The effects of diaspirin cross-linked hemoglobin on hemodynamics, metabolic acidosis, and survival in burned rats

OBJECTIVE: Diaspirin cross-linked hemoglobin (DCLHb) is a vasoactive hemoglobin-based oxygen carrier or "blood substitute" that has been shown to improve base deficit in several experimental studies of hemorrhagic shock. Our objective was to determine if the addition of DCLHb to the resuscitation regimen would improve hemodynamic parameters, metabolic acidosis, and survival in our rat burn shock model compared with currently used resuscitation therapy. METHODS: This was a randomized, controlled, experimental rat study. Male Wistar rats, weighing 200 to 250 g, were surgically prepared for an acute study. After placement of indwelling catheters, baseline hemodynamic values (mean arterial pressure, cardiac output, systemic vascular resistance, stroke volume, and base excess) were obtained. Thirty-two rats were used in the study, and they were either subjected to a 30% scald burn (experimental group) or sham burned (control group). The experimental animals were immediately intravenously resuscitated and followed for 6 hours. The resuscitation was based on the Parkland formula (4 mL/kg for each 1% of total body surface area [TBSA] burn), with 50% of the calculated fluid amount to be administered at a constant rate during the first 8 hours after burn. The animals were resuscitated for 6 hours and received between 9.00 and 11.25 mL of fluid depending on weight. The experimental animals were randomly assigned to one of three treatment groups: group I, lactated Ringer's solution; group II, lactated Ringer's solution-human serum albumin; group III, lactated Ringer's solution-DCLHb. Group I (n = 8) received 4 mL/kg lactated Ringer's solution for each 1% of TBSA burn. Group II (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg human serum albumin for each 1% of TBSA burn. Group III (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg DCLHb for each 1% of TBSA burn. The sham group (n = 8) was not burned and was not resuscitated. Animals that survived up to 6 six hours were killed. RESULTS: We found that mean arterial pressure, cardiac output, stroke volume, and base excess were all improved in the DCLHb-lactated Ringer's solution-treated animals compared with the other experimental treatment groups. The 6-hour mortality rates were zero of eight (lactated Ringer's solution-DCLHb group), zero of eight (sham group), three of eight (lactated Ringer's solution-human serum albumin group), and six of eight (lactated Ringer's solution only group). CONCLUSION: Early resuscitation with DCLHb is superior to non-oxygen-carrying resuscitative fluids in improving hemodynamics and survival in this model of burn shock. DCLHb might improve general tissue perfusion in the acute postburn period, and it could be useful in the early management of patients with severe burns.     

Hemoglobin and methemoglobin concentrations after large-dose infusions of diaspirin cross-linked hemoglobin

Diaspirin cross-linked hemoglobin (DCLHb) solution is a purified human hemoglobin product chemically stabilized to deliver oxygen to tissues. We determined the peak plasma hemoglobin concentration and assessed changes in methemoglobin concentration after the infusion of 1 g/kg DCLHb in large blood loss surgical patients. This prospective, randomized study included 26 surgical patients who were either infused with up to three 250-mL units of 10% DCLHb or transfused with up to three units of packed red blood cells during the study infusion period. Serial plasma hemoglobin, plasma methemoglobin, and whole blood methemoglobin levels were measured before and at intervals up to 48 h after the study infusion period. Plasma hemoglobin and blood methemoglobin concentrations increased during the infusion of DCLHb. The plasma hemoglobin values in the DCLHb group continued to increase during each of the infusion periods to reach a peak plasma concentration of 1450 +/- 176 mg/dL. The fraction of whole blood methemoglobin increased from 0.84 +/- 0.77% at baseline to 4.08 +/- 1.36%. With a median DCLHb dose of 936 mg/kg (range 658-1500 mg/kg), the harmonic mean half-life was 10 h, and the increased whole blood methemoglobin reached a range not associated with complications. Implications: The dose of diaspirin cross-linked hemoglobin (DCLHb) (936 +/- 276 mg/kg) used in this study was one of the largest reported in humans to date. The DCLHb mean half-life was 10 h. The half-life observed was 2-4 times that found at smaller doses in previous studies. Whole blood methemoglobin fraction increased during DCLHb infusion but did not reach a range associated with complications.     

吸烟对大隐静脉旁路血管张力的影响

目的 探讨吸烟对大隐静脉旁路血管张力的影响.方法 选取吸烟10年以上(A组,12例)、戒烟1年以上(B组,9例)、不吸烟(C组,10例)行冠状动脉旁路移植术病人,每例术中留取其1 cm长大隐静脉旁路血管,修剪成3条3 mm宽血管环.采用器官管槽法,在37℃有氧条件下,观察比较各组血管环在不同浓度(10-9～10-5mmol/L)的苯肾上腺素作用下的血管收缩反应,及待10-5mmol/L苯肾上腺素收缩达到一定平台后,不同浓度乙酰胆碱(10-9～10-5 mmol/L)和硝酸甘油(10-9～10-4mmol/L)引发的血管舒张反应.结果 苯肾上腺素引发的血管收缩反应及硝酸甘油引发的血管舒张反应在三组之间差异无统计学意义;乙酰胆碱引发的血管舒张反应,A组明显低于B组与C组,但B组与C组两组差异无统计学意义.结论 长期吸烟对大隐静脉旁路血管内皮依赖性舒张有抑制作用,戒烟1年以上有利于恢复因长期吸烟所抑制的内皮依赖性舒张功能.

Abstract：

Objective To observe the effect of smoking on the great saphenous vein tension. Methods The rings of great saphenous vein in 3mm long of selected from 31 patients with coronary artery bypass grafting were divided into three groups :smoking over 10 years( group A, n = 12 ), ex-smoking over 1 years ( group B, n =9 ) and non-smoking( group C, n =10). The changes of the tone were measured in organ chamber at 37℃ with a constant supply of oxygen when vasoconstriction induced by phenylephrine ( 10 -9 - 10 -5 mmol/L), and vasodilatation by acetylcholine ( 10 -9 - 10 -5 mmol/L) or nitroglycerin( 10 -9 - 10 -4 mmol/L)after the rings were precontracted by 10 -5 mmol/L phenylephrine. Results Vasoconstriction induced by phenylephrine and vasodilatation by nitroglycerin is no significant difference among three groups. Compared with group A, vasodilatation by acetylcholine was significantly increased in group B or C, while there is no significant difference between group B and C. Conclusion Smoking has a deleterious effect on the endothelial function of great saphenous vein, however, smoking cessation over 1 year may help to restore the endothelial function impaired by smoking.     

The action of diaspirin cross-linked haemoglobin blood substitute on human arterial bypass conduits.

BACKGROUND: Immediately available blood substitutes could transform medicine. In coronary artery surgery, vasoconstriction induced by some of these agents could have serious implications. We have examined some of the vasoactive effects of one of these blood substitute, diaspirin cross-linked haemoglobin (DCLHb), on isolated rings of human arterial conduits. METHODS: Sections of human left internal mammary artery (LIMA) and radial artery (RA) were cut into 3-mm rings, mounted in individual organ baths containing aerated (95% O(2)/5% CO(2)) Krebs-Heinseleit solution at 37 degrees C and attached to isometric strain gauge for measurements of tension. All rings were tested for the presence of endothelium by addition of carbachol to rings pre-contracted with phenylephrine. The relative importance of nitric oxide (NO) in contraction mediated by the addition of DCLHb was studied. RESULTS: Carbachol relaxed phenylephrine precontracted LIMA by 72.3+/-1.7% and RA by 97+/-0.7% confirming the presence of a functional endothelium. Sodium nitroprusside (SNP) caused complete relaxation of LIMA with an EC(50) value of 2.0+/-0.1x10(-8) M and RA with an EC(50) value of 1. 9+/-0.1x10(8) M. In the presence of DCLHb (10(-7) M), carbachol-induced relaxation was significantly reduced to 46.3+/-0. 7% (P<0.01) and the BC(50) value for SNP relaxation increased to 1. 2+/-0.1x10(-7) M (P<0.01). DCLHb caused rings to contract in the absence of phenylephrine with EC(50) values of 1.6+/-0.1x10(-7) M (LIMA) and 1.8+/-0.1x10(-7) M (RA). Presence of L-NAME (300 microM) caused no alteration in DCLHb-induced contraction. CONCLUSION: In this study of isolated rings of human vessels, DCLHb causes a significant reduction in relaxation mediated by carbachol and SNP, which is likely to be due to its ability to bind NO. However, it is possible that other mechanisms might contribute to the vasoconstrictor effects of DCLHb and these might be amenable to anti-vasospastic strategies.     

The effects of cooling on human saphenous vein reactivity to adrenergic agonists

Human saphenous veins were obtained at surgery and assayed immediately (n = 10). The veins were cut into rings, suspended in organ chambers, and connected to force transducers for the recording of isometric tension. One ring served as control whereas others were treated with the alpha 1-adrenoceptor antagonist prazosin (3 X 10(-7) mol/L), or the alpha 2-adrenoceptor antagonist rauwolscine (10(-7) mol/L). In quiescent rings cooling from 37 degrees C to 24 degrees C had no significant effect. Norepinephrine (10(-8)-10(-5) mol/L) caused concentration-dependent contractions with an EC20 (-log concentration of norepinephrine required to induce contractions 20% of maximal) = 6.97 +/- 0.10. The contractions were inhibited by prazosin (EC20 = 5.89 +/- 0.17, p less than 0.001) and rauwolscine (ED20 = 5.78 +/- 0.11, p less than 0.001). In control rings cooling potentiated contractions evoked at concentrations of norepinephrine below 10(-6) mol/L and inhibited those at higher concentrations. In rings treated with alpha-antagonists cooling depressed the maximal contractile responses. Contractions to the alpha 1-agonist, phenylephrine (10(-7)-10(-4) mol/L), were inhibited by cooling, whereas those to the alpha 2-specific agonist B-HT 920 (10(-7)-10(-4) mol/L) showed a pattern similar to that seen with norepinephrine. The data indicate that the human saphenous vein possesses both alpha 1- and alpha 2-adrenoceptors postjunctionally, and that both contribute to contractile responses. Cold augments saphenous vein reactivity to norepinephrine by an apparent increase in the responsiveness of alpha 2-adrenoceptors to agonists. The relationship between temperature and adrenoceptor responsiveness may be of pivotal importance in defining the mechanism of cold-induced vasospasm.     

Post hoc mortality analysis of the efficacy trial of diaspirin cross-linked hemoglobin in the treatment of severe traumatic hemorrhagic shock

BACKGROUND: The efficacy trial of diaspirin cross-linked hemoglobin (DCLHb) in traumatic hemorrhagic shock demonstrated an unexpected mortality imbalance, prompting a three-step review to better understand the cause of this finding. METHODS: Patients were enrolled in this DCLHb hemorrhagic shock study using 28-day mortality as the primary endpoint. Mortality data were primarily analyzed using the TRISS method and a nonblinded clinical review, followed by an independent Pennsylvania Trauma Outcome Study (PTOS)-derived probability of survival analyses. Finally, a trauma expert conducted a blinded clinical review of cases incorrectly predicted by these PTOS analyses. RESULTS: More of the DCLHb patients predicted to survive using TRISS actually died than in the control subgroup (24% vs. 3%, p < 0.002). Nonblinded clinical review noted that 72% of the patients who died had prior traumatic arrest, a presenting Glasgow Coma Scale score of 3, or a base deficit > 15 mEq/L. DCLHb patients predicted to survive using PTOS also more often died than did control patients (30% vs. 8%, p < 0.04). Blinded clinical review determined that 94% of the deaths were clinically justified. Both the TRISS and the PTOS models gave an adjusted mortality relative risk of 2.3, similar to the unadjusted risk data. CONCLUSION: Mortality analysis in this shock study involved both clinical case reviews and mortality prediction models. Despite the observation that nearly all of the deaths were clinically justified, the TRISS and PTOS models demonstrated excess unpredicted deaths in the DCLHb subgroup. A combined process, using both mortality prediction models and clinical case reviews, is useful in trauma studies that use a mortality endpoint.     

Fluid resuscitation from severe hemorrhagic shock using diaspirin cross-linked hemoglobin fails to improve pancreatic and renal perfusion

BACKGROUND: Fluid resuscitation from hemorrhagic shock is intended to abolish microcirculatory disorders and to restore adequate tissue oxygenation. Diaspirin cross-linked hemoglobin (DCLHb) is a hemoglobin-based oxygen carrier (HBOC) with vasoconstrictive properties. Therefore, fluid resuscitation from severe hemorrhagic shock using DCLHb was expected to improve perfusion pressure and tissue perfusion of kidneys and pancreas. METHODS: In 20 anesthetized domestic pigs with an experimentally induced coronary stenosis, shock (mean arterial pressure 45 mmHg) was induced by controlled withdrawal of blood and maintained for 60 min. Fluid resuscitation (replacement of the plasma volume withdrawn during hemorrhage) was performed with either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). Completion of resuscitation was followed by a 60-min observation period. Regional blood flow to the kidneys and the pancreas was measured by use of the radioactive microspheres method at baseline, after shock and 60 min after fluid resuscitation. RESULTS: All animals (10/10) resuscitated with DCLHb survived the 60-min observation period, while 5/10 control animals died within 20 min due to persisting subendocardial ischemia. In contrast to HSA survivors, pancreas and kidneys of DCLHb-treated animals revealed lower total and regional organ perfusion and regional oxygen delivery. Renal and pancreatic blood flow heterogeneity was higher in the DCLHb group. CONCLUSION: DCLHb-induced vasoconstriction afforded superior myocardial perfusion, but impaired regional perfusion of the kidneys and the pancreas.     

Pressure-diameter relationship in the human greater saphenous vein

BACKGROUND: Compliance of artificial and autologous vascular grafts is related to future patency. We investigated whether differences in compliance exist between saphenous vein grafts derived from the upper or lower leg, which might indicate upper or lower leg saphenous vein preference in coronary artery bypass surgery. Furthermore, the effect of perivenous application of fibrin glue on mechanical vein wall properties was studied to evaluate its possible use as perivenous graft support. METHODS: Vein segments (N = 10) from upper or lower leg saphenous vein grafts were collected for histopathologic examination and smooth muscle cell/extracellular matrix (SMC/ECM) ratio was calculated. This ratio is suggested to be related with vascular elastic compliance. In a second group vein graft segments (N = 6) from upper and lower leg were placed in an in vitro model generating stepwise increasing static pressure up to 150 cm H(2)O. Outer diameter was measured continuously with a video micrometer system. Distensibility was calculated from the pressure-diameter curves. A third group of vein graft segments (N = 7) was pressurized after fibrin glue application to prevent overdistension, and studied in the same setup. RESULTS: Vein segments from the lower leg demonstrated a consistent higher relative response compared with the upper leg saphenous vein graft (0.9176 +/- 0.03993 vs 0.5245 +/- 0.02512). Both reach a plateau in the high-pressure range (> 100 cm H(2)O). A significant difference in in vitro distensibility between upper and lower leg saphenous vein was only found at a pressure of 50 cm H(2)O (p < 0.05). With fibrin glue, support overdistension is prevented as revealed by the maximum relative response between fibrin glue supported upper and lower leg saphenous vein segments (0.4080 +/- 0.02464 vs 0.582 +/- 0.051), and no plateau is reached in the pressure range up to 150 cm H(2)O. CONCLUSIONS: No upper or lower leg saphenous vein preference could be deduced from the differences in pressure-diameter response due to loss of distensibility (and thus of compliance) in the high-pressure range. Fibrin glue effectively prevents overdistension and preserves some distensibility in the high-pressure range in both the upper and lower leg saphenous vein. This might provide a basis for clinical application of perivenous support.     

Metabolism of prostaglandins in human saphenous vein

The described methodology allows for analysis of metabolism of the prostaglandin PGH₂ in subcellular fractions (microsomes) obtained from human saphenous veins. Prostacyclin (PGI₂) synthetase as identified by its stable breakdown product 6-keto-PGF_1a is present in human saphenous vein. Thromboxane A₂ is absent. The enzymatic formation of PGE₂ was demonstrated by the addition of glutathione (GSH) indicating the presence of an active PGE₂ isomerase. The data suggest that the enzymatic endoperoxide-metabolizing pathways in human saphenous vein microsomes are prostacyclin synthetase and prostaglandin E isomerase. It is suggested that the ability of the vein graft to produce prostacyclin and PGE₂ may contribute to short- and long-term graft patency.     

Multi-photon microscopy in the evaluation of human saphenous vein

BACKGROUND: The use of conventional fluorescence microscopy to image biological systems at the cellular level is limited by its inability to spatially resolve thick tissues. We have applied the technique of multi-photon fluorescence microscopy to study the structure and function of endothelial cells in living human saphenous vein taken from patients undergoing coronary artery bypass surgery. MATERIALS AND METHODS: Vein segments were preserved for 1-4 h to determine the temporal effects of storage. The effect of pH on endothelial and smooth muscle cell viability was examined by storing segments at pH 6.0, 7.4, and 8.0. Calcein-mediated green fluorescence and ethidium homodimer-mediated red fluorescence were used to differentiate cell viability. Increases in diaminofluorescein fluorescence were used to measure bradykinin activation of endothelial nitric oxide synthase (eNOS) with or without N-nitro-l-arginine (L-NNA). Multi-photon imaging was performed with the BioRad MRC1024ES system. RESULTS: Successful imaging of endothelial and smooth muscle cells of vein segments was achieved. Cell viability was well preserved up to 3 h of storage but dramatically decreased after 4 h. Cell viability was maintained at pH 7.4, diminished at pH 8.0, and was completely lost at pH 6.0. A two- to threefold increase in eNOS activity was observed upon activation by bradykinin which was completely inhibited in L-NNA-treated samples. CONCLUSIONS: We have demonstrated the successful application of multi-photon microscopy in imaging and quantifying nitric oxide production and cell viability under various storage conditions in human saphenous veins. This imaging technique allows for the functional imaging of cellular processes and may have diagnostic potential in cardiovascular surgery for patients undergoing bypass operations.     

Material and structural characterization of human saphenous vein

Saphenous vein patch rupture after carotid endarterectomy is an infrequent but devastating complication. This study was undertaken to evaluate the material and structural properties of fresh human saphenous veins to understand the causes of this complication. Segments of saphenous veins were obtained from 22 patients from vein harvested during coronary artery bypass surgery. Ninety-three specimens, oriented in both circumferential (n = 45) and longitudinal (n = 48) directions, were prepared from the available vein segments for testing. Specimens were mounted on specially designed grips and then subjected to uniaxial tension testing. For each specimen the following material and structural parameters were determined: vessel diameter, tensile stiffness, failure and ultimate forces, and tensile modulus, failure stress, and strain. The physical properties of specimens evaluated in longitudinal orientations and thus limit the inherent strength of the vein. The physical properties of circumferentially tested vein specimens were negatively correlated to age, female gender, diabetes, and hypertension. The data obtained in this investigation suggest that age, hypertension, as well as diabetes and gender may adversely influence the circumferential tensile strength of human saphenous veins used as patch grafts.     

Randomized trial of diaspirin cross-linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. The DCLHb Cardiac Surgery Trial Collaborative Group

BACKGROUND: Risks associated with transfusion of allogeneic blood have prompted development of methods to avoid or reduce blood transfusions. New oxygen-carrying compounds such as diaspirin cross-linked hemoglobin (DCLHb) could enable more patients to avoid allogeneic blood transfusion. METHODS: The efficacy, safety, hemodynamic effects, and plasma persistence of DCLHb were investigated in a randomized, active-control, single-blind, multicenter study in post-cardiac bypass surgery patients. Of 1,956 screened patients, 209 were determined to require a blood transfusion and met the inclusion criteria during the 24-h post-cardiac bypass period. These patients were randomized to receive up to three 250-ml infusions of DCLHb (n = 104) or three units of packed erythrocytes (pRBCs; n = 105). Further transfusions of pRBCs or whole blood were permitted, if indicated. Primary efficacy end points were the avoidance of blood transfusion through hospital discharge or 7 days postsurgery, whichever came first, and a reduction in the number of units of pRBCs transfused during this same time period. Various laboratory, physiologic, and hemodynamic parameters were monitored to define the safety and pharmacologic effect of DCLHb in this patient population. RESULTS: During the period from the end of cardiopulmonary bypass surgery through postoperative day 7 or hospital discharge, 20 of 104 (19%) DCLHb recipients did not receive a transfusion of pRBCs compared with 100% of control patients (P < 0.05). The overall number of pRBCs administered during the 7-day postoperative period was not significantly different. Mortality was similar between the DCLHb (6 of 104 patients) and the control (8 of 105 patients) groups. Hypertension, jaundice/hyperbilirubinemia, increased serum glutamic oxalo-acetic transaminase, abnormal urine, and hematuria were reported more frequently in the DCLHb group, and there was one case of renal failure in each group. The hemodynamic effects of DCLHb included a consistent and slightly greater increase in systemic and pulmonary vascular resistance with associated increases in systemic and pulmonary arterial pressures compared with pRBC. Cardiac output values decreased more in the DCLHb group patients after the first administration than the control group patients. At 24 h postinfusion, the plasma hemoglobin level was less than one half the maximal level for any amount of DCLHb infused. CONCLUSIONS: Administration of DCLHb allowed a significant number (19%) of cardiac surgery patients to avoid exposure to erythrocytes postoperatively.     

Effect of moderate pressure distention on the human saphenous vein vasomotor function

BACKGROUND: Manual pressure distension, which is commonly applied to the human saphenous vein graft for coronary artery bypass, is believed to have detrimental consequences for the graft patency. The vasomotor function of the vein after distention during surgical preparation for grafting and after distention in laboratory conditions at pressure of 50 to 600 mm Hg was studied. The effect of a combination of vasodilative agents to prevent vasospasm was also tested. METHODS: The contractile and dilatory responses of distended and undistended human saphenous veins and those after drug treatment were examined in organ baths under isometric conditions. RESULTS: Distention at the pressure range 100 to 300 mm Hg resulted in an increased contractile response of the saphenous vein to both alpha-adrenergic activation with 50 micromol/L phenylephrine (153.73% +/- 15.69%) and depolarization with 80 mmol/L K(+) (141.03% +/- 15.13%) in comparison with the undistended vein and did not impair the relaxation. In contrast manual distention during surgical preparation abolished the contractile response and impaired the relaxation. The application of a combination of vasodilative drugs (alpha-adrenergic antagonist phenoxybenzamine, 10 micromol/L, Rho-kinase inhibitor HA-1077, 50 micromol/L, and calcium blocker nicardipine, 1 micromol/L) eliminated the contractile response of the vein to phenylephrine and 80 mmol/L K(+). This effect was sustained more than 20 hours after the washout of the drugs. CONCLUSIONS: The distention of the human saphenous vein at moderate pressure combined with the application of the effective combination of vasodilative drugs before grafting into the arterial circulation could be a beneficial alternative to the current practice of uncontrolled pressure distension.     

The short saphenous vein: an alternative to the long saphenous vein for aortocoronary bypass.

The long saphenous vein and internal mammary artery are considered at present to be the best grafts available for coronary artery bypass. Patients who have had bilateral long saphenous vein stripping and who require multiple aortocoronary bypass grafts present a challenge to the cardiac surgeon. The short saphenous vein appears to be a suitable alterative.     

The healing characteristics of autogenous saphenous vein used in the reconstruction of previously implanted arterial saphenous vein grafts

Aortocoronary saphenous vein grafts with early isolated stenoses pose the technical problem of how to deal with these grafts at reoperation. The advisability of using a portion of old graft when reconstructing these grafts was examined. An experimental model was devised in which the anatomical and pathological interfaces between fresh vein and previously inserted vein were studied. Superficial femoral artery from the thigh of 15 dogs was replaced by reversed autogenous saphenous vein. Four months later, the animals were divided into two groups. Group 1 consisted of 8 animals that underwent transection and reimplantation of the middle 4 cm of the vein graft in exactly the same position in which it had been. In Group 2, the 7 animals had the middle 4 cm of the graft replaced with newly harvested reversed saphenous vein. Six months after initial vein graft implantation, the animals were studied. No critical stenoses were seen in the grafts. Pathological study of Group 1 grafts revealed fibrous graft disease of uniform severity throughout the graft, thereby demonstrating that new anastomoses in an old graft do not affect graft disease. Group 2 grafts revealed that the severity of disease in the new interposed segment of the vein graft was less than in the old retained portions of the graft. No untoward reaction causing acceleration of graft disease occurred between old and new vein. Operations using undiseased portions of old vein grafts should be considered a viable option in repeat coronary revascularization for early stenoses.     

一氧化氮对人培养血管内膜增生的抑制作用

目的 研究一氧化氮（ＮＯ）对体外培养人正常大隐静脉片内膜增生的影响。方法 取来自同一条正常大隐静脉的３段长５ｍｍ血管,随机分入３组,共用６条大隐静脉。体外培养２组大隐静脉片,其中１组加入ＮＯ供体亚硝基乙酰青霉胺（Ｓ－ｎｉｔｒｏｓｏ－Ｎ－ａｃｅｔｙｌ ｐｅｎｉｅｌｌａｍｉｎｎｅ,ＳＮＡＰ）,免疫组织化学染色后观察内膜增生及细胞增殖。结果 培养静脉片可见明显内增生和平滑肌细胞增殖。与对照组相比,加入Ｓ