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PubMed1974

The significance of circulating and cell-bound antibodies in experimental allergic encephalomyelitis.

Conjugates of horseradish peroxidase with myelin basic protein (BP) of guinea pig or Lewis rat were used to identify antibody-containing cells in draining lymph nodes during experimental allergic encephalomyelitis (EAE). Peroxidase activity was revealed for light and electron microscopic preparations with the diaminobenzidine reaction of Graham and Karnovsky. Basic proteins (BP) were also iodinated with (125)I for determination of circulating antibody against BP by radio-immunoassay of (125)I BP using coprecipitation with antirat IgG or with antirat serum proteins. Encephalitogenicity was lost after conjugation of guinea pig BP or Lewis rat BP with peroxidase, whereas iodination did not affect the encephalitogenicity of guinea pig or Lewis rat BPs. EAE was induced in Lewis rats with guinea pig or Lewis rat spinal cord BPs in complete Freund's adjuvant. Draining lymph nodes were studied by light and electron microscopy during the course of the immune reaction, and cells with specific antibody against BP were identified with the use of BP-horseradish peroxidase conjugates. Lymph node sections from animals immunized with high antigen doses (500 mug) showed numerous plasma cells with intracellular antibody against BP in medullary cords 10 days after immunization and 4 days prior to histologic appearance of EAE. Numbers of positive cells correlated with levels of circulating antibody against BP. Immunization with a low antigen dose (5 mug) resulted in EAE, few or no antibody-containing cells, and significantly lower levels of circulating antibody. Brown Norwegian rats, a strain resistant to EAE, immunized with 500 mug of BP had positive cells in draining lymph nodes and high levels of circulating antibody against BP in the absence of histologic evidence of EAE. Lewis rats injected with Lewis rat small BP failed to develop EAE. Nevertheless, these animals showed levels of circulating antibody and antibody-containing cells similar to those of animals which developed EAE after injection of the mixture of Lewis rat large and small BP. It is concluded that although the BP-peroxidase labeling method reveals cells with specific anti-BP antibody, these cells are probably unrelated to EAE. The lack of correlation between EAE induced by low antigen doses and levels of circulating anti-BP antibody (determined with the use of highly encephalitogenic (125)I-BP) suggests that effector cells can be stimulated at low antigen doses, but higher antigen doses are required to induce the production of levels of circulating antibody detectable by the method of immune coprecipitation.

Animals↗
PubMed1981

Autoimmunity and circulating immune complexes in retinal vasculitis.

This paper presents the results of a point-prevalence study of circulating autoantibodies and immune complexes in 44 patients with isolated retinal vasculitis (RV alone), 38 patients with retinal vasculitis accompanied by systemic inflammatory disease (RV + SID), and 33 patients with a similar range of systemic inflammatory disease but without eye involvement (SID alone). In isolated retinal vasculitis, antiretinal antibodies, non-retinal antibodies, and circulating immune complexes each showed a prevalence of about 50 per cent, but there was an inverse relationship between marked antiretinal autoimmunity and the occurrence of circulating immune complexes. In SID alone, antiretinal antibodies (ret-AB) were of lower prevalence (about 20 per cent) and occurred only in patients who had circulating immune complexes (CIC). Patients with RV + SID fell into two principal categories: (a) ret-AB with CIC, and (b) ret-AB without CIC. In isolated retinal vasculitis, the occurrence of high levels of retinal autoimmunity in the absence of circulating immune complexes was associated with the more severe retinal disease, while in those RV + SID patients who did not express autoimmunity, the more severe retinal disease was associated with the presence of circulating immune complexes. It is suggested that the formation of circulating autoimmune complexes, possibly of an idiotypic: anti-idiotypic character, may be a 'risk' mechanism for limiting retinal-specific autoimmunity, and that certain patients with severe retinal vasculitis may undercompensate or overcompensate in this way.

Antigen-Antibody Complex↗
PubMed1978

[Retinal circulation times as determined by fluorescein angiography (author's transl)].

Using a standardized technique of rapid fluorescein angiography applying a special diaphragm in the camera to reduce the patient stress by the frequent flashes and an automatic dye injection retinal circulation times of 173 healthy eyes were measured and statistically analysed. Circulation time was defined as the time interval between first visible arterial and venous fluorescence of corresponding vessels near the disc margin. The circulation time for the temporal vessels (1.1--1.2 s) was significantly faster than that of the nasal vessels (1.3 s) whereas there was no significant difference between the upper and lower main vessels. The very short circulation times are caused by short circuits near the disc. The difference between the shorter temporal and longer nasal times is caused by the macular circulation. It would therefore be more accurate to speak of peripapillary circulation times or of circulation times of the posterior pole of the fundus.

Capillaries↗
PubMedDate not supplied

Relationship of increased levels of circulating intercellular adhesion molecule 1 after heart transplantation to rejection: human leukocyte antigen mismatch and survival.

Noninvasive methods to assess immune activation would be helpful in optimizing therapy after heart transplantation to reduce rejection (acute and chronic) and complications caused by excessive immunosuppressive therapy. Intercellular adhesion molecule 1 has been shown to play an important role in T-cell activation and allograft rejection. A soluble form of intercellular adhesion molecule 1 has been discovered to be circulating in plasma. To test the hypothesis that increased levels of circulating intercellular adhesion molecule 1 may have prognostic value as a marker of immune activation, we examined whether levels of circulating intercellular adhesion molecule 1 during the early postoperative period correlated with endomyocardial biopsy scores, soluble interleukin-2 receptor levels, human leukocyte antigen mismatch, and survival. For the first 3 weeks after surgery, serum was obtained once weekly on the same day as endomyocardial biopsy samples from 52 patients who survived more than 30 days after heart transplantation. A sandwich enzyme-linked immunosorbent assay was used to measure circulating intercellular adhesion molecule 1 and soluble interleukin-2 receptor. Increased circulating intercellular adhesion molecule 1 levels did not correlate with endomyocardial biopsy scores but were associated with greater mismatch at the human leukocyte antigen-B and -DR loci (p = 0.02). A significant correlation was found (p = 0.002) between circulating intercellular adhesion molecule 1 levels and soluble interleukin-2 receptor, albeit with a low r value of 0.27. Survival was reduced in patients with high levels of circulating intercellular adhesion molecule 1 (p = 0.006) or soluble interleukin-2 receptor (p = 0.001) with the greatest reduction in survival when both were elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1995

Accumulation of protein-coated liposomes in an extravascular site: influence of increasing carrier circulation lifetimes.

The primary objective of this work was to test whether increased blood levels and circulation lifetimes result in increased passive targeting of protein-coated liposomal drug carriers. The system used to evaluate this was based on i.v. injection of 100 nm of distearoyl phosphatidylcholine/cholesterol liposomes with covalently bound streptavidin. The circulation lifetime of these liposomes was increased by procedures that involved blockade of liposome uptake by phagocytic cells in the liver and/or the incorporation of a poly(ethylene glycol)-modified phospholipid [poly(ethylene glycol)2000-modified distearoyl phosphatidylethanolamine]. Blockade of liver phagocytic cells with a low predose (2 mg/kg of drug) of liposomal doxorubicin increased the circulation half-life of the streptavidin liposomes from less than 1 hr to greater than 3 hr. A further 2-fold increase in circulating half-life (to approximately 7.5 hr) was achieved by using liposomes with 2 mole % of poly(ethylene glycol)2000-modified phosphatidylethanolamine. In combination with RES blockade, the circulation lifetimes of poly(ethylene glycol)phosphatidylethanolamine containing streptavidin liposomes could be increased to greater than 12 hr. The ability of these liposomes to move from the plasma compartment to an extravascular compartment was measured by using the peritoneal cavity as a convenient, accessible, extravascular site. The tendency for liposomes to accumulate in this site was not, however, clearly dependent on circulating blood levels. Comparable levels of liposomes in the peritoneal cavity were achieved when using systems that exhibited significantly different circulation lifetimes.

Animals↗
PubMed1996

Specificity of circulating and tissue-bound autoantibodies in Goodpasture syndrome.

Goodpasture syndrome is an often fatal autoimmune disease associated with glomerulonephritis and/or pulmonary hemorrhage. The clinical manifestations of this disease correlate well with the presence of circulating antiglomerular basement membrane (GBM) autoantibodies. The primary target antigen in glomerular and alveolar basement membranes is thought to be the alpha 3 chain of type IV collagen. Nearly all that is known about anti-GBM antibodies in humans comes from work on unbound circulating antibody. We recently had the unique and rare opportunity to obtain early postmortem antibody and tissues from a patient who died with catastrophic Goodpasture syndrome. The specificity of circulating, kidney-bound and lung-bound autoantibodies from this patient was evaluated against a variety of purified basement membrane constituents. The results indicate that the primary target for the circulating and tissue-bound autoantibodies is the NC1 domain of the alpha 3(IV) chain of type IV collagen. Additionally, all the antibodies recognize a cryptic epitope/s on the alpha 3(IV)NC1 hexamer. Furthermore, tissue-bound and circulating antibodies compete with one another for overlapping epitopes on the antigen. These findings demonstrate that circulating autoantibodies in Goodpasture syndrome are highly representative of those bound to organ tissues, strengthening the notion that pathogenic autoantibodies are targeted to the alpha 3(IV)NC1 collagen, and that previous reports of findings in the circulation may be applicable to tissue injury.

Adolescent↗
PubMed1994

Preferential dilation of recipient coronary arteries of the collateral circulation by intracoronary administration of nitroglycerin.

OBJECTIVES: The purpose of this study was to test the hypothesis that the sensitivity to nitroglycerin of collateral vessels and recipient arteries is greater than that of donor arteries of the collateral circulation. BACKGROUND: The collateral circulation responds vigorously to nitroglycerin. However, the mechanisms of the efficacy of nitroglycerin for improving collateral circulation are not fully elucidated. METHODS: The diameter of donor and recipient arteries of the collateral circulation was measured with a computer-assisted analysis system in eight patients with well developed collateral vessels. Coronary angiography was repeated before and after the intracoronary injection of 50 micrograms of nitroglycerin. RESULTS: After nitroglycerin, the mean diameter +/- SD of donor arteries increased to 1.61 +/- 0.53 from 1.29 +/- 0.39 mm (p < 0.01), whereas the diameter of recipient arteries increased to 1.59 +/- 0.50 from 1.10 +/- 0.49 mm (p < 0.01). The change in the diameter of recipient arteries was significantly greater than that of donor arteries (52.3 +/- 24.6% vs. 24.7 +/- 11.5%, p < 0.05). These changes induced by the intracoronary injection of nitroglycerin were accompanied by a decrease in pacing-induced ST segment depression (0.16 +/- 0.06 to 0.06 +/- 0.04 mV, p < 0.01), suggesting increased flow reserve through collateral channels. CONCLUSIONS: These findings indicate that the sensitivity to nitroglycerin of recipient arteries of the collateral circulation is significantly greater than that of donor arteries. This observation may explain the strong response of the collateral circulation to nitroglycerin in patients with functionally significant collateral channels.

Aged↗
PubMed1985

Effect of pulmonary and renal circulations on activity of atrial natriuretic factor.

The effect of passage through the pulmonary and renal circulation on the activity of extracted and synthetic atrial natriuretic factors was determined by monitoring the amount of the vascular relaxing activity surviving passage through the organ. When crude atrial extract was infused through isolated perfused lungs of the guinea pig, approximately 75% of its activity survived. The activity of a 23-amino acid synthetic atrial peptide was decreased 21% on passage through these lungs, but this loss of activity was not significantly different from the crude extract. Analogous experiments in vivo showed that passage through the pulmonary circulation of the dog did not alter the activity of either the crude atrial extract or of synthetic atrial peptide. In contrast to the lack of effect of the pulmonary circulation, approximately 80% of the activity of crude atrial extract and synthetic atrial peptide was removed by the isolated perfused kidney of the rabbit, and in vivo the dog kidney removed approximately 80% of the activity of both these atrial substances. By surviving transit through the pulmonary circulation, these materials exhibit a necessary property of a circulating hormone stored in the right atrium, and the fact that the renal circulation extracts most of these materials is consistent with the kidney being a target organ of this putative hormone.

Animals↗
PubMed1991

Vital organ perfusion during assisted circulation by manipulation of intrathoracic pressure.

BACKGROUND: We have previously shown, in dogs with severe cardiac depression, that modest cyclic increases in intrathoracic pressure, starting synchronously with left ventricular isovolumic contraction, significantly increase aortic flow and pressure. However, little is known of changes in vital organ perfusion during this technique of assisted circulation. METHODS AND RESULTS: We studied regional organ flow using radioactive labeled microspheres in 13 20-25-kg mongrel dogs. In the control group, after chemical induction of cardiac depression with verapamil and propranolol, coronary flow fell from 129.1 +/- 14.4 to 51.6 +/- 11.3 ml/100 g/min (p less than 0.005) and continued to decline over a 14-minute time period (flow was 32.2 +/- 11.5 ml/100 g/min at 7 minutes and 20.7 +/- 9.5 ml/100 g/min at 14 minutes [n = 6]; all p less than 0.05). In the intervention group, regional blood flow was evaluated before and after the induction of cardiac depression and also during assisted circulation using 400-msec, 20-25-mm Hg intrathoracic pressure increases delivered by a circumthoracic pneumatic vest, starting synchronously with left ventricular isovolumic contraction. In the intervention group, coronary flow fell from 119 +/- 26.7 to 47.9 +/- 13.1 ml/100 g/min 1 minute after the induction of cardiac depression (p less than 0.005). With the initiation of assisted circulation, coronary flow increased to 55.8 +/- 19.2 ml/100 g/min at 7 minutes and fell to 23.1 +/- 15.9 ml/100 g/min on termination of assisted circulation at 14 minutes (p less than 0.05 and p = NS versus control group flows at 1 and 14 minutes, respectively). During assisted circulation, cerebral, renal, and small intestinal flows also increased (all p less than 0.05 versus flows during myocardial depression). No significant increase in hepatic flow was observed. CONCLUSIONS: In the canine model, manipulation of intrathoracic pressure appears to be an effective, short-term, noninvasive means of not only increasing aortic pressure but also increasing vital organ perfusion during cardiogenic shock. Further studies are needed to assess the usefulness of this technique of assisted circulation in humans.

Animals↗
PubMed2003

Collateral circulation.

BACKGROUND: The collateral circulation plays a pivotal role in the pathophysiology of cerebral ischemia. Current knowledge of the collateral circulation remains sparse, largely because of prior limitations in methods for evaluation of these diminutive routes of cerebral blood flow. SUMMARY OF REVIEW: Anatomic descriptions of the collateral circulation often focus on more proximal anastomoses at the circle of Willis, neglecting secondary collateral pathways provided by leptomeningeal vessels. Pathophysiological recruitment of collateral vessels likely depends on the temporal course of numerous compensatory hemodynamic, metabolic, and neural mechanisms. Subsequent endurance of these protective vascular pathways may determine the severity of ischemic injury. Characterization of the collateral circulation with advanced neuroimaging modalities that provide angiographic information and perfusion data may elucidate critical determinants of collateral blood flow. Such information on the status of the collateral circulation may be used to guide therapeutic interventions. Prognostication and risk stratification may also be improved by routine evaluation of collateral blood flow. CONCLUSIONS: Contemporary understanding of the collateral circulation may be greatly enhanced through further refinement of neuroimaging modalities that correlate angiographic findings with perfusion status, providing the basis for future therapeutic and prognostic applications.

Brain↗
PubMed2003

Coronary collateral circulation is less developed when ischaemic heart disease coexists with diabetes.

BACKGROUND: The extent of myocardial ischaemia and the magnitude of systolic function impairment following myocardial infarction (MI) depend to a large degree on the performance of coronary collateral circulation. Endothelial function is altered in several disorders, including diabetes. An impaired development of coronary collateral circulation may be a factor responsible for post-MI complications in patients with diabetes. AIM: To compare the degree of coronary collateral circulation development between patients with advanced ischaemic heart disease (IHD), with or without diabetes. METHODS: The study group consisted of 70 consecutive patients with diabetes who underwent coronary angiography between September 1998 and December 1999 and had total occlusion of at least one of the main coronary vessels. The control group consisted of 70 age-, gender, and MI history-matched non-diabetic patients. Coronary collateral circulation was assessed using the collateral score (CS). RESULTS: Patients with diabetes had less developed coronary collateral circulation than the patients without diabetes which was reflected by a significantly lower CS value - 1.47+/-1.56 vs 2.03+/-1.81; p < 0.05. No significant relationship was found between CS and age, gender, body mass index, history of MI or the presence of IHD risk factors. There was a significant association between the number of vessels with lesions and CS: r=0.40, p=0.0006 in the control group and r=0.42, p=0.0003 in patients with diabetes. The CS values in patients with single-, two- or three-vessel disease were 1.27+/-1.34, 2.38+/-1.85 and 2.98+/-2.07 in the control group, and 0.70+/-0.90, 1.10+/-1.30 and 2.23+/-1.76 in patients with diabetes, respectively. A multivariate analysis revealed that the presence of diabetes (t=-3.04, p=0.003) and the number of affected vessels (t=5.23, p=0.0001) were independently related to the CS values. CONCLUSIONS: Patients with IHD and diabetes have less developed coronary collateral circulation than IHD patients without diabetes, regardless of the extent of coronary lesions. Patients with diabetes who undergo coronary angiography, have more advanced coronary atherosclerotic lesions than patients without diabetes.

Aged↗
PubMed1991

End-tidal carbon dioxide tension as a monitor of native blood flow during resuscitation by extracorporeal circulation.

In a porcine model of cardiac arrest, we investigated end-tidal carbon dioxide tension as a monitor of native blood flow during resuscitation by extracorporeal circulation. After 15 minutes of cardiac arrest and after precordial compression and transthoracic countershocks had failed, extracorporeal circulation consistently restored spontaneous circulation. Native end-tidal carbon dioxide tension, which averaged 29.8 +/- 1.0 mm Hg before arrest, was only 5.2 +/- 0.8 mm Hg during precordial compression. After the start of extracorporeal circulation, native end-tidal carbon dioxide tension was measured during 15-second interruptions of pump flow. End-tidal carbon dioxide tension progressively increased with a corresponding increase in native cardiac index. The correlation coefficients between end-tidal carbon dioxide tension and native cardiac index averaged 0.92 +/- 0.03 (mean +/- standard error of the mean). When end-tidal carbon dioxide tension exceeded 15 mm Hg, mean aortic pressure in each instance was 60 mm Hg or greater, and the animal was successfully weaned from extracorporeal support. We conclude that end-tidal carbon dioxide tension serves as a reliable monitor of blood flow through the lung and therefore of native cardiac output during weaning from extracorporeal circulation. It therefore indicates when native cardiac output is likely to be adequate to sustain spontaneous circulation.

Animals↗
PubMed1990

Development of collateral circulation after acute myocardial infarction: its role in preserving left ventricular function.

The present study evaluated the effects of coronary collateral circulation developing after acute myocardial infarction on global and regional left ventricular function during the chronic stage. The study group consisted of 16 patients with initial myocardial infarction having total occlusion of the proximal left anterior descending coronary artery. To eliminate the effects of collateral circulation existing at the onset of infarction, patients with pre-infarction angina were excluded from this study. The patients were categorized in two groups depending on the extent of their collateral circulation (collateral index: CI 0-3): group A--patients with significant collateral circulation (CI = 2 or 3) to the infarct-related coronary artery; group B--patients without significant collateral circulation (CI = 0 or 1). Their heart rate, left ventricular peak systolic and end-diastolic pressures and cardiac index were similar in the two groups. The left ventricular end-systolic volume index in the group B was significantly greater than that in the group A (60 +/- 21 ml/m2 vs 34 +/- 9 ml/m2, p less than 0.05). Left ventricular ejection fraction in the group A was significantly greater than that of the group B (55 +/- 9% vs 39 +/- 15%, p less than 0.05), and a significant difference was observed in the percentage of segment shortening in the infarct area between the groups A and B (10.8 +/- 9.2% vs -0.2 +/- 5.4%, p less than 0.01). It was concluded that coronary collateral circulation which develops after acute myocardial infarction exerts beneficial effects on global and regional left ventricular function during the chronic stage.

Adult↗
PubMedDate not supplied

[Functional significance of collateral coronary circulation in univascular obstructions (1)].

The presence, degree and functional significance of the coronary collateral circulation was investigated in a group of 68 patients with angiographycally important (greater than 60%) univascular coronary obstruction. The following clinical parameters were reviewed. Smoking, hypertension, diabetes mellitus, functional class (NYHA), and degree of angina pectoris. In the ECG the presence of abnormal Q waves and the response to the stress test were analysed. To evaluate the functional significance of the collateral circulation the following angiographic and hemodynamic parameters were measured: ejection fraction (FE 100), mid sistolic ejection fraction (FE 50), percent of regional shortening of the left ventricular wall and finally the end diastolic pressure. According to the obstructed vessel (R, DA, Cx) the degree of obstruction (parcial or complete) and the degree of collateral circulation (O, I, II, III) several groups were formed. Statistical analysis of all the above mentioned clinical, electrocardiographic and angiographic findings were compared amongst the various groups. Coronary collateral circulation was demonstrated in 45 patients (68%) being present in 82% of those with complete coronary obstruction. In most of the patients (87%) an abundant collateral network was present (grade II or III). No statistical differences were demonstrated between the groups with abundant or poor collateral circulation in all the clinical, electrocardiographic or angiographic parameters. Finally we conclude that important collateral circulation usually develops in the presence of severe coronary obstruction; however its functional value is limited.

Adult↗
PubMed1980

[Collateral circulation syndromes in the brachiocephalic artery system].

In 56 patients qualitative and quantitative characteristics of variants of collateral circulation in the system of occluded brachiocephalic arteries were studied. The objects of the studies were angiographic and clinical appearance of the variants of retrograde blood flow and the latter's connection with cerebral circulation. It was shown that the reversion of the blood flow from the Willis circle system was observed in 25% of patients with occlusive affections of the brachiocephalic arteries. The most frequent was the flow through the spinal arteries. The subclavicular steal syndrome led to cerebral circulation disturbances that manifested mostly in the form of transitory disturbances of the circulation in the vertebrobasilar and less often the carotid basins of the cerebral circulation. The neurological disturbances were the most specific in patients with isolated affections of the brachiocephalic stem or the subclavicular arteries. At the same time the intensity of the retrograde flow from the Willis circle system is regulated by the level of cerebral circulation, and depends on the degree of the vasocerebral insufficiency.

Adolescent↗
PubMed1996

Acute multiple infarction involving the anterior circulation.

OBJECTIVE: To evaluate the frequency and clinical, topographic, and etiologic patterns of acute multiple infarction involving the anterior circulation. DESIGN: Data analysis from a prospective acute stroke registry in a community-based primary care center. RESULTS: Among 751 patients with first ischemic stroke in the anterior circulation over a 4-year period, 40 patients (5%) had acute multiple infarcts involving the anterior circulation. On computed tomography and magnetic resonance imaging with gadolinium enhancement, there were four topographic patterns of infarction: (1) superficial infarcts (11 patients [28%]); (2) superficial and deep infarcts (12 patients [30%]); (3) deep infarcts (three patients [8%]); and (4) infarcts involving the anterior and the posterior circulation (14 patients [35%]). Both cerebral hemispheres were involved in one fourth of the cases. A specific clinical picture was found in up to 20% of the patients. This included global aphasia with left hemianopia, hemisensory loss or hemiparesis (in right-handed patients), transcortical mixed aphasia with hemianopia, and acute pure cognitive impairment ("dementia"). Large-artery disease was found in 13 patients (33%); a cardiac source of embolism was found in 11 patients (28%); and both were found in three patients (8%). Bilateral infarcts were related to cardioembolism (four patients) and bilateral large-artery disease (three patients). One month after stroke, one fourth of the patients were independent, one third had some disability, and 40% were either dead or completely dependent. CONCLUSIONS: Acute multiple infarcts involving the anterior circulation may be bilateral more frequently than is currently thought, and they are often associated with posterior circulation infarcts. They mainly involve the pial hemispheral territories, commonly being caused by cardioembolism or bilateral carotid atheroma. They may be associated with a specific neurologic-neuropsychological dysfunction pattern in up to one fifth of the patients, allowing diagnosis before brain imaging.

Adult↗
PubMed1994

Alternative continuous infusion method for analysis of enterohepatic circulation and biliary excretion of cefixime in the rat.

The enterohepatic circulation and biliary excretion of cefixime during continuous infusion were evaluated in rats based on the recirculatory concept. The Laplace-transformed equations for the enterohepatic circulation according to this concept were derived by means of the combination of transfer function. The transformed equations were simultaneously fitted to the time courses of plasma concentration in rats with laparotomy and with bile duct cannula by means of a nonlinear regression program, MULTI(FILT), into which the fast inverse Laplace transform was incorporated. The optimum model was selected on the basis of Akaike's information criterion (AIC). The time course of drug accumulation in the bile during infusion starts with a relatively gentle slope and finally approaches the asymptote with a constant slope. The kinetic significance of this asymptote was explained using the time courses of the cumulative amount excreted into the bile of rats with bile duct cannulation. The local moment characteristics for a single pass through enterohepatic circulation were further calculated from the time courses of both the plasma concentration and the excreted amount into the bile. The recovery ratio (Fc) and the mean circulatory time (tc) through a single pass of enterohepatic circulation were estimated to be 31.1% and 0.925 h, respectively. The recovery ratio (Fa) and the mean transit time (ta) for the complicated process from the access to the bile duct into the systemic circulation such as transport through the bile duct, absorption from the intestinal tract, and transit through the portal system were 76.4% and 0.0231 h, respectively. The recovery ratio (Fb) and the mean transit time (tb) for the disposition process through the systemic circulation into the bile were 40.7% and 0.902 h, respectively.

Animals↗
PubMed1990

Analysis of enterohepatic circulation of cefixime in rat by fast inverse Laplace transform (FILT).

The enterohepatic circulation of cefixime in rat was evaluated by a nonlinear least square analysis program, MULTI(FILT), into which the fast inverse Laplace transform (FILT) was incorporated. The plasma time course in the bile duct-cannulated rat exhibited a biexponential curve after the rapid iv administration of cefixime. Several pharmacokinetic models for the enterohepatic circulation were constructed based on the recirculatory concept and the Laplace-transformed equations corresponding to these models were derived by means of the method of transfer function. The transformed equations were simultaneously fitted to the time courses of plasma concentration in rats with laparotomy and with bile duct cannula. The optimum model was selected based on the Akaike's information criterion (AIC). The local moment characteristics for a single pass through enterohepatic circulation were further calculated from the time courses of both the plasma concentration and the amount excreted into the bile. The recovery ratio (Fc) and the mean circulatory time (-tc) through a single pass of enterohepatic circulation were estimated 27.9% and 1.07 hr, respectively. The recovery ratio (Fa) and the mean absorption time (-tc) for the absorption process from the intestinal tract into the systemic circulation were 68.3% and 0.0234 hr, respectively. The recovery ratio (Fb) and the mean transit time (-tb) for the disposition process through the systemic circulation into the bile were 40.8% and 1.05 hr, respectively.

Animals↗