^31P—MRS无创评估梗阻性黄疸肝功能损害的价值

目的:探讨31P-MRS技术评价梗阳性黄疸旰功能损害的价值.方法:对36例梗阻性黄疸患者(黄疸组)进行单体素31P-MRS扫描,计算肝细胞内pH值(pHi)、磷酸单脂(PME)、磷酸双脂(PDE)、无机磷(Pi)、γ-ATP、β-ATP、α-ATP、PME/ATP、Pi/ATP、PME/PDE、PME/Pi、PDE/Pi、PDE/ATP和低能磷酸盐(LEP)等.检测临床肝功能血清学指标.以40例正常人为对照组,分析黄疸对31P-MRS检测参数的影响及其与肝功能血清检测指标之间的关系.结果:黄疸组肝脏PME、PDE、PME,ATP、PME/Pi、PDE/ATP及LEP均明显大于对照组,两组差异有统计学意义(P<0.05).PME/Pi与ALP正相关(r=0.592,P=0.043).PDE与DBIL(r=0.588,P=0.034)正相关,PDE/Pi分别与DBIL(r=0.647,P=0.017)、IBIL(r=0.583,P=0.037)及ALT(r=0.568,P=0.027)正相关;PME/PDE与ALB负相关(r=-0.739,P=0.003).而Pi/ATP与A/G负相关(r=-0.569,P=0.034).其余参数与各肝功检测值之间未见相关性(P>0.05).结论:31P-MRS可以对梗阻性黄疸导致的肝功能损害进行无创性评估,PME和PDE代谢物可能是反映肝功能损害较为敏感的指标.     

DLL4和血管内皮生长因子在肝细胞癌的表达及其在肿瘤血管生成的作用

目的 探讨Delta样配体(DLL4)及血管内皮生长因子(VEGF)在肝细胞癌中的表达及其与血管生成的关系.方法 免疫组织化学法检测75例肝细胞癌(HCC)中DLL4和VEGF的表达,用CD34进行微血管内皮细胞染色,计算微血管密度(MVD),分析其相关性.结果 DLL4和VEGF表达在HCC组明显高于肝硬化组和正常肝组(P＜0.01),与HCC的临床病理学分级相关(P＜0.01),HCC组中的CD34表达与DLL4的表达呈明显负相关(P＜0.05,r=-0.778);与VEGF的表达呈明显正相关(P＜0.05,r=0.747),32例共表达DLL4和VECF蛋白者,其平均微血管数(19.70±5.82)个/HP,明显高于非共表达组(7.60±2.12)个/HP(P＜0.01).结论 DLL4、VEGF在肝细胞癌血管生成中可能起重要作用.     

原发性肝细胞癌以及近癌旁组织微血管密度CD105表达及其临床意义

目的 研究肝细胞癌(HCC)及其近癌旁组织微血管密度(MVD-CD105)分布,探讨MVD-CD105在HCC、近癌旁组织的分布规律、临床意义以及CD105标染HCC组织微血管的特异性.方法 采用免疫组织化学方法检测63例HCC组织、近癌旁组织MVD-CD105,比较HCC组织和近癌旁组织MVD-CD105分布特点及其与临床参数的关系.结果 63例HCC及其近癌旁组织血管CD105阳性表达率为100％,近癌旁组织表达强度高于癌组织(χ2=9.184,P＜0.01).HCC组织MVD-CD105为(58.37±21.45)/0.74mm2,近癌旁组织为(81.62±19.86)/0.74mm2,近癌旁组织MVD-CD105分布显著高于癌组织(t=2.438,P＜0.05).HCC组织中的MVD-CD105阳性表达分布与肿瘤转移及TNM分期有关(P＜0.01).近癌旁组织的MVD-CD105阳性表达分布与肿瘤TNM分期及2年存活时间有关(P＜0.05).结论 CD105标染HCC组织MVD未体现出肿瘤微血管标染特异性.HCC组织MVD-CD105高表达、分布意味着肿瘤的局部转移和进展.CD105分子不能作为抗肝癌肿瘤血管生成靶向治疗的靶标,但肝癌MVD-CD105的检测对于后续综合治疗有指导意义.     

NF-κBp65、VEGF在肝癌血管生成中的作用与相关性研究

目的 通过对肝细胞癌(HCC)组织、癌旁组织、肝硬化组织及正常肝组织中核转录因子-κBp65(NF-κBp65)、血管内皮生长因子(VEGF)的蛋白表达和微血管密度(MVD)的检测,探讨NF-κBp65、VEGF的蛋白表达与HCC新生血管生成的关系及相关性,阐述二者在HCC血管生成中的机制.方法 选用45例HCC组织和32例癌旁肝组织、15例肝硬化组织、10例正常肝组织标本作对照,采用免疫组化法(SABC)检测其NF-κBp65、VEGF的表达和计数MVD值,并结合患者的临床病理指标进行统计学分析.结果 HCC中NF-κBp65、VEGF的表达和MVD值显著高于癌旁肝组织、肝硬化组织和正常肝组织(P＜0.05);HCC组织中NF-κBp65、VEGF阳性表达组显著高于阴性表达组(P＜0.05);NF-κBp65、VEGF的表达在有血管侵犯组显著高于无血管侵犯组(P＜0.05);Spearman等级相关分析NF-κBp65与VEGF表达之间存在正相关性(r=0.72,P＜0.05).结论 HCC中NF-κBp65、VEGF的表达与肝癌血管生成有关;HCC组织中NF-κBp65的表达与VEGF存在相关性,它们之间在肝癌血管生成中可能存在调节关系.     

血管生成及其成熟度在肝细胞癌边缘与中心的差异研究

目的:探讨肝细胞癌 (hepatocellular carcinoma, HCC) 边缘和中心血管生成及其成熟度的差异.方法:利用免疫组织化学技术检测病灶边缘(A组)和中心区域组织(B组)血管内皮生长因子(vascular endothelial growth factor, VEGF)、Flk-1、增殖细胞核抗原(proliferating cell nuclear antigen, PCNA)的表达情况,并对微血管和成熟血管的数目、平均面积、总面积、周长、直径、异型指数、血管间距、表达部位,以及动脉数、静脉数、动脉比、静脉比、血管成熟指数和平均灌注分数等进行计数.分析以上血管生成相关参数在肿瘤边缘和中心的差异.结果:两组微血管的数目、直径及异型指数,成熟血管的数目、总面积、动脉数、动脉比及静脉比,血管成熟指数及平均灌注分数差异均有统计学意义(P<0.05).A组微血管和成熟血管的数目、平均面积、总面积、直径、异型指数及血管间距差异均有统计学意义(P<0.05).而B组微血管和成熟血管的数目、总面积、异型指数及血管间距差异也均有统计学意义(P<0.05) ,但平均面积、周长和直径比较差异无统计学意义 (P>0.05).结论:HCC边缘和中心的微血管和成熟血管的多个形态学特征存在差异,病灶中心血管多为幼稚的微血管,边缘则以成熟血管居多.     

肝癌切除术患者围手术期血脂代谢的变化及其临床意义

目的 分析肝细胞肝癌(HCC)肝切除术患者围手术期血脂的变化及其与前清蛋白、转氨酶变化的关系.方法 选取HCC肝手术患者126例,测定术前及术后1,3,7 d的甘油三酯、胆固醇、前清蛋白、转氨酶水平.结果 HCC患者术前胆固醇降低,与对照组有显著差异(P＜0.01),术后第1,3,7天甘油三酯、胆固醇较术前明显降低(P＜0.01).胆固醇变化与谷丙转氨酶呈负相关(r=-0.231,P＜0.05),与前清蛋白无相关性(r=0.082,P＞0.05).甘油三酯水平与术前清蛋白及谷丙转氨酶水平无相关性(r=0.091,P＞0.05;r=0.086,P＞0.05).结论 HCC患者存在血脂代谢紊乱,术后血脂降低可能与肝功能损害及手术应激有关.     

颈动脉粥样硬化斑块中VEGF受体Flk-1和Flt-1表达的改变及其意义

目的探讨颈动脉粥样硬化(CAS)斑块中血管内皮生长因子受体Flk-1和Flt-1表达的改变,并分析其与斑块内炎症细胞浸润和新生血管的相关性.方法应用免疫组化和原位分子杂交方法分别检测CAS斑块中Flk-1和Flt-1蛋白和mRNA表达的改变,以CD34免疫组化染色标记斑块内新生血管.结果Flk-1和Flt-1均主要表达于炎症细胞浸润区的巨噬细胞和单核细胞,在坏死区周边基质内,也存在不同程度的Flk-1和Flt-1染色带,二者与炎症细胞浸润之间均具有明显的相关性(Flk-1r=0.41,P＜0.05;Flt-1r=0.71,P＜0.01);而新生血管内皮细胞仅有Flk-1表达,与新生血管之间具有明显的相关性(r=0.64, P＜0.01),而无Flt-1表达.结论在CAS病理中,血管内皮生长因子Flk-1和Flt-1均参与了炎症介导过程,而在新生血管生成中可能仅有Flk-1的参与.     

CTGF和VEGF在肝癌中的表达及相关性研究

目的 探讨结缔组织生长因子(CTGF)及血管内皮生长因子(VEGF)在肝细胞性肝癌(HCC)组织中的表达及其相关性.方法 采用免疫组织化学SABC法检测48例HCC和26例癌旁组织中CTGF、VEGF的表达,并分析两者之间的相关性.结果 在HCC组织中,CTGF和VEGF的阳性表达率分别为77.08%、85.42%,而在癌旁组织中的阳性表达率分别为23.08%、34.62%,其差异均有统计学意义(P＜0.05);CTGF的表达与肿瘤的侵袭转移能力、肝硬化程度、肿瘤大小、肿瘤分化程度密切相关(P＜0.05),VEGF的表达和肿瘤的侵袭转移能力、肿瘤大小及肿瘤分化程度密切相关(P＜0.05);HCC组织中,CTGF和VEGF的阳性表达相关性分析显示两者成正相关(r=0.381,P＜0.05). 结论 CTGF和 VEGF参与了肝癌组织的发生发展,联合检验CTGF、VEGF可以作为肝癌的诊断及判断预后的指标.     

COX-2在肝细胞肝癌中的表达及其与细胞凋亡的关系

目的 探讨肝细胞癌(HCC)中环氧化酶-2(COX-2)的表达与细胞凋亡的关系及其可能的机制.方法 选用44例HCC组织制作组织芯片,应用免疫组织化学S-P法检测癌组织COX-2、caspase-3和survivin的表达情况.应用末端标记法(TUNEL)检测细胞凋亡指数(AJ).结果 HCC中COX-2蛋白阳性率为52.3%,其表达与AJ呈显著负相关r=-0.354,P＜0.05),与caspase-3蛋白表达也呈显著负相关(r=-0.447,P＜0.01),但与survivin蛋白的表达呈显著正相关(r=0.394,P＜0.01).AI与caspase-3呈显著正相关(r=0.381,P＜0.05),但与survivin呈显著负相关(r=-0.458,P＜0.01).结论 本研究证实了HCC中COX-2的抗肿瘤细胞凋亡作用;其机制可能是通过上调肿瘤细胞survivin表达,同时下调caspase-3表达途径实现的.     

肝动脉灌注化疗后肝细胞癌8-OHdG、p53和p21~(waf1/cip1)的表达研究

目的 探讨肝细胞癌(hepatocellular carcinoma,HCC)患者经导管肝动脉灌注化疗(transcathcter arterial chemotherapy,TAC)后肝组织8-羟基-2'脱氧鸟嘌呤核苷(8-hydroxy-2'-deoxyguanosine,8-OHdG)、p53和p21_(waf1/cip1)蛋白的表达.方法 HCC患者分为两组,术前行TAC治疗的HCC患者39例(TAC组),术前未行TAC治疗的HCC患者50例(非化疗组),肝血管瘤和肝内胆管结石患者15例为对照组.免疫组织化学法检测肝组织的8-OHdG、p53和p21~(waf1/cip1)蛋白表达水平.结果 8-OHdG表达在癌组织中表现为非化疗组高于TAC组(F=9.516,P＜0.05),对照组最低(F=9.516,P＜0.01);在TAC组与非化疗组均为癌组织高于痛旁组织(分别t=7.101,t=8.020,均P＜0.001);癌旁组织与对照组的8-OHdG水平差异尤统计学意义;TAC组与非化疗组巾的癌组织和癌旁组织的8-OHdG表达呈正相关(r=0.651,r=0.493,均P＜0.001).p53表达在TAC组和非化疗组差异无统计学意义.p21~(waf1/cip1)三组间有差异表达.在癌组织中和癌旁组织p21~(waf1/cip1)表达均为对照组最高(F=13.459,F=16.613,均P＜0.001),TAC组高于非化疗组(F=13.459,F=16.613,均P＜0.01),但癌组织和癌旁组织比较差异无统计学意义.21_(waf1/cip1)在非化疗组中癌组织和癌旁组织表达的水平呈正相关(r=0.872,P＜0.001).结论 HCC痛组织的8-OHdG、p53和p21~(waf1/cip1)的表达高于痛旁和非HCC肝组织;癌细胞可能经由增强的氧化应激修复机制逃脱介入化疗.     

In vivo 31P MR spectroscopy of human kidney grafts using the 2D-chemical shift imaging method

The aim of this work was to evaluate the possibility to use in vivo ³¹P magnetic resonance spectroscopy (MRS) for the diagnosis of kidney graft dysfunction after transplantation.We examined 68 kidney grafted patients using a 1.5 T MR scanner. ³¹P MRS was performed using the 2D-chemical shift imaging method. The patients were divided into 4 groups: acute rejection episode; acute tubular necrosis; late graft dysfunction; or good renal function. We measured the signal intensities of phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), and α-, β-, γ-adenosine triphosphate (ATP; with contributions of α- and β-adenosine diphosphate) and their ratios.Patients with an acute rejection episodes showed a significantly elevated PME/β-ATP and PDE/β-ATP, PME/Pi, and PDE/Pi signal ratios compared with the control group. The group with acute tubular necrosis had decreased ratios. Patients with late graft dysfunction revealed only an insignificant decrease in PME/Pi and PDE/Pi ratios. We concluded that ³¹P MRS was capable of distinguishing the two main causes of graft dysfunction early after transplantation.     

Persistent metabolic sequelae of severe head injury in humansin vivo

Summary Six patients who had suffered severe non-penetrating high velocity head injuries were investigated with phosphorus (³¹P) magnetic resonance spectroscopy (MRS) to determine, non-invasively, long-term alteration in intracellular biochemistry. The normal subjects were found to have a constant intracellular pH (pHi, 7.03±0.03) with depth into the brain. The adenosine triphosphate (ATP, 3.46±0.66mmol/L of brain tissue), inorganic phosphate (Pi, 1.15±0.41 mmol/L) and phosphomonester (PME, 2.76±1.0 mmol/L) tissue concentrations did not alter significantly with depth into normal brain. The phosphocreatine (PCr, 2 cm = 5.21±1.25, 5 cm=4.85±1.49 mmol/L) was slightly reduced, whilst phosphodiesters (PDE, 2 cm=9.53 ±2.6, 5 cm=14.41±4.2 mmol/L) rose significantly between tissue comprising mainly of gray (2 cm) and white matter (5 cm). In comparison the contra-lateral hemisphere to the side of worst spasticity showed significant changes a considerable time after injury (6–18 months). The intracellular metabolite tissue concentrations were all reduced by 30% (ATP 2.53±1.0 mmol/L, PCr 3.44±0.8 mmol/L) with PDE reduced most significantly at depth (5 cm=8.4±3.4 mmol/L), compatible with the cerebral atrophy seen in these patients. In white matter the pHi also decreased with depth (2 cm=7.03±0.03, 5 cm=6.89±0.05). The reduction in pHi so long after injury is difficult to explain in these steady-state conditions. A structural abnormality, such as a disorder in the blood brain barrier or accumulation of large acidic lysosomes, could cause these pHi changes. There may also be a failure in blood flow regulation, with near critical fluctuations in blood flow both with time and space.     

Pretransplant assessment of renal viability by phosphorus-31 magnetic resonance spectroscopy. Clinical experience in 40 recipient patients

A group of 40 cadaveric kidneys was studied just prior to planned transplantation to further assess the applicability of 31P-MRS in the analysis of clinical renal transplant viability. Renal intracellular high-energy phosphorus metabolites (ATP [or NADP], phosphomonoester [PME] and inorganic phosphate [Pi]) and pH were measured noninvasively with MRS surface coils external to cold storage containers. Pretransplant MRS parameters were correlated with subsequent renal function in recipient patients (measured one week postoperatively by the need of dialysis, drop in serum creatinine, urine output, and 123I or 131I Hippuran assessed renal tubular function). ATP and NADP was detected in eleven kidneys and was significantly (P less than 0.001) associated with the best renal function posttransplantation. These kidneys also had the highest PME/Pi ratios (1.66-0.54), while lower ratios (0.36-0.10) were associated with prolonged acute tubular necrosis. The PME/Pi ratios significantly (P less than 0.0001) correlated with subsequent clinical renal function, whereas cold storage times (37 +/- 10 hr) or intracellular renal pH (6.53-7.91) did not. These preliminary data suggest that MRS is a noninvasive, nondestructive and sterile method for assessing clinical viability during hypothermic storage of human cadaver kidneys and the subsequent recovery of renal function postrenal transplantation.     

In vivo 31P NMR spectroscopic changes during liver regeneration

Liver regeneration following partial hepatectomy involves rapid cell division 24 to 72 hr postresection. This cell division would necessarily involve changes in intracellular energy stores and cell membrane phospholipid precursors. In tumor models 31P nuclear magnetic resonance (NMR) has been shown to identify intracellular substrate changes associated with cell growth. The ability to monitor early changes in adenosine triphosphate (ATP), inorganic orthophosphate (Pi), phosphomonoesters (PME), or phosphodiesters (PDE) after liver resection could indicate the intracellular changes necessary for hepatocellular regeneration. In vivo 31P NMR scans of the liver were performed in both normal rats and in rats at 24, 48, 72, and 120 hr after 70% hepatectomy. At 48 hr, total ATP fell to 18.9% (P less than 0.05) and both Pi/beta-ATP and PME/beta-ATP were significantly elevated (P less than 0.01) from controls. These changes correlate with the known mitotic peak in the rat following hepatectomy. We conclude that in vivo 31P NMR is a potentially valuable tool for studying hepatic regeneration. The data also suggest that hepatocellular regeneration may be critically dependent on cellular ATP stores.     

Experimental study on pathophysiology and treatment of congenital hydrocephalus evaluated by magnetic resonance imaging and magnetic resonance spectroscopy]

I. Experimental Study on Pathophysiology of Congenital Hydrocephalus It is well known that the major pathogenic mechanism of hydrocephalus is disturbance in cerebrospinal fluid (CSF) circulation. For this reason, many studies on hydrocephalus were intended from the viewpoint of CSF circulation both experimentally and clinically. However, few studies have yet been done on the correlation between the morphological changes and the changes in cerebral energy metabolism in hydrocephalus in vivo. So, in this study, the correlation between the morphological changes and the changes in cerebral energy metabolism in congenital hydrocephalic rats was evaluated experimentally. The morphological changes were estimated by using magnetic resonance imaging (MRI), and the longitudinal relaxation time (T1) of brain tissue at parietal area was also measured. The cerebral energy metabolism was evaluated by using 31P magnetic resonance spectroscopy (MRS) method, and cerebral phospholipid membrane metabolism was also evaluated by using 31P-MRS method. The region of interest (ROI) giving rise to the 31P spectra was placed at fore-brain and parietal area. The PCr/Pi ratio was used as the chosen indicator of cellular bioenergetic status. The PME/beta-ATP ratio and PDE/beta-ATP ratio were used as the chosen indicator of cerebral phospholipid membrane metabolism. The intracellular pH was also evaluated by using 31P-MRS method. Fifty congenital hydrocephalic rats of the HTX strain were used. The animals were divided into two groups--non-hydrocephalic group (n = 15) and hydrocephalic group (n = 35)--. The rats of hydrocephalic group were subdivided into three smaller groups according to the degree of hydrocephalus--mild (n = 15), moderate (n = 10) and severe (n = 10)--, which was estimated by using the cerebro-ventricular ratio (CVR) in coronal section of MRI. Experimental results were as follows: 1) The T1 values in rats of mild, moderate and severe hydrocephalic groups showed significant elongation in comparison with the value in non-hydrocephalic group (p less than 0.01), which indicated the expansion of interstitial edema in cerebral cortex. 2) The correlation between the T1 value and the CVR was evaluated and the correlation coefficient (r) was 0.932 which indicated high correlation. 3) The PCr/Pi ratios in rats of mild, moderate and severe hydrocephalic groups were decreased significantly in comparison with the value in non-hydrocephalic group (p less than 0.01), which demonstrated the disturbance of cerebral energy metabolism in congenital hydrocephalic rats. 4) The PCr/Pi ratio seemed to give the indicative data concerning the prognosis of congenital hydrocephalus.(ABSTRACT TRUNCATED AT 400 WORDS)     

Image-guided 31P magnetic resonance spectroscopy of normal and transplanted human kidneys

Image-guided 31-phosphorus magnetic resonance spectroscopy (MRS) was used to obtain spatially localized 31P spectra of good quality from healthy normal human kidneys and from well-functioning renal allografts. A surface coil of 14 cm diameter was used for acquiring phosphorus signals solely from a volume-of-interest located within the kidney. To determine the effects of kidney transplantation on renal metabolism, patients with well functioning allografts were studied. Little or no phosphocreatine in all spectra verifies the absence of muscle contamination, and is consistent with proper volume localization. The intensity ratio of phosphomonoesters (PME) to adenosine triphosphate (ATP) resonances in transplanted kidneys (PME/ATP = 1.1 +/- 0.4) was slightly elevated (P = 0.2) compared to that of healthy normal kidneys (PME/ATP = 0.8 +/- 0.3). The inorganic phosphate (Pi) to ATP ratio was similar in the two groups (Pi/ATP = 1.1 +/- 0.1 in transplanted kidneys vs. 1.2 +/- 0.6 in normal kidneys). Acid/base status, as evidenced from the chemical shift of Pi, was the same in both normal controls and transplanted kidneys. Despite the practical problems produced by organ depth, respiratory movement, and tissue heterogeneity, these results demonstrate that image-guided 31P MR spectra can reliably be obtained from human kidneys.     

Long-term assessment of posttransplant renal prognosis with 31 P magnetic resonance spectroscopy.

BACKGROUND: 31P-magnetic resonance spectroscopy (MRS) has been widely used to study pretransplantation renal viability, and although some had discussed posttransplant renal viability, no one has examined long-term posttransplant renal prognosis. We discuss the use of 31P-MRS to assess the long-term prognosis from the time when MRS was performed. METHODS: We studied 20 patients with renal allografts. 1.5 Tesla clinical magnetic resonance imaging (MRI) and 15 cm surface coil was used for 31P-MRS. Localized 31P-MRS was done using image selected in vivo spectroscopy (ISIS) method. Individual peaks were fitted by Lorenzian line-shapes with a least square method and peak area ratios were calculated. RESULTS: A beta-adenosine triphosphate/inorganic phosphate (beta-ATP/Pi) ratio >1.2 had sensitivity of 92.8%, specificity of 100%, and accuracy of 95% for predicting 3-year renal survival; a beta-ATP/Pi ratio >1.2 had sensitivity of 90.9%, specificity of 66.7%, and accuracy of 76.9% for predicting 5-year renal survival. We compared 31P-MRS spectra data between the survived group and failed group. The survived group had significantly higher beta-ATP/Pi, alpha-ATP/Pi, and phosphodiester (PDE)/Pi ratios than the failed group. CONCLUSIONS: We discussed the beta-ATP/Pi value as a parameter for predicting long-term survival of a transplanted kidney from the time when MRS was performed. A value above 1.2 suggests a high probability of 3-year renal survival, whereas a value over 2.5 indicates that the transplanted kidney could survive over 5 years. 31P-MRS may be useful for predicting long-term survival of transplanted kidneys, but additional studies are needed.     

High energy compound stability during experimental brain death

The aim of this study was to examine the effect of sudden brain death (BD) on myocardial function and high energy phosphate (HEP) stores. BD was induced by cerebral vessel ligation in six swine (BD group) that were compared to six control swine. At the end of the BD period (3 hours), harvested hearts were stored at 4 degrees C. Myocardial tissue HEP were assessed by: (i) (31)P-NMR spectroscopy of left ventricle for phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi) and intracellular pH (pHi), and by (ii) HPLC for ATP, ADP, and AMP levels in left ventricle biopsies. Brain death resulted in a instantaneous major increase in catecholamines (>50-fold, P < .001) and paradoxically a significant progressive decrease in the regional contractility of the left ventricle. After cardioplegia, no significant differences on HEP compounds (ATP/Pi, PCr/Pi, ATP, energetic index) or in pHi were observed between BD and control groups. These data suggest that early heart injury occurring during BD does not seem to be an ischemic phenomenon.     

Brain death-related energetic failure of the donor heart becomes apparent only during storage and reperfusion: an ex vivo phosphorus-31 magnetic resonance spectroscopy study on the feline heart.

BACKGROUND AND OBJECTIVE: Recently, we have shown, by using localized in vivo phosphorus-31 magnetic resonance spectroscopy (31P MRS) of the anterior left ventricular wall, that brain death (BD) is not associated with reduced myocardial energy status. In this study, we applied ex vivo 31P MRS of the entire heart to study the effects of BD on the energy status of the feline donor heart following explantation. METHODS: We used cats (6 BD and 6 controls [C]) in a 26-hour protocol. After 2 hours of preparation, we induced BD by filling an intracranial balloon at t = 0 hour. At t = 6 hours, the hearts were arrested with St. Thomas' Hospital cardioplegic solution, explanted, and stored in the same solution at 4 degrees C in a 4.7 Tesla magnet for 17 hours. Subsequently, the hearts were reperfused in the Langendorff mode at 38 degrees C for 1 hour. The first 5-minute 31P MRS spectrum was obtained 1 hour after crossclamping the aorta; we obtained subsequent spectra every hour during storage and every 5 minutes during reperfusion. At the end, the hearts were dried and weighed. Phosphocreatine (PCr), gamma-adenosine triphosphate (gamma-ATP), inorganic phosphate (Pi), and phosphomonoesters (PME), were expressed per g dry heart weight. The intracellular pH (pH(i)) and the PCr/ATP ratio were calculated. RESULTS: During storage, we identified a significant but similar decrease of pH(i), PCr/ATP ratio, and PCr in both groups. During reperfusion, pH(i) and PCr/ATP ratio recovered similarly in both groups, whereas the recovery of PCr in the BD group was significantly lower (p < 0.05). The Pi and PME increased in both groups during storage but to a lesser extent in the BD group (p < 0.05). This difference disappeared during reperfusion. The gamma-ATP was already significantly lower in the BD group at the onset of storage, and this remained so throughout storage and reperfusion (p < 0.05 vs C). Contractile capacity was lost in all hearts, except for 1 heart in the BD group. CONCLUSION: Brain death-related failure of the energetic integrity of the feline donor heart becomes apparent only when using 31P MRS during ischemic preservation and subsequent reperfusion.     

Usefulness of 31P-MRS as a method of evaluating the viability of preserved and transplanted rat liver

We used phosphorus-31 magnetic resonance spectroscopy (³¹P-MRS) to evaluate the viability of transplanted rat liver. Wistar rats were used as donors and recipients. The donor livers were preserved in saline (group 1), Euro-Collins solution (group 2), or in University of Wisconsin (UW) solution (group 3) for 3 and 6 h in groups 1, 2 and 3 and for 9 h in groups 2 and 3. Thereafter the livers were orthotopically transplanted. ³¹P-MRS spectra were measured after portal reperfusion. Finally, all the recipients were divided into survivors and non-survivors. Survival rates were better in group 3 than in groups 1 and 2. In the 9-h-preserved livers, the livers in group 3 showed a significantly higher β-ATP/Pi ratio than those in group 2. Comparing survivors and non-survivors in the 6-h-preserved livers in group 2, survivors' livers showed significantly higher (3-ATP/Pi ratio than those of non-survivors. We concluded that ³¹P-MRS is a useful method for assessing viability of rat liver grafts.