The Safety of Simultaneous Arterial and Coronary Sinus Perfusion: Experimental Background and Initial Clinical Results

Concern over myocardial damage from simultaneous arterial (antegrade) and coronary sinus (retrograde) perfusion has led to alternating between these delivery routes to maximize their individual benefits. Based upon predominant retrograde drainage via Thebesian veins, this study: (1) confirms experimentally the safety of simultaneous arterial and coronary sinus perfusion; and (2) reports initial clinical application of this combined strategy in 155 consecutive patients. Experimental: Five mini-pigs (25 to 30 kg) underwent 1 hour of aortic clamping with simultaneous aortic and coronary sinus perfusion at 200 mUmin with normal blood (37°C) before and after 30 minutes of perfusion with either warm (37°C) or cold (4°C) blood cardioplegia. Coronary sinus pressure was always less than 30 mmHg. There was no right or left ventricular edema, lactate production, or lipid peroxidation as transmyocardial and myocardial conjugated dienes were unaltered, and postbypass recovered left ventricular end-systolic elastance (conductance catheter) and preload recruitable stroke work Index 101%± 3% and 109%± 90%, respectively. Clinical: Simultaneous arteriaVcoronary sinus perfusion was used in 155 consecutive high risk patients (New York Heart Association Class III to IV) undergoing isolated coronary artery bypass grafting (CABG) (n = 109) and CABG + valve replacementlrepair or aneurysm (n = 46). Included were 16 patients in cardiogenic shock and 24 undergoing reoperation. Mean aortic clamping time averaged 90 ± 4 minutes (range 30 to 207), with 3.5 ± 0.1 grafts per patient; all anastomoses were performed with the aorta clamped. Cold intermittent blood cardioplegia was used for distal anastomoses and valve implantationhepair in 123 patients, and warm continuous blood cardioplegia was used in 32 patients. Following a warm cardioplegic reperfusate, all patients received warm non-cardioplegic blood perfusion simultaneously via grafts and coronary sinus. Coronary sinus pressure was always less than 40 mmHg. Of 18 patients requiring postoperative mechanical circulatory support (IABP), 16 had IABP placed preoperatively for cardiogenic shock. There were three postoperative myocardial infarctions (2%), and six patients died (3.9% mortality). Conclusion: These experimental and clinical findings overcome perceived concerns about myocardial damage from simultaneous arterial and coronary sinus perfusion, and suggest this approach may add to the armamentarium of cardioprotective strategies. (J Card Surg 1994;9:15–25)     

Plasmolemmal potassium gradient does not affect lung protection by an ATP-regulated potassium channel opener

BACKGROUND: We have previously shown that metabolic arrest induced with ATP-regulated potassium channel openers (PCOs) can improve lung preservation by adding Aprikalim (a PCO, Rhone-Poulene Roher) to modified Euro-Collins solution for pulmonary artery flush. Because the membrane hyperpolarizing effects of a PCO potentially competes with the depolarizing effects of a hyperkalemic solution, this study evaluated the effects of the potassium gradient on PCO-mediated lung protection. STUDY DESIGN: Twenty rabbits underwent lung protection in four groups. Group 1 underwent harvest and reperfusion as a "no ischemia" control. Groups 2, 3, and 4 underwent harvest followed by 18 hours of cold ischemic storage before reperfusion. Groups 1 and 4 received Euro Collins as the pulmonary flush at induction of ischemia. Group 2 received Euro Collins plus Aprikalim (100 microM); and group 3 received lactated Ringer's plus Aprikalim. After ischemic storage, the lungs were reperfused with autologous blood for 2 hours. Every 30 minutes, the lungs were given a 10-minute 100% fractional inspired oxygen (F(i)O(2)) challenge to measure maximal gas exchange as an indication of graft function. RESULTS: Repeated measures ANOVA showed Aprikalim improved graft function after 18 hours of cold ischemia (p < 0.0001). No significant differences were found when Aprikalim was used in either Euro-Collins (group 2) or lactated Ringer's (group 3) solution. CONCLUSIONS: The ability of the PCO Aprikalim to preserve gas exchange in a model of hypothermic pulmonary ischemia-reperfusion injury was not affected by the plasmolemmal potassium gradient. This is consistent with recent findings in myocardial protection studies that the protective effects of PCOs may be intracellular.     

不同幅度脉冲膈肌起搏对兔膈肌SOD、MDA、总抗氧化能力的影响

目的　探讨不同幅度脉冲膈肌起搏 (diaphragmpacing ,DP)对新西兰大白兔膈肌的影响。方法　建立兔颈部DP模型 ,测定无起搏 (A)组及脉冲幅度匀速增加 (B)组、恒定 (C)组、匀速减小 (D)组起搏后膈肌组织SOD、MDA及T AOC。结果　①DP后 ,B组较A组MDA含量增加 ,SOD及T AOC减小 (P >0 .0 5 ) ;②DP后 ,C组及D组较A组MDA含量增加 ,SOD及T AOC减小 (P <0 .0 5 ) ;③DP后 ,B组较C及D组MDA含量少 ,SOD及T AOC活力强 (P <0 .0 5 )。结论　①脉冲幅度匀速增加通过减少氧自由基的产生 ,抗氧化能力的干扰 ,可能减缓了膈肌疲劳 (diaphragmfailure ,DF)的发生 ,②脉冲幅度匀速增加与脉冲幅度恒定和匀速减小相比 ,是一种更为合理的DP方式。     

原位心脏移植治疗终末期心脏病141例

目的分析总结原位心脏移植治疗终末期心脏病的临床疗效及经验。方法为141例终末期心脏病患者施行原位心脏移植术,原发病包括扩张性性心肌病118例,肥厚性心肌病2例,限制性心肌病2例,缺血性心肌病9例,原发性心脏恶性肿瘤4例,瓣膜性心肌病3例,其它病因3例。供心冷缺血时间为(191.0±28.5)m in,供心卵圆孔未闭者9例,大室间隔缺损者1例,冠状动脉开口异常者1例。9例卵圆孔未闭的供心,先行卵圆孔缝闭术,然后再行移植;1例大室间隔缺损的供心,先行室间隔缺损修补术,然后再行移植;1例冠状动脉开口异常的供心,复跳后心肌收缩乏力,遂施行右冠状动脉松解术,其后复跳良好。120例行双腔静脉吻合法原位心脏移植术,19例行标准Stanford原位心脏移植术,2例行全心脏移植术。主动脉阻断时间为(53.0±4.5)m in,吻合时间为(41.5±5.5)m in。术后应用环孢素A(或他克莫司)、激素及霉酚酸酯预防排斥反应,28例患者同时应用达利珠单抗1~5剂。结果手术成功率为97.9%,术后随访1~65个月,1年、3年、5年存活率分别为90.8%、84.6%、81.4%,术后1年内的主要死因是急性排斥反应、感染、移植物功能衰竭及心脏肿瘤转移,术后中远期的主要死因是急性排斥反应、感染、肾功能衰竭及移植心脏冠状动脉硬化。术后并发症以急性排斥反应、感染、肾功能异常、移植心脏功能衰竭多见。结论终末期心脏病行原位心脏移植的临床疗效良好;远期需注意对急性排斥反应、感染及移植心脏冠状动脉硬化的监测及治疗。     

冷冻保存同种带瓣管道的活性研究

目的　探讨液氮冷冻保存对带瓣管道的细胞活性的影响。方法　将 40份同种主、肺动脉管道 ,经修剪、抗生素液处理 ,液氮冷冻保存 4～ 12个月后取出 ,留取主、肺动脉壁片、二尖瓣作细胞培养、光镜和电镜检查 ,并取新鲜主、肺动脉壁片、二尖瓣 4份作对照。结果　冷冻保存 4～ 7个月的管道 ,于 4周后成纤维细胞长满视野 ,细胞收获数为 :二尖瓣 (67.64± 2 5 .60 )万～ (74.5 8±12 .3 4)万 ,主肺动脉壁片 (3 2 .45± 4.75 )万～ (3 8.67± 18.3 2 )万 ,冷冻 1年的管道极少量细胞生长 ,为 (3 0 .61± 17.3 3 )万和 (15 .64± 8.73 )万。保存 4～ 7个月组和新鲜组相比 ,差异无显著性 (P >0 .0 5 ) ,与保存 12组相比 ,差异有非常显著性 (P <0 .0 1)。病理改变见内皮细胞层消失 ,电镜下见成纤维细胞及平滑肌细胞形态正常 ,胶原纤维排列整齐。结论　液氮冷冻保存 7月内 ,带瓣管道仍具有较强的细胞活性。     

同种异体反应性淋巴细胞克隆疫苗回输诱导受体特异性免疫耐受的研究

目的：探讨同种异体移植抗原抗原特异性免疫耐受诱导的新途径，以达到心肺移植长期存活的目的。方法：以同种异体反应性淋巴细胞克隆在体外培养条件下大量增殖后，作为自身独特性疫苗，体内注射免疫家兔，以混合淋巴细胞反应来观察免疫前和免疫后对供体淋巴细胞刺激指数（SI）的变化。结果：同种异体反应性自身独特型淋巴细胞疫苗具有显著诱导特异性免疫应答移植现象，SI值显著降低（P＜0．05），而对卡介苗诱导的特异性免疫应答并未因独特型淋巴细胞疫苗的应用而下降，结论：同种异体反应性自身独特型淋巴细胞疫苗有可能成为诱导抗原特异性免疫耐受的一种手段。     

Focal liver necrosis appears early after partial hepatectomy and is dependent on T cells and antigen delivery from the gut

Introduction: Progressive liver failure may develop following removal of a large part of the liver or transplantation of a small for size liver graft. The pathophysiology of this clinical syndrome is only partially understood. Methods: We assessed liver damage and hepatocyte 5‐bromo‐2′‐deoxyuridine (BrdU) incorporation following partial hepatectomy (PH) in C57BL/6, BALB/C and immune‐deficient mice. Hepatic lymphocyte subpopulations were characterized. Lipopolysaccharide (LPS) treatment and bowel decontamination determined the role of gut antigens. Results: Discrete, round necrotic lesions were observed as early as 2 h following 70%, but not 30% PH. In immune competent mice the extent of hepatocyte necrosis inversely correlated with BrdU incorporation. T, natural killer and natural killer T cells were recruited to the liver early after PH; however, only T‐cell depletion abrogated hepatic necrosis. Hepatic injury was significantly reduced in non‐obese diabetic/severe combined immunodeficient mice undergoing PH, while BrdU incorporation was not affected. Liver injury was augmented by LPS injection and reduced by gut decontamination. Conclusions: A distinct pattern of early focal hepatic necrosis is observed following extensive PH in mice. T cells infiltrating the liver immediately after PH and gut‐derived antigens are indispensable for the observed liver necrosis and may thus provide therapeutic targets to ameliorate liver damage following PH.     

Results of A trial with topotecan dose escalation and concurrent thoracic radiation therapy for locally advanced, inoperable nonsmall cell lung cancer

: To conduct a dose escalation clinical study with topotecan and concurrent standard dose thoracic irradiation to assess its feasibility and toxicity in the treatment of patients with locally advanced, inoperable nonsmall cell lung cancer (NSCLCA).

: Between April 1993 and August 1994, 12 patients with inoperable, loco-regionally advanced NSCLCA were entered in a prospective dose escalation trial and assigned to receive concurrent thoracic radiotherapy and topotecan. Patients received thoracic irradiation to a total tumor dose of 60 Gy in 30 fractions. Initial fields were to encompass the gross disease plus the mediastinum. Topotecan was delivered by bolus injection days 1 through 5, and days 22 through 26, beginning on the same day as the radiation therapy. The initial dose level was 0.5 mg/m². Two additional dose levels of 0.75 mg/m² and 1.0 mg/m² were tested.

: Six patients were accessioned to the 0.5 mg/m² dose level, three patients to the 0.75 mg/m² dose level, and three patients to the 1.0 mg/m² dose level. At the 0.5 mg/m² dose level, zero of six patients had ≥Grade 4 hematologic toxicity. One of the six had Grade 3 esophagitis. At the 0.75 mg/m² dose level, two of three patients had ≥Grade 3 nonhematologic toxicity including anorexia, fatigue, nausea, vomiting, and weakness; zero patients experienced ≥Grade 4 hematologic toxicity. At the 1.0 mg/m² dose level one of three patients had ≥Grade 3 esophagitis, and two of three patients experienced Grade 4 neutropenia. With a follow-up of 12 to 24 months, two patients are alive and free of disease, three patients are alive with disease (two with distant metastasis, one with local disease and distant metastasis), and the remaining seven patients are dead of disease.

: The combination of topotecan and thoracic radiotherapy for nonsmall lung cancer, in the manner given by this protocol, could be safely given at a dose level of only 0.5 mg/m² days 1 to 5 and 22 to 26 with 60 Gy of external beam radiotherapy. Higher doses of topotecan were associated with high hematologic and gastrointestinal toxicity. Distant metastasis was the primary pattern of failure.     

局部灌注和全心灌注对兔缺血再灌注心肌保护作用的对比研究

目的研究经左冠状动脉回旋支局部灌注腺苷对兔缺血再灌注心肌损伤模型的保护作用,以及这一作用与全心脏灌注腺苷的区别。方法实验将麻醉后的家兔分为三组各10只:A组即对照组,B组为经回旋支局部灌注腺苷组,C组为经右侧颈总动脉全心脏灌注腺苷组。各组均建立局部心肌缺血模型。30min后,A组实现缺血心肌再灌注;B组向缺血区再灌注含腺苷浓度为10μmol/L的动脉血;C组全心灌注含腺苷浓度为10μmol/L的动脉血。收集血流动力学、心电图、心肌酶CK-MB、髓过氧化物酶(MPO)、电镜等指标。结果与对照组相比,局部灌注组和全心灌注组都能够明显改善缺血再灌注后心肌的收缩和舒张功能(P<0.05),并且局部灌注组的舒缩功能要好于全心灌注组(P<0.05)。髓过氧化物酶活性也是同样结果。两组CK-MB漏出浓度和心肌含水量与对照组相比均有明显减低(P<0.05),但是局部灌注和全心灌注之间差异无统计学意义。电镜超微结构显示两个腺苷灌注组的心肌结构要好于对照组。结论局部灌注腺苷和全心脏灌注腺苷都能够起到保护心脏、减轻缺血-再灌注损伤和抗心肌坏死的作用。但局部灌注组在心肌舒缩功能和MPO活性两方面与全心脏灌注组的显著性差异能够说明前者在心肌保护方面具有更强的优越性。