The effects of thermogenic agents on hindlimb oxygen consumption in the dog: ICI D7114 and noradrenaline

OBJECTIVES: The purpose of this study was to test the hypothesis that the diameter of the recipient coronary artery of the well developed collateral circulation in patients with acute myocardial infarction increases because of the augmented intravascular pressure caused by subsequent collateral development. BACKGROUND: It is well known that collateral circulation develops after acute myocardial infarction. However, some patients have a well developed collateral circulation at the onset of infarction, which may limit the angiographic evaluation of further development of collateral circulation. METHODS: We measured the diameter of the donor and recipient arteries of the collateral circulation by means of a computer-assisted analysis system in seven patients with acute myocardial infarction who had a totally occluded infarct-related coronary artery during the acute and chronic stages of infarction. All coronary angiograms were obtained after the administration of sublingual nitroglycerin. The measurement was repeated immediately after (within 6 h) and late after (42 +/- 11 days) the onset of acute myocardial infarction. RESULTS: The diameter of the donor artery remained unchanged (1.32 +/- 0.98 vs. 1.42 +/- 1.12 mm). In contrast, the diameter of the recipient artery increased from 1.25 +/- 0.63 to 1.55 +/- 0.61 mm (p < 0.01). These changes in coronary artery diameter were associated with an improvement in regional myocardial wall motion at rest in infarct areas (6.7 +/- 7.0% vs. 13.6 +/- 10.7%, p < 0.05). CONCLUSIONS: These findings indicate that serial measurement of coronary artery diameter is useful for the evaluation of collateral development after acute myocardial infarction.     

Correlation between evoked motor response of the sciatic nerve and sensory blockade

OBJECTIVE: The development of collateral microvessels following therapeutic angiogenesis with vascular endothelial growth factor (VEGF) was investigated using a new system of microangiography that employs monochromatic synchrotron radiation (SR) and a high definition video system to visualize arteries with a spatial resolution of 30 microns. METHODS: Ischemia was induced in the hindlimb of 20 rats by excision of the femoral artery, followed by transfection of the plasmid (400 micrograms) encoding VEGF or beta-galactosidase (control) into limb muscles. Microangiography was used to assess the development of collaterals in the ischemic limb four weeks after treatment. RESULTS: Gene transfer of VEGF produced morphologically similar, but significantly more extensive, collateral networks at the microvascular level as compared with the naturally occurring collateral arteries in the control animals (angiographic score: 0.88 +/- 0.08 versus 0.54 +/- 0.05, p < 0.01). No adverse vascular effects such as hemangiomas and/or arteriovenous (AV) fistulae were observed following VEGF treatment. The vasodilator effect of papaverine was evident in relatively large vessels in both groups. At the microvascular level (diameter < 100 microns), however, papaverine induced significant vasodilation in the VEGF-treated animals, and almost no vasodilation in the controls. CONCLUSIONS: SR microangiography allowed us to assess the development of small collateral arteries following VEGF-gene transfer. The information obtained may provide new insights regarding the collateral microcirculation and therapeutic angiogenesis.     

Angiogenesis

The formation of new blood vessels, angiogenesis, is a complex process which is central to normal development and homeostasis. However, uncontrolled angiogenesis plays a critical role in both inflammatory and neoplastic disorders. Our understanding of angiogenesis has expanded greatly over the past two decades due to the development of in vivo and in vitro models to study this important process. A variety of cytokines and growth factors have been shown to induce new blood vessel formation in vivo, and in vitro studies have been able to define whether agents have direct or indirect effects upon vascular endothelial cells. Our improved understanding of the mechanisms which regulate angiogenesis has now created important opportunities for the development of new therapies for the treatment of inflammatory and neoplastic skin disease.     

Coronary stenosis and mechanisms of collateral vessel growth

The presence or absence of collateral circulation significantly impacts the natural history of coronary artery disease. Collateral growth involves two different mechanism; capillary collaterals develop by sprouting (angiogenesis) and muscular collaterals develop in situ from preexisting arterioles (arteriogenesis). The process is mediated by various angiogenic growth factors such as VEGF, FGFs, IGF-1 and PDGF. Although these growth factors have been studied extensively, controversies still exist as to whether angiogenesis depends on increased supply of these growth factors or their receptors are upregulated by the underlying pathological situation. An increased understanding of the basic biology of collateral vessel development would be instrumental in the establishment of therapeutic angiogenesis.     

Breast cancer angiogenesis--new approaches to therapy via antiangiogenesis, hypoxic activated drugs, and vascular targeting

Several groups have shown that quantitation of tumor angiogenesis by counting blood vessels in primary breast cancer gives an independent assessment of prognosis. Poor prognosis is associated with high blood vessel counts. We have shown that the rate of cell division in endothelial cells is much higher in breast tumours than in normal breast. Breast cancer cell lines and primary human breast tumours express a wide range of vascular growth factors, including VEGF, placenta growth factor, pleiotrophin, TGF beta 1, acidic and basic FGF, and platelet-derived endothelial cell growth factor. Inhibiting angiogenesis by blocking vascular growth factors would be difficult with highly specific agents, but drugs with a broader spectrum of antagonism may be effective. We have developed several suramin analogues which are less toxic than suramin in vivo but more potent in inhibiting angiogenesis, and these have been developed for Phase I. A combination of anti-angiogenesis agents with drugs activated by hypoxia may also be useful, because anti-angiogenesis alone may not kill cells, whereas activation of hypoxic drugs could synergize. New endpoints may be necessary because inhibition of new blood vessel formation may not cause tumour regression. Thus, the endpoint of stable disease and biochemical assessment of inhibition of angiogenesis may be much more important in therapeutic studies and for drug development in the future. The prognostic importance of angiogenesis suggests that this should be a major new therapeutic target.     

Relationship of angiographic finding with neovascular structure detected by immunohistochemical staining of alpha-smooth muscle actin in small hepatocellular carcinoma

To elucidate the relationship between angiographic features and histological findings, an immunohistological study of alpha-smooth muscle actin was performed in 106 patients with small hepatocellular carcinoma. Arterial dominance or portal blood paucity were found in 73 patients (68.9%) on digital subtraction angiography, 88 (83.0%) on computerized tomographic arterial portography and 87 (82.1%) on carbon dioxide-enhanced ultrasonography. Among 73 patients with hypervascularity on angiography, 57 (78.1%) had thick-walled, nuclei-rich and slender-shaped vessels (type II), eight (11.0%) had thin-walled, nuclei-poor and oval-shaped vessels (type I) and the remaining eight had a mixed type of II and I. Conversely, among 33 patients without hypervascularity, five (15.2%) had a type II, 21 (63.6%) had a type I, five had a mixed type and two had no positive vessel. Tumour size, histological classification and amount of non-triadal vessels were also associated with the angiographic appearance of the tumours. Among varied aspects of the cancer including tumour size, tumour multiplicity, microscopic portal invasion, histological classification, amount of alpha-smooth muscle actin-positive vessels and shape of alpha-smooth muscle actin-positive vessels, multivariate logistic regression analysis demonstrated that the shape of alpha-smooth muscle actin-positive vessels was solely associated with angiographic hypervascularity independently (P<0.0001). Although the existence of non-triadal vessels characterized hepatocellular carcinoma, angiographic hypervascularity was closely associated with the type II vessel. A morphological change of non-triadal vessel from type I to type II was considered to occur in an early stage of hepatocellular carcinoma.     

Angiogenesis: a dynamic balance of stimulators and inhibitors

Angiogenesis, the formation of new blood vessels from a pre-existing vasculature, is tightly regulated in normal adults. Under physiological circumstances, angiogenesis occurs in only a few instances; e.g., the female reproductive system in response to ovulation or gestation, the normal hair cycle, etc. In these examples, growth of new capillaries is tightly controlled by an interplay of growth regulatory proteins which act either to stimulate or to inhibit blood vessel growth. Normally, the balance between these forces is tipped in favor of inhibition and consequently capillary growth is restrained. Under certain pathological circumstances, however, local inhibitory controls are unable to restrain the increased activity of angiogenic inducers. Thus, in wound healing, inflammation and tumors, to name just a few examples, angiogenesis is integral to the pathology, engendering the hope that these pathological entities could be regulated by pharmacological and/or genetic suppression (or enhancement) of blood vessel growth. This hope, in turn, has fostered interest in the molecular mechanisms that regulate angiogenesis. In this chapter, we have reviewed the current literature regarding some angiogenic stimulators and inhibitors, emphasizing vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), as a major angiogenic inducer, and thrombospondin (TSP) as the best known example of a natural inhibitor of vessel growth.     

Changes in coronary and collateral flows and adequacy of perfusion in the dog following one and three months of circumflex occlusion

We investigated changes in circumflex, left anterior descending (LAD), and right coronary artery flows as well as changes in collateral flows to these vessels after long-term circumflex occlusion. Coronary and collateral flows of each vessel were determined simultaneously in an isolated heart preparation in which the vasculature was maximally dilated with dipyridamole. The resistances as related to total heart weight of the circumflex, LAD, and right coronary arteries of 16 control dogs were found to be 0.59 +/- 0.06, 0.93 +/- 0.09, and 2.37 +/- 0.17 (mean +/- SEM) mm Hg/[(ml/min)/100 g], respectively. Total minimal coronary resistance was 0.21 +/- 0.01. In 10 dogs subjected to occlusion for 1 month no significant change in circumflex coronary resistance was observed, but the resistance of the unimpaired vessels decreased significantly. The resistances of the LAD and right coronary arteries were 0.66 +/-0.04 and 1.72 +/- 0.13, respectively. Both values were considerably less (P less than 0.01) than control. In nine dogs subjected to occlusion for 3 months the resistance of the unimpaired LAD and right arteries, as well as the circumflex coronary resitance, were not significantly different from control. We also found that retrograde flows for all vessels increased 7-fold after 1 month and 10.5-fold (relative to control) after 3 months of occlusion. From these data we conclude that vascular adaptations, which occurred in response to an ischemic stimulus, are responsible for the long-term regulation of the metabolic needs of the myocardium.     

Spontaneous angiographic obliteration of cerebral arteriovenous malformations

OBJECTIVE: The factors associated with spontaneous angiographic obliteration of cerebral arteriovenous malformations (AVMs) are not well understood. We present a review of the literature and a report of our experience with six cases (four with no previous treatment intervention and two postoperative residual malformations) that were identified as having occurred during a 20-year period and describe the clinical and lesion features associated with this rare phenomenon. We present the first detailed histological study of a spontaneously thrombosed AVM specimen, including immunohistochemical analysis of angiogenesis factor expression. METHODS: A combined experience in the management of approximately 700 AVMs during 20 years identified six cases of spontaneous angiographic obliteration of cerebral AVMs. A literature review revealed another 24 cases with angiographic documentation of the initial AVMs and follow-up data showing nonfilling of the lesions. Histological analysis of a recently excised lesion included immunostaining with monoclonal antibodies to the antigens of Factor VIII, Tie, vascular endothelial growth factor, and its receptors, Flt-1 and Flk. RESULTS: A single draining vein was a feature in each of our 6 cases and in 12 of 14 (86%) cases from the literature. Hemorrhage as the presenting symptom was identified in 5 of our 6 (83%) cases and in 17 of 24 (71%) of the literature cases. The size of the AVM was less than 6 cm in each of our 6 cases and in 22 of 24 (92%) of the literature cases. A histological examination of a thrombosed AVM surgical specimen revealed persistent patent vascular channels within the lesion. Immunohistochemical analysis with angiogenesis and endothelia-specific factors showed expression of these factors within the lumen of the thrombosed nidus vessels. CONCLUSION: We propose that the occlusion of a single draining vein may lead to total venous outflow obstruction and lesion thrombosis. Hemorrhagic presentation and small nidus may also predispose to this phenomenon. Immunohistochemical analysis of a thrombosed AVM revealed possible ongoing angiogenic changes within the AVM vessels 1 month after angiographically documented thrombosis. It is possible that neovascularization within a thrombosed AVM may lead to lesion recanalization; however, this phenomenon seems to be clinically exceedingly rare.     

Acceleration of ageing processes by ionizing radiation (author''s transl)]

The dynamics of arterial, venous, and lymphatic flow in the mesentery were studied in dogs, using an electromagnetic flowmeter for the blood and cannulation and gravimetric measurement for the lymph. Ligation of veins caused an increased venous outflow in adjacent veins and a marked increase in lymph flow. When marginal vessels were ligated, eliminating the major collateral flow, venous flow decreased, but elevated lymph flow persisted. Simultaneous ligation of arteries and veins resulted in increases of both arterial and venous flow in adjacent vessels. Lymph flow decreased unless excessive arterial collateral flow persisted. When collateral marginal vessel flow was occluded, adjacent venous and arterial blood flow decreased to control levels. With arterial ligation, collateral arterial blood flow increased slightly, but venous and lymph flow decreased sharply. When collateral marginal vessels were eliminated, adjacent arterial blood flow decreased to control levels and venous flow virtually stopped. As a result of these studies, the technic of early primary arterial ligation followed by marginal vessel ligation appears to be the most satisfactory procedure for decreasing venous and lymphatic outflow and hopefully avoiding dissemination of cancer cells during the operation. This technic is now being used as a modification of the "no touch" technic for cancer of the colon.     

Noninvasive prediction of residual blood flow within the risk area during acute myocardial infarction: a multicenter validation study of patients undergoing direct coronary angioplasty

BACKGROUND: In a previous study from a single center, radionuclide measures of collateral flow with technetium 99m sestamibi have been shown to be significantly associated with angiographic residual (antegrade and collateral) flow and independent predictors of final infarct size in acute myocardial infarction. This study examined whether the previously described radionuclide measures of blood flow to the infarct zone were reproducible with different laboratories and imaging systems. METHODS AND RESULTS: Residual flow to the infarct zone was assessed by both invasive and noninvasive methods in 77 patients with first-time myocardial infarction (32 anterior, 45 nonanterior). All patients underwent acute coronary angiography before any intervention within 8 hours of the onset of chest pain (4.0 +/- 1.5 hours; range 1.2 to 7.9 hours). 99mTc sestamibi was injected intravenously before reperfusion therapy, and tomographic imaging was performed 1 to 6 hours after injection. A central core laboratory processed the acquired images from three centers, each with a unique camera and computer system. Three previously published methods based on the severity of the acute perfusion defect were used to measure residual flow to the infarct zone (nadir, severity index, area). Antegrade (Thrombolysis in Myocardial Infarction flow) and collateral flow before direct angioplasty were blindly graded on a four-point scale (0 to 3) from the acute angiogram. The simple sum of the two grades was defined as the angiographic flow index, representing residual flow to the jeopardized zone. All three noninvasive measures of residual flow were highly associated with the angiographic flow index in a linear fashion: severity index (p = 0.0006), area (p = 0.003), and nadir (minimum/maximum counts; p = 0.004). This association was independent of the laboratory where the data were acquired. CONCLUSIONS: Despite different laboratories and camera systems, radionuclide measures of residual flow were highly associated with the angiographic flow index before reperfusion therapy. These results suggest that these measures are applicable on a broader scale for the noninvasive determination of collateral and antegrade flow in acute myocardial infarction.     

Current concepts of tumor-induced angiogenesis

Tumor induced angiogenesis is responsible for the nutrition of the growing tumor and can also increase the probability of hematogenous tumor dissemination. Data obtained from morphological analysis of tumor angiogenesis can contribute to the development of new anti-angiogenic therapies. Based on in vitro and in vivo observations several models of angiogenesis were introduced, explaining the mechanism of lumen formation and the timing of basement membrane depositon. (1) Lumen is formed either by cell body curving or by fusion of intracellular vacuoles of nonpolarized endothelial cells. New basement membrane is deposited after lumen formation. (2) Slit-like lumen is immediately formed by migrating polarized endothelial cells. Basement membrane is continuously deposited during endothelial cell migration, only cellular processes of the endothelial cell migrating on the tip of the growing capillary are free of deposited basement membrane material. (3) Development of transluminal bridges in larger vessels a process called intussusceptive growth leads to the division of the vessels. These models, however, describe angiogenesis in tissues rich in connective tissue. Different processes of angiogenesis take place in organs such as liver, lungs, adrenals, which are the most frequent sites of metastasis having high vessel density without sufficient space for capillary sprouting. In the case of liver metastases of Lewis lung carcinoma the proliferation of endothelial cells was elicited only by direct contact between tumor and endothelial cells, leading to the development of large convoluted vessels inside the metastases. These vessels were continuous with the sinusoidal system, suggesting that these metastases have dual blood supply. This observation, among others, is in contrast to the generally accepted view that liver tumors have arterial blood supply. The increasing number of data demonstrating the dual or venous blood supply of liver metastases should be taken into consideration in the therapy of liver metastasis.     

Differences in restenosis propensity of devices for transluminal coronary intervention. A quantitative angiographic comparison of balloon angioplasty, directional atherectomy, stent implantation and excimer laser angioplasty. CARPORT, MERCATOR, MARCATOR, PARK, and BENESTENT Trial Groups

With the increasing clinical application of new devices for percutaneous coronary revascularization, maximization of the acute angiographic result has become widely recognized as a key factor in maintained clinical and angiographic success. What is unclear, however, is whether the specific mode of action of different devices might exert an additional independent effect on late luminal renarrowing. The purpose of this study was to investigate such a difference in the degree of provocation of luminal renarrowing (or 'restenosis propensity') by different devices, among 3660 patients, who had 4342 lesions successfully treated by balloon angioplasty (n = 3797), directional coronary atherectomy (n = 200), Palmaz-Schatz stent implantation (n = 229) or excimer laser coronary angioplasty (n = 116) and who also underwent quantitative angiographic analysis pre- and post-intervention and at 6-month follow-up. To allow valid comparisons between the groups, because of significant differences in coronary vessel size (balloon angioplasty = 2.62 +/- 0.55 mm, directional coronary atherectomy = 3.28 +/- 0.62 mm, excimer laser coronary angioplasty = 2.51 +/- 0.47 mm, Palmaz-Schatz = 3.01 +/- 0.44 mm; P < 0.0001), the comparative measurements of interest selected were the 'relative loss' in luminal diameter (RLoss = loss/vessel size) to denote the restenosis process, and the 'relative lumen at follow-up' (RLfup = minimal luminal diameter at follow up/vessel size) to represent the angiographic outcome. For consistency, lesion severity pre-intervention was represented by the 'relative lumen pre' (RLpre = minimal luminal diameter pre/vessel size) and the luminal increase at intervention was measured as 'relative gain' (relative gain = gain/ vessel size). Differences in restenosis propensity between devices was evaluated by univariate and multivariate analysis. Multivariate models were constructed to determine relative loss and relative lumen at follow-up, taking account of relative lumen pre-intervention, lesion location, relative gain, vessel size and the device used. In addition, model-estimated relative loss and relative lumen at follow-up at given relative lumen pre-intervention relative gain and vessel size, were compared among the four groups. Significant differences were detected among the groups both with respect to these estimates, as well as in the degree of influence of progressively increasing relative gain, on the extent of renarrowing (relative loss) and angiographic outcome (relative lumen at follow-up), particularly at higher levels of luminal increase (relative gain). Specifically, lesions treated by balloon angioplasty or Palmaz-Schatz stent implantation (the predominantly 'dilating' interventions) were associated with more favourable angiographic profiles than directional atherectomy or excimer laser (the mainly 'debulking' interventions). Significant effects of lesion severity and location, as well as the well known influence of luminal increase on both luminal renarrowing and late angiographic outcome were also noted. These findings indicate that propensity to restenosis after apparently successful intervention is influenced not only by the degree of luminal enlargement achieved at intervention, but by the device used to achieve it. In view of the clinical implications of such findings, further evaluation in larger randomized patient populations is warranted.     

Analysis of subcutaneous angiogenesis by gradient echo magnetic resonance imaging

The goal of this study was to develop an experimental method for noninvasive analysis of angiogenesis, namely the sprouting of capillaries from existing blood vessels. Angiogenesis was assayed in the subcutaneous vasculature of nude mice in a region of 3 x 3 cm that included in its center a defined angiogenic stimulus. Angiogenic stimuli included agarose beads containing angiogenic growth factors, multicellular tumor spheroids, and dermal incisions. Highly significant correlation (r = 0.905, P = 0.0001) was found between the apparent vessel density determined by gradient echo MRI and the density of blood-containing vessels determined postmortem. The functionality of the neovasculature was demonstrated in mice breathing alternatingly carbogen or 95% air/5% CO2. Large signal enhancement with carbogen breathing corresponded to regions of high vessel density. The assay reported here can be applied for the study of dermal wound healing, primary vascularization of subcutaneous implants, and for measuring the activity of angiogenic and antiangiogenic agents.     

Endothelium-dependent relaxation and vasospasm in the single-hemorrhage canine model

We have investigated the relationship between angiographic vasospasm and the ability of spastic vessels to relax in response to agents which promote release of endothelium derived relaxing factor. Vasospasm was induced in dogs by the 'single hemorrhage' technique. Animals received a single intracisternal injection of blood, blood activated with thromboplastin or collagen, or inert material, and angiograms were obtained day 0 and day 7. Vasospasm was estimated by measuring the ratio of the diameter of the vessel before and after treatment. Rings of cerebral artery obtained from these animals were suspended in a standard organ-bath arrangement, contracted with prostaglandin F2 alpha and then treated with increasing doses of adenosine triphosphate or bradykinin, both of which cause relaxation by an endothelium-dependent process. The arteries from animals with moderate to severe vasospasm showed a response to bradykinin and adenosine-triphosphate which was reduced, absent or converted to a contraction, when compared with normal vessels. Vessels in which vasospasm was mild or absent relaxed as expected to these agents. The reduction in vessel diameter showed a highly significant correlation with the reduction in relaxation to bradykinin or adenosine-triphosphate. These results have demonstrated that impairment of endothelium-dependent vasorelaxation correlates with the existence of vasospasm.     

Chronic total occlusion of the left main coronary artery

Total chronic occlusion of the left main coronary artery is a rare angiographic finding in a catheterization laboratory. After reviewing the coronary angiographies performed in our laboratory between 1986 to 1995, we found a prevalence of 0.04%. These patients presented unspecific symptoms similar to other kinds of coronary artery disease. In all cases, the right coronary artery was dominant with extensive collateral circulation to the left coronary artery. Ventricular function was normal in 50% of the cases. Probably, in these unusual cases, the best therapeutic approach is surgical revascularization.     

Angiostatic treatment of neuroblastoma

The growth of solid tumours has been shown to be dependent on new blood vessel formation, i.e. angiogenesis. Several steps in the metastatic process have also been found to be angiogenesis dependent. The mediators of tumour angiogenesis are now being elucidated, and angiostatic agents have been developed. Some of these agents are currently undergoing clinical trials. In addition to inhibition of angiogenesis, two other clinical applications of angiogenetic research in tumour diseases are monitoring of disease activity by analyses of circulating angiogenic peptides and prediction of a poor outcome by tumour microvascular counts. Neuroblastomas grow quickly, are highly vascularised and metastasise early and hence inhibition of angiogenesis--angiostatic therapy--may be indicated in this disease. The effects of treatment with the angiostatic agent TNP-470 in an experimental model results in a significant reduction of the tumour growth rate, reduced microvascular counts and a reduced fraction of viable tumour cells compared to controls. TNP-470 as single therapy has an objective tumoristatic effect in our neuroblastoma model. Angiostatic treatment of neuroblastoma is a new and theoretically promising treatment modality that merits clinical investigations. The feasibility of assessing disease activity by repeated determinations of the levels of circulating angiogenic peptides should also be determined, as well as the use of microvascular counts to predict a poor outcome.     

Abdominal CT findings when the superior vena cava, brachiocephalic vein, or subclavian vein is obstructed

OBJECTIVE: We evaluated findings on contrast-enhanced abdominal CT scans that suggest obstruction of the superior vena cava, brachiocephalic vein, or subclavian vein. SUBJECTS AND METHODS: We conducted a retrospective review of 22 patients with superior vena caval, brachiocephalic vein, or subclavian vein obstruction and analyzed the upper abdominal images on a chest CT scan or an abdominal CT scan. We assessed collateral vessels in the upper abdomen to answer the following question: Did enhancement approach undiluted IV contrast or were there other findings? In the second part of our study, we conducted a prospective review of abdominal CT scans of 200 patients without known mediastinal disease or known upper extremity venous occlusion to determine the frequency of abnormal enhancement of these vessels in a healthy population. RESULTS: The groups of collateral vessels revealed on abdominal CT scans were azygos or hemiazygos veins, internal mammary veins, lateral thoracic and superficial thoracoabdominal veins, vertebral venous plexus veins, and small mediastinal collateral veins. In the retrospective series, one patient had focal enhancement of the liver and early inferior vena caval enhancement due to collateral vessels. In the prospective series, abdominal CT scans of two patients (1%) revealed dense undiluted enhancement of one or more groups of collateral vessels: One patient had an ipsilateral pacemaker, and the other patient had an anterior neck phlegmon to the upper mediastinum. Both conditions may have been factors in the revealing of the collateral vessels. Two other patients (1%) in the prospective series had mild to moderate vessel enhancement that was less than that from undiluted contrast material. In one of these patients, the enhancement was related to abdominal wall hyperemia after surgery. In the other patient, enhancement may have been the result of ipsilateral axillary nodes. CONCLUSION: On upper abdominal CT scans, dense undiluted contrast material in the collateral vessel groups that we studied suggests possible obstruction of the superior vena cava, brachiocephalic vein, or subclavian vein.     

Iron-manganese interactions in the evolution of iron deficiency

Since the publication of prior reviews on this topic, substantial clinical experience with a variety of operative strategies to prevent ischaemic cord complications has been reported. The available data on angiographic localisation of critical intercostal vessels, and, in particular, the evoked potential response to cross-clamping in patients indicates that risk of paraplegia varies considerably even among patients with equivalent TAA extent. Factors such as individual development of the ASA, patent critical intercostals, and the particulars of collateral circulation when intercostal aortic ostia are already occluded likely account for this variability. Information available from SSEP monitoring relative to the dynamic course of cord ischaemia with cross-clamping, and the parallel, if not, frustrating experience with angiographic localisation and intercostal vessel reconstruction indicates that a narrow temporal threshold of cord ischaemia with clamping is present in many patients. This reinforces the importance of both expeditious clamp intervals, critical intercostal re-anastomoses, and the desirability of neuroprotective manoeuvres during cross-clamp induced cord ischemia. As suggested in compelling experimental work our contemporary clinical experience, and predicted by prior reviewers, regional cord hypothermia provides significant promise for limiting or eliminating, in particular, immediate perioperative deficits. Avoidance of postoperative hypotension, spinal cord oedema, and preservation of critical intercostal vessels are additional strategies necessary to impact the development of delayed deficits favourably.     

Vascular remodeling and altered protein expression during growth of coronary collateral arteries

The cellular mechanism of growth of coronary collateral vessels (adaptive arteriogenesis) is still poorly understood. To define a possible role of an altered expression pattern of cellular and matrix proteins in this process we implanted a constricting device around the left circumflex artery in 25 canine hearts and sacrificed the animals at the time of initiation (3 weeks), high activity (6 weeks) and discontinuation (8 weeks) of vessel growth. Methods were electron microscopy, labeling with Ki-67, the TUNEL method and immunofluorescence with confocal laser microscopy. As described earlier, the collateral vessels increased in wall thickness by the formation of a neointima without luminal narrowing. We report here for the first time that extensive vascular remodeling including migration, proliferation and apoptosis in all cell types takes place during the growth phase but not in more mature vessels. The most obvious difference with normal vessels is the reiteration of an embryonal expression pattern in smooth muscle cells of the neointima which includes a significant reduction of desmin and alpha-smooth muscle actin, calponin and vinculin. Fibronectin as a promoter of migration and adhesion was abundant, its antagonist tenascin and chondroitin sulfate showed patchy localization. A completely new finding in arteriogenesis is the involvement of mast cells releasing histamine and serotonin and probably cytokines. Vascular protein expression returned to almost normal at 8 weeks indicating cessation of remodeling. We conclude that in collateral vessel development an altered cellular and matrix protein expression is involved in a drastic case of positive vascular remodeling finally resulting in mature vessels 20-fold increased in size which are capable of maintaining the functional and structural integrity of the myocardium at risk.