmol/g versus 1.63+/-0.8 nmol/g; p = 0.032), and reduced myeloperoxidase activity (0.56+/-0.1 deltaOD x mg(-1) x min(-1) versus 1.01+/-0.2 deltaOD x mg(-1) x min(-1); p = 0.032). Bronchoalveolar lavage nitrite levels in the transplanted lungs were significantly lower in group II than in group I (0.34+/-0.06 micromol/L versus 1.65+/-0.6 micromol/L; p = 0.016). In group II significant reduction in peak airway pressure was noted compared with group I (p = 0.002). CONCLUSIONS: In this model, exogenously administered melatonin effectively protected lungs from reperfusion injury after prolonged ischemia.     

N-acetylcysteine reduces malondialdehyde levels in chronic hemodialysis patients--a pilot study

BACKGROUND: Oxidative stress has been implicated in the development of endothelial damage in hemodialysis (HD). We have assessed the effects of N-acetylcysteine (NAC), a compound with antioxidant effects, on malondialdehyde (MDA), a marker of oxidative stress on lipid peroxidation. METHODS: A clinical trial was conducted in which 24 chronic HD patients were divided into 2 groups according to gender, age, time on HD and cause of renal failure. The NAC group (n = 12) received 600 mg of NAC twice a day for 30 days. The remaining patients constituted the control group (n = 12). MDA levels were measured pre- and post-dialysis at the beginning of the study (baseline) and on day 30 (30 days). RESULTS: Baseline pre- and post-dialysis MDA levels were not different between both groups and were above normal values. A significant decrease was found in the NAC group when either pre- or post-dialysis MDA levels were compared to the corresponding control group levels on day 30 (pre-dialysis NAC vs control group 3.01 +/- 0.6 vs 4.5 +/- 0.73 micromol/l, p < 0.0001, post-dialysis NAC vs control group 2.76 +/- 0.5 vs 4.39 +/- 0.7 micromol/l, p < 0.0001). Only in the NAC group were pre-dialysis MDA 30-day levels different from pre-dialysis baseline levels (3.01 +/- 0.6 vs 5.07 +/- 1.6 micromol/l, p < 0.002). Post-dialysis MDA 30-day concentrations were significantly lower than post-dialysis MDA baseline levels (2.76 +/- 0.5 vs 4.32 +/- 0.7 micromol/l, p < 0.002) and pre-dialysis MDA 30-day measurements (2.76 +/- 0.5 vs 3.01 +/- 0.6 micromol/l, p < 0.011). CONCLUSIONS: MDA levels are elevated in chronic HD patients and are not significantly reduced by HD. NAC significantly reduces malondialdehyde levels in chronic HD patients.     

Influence of cardiopulmonary bypass on plasma lipid peroxides

In 22 patients who underwent cardiac surgery with cardiopulmonary bypass (CPB), we studied the influence of CPB on the level of lipid peroxides (LPO) in plasma by means of measuring the time course of plasma LPO level during and after CPB. We expressed LPO level, which was measured by thiobarbituric acid reaction, as the level of malondialdehyde. In our preliminary study, it was found necessary to correct the plasma LPO level diluted by priming fluids of CPB machine and the concentration of plasma protein was fitted for its correction. In the following study, we used the plasma LPO level corrected by the concentration of plasma protein. LPO were significantly decreased since the initiation of CPB (1.669 +/- 0.208 versus pre-CPB 1.785 +/- 0.158 log nmol MDA/gm protein, p less than 0.05) to the post CPB 30 minutes, except around 60 minutes after initiation of CPB (1.735 +/- 0.242 log nmol MDA/gm protein, p greater than 0.05). As the initial change (the values at 30 minutes after CPB initiation) may express the effect of CPB directly in this time course of LPO, we analyzed the initial change on different background factors. By ordinary analysis of the initial change, as to the effect of type of disease (congenital and acquired), LPO were decreased in the acquired group (1.617 +/- 0.197 versus pre-CPB 1.779 +/- 0.163 log nmol MDA/gm protein, p less than 0.05). At that time the acquired group was significantly different from the congenital group (1.799 +/- 0.191 versus pre-CPB 1.800 +/- 0.157 log nmol MDA/gm protein, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuous infusion of prostaglandin E1 facilitates weaning from cardiopulmonary bypass

Vasodilators expedite the rewarming process and facilitate weaning from cardiopulmonary bypass (CPB). We continuously infused prostaglandin E1 (PG-E1) at 0.02-0.05 microgram.kg-1.min-1 (n = 11) or phentolamine (PHENT) at 5-10 micrograms.kg-1.min-1 (n = 13) during rewarming from mild hypothermic CPB. Rectal temperature was 33.3 +/- 1.7 degrees C in PG-E1 group vs. 31.3 +/- 1.3 degrees C in PHENT group at 30 minutes, and 34.0 +/- 1.2 degrees C vs. 32.7 +/- 1.1 degrees C at 40 minutes from the start of rewarming. There were significant differences (P less than 0.01 at 30 min, P less than 0.05 at 40 min) in rectal temperature between the two groups. There were no differences in perfusion index of CPB, arterial perfusion temperature, mean arterial pressure, systemic vascular resistance as well as esophageal, forehead or palm skin temperatures at any point between the two groups. The required time for weaning from CPB was significantly shorter in PG-E1 than in PHENT group (P less than 0.01, 36 +/- 8 min vs. 46 +/- 11 min). Our results also strongly suggest that PG-E1 preferentially improves splanchnic blood flow.     

Effects of phentolamine on tissue perfusion in pediatric cardiac surgery

OBJECTIVE: To evaluate whether the deleterious effects of cardiopulmonary bypass (CPB) can be overcome by phentolamine-induced pharmacologic vasodilation in pediatric patients with congenital heart disease. DESIGN: Prospective, randomized, clinical study. SETTING: Single university hospital. PARTICIPANTS: Forty-three pediatric patients undergoing open cardiac surgery for repair of congenital heart disease. INTERVENTIONS: Patients were randomly allocated into two groups. Patients in group 1 (n = 22) received 0.2 mg/kg of phentolamine during the cooling and rewarming periods of CPB. Group 2 patients (n = 21) did not receive phentolamine. Temperature measurements (rectal [R], nasopharyngeal [N], and toe [P]) and serum lactate values were obtained before, during, and after CPB; systemic oxygen consumption was evaluated during CPB. MEASUREMENTS AND MAIN RESULTS: At the end of the CPB period and at the end of the operation, lactate values of group 1 (1.87+/-0.37 and 1.8+/-0.39 mmol/L, respectively) were significantly lower than values of group 2 (2.24+/-0.28 and 2.33+/-0.33 mmol/L; p < 0.05 and p < 0.05, respectively). At the beginning of the rewarming period N-R temperature gradients of group 1 (0.14 degrees C+/-0.92 degrees C) were lower than group 2 (-0.58 degrees C+/-1.84 degrees C) values (p < 0.05). Central-peripheral temperature gradients of group 1 obtained at the end of the CPB period (N-R = 2.18 degrees C+/-0.69 degrees C; N-P = 7.84 degrees C+/-1.54 degrees C; R-P = 5.66 degrees C+/-1.70 degrees C) were significantly lower than the values of group 2 (N-R = 2.80 degrees C+/-0.91 degrees C, N-P = 9.97 degrees C+/-2.02 degrees C; R-P = 7.18 degrees C+/-2.10 degrees C; p < 0.05; p < 0.001; p < 0.05). At the end of the operation values of group 1 (N-R = 0.48 degrees C+/-0.31 degrees C; N-P = 6.30 degrees C+/-1.23 degrees C; R-P = 5.82 degrees C+/-1.16 degrees C) were significantly lower than the values of group 2 (N-R = 0.94 degrees C+/-0.56 degrees C; N-P = 8.69 degrees C+/-0.28 degrees C; R-P = 7.75 degrees C+/-2.15 degrees C; p < 0.05; p < 0.001; p < 0.001). The systemic oxygen consumption values of group 1 were higher than group 2 (6.26+/-1.82 v 5.17+/-1.05 mL/min/kg; p < 0.05) after complete rewarming. Mean arterial pressure (MAP) values of group 1 (58.9+/-6.4 mmHg) were lower than group 2 (63.4+/-6.7 mmHg) at the period after CPB (p = 0.03). CONCLUSION: The results suggest that the use of phentolamine during CPB is associated with limited systemic anaerobic metabolism and more uniform body perfusion.     

N-乙酰半胱氨酸对体外循环下心脏瓣膜置换术患者心肌缺血再灌注损伤的影响

目的 探讨N-乙酰半胱氨酸对体外循环(CPB)下心脏瓣膜置换术患者心肌缺血再灌注损伤的影响.方法 择期CPB下行心脏瓣膜置换术的风湿性心脏病患者22例,性别不限,年龄21-60岁,ASA Ⅱ或Ⅲ级,心功能Ⅱ或Ⅲ级,随机分为2组(n=11):对照组(C组)和N-乙酰半胱氨酸组(N组).N组预充液中加入N-乙酰半胱氨酸100 mg/kg,停搏液中加入50 mg/kg,C组给予生理盐水替代.于麻醉诱导前10 min和术毕时,记录HR、MAP、中心静脉压(CVP)、肺动脉压(PAP)、肺毛细血管楔压(PCWP)、心输出量(CO)和心脏指数(CI).于切皮前即刻、主动脉开放后0.5、6、12和24 h时,采集桡动脉血样行血气分析,采集中心静脉血样测定血浆白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、丙二醛(MDA)、心肌肌钙蛋白I(cTnI)的浓度和超氧化物歧化酶(SOD)活性.于CPB前即刻和停机即刻,取心肌组织,计数凋亡细胞,观察心肌细胞超微结构.结果 与c组比较,N组HR、MAP、CVP、PAP、PCWP、pH值、红细胞压积、动脉血氧分压、动脉血二氧化碳分压和剩余碱差异无统计学意义(P>0.05),主动脉开放后TNF-α、IL-6、cTnI和MDA的浓度降低,SOD活性升高,CPB停机即刻心肌凋亡细胞计数降低,术毕CO和CI升高(P<0.05或0.01),心肌病理损伤减轻.结论 N-乙酰半胱氨酸可减轻体外循环下心脏瓣膜置换术患者心肌缺血再灌注损伤.     

Postoperative ventilatory and circulatory effects of extended rewarming during cardiopulmonary bypass

Postoperative effects of extended rewarming (ECR) after hypothermic cardiopulmonary bypass (CPB) were studied. All (n = 28) patients were rewarmed to a nasopharyngeal temperature exceeding 38 degrees C before terminating CPB. In 12 patients (control group) the rectal temperature (Tre) was 33.8 +/- 1.7 degrees C (mean +/- sd) at termination of CPB. In sixteen patients (ECR group) rewarming during CPB was continued to a Tre of 36.8 +/- 0.5 degrees C. Postoperative body temperatures, heat content, shivering, oxygen uptake, CO2 production and haemodynamic variables were measured. ECR reduced the heat gain required to complete core rewarming to 665 +/- 260 kJ, compared with 1037 +/- 374 kJ in the control group (p less than 0.01). The incidence of shivering was reduced (p less than 0.05) as well as shivering intensity and duration. In seven non-shivering ECR group patients this coincided with significantly reduced metabolic and ventilatory demands but these improvements were not valid for the group as a whole. The required ventilation temporarily during postoperative rewarming in both groups increased to 250 per cent of the basal need. Extending CPB rewarming (to at least 36 degrees C Tre) was inefficient when used as the sole measure to reduce the untoward effects of residual hypothermia during recovery after cardiac surgery with hypothermic CPB.     

Recipient treatment with trimetazidine improves graft function and protects energy status after lung transplantation.

BACKGROUND: Ischemia-reperfusion injury remains an important obstacle to successful lung transplantation. Trimetazidine is an anti-ischemic drug that restores the ability of ischemic cells to produce energy and reduces the generation of oxygen-derived free radicals. The aim of this study was to assess the protective effect of trimetazidine after prolonged ischemia in lung transplantation. METHODS: Rat single-lung transplantation was performed in 4 experimental groups (n = 5 each). In all groups, transplantation was performed after 18 hours of cold (4 degrees C) ischemia. All donor lungs were flushed with low-potassium dextran-glucose (LPDG) solution that also contained 500 microg/liter prostaglandin estradiol (E(1)). Groups studied included: Group I: flush solution was administered containing 10(-6) mol/liter trimetazidine (TMZ), neither donor nor recipient treatment given; Group II: donors were treated with 5 mg/kg intravenous TMZ 10 minutes prior to harvest, but the flush solution did not contain TMZ; Group III: recipients treated with 5 mg/kg intravenous TMZ 10 minutes before reperfusion, and flush solution contained 10(-6) mol/liter trimetazidine; Group IV: ischemic control group. After 2 hours of reperfusion, oxygenation was measured and lung tissue was frozen and assessed for adenosine triphosphate (ATP) content, myeloperoxidase (MPO) activity and thiobarbituric acid-reactive substances (TBARS). Peak airway pressure (PawP) was recorded throughout the reperfusion period. RESULTS: Group III showed significantly higher levels of ATP content (11.1 +/- 5.01 pmol vs Group I, 3.36 +/- 1.8 pmol, p = 0.008; vs Group II, 4.7 +/- 1.9 pmol, p = 0.03; vs Group IV, 0.7 +/- 0.2 pmol, p = 0.008), better oxygenation (442.5 +/- 26.5 mm Hg, vs Group I, 161.06 +/- 54.5 mm Hg; vs Group II, 266.02 +/- 76.9 mm Hg; vs Group IV, 89.4 +/- 14.7 mm Hg, p = 0.008) and reduced lipid peroxidation (TBARS) (0.15 +/- 0.03 nmol/g; vs Group I, 1.04 +/- 0.76 nmol/g; vs Group II, 0.69 +/- 0.4 nmol/g; vs Group IV, 2.29 +/- 0.4 nmol/g, p = 0.008). PawP and MPO activity were comparable in the 4 study groups. CONCLUSION: Recipient treatment with TMZ provided significant protection of energy status, better oxygenation and reduced lipid peroxidation. Our data suggest that TMZ may be an important adjunct in the prevention of post-transplant lung ischemia-reperfusion injury.     

Changes of microvascular vasomotion and oxygen metabolism during cooling and rewarming period of cardiopulmonary bypass

Microcirculation plays an important role in keeping a stable tissue metabolism during cardiopulmonary bypass (CPB). The relationship between microvascular vasomotion (MV) and total body's oxygen metabolism with temperature alteration during CPB remains unclear. Is there a relationship, or is the autoregulation a consequence of CO2, pressure and/or blood flow? The purpose of this study was to investigate the effect of temperature alteration on cutaneous MV and the total body's oxygen metabolism during CPB. Sixteen consecutive patients scheduled for elective cardiac valve replacement surgery were included in this study. The pump flow varied from 1.8-3.0 L/m(-2)min(-1) to maintain venous oxygen saturation above 65% and mean arterial blood pressure above 60 mmHg. At a nasopharyngeal temperature of 30 degrees C, oxygen consumption (VO2) and oxygen extraction (O2 ext) were measured during the cooling and rewarming periods. MV and skin microcircular flow (SMF) were monitored dynamically at the middle of two sides of the eyebrow with a laser Doppler flowmeter simultaneously VO2 and O2 ext at 30 degrees C were significantly lower during the cooling period (VO2, 49.9 +/- 17.7 mL/m(-2)/min(-1); O2 ext, 19.3 +/- 6.2%) than that during the rewarming period (VO2, 133.3 +/- 40.0 mL/m(-2)/min(-1); O2 ext, 35.2 +/- 9.2%) (p < .05). SMF was significantly depressed during CPB (p < .05). SMF during the cooling period (50.2% +/- 10.1%) was significantly less than that during the rewarming period (79.5% +/- 12.3%) (p < .05). MV was significantly less active during CPB than that before CPB (5.8 +/- 1.2 cyc/min) (p < .05), whereas there was no significant difference in MV between the cooling (3.7 +/- 1.8 cyc/min) and the rewarming period (4.1 +/- 1.5 cyc/min) and (p > .05). SMF and MV were depressed during hypothermic CPB, and there was some recovery during the rewarming period. Compared to baseline, SMF and MV were still significantly reduced during the warming period, indicating microvascular function was abnormal. Some measures should be taken for improvement of microvascular function during CPB.     

Biologically variable pulsation improves jugular venous oxygen saturation during rewarming

BACKGROUND: Conventional pulsatile (CP) roller pump cardiopulmonary bypass (CPB) was compared to computer controlled biologically variable pulsatile (BVP) bypass designed to return beat-to-beat variability in rate and pressure with superimposed respiratory rhythms. Jugular venous O2 saturation (SjvO2) below 50% during rewarming from hypothermia was compared for the two bypass techniques. A SjvO2 less than 50% during rewarming is correlated with cognitive dysfunction in humans. METHODS: Pigs were placed on CPB for 3 hours using a membrane oxygenator with alpha-stat acid base management and arterial filtration. After apulsatile normothermic CPB was initiated, animals were randomized to CP (n = 8) or BVP (roller pump speed adjusted by an average of 2.9 voltage output modulations/second; n = 8), then cooled to a nasopharyngeal temperature of 28 degrees C. During rewarming to stable normothermia, SjvO2 was measured at 5 minute intervals. The mean and cumulative area for SjvO2 less than 50% was determined. RESULTS: No between group difference in temperature existed during hypothermic CPB or during rewarming. Mean arterial pressure, arterial partial pressure O2, and arterial partial pressure CO2 did not differ between groups. The hemoglobin concentration was within 0.4 g/dL between groups at all time periods. The range of systolic pressure was greater with BVP (41 +/- 18 mm Hg) than with CP (12 +/- 4 mm Hg). A greater mean and cumulative area under the curve for SjvO2 less than 50% was seen with CP (82 +/- 96 versus 3.6% +/- 7.3% x min, p = 0.004; and 983 +/- 1158 versus 42% +/- 87% x min; p = 0.004, Wilcoxon 2-sample test). CONCLUSIONS: Computer-controlled BVP resulted in significantly greater SjvO2 during rewarming from hypothermic CPB. Both mean and cumulative area under the curve for SjvO2 less than 50% exceeded a ratio of 20 to 1 for CP versus BVP. Cerebral oxygenation is better preserved during rewarming from moderate hypothermia with bypass that returns biological variability to the flow pattern.     

An experimental study of tissue injury associated with reperfusion in ischemic limbs

Twenty adult mongrel dogs were divided into three groups. Group I: control (n = 7), group II: limb ischemia for 6 hours followed by reperfusion (n = 6), and group III: administration of alpha-tocopherol after 6 hours of ischemia, and reperfusion (n = 7). In group II, serum CPK and LPO increased after reperfusion with peak levels of 38,000 +/- 9,800 mU/ml and 20.4 +/- 3.7 nmol/ml respectively, which were significantly higher than those in group I. (CPK: p less than 0.02, LPO less than 0.03). In group III, the peak levels of serum CPK and LPO were regulated to the low level of 1,060 +/- 290 mU/ml and 9.2 +/- 4.5nmol/ml, respectively, which were significantly lower than those in group II. (CPK: p less than 0.02, LPO less than 0.04). Additional 13 dogs were divided into two groups in order to assess tissue LPO in the limb, liver, and kidney. Group A: control (n = 5), group B: reperfusion after 6 hours of ischemia (n = 8). Tissue LPO level of 1.89 +/- 0.74nmol/mg-protein in the gastrocnemius muscle in group B was significantly higher than that in group A (p less than 0.02), although there was no significant difference in the gracilis muscle, liver, and kidney. These results prove indirectly the participation of lipid peroxidative reaction by active oxygen in the mechanism of development of reperfusion injury, and suggest the preventive effect of alpha-tocopherol to reperfusion injury.