Myocardial and vascular lesions in the LA/N-corpulent rat

The LA/N-corpulent (LA/N-cp) rat is a normotensive strain derived from Koltesky's original mutant strain of the spontaneously hypertensive rat (SHR). When homozygous for the cp gene (cp/cp), the rats are hyperphagous, hyperlipidemic, hyperinsulinemic, and obese. The rats have been shown, by scanning electron microscope observation of the arterial system, to develop arterial lesions and occasional occlusive thrombi. These are significantly more frequent in the corpulent rats. Histological examination of the heart has shown the presence of four distinguishable types of lesions: type A, muscle scar or cell dropout with pigment deposition and inflammatory cell accumulation; type B, necrosis of a small number of myocytes with reactive inflammatory cells; type C, nodule of chronic inflammatory cells; type D, muscle scar without chronic inflammatory cells. Complete transverse sections of three regions of the heart were examined from rats 3, 6, and 9 months of age. Rats that were homozygous normal (+/+) showed an absence of all types of cardiac lesions. Male corpulent rats showed frequent lesions of all types with the frequency rising consistently with age. Female corpulent rats showed a similar incidence of types C and D lesions to males, but no type B lesions were found. Type A lesions, the most common in corpulent males, were found at a greatly reduced relative frequency. In some instances, we have found occlusive thrombi in a coronary artery of corpulent rats. The disease process in these animals occurs with a normal low fat, virtually cholesterol-free diet and no experimental manipulation.     

Long-term results of chronic occlusion recanalization in patients with coronary heart disease

The study was undertaken to assess the long-term results of recanalization of chronically occluded coronary arteries, by applying drug-eluting stents to patients with coronary heart disease. The study enrolled 585 patients with one-vessel occlusive lesion of one of three great coronary arteries (TIMI 0; occlusion duration, > or = 3 months): 321 patients who underwent successful recanalization of chronic occlusion and further implantation of drug-eluting stents and 264 patients who received drug therapy (a control group). The short- and long-term results of recanalization were investigated. The follow-up averaged 1095 +/- 36 days; reexaminations were made after 1, 2, and 3 years. The direct success rate of recanalization of chronically occluded coronary arteries was 84.9% (321/378). The results of a 3-year follow-up showed the efficiency and expediency of endovascular recanalization of chronic occlusions: the invasively treated patients had the symptoms of angina pectoris and heart failure significantly less frequently, showed higher exercise tolerance and a less need for antianginal therapy, and had a better long-term prognosis.     

The nonspecific nature of fibrin thrombi in ischemic bowel disease.

Twenty cases of ischemic bowel disease were analysed to determine the frequency and significance of fibrin thrombi in this condition. Fibrin thrombi were present in all 10 patients with occlusive ischemic bowel disease and in 7 of the 10 patients with nonocclusive ischemic bowel disease. In addition, fibrin thrombi were noted in a wide variety of specific and nonspecific inflammatory bowel diseases and in acute appendicitis. We conclude that fibrin thrombi are a nonspecific feature of tissue necrosis and that their mere presence in the bowel should not be regarded as an expression of disseminated intravascular coagulation.     

Treatment of deep vein thrombosis with streptokinase.

From September 1962 to May 1972 145 patients with acute or subacute deep vein thrombosis confirmed by phlebography were treated with streptokinase. During the same period 42 patients considered unfit for thrombolytic therapy were treated with herapin and oral anticoagulants. The results, assessed by repeat phlebography, in 93 of the patients treated with streptokinase were compared with those in 42 patients treated with heparin. The age, sex, and severity of occlusion were roughly similar in both groups. Streptokinase treatment was successful in 42 per cent, partially successful in 25 per cent, and unsuccessful in 32 per cent of the 93 patients compared with none, 10 per cent, and 88 percent respectively in the 42 patients treated with heparin. Streptokinase was more effective when the thrombus was in proximal rather than calf veins. Thrombi of more than six days old were readily lysed. Plasma fibrinogen levels were below 0-8 g/1 (80 mg/100 ml) in nearly all patients successfully treated. The incidence of pulmonary embolism was no greater with streptokinase than with heparin treatment. Only prolonged follow-up would show whether thrombolytic treatment would be effective in preventing late complications of deep vein thrombosis such as chronic venous insufficiency.     

Cerebral Strokes Associated with Pregnancy and the Puerperium

Thirty-one cases of ischaemic cerebral stroke occurring in association with childbirth were fully investigated. The pathological basis of non-haemorrhagic carotid territory strokes in pregnant or puerperal women proved to be similar to that in non-pregnant women of the same age group. Over 70% were due to occlusive cerebral arterial disease or ischaemic lesions unrelated to thrombosis of the intracranial venous system. Comparisons are made with some other reported series in which only a minority of the patients were investigated by angiography, but in which intracranial venous occlusion was assumed to be the primary lesion. It seems likely that many of these patients may also have suffered arterial rather than venous lesions.     

New concepts in characterization of ischemically injured myocardium by MRI

New concepts regarding the assessment of ischemic myocardial injuries have been addressed in this Minireview using magnetic resonance imaging (MRI). MRI, with its different techniques, brings not only anatomic, but also physiologic, information on ischemic heart disease. It has the ability to measure identical parameters in preclinical and clinical studies. MRI techniques provide the ideal package for repeated and noninvasive assessment of myocardial anatomy, viability, perfusion, and function. MR contrast agents can be applied in a variety of ways to improve MRI sensitivity for detecting and assessing ischemically injured myocardium. With MR contrast agents protocol, it becomes possible to identify ischemic, acutely infarcted, and peri-infarcted myocardium in occlusive and reperfused infarctions. Necrosis specific and nonspecific extracellular contrast-enhanced MRI has been used to assess myocardial viability. Contrast-enhanced perfusion MRI can explore the disturbances in large (angiography) and small coronary arteries (myocardial perfusion) as the underlying cause of myocardial dysfunction. Perfusion MRI has been used to measure myocardial perfusion (ml/min/g) and to demonstrate the difference in transmural myocardial blood flow. Information on no-reflow phenomenon is derived from dynamic changes in regional signal intensity after bolus injection of MR contrast agents. Another development is the near future availability of blood pool MR contrast agents. These agents are able to assess microvascular permeability and integrity and are advantageous in MR angiography (MRA) due to their persistence in the blood. Noncontrast-enhanced MRI such as cine MRI at rest/stress, sodium MRI, and MR spectroscopy also have the potential to noninvasively assess myocardial viability in patients. Futuristic applications for MRI in the heart will focus on identifying coronary artery disease at an early stage and the beneficial effects of new therapeutic agents such as intra-arterial gene therapy. MR techniques will have great future in the drug discovery process and in testing the effects of drugs on myocardial biochemistry, physiology, and morphology. Molecular imaging is going to bloom in this decade.     

SUPRACONDYLAR AMPUTATION IN THE AGED

Of 105 consecutive supracondylar amputations done at the San Diego County General Hospital during the five-year period, 1953-58, 88 were in patients more than 60 years of age. Occlusive arterial disease was the reason for operation in 85 of the 88 cases.Presenting complaints at the time of amputation were gangrene in 45 cases, pre-gangrene associated with severe pain in 34. Acute arterial occlusion as a cause of thigh amputation was infrequent.The average age of patients requiring thigh amputation from complications of arteriosclerosis obliterans was 78.3 years; for those with diabetic arteriosclerosis or embolism it was about seven and a half years less.Supracondylar amputation was considered the procedure of choice in the elderly debilitated patients with far-advanced occlusive diffuse arteriosclerosis, complicated by gangrene, ulcer and infection of the toes or feet. Sympathectomy and direct arterial operation if done early in the course of the disease may postpone or prevent subsequent amputation.The surgical mortality rate (first two weeks) for supracondylar amputation was 12.5 per cent. More than two-thirds of the deaths were due to bronchopneumonia.     

Thermography in Occlusive Cerebrovascular Diseases

Cooling of the skin over the medial supraorbital region in 80% of patients who have an occlusion or severe stenosis of a carotid artery can be demonstrated by facial thermography. Minor stenotic lesions in the carotid arteries do not produce characteristic thermographic changes, while thermography is of no help in the diagnosis of vertebrobasilar arterial disease.Thermographic changes suggestive of carotid arterial lesions are found occasionally in patients whose angiograms are normal, owing to variations in the size of the frontal sinuses, or factors such as fever or inflammatory lesions.It is suggested that facial thermography is of value in the preliminary investigation of patients with occlusive cerebrovascular disease.     

Crystal structure of a non-hemorrhagic fibrin(ogen)olytic metalloproteinase complexed with a novel natural tri-peptide inhibitor from venom of Agkistrodon acutus

Thrombotic occlusive diseases pose a great threat to human health. Thrombolytic agents are in widespread use for the dissolution of arterial and venous pathologic thrombi in these kinds of diseases. Snake venom metalloproteinases (SVMPs) can act directly on fibrin/fibrinogen and are therefore potential candidates for therapeutic use against thrombotic occlusive diseases. In this study, we have determined the crystal structure of FII, a novel non-hemorrhagic SVMP isolated from Anhui Agkistrodon acutus snake venom by molecular replacement. The structure reveals that FII is a member of the P-I class SVMPs. The Zn2+ ion essential for hydrolytic activity is found in the active site and is tetrahedrally co-ordinated by three histidine residues and water molecule. Unambiguous electron density for a tri-peptide with sequence KNL is also found located near the active site. Biochemical evidences show that the tri-peptide KNL can inhibit the enzymatic activity of FII.     

Quantitative Measurement of Cerebral Oxygen Extraction Fraction Using MRI in Patients with MELAS

Objective

To quantify the cerebral OEF at different phases of stroke-like episodes in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) by using MRI.

Methods

We recruited 32 patients with MELAS confirmed by gene analysis. Conventional MRI scanning, as well as functional MRI including arterial spin labeling and oxygen extraction fraction imaging, was undertaken to obtain the pathological and metabolic information of the brains at different stages of stroke-like episodes in patients. A total of 16 MRI examinations at the acute and subacute phase and 19 examinations at the interictal phase were performed. In addition, 24 healthy volunteers were recruited for control subjects. Six regions of interest were placed in the anterior, middle, and posterior parts of the bilateral hemispheres to measure the OEF of the brain or the lesions.

Results

OEF was reduced significantly in brains of patients at both the acute and subacute phase (0.266 ± 0.026) and at the interictal phase (0.295 ± 0.009), compared with normal controls (0.316 ± 0.025). In the brains at the acute and subacute phase of the episode, 13 ROIs were prescribed on the stroke-like lesions, which showed decreased OEF compared with the contralateral spared brain regions. Increased blood flow was revealed in the stroke-like lesions at the acute and subacute phase, which was confined to the lesions.

Conclusion

MRI can quantitatively show changes in OEF at different phases of stroke-like episodes. The utilization of oxygen in the brain seems to be reduced more severely after the onset of episodes in MELAS, especially for those brain tissues involved in the episodes.     

Occlusion following laser resurfacing promotes reepithelialization and wound healing

One of the critical parameters that has not been examined carefully following laser skin resurfacing is the effect of eschar on the wound healing process. Because occlusive dressings minimize the occurrence of eschar, the present study was undertaken to evaluate the effect of occlusion following laser resurfacing. It is clear that CO2 lasers promote epidermal cell loss and variable amounts of dermal injury. To characterize the wound repair process after laser treatment, biopsy specimens were obtained 2 to 4 days after treatment. Specimens from 15 patients were examined; the preauricular biopsy specimens were paired such that one specimen was from skin that had been occluded and the other specimen (from the same patient) was from skin treated without occlusion. Skin specimens were examined by indirect immunofluorescence using antibodies to specific epidermal and dermal antigens. The results indicate that the keratinocytes that repopulate the epidermis migrate from the hair follicles and express keratin 17, an intermediate filament protein expressed in keratinocytes during the early stages of wound healing. The migration of keratin 17-expressing cells begins 48 hours following laser resurfacing in skin treated with occlusion, whereas cell migration from the follicles of skin treated without occlusion is delayed. In summary, occlusion promotes enhanced cell migration and diminished eschar formation, resulting in more rapid healing.     

Detection of Tissue Factor Antigen and Coagulation Activity in Coronary Artery Thrombi Isolated from Patients with ST-Segment Elevation Acute Myocardial Infarction

Introduction

Although ruptured atherosclerotic plaques have been extensively analyzed, the composition of thrombi causing arterial occlusion in patients with ST-segment elevation acute myocardial infarction has been less thoroughly investigated. We sought to investigate whether coagulant active tissue factor can be retrieved in thrombi of patients with STEMI undergoing primary percutaneous coronary intervention.

Methods

Nineteen patients with ST-segment elevation acute myocardial infarction referred for primary percutaneous coronary intervention were enrolled in this study. Coronary thrombi aspirated from coronary arteries were routinely processed for paraffin embedding and histological evaluation (4 patients) or immediately snap frozen for evaluation of tissue factor activity using a modified aPTT test (15 patients). Immunoprecipitation followed by immunoblotting was also performed in 12 patients.

Results

Thrombi aspirated from coronary arteries showed large and irregular areas of tissue factor staining within platelet aggregates, and in close contact with inflammatory cells. Some platelet aggregates stained positive for tissue factor, whereas others did not. Monocytes consistently stained strongly for tissue factor, neutrophils had a more variable and irregular tissue factor staining, and red blood cells did not demonstrate staining for tissue factor. Median clotting time of plasma samples containing homogenized thrombi incubated with a monoclonal antibody that specifically inhibits tissue factor-mediated coagulation activity (mAb 5G9) were significantly longer than their respective controls (88.9 seconds versus 76.5 seconds, respectively; p<0.001). Tissue factor was also identified by immunoprecipitation in 10 patients, with significant variability among band intensities.

Conclusions

Active tissue factor is present in coronary artery thrombi of patients with ST-segment elevation acute myocardial infarction, suggesting that it contributes to activate the coagulation cascade ensuing in coronary thrombosis.     

Risk Factors for Vascular Occlusive Events and Death Due to Bleeding in Trauma Patients; an Analysis of the CRASH-2 Cohort

Background

Vascular occlusive events can complicate recovery following trauma. We examined risk factors for venous and arterial vascular occlusive events in trauma patients and the extent to which the risk of vascular occlusive events varies with the severity of bleeding.

Methods and Findings

We conducted a cohort analysis using data from a large international, double-blind, randomised, placebo-controlled trial (The CRASH-2 trial) [1]. We studied the association between patient demographic and physiological parameters at hospital admission and the risk of vascular occlusive events. To assess the extent to which risk of vascular occlusive events varies with severity of bleeding, we constructed a prognostic model for the risk of death due to bleeding and assessed the relationship between risk of death due to bleeding and risk of vascular occlusive events. There were 20,127 trauma patients with outcome data including 204 (1.01%) patients with a venous event (pulmonary embolism or deep vein thrombosis) and 200 (0.99%) with an arterial event (myocardial infarction or stroke). There were 81 deaths due to vascular occlusive events. Increasing age, decreasing systolic blood pressure, increased respiratory rates, longer central capillary refill times, higher heart rates and lower Glasgow Coma Scores (all p<0.02) were strong risk factors for venous and arterial vascular occlusive events. Patients with more severe bleeding as assessed by predicted risk of haemorrhage death had a greatly increased risk for all types of vascular occlusive event (all p<0.001).

Conclusions

Patients with severe traumatic bleeding are at greatly increased risk of venous and arterial vascular occlusive events. Older age and blunt trauma are also risk factors for vascular occlusive events. Effective treatment of bleeding may reduce venous and arterial vascular occlusive complications in trauma patients.     

Differential MR Delayed Enhancement Patterns of Chronic Myocardial Infarction between Extracellular and Intravascular Contrast Media

Objectives

Because the distribution volume and mechanism of extracellular and intravascular MR contrast media differ considerably, the enhancement pattern of chronic myocardial infarction with extracellular or intravascular media might also be different. This study aims to investigate the differences in MR enhancement patterns of chronic myocardial infarction between extracellular and intravascular contrast media.

Materials and Methods

Twenty pigs with myocardial infarction underwent cine MRI, first pass perfusion MRI and delayed enhancement MRI with extracellular or intravascular media at four weeks after coronary occlusion. Myocardial blood flow (MBF) was determined with microsphere measurement. The infarction histopathological changes were evaluated by hematoxylin and eosin staining and Masson''s trichrome method.

Results

Cine MRI revealed the reduced wall thickening in chronic infarction compared with normal myocardium. Moreover, significant wall thinning in chronic infarction was observed in cine MRI. Peak first-pass signal intensity didn’t significantly differ between chronic infarction and normal myocardium no matter what kinds of contrast media. At the following delayed enhancement phase, extracellular media-enhanced signal intensity was significantly higher in chronic infarction than in normal myocardium. Conversely, intravascular media-enhanced signal intensity was almost equivalent among chronic infarction and normal myocardium. At four weeks after infarction, MBF in chronic infarction approached to that in normal myocardium. Large thick-walled vessels were detected at peri-infarction zones. The cardiomyocytes were replaced by scar tissue consisting of dilated blood vessels and discrete fibers of collagen.

Conclusions

Chronic infarction was characterized by the significantly reduced wall thickening and the definite wall thinning. First-pass myocardial perfusion defect was not detected in chronic infarction with two media due to the significantly recovered MBF and well-developed collateral vessels. Infarction remodeling enlarged the extracellular compartment, which was available for extracellular media but not accessible to intravascular media. Extracellular media identified chronic infarction as the hyper-enhancement; nonetheless, intravascular media didn’t provide delayed enhancement.     

Mapping of Autogenous Saphenous Veins as an Imaging Adjunct to Peripheral MR Angiography in Patients with Peripheral Arterial Occlusive Disease and Peripheral Bypass Grafting: Prospective Comparison with Ultrasound and Intraoperative Findings

Background

Mapping of the great saphenous vein is very important for planning of peripheral and coronary bypass surgery. This study investigated mapping of the great saphenous vein as an adjunct to peripheral MR angiography using a blood pool contrast agent in patients who were referred for evaluation of peripheral arterial occlusive disease and bypass surgery.

Methods

38 patients with peripheral arterial occlusive disease (21 men; mean age: 71 years, range, 44–88 years) underwent peripheral MR angiography using the blood pool contrast agent Gadofosveset trisodium. Apart from primary arterial assessment images were evaluated in order to determine great saphenous vein diameters at three levels: below the saphenofemoral junction, mid thigh and 10 cm above the knee joint (usability: diameter range: >3 and <10 mm at one level and >3.5 and <10 mm at a neighboring level). Duplex ultrasound was performed by an independent examiner providing diameter measurements at the same levels. Additionally, vessel usability was determined intraoperatively by the vascular surgeon during subsequent bypass surgery.

Results

Mean venous diameters for MR angiography/duplex ultrasound were 5.4±2.6/5.5±2.8 mm (level 1), 4.7±2.7/4.6±2.9 mm (level 2) and 4.4±2.2/4.5±2.3 mm (level 3), respectively, without significant differences between the modalities (P = 0.207/0.806/0.518). Subsequent surgery was performed in 27/38 patients. A suitable saphenous vein was diagnosed in 25 and non-usability was diagnosed in 2 of the 27 patients based on MR angiography/duplex ultrasound, respectively. Usability was confirmed by intraoperative assessment in all of the 24 patients that received a venous bypass graft in subsequent bypass surgery. In 1 case, in which the great saphenous vein was assessed as useable by both MR angiography and duplex ultrasound, it was not used during subsequent bypass surgery due to the patients clinical condition and comorbidities.

Conclusion

Simultaneous mapping of the great saphenous vein as an imaging adjunct to peripheral MR angiography with a blood pool contrast agent is an alternative to additive duplex ultrasound in patients undergoing subsequent peripheral bypass grafting.     

Induced hypertension for the treatment of acute MCA occlusion beyond the thrombolysis window: case report

Background  

A minority of stroke patients is eligible for thrombolytic therapy. Small pilot case series have hinted that elevation of incident arterial blood pressure might be associated with a favorable prognosis either in acute or subacute stroke. However, these patients were not considered for thrombolytic therapy and were not followed – up systematically. We used pharmacologically induced hypertension in a stroke patient with middle cerebral artery (MCA) occlusion ineligible for thrombolysis that was followed-up by radiological, clinical and functional outcome assessment.     

Comparison of results for operative and conservative treatment of multisegmental atheromatous arterial occlusion in the lower limbs after a 2-year period of observation]

Two hundred eighty seven patients treated surgically and 139 patients treated conservatively for multisegmental arterial occlusion in the lower limbs were followed up for two years. The results of therapy have been compared according to the site of arterial occlusion and the degree of ischemia. Surgery produces more chances for favourable results but an amputation rate or deaths are more frequent, than in case of the conservative treatment. No expected relationship between the results of surgery and of conservative therapy, localization and extension of the atheromatous process has been shown after a 2-year follow up.     

Increased endogenous nitric oxide production induced by physical exercise in peripheral arterial occlusive disease patients

The effects of 14-day physical exercise or iloprost treatment (0.5-2 ng/Kg/min) on endogenous nitric oxide production and neutrophil adhesion were evaluated in 20 patients with peripheral arterial occlusive disease (Fontaine Stage II). Peripheral venous blood samples and 4-h urine samples were collected before, immediately after 14 days of therapy and 7-10 days after therapy in order to evaluate neutrophil adhesion, nitrite/nitrate and cGMP excretion rates. A longer pain free walking distance was observed after exercise, compared to iloprost (>500 m in 3/10 subjects). Urinary nitrite/nitrate, as well as cGMP concentrations, significantly increased after exercise. Nitrite/nitrate excretion rate inversely correlated to neutrophil adhesion. No variations were observed in these parameters in iloprost treated patients. The improvement in claudication and the transient increase in urinary nitrite/nitrate suggest a possible nitric oxide-dependent mechanism for the clinical efficacy of physical exercise. The results from the present and previous observations indicate that, besides pharmacological treatments, a regular aerobic exercise improves peripheral arterial occlusive disease.     

Hepatocellular Carcinoma in Budd-Chiari Syndrome: Enhancement Patterns at Dynamic Gadolinium-Enhanced T1-Weighted MR Imaging

The objective of this study was to analyze the enhancement patterns at dynamic gadolinium-enhanced T1-weighted MR imaging in patients of Hepatocellular Carcinoma (HCC) with associated Budd-Chiari syndrome (BCS). The MR imaging findings in 10 patients of HCC with associated BCS were compared to those of 32 other patients of HCC without BCS. During the arterial phase, significantly more lesions with BCS were hyperintense than lesions without BCS; during the equilibrium phase, significantly more lesions with BCS were slightly hyperintense or isointense than lesions without BCS (P < 0.05 for both). For HCC, contrast enhancement on MRI shows different enhancement patterns between patients of HCC with associated BCS and those without BCS.     

脑磁共振灌注成像在大脑中动脉狭窄与闭塞患者中的应用价值分析

目的:研究脑磁共振灌注成像(PWI)在大脑中动脉(MCA)狭窄与闭塞患者中的应用价值。方法:纳入我院从2017年5月~2019年3月收治的单侧MCA狭窄与闭塞患者80例,对所有患者均实施经颅内数字减影血管造影(DSA)以及PWI检查,并将所有患者按照狭窄程度的不同分成轻度/中度组与重度/闭塞组。分析两组患者患侧与健侧大脑半球PWI相关参数,并作相关性分析。此外,分析PWI检查MCA狭窄或闭塞所致脑梗死类型分布情况。结果:DSA诊断结果显示:MCA轻度/中度狭窄患者35例,MCA重度/闭塞患者45例,其中MCA重度/闭塞的PWI检出率为100.00%,显著高于MCA轻度/中度狭窄的80.00%(P<0.05)。MCA轻度/中度组、重度/闭塞组患者患侧大脑半球的平均通过时间(rMTT)、达峰时间(rTTP)均显著高于健侧(均P<0.05)。经Spearman相关性分析可得:MCA患者狭窄程度与患侧大脑半球rMTT、rTTP均呈正相关关系(均P<0.05)。PWI检查结果显示,80例患者共检查出脑梗死患者53例,其中重度/闭塞组脑梗死总检出率以及纹状体内囊区脑梗死检出率分别为82.22%、11.11%,均明显高于轻度/中度组的45.71%、0.00%(均P<0.05)。结论:PWI应用于MCA狭窄与闭塞患者中的价值较高,可作为临床诊断MCA狭窄与闭塞的有效手段之一,值得临床推广应用。