Development Of Collateral Circulation Research Articles

Elevation of nitric oxide metabolites in the cerebrospinal fluid of patients with moyamoya disease.

To investigate whether nitric oxide (NO) contributes to formation of abnormal collateral circulation in patients with moyamoya disease. Cerebrospinal fluid (CSF) samples were obtained from the subarachnoid space of the Sylvian fissure during combined bypass surgery for moyamoya disease and kept frozen until NO metabolites, nitrate and nitrite, were measured using a Griess method. Compared with control CSF obtained from 18 patients with hemifacial spasm, unruptured aneurysm, etc., concentrations of NO metabolites in 26 CSF samples of 18 patients with moyamoya disease were significantly higher (mean +/- SE; 17.6 +/- 1.2 vs. 10.5 +/- 1.0 microM, p < 0.01). In eight patients, the CSF samples from both the first and second operation could be obtained. NO metabolite concentrations (20.5 +/- 2.3 microM) in CSF obtained from the first surgery decreased to 15.7 +/- 1.8 microM (p < 0.01) in CSF obtained from the second, contralateral procedure. The cases of moyamoya disease with greater development of moyamoya vessels at angiographic stage 3 and 4 tended to show higher concentrations of NO metabolites than cases at earlier or later stages with a few moyamoya vessels. Nitric oxide concentrations in CSF are chronically elevated in moyamoya disease, probably reflecting development of abnormal collateral circulation. i.e. moyamoya vessels. Vascular bypass surgery can reduce abnormal collateral circulation with reduced production of nitric oxide.

Increased Blood Vascular Endothelial Growth Factor Levels in Patients with Acute Myocardial Infarction

Vascular endothelial growth factor (VEGF) is a growth factor for vascular endothelial cells in vitro. The present study was designed to determine whether serum VEGF levels increase in patients with acute myocardial infarction (AMI) compared with patients with stable exertional angina and control subjects, and to examine the serial changes of serum VEGF levels in patients with AMI. We examined serum VEGF levels by using antibody prepared from serum immunized with human VEGF₁₂₁. The serum VEGF level (pg/ml) was higher (p < 0.0001) on admission in the patients with AMI (177 ± 19) than in those with stable exertional angina (61 ± 7) and control subjects (62 ± 6). The serum VEGF level (pg/ml) of the patients with AMI was 177 ± 19 on admission, 125 ± 9 on day 3, 137 ± 11 on day 5, 242 ± 18 at 1 week, and 258 ± 22 at 2 weeks after admission. The value was higher on admission than on day 3 after admission (p = 0.014), the values were higher at 1 week and 2 weeks than on admission, on day 3, and 5 (p < 0.01). Furthermore, there were correlations between peak VEGF levels at 1 week or 2 weeks after admission and peak creatine kinase levels. The increase of VEGF on admission in the patients with AMI may be due to the hypoxia of acute myocardial ischemia. The elevation at 1 week and 2 weeks from the onset may cause the development of collateral circulation in relation to the healing of the infarction site.

The Development of Collateral Circulation in Patients with Total Occlusion of Coronary Artery and its Clinical Significance

Background and Objectives:Coronary collateral circulation is known to have beneficial effects in patients with angina pectoris and myocardial infarction. The purpose of this study is to determine the predictors of collateral vessels development, the pathways of collateral circulation and the changes in collateral flow after coronary intervention and its functional significance in patients with total occlusion. Materials and Methods: One hundred thirty five patients who underwent coronary angiogram between Jan ’97 and Dec ’97 in Chonnam University Hospital (out of 3,264 cases) had total occlusion of one coronary artery were classified into two groups;angina pectoris (Group I:50 M, 19 F, 62.4±11.0 years) and acute myocardial infarction (Group II:47 M, 19 F, 62.0±9.5 years). Results:Among 135 patients, 123 patients had collateral circulation. Collaterals were more frequently observed and better developed (grade 2 or 3) in Group I than Group II. Proximal and ostial lesions were associated with well developed collaterals. Collateral circulation was more frequently observed and well developed in proportion to the duration of angina in Group I. In 123 patients with collateral circulation, 247 collateral circulations were observed. Right coronary artery (RCA) and Left circumflex coronary artery (LCX) were more frequent recipient arteries than left anterior descending coronary artery (LAD)(RCA:2.20±1.02, LCX:1.88±0.94, LAD:1.29±0.8 respectively, RCA vs. LAD:p<0.001, LCX vs. LAD:p=0.014). Coronary interventions were performed in 50 out of 135 patients, collateral flow of Group II decreased much more than Group I after intervention (Group I:5/14, Group II: 24/36, p=0.046). The wall motion score was lower in patients with well developed than poorly developed collaterals (20.7±4.91 vs. 23.7±6.22, p=0.015). Conclusion:Proximal or ostial lesion and duration of 논문접수일:1999년 8월 24일 심사완료일:2000년 2월 17일 교신저자:정명호, 501-757 광주광역시 동구 학1동 8번지 전남대학교병원 심장센터 전화:(062) 220-6243·전송:(062) 228-7174 E-mail:myungho@chollian.net

Comparison of coronary collateral circulation in diabetic and nondiabetic patients suffering from coronary artery disease.

Although it is well established that diabetes mellitus (DM) induces more severe coronary artery disease (CAD), it is not known whether it contributes to the development of coronary collateral circulation. The present study examines coronary collateral circulation in diabetic and nondiabetic patients with angiographically verified CAD. The study group consisted of 463 diabetic patients (382 men, 81 women) with a mean age of 60.3 +/- 8.8 years, and 227 nondiabetic subjects (159 men, 68 women) with a mean age of 59.2 +/- 9 years. The extension and functional capacity of coronary collateral circulation was assessed according to the Cohen and Rentrop grading system of 0 to III. We found that diabetic patients had grade III collateral circulation more frequently than nondiabetic subjects (13.2 vs. 8.5%, p < 0.01). This finding was even more pronounced in diabetic men aged < 55 years compared with both nondiabetic men (20 vs. 3.4%, p < 0.001) and diabetic women (20 vs. 2.2%, p < 0.001). Grade III collateral circulation was found to develop mainly at the left anterior descending (LAD) coronary artery and the right coronary artery (RCA), where complete occlusions of coronary arteries usually occur. Diabetic patients with CAD develop more extensive coronary collateral circulation than nondiabetic subjects, especially men aged < 55 years. The collateral circulation mainly develops at the LAD and RCA.

Effects of ischemia on voiding function and nerve growth factor of the rat urinary bladder

Nerve growth factor (NGF) is synthesized in the target organs innervated by autonomic and sensory nerves so as to grow, maintain and/or repair the neurons. The present study evaluated the effects of ischemia on NGF synthesis and voiding function of the rat urinary bladder. Bladder ischemia was induced by ligating of bilateral internal iliac arteries in the female rats. We examined the changes in the blood flow, histological structure, voiding function and NGF content of the bladder immediately, 1, 7, 14 and 28 days after the surgery. Blood flow was estimated by measuring absorbance of homogenized bladder tissue after dye injection into the abdominal aorta. Voiding function was assessed by continuous cystometry under an awake restrained condition. NGF was quantified by enzyme immunoassay (ELISA method). Blood flow decreased to 18% of the control immediately after the vascular ligation, and gradually recovered to 66% of the control on day 28. Histologically, epithelial ablation and thinning of muscle layer were observed on days 1 and 7. These histological disorders gradually improved to normal appearance on day 14. On day 1, while the maximum contraction pressure significantly decreased, the contraction frequency and small prevoiding contraction increased. On the other hand, the voiding efficacy markedly decreased on day 7. These functional changes recovered nearly to the control levels after day 14. NGF content transiently increased 2.4 times as the control on day 1. The present results will indicate that the voiding function deteriorated by acute ischemia is temporarily compensated by detrusor hyperrefrexia, which may be attributable to an enhanced NGF synthesis, and then improves by the development of collateral blood circulation.

髄液中NO代謝物はもやもや病側副血行発達の指標となりうるか

Moyamoya disease is a unique disease of unknown etiology typically characterized by progressive occlusion of both internal carotid arteries accompanied by an abnormal collateral circulation referred to as moyamoya vessels. To compensate for lack of blood flow in the frontal region, the collateral circulation develops from delicate basal networks and the vertebrobasilar system, and often is demonstrated by angiography, MRI or MRA. To investigate whether nitric oxide (NO) contributes to formation of abnormal collateral circulation in patients with moyamoya disease, we measured concentrations of NO metabolites in cerebrospinal fluid (CSF) obtained during treatment of this disease with bypass surgery.CSF samples were obtained from the subarachnoid space of the sylvian fissure during combined bypass surgery for moyamoya disease and kept frozen untill NO metabolites, nitrate and nitrite were measured using a Griess method.Compared with control specimens of CSF obtained from 16 patients with hemifacial spasm (n=8), trigeminal neuralgia (n=2), nonruptured aneurysm (n=5), or tremor (n=1), concentrations of NO metabolites in the CSF of 23 patients with moyamoya disease were significantly higher (18.6+1.1 vs. 11.0+1.0μM). NO metabolite concentrations (21.6+2.3μM) in CSF obtained during initial surgery in 7 resampled patients decreased to 16.9+1.5 μM in CSF obtained during a second, contralateral precedure. Angiographically early moyamoya disease tended to show lower concentrations of NO metabolites than cases of with greater development of moyamoya vessels.NO concentrations in CSF were chronically elevated in moyamoya disease, probably reflecting development of collateral circulation. Vascular bypass surgery can reduce NO metabolites together with abnormal collateral circulation.

Role of vascular endothelial growth factor in the response to vessel injury

In the post-embryonic life, physiological angiogenesis is tightly controlled. Angiogenesis also occurs in pathological circumstances such as tumor vessel proliferation, retinal neovascularization and ischemia. The development of collateral circulation is not only not deleterious, but life saving. Other cases such as neoplastic neovascularization are the basis of the continuous growth of tumors and metastases, and therefore constitute a target of therapeutical efforts. Among a list of molecules able to control angiogenesis, we emphasize the pivotal role of vascular endothelial growth factor (VEGF). VEGF is a potent mitogen for endothelial cells, but is devoid of mitogenic activity for other cell types. VEGF is a polypeptide with four main different isoforms that are remarkably different in terms of solubility and affinity for matrix proteins. VEGF interacts with two endothelial cell-specific tyrosine kinase receptors. The main interest of its study lies in VEGF's role in pathological angiogenic processes, where an increase in the VEGF mRNA expression has been consistently observed. An interesting example is the up-regulation of VEGF's and VEGF receptors' mRNA in a considerable number of human tumors and retina, where they have a critical role in the development of neovascularization. In recent work in our laboratory, we have found further potential interactions of VEGF with pathophysiological mechanisms, namely, the increase in VEGF gene expression under exposure to reactive oxygen species and the positive interaction between VEGF and erythropoietin. VEGF has outstanding possibilities for therapeutic applications aimed at inhibiting or favoring the development of new vessels.

Aortic foreign body resulting in ischemic neuromyopathy and development of collateral circulation in a cat

Ischemic neuromyopathy and paraplegia in cats are commonly associated with aortic thromboembolism. Occlusion of the abdominal aorta by a foreign body may also result in ischemic neuromyopathy and paraplegia; however, the prognosis for cats with paraplegia secondary to an aortic foreign body may be better than that for cats with paraplegia secondary to aortic thromboembolism. Collateral circulation may develop as a result of aortic occlusion by a foreign body. Progression of the collateral circulation may allow for clinical improvement without surgical intervention.

External Leg Compression in the Treatment of Vascular Disease

In summary, external compression of the limbs is a mode of therapy that has enjoyed a long history in the treatment of venous and arterial disease. Evidence suggests that its beneficial effects are mediated through enhancement of venous and arterial blood flow, promotion of vasodilation, enhancement of fibrinolysis, and, in the case of obstructive arterial disease, promotion of the development of collateral circulation. The utility of external leg compression in the prevention of deep venous thrombosis and in the management of chronic venous stasis disease has been well documented, and it has become an accepted treatment for these disorders. The use of pneumatic compression in the treatment of atherosclerotic peripheral vascular and cardiovascular disease is less widespread and its indications are less well defined. Though the work of a few investigators in each of these areas shows striking benefits of the technique, further investigation in these areas is warranted. Potential benefits to patients of external limb compression therapy include its non-invasive nature, its ability to be applied in an out-patient setting, and long-term cost savings through possible avoidance of hospitalization and invasive procedures.

Evaluation of Superficial Femoral Artery Compromise and Limb Growth Retardation After Transfemoral Artery Balloon Dilatations

Abnormalities of arterial pulse and limb growth after retrograde femoral arterial catheterization have been well documented. However, the magnitude of such complications after transfemoral artery balloon dilatation has not been thoroughly investigated. This study sought to evaluate the prevalence of these abnormalities in children who have undergone transfemoral artery balloon dilatation. Data on 43 consecutive patients (1 day to 15.5 years old at the time of balloon dilatation) seen on follow-up (42 +/- 23 months) (group 1) were compared with those of 35 patients undergoing retrograde femoral arterial catheterization (group 2) and 47 control patients. Interventional ankle/control ankle blood pressure index (AAI), ratio of interventional/control lower limb length (LLI), and leg length difference (LLD) were measured. Ages and weights at study were similar in all three groups, as were the ages and weights at intervention and duration of follow-up in groups 1 and 2. The AAI was lower (P = .023) in group 1 (0.95 +/- 0.13) than in groups 2 (1.0 +/- 0.1) and 3 (1.01 +/- 0.09). The prevalence of subjects with AAI < or = 0.9 was higher (P = .003) in group 1 than in the other two groups. The LLI and LLD were similar (P > .1) in all three groups. AAI and LLD in the balloon group are not significantly associated with age and weight at intervention, duration of follow-up, or size of the balloon or balloon catheter shaft. Transfemoral artery balloon dilatation procedures produce superficial femoral artery compromise, but there was no significant limb growth retardation at a 3.5-year mean follow-up, which may be related to development of collateral circulation. Study of a larger number of children at a longer follow-up interval may be necessary to further confirm these observations.

SLE and Sjögren's Syndrome Associated with Unilateral Moyamoya Vessels in Cerebral Arteries

Moyamoya disease is a rare clinical entity, diagnosed by cerebral angiography and characterized by occlusion of the internal carotid artery system and the development of collateral arteries. A 30-year-old woman with systemic lupus erythematosus and Sjogren's syndrome recurrently presented transient right homonymous hemianopsia. Cerebral angiography showed occlusion of the left posterior cerebral artery associated with the development of collateral circulation (“moyamoya vessels”). In a young adult, as in this case, the unilaterality of the lesion and the presentation of transient ischemic attacks rather than subarachnoid hemorrhage are rare features for Moyamoya disease. Antiphospholipid syndrome was absent.

The Influence of Morphological Characteristics of lesions on the Development of Collateral Circulation in Angina Pectoris

Background:It is well known that collateral circulation has important roles in ischemic heart di- sease. It reduce ventricular remodeling and infarct size to improve ventricular function and survival. Extents and duration of ischemia are critical stimulants of the development of coronary collaterla circulation. We hypothesize that collateral circulation is poor in patients with lesions at branching points because atherosclerosis progress more rapidly not to allow the collateral circulation to develop. Method:We studied total 330 coronary angiography, which have more than 50% stenosis in any coronary artery, normal left ventriculography and no history of myocardial infarction. In each coro- nary angiography, severity, site, proximity, length of lesions were analyzed, classified, and collaterale circulation was graded. We also observed whether the lesions involve branching points or not. Results:While coronary collateral circulation developed well when stenosis was more than 90% in the severity, it was poor when the lesions involve branching points. Collateral circulation tended to be poor in case of eccentric lesions, but it was statistically insignificant. The above findings support our hypothesis of the accelerated atherosclerosis at branching points. Conclusions:The facts that the development of coronary collaterals is poor with lesions in- volving branching points suggest that atherosclerosis is accelerated at these lesions that is chara- cterized by blood stasis, turbulence and lower arterial wall tension.

The role of venous outflow obstruction in patients with chronic venous dysfunction.

To quantify the functional venous outflow obstruction with different location and extent of obstruction attributed to previous deep vein thrombosis. Case-control study. Vascular Laboratory, St Mary's Hospital Medical School, London, England. Two groups: group 1, 25 case patients and 9 control subjects, and group 2, 45 case patients and 30 control subjects. Ascending venography, duplex scanning, air plethysmography, and venous pressure measurements in the foot and the arm via a 21-gauge butterfly needle. Venous outflow fraction (VOF), venous outflow resistance (VOR), and arm-foot pressure differential (A-F PD) at rest and after reactive hyperemia. Venous outflow resistance was evaluated in group 1. Twenty-two case patients underwent VOF testing, and 16 had A-F PD measurement performed. Case patients in group 2 underwent VOF testing. Signs and symptoms of chronic venous dysfunction were associated with the anatomical extent of obstruction. Limb swelling and ache were present in most of the patients; skin changes were noted in about 30% and ulceration in 10% of patients. The results of all tests showed no evidence of obstruction in control subjects. In most case patients with popliteal vein obstruction, test results were similar to those in control subjects: the more proximal the veins involved, the more severe the obstruction. In 16 case patients, all 3 tests were performed and agreement between A-F PD and VOR test results was found in 14 of them. The VOF test results agreed with the results of A-F PD and VOR tests in 9 case patients. In group 2, 50% of the limbs with obstruction proximal to the popliteal vein had a reduced VOF, which became worst in the limbs with extensive obstruction, particularly when the iliac veins were involved. Of the 73 limbs tested for VOF in both groups, only 7 limbs (9.6%) had their venous outflow markedly reduced by occlusion of the superficial veins. The anatomical extent of venous obstruction and the development of collateral circulation determine the hemodynamic severity of the chronic venous obstruction. The deep collaterals seem to be more important than the superficial venous system in bypassing the obstruction. The VOR and the A-F PD tests can be used to identify those patients who have venous obstruction, whereas the use of the VOF test may reduce the need for performing the above tests in 50% of the patients.

Evaluation of coronary collateral circulation in early ischemia in rat hearts. A morphological study.

Histological changes were examined in the left ventricular free wall of the heart in 40 rats after ligation of the distal anterior descending coronary artery for 15, 30 minutes and 1, 2, 3, 4, 5, 6 hours. Auto-injection of tracers for light microscopy was used to examine the development of collateral circulation. Morphological changes of the ischemic myocardium were observed by PAS staining and transmission electron microscopy. Fifteen minutes after coronary occlusion, the dye was observed in the vein of the ischemic zone; however, 30 minutes after coronary occlusion, the dye appeared in the capillaries of the outer-third layer. These findings suggested that the collateral circulation becomes functional between 15 and 30 minutes after coronary occlusion. Collateral circulation increased gradually in the capillaries of the ischemic zone. Thirty minutes after coronary occlusion the dye was seen only in the outer-third layer of the ventricular ischemic zone. One hour after occlusion, the dye appeared in the superficial space and the middle-third layer. Three hours after occlusion, the dye was seen in all layers of the ischemic zone. The dye appeared in the ischemic zone, where myocardium damage was not homogeneous. The positive reaction obtained by PAS staining corresponded with the capillaries, veins and superficial spaces in which the dye was evident. These results suggest that collateral circulation, verural back flow and superficial space flow are able to prevent myocardial infarction in early ischemia.

Pial Synangiosis for Treatment of Moyamoya Syndrome in Children

Moyamoya syndrome is a chronic cerebrovascular disorder that is characterized by a progressive narrowing of the intracranial internal carotid arteries and their main branches and a compensatory dilation of smaller arteries (ie, moyamoya vessels) at the base of the brain. Common signs and symptoms in children include recurrent episodes of cerebral ischemia, transient hemiparesis, seizures, and cerebrovascular accidents (CVAs). The diagnosis is made primarily by cerebral angiography, and surgical treatment consists of pial synangiosis, whereby surgeons suture the superficial temporal artery to the pla mater under microscopic visualization. The goal of surgical intervention is to promote the development of collateral circulation to the brain and decrease the risk of CVAs, transient ischemic attacks, and seizures. Follow-up angiography demonstrates that pial synangiosis results in excellent postoperative collaterization of ischemic areas of the brain.

Collateral vessels assessed by myocardial contrast echocardiography in patients with coronary artery lesions after Kawasaki disease.

Using myocardial contrast echocardiography (MCE), coronary arteriography, and thallium-201 myocardial imaging (TMI), we examined the characteristics and the role of collateral vessels in 35 patients with coronary artery lesions after Kawasaki disease. The male/female ratio was 25:10. The patients' ages are examination ranged from 1.0 to 20.3 years (mean, 10.8 years). The age at onset of Kawasaki disease ranged from 0.3 to 11.6 years (mean, 2.6 years). The coronary artery lesions were: dilated lesions without coexistent stenotic lesions in 5 patients (14%), localized stenosis with less than 50% narrowing in 5 patients (14%), localized stenosis with 50% or more narrowing in 4 patients (11%), and obstructive lesions, such as occlusion and/or segmental stenosis, in 21 patients (60%). In the group with no stenotic lesions and the group with less than 50% localized stenosis, the perfusion area of the right coronary artery was 32.6 +/- 8.4% and that of the left coronary artery was 76.3 +/- 7.9%. The total perfusion area of the right and the left coronary arteries was 108.9 +/- 2.6%, which value was inversely correlated with age at examination (r = 0.716, P = 0.020). In the group more than 50% localized stenosis, an increase in overlap areas detected by MCE, where a perfusion defect was seen on TMI, was not found, except in 1 patient with 99% stenosis. In the patients with obstructive lesions development of collateral channels was better in the perfusion area of the occluded right coronary artery than in that of the occluded left coronary artery, and well developed collateral channels were significantly correlated with good wall motion. We conclude that overlapping perfusion occurs in younger rather than in older children without stenotic coronary systems, and this may contribute to the food development of collateral circulation in infants and young children with coronary artery lesions after Kawasaki disease.

Relation between preexistent coronary collateral circulation and the incidence of restenosis after successful primary coronary angioplasty for acute myocardial infarction

Objectives.The purpose of this study was to test the hypothesis that the incidence of restenosis after primary percutaneous transluminal coronary angioplasty for acute myocardial infarction is largely influenced by the preexistent coronary collateral circulation to the infarct-related coronary artery.Background.The occurrence of restenosis after coronary angioplasty is the most limitation of this procedure. However, prediction of restenosis is difficult. Severe preexistent stenosis of the infarct-related coronary artery causing the development of collateral circulation may result in a high frequency of restenosis.Methods.The study group consisted of 152 consecutive patients undergoing primary coronary angioplasty within 12 h after the onset of a first acute myocardial infarction. Of this group, 124 patients were angiographically followed up during the convalescent period of infarction and were classified into two groups according to the extent of preexistent collateral circulation to the infarct-related coronary artery.Results.Restenosis occurred in 26 (38%) of 69 patients with poor or no collateral circulation (group A) in contrast to 35 (64%) of 55 patients with good angiographic collateral circulation (group B, p < 0.005). The frequency of preinfarction angina was significantly lower (p < 0.05) in group A (26% [18 of 60]) than in group B (44% [24 of 55]).Conclusions.These findings indicate that the presence of well developed collateral circulation to the infarct-related coronary artery predicts a higher frequency of restenosis after primary coronary angioplasty. The difference in restenosis rates observed between the patients with and without good collateral circulation probably reflects the impact of underlying severity of stenosis on the long-term outcome after coronary angioplasty.

Indirect revascularization for moyamoya disease: Is there a beneficial effect for adult patients?

It is generally accepted that excellent development of collateral circulation can be achieved through indirect nonanastomotic bypass procedures for pediatric patients with moyamoya disease. However, there are no definitive conclusions about the effect of indirect revascularization for adult patients. To clarify the value of indirect bypass surgery for adult moyamoya disease, we have analyzed their follow-up angiographic results in comparison with those of the pediatric patients. Between 1989 and 1993, 23 patients underwent combined direct and indirect bypass surgery. They consisted of 16 adults (mean age, 35; range, 20-59) and seven children (mean age, 10; range, 3-16). The main symptoms were those due to cerebral ischemia in all but 1 of 23 patients. Preoperative cerebral blood flow studies showed all patients to have decreased vascular reserve (misery perfusion). Postoperative follow-up angiography was done in all patients at a median of 6 months after the surgery. All pediatric patients showed good or moderate development of collaterals through the indirect bypass. Among the adult group, seven patients aged 20 to 29 had angiographic results similar to those of the pediatric group . On the other hand, nine patients older than 30 had results contrary to those of pediatric patients: (1) the degree of indirect revascularization declined to moderate or poor grades (especially in patients older than 40) and (2) the degree of direct bypass filling improved to high or medium grades. The results suggest that advancing age apparently affects the development of collateral formation through the indirect bypass. Consequently, direct bypass is thought to be the main treatment option for patients older than 40.

Portal‐systemic shunting in a patient with normal portal vein pressures and histological evidence of idiopathic portal hypertension

Although idiopathic portal hypertension (IPH) is clinically characterized by portal hypertension and marked splenomegaly, we have experienced a case of spontaneous portal-systemic shunt without splenomegaly in whom the liver histology resembled IPH but with normal portal pressure. We admitted a 64 year old man who had suffered from hepatic encephalopathy for 2 years. Laparoscopy revealed a dark grey liver with a sharp edge and a concave surface. Examination of a liver biopsy specimen revealed peri-portal fibrosis consistent with IPH. A single, large, portal-systemic shunt was identified by percutaneous transhepatic portography. The shunt arose from the left gastric vein and flowed through the left renal vein into the inferior vena cava. No varices were identified. There were no morphological changes in the hepatic or portal veins. Portal vain pressure was normal. There was a slight difference between the portal pressure and the wedged hepatic vein pressure, suggesting a presinusoidal block. This case raises important questions concerning the aetiology of IPH and the relationship between portal hypertension and the development of collateral venous circulation.

Postnatal growth of the heart and its blood vessels.

Although rapid growth of the heart during early postnatal development ceases with maturation of the organism, the potential for cardiomyocyte growth is not lost and may be observed even in senescent hearts. Rapid developmental heart growth is accompanied by a proportional growth of capillaries but not always of larger vessels, and thus coronary vascular resistance gradually increases. Growth of adult hearts can be enhanced by thyroid hormones, catecholamines and the renin-angiotensin system hormones, but these do not always stimulate growth of coronary vessels. Likewise, chronic exposure to hypoxia leads to growth, mainly of the right ventricle and its vessels but without vascular growth elsewhere in the heart. On the other hand, ischaemia is a potent stimulus for the release of various growth factors involved in the development of collateral circulation. Heart hypertrophy develops in response to training, pressure or volume overload. Training usually leads to growth of larger coronary vessels but little growth of capillaries, except in young animals. However, growth of the capillary bed, but not the resistance vasculature capacity, can be induced by either increased coronary blood flow, bradycardia (electrically or pharmacologically induced) or increased inotropism, all of which are involved in the training stimulus. Thus, what actually promotes growth of larger vessels as opposed to capillaries in training is unclear. Pressure overload hypertrophy is mediated by both the renin-angiotensin system and the response of cardiomyocytes to stretch; both lead to activation of early oncogenes (c-fos, c-jun, c-myc) and angiotensin II activates several protein kinases involved in cell growth. In this condition, growth of larger vessels is inadequate, although some capillary growth may occur. Volume overload leads to cardiomyocyte hypertrophy and hyperplasia and some increase in vascular supply. Deficits in capillary supply in pressure or volume overload hypertrophy can be reversed by chronic administration of ACE inhibitors, dipyridamole, the bradycardic drug alinidine or pacing-induced bradycardia respectively, but in neither case is training effective. Mechanical and humoral factors are involved in growth of cardiomyocytes and vessels. For cardiomyocytes, stretch is most important, activating oncogenes, protein kinases and possibly the inositol phosphate pathway, but not ion channels, with regulation by the balance of angiotensin II, TGF-beta 1 and IGF-1, but not FGFs. For vessels, growth is stimulated by stretch and shear stress, possibly with involvement of VEGF. Increased shear stress disrupts the glycocalyx on the luminal side of vessels and releases plasminogen activator and metalloproteinases which disrupt the basement membrane and enable endothelial cell migration and proliferation. It also causes rearrangement of the endothelial cytoskeleton and transmission of mechanical signals to the abluminal side disturbing extracellular matrix and causing distortion of capillary basement membrane. Stretch acting from the abluminal side has a similar effect resulting also in basement membrane disruption and endothelial cell proliferation.