A new model of chronic cardiac ischemia in rabbits.

Chronic cardiac ischemia has mainly been studied in large species such as pigs or dogs. Little research has been performed using small species such as rabbits. In the present study, 1-3 wk after implantation of a novel device (ameroid) on the circumflex coronary artery of New Zealand White rabbits, vessel patency was evaluated by coronary angiography, corrosion cast, and radiolabeled microspheres. Coronary angiograms showed, after 21 days, either total occlusion or severe stenosis in seven of eight arteries, which was confirmed by corrosion casts. The ameroid group had less blood flow in the epicardial (-62%) and endocardial (-54%) layers of the ischemic area compared with sham-operated rabbits (P < 0.05). Blood flow increased in the ischemic area compared with day 0 during acute occlusion, suggesting that progressive coronary occlusion initiated the growth of de novo collateral vessels. Thus we have developed a new model of chronic cardiac ischemia in rabbits with documented progressive coronary stenosis and occlusion that is suitable to test various therapeutic angiogenesis strategies.     

The value of preoperative Doppler sonography for planning free perforator flaps

The individual perforating vessels have a high degree of anatomical variation, therefore it is desirable to conduct a careful examination of them before undertaking a perforator flap operation. Because locating the vessels beforehand makes performing the operative procedure much easier, the aim of the present study was to assess the value of using simple acoustic Doppler sonography to plan a perforator flap operation. The vessel examinations were carried out before taking 46 free microvascular flaps from either the lower abdominal wall or the buttock for reconstructive breast surgery. The perforating vessels located were marked, and their position relative to the umbilicus or the most cranial point of the rima ani recorded using a coordinate system. In 40 patients, a perforator flap operation (deep inferior epigastric perforator flap, n = 32; superior gluteal artery perforator flap, n = 8) was actually carried out; in six of these patients, a myocutaneous flap was used because of the insufficient availability of perforating vessels. Before the operation, perforating vessels were marked for each patient, with an average of 7.3 for the deep inferior epigastric perforator flap and 6.5 for the superior gluteal artery perforator flap. Out of 286 vessels marked for later perforator flaps, 162 were identified during the operation. A preoperatively marked vessel was used in 37 of 40 patients. In the remaining patients, a vessel was used that had not been previously marked. The vertical and horizontal distance between the perforating vessels identified during the operation and the preoperative marks averaged 0.8 cm. The results show preoperative Doppler sonography to be useful for locating the position of individual perforating vessels, making it much easier to find them during the operation.     

亚低温联合镁剂对脑缺血再灌注大鼠保护作用的研究

目的:rt-PA溶栓为缺血性卒中最有效的治疗方法,脑血流再通后挽救濒临死亡的神经细胞同时,也可能发生更为严重而持久的脑缺血再灌注损伤。本研究探讨联合应用局部亚低温(32-35℃)及硫酸镁对局灶性脑缺血再灌注大鼠的保护作用及其可能机制。方法:通过线栓法建立大鼠大脑中动脉阻塞(MCAO)及再通模型,将50只雄性Wistar大鼠随机分为假手术组、常温组、亚低温组、硫酸镁组、亚低温+硫酸镁组,每组10例,采用Longa神经功能评分、TTC染色、干湿重法、TUNEL技术,检测和比较各组脑缺血再灌注后大鼠的神经功能、脑梗死体积、脑组织含水量及凋亡细胞数。结果:与常温组相比,亚低温组与亚低温+硫酸镁组的梗死体积、神经功能评分、脑组织含水量、凋亡细胞数均明显降低,差异有显著意义(P0.05);而与亚低温组相比,亚低温+硫酸镁组局灶脑缺血大鼠的脑梗死体积、神经功能评分、脑组织含水量、凋亡细胞数均显著减少,差异有显著意义(P0.05)。结论:与单独应用亚低温相比,局部亚低温与硫酸镁联合应用,对局灶性脑缺血再灌注大鼠可发挥更有效的脑保护作用。其机制可能与抑制脑缺血再灌注后凋亡及减轻脑水肿有关。二者联用可能为缺血性卒中患者提供一种减轻溶栓后再灌注损伤的有效脑保护方法。     

Inducing occlusion effect in Y-shaped vessels using high-intensity focused ultrasound: finite element analysis and phantom validation

High-intensity focused ultrasound (HIFU) surgery offers a truly non-invasive treatment method with no skin incision, but precise targeting of tumour tissues for thermotherapy. Clinical experience reveals that the efficacy of tumour destruction not only involves in coagulating necrosis, but also involves in damaging the tumour vessels, which play an important role in tumour progression. These vessels take the elevated temperature away by perfusion, resulting in uncertainty of the occlusion effect during HIFU treatment. In this study, a Y-shaped vessel model comprising common and tumour vessels and an indirect fabrication method are proposed. The physical properties of the fabricated vessel phantom are measured and compared with human tissue. Simulation is performed using finite element modelling according to the tissue parameter, perfusion rate of the tumour vessel and treatment parameters including power intensity and exposure duration. The phantom experiments are carried out with perfusion of egg white to validate the threshold time prediction obtained from the simulation results. Our findings reveal that the threshold time obtained from experiments is consistent with the simulated one.     

The delay phenomenon: the story unfolds

Our previous studies have shown that when a flap is delayed, there is dilation of existing vessels within the flap not ingrowth of new vessels. The maximal anatomic effect on the arterial tree occurs at the level of the reduced-caliber "choke" anastomotic vessels that link adjacent vascular territories. To further investigate the sequence of anatomic changes that occurs during the delay phenomenon, a large series of 200 rabbits and 17 dogs underwent a flap delay procedure in either skin or muscle and the tissues were examined at postoperative periods between 1 hour and 1 year by using well-established fluorescein, angiographic, light microscopic, immunohistochemical, and electron microscopic techniques. These data in the rabbit skin consistently demonstrated an initial period of vasoconstriction that resolved within 3 hours postoperatively and was followed by an active and progressive dilation of choke vessels that was most dramatic between 48 and 72 hours. In vivo intravenous fluorescein dye testing revealed an interesting parallel in that there was a temporary barrier to the flow of fluorescein that occurred at the level of the choke vessels immediately after the flap was raised and that this temporary barrier-continued to impede the flow toward the flap tip in rabbits where flaps had been delayed for periods up to 72 hours. Thereafter, there was no obstruction to the flow of fluorescein along the flap. During this early delay period of 3 days, light microscopy revealed a decrease in vessel wall thickness associated with an increase in lumen diameter. Over the next 4 days, the luminal diameter continued to dilate to a lesser extent and the vessel wall thickened. Immunohistochemical analysis showed increased cell division, maximal between 24 and 72 hours, in all layers of the choke vessel wall. During this same postoperative interval, transmission electron microscopy revealed phenotypic changes in smooth muscle cells from contractile to synthetic cells. Hypertrophy of the smooth muscle cells was also observed. The vascular endothelium, which initially showed evidence of denudation, was restored to a healthy intact appearance within the first week after delay. When followed for longer periods, long-term studies of the delayed flap of up to 1 year demonstrated dramatically a permanent dilation of the choke vessel lumen and a thickening of the choke vessel wall. In canine studies, one rectus abdominis muscle was delayed by ligating the deep inferior epigastric artery. The time sequence of choke vessel dilation, studied by sequential angiograms in vivo, was comparable to that of the rabbit skin model. To ascertain the permanence and irreversibility of this dilation, the normal circulation of the delayed rectus abdominis muscle was restored by reanastomosing the deep inferior epigastric artery. Even after a recovery period of up to 3 months, the choke vessels remained dilated and tortuous instead of reverting to their original narrow diameters. From this work, it is suggested that the choke vessel dilation seen in the delay period is a permanent and irreversible event. It is an active process associated with both an increase (hyperplasia) and an enlargement (hypertrophy) of the cells in all layers of the choke artery wall and a resultant increase in caliber of these vessels. The time sequence for delay appears to be similar in different species and in different tissues, suggesting the possibility of a universal process for delay.     

Pro-Inflammatory Mediators and Apoptosis Correlate to rt-PA Response in a Novel Mouse Model of Thromboembolic Stroke

Background

A recent study suggests that patients with persistent occlusion of the middle cerebral artery (MCA) following treatment with recombinant tissue plasminogen activator (rt-PA) have better outcomes than patients with MCA occlusion not receiving rt-PA. We performed a study to elucidate possible mechanisms of this finding in a new model of thromboembolic stroke closely mimicking human pathophysiology.

Methods

Thromboembolic stroke was induced by local injection of thrombin directly into the right MCA of C57 black/6J mice. Rt-PA was administered 20 and 40 min after clot formation. The efficiency of rt-PA to induce thrombolysis was measured by laser Doppler. After 24 h, all animals were euthanized and interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP)-9, Caspase-3, hsp 32 and hsp 70 protein levels were investigated by immunofluorescence. Presence of hemorrhage was verified and infarct volume was measured using histology.

Results

Thrombin injection resulted in clot formation giving rise to cortical brain infarction. Early rt-PA treatment starting at 20 min after the clot formation resulted in 100% recanalization. However, rt-PA-induced thrombolysis dissolved the clot in only 38% of the animals when administered 40 min after clot formation. Protein levels of IL-6, TNF-α, MMP-9, Caspase-3, hsp 32 and hsp 70 were increased after MCAO, whereas treatment with rt-PA attenuated the expressions of inflammatory markers in those animals where the thrombolysis was successful. In addition, the infarct size was significantly reduced with rt-PA treatment compared to non-treated MCAO, regardless of whether MCA thrombolysis was successful.

Conclusions

The present study demonstrates a clear correlation of the protein expression of inflammatory mediators, apoptosis and stress genes with the recanalization data after rt-PA treatment. In this model rt-PA treatment decreases the infarct size regardless of whether vessel recanalization is successful.     

Inhibition of inducible nitric oxide synthase attenuates platelet adhesion in subpleural arterioles caused by lung ischemia-reperfusion in rabbits.

Oxidative stress, induced by lung ischemia-reperfusion, leads to platelet and leukocyte activation and may contribute to decreased alveolar perfusion by platelet adhesion to the arteriolar wall. We investigated the hypothesis that ischemia-reperfusion injury increases inducible nitric oxide synthase (iNOS) activity and subsequent generation of reactive nitrogen species with P-selectin-dependent platelet-endothelial interactions and vasoconstriction during lung reperfusion. Subpleural arterioles, labeled platelets, and leukocytes were examined in anesthetized, open-chest rabbits by intravital fluorescence microscopy. Ischemia was caused by reversible occlusion of the right pulmonary artery for 1 or 2 h (1IR and 2IR groups). During 2 h of reperfusion, postischemic platelet rolling and adhesion were independent from leukocyte-arteriolar wall interactions and correlated with pulmonary arteriolar constriction in proportion to the length of ischemia. In rabbits treated with an iNOS inhibitor (1400W) before occlusion (2IR + 1400W group), platelet-arteriolar wall interactions and vasoconstriction were prevented. iNOS expression and activity in ischemic lung tissue were markedly greater than control and also were proportional to ischemia duration. NOS activity, immunochemically detected P-selectin, and nitrotyrosine expression in ischemic lung tissue from animals subjected to ischemia-reperfusion, as well as the plasma level of soluble P-selectin, were significantly higher than in nonischemic lungs and were inhibited by pretreatment with 1400W. These results show that platelet adhesion and arteriolar constriction during early reperfusion in the ventilated lung can result from increased iNOS activity and is highly correlated with reactive nitrogen species and P-selectin expression.     

Homogeneous repair of nuclear genes after experimental stroke

The repair of oxidative DNA lesions (ODLs) in the nucleus of ischemic cortical brain cells was examined following experimentally induced stroke by occluding the right middle cerebral artery and both common carotid arteries for 60-90 min followed by reperfusion in male long-Evans hooded rats. The control group consisted of sham-operated animals undergoing the same surgery without vessel occlusion. Using a gene-specific assay based upon the presence of Escherichia coli Fpg protein-sensitive sites, we noted that animals with stroke exhibited six and four ODLs per gene in the actin and DNA polymerase-beta genes, respectively. This was increased from one per four copies of each gene in the sham-operated control (p < 0.01). One half of the initial ODLs was repaired within 30 min, and 83% of them were repaired as early as 45 min of reperfusion. There was no further increase when gene repair was measured again at 2 h of reperfusion. The rates of active repair within 45 min of reperfusion were the same in these two genes (p = 0.103, ANOVA). BrdU (10 mg/kg) was administered via intraperitoneal injection at least one day before surgery. We observed that there was no significant incorporation of BrdU triphosphates into genomic DNA during active repair, but there were significant amounts of BrdU triphosphate in nuclear DNA after active repair. The result indicates that genomic repair of ODLs in the brain did not significantly incorporate BrdU, and the initiation of neurogenesis probably starts after the completion of repair in the brain.     

A surgical model of permanent and transient middle cerebral artery stroke in the sheep

Background

Animal models are essential to study the pathophysiological changes associated with focal occlusive stroke and to investigate novel therapies. Currently used rodent models have yielded little clinical success, however large animal models may provide a more suitable alternative to improve clinical translation. We sought to develop a model of acute proximal middle cerebral artery (MCA) ischemic stroke in sheep, including both permanent occlusion and transient occlusion with reperfusion.

Materials and Methods

18 adult male and female Merino sheep were randomly allocated to one of three groups (n = 6/gp): 1) sham surgery; 2) permanent proximal MCA occlusion (MCAO); or 3) temporary MCAO with aneurysm clip. All animals had invasive arterial blood pressure, intracranial pressure and brain tissue oxygen monitoring. At 4 h following vessel occlusion or sham surgery animals were killed by perfusion fixation. Brains were processed for histopathological examination and infarct area determination. 6 further animals were randomized to either permanent (n = 3) or temporary MCAO (n = 3) and then had magnetic resonance imaging (MRI) at 4 h after MCAO.

Results

Evidence of ischemic injury in an MCA distribution was seen in all stroke animals. The ischemic lesion area was significantly larger after permanent (28.8%) compared with temporary MCAO (14.6%). Sham animals demonstrated no evidence of ischemic injury. There was a significant reduction in brain tissue oxygen partial pressure after permanent vessel occlusion between 30 and 210 mins after MCAO. MRI at 4 h demonstrated complete proximal MCA occlusion in the permanent MCAO animals with a diffusion deficit involving the whole right MCA territory, whereas temporary MCAO animals demonstrated MRA evidence of flow within the right MCA and smaller predominantly cortical diffusion deficits.

Conclusions

Proximal MCAO can be achieved in an ovine model of stroke via a surgical approach. Permanent occlusion creates larger infarct volumes, however aneurysm clip application allows for reperfusion.     

Dietary supplementation of fermented soybean,natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery

We have previously demonstrated that natto-extracts containing nattokinase (NK) inactivates plasminogen activator inhibitor type 1 and then potentiates fibrinolytic activity. In the present study, we investigated the effects of dietary supplementation with natto-extracts on neointima formation and on thrombolysis at the site of endothelial injury. Endothelial damage in the rat femoral artery was induced by intravenous injection of rose bengal followed by focal irradiation by transluminal green light. Dietary natto-extracts supplementation containing NK of 50 or 100 CU/body was started 3 weeks before endothelial injury and then continued for another 3 weeks. Intimal thickening in animals given supplementation was significantly (P<0.01) suppressed compared with controls and the intima/media ratio in animals with 50 and 100 CU/body NK and control group was 0.09 +/- 0.03, 0.09 +/- 0.06 and 0.16 +/- 0.12, respectively. Although femoral arteries were reopened both in control animals and those treated with NK within 8 hours after endothelial injury, mural thrombi were histologically observed at the site of endothelial injury. In the control group, the center of vessel lumen was reopened and mural thrombi were attached on the surface of vessel walls. In contrast, in NK-treated groups, thrombi near the vessel wall showed lysis and most of them detached from the surface of vessel walls. In conclusion, dietary natto-extracts supplementation suppressed intimal thickening produced by endothelial injury in rat femoral artery. These effects may partially be attributable to NK, which showed enhanced thrombolysis near the vessel wall.     

Effects of allopurinol pretreatment on myocardial ultrastructure and arrhythmias following coronary artery occlusion and reperfusion

The effect of the xanthine oxidase inhibitor, allopurinol, on myocardial ultrastructure after left circumflex coronary artery occlusion (40 min) with or without reperfusion (60 min) was examined in rabbits. Pretreatment of rabbits for 7 days with allopurinol (0.1% in the drinking water) resulted in a lower incidence of ventricular fibrillation in both ischemic and reperfusion phases. However, the number of Q waves, ST-segment elevation and premature ventricular contractions were similar in both groups of animals. Examination of hearts from allopurinol-treated animals revealed a distinct decrease in ultrastructural alterations following ischemia and reperfusion. Among the subcellular organelles studied, allopurinol had a preferential protective effect on the mitochondria both during the ischemic and reperfusion phases. In the allopurinol-treated animals, most mitochondria were intact and the cristae network preserved. Our study suggests that the preservation of mitochondrial structural and functional integrity by allopurinol may be an important determinant of its protective actions in myocardial ischemic/reperfusion injury.     

Mesenchymal stem cells-based therapy of brain ischemic stroke in rat

Mesenchymal stem cells (MSCs)-based therapy is a promising modern attempt to improve the recovery after stroke. Experiments were carried out on inbred Wistar-Kyoto rats. MSCs were isolated, expanded in cultute and labeled with vital fluorescent dye PKH-26. Animals were subjected to middle cerebral artery occlusion (MCAO), followed by injection of 5 x 10(6) rat MSCs into the tail vein 3 days after MCAO. Control group animals received PBS injection (negative control). Therapy results were estimated by the following parameters: behavioral and neurological testing, the brain injure area, the state of damaged region "border" zone and the vessels quantity in the "borden" area. It was shown that control group animals (PBS injection) did not restore their initial behavioral and neurological state, while the experimental group animals (MSCs injection) showed the same parameters as intact rats at 2-3 weeks after MCAO. The size of the damaged region in the control group was approximately 1.5 as large as in the experimental group. The damage in the experimental group was limited to neocortex; caudate nucleus, capsula externa and piriform cortex remained uninjured. Small vessels quantity in the "border" regions was twine higher compared to control group and was approximately equal to an intact brain vessel number. Moreover, it was shown for the first time that after MSCs transplantation the vessels quantity in the neocortex and caudate putamen of contralateral hemisphere was twice as much as in control. We demonstrated that the MSCs transplantation definitely exerted a positive influence upon the brain tissue reparation after stroke.     

Assessment of radical activity during the acute phase of myocardial infarction following fibrinolysis: Utility of assaying plasma malondialdehyde

Numerous experimental and clinical studies have reported a role of radical forms of oxygen in the etiology of the manifestations of reperfusion of the ischemic myocardium. However, clinical results remain controversial. The aim of this study was to ascertain the existence of reperfusion-related radical stress after thrombolysis with a marker that is easy to use and reliable. Thirty patients hospitalized for acute myocardial infarction were involved in the study. Of these, 18 had been subjected to intravenous thrombolysis (Group I) and 12 had not (Group II). They were compared to two control groups who had no history of myocardial infarction. Of these, 16 were patients with coronary heart disease hospitalized for stable angina (Group III) and 17 were patients free of any known cardiovascular disease (Group IV). Radical activity was assessed in plasma samples taken from a peripheral vein over a 10-day period of hospitalization by measuring (1) malondialdehydes (MDA) concentration using fluorometry techniques or HPLC, (2) the antioxidant activity of glutathione peroxidase (GPx), and (3) the concentration of various antiradical compounds (β-carotene, vitamins A and E, uric acid). All patients in Group I had a patent artery on coronary angiography and showed a significant increase in plasma MDA when compared to those who had not been subjected to thrombolysis (3.15 ± 0.62 and 2.70 ± 0.40 mole/l of plasma, respectively). Furthermore, GPx plasma activity was also significantly increased following thrombolysis. By contrast, there was no significant alteration in the antiradical compounds measured. These data suggest that MDA measurements (an early measurement 1–2 days and a late measurement 5–7 days after reperfusion) by fluorometry is a good marker of radical stress during reperfusion in man. The assessment of this marker in patients might represent a simple and reliable test of reperfusion efficacy following thrombolysis, and it might enable one to test the effect of various antioxidant therapies associated with thrombolytic treatment.     

兔后肢动静脉短路诱导动脉生成过程中VEGF(A)及其受体Flk-1的表达

目的探讨兔后肢动脉生成过程中VEGF(A)及其受体Flk-1的表达特征。方法兔双侧股动脉结扎,并将一侧结扎的股动脉远侧端缝到伴行的静脉上造成动静脉短路,另一侧为对照组。一周后动物被处死。应用免疫荧光组织化学技术检测侧支血管中VEGF(A)及其受体Flk-1的表达。结果在正常血管,VEGF(A)没有表达,Flk-1只在内皮细胞上有微弱表达;对照侧,VEGF(A)和Flk-1在平滑肌细胞和内皮细胞的表达明显上调;在动静脉短路侧,VEGF(A)和Flk-1的表达显著增加,分别是对照侧的2·3倍和2倍。结论在侧支血管发育过程中,VEGF(A)及其受体Flk-1在平滑肌细胞和内皮细胞同时表达上调,在快速生长的侧支血管它们的表达更为显著,提示Flk-1的表达在VEGF促动脉生成作用中具有重要意义。     

Impact of Temporary Opening Using a Stent Retriever on Clinical Outcome in Acute Ischemic Stroke

Background

Stent retriever has a distinct ability to restore blood flow temporarily before achieving final reperfusion. There has been a limited report regarding the clinical impact of it. We investigated if temporary opening of occluded vessels using a stent retriever before final reperfusion might improve clinical outcome in acute ischemic stroke patients who received the endovascular reperfusion treatment.

Methods

We enrolled consecutive ischemic stroke patients who had an initial occlusive lesion in the anterior circulation and achieved final reperfusion (Thrombolysis In Cerebral Infarction [TICI] ≥2) by endovascular treatment. Temporary opening was defined as the presence of ante grade flow (TICI≥2) during deployment of a stent retriever. Favorable outcome was defined as a modified Rankin scale score≤2 at 90 day.

Results

A total of 98 patients were included in the study and temporary opening was achieved in 49 (50%). Temporary opening was associated with favorable outcome (odds ratio, 7.825; 95% confidence interval, 1.592–38.461; p = 0.011) in the multivariate analysis. The probability of having a favorable outcome tended to decrease as time from onset to final reperfusion increased in patients without temporary opening. However, this trend was not evident in the patient with temporary opening. The beneficial effect of temporary opening on clinical outcome seemed to be present in patients with good collaterals but not in patients with poor collaterals.

Conclusions

Temporary opening of occluded vessel using a stent retriever may be beneficial for improving clinical outcome in acute ischemic stroke patients.     

川芎嗪对家兔肺缺血/再灌注损伤时Fas/FasL基因表达的影响

目的:探讨川芎嗪对肺缺血/再灌注损伤(PI/RI)时Fas/FasL基因表达的影响。方法:采用在体兔单肺原位缺血-再灌注模型。实验兔90只,随机均分为假手术对照组(Sham)、肺缺血/再灌注组(I/R)和肺缺血/再灌注加川芎嗪治疗组(LGT)。每组又分为再灌注1h3、h、5 h三个亚组,每个亚组10只,分别于再灌注1 h3、h、5 h三个时点取左肺组织,观察Fas/Fas配体(Fas/FasL)mRNA定位表达、凋亡指数(AI)、肺组织湿、干重比(W/D)、肺损伤组织学定量评价指标(IQA)及光镜、电镜下的组织形态学改变。结果:肺再灌注1 h、3 h、5 h,LGT组Fas/FasLmRNA在肺小动脉内(外)膜、肺小静脉内膜、肺泡上皮及肺支气管上皮弱阳性表达,与I/R组同一时点比较阳性表达明显减弱;AI、W/D和IQA值显著低于I/R组(P<0.01和P<0.05);肺组织形态学异常改变不同程度减轻。结论:川芎嗪可下调肺组织Fas/FasL mRNA的表达而减轻细胞凋亡,对PI/RI发挥积极的防护作用。     

同种异体血管移植后肿瘤坏死因子表达的变化

目的探讨同种异体血管移植后移植血管和心肌肿瘤坏死因子(tumornecrosisfactor,TNF)表达的变化。方法取成年、雄性日本大白兔作为血管受者,新西兰大白兔为血管供者,进行颈动脉血管移植,通过免疫组织化学方法检测移植血管和心肌TNF表达的变化。结果自体原位移植组和液氮冷冻组TNF表达率低于新鲜移植组和抗生素处理组,新鲜移植组TNF表达率最高,与其它各组比较有显著性差异,P<0·05。血管移植后,心肌组织切片结果与血管移植组有类似结果:新鲜移植组心肌的TNF表达最高,与原位移植组和液氮冷冻组比较有显著性差异,P<0·05,而与抗生素处理组比较无显著差异性。结论液氮冷冻处理可降低移植血管和心肌TNF的产生;缺血再灌注损伤和/或免疫排斥反应能激发移植血管和全身各组织器官TNF的产生,从而造成移植血管的病理损害。     

Effect of thrombolysis on myocardial injury: recombinant tissue plasminogen activator vs. alfimeprase

Plasmin-dependent thrombolytic agents are potentially prothrombotic and proinflammatory. Alfimeprase, a zinc-containing metalloproteinase, degrades fibrin directly and achieves thrombolysis independent of plasmin formation. This study examines the hypothesis that thrombolysis in the absence of plasmin generation results in improved myocardial salvage on reperfusion. The thrombolytic effects of recombinant tissue plasminogen activator [rt-PA; 0.022 mg/kg, 1/10 of which was administered as a loading dose; the rest (9/10) was infused over 60 min by intracoronary (ic) administration] or alfimeprase (0.5 mg/kg over 1 min ic) were evaluated in a canine model of arterial thrombosis involving electrolytic injury of the left circumflex (LCX) coronary artery. Both agents induced thrombolysis, with onset of reperfusion being more rapid after alfimeprase compared with rt-PA (1.5 +/- 0.6 vs. 10.1 +/- 2.1 min). In the absence of adjunctive therapy, time to reocclusion after alfimeprase was 3.2 +/- 0.5 min compared with 77.5 +/- 31.9 min with rt-PA. The glycoprotein IIb/IIIa platelet receptor antagonist CRL-42796 prolonged reperfusion time after thrombolysis with alfimeprase or rt-PA. The effect of each lytic agent on myocardial infarct size was examined in a separate group of dogs subjected to 60 min of LCX coronary artery ligation and 4 h of reperfusion. Myocardial infarct size, expressed as percentage of the risk region, was larger (32.16 +/- 3.95%) after rt-PA compared with alfimeprase (19.85 +/- 3.61%) or that of the saline control group (18.46 +/- 3.34%). rt-PA in contrast to alfimeprase, a direct-acting fibrinolytic agent, is associated with an increase in myocyte reperfusion injury.     

Effect of transient ischemia on monoamine levels in the cerebral cortex of gerbils

Abstract— Cortical monoamine changes during ischemic episodes of varied duration and their sequence of changes following cerebral reperfusion were studied in the gerbil. Forty-one percent of 280 animals exhibited signs of cerebral hemispheric ischemia (stroke) after unilateral common carotid artery occlusion. Norepinephrine (NE) levels decreased after 60 min in the occluded hemisphere of stroked animals but dopamine (DA) levels were unaltered. S-Hydroxytryptamine (5-HT) levels became bilaterally reduced in both stroked and non-stroked animals as soon as S min after occlusion. Upon reperfusion after periods of 30 or 60 min of occlusion there was a bilateral rebound increase of cortical NE and DA levels to well above control values in stroked and non-stroked animals. 5-HT levels remained reduced in both groups. Results suggest disorder of monoamine metabolism in ischemic brain which persists during the early reperfusion period, perhaps contributing to deficits in neurological function. Monoamine changes in contralateral non-ischemic hemispheres both during the occlusion and reperfusion periods are thought further evidence of diaschisis.     

Thrombolysis for acute myocardial infarction: drug review

The proof of efficacy of thrombolysis for acute myocardial infarction (AMI) depends on 9 randomized placebo-controlled trials totaling 58,511 patients. The meta-analysis of these trials showed an overall survival advantage of about 2% (11.5% vs 9.6%) in favor of thrombolysis. Iatrogenic deaths from thrombolysis complications occur in about 1% of AMI patients. Timely opening of the infarct-related artery (IRA) allowing myocardial reperfusion has been proposed to explain any survival advantage seen with thrombolysis ("open-artery hypothesis"). Angiographic data does not support the open-artery hypothesis as the mechanism of any benefit of thrombolysis. The "early hazard" (ie, increased mortality in the first 12 hours after thrombolysis) also suggests that the supposed survival benefit is due to something other than early reperfusion. The variable use of aspirin in the meta-analysis trials may have confounded the results and conclusions. In the 4 studies of the meta-analysis in which aspirin was used routinely (n = 21,144), the survival benefit was not statistically significant (P =.14). Lack of blinding in some studies and other methodologic problems may also call the conclusions of the meta-analysis into question. AMI registry reports comparing patients with and without thrombolysis have not borne out a significant survival advantage with thrombolysis. The National Registry of Myocardial Infarction (NRMI) registry data suggest that a significant number of AMI patients may be inappropriately receiving thrombolytics. An independent analysis of the NRMI mortality data adjusted for age and other risk factors would help determine whether thrombolysis for AMI improves survival.