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PubMed1981

Effects of calcium and its antagonists on the canine mesenteric circulation.

We studied circulatory and metabolic responses of the intestinal circulation to intraarterial infusions of solutions containing calcium chloride or calcium antagonists in anesthetized dogs. Measurements included blood flow to the terminal ileum, arteriovenous oxygen content difference, distribution of radiolabeled microspheres to the mucosal-submucosal compartment and intraluminal pressure. Calculated parameters included oxygen consumption and fractional mucosal-submucosal blood flow. Both calcium antagonists, nifedipine and diltiazem, increased intestinal blood flow, mainly to the mucosa-submucosa, depressed intestinal motility, and did not change oxygen consumption. Thus, both agents appear to act mainly on resistance vessels without increasing the nutrient circulation. Calcium chloride (1.0-500.0 microgram/kg per min) had a mild constrictor effect; at a dose of 1000.0 microgram/kg per min, calcium chloride became a dilator agent in the mesenteric circulation. The dilator effect of the highest dose of calcium was reversed by digoxin, suggesting the involvement of Na+,K+-ATPase. Nifedipine completely blocked calcium-induced constriction of the intestinal circulation and partly inhibited norepinephrine-induced constriction. Studies on isolated mesenteric arterial smooth muscle revealed that nifedipine relaxed KCl-contracted strips in the presence of external calcium and relaxed norepinephrine-contracted strips in both the presence and absence of external calcium. These in vitro findings suggest that calcium antagonists interfere with the release of calcium from intracellular sites as well as with the slow inward current of calcium.

Animals↗
PubMed1986

Adrenergic coronary tone during submaximal exercise in the dog is produced by circulating catecholamines. Evidence for adrenergic denervation supersensitivity in the myocardium but not in coronary vessels.

The goal of this study was to test the hypothesis that circulating catecholamines are primarily responsible for alpha-adrenergic coronary vasoconstriction during submaximal exercise. The experimental series consisted of chronic studies in which a regional left ventricular sympathectomy was performed with phenol. Myocardial perfusion to the innervated and sympathectomized left ventricular regions was measured in these animals during (1) a control period, (2) treadmill exercise, (3) exercise during beta-adrenergic blockade, and (4) exercise during combined alpha- + beta-adrenergic blockade. We found no differences in myocardial perfusion between the innervated and sympathectomized regions or the transmural distribution of perfusion during any of these interventions. Thus, there is no evidence for neurogenic alpha-adrenergic coronary vasoconstriction. However, during exercise in the presence of alpha- and beta-blockade, coronary resistance (mmHg X min X 100 g/ml) was significantly less in both the innervated (0.65 +/- 0.07) and sympathectomized (0.68 +/- 0.07) regions than during beta-blockade, 0.90 +/- 0.17 and 0.89 +/- 0.16, respectively. This suggests that coronary alpha-adrenergic constriction was produced by circulating catecholamines. This concept of humorally mediated, alpha-adrenergic coronary vasoconstriction was strengthened by in vivo and in vitro studies that demonstrated that alpha-adrenergic supersensitivity of the coronary vasculature was not present. Myocardial beta-adrenergic supersensitivity was observed in the phenol regional sympathectomy model; however, this effect was blocked by propranolol (1 mg/kg). This indicates that alpha-adrenergic vasoconstriction in both myocardial regions during submaximal exercise is produced by circulating catecholamines. The major conclusion of this study is that, during submaximal exercise in the canine, alpha-adrenergic coronary vasoconstrictor tone is predominantly due to circulating catecholamines rather than direct neural effects.

Animals↗
PubMed1987

Mechanism of attenuated pressure-flow autoregulation in right coronary circulation of dogs.

Right coronary autoregulation was assessed in 14 open-chest, anesthetized dogs. In Group 1 (n = 5), the left common and right coronary arteries were cannulated and perfused independently. As coronary perfusion pressures varied simultaneously between 70 and 120 mm Hg, right coronary blood flow changed by 48%, whereas left coronary flow changed by 13%. In this pressure range, the autoregulatory closed-loop gain of the right coronary circulation averaged 0.37 +/- 0.01, reflecting a modest autoregulatory capability but significantly less than that of the left coronary circulation, 0.78 +/- 0.08. In Group 2 (n = 9), only the right coronary artery was perfused, and right coronary venous blood was collected for determining arteriovenous oxygen extraction. Autoregulatory gain was similar to that of Group 1, indicating that collateral flow associated with intercoronary pressure gradients does not mask right coronary autoregulation. Right ventricular myocardial oxygen consumption varied directly with perfusion pressure, ranging from 7.1 +/- 1.0 to 2.9 +/- 0.8 ml O2/min/100 g as pressure was reduced from 160 to 40 mm Hg. Thus, right coronary autoregulation is masked by an opposing change in oxygen demand. When right ventricular oxygen consumption was altered by pacing, a linear flow-oxygen consumption relationship was observed (8.2 +/- 0.4 ml/min/100 g per ml O2/min/100 g). Subtraction of flows associated with pressure-induced changes in metabolism revealed a potential autoregulatory capability of the right coronary circulation similar to that manifested by the left coronary circulation.

Animals↗
PubMed1993

Tissue factor is expressed on monocytes during simulated extracorporeal circulation.

Certain forms of extracorporeal circulation exemplified by cardiopulmonary bypass require continuous high-dose anticoagulation to prevent thromboembolic complications. We hypothesized that monocytes may be stimulated to express tissue factor (TF) during prolonged simulated extracorporeal circulation. TF was identified both by flow cytometry by using three TF-specific monoclonal antibodies and functional assay of procoagulant activity (PCA). TF significantly increased between 2 and 6 hours of simulated extracorporeal circulation by both analyses. Relative fluorescence on monocytes increased from a control value of 100 to 313 +/- 79 on cells from the simulated extracorporeal circuit (p < 0.05). PCA increased from 21 +/- 8 to 775 +/- 326 pg TF/10(6) monocytes (p < 0.05) and was blocked 99.6% by preincubation of cells with a mixture of monoclonal antibodies to TF. By 6 hours, the number of leukocytes in the circuit was decreased by 43%. The cells were recovered from the oxygenator membrane by washing with EDTA. Compared with initial values, by 6 hours, both TF antigen at 378 +/- 90 (p < 0.05) and PCA at 1,357 +/- 280 pg TF/10(6) monocytes (p < 0.01) were highest in the recovered cells. Cells incubated for 6 hours and not subjected to simulated extracorporeal circulation did not increase TF. Examination of monocytes for the adhesive receptor CD11b/18 (Mac-1) paralleled TF expression, providing an additional putative receptor for the coagulant proteins, factor X and fibrinogen or fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed2002

Dissecting aneurysms of intracranial carotid circulation.

BACKGROUND AND PURPOSE: Clinical features of nontraumatic dissecting aneurysms of intracranial carotid circulation remain unclear because investigation of this disease has been limited to case reports. The aim of this study was to investigate the clinical features of this disease through the use of cooperatively collected cases. METHODS: The cases diagnosed as dissecting aneurysms of intracranial carotid circulation on the basis of clinical signs and neuroradiological findings in 46 stroke centers from 1995 through 1999 were collected, and their clinical features were analyzed. RESULTS: Forty-nine cases of dissecting aneurysms of intracranial carotid circulation were collected. Thirty-two patients presented with subarachnoid hemorrhage (SAH), and 17 presented with cerebral ischemia. The ratio of this disease to all intracranial dissecting aneurysms treated in the same institutes for the same period was 19.1%, and the ratio of SAH resulting from this disease to SAH of unverified origin treated in the same institutes for the same period was 6.2%. The predominant site of lesion was the internal carotid artery in 18 of 32 patients (56%) with SAH and the anterior cerebral artery in 13 of 17 patients (76%) with cerebral ischemia. The predominant angiographic findings were that stenosis with dilatation occurred in 20 of 32 patients (63%) with SAH and stenosis without dilatation was seen in 11 of 17 patients (65%) with cerebral ischemia. Poor prognosis was seen in 21 of 32 patients (66%) with SAH, which was due largely to rebleeding seen preoperatively, during operation, and even postoperatively when clipping or wrapping of the aneurysmal bulge was performed. CONCLUSIONS: Nontraumatic dissecting aneurysm of intracranial carotid circulation is not as rare as expected. It seems to be one of the important causes of SAH of unverified origin.

Adolescent↗
PubMed2002

Guglielmi detachable coil embolization of posterior circulation aneurysms: a systematic review of the literature.

BACKGROUND: Early multicenter trials of Guglielmi detachable coil embolization of posterior circulations aneurysms have been followed by the publication of numerous single-center experiences. Summary of Review- We performed a MEDLINE literature search and extracted data from single-center reports containing at least 10 posterior circulation aneurysms. Twelve reports (495 aneurysms) were specific to the posterior circulation. Eighty-two percent of aneurysms arose near the basilar apex. Eighty-one percent of patients harbored unruptured aneurysms or presented in good clinical condition. Sixty-three percent of lesions were small, and 41% exhibited a narrow neck. Coil deposition was achieved in 97.6% of cases. Procedural complication and morbidity rates were 12.5% and 5.1%, respectively. Procedural and 30-day mortality rates were 1.4% and 6.7%, respectively. Complete aneurysm occlusion was achieved in 47.6%, near-complete occlusion (90% to 99%) in 43.4%, and incomplete occlusion in 9.0% of cases. There were a total of 52 recurrences (22.2%) in a subset of 234 evaluable patients. Ninety-two percent of these aneurysms exhibited wide necks. The annual risk of subarachnoid hemorrhage after embolization was 0.8%. Eighty-five percent of patients achieved functional independence, while only 5.3% lived dependent lifestyles. The overall mortality rate was 9.8%. CONCLUSIONS: The published literature approximates a large series of basilar apex aneurysms. Embolization is moderately effective in completely excluding an aneurysm from the posterior circulation. The incidence of recurrence in wide-neck aneurysms and incompletely coiled aneurysms is substantial. Coil embolization is effective in preventing early rebleeding. Its role in the treatment of unruptured aneurysms remains unclear.

Cerebrovascular Circulation↗
PubMed1975

Gas exchange in the pulmonary collateral circulation of dogs. Effects of alveolar hypoxia and systemic hypoxemia.

The left main pulmonary artery was ligated in 7 fully grown dogs. This resulted in an enlarged pulmonary collateral (systemic) flow to the left lung. By collecting gas from each lung separately, gas exchange in the pulmonary collateral circulation was studied and compared to that in the normal contralateral side. Studies were done repeatedly during a period of 3 years. Compared to that in the preoperative period, the ligated (left) side showed a decrease in ventilation (42.5 to 34.5 per cent of total), a marked increase in wasted ventilation (0.30 to 0.55), and a marked decrease in O2 uptake (45 to 11.2 per cent of total) and CO2 production (27.5 to 15.3 per cent of the total). There were no changes in arterial blood gases or pH. A significant, sustained, systemic hypertension was noted in all dogs in which the left main pulmonary artery was ligated (190/120). The mean blood flow through the pulmonary collateral circulation of the left lung with the dogs breathing room air was estimated to be 94 ml per min. When the dogs were made hypoxemic by breathing 12 per cent O2 through the normal right lung, there was a marked increase in pulmonary collateral (systemic) flow to the contralateral side (194 ml per min). This resulted in an increase in O2 consumption (29.4 per cent of total) and CO2 production (23.1 per cent of total) of the left lung. When the dogs were given 12 per cent O2 to breathe through the ligated left lung, there was no change in arterial PO2. There was a significant increase in blood flow through the pulmonary collateral circulation to 136 ml per min. Because of the gradient of O2 between the blood flowing into the left lung and that present in the alveoli, there was a net production of O2 from the left lung of 4.5 ml per min. When the pulmonary systemic circulation participates in gas exchange, it appears to increase during hypoxemia as well as during alveolar hypoxia.

Animals↗
PubMed1983

Description and simulation of a physiological pharmacokinetic model for the metabolism and enterohepatic circulation of bile acids in man. Cholic acid in healthy man.

A multicompartmental pharmacokinetic model based on physiological principles, experimental data, and the standard mathematical principles of compartmental analysis has been constructed that fully describes the metabolism and enterohepatic cycling in man of cholic acid, a major bile acid. The model features compartments and linear transfer coefficients. The compartments are aggregated into nine spaces based on physiological considerations (liver, gallbladder, bile ducts, jejunum, ileum, colon, portal blood sinusoidal blood, and general circulation). The transfer coefficients are also categorized according to function: flow, i.e., emptying of gallbladder or intestinal spaces, and circulation of the blood; biotransformation, i.e., conjugation, deconjugation, or dehydroxylation; and transport, i.e., active or passive transport. The model is made time dependent by introducing meals, which trigger discrete increases in gallbladder emptying and intestinal flow. Each space contains three compartments. For cholic acid, these are unconjugated cholic acid, cholylglycine, and cholyltaurine. The model was then used with all existing experimental data to simulate cholic acid metabolism in healthy man over a 24-h period. Satisfactory agreement was obtained between simulated and experimental results for serum bile acid levels, hepatic bile acid secretion, and bile acid secretion into the intestine. The model was also used to classify 16 clinical instances in which the enterohepatic circulation of bile acids is altered by drugs or disease. The model can be extended to describe completely the metabolism and enterohepatic circulation of any bile acids in man in health and digestive disease. The model should also be broadly applicable to the description of the pharmacokinetics of all other drugs whose metabolism is similar to that of bile acids, i.e., drugs for which there are tissue and bacterial biotransformations, enterohepatic cycling, and appreciable first-pass clearance.

Bile Acids and Salts↗
PubMed1985

Vascular headaches and cerebral circulation: an overview.

A complex network of neurotransmission systems underlies the control of the cerebral circulation. Classical neurotransmitters, vasoactive peptides and receptors have been found in cerebral arteries. Central and peripheral structures are also probably involved in the neurogenic control of the cerebral circulation. Vascular and neurotransmission changes reported in vascular headaches suggest that an alteration of the neurogenic control of the brain circulation may be implicated in vascular headaches. In particular, locus coeruleus, which may control the intracerebral adrenergic pathway, can induce vascular changes similar to those of migraine. Moreover, the trigeminal ganglion, which may induce the release of substance P, can change the extracranial and intracranial vasodilator activity. The vascular theory of migraine, proposed by Wolff, is re-evaluated on the grounds of a possible mediation of the vascular responses by neurotransmitters. It is hypothesized that a deficient modulation by enkephalins may cause alterations of locus coeruleus and/or trigeminal ganglion. The problem of pain in vascular headaches is also considered: whether it is of vascular origin or whether it is due to a dysfunction of the central nociceptive pathway. Knowledge of the neurogenic control of the cerebral circulation may be useful in understanding some pathogenetic mechanisms of vascular headaches.

Acetylcholine↗
PubMed2002

Circulation is established in a stepwise pattern in the mammalian embryo.

To better understand the relationship between the embryonic hematopoietic and vascular systems, we investigated the establishment of circulation in mouse embryos by examining the redistribution of yolk sac-derived primitive erythroblasts and definitive hematopoietic progenitors. Our studies revealed that small numbers of erythroblasts first enter the embryo proper at 4 to 8 somite pairs (sp) (embryonic day 8.25 [E8.25]), concomitant with the proposed onset of cardiac function. Hours later (E8.5), most red cells remained in the yolk sac. Although the number of red cells expanded rapidly in the embryo proper, a steady state of approximately 40% red cells was not reached until 26 to 30 sp (E10). Additionally, erythroblasts were unevenly distributed within the embryo's vasculature before 35 sp. These data suggest that fully functional circulation is established after E10. This timing correlated with vascular remodeling, suggesting that vessel arborization, smooth muscle recruitment, or both are required. We also examined the distribution of committed hematopoietic progenitors during early embryogenesis. Before E8.0, all progenitors were found in the yolk sac. When normalized to circulating erythroblasts, there was a significant enrichment (20- to 5-fold) of progenitors in the yolk sac compared with the embryo proper from E9.5 to E10.5. These results indicated that the yolk sac vascular network remains a site of progenitor production and preferential adhesion even as the fetal liver becomes a hematopoietic organ. We conclude that a functional vascular system develops gradually and that specialized vascular-hematopoietic environments exist after circulation becomes fully established.

Animals↗
PubMed2006

Recent translational research: circulating tumor cells in breast cancer patients.

In breast cancer patients, hematogenous tumor cell dissemination can be detected, even at the single cell level, by applying immunocytochemical and molecular assays. Various methods for the detection of circulating tumor cells in the peripheral blood have been described. Results from recently reported studies suggest that circulating tumor cell levels may serve as a prognostic marker and for the early assessment of therapeutic response in patients with metastatic breast cancer. However, in early-stage breast cancer, the impact of circulating tumor cells is less well established than the presence of disseminated tumor cells in bone marrow; several clinical studies have demonstrated that cells of the latter type are an independent prognostic factor at primary diagnosis. In this article we briefly summarize recent studies examining the presence of circulating tumor cells in the blood and discuss further clinical applications.

Breast Neoplasms↗
PubMed1996

Detection of circulating neoplastic cells by reverse-transcriptase polymerase chain reaction in malignant melanoma: association with clinical stage and prognosis.

PURPOSE: Circulating melanoma cells can be detected in peripheral blood by means of tyrosinase mRNA amplification by reverse-transcriptase polymerase chain reaction (RT-PCR). We conducted a prospective study to evaluate the clinical significance of the presence of circulating neoplastic cells in the blood of patients with malignant melanoma (MM). METHODS: A sensitive RT-PCR assay was used to detect tyrosinase mRNA in the peripheral blood of patients with stages I to IV melanoma. Healthy subjects or patients with other malignancies were used as negative controls. RESULTS: Ninety-one assessable patients were included in the study. There was a statistically significant association between RT-PCR positivity and clinical stage. Circulating melanoma cells were detected in 36% of patients with localized disease (stages I and II), in 45% of patients with regional nodal involvement (stage III), and in 94% of patients with metastatic disease (stage IV) (P < .001). In stage II-III patients who were RT-PCR-positive for mRNA tyrosinase in blood, the recurrence rate and disease-free survival were significantly worse than patients who were RT-PCR-negative. In multivariate analysis, RT-PCR was an independent prognostic factor for recurrence in patients with nonmetastatic disease (P = .002). CONCLUSION: The detection of circulating melanoma cells in peripheral blood by RT-PCR correlated with the clinical stage of patients with melanoma and was an independent prognostic factor for recurrence. Further studies are warranted to better assess the significance of this test in the evaluation of prognosis, early detection of relapse, and in monitoring the effectiveness of systemic therapy.

Adult↗
PubMed2004

Enhanced iNOS expression in leukocytes and circulating endothelial cells is associated with the progression of coronary artery lesions in acute Kawasaki disease.

Nitric oxide (NO) serves many vasoprotective roles, but the massive release of NO causes arterial wall degeneration. We investigated whether enhanced nitric oxide synthase (iNOS) expression in peripheral blood leukocytes and circulating endothelial cells mirrors the progression of coronary arterial lesions in 55 children with acute Kawasaki disease (KD), including 24 with and 31 without coronary artery lesions (CAL). Patients were treated with i.v. gamma-globulin at the time of diagnosis and blood samples were collected before and after treatment. The cellular origin of NO synthesis was determined by flow cytometric analysis of iNOS expression in peripheral blood, and by immunohistochemical analysis of circulating endothelial cells and coronary arteries. iNOS expression in neutrophils peaked at the time of diagnosis, but did not peak in monocytes until 2 wk post onset of disease. Levels were significantly higher in both cell types in patients with CAL (p = 0.001 and p = 0.035, respectively). In addition, the number of circulating endothelial cells and levels of iNOS expression were higher in patients with CAL (p = 0.011 and p = 0.012, respectively). Immunohistochemical analysis of the coronary arteries from three patients with acute KD revealed iNOS immunoreactivity in endothelial cells, as well as infiltrating monocytes/macrophages in the aneurysms. We conclude that the expression of iNOS in peripheral blood leukocytes, as well as circulating endothelial cells, correlates with the severity of coronary arterial wall injury and the progression of CAL in patients with acute KD.

Arteries↗
PubMed2005

Effect of lung hypoplasia on birth-related changes in the pulmonary circulation in sheep.

Lung hypoplasia (LH) is a serious cause of neonatal compromise, but little is known of its functional effects on the pulmonary circulation. Our aim was to characterize birth-related changes in the pulmonary circulation of newborn lambs with LH and to compare them with alterations in respiratory function. LH was induced in six ovine fetuses by the creation of a tracheo-amniotic shunt as well as amniotic fluid drainage starting at 105.6+/-1.5 (mean+/-SEM) days of gestation (term approximately 147 d). At 139.9+/-0.3 d, fetuses were exteriorized under anesthesia to implant vascular catheters and an ultrasonic flow probe around the left pulmonary artery. The lambs then were delivered and ventilated for 2 h, during which systemic and pulmonary artery pressures, left pulmonary blood flow, and measures of respiratory function were recorded. At autopsy, lungs were weighed and volume was measured at 20 cm H2O. In LH lambs, lung weight was 25% lower and respiratory system compliance was 30% lower than in controls. Mean pulmonary blood flow in LH lambs was 42% lower and pulmonary vascular resistance was 138% higher than in controls. Morphometry showed that volume density of pulmonary arteries in LH was 30% lower than in controls. We conclude that, in this LH model, changes in ventilatory indices were proportional to the change in lung size, whereas changes in the pulmonary circulation were greater than the change in lung size and were associated with reduced density of pulmonary arteries. LH severely impairs normal adaptation of the pulmonary circulation in the perinatal period.

Animals↗
PubMed2004

Bypass grafting and revascularization in the management of posterior circulation aneurysms.

OBJECTIVE: To describe the bypass techniques, cranial base approaches, results of treatment, causes of failure, and lessons that are learned in patients with posterior circulation aneurysms requiring revascularization. METHODS: Retrospectively, 19 patients with posterior fossa aneurysms requiring revascularization procedures operated on between 1991 and 2002 were reviewed. Preoperative and postoperative clinical information, neurological examinations, imaging data, and updated follow-ups were reviewed. Patient outcome is reported as the most current Karnofsky Performance Scale score. RESULTS: A total of 22 arterial bypasses were performed in 19 patients for posterior fossa circulation aneurysms between 1991 and 2002. The mean follow-up was 41 months. Total graft patency rate (including patients requiring reoperation) was 86.4% (before) and 100% (after) salvage procedures. Patient outcome was 84.2% with Karnofsky Performance Scale score 80 to 90, and three deaths occurred perioperatively. Only one death could be attributed to the failure of the radial artery graft because of spasm and subsequent rupture during angioplasty. CONCLUSION: Certain graft selection criteria and technical considerations contribute to the success or failure of bypass grafts in the management of posterior circulation aneurysms. Bypass procedures remain an important method of management of complex posterior circulation aneurysms, in addition to endovascular procedures.

Adolescent↗
PubMed2005

Color Doppler sonographic evaluation of collateral circulation in patients with cerebral aneurysms and the occlusion of the brachiocephalic vessels.

OBJECTIVE: The objective of this study was to assess the collateral circulation and blood flow velocity in arteries forming collateral circulation in patients with cerebral aneurysms and the occlusion of the brachiocephalic vessels. METHODS: Between 1989 and 2004 we examined a group of seven consecutive patients with diagnosed cerebral aneurysm and occlusion of the extracranial artery by means of cerebral angiography, transcranial color-coded sonography (TCCS) and color Doppler sonography of extracranial arteries. The Doppler examination results achieved in this group were compared with the Doppler results of 40 healthy subjects from a control group. RESULTS: Three patients were diagnosed with an occluded innominate artery. In four other cases an occlusion of the extracranial segment of the internal carotid artery was found. The aneurysms were located on intracranial arteries of collateral flow. The innominate artery occlusion resulted in a hemodynamic effect which was a complete vertebral steal and systolic deceleration (in one case) or alternating flow (in two cases) in the right common carotid artery. An additional route of collateral circulation in all these cases led from extracranial carotid branches through the right external carotid artery to the ipsilateral internal carotid artery. In all seven patients, 13 intracranial collateral pathways were examined. In eight of them, including four cases with cerebral aneurysms, an increase in blood flow velocity was observed. In the remaining five cases, including three cases with cerebral aneurysms, the mean blood velocity was within the normal range. The anterior communicating artery (AComA) formed the main intracranial collateral pathway which was found in seven patients, including three patients with diagnosed AComA aneurysm. Blood flow velocity in ipsilateral (on the obstructed side) and contralateral (on the unobstructed side) anterior cerebral artery, as well as pulsatility and resistance indexes in contralateral anterior cerebral and middle cerebral arteries were higher compared with healthy control subjects. In the ipsilateral middle cerebral artery a relative, insignificant decrease of pulsatility and resistance indexes was detected. Ipsilateral and contralateral middle cerebral artery blood flow velocities were lower compared with the control group. CONCLUSION: Occlusion of the brachiocephalic vessels leads to formation of collateral circulation through the circle of Willis and the extracranial collaterals connecting the external and internal carotid arteries. An increase in blood flow velocity is commonly observed in intracranial arteries forming a collateral pathways. In some cases, not excluding arteries with a cerebral aneurysm, the increase in blood flow velocity is insignificant or none at all. This study shows that formation of a cerebral aneurysm is not always related to an increase in the flow velocity of collateral arteries.

Adult↗
PubMed1997

Pharmacokinetic analysis of enterohepatic circulation of etodolac and effect of hepatic and renal injury on the pharmacokinetics.

This study was designed to evaluate the enterohepatic circulation of racemic etodolac in rats. Additionally, the effect of hepatic and renal failure on the pharmacokinetics was estimated. The biliary excretion and the reabsorption of the drug excreted in bile were examined in order to clarify the effect of enterohepatic circulation on the disposition, and a pharmacokinetics model was applied to describe the enterohepatic circulation. The relatively rapid elimination of etodolac was seen in the bile-exteriorized rats (BE rat) compared with that in control rats. Total biliary excretion of etodolac, mainly as glucuronides, after intravenous administration was about 45% of the dose, indicating extensive enterohepatic circulation of the drug. The plasma concentrations of the drug in bile duct-linked rats approximately agreed with the simulation curve by the model, with the peak concentration 6-7 h after dosing. The elimination of the drug was markedly retarded in rats with hepatic (CCI4-induced) and renal (uranyl acetate-induced) failure, and high plasma levels were maintained over the longer times, due to greatly decreased distribution volume. The biliary excretion of etodolac enantiomers was not significantly different between the control and CCI4-groups, suggesting that hepatic glucuronyl transferase activity was preserved in rats impaired by CCI4.

Acute Kidney Injury↗
PubMed1984

Pharmacokinetic study of the enterohepatic circulation of acetaminophen glucuronide in rats.

A pharmacokinetic model of the enterohepatic circulation of acetaminophen glucuronide was investigated in rats with particular attention to a lag time between biliary excretion and reabsorption. The plasma drug data obtained after acetaminophen glucuronide injection into the various sites of the gut confirmed that there is a lag time in the enterohepatic circulation and that the lag time is due to the intestinal transit period of the conjugate to the site of the hydrolysis. The value of the lag time was fairly close to that reported previously in the rat. Based on the result, a compartment model with periodic trigonometric function for the enterohepatic circulation was built up and the urinary excretion data were fitted to this model. Same parameters which are considered to be common to other glucuronide conjugates were in good agreement with those reported previously, indicating that the model and those values are useful to study the enterohepatic circulation for glucuronides of other compounds in the rat.

Acetaminophen↗