Endovascular model of rabbit hindlimb ischemia: a platform to evaluate therapeutic angiogenesis

PURPOSE: Current animal hindlimb ischemia models involve surgical ligation of the femoral artery and delivery of therapeutic angiogenic agents into the adductor compartment. The authors hypothesize that an endovascular model of hindlimb ischemia would be a more appropriate platform, closely resembling atherosclerosis by occluding the vessel from within, causing less inflammation, wound healing and subsequent collateralization. MATERIALS AND METHODS: The left superficial femoral artery in 17 rabbits was occluded by endovascular coil embolization (n=9) or surgical ligation (n=8). Animals (n=3; in each group) were sacrificed on day 3 to determine the arteriolar luminal area, number of arterioles, microsphere determined perfusion, and degree of inflammation. On day 28, the remaining animals underwent calf blood pressure measurements and angiography to determine the number of collaterals and diameter of vessels supplying the hindlimb. RESULTS: Immediate postprocedure (day 0) and presacrifice (day 3 or 28) occlusion rates were 89% (eight of nine rabbits) and 100% for the endovascular model; 100% and 100% for the surgical model, respectively. Hindlimb paralysis and muscle atrophy was found in one surgical animal. On day 3, there was an increase in hindlimb perfusion (surgery, 0.04+/-0.01; endovascular, 0.02+/-0.01; P=.02), an increase in arteriolar luminal area (surgery, 481 microm+/-240; endovascular, 345 microm+/-151; P=.04), and a trend toward more inflammation (surgery, 5.5+/-3.8; endovascular, 2.5+/-3.0; P=.08) in the surgical group. There was no difference in number of vessels between both groups. On day 28 there was no difference in the calf blood pressure ratios or in the number of collaterals. However, there was enlargement of the distal profunda femoris artery, the vessel closest to the surgical incision, in the surgical group (L/R ratio: immediate post-occlusion, 1.06+/-0.11; day 28, 1.27+/-0.08; P=.02). CONCLUSION: The endovascular model was efficacious in providing occlusion of the superficial femoral artery, and induced less of an arteriogenic response compared with the surgical model. The authors believe that this endovascular model is a superior platform for studying therapeutic angiogenic agents.     

Radiolabeled RGD uptake and alphav integrin expression is enhanced in ischemic murine hindlimbs.

Radiolabeled RGD peptides that target alpha(v)beta3 integrin are promising tracers for imaging tumor angiogenesis. Integrins and angiogenesis also play important roles in healing of ischemic lesions. Thus, we investigated the biodistribution of radiolabeled RGD and expression of alpha(v) integrin in a mouse model of hindlimb ischemia. METHODS: 125I-3-Iodo-D-Tyr4-cyclo(-Arg-Gly-Asp-D-Tyr-Val-) (125I-c(RGD(I)yV)) was synthesized and tested for endothelial binding. Hindlimb ischemia was induced in ICR mice through femoral artery ablation, and perfusion was measured with laser Doppler blood flowmetry. 125I-c(RGD(I)yV) biodistribution was evaluated in control animals (n = 7) and ischemic models on day 3, 8, or 14 (n = 6 each). Control experiments were performed using a radiolabeled peptide with a scrambled amino acid sequence (125I-GfVGV). Microsections of hindlimb tissue were immunostained for alpha(v) integrin expression and stained with alkaline phosphatase to localize vascular endothelial cells. RESULTS: 125I-c(RGD(I)yV) retained specific binding to human umbilical vein endothelial cells. Perfusion in ischemic hindlimbs immediately fell to 10% +/- 4% of contralateral levels and gradually recovered to 22% +/- 11% and 64% +/- 9% on days 8 and 14, respectively. 125I-c(RGD(I)yV) uptake in ischemic muscles significantly increased from a control level of 0.16 +/- 0.05 %ID/g (percentage injected dose per gram of tissue) to 0.85 +/- 0.76 %ID/g at day 3, 0.43 +/- 0.23 %ID/g at day 8, and 0.43 +/- 0.28 %ID/g at day 14 (all P < 0.05). Ischemic muscle-to-lung count ratios had a virtually identical trend: 0.42 +/- 0.25 for controls, 2.34 +/- 1.70 at day 3 (P < 0.02), 1.46 +/- 0.52 at day 8 (P < 0.001), and 1.39 +/- 0.94 at day 14 (P < 0.02). In contrast, uptake of the control peptide in ischemic hindlimbs was not different from that of controls. Immunohistochemistry revealed substantially increased alpha(v) integrin staining in ischemic hindlimb tissue. CONCLUSION: Radioiodine RGD uptake is significantly enhanced in ischemic hindlimbs of a mouse model, and is accompanied by an increase in alpha(v) integrin expression. Further investigation is thus warranted to illuminate the potential role of radiolabeled RGD for noninvasive monitoring of peripheral ischemic lesions.     

A New Ischemic Model Using a Radiofrequency Wire Electrode in a Rabbit Hindlimb

The purpose of this study was to establish an ischemic rabbit hindlimb model using a radiofrequency (RF) wire electrode. We inserted a polytetrafluoroethylene-coated wire with a 2-cm exposed tip into the left superficial femoral artery of seven New Zealand white rabbits and performed RF ablation (RFA) while pulling the wire back. We assessed the clinical findings, angiography, computed tomography perfusion, and permeability surface until 6 weeks after RFA. The angiography demonstrated complete obstruction from the proximal external iliac artery to the distal superficial femoral artery and showed a gradual increment in the angiogenic score, which represents the degree of angiogenesis (r = 0.86, p < 0.0001). The left-to-right ratios of the computed tomography perfusion and permeability surface were significantly reduced after 4 days (p < 0.05), and then they gradually increased with time. We conclude that endovascular RFA using an RF wire electrode is a reproducible and measurable way to create an ischemic rabbit hindlimb model.     

犬下肢缺血后pUDKH基因治疗对股神经的保护作用

目的：观察pUDKH基因治疗犬下肢缺血后对其神经组织病理学的影响。方法：杂种犬静脉注射戊巴比妥钠麻醉后,结扎左侧股动脉起始部,建立下肢缺血模型。股动脉结扎后即刻,大腿肌肉局部注射pUDK（对照组）或不同剂量pUDKH（pUDKH处理组,0．15、0．3、0．6mg／kg）。术后3个月,取股神经及其周围肌肉组织行病理学检查。结果：对照组股神经及其细小分支均发生显著的退行变,累及轴突、髓鞘和施旺氏细胞核,而经pUDKH处理组各级神经病变不明显,有的甚至与正常犬无差别。结论：pUDKH的局部注射可减轻或阻遏犬下肢缺血后股神经的组织损伤,具有一定的神经组织保护作用。     

256层CT灌注成像评价兔失神经支配缺血后肢急性期毛细血管床血容量的动态变化

目的 探讨兔失神经支配缺血后肢急性期毛细血管床血容量(blood volume,BV)动态变化及256层CT灌注成像的评估价值.方法 健康成年大耳白兔40只,采用数字表法随机分为联合造模组、缺血组、失神经组和假手术组,每组10只.分别制作右后肢股动脉切除联合股神经离断、单纯股动脉切除、单纯股神经离断及单纯分离股动脉假手术模型.于术后第1、7、14、21和28天行256层CT灌注扫描,计算各组右后肢与左后肢肌肉组织的BV比值(rBV).于术后第14和28天各组采用数字表法随机处死动物4只,分别切取双侧内收肌进行免疫组织化学染色,计算右后肢与左后肢内收肌毛细血管密度比值(rMVD).各组不同时点rBV采用2×2析因设计方差分析,采用Pearson相关分析rBV与内收肌rMVD的相关性.结果 术后第1天,联合造模组、缺血组、失神经组和假手术组rBV分别为0.31 ±0.15(6只)、0.29±0.12(6只)、0.98±0.08(6只)、0.98±0.07(6只),术后第7天分别为1.69±0.45(5只)、1.63±0.43(6只)、0.99±0.07(6只)、1.00±0.08(6只),术后第14天分别为1.58±0.18(5只)、1.49±0.25(6只)、0.94±0.08(6只)、1.01±0.05(6只),术后第21天分别为1.42±0.41(4只)、1.43 ±0.31(4只)、0.94 ±0.05(5只)、1.02±0.05(5只),术后第28天分别为1.00±0.25(4只)、0.99±0.08(4只)、0.92±0.09(5只)、1.02±0.13(5只),除术后第28天外(F(A)=0.214,P>0.05),缺血因素对灌注参数rBV的影响具有主效应(F(A)值分别为274.268、30.044、65.787、18.886,P值均<0.01),而单纯失神经因素在各时点均未表现出主效应,两因素在各时点均无交互作用.各组rMVD支持上述改变;rBV与rMVD的相关系数为r=0.862(P<0.01).结论 兔后肢缺血后急性期毛细血管床血流灌注表现呈动态变化,合并失神经支配时,并未影响此过程.256层CT可以无侵袭性、半定量评估兔失神经缺血后肢急性期毛细血管床的动态变化.     

Quantitation of the critically ischemic zone at risk during acute coronary occlusion using PET

Critical myocardial ischemia has been defined experimentally during acute coronary occlusion as flow reduction of 50% or more since cellular ATP depletion begins to occur beyond this flow reduction threshold, placing tissue at risk of cellular injury. To test the hypothesis that critically ischemic fractional left ventricular mass can be measured noninvasively with PET, nine dogs were imaged in a multi-slice positron camera using the perfusion tracer 13N-ammonia, while radiolabeled microspheres were injected into the left atrium during acute coronary occlusion. Images were processed using a 50% threshold and the size of the resulting perfusion defect was expressed as a fraction of total left ventricular image volume. The critically ischemic left ventricular fraction determined in vitro from the microsphere perfusion data, ranged from 5% to 30% of the total left ventricular weight and correlated closely with that determined noninvasively by PET with r = 0.94 (y = 1.05X - 2.0%). We conclude that the fraction of left ventricular myocardium rendered critically ischemic during acute coronary occlusion can be measured accurately and noninvasively in vivo using perfusion imaging with positron emission tomography.     

Quantification of MRI measured myocardial perfusion reserve in healthy humans: a comparison with positron emission tomography

PURPOSE: To validate a noninvasive quantitative MRI technique, the K(i) perfusion method, for myocardial perfusion in humans using (13)N-ammonia PET as a reference method. MATERIALS AND METHODS: Ten healthy males (64 +/- 8 years) were examined with combined PET and MRI perfusion imaging at rest and during stress induced by dipyridamole in order to determine the myocardial perfusion reserve. Myocardial and blood time concentration curves obtained by Gd-DTPA-enhanced MRI and (13)N-ammonia PET were fitted by a two-compartment perfusion model. RESULTS: Mean perfusion values (+/-SD) derived from the MRI method at rest and at hyperemia were 80 +/- 20 and 183 +/- 56 mL/min/100 g, respectively. The same data for PET were 71 +/- 16 and 203 +/- 67 mL/min/100 g. A linear relationship was observed between MRI and PET-derived myocardial perfusion reserve for regional and global data. Linear regression for the global absolute perfusion reserve gave a correlation coefficient of 0.96 (P < 0.004, y=0.83x-6.9). A good agreement between the two methods to determine low or high perfusion reserves was found. CONCLUSION: Our data provide validation of the perfusion marker K(i) derived by the MRI method as a quantitative marker for myocardial perfusion in healthy humans.     

Partial rescue of the perfusion deficit area by thrombolysis

PURPOSE: To investigate the evolution of the perfusion deficit area following systemic thrombolysis with recombinant tissue plasminogen activator (rtPA) in a clinical study on acute cerebral ischemia. MATERIALS AND METHODS: We performed volumetric measurements of the acute ischemic lesions in MR images of perfusion (TTP, MTT, and rCBV) and in diffusion-weighted (DW) images, as well as the manifest stroke lesions in T2-weighted MR images on day 8. We compared the data of 29 patients who were subjected to systemic thrombolysis with those of 18 patients who were not eligible for thrombolysis. RESULTS: In the treated patients there were prominent MTT/DWI and TTP/DWI mismatches (P < 0.0006). The acute TTP volumes were smaller than the acute MTT volumes, but as large as the T2 lesions on day 8. The MTT/T2 lesion volume reduction was significant (P < 0.03) in patients who received the GPIIb/IIIa receptor antagonist tirofiban (N = 13) in addition to the low-dose rtPA. This corresponded to a greater neurological improvement compared to patients who received rtPA alone (P < 0.05). In contrast, in the nontreated patients the initial MTT and TTP lesion volumes were of similar magnitude and predicted the T2 lesions on day 8. In the treated and nontreated patients the TTP lesion signified the viability threshold of acute ischemia, which corresponded to a rCBF of 25 +/- 11 mL/100 g/min. CONCLUSION: The perfusion deficit area comprises the ischemic core that is destined to undergo necrosis, and an ischemic rim that is salvageable by systemic thrombolysis.     

Gd(ABE-DTTA)-enhanced cardiac MRI for the diagnosis of ischemic events in the heart

PURPOSE: To demonstrate that contrast-enhanced MRI (ceMRI) with the aid of Gd(ABE-DTTA) is able to detect ischemic events in the heart in a canine ischemia/reperfusion (30/40 minutes) model. MATERIALS AND METHODS: ECG-gated, T1-weighted MR image sets (four to five slices each) with three-minute time resolution were collected in transiently LAD-occluded dogs. Following the acquisition of control image sets, ischemia was started by occluding the LAD. Either Gd(ABE-DTTA) (N = 6) or Gd(DTPA) (N = 6) was injected, and imaging was continued for 30 minutes of ischemia and 40 minutes of reperfusion. The contrast agent (CA)-induced MRI signal intensity enhancement (SIE) and contrast were monitored. Microspheres measured myocardial perfusion (MP) to verify areas of ischemia and reperfusion. RESULTS: SIEs of 86% +/- 3% and 97% +/- 3% in nonischemic, and 25% +/- 5% and 29% +/- 8% in ischemic regions were found within three minutes of onset of ischemia with Gd(ABE-DTTA) and Gd(DTPA), respectively. For the rest of the 30 minutes of ischemia, with Gd(ABE-DTTA) SIE of 60% +/- 3% and 25% +/- 5% persisted in the nonischemic and ischemic regions, respectively. With Gd(DTPA), however, SIE in the nonischemic areas decreased rapidly after the first three minutes of ischemia, while SIE in the ischemic areas increased, abolishing contrast. Thus, there was a persistent contrast with Gd(ABE-DTTA) and a short-lived contrast with Gd(DTPA) during ischemia. Furthermore, with Gd(ABE-DTTA) some contrast was still visible in the early reperfusion period. CONCLUSION: Gd(ABE-DTTA) in an ischemia/reperfusion model induces a persistent MRI contrast between regions of normal and ischemic myocardium, and verifies reperfusion. Therefore, it can be used to detect myocardial ischemic events.     

The effect of ischemic injury on the cardiac transport of Tc-99m N-NOET in the isolated rabbit heart

BACKGROUND: Bis (N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium-99m (V) (TcN-NOET) is a neutral lipophilic myocardial perfusion agent. The effect of ischemic injury on the cardiac transport of TcN-NOET and thallium-201 was determined in isolated rabbit hearts. METHODS AND RESULTS: The multiple indicator dilution method was used to determine the maximum (Emax) and net extraction (Enet, at 5 minutes) of TcN-NOET and TI-201 at control and after 10 minutes (n = 4) or 45 minutes (n = 4) of no-flow ischemia. After 10 minutes of ischemia the mean Emax for T1-201 was unchanged, 0.86 +/- 0.03 vs 0.85 +/- 0.02, whereas TI-201 Enet showed a small decrease from 0.46 +/- 0.03 to 0.40 +/- 0.03, P < .001. Forty-five minutes of ischemia mildly reduced Emax for TI-201 (0.87 +/- 0.04 to 0.74 +/- 0.04, P < .001) and severely reduced Enet (0.46 +/-0.03 vs 0.16 +/- 0.04, P < .001). Neither Emax nor Enet for TcN-NOET was significantly affected by 10 minutes of ischemia (0.54 +/- 0.04 vs 0.58 +/- 0.03 and 0.24 +/- 0.04 vs 0.26 +/- 0.04, respectively). However, severe ischemic injury caused significant reductions versus control in both Emax (0.59 +/- 0.06 vs 0.42 +/- 0.05, P < .001) and Enet (0.27 +/- 0.03 vs 0.18 +/- 0.05, P < .01). CONCLUSIONS: TcN-NOET is a new myocardial perfusion agent with moderate myocardial extraction. Although less sensitive than TI-201 to mild ischemic injury, TcN-NOET extraction and retention are decreased by severe ischemic injury, making uptake of TcN-NOET a possible marker of myocardial viability.     

Rat Model of Hindlimb Ischemia Induced via Embolization with Polyvinyl Alcohol and N-Butyl Cyanoacrylate

Objective

To investigate the feasibility of a rat model on hindlimb ischemia induced by embolization from the administration of polyvinyl alcohol (PVA) particles or N-butyl cyanoacrylate (NBCA).

Materials and Methods

Unilateral hindlimb ischemia was induced by embolization with NBCA (n = 4), PVA (n = 4) or surgical excision (n = 4) in a total of 12 Sprague-Dawley rats. On days 0, 7 and 14, the time-of-flight magnetic resonance angiography (TOF-MRA) and enhanced MRI were obtained as scheduled by using a 3T-MR scanner. The clinical ischemic index, volume change and degree of muscle necrosis observed on the enhanced MRI in the ischemic hindlimb were being compared among three groups using the analysis of variance. Vascular patency on TOF-MRA was evaluated and correlated with angiographic findings when using an inter-rater agreement test.

Results

There was a technical success rate of 100% for both the embolization and surgery groups. The clinical ischemic index did not significantly differ. On day 7, the ratios of the muscular infarctions were 0.436, 0.173 and 0 at thigh levels and 0.503, 0.337 and 0 at calf levels for the NBCA, PVA and surgery groups, respectively. In addition, the embolization group presented increased volume and then decreased volume on days 7 and 14, respectively. The surgery group presented a gradual volume decrease. Good correlation was shown between the TOF-MRA and angiographic findings (kappa value of 0.795).

Conclusion

The examined hindlimb ischemia model using embolization with NBCA and PVA particles in rats is a feasible model for further research, and muscle necrosis was evident as compared with the surgical model.     

Swim training improves myocardial resistance to ischemia in rats

As the relationship between training and ischemic heart disease is not yet unraveled, we test the hypothesis that, in a model free from environmental, behavioural, and neuro-hormonal factors, endurance training improves myocardial resistance to ischemia. As carbohydrate metabolism is relevant for myocardial resistance to ischemia, we also test whether hyperglycemia blunts the protective effect of training. Eight-week old rats were randomly assigned to four groups (n = 6-8): sedentary or trained (3-week swim program, up to 2 h/day), and normal or high-carbohydrate diet (50 g/l sucrose in drinking water). Excised hearts were perfused isovolumically (flow = 15 ml/min) with Krebs-Henseleit (2 mM free Ca++, 11 mM glucose, pH 7.38 +/- 0.02, PO2 = 670 +/- 6 mmHg, PCO2 = 43 +/- 1 mmHg, mean +/- SE), exposed to 60 min low-flow (1.5 ml/min) ischemia, and then reperfused for 30 min (15 ml/min). In normally fed rats training increased the stroke volume index (97.5 +/- 13.0 vs. 72.6 +/- 6.2 microl, P = 0.05), depressed diastolic contracture (+2.3 +/- 2.0 vs. +24.2 +/- 6.7 mmHg, P = 0.02), improved the recovery of developed pressure x heart rate (33.8 +/- 2.3 vs. 24.1 +/- 3.3 mmHg/min/1000, P = 0.05), and decreased arrhythmias (P = 0.05). In high-carbohydrate-fed rats training induced myocardial hypertrophy (1.95 +/- 0.08 vs. 1.67 +/- 0.03 g, P = 0.02) and decreased arrhythmias but did not affect stroke volume, developed pressure x heart rate, and diastolic contracture. Thus endurance training improves myocardial resistance to ischemia but a high-carbohydrate diet partially blunts this protection. The occurrence of an inducible alteration able to modulate myocardial tolerance to ischemia may give clues to extend our knowledge of ischemic preconditioning.     

Diffusion MRI in ischemic epiphysis of the femoral head: an experimental study

PURPOSE: To evaluate whether line-scan diffusion-weighted imaging (LSDWI) can provide temporal information of epiphyseal ischemia. MATERIALS AND METHODS: Ischemia was induced by ligation of arteries of the unilateral femoral head in piglets (N = 25). LSDWI was performed at several time points after ligation. A comparison of apparent diffusion coefficients (ADCs) was made between ischemic and control sides. The difference in percentage change of ADC in the ischemic hips between two neighboring time points was evaluated. A histological study was made after MR scanning. RESULTS: Three hours after ligation, ADCs were significantly lower in the ischemic hips than in the contralateral (control) hips. At 72 hours after surgery, ADCs in the ischemic hips were significantly higher than in the control hips and continued to rise up until the sixth week after operation. Histological study revealed necrosis of chondrocytes and osteocytes and abnormal thickening of the epiphyseal cartilage in the ischemic femoral head. CONCLUSION: The ADCs may be used as a marker of ischemia and necrosis in the femoral head; changes in the ADCs after the acute ischemia may reflect the evolution of ischemia and subsequent necrosis. LSDWI can be used for the evaluation of the duration and extent of ischemic injury in the epiphysis.     

Effect of intramyocardial injection of autologous bone marrow-derived mononuclear cells on perfusion, function, and viability in patients with drug-refractory chronic ischemia.

Intramyocardial injection of bone marrow cells has been proposed as a new therapeutic option for patients with chronic ischemic heart disease. We investigated whether autologous bone marrow-derived mononuclear cell injection into the myocardium of patients with drug-refractory ischemia reduces anginal symptoms, improves left ventricular (LV) function, increases myocardial perfusion, and alters the extent of scar tissue. METHODS: In 25 patients (mean age +/- SD, 64 +/- 10 y; 21 male) with drug-refractory angina pectoris (Canadian Cardiovascular Society [CCS] class III-IV), despite optimized medical therapy and without options for conventional revascularization, bone marrow was aspirated from the iliac crest. Mononuclear cell injections were targeted at myocardial regions with stress-induced ischemia on gated (99m)Tc-tetrofosmin SPECT. Anginal symptoms were reassessed at 3- and 6-mo follow-up. At baseline and 3-mo follow-up, gated (99m)Tc-tetrofosmin SPECT and (18)F-FDG SPECT were performed to assess LV function, LV volumes, myocardial perfusion (stress and rest, 17-segment model), and extent of scar tissue. RESULTS: Mean CCS score improved from 3.4 +/- 0.6 at baseline to 2.3 +/- 0.6 at 3 mo (P < 0.01) and remained unchanged at 6 mo (2.3 +/- 0.6; P < 0.01 vs. baseline and P = not significant [NS] vs. 3 mo). Gated (99m)Tc-tetrofosmin SPECT demonstrated an increased LV ejection fraction (from 47.6% +/- 13.5% to 54.1% +/- 16.9%; P < 0.01) and a reduced LV end-systolic volume (from 81 +/- 68 mL to 75 +/- 70 mL; P < 0.01). Segmental regional wall thickening increased from 34% +/- 12% at baseline to 39% +/- 17% at 3-mo follow-up (P = 0.01). The number of segments with stress-inducible ischemia per patient decreased from 4.6 +/- 3.2 to 2.0 +/- 2.6 (P < 0.01). Both segmental stress and segmental rest score improved, although the improvement in stress score was more pronounced (decrease in segmental stress score 0.22 +/- 0.20 vs. decrease in segmental rest score 0.04 +/- 0.06; P < 0.01). Myocardial perfusion improved in 53% of the injected segments and in 13% of the noninjected segments (P < 0.01). The percentage of myocardial segments with some extent of scar remained unchanged at 3-mo follow-up (13% vs. 12%; P = NS). CONCLUSION: Autologous bone marrow-derived mononuclear cell injection in patients with drug-refractory angina and chronic ischemia improves anginal symptoms, increases LV function, and predominantly enhances myocardial stress perfusion in injected segments, whereas the extent of myocardial scar tissue remains unchanged.     

经皮腔内球囊扩张联合动脉内灌注药物治疗慢性下肢缺血

目的临床观察球囊扩张联合动脉内灌注药物治疗慢性下肢缺血的近期疗效。方法慢性下肢缺血患者21例,采用经股或腋动脉入路,先用球囊扩张闭塞段血管,然后经导管向动脉内灌注尿激酶、前列腺素E1、银杏叶注射液。胫腓动脉闭塞的部分患者保留血管鞘,经鞘灌注上述药物,每日1次,共5～7 d。术后观察患肢缺血症状、皮肤溃疡和趾端坏疽的改善情况。结果21例中20例成功实现经皮经腔球囊扩张和动脉内灌注药物治疗,技术成功率95.2%。无严重并发症。其中5例患者术后保留血管鞘,灌注药物5～7 d后复查造影,显示经球囊扩张后血管腔保持通畅。术后20例患者均出现诸如患肢皮温升高、间歇性跛行消失、静息痛减轻或消失等临床症状改善情况;随访2～7个月,4例皮肤溃疡愈合,2例坏死足趾脱落,创面愈合,已坏疽的足趾均变干燥,坏死范围停止扩大,未出现需截肢现象。结论经皮腔内球囊扩张联合动脉内灌注尿激酶、前列腺素E1、银杏叶注射液治疗慢性下肢缺血安全有效,能够改善肢体缺血症状,促进溃疡愈合,阻止病变发展;保留血管鞘连续灌注药物有助于保持扩张后的血管通畅。     

Effect of Arterial Deprivation on Growing Femoral Epiphysis: Quantitative Magnetic Resonance Imaging Using a Piglet Model

Objective

To investigate the usefulness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion MRI for the evaluation of femoral head ischemia.

Materials and Methods

Unilateral femoral head ischemia was induced by selective embolization of the medial circumflex femoral artery in 10 piglets. All MRIs were performed immediately (1 hour) and after embolization (1, 2, and 4 weeks). Apparent diffusion coefficients (ADCs) were calculated for the femoral head. The estimated pharmacokinetic parameters (Kep and Ve from two-compartment model) and semi-quantitative parameters including peak enhancement, time-to-peak (TTP), and contrast washout were evaluated.

Results

The epiphyseal ADC values of the ischemic hip decreased immediately (1 hour) after embolization. However, they increased rapidly at 1 week after embolization and remained elevated until 4 weeks after embolization. Perfusion MRI of ischemic hips showed decreased epiphyseal perfusion with decreased Kep immediately after embolization. Signal intensity-time curves showed delayed TTP with limited contrast washout immediately post-embolization. At 1-2 weeks after embolization, spontaneous reperfusion was observed in ischemic epiphyses. The change of ADC (p = 0.043) and Kep (p = 0.043) were significantly different between immediate (1 hour) after embolization and 1 week post-embolization.

Conclusion

Diffusion MRI and pharmacokinetic model obtained from the DCE-MRI are useful in depicting early changes of perfusion and tissue damage using the model of femoral head ischemia in skeletally immature piglets.     

Evaluation of tissue perfusion in a rat model of hind-limb muscle ischemia using dynamic contrast-enhanced magnetic resonance imaging

PURPOSE: To evaluate the feasibility of using dynamic contrast-enhanced magnetic resonance imaging (MRI) for assessment of muscle perfusion in a rat model of hind-limb ischemia. MATERIALS AND METHODS: The acute alteration and chronic recovery in muscle perfusion and perfusion reserve after femoral artery ligation were quantified using the maximum Gd-DTPA uptake rate obtained by a T(1)-weighted gradient-recalled echo sequence. Radionuclide-labeled microsphere blood flow measurements were performed for comparison with the MR perfusion measurement on a separate set of animals. RESULTS: After femoral artery ligation, a significant reduction in resting muscle perfusion was only observed at 1 hour post-ligation during the 28-day follow-up period. Muscle perfusion reserve was severely diminished following the ligation. Despite significant recovery over time, perfusion reserve to the ligated limb reached only 63% of the perfusion capacity in the unaffected limb by 42 days post ligation. A strong correlation (r = 0.86) between MR perfusion and microsphere blood flow measurements was observed for evaluation of relative changes in muscle perfusion. CONCLUSION: Dynamic contrast-enhanced MRI with Gd-DTPA is useful to assess time-dependent changes in muscle perfusion and perfusion reserve in this hind-limb ischemia model.     

Myocardial kinetics of fluorine-18 misonidazole: a marker of hypoxic myocardium

Fluoromisonidazole, a member of a class of compounds referred to as "hypoxic sensitizers," accumulates in hypoxic, viable tumor cells. We hypothesized that it might therefore accumulate also in ischemic, but non-necrotic myocardium potentially salvageable by interventional therapy. To evaluate the myocardial kinetics of [18F]fluoromisonidazole (FM), 20 isolated perfused rabbit hearts were used to characterize the uptake and binding of tracer under control conditions (n = 6), or with ischemia (flow 10% of control, n = 5), hypoxia without low flow (control flow rates with hypoxic medium, n = 5), or with reperfusion (n = 4). Myocardial retention of tracer detected externally with gamma scintillation probes after 20 min of constant [18F]FM infusion followed by 20 min of washout with nonradioactive buffer was 41 +/- 7% and 46 +/- 8% of peak activity in hearts subjected to ischemia or hypoxia, respectively, and significantly higher than in hearts subjected to either control perfusion or to ischemia followed by reperfusion (18 +/- 6 and 16 +/- 5% of peak activity, respectively, p less than 0.01). The biologic half-time of retained tracer was 40 hr in all hearts indicating essentially irreversible binding. Based on these findings, we measured uptake of [18F]FM using positron emission tomography in five dogs subjected to acute coronary occlusion. Five to thirteen millicuries of tracer were injected within 3 hr of occlusion. Within 30 min after administration of tracer, 18F accumulation in ischemic myocardium was greater than that observed in normal myocardium. The results indicate that [18F]FM accumulates in ischemic myocardium in relation to diminished tissue oxygen content and not simply because of diminished flow. Thus, this class of compounds may be potentially useful to help identify hypoxic myocardium.     

Femoral, popliteal, and tibial arteries: percutaneous transluminal angioplasty

We attempted percutaneous transluminal angioplasty in 70 patients with obliterative atherosclerosis of the femoral, popliteal, and tibial arteries. Patients with limb threatening ischemia (rest pain, nonhealing ulcer, or gangrene) or lifestyle-limiting claudication were acceptable candidates. Stenoses less than 4 cm long or occlusions less than 10 cm long and less than 2 years old were considered favorable for angioplasty, but less desirable lesions were accepted for limb salvage. Patients with increased surgical risk, inadequate saphenous veins, poor runoff, or in whom temporizing was necessary or desirable, were offered angioplasty for revascularization as an alternative to surgical reconstruction. Technical success was achieved in 62 (88%) of 70 patients with five early failures for an overall initial success rate of 57 (81%) of 70. Complete relief of clinical symptoms was achieved in 53 patients (92%) and 54 had improved lower limb perfusion when measured noninvasively. Patency rate at 1 year was 89% +/- 5% and in 2 years 84% +/- 6% by life table analysis. Major complications occurred in eight (11.4%) of 70 procedures. We conclude that angioplasty of femoral, popliteal, and tibial vessels is an effective and safe alternative to traditional surgical bypass grafting for revascularization of the ischemic lower extremity. Early patency rates are comparable to saphenous vein grafts and considerably better than prosthetic reconstruction.     

兔骨骼肌缺血模型扩散张量成像研究

目的 初步探讨MR DTI在定量评估兔后肢缺血模型骨骼肌缺血中的应用价值.方法 对14只新西兰大白兔进行结扎并切除一侧后肢股动脉,成功建立兔后肢缺血模型共12只,分别于术后3 d(12只)、10 d(10只)、28 d(7只)、56 d(5只)对两侧小腿行DTI检查,并在每个时间点留取病理组织.观察两侧肌组织在DWI、本征向量(λ)_1图、λ_2图、λ_3图、ADC图和部分各向异性(FA)图上的表现,并测量后组肌群的λ_1、λ_2、λ_3、ADC值和FA值,采用配对t检验比较两侧小腿的差异,并与病理组织对照.结果 术后3 d手术侧ADC值升高(ADC_(术侧)=1.72±0.16,ADC_(健侧)=1.53±0.16,t=6.48,P<0.01),其中λ_2和λ_3 2个特征矢量值升高明显(入_(2术侧)=1.70±0.15,入_(2健侧)=1.51±0.06,t=10.87,P<0.01;入_(3术侧)=1.17±0.12,λ_(3健侧)=0.88±0.12,t=6.67,P<0.01),FA值急骤下降(FA_(术侧)=0.24±0.04,FA_(健侧)=0.39±0.03,t=-10.61,P<0.01);术后10 d缺血骨骼肌ADC值及λ_2、λ_3值下降,但两侧仍有差异(ADC_(术侧)=1.65±0.16,ADC_(健侧)=1.50±0.12,t=6.42,P<0.01;λ_(2术侧)=1.62±0.32,λ_(2健侧)=1.48±0.31,t=5.09,P<0.01);λ_(3术侧)=1.11±0.13,λ_(3健侧)=0.85±0.09,t=6.26,P<0.01),λ_1值恢复正常(λ_(1术侧)=2.20±0.21,λ_(1健侧)=2.18±0.20,t=0.87,P=0.40);术后28 d ADC及λ_3值恢复正常(ADC_(术侧)=1.51±0.16,ADC_(健侧)=1.55±0.14,t=-1.35,P=0.23;λ_(3术侧)=0.95±0.10,λ_(3健侧)=0.92±0.06,t=1.70,P=0.14),但λ_2及FA值仍有差异(λ_(2术侧)=1.45±0.23,λ_(2健侧)=1.52±0.95,t=-3.56,P=0.012;FA_(术侧)=0.35±0.02,FA_(健侧)=0.40±0.03,t=-3.83,P<0.01);术后56 d各观测指标均恢复正常(ADC_(术侧)=1.57±0.18,ADC_(健侧)=1.58±0.23,t=-0.71,P=0.52;λ_(1术侧)=2.18±0.18;λ_(1健侧)=2.24±0.14;t=-0.22,P=0.10;λ_(2术侧)=1.64±0.13,λ_(2健侧)=1.59±0.15,t=0.89,P=0.42;λ_(3术侧)=0.89±0.1,λ_(3健侧)=0.91±0.07,t=-1.64,P=0.18;FA_(术侧)=0.39±0.03,FA_(健侧)=0.41±0.02,t=-0.83,P=0.47).组织学观察,在缺血后3、10 d见肌肉损害,28 d后缺血肌肉逐渐恢复,56 d恢复正常形态.结论 DTI可以定量且较准确地评估动物后肢缺血模型随时间推移发生的肌肉组织损伤及修复过程.