Silatranes as stimulators of the development of granulation tissue

Experiments on rats were made to study the effect of I-(chloromethyl) silatrane and I- (ethoxy) silatrane and that of triethanolamine and chloromethyl triethoxysilane on biochemical parameters of granular-fibrous tissue. The preparations were applied to a wound defect in the form of liniments. Silatranes were found to stimulate proliferation of the cells and to increase their biosynthetic activity, to favour accumulation of collagen and non-collagenic proteins, and reduction of the inflammatory phenomena. The silicon-containing fragment of the silatrane molecule chloromethyl triethoxysilane produced an analogous but less marked action. Triethanolamine containing no silicon was found to be as less active. These data indicate that silicon entering the silatrane grouping is of great importance for the occurrence of its biological activity.     

Possible mechanisms of anti-ulcer action of silatranes

A stimulating effect of methylethyl(silatrane-I-ilmethyl)-sulphonium iodides, 1-(ethoxy)silatranes and 1-(chloromethyl)silatrane on the processes of rat test acetate ulcer healing is studied. Silatranes efficiency is not inferior to oxyferriscorbone and exceeds that of methacil. It is shown that all preparations inhibit the processes of lipids peroxidation in the blood, in liposomes and stomach tissue.     

Role of beta-adrenergic agonists in the control of vascular capacitance

The role of beta-adrenergic agonists, such as isoproterenol, on vascular capacitance is unclear. Some investigators have suggested that isoproterenol causes a net transfer of blood to the chest from the splanchnic bed. We tested this hypothesis in dogs by measuring liver thickness, cardiac output, cardiopulmonary blood volume, mean circulatory filling pressure, portal venous, central venous, pulmonary arterial, and systemic arterial pressures while infusing norepinephrine (2.6 micrograms.min-1.kg-1), or isoproterenol (2.0 micrograms.min-1.kg-1), or histamine (4 micrograms.min-1.kg-1), or a combination of histamine and isoproterenol. Norepinephrine (an alpha- and beta 1-adrenergic agonist) decreased hepatic thickness and increased mean circulatory filling pressure, cardiac output, cardiopulmonary blood volume, total peripheral resistance, and systemic arterial and portal pressures. Isoproterenol increased cardiac output and decreased total peripheral resistance, but it had little effect on liver thickness or mean circulatory filling pressure and did not increase the cardiopulmonary blood volume or central venous pressure. Histamine caused a marked increase in portal pressure and liver thickness and decreased cardiac output, but it had little effect on the estimated mean circulatory filling pressure. Isoproterenol during histamine infusions reduced histamine-induced portal hypertension, reduced liver size, and increased cardiac output. We conclude that the beta-adrenergic agonist, isoproterenol, has little influence on vascular capacitance or liver volume of dogs, unless the hepatic outflow resistance is elevated by agents such as histamine.     

Relation between zinc, copper, and magnesium concentrations following cardiopulmonary bypass and postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting

Atrial fibrillation is the most frequently encountered arrhythmia following cardiac surgery. Since the essential trace elements zinc, copper, and magnesium are suspected to have an effect on postoperative atrial fibrillation, the concentrations of these elements were determined by flame atomic absorption spectrophotometry in the plasma of 60 patients undergoing elective coronary artery bypass grafting. Blood samples were collected every 30 min during cardiopulmonary bypass and postoperatively. Plasma concentrations of copper, zinc, and magnesium were measured with flame atomic absorption spectrophotometry. All patients were monitored by continuous electrocardiography until they became outpatients or immediately after atrial fibrillation had taken place. Atrial fibrillation occurred in 13 of the 60 patients, corresponding to 21.7%. The zinc and copper concentrations at postoperative days 1 and 3 were significantly different (P < 0.05) between patients with and without atrial fibrillation. The concentrations of zinc following cardiopulmonary bypass recovered more slowly in patients with postoperative atrial fibrillation than in patients without it. Whether or not supplemental zinc could lower the incidence of postoperative atrial fibrillation should be evaluated in future prospective randomized clinical trials.     

Alteration of Plasma Trace Elements in Patients Undergoing Open Heart Surgery

Trace elements may contribute to myocardial dysfunction and susceptibility of the phospholipid cell membrane to free-radical damage and oxidative changes. We studied the concentration of trace elements copper, zinc, and magnesium in cardiac surgery. Fifty-four consecutive patients for elective coronary artery bypass grafting (n?=?30) and valve replacement (n?=?24) were studied. Blood samples were collected every 30 min (T1–T5) during cardiopulmonary bypass and postoperatively (T6–T9). Plasma concentrations of copper, zinc, and magnesium were measured with flame atomic absorption spectrophotometry. The concentrations of copper, zinc, and magnesium were significantly different during and after cardiopulmonary bypass (p?<?0.01). The zinc concentration at T7 and T8 (p?<?0.01) and the copper concentration at T1, T9 (p?<?0.05) were significantly different between two groups. However, the magnesium concentration had no significant differences between the two groups (p?>?0.05). In patients undergoing valve replacement or coronary artery bypass grafting, the concentrations of copper and zinc decreased significantly during cardiopulmonary bypass. Our study suggests that the current cardiopulmonary bypass protocol is adequate in the maintenance of c magnesium. However, the low copper and zinc concentrations found in the present study may suggest that in the future, supplementation particularly of copper and zinc may become a necessary procedure in cardiac surgery with cardiopulmonary bypass.     

Changes in plasma atrial natriuretic peptide--immunoreactivity in patients undergoing coronary artery bypass graft placements

Plasma atrial natriuretic peptide immunoreactivity (IrANP) was measured before, during, and after cardiopulmonary bypass for coronary artery bypass graft placement. Eight subjects scheduled for elective operation had in the premedicated preoperative state slightly elevated IrANP compared to controls. Neither induction of anesthesia with a high dose narcotic/non-depolarising relaxant/diazepam technique nor cardiopulmonary bypass changed IrANP significantly. Mixed venous and arterial IrANP increased immediately after discontinuing bypass, and remained elevated 1 h later. Because ANPs affect peripheral resistance as well as urinary sodium loss, the post-bypass elevations in these peptides may contribute to cardiovascular and diuretic effects after cardiopulmonary bypass.     

Implementation of intrinsic lumped parameter modeling into computational fluid dynamics studies of cardiopulmonary bypass

Stroke and cerebral hypoxia are among the main complications during cardiopulmonary bypass (CPB). The two main reasons for these complications are the cannula jet, due to altered flow conditions and the sandblast effect, and impaired cerebral autoregulation which often occurs in the elderly. The effect of autoregulation has so far mainly been modeled using lumped parameter modeling, while Computational Fluid Dynamics (CFD) has been applied to analyze flow conditions during CPB. In this study, we combine both modeling techniques to analyze the effect of lumped parameter modeling on blood flow during CPB. Additionally, cerebral autoregulation is implemented using the Baroreflex, which adapts the cerebrovascular resistance and compliance based on the cerebral perfusion pressure.     

大鼠体外循环模型的建立及改进

目的对现有大鼠体外循环模型予以改进,降低模型复制难度,并使之更适合用于研究体外循环对肺功能的影响。方法成年雄性SD大鼠16只,体重300～350g,各8只分别用于建模和供血。经右颈静脉、左股静脉引流,右股动脉人工灌注建立体外循环,血气分析监测内环境变化。实验过程中,保留大鼠自主呼吸,不进行机械通气。结果成功建成8只大鼠体外循环模型并按计划顺利脱离人工循环。体外循环期间转流量为70～80mL/（kg·min）,血流动力学监测和血气分析结果基本正常。结论进一步简化了建立大鼠体外循环模型的操作,最显著的改进之处在于避免了机械通气对大鼠肺功能潜在的不良效应,从而更加适合用于研究体外循环对肺功能的影响。     

Establishment of persistent infection with HIV-1 abrogates the caspase-3-dependent apoptotic signaling pathway in U937 cells

Treatment of 26L cells, a subclone obtained from U937 cells, with TNF-alpha or DNA-damaging agents such as teniposide (VM26) and camptothecin (CPT) induced morphologically and biochemically typical apoptotic changes, including the activation of procaspase-3. The cells persistently infected with HIV-1 (26L/HIV), however, showed a marked resistance to VM26 and CPT, whereas they hardly lost the sensitivity to TNF-alpha. TNF-alpha-induced apoptosis of 26L/HIV cells proceeded without the increase in caspase-3 activity, indicating that signaling for apoptosis in the infected cells proceeded through an alternative caspase-3-independent pathway which could respond to TNF-alpha but not to VM26 and CPT. The evidence that p-toluenesulfonyl-l-lysine chloromethyl ketone (a trypsin-like serine protease inhibitor) blocked VM26- and CPT-induced apoptotic changes but not TNF-alpha-induced apoptosis also supported the existence of the alternative TNF-alpha-inducible pathway. The results also suggest that a TLCK-sensitive protease is involved upstream of the procaspase-3 activation process and that the protease is essential for the progress of VM26- and CPT-induced apoptosis. The similar effect of HIV-1-productive infection on the apoptosis induced by the DNA-damaging agents was also confirmed by utilizing U1 cells, which are latently HIV-1-infected U937 cells. The cells became resistant to these agents after induction of the viral production by pretreatment with PMA. These results suggest that persistent HIV-1 infection blocks an apoptotic pathway triggered by DNA damaging agents through the inhibition of the procaspase-3 activation process.     

Effect of bronchial artery blood flow on cardiopulmonary bypass-induced lung injury

Cardiovascular surgery requiring cardiopulmonary bypass (CPB) is frequently complicated by postoperative lung injury. Bronchial artery (BA) blood flow has been hypothesized to attenuate this injury. The purpose of the present study was to determine the effect of BA blood flow on CPB-induced lung injury in anesthetized pigs. In eight pigs (BA ligated) the BA was ligated, whereas in six pigs (BA patent) the BA was identified but left intact. Warm (37 degrees C) CPB was then performed in all pigs with complete occlusion of the pulmonary artery and deflated lungs to maximize lung injury. BA ligation significantly exacerbated nearly all aspects of pulmonary function beginning at 5 min post-CPB. At 25 min, BA-ligated pigs had a lower arterial Po(2) at a fraction of inspired oxygen of 1.0 (52 +/- 5 vs. 312 +/- 58 mmHg) and greater peak tracheal pressure (39 +/- 6 vs. 15 +/- 4 mmHg), pulmonary vascular resistance (11 +/- 1 vs. 6 +/- 1 mmHg x l(-1) x min), plasma TNF-alpha (1.2 +/- 0.60 vs. 0.59 +/- 0.092 ng/ml), extravascular lung water (11.7 +/- 1.2 vs. 7.7 +/- 0.5 ml/g blood-free dry weight), and pulmonary vascular protein permeability, as assessed by a decreased reflection coefficient for albumin (sigma(alb); 0.53 +/- 0.1 vs. 0.82 +/- 0.05). There was a negative correlation (R = 0.95, P < 0.001) between sigma(alb) and the 25-min plasma TNF-alpha concentration. These results suggest that a severe decrease in BA blood flow during and after warm CPB causes increased pulmonary vascular permeability, edema formation, cytokine production, and severe arterial hypoxemia secondary to intrapulmonary shunt.     

体外循环长时间转流535例临床估价

目的：介绍长时间体外循环管理的方法和经验。方法：我院自1984年至1995年12月共施行体外循环时间超过120分钟的心脏直视手术535例,其中男性345例,女性190例;年龄3～71岁．体表面积0．55～2．2平方米。双瓣替换术151例．二尖瓣替换术113例,法乐氏四联症107例,冠状动脉旁路移植术62例,主动脉瓣替换术30例．复杂畸形25例．其它47例。全组病例均采用中深度低温及中深度血液稀释,心肌保护采用灌注含钾冷停跳液。复跳后．适当延长辅助循环时间。术中采用血液超滤法,并尽可能采用搏动性血流,以确保重要脏器有充沛的血供。结果：全组病例中．体外循环时间为70～214分钟,心脏停跳时间72～230分钟。术中自动复跳209例．自动复跳率占39％。结论：在长时间体外循环心脏直视手术中．综合应用上述措施．可显著提高体外循环质量．增加手术成功率。     

Pulsatile flow during cardiopulmonary bypass preserves postoperative microcirculatory perfusion irrespective of systemic hemodynamics

The onset of nonpulsatile cardiopulmonary bypass is known to deteriorate microcirculatory perfusion, but it has never been investigated whether this may be prevented by restoration of pulsatility during extracorporeal circulation. We therefore investigated the distinct effects of nonpulsatile and pulsatile flow on microcirculatory perfusion during on-pump cardiac surgery. Patients undergoing coronary artery bypass graft surgery were randomized into a nonpulsatile (n = 17) or pulsatile (n = 16) cardiopulmonary bypass group. Sublingual mucosal microvascular perfusion was measured at distinct perioperative time intervals using sidestream dark field imaging, and quantified as the level of perfused small vessel density and microvascular flow index (vessel diameter < 20 μm). Microcirculation measurements were paralleled by hemodynamic and free hemoglobin analyses. The pulse wave during pulsatile bypass estimated 58 ± 17% of the baseline blood pressure waveform. The observed reduction in perfused vessel density during aorta cross-clamping was only restored in the pulsatile flow group and increased from 15.5 ± 2.4 to 20.3 ± 3.7 mm/mm(2) upon intensive care admission (P < 0.01). The median postoperative microvascular flow index was higher in the pulsatile group [2.6 (2.5-2.9)] than in the nonpulsatile group [2.1 (1.7-2.5); P = 0.001]. Pulsatile flow was not associated with augmentation of free hemoglobin production and was paralleled by improved oxygen consumption from 70 ± 14 to 82 ± 16 ml·min(-1)·m(-2) (P = 0.01) at the end of aortic cross-clamping. In conclusion, pulsatile cardiopulmonary bypass preserves microcirculatory perfusion throughout the early postoperative period, irrespective of systemic hemodynamics. This observation is paralleled by an increase in oxygen consumption during pulsatile flow, which may hint toward decreased microcirculatory heterogeneity during extracorporeal circulation and preservation of microcirculatory perfusion throughout the perioperative period.     

Short-term variability of blood pressure: effects of lower-body negative pressure and long-duration bed rest

Mild lower-body negative pressure (LBNP) has been utilized to selectively unload cardiopulmonary baroreceptors, but there is evidence that arterial baroreceptors can be transiently unloaded after the onset of mild LBNP. In this paper, a black box mathematical model for the prediction of diastolic blood pressure (DBP) variability from multiple inputs (systolic blood pressure, R-R interval duration, and central venous pressure) was applied to interpret the dynamics of blood pressure maintenance under the challenge of LBNP and in long-duration, head-down bed rest (HDBR). Hemodynamic recordings from seven participants in the WISE (Women's International Space Simulation for Exploration) Study collected during an experiment of incremental LBNP (-10 mmHg, -20 mmHg, -30 mmHg) were analyzed before and on day 50 of a 60-day-long HDBR campaign. Autoregressive spectral analysis focused on low-frequency (LF, ~0.1 Hz) oscillations of DBP, which are related to fluctuations in vascular resistance due to sympathetic and baroreflex regulation of vasomotor tone. The arterial baroreflex-related component explained 49 ± 13% of LF variability of DBP in spontaneous conditions, and 89 ± 9% (P < 0.05) on day 50 of HDBR, while the cardiopulmonary baroreflex component explained 17 ± 9% and 12 ± 4%, respectively. The arterial baroreflex-related variability was significantly increased in bed rest also for LBNP equal to -20 and -30 mmHg. The proposed technique provided a model interpretation of the proportional effect of arterial baroreflex vs. cardiopulmonary baroreflex-mediated components of blood pressure control and showed that arterial baroreflex was the main player in the mediation of DBP variability. Data during bed rest suggested that cardiopulmonary baroreflex-related effects are blunted and that blood pressure maintenance in the presence of an orthostatic stimulus relies mostly on arterial control.     

Hemodynamic aspects of the hypotensive action of captopril

Captopril was tested in acute experiments on anesthetized cats subject to cardiopulmonary bypass. The drug was shown to reduce total peripheral vascular resistance and to increase vascular bed capacity.     

单唾液酸神经节苷脂对体外循环大鼠海马神经元的影响

目的:探讨单唾液酸神经节苷脂(GM1)对体外循环大鼠海马神经元凋亡的影响及机制。方法:18只健康成年雄性SD大鼠,随机分为3组:正常对照组、CPB组和GM1组。经右颈静脉插管引流,右颈动脉插管灌注建立CPB,转流时间60 min,建立CPB动物模型。CPB后3 h时处死大鼠,4%多聚甲醛灌注固定后取左侧大脑组织,利用TUNEL法观察海马神经元凋亡,免疫组化法检测海马神经元Caspase-3蛋白表达,并用电子显微镜观察神经元超微结构变化。结果:与正常组比较,GM1组和CPB组海马神经元凋亡细胞平均积分光密度(IA)、Caspase-3蛋白表达均增强(P<0.01)。GM1组海马神经元凋亡细胞平均积分光密度(IA)为8.94±0.42,与CPB组(14.87±0.70)相比明显降低(P<0.01);GM1组海马Caspase-3阳性神经细胞平均积分光密度比CPB组降低了38.84%(P<0.01)。电镜下CPB组海马可见异染色质明显边集、凝聚,线粒体嵴减少或空泡变性,细胞器消失等不可逆性的损伤改变;GM1组神经元细胞核圆形,线粒体嵴少量减少,细胞器仍可见。结论:单唾液酸神经节苷脂对体外循环大鼠海马神经元凋亡具有明显的抑制作用,其机制与抑制Caspase-3的表达有关。     

The total antioxidant capacity of blood plasma during cardiovasculary bypass surgery in patients with coronary heart disease

We studied he effect of ischemia and reperfusion on the total antioxidant capacity (TAC) of blood plasma during cardiopulmonary bypass surgery employing the modified St. Thomas Hospital cardioplegic solution. TAC was determined using the FRAP method. TAC decreased during surgery, but no further decrease in TAC was observed during reperfusion, indicating that it is a relatively stable parameter of the antioxidative barrier of the body.     

The effect of methylprednisolone on cytokine concentration and leukocyte adhesion molecule expression in an isolated cardiopulmonary bypass system

This study examines the effect of methylprednisolone on cytokine balance and adhesion molecule expression within an isolated cardiopulmonary bypass (CPB) system. This isolated CPB system is an in vitro model which simulates the pro-inflammatory immune response. Whole blood from 10 volunteers was obtained in two equal amounts. Heparin and saline were added to the control group while heparin and methylprednisolone were added to the methylprednisolone group. The blood was added to two identical CPB circuits and bypass commenced by a trained perfusionist. Samples were taken at blood donation (Sample 0), 10 min after the addition of drugs (Sample 1) and after 30, 60 and 90 min of CPB (Samples 2, 3 and 4, respectively). Cytokines interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1ra) and tumour necrosis factor soluble receptor 2 (TNFsr2) and the leucocyte adhesion molecules L-selectin, HLA DR, CD18 and CD11b were determined. IL-8 increased in both groups. This increase was significantly less in the methylprednisolone group. Increases in granulocyte CD11b and CD18 expression were less in the methylprednisolone group than in the control group but did not reach statistical significance. These results indicate that methylprednisolone significantly reduces the production of IL-8 in an isolated CPB system. This effect occurs in the absence of IL-10.     

Comparative effects of vasodilator drugs on flow distribution and venous return

Systemic vascular effects of hydralazine, prazosin, captopril, and nifedipine were studied in 115 anesthetized dogs. Blood flow (Q) and right atrial pressure (Pra) were independently controlled by a right heart bypass. Transient changes in central blood volume after an acute reduction in Pra at a constant Q showed that blood was draining from two vascular compartments with different time constants, one fast and the other slow. At three dose levels producing comparable reductions in systemic arterial pressure (30-40% at the highest dose), these drugs had different effects on flow distribution and venous return. Hydralazine and prazosin had parallel and balanced effects on arterial resistance of the two vascular compartments, and flow distribution was unaltered. Captopril preferentially reduced arterial resistance of the compartment with a slow time constant for venous return (-26 +/- 6%, -30 +/- 6%, -50 +/- 5% at 0.02, 0.10, and 0.50 mg X kg-1 X h-1, respectively; means +/- SEM) without altering arterial resistance of the fast time-constant compartment. Blood flow to the slow time-constant compartment was increased 43 +/- 14% at the highest dose, and central blood volume was reduced 108 +/- 15 mL. In contrast, nifedipine had a balanced effect on arterial resistance with the lowest dose (0.025 mg/kg) but caused a preferential reduction in arterial resistance of the fast time-constant compartment at higher doses (-38 +/- 4% and -55 +/- 2% at 0.05 and 0.10 mg/kg, respectively). Blood flow to the slow time-constant compartment was reduced 36 +/- 5% at the highest dose of nifedipine, and central blood volume was increased 66 +/- 12 mL. Total systemic venous compliance was unaltered or slightly reduced by each of the four drugs. These results add further evidence to the hypothesis that peripheral blood flow distribution is a major determinant of venous return to the heart.     

Protective effect of dexmedetomidine on intestinal mucosal barrier function in rats after cardiopulmonary bypass

Cardiopulmonary bypass can result in damage to the intestines, leading to the occurrence of systemic inflammatory response syndrome. Dexmedetomidine is reported to confer anti-inflammatory properties. Here, the purpose of this study is to investigate the effect of dexmedetomidine on the intestinal mucosa barrier damage in a rat model of cardiopulmonary bypass. It was observed that cardiopulmonary bypass greatly decreased the levels of hemodynamic parameters than SHAM group, whereas dexmedetomidine pretreatment in a cardiopulmonary bypass model rat prevented this reduction. Also, it showed that compared with control animals, cardiopulmonary bypass caused obvious mucosal damage, which was attenuated in dexmedetomidine + cardiopulmonary bypass group. The above findings were in line with that of dexmedetomidine pretreatment, which increased the expression of tight junction proteins, but it decreased the levels of DAO, D-LA, FABP2, and endotoxin. Moreover, the results demonstrated that due to pre-administration of dexmedetomidine, the level of pro-inflammatory factors was decreased, while the level of anti-inflammatory cytokine was increased. Also, it showed that dexmedetomidine suppressed TLR4/JAK2/STAT3 pathway that was activated by cardiopulmonary bypass. Together, these results revealed that dexmedetomidine pretreatment relieves intestinal microcirculation, attenuates intestinal damage, and inhibits the inflammatory response of cardiopulmonary bypass model rats, demonstrating that in CPB-induced damage of intestinal mucosal barrier function, dexmedetomidine pretreatment plays a protective role by inactivating TLR4/JAK2/STAT3-mediated inflammatory pathway.