Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “circulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources
PubMed2004

The influence of pH strategy on cerebral and collateral circulation during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease: results of a randomized trial and real-time monitoring.

OBJECTIVE: The optimal pH strategy during hypothermic cardiopulmonary bypass remains controversial. Systemic pulmonary collateral circulation may develop in patients with cyanotic anomalies. The purpose of this study was to evaluate the effect of pH strategies on cerebral oxygenation and systemic pulmonary collateral circulation during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease. METHODS: Forty cyanotic patients (age > 1 year) with heart disease were prospectively randomized into 2 groups. Group 1 (n = 19, 14.3 +/- 1.5 kg) underwent hypothermic cardiopulmonary bypass with alpha-stat strategy and group 2 (n = 21, 12.5 +/- 0.9 kg) with pH-stat. Cardiopulmonary bypass was established with pump-assisted drainage. Cerebral oxygenation was assessed by near-infrared spectroscopy and the systemic pulmonary collateral circulation was calculated by pump flows [% systemic pulmonary collateral circulation = perfusion flow - drainage flow)/perfusion flow x 100]. Lactate was measured as an index of systemic anaerobic metabolism. RESULTS: There were no significant differences in preoperative hematocrit, oxygen saturation, Qp/Qs, cardiopulmonary bypass duration, minimum temperatures, perfusion flow and pressure, urine output, and depth of anesthesia between the groups. Oxyhemoglobin signal and tissue oxygenation index of near-infrared spectroscopy monitoring were significantly lower in group 1 compared with group 2 (P =.008 and P <.0001, respectively), suggesting inadequate cerebral oxygenation with alpha-stat. Deoxygenated hemoglobin signal was significantly higher in group 1 relative to group 2 (P <.0001). The % systemic pulmonary collateral circulation was significantly lower in group 2 compared with group 1, suggesting a reduced pulmonary collateral circulation with pH-stat (P <.0001, average; group 1, 20.1% +/- 1.2%; group 2; 7.7% +/- 0.7%). Serum lactate was significantly lower in group 2 (P <.0001). CONCLUSIONS: The pH-stat strategy results in an improved environment, including sufficient cerebral oxygenation, decreased systemic pulmonary collateral circulation, and lower lactate level during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease. Future studies should investigate the long-term neurological outcome.

Analysis of Variance↗
PubMedDate not supplied

Myocardial perfusion in patients with total occlusion of a single coronary artery with and without collateral circulation.

BACKGROUND: Previous studies that investigated the effects of coronary collateral circulation on myocardial perfusion were compromised by inclusion of patients with multivessel coronary artery disease, incomplete occlusion, prior myocardial infarction, or a combination of these. In this study we ascertained the relationship between angiographic collateral circulation and myocardial perfusion only in patients with total occlusion of a single coronary artery, in the absence of myocardial infarction or significant stenosis in the other coronary arteries. METHODS AND RESULTS: Seventy-one consecutive patients underwent stress myocardial single photon emission computed tomography within 90 days of angiography. Collateral circulation was present in 49 patients and absent in 22 patients. All but 2 patients had abnormal perfusion by single photon emission computed tomography imaging, with a mean defect size of 19% +/- 12%, and most (83%) had reversible perfusion defects. Defect count activities improved from stress to rest (or redistribution) (45% +/- 13% to 59% +/- 14%, P <.001). Abnormal myocardial perfusion occurred with similar frequency in patients with collateral circulation and in those without it. Total defect size was 19% +/- 12% in patients with and 18% +/- 11% in those without collateral circulation (P = not significant). The extent of reversibility and defect count activity during stress and rest were similar in patients with collateral circulation and in those without it. CONCLUSIONS: In patients with a single-vessel total coronary occlusion and without myocardial infarction, stress-induced myocardial ischemia is almost always present, irrespective of presence or absence of angiographic collaterals. These data lend support to the premise that collateral circulation is rather insufficient to prevent stress-induced ischemia, although it can preserve myocardial viability.

Aged↗
PubMed1995

A proposed blood circulation model for Reference Man.

As part of the revision of the Reference Man model of the International Commission on Radiological Protection (ICRP), we have reviewed and reanalyzed available data on blood flow and in previous publications have proposed reference values for total and regional blood volumes, total cardiac output, and the distribution of cardiac output. In this paper we unify these proposed features of the revised Reference Man within the framework of a dynamic blood circulation model and show how the model can be used to predict the distribution of decays of short-lived radionuclides after injection or absorption into blood. The total blood volume is partitioned into the blood contents of 24 separate organs or tissues, right heart chambers, left heart chambers, pulmonary circulation, arterial outflow to the systemic tissues (aorta and large arteries), and venous return from the systemic tissues (large veins). As a compromise between physical reality and computational simplicity, the circulation of blood is viewed as a system of first-order transfers between blood pools, but outflow from any given pool is delayed during the first pass of material through the circulation with the delay time depending on the mean transit time across the pool. The model can be used to predict the movement and gradual dispersal of a bolus of material in the circulation after intravascular injection. In contrast to the treatment of the circulation in ICRP Publication 53, Radiation Dose to Patients from Radiopharmaceuticals, the present model allows consideration of incomplete, tissue-dependent extraction of material during passage through the circulation and return of material from tissues to plasma.

Adult↗
PubMed2004

Evaluation of luminal endothelin-converting enzyme activity in the pulmonary and coronary circulations.

The endothelin-converting enzymes are distributed on both the surface of the endothelium and intracellularly. Whether circulating big-endothelin-1 can be hydrolyzed in plasma by lumen-bound endothelin-converting enzymes is unknown. The lung is the major site for hydrolysis of angiotensin-I to angiotensin-II by the angiotensin-converting enzyme; because of its high content in endothelin-converting enzymes, we hypothesized that the lung could similarly hydrolyze circulating big-endothelin-1. Since big-endothelin-1 produced by the lung can modulate coronary vascular tone, the heart may also have the capacity to hydrolyze circulating big-endothelin-1. Isolated lungs and hearts from Sprague-Dawley rats were perfused at 10 mL/min. Clearance of trace doses of human I125big-endothelin-1 was quantified using the indicator-dilution curves technique with labeled albumin as a vascular reference. Single-pass hydrolysis was assessed by bolus injection of human big-endothelin-1 (24 fmol) followed by serial ELISA determinations of big-endothelin-1 and endothelin-1 levels in effluent samples. To exclude possible uptake of produced endothelin-1, 10(-6) M BQ788 was added to the perfusate. The injections had no effect on perfusion pressures. There was no detectable clearance of I125big-endothelin-1 in the lung; however the heart extracted 14 +/- 1% of the injected tracer. There was no detectable big-endothelin-1 hydrolysis in the pulmonary as well as in the coronary circulations. The pulmonary circulation does not clear or hydrolyze circulating big-endothelin-1 suggesting that endothelin-converting enzymes are predominantly used for intracellular and/or abluminal conversion of locally produced big-endothelin-1. Mild coronary uptake of big-endothelin-1 suggests that this circulating peptide could modulate coronary vascular tone.

Animals↗
PubMed1996

Sympathetic nerve activities in pulsatile and nonpulsatile systemic circulation in anesthetized goats.

To investigate the effects of pulsatile and nonpulsatile systemic circulation on the sympathetic nerve activity, using a left heart bypass technique, we converted systemic circulation between the pulsatile and the nonpulsatile mode in anesthetized goats and analyzed differences in periodicity and quantity of renal nerve activity (RNA). After pulsatile systemic circulation was converted to the nonpulsatile mode, the mean RNA was significantly increased from 10.7 +/- 3.6 to 13.1 +/- 3.4 microV and periodic discharges of RNA, which corresponded to pulse-related rhythm during pulsatile circulation, became obscure, whereas an 8-12 cycle/s rhythm, which was distinguished and accounted for 30 +/- 9% of total intervals during pulsatile circulation, became dominant (48 +/- 11%). These results clarified a significant increase in mean RNA after depulsation of the systemic circulation and indicated that the cardiac-related rhythm in RNA could be produced by periodic inputs from arterial baroceptors alone, whereas the 8-12 cycle/s rhythm that was present regardless of the type of circulation was the fundamental rhythm originating from the vasomotor center.

Animals↗
PubMed1993

Relative contribution of endothelium-derived relaxation factor to vascular tone in the systemic, pulmonary, and cerebral circulations of piglets.

UNLABELLED: We determined the contribution of endothelium-derived relaxation factor (EDRF) to vascular tone in the systemic, pulmonary, and cerebral circulations of piglets. METHODS: 11 piglets were anesthetized and mechanically ventilated. Systemic cardiac output was determined by an electromagnetic flow probe placed on the main pulmonary artery. Cerebral blood flow was assessed by determining unilateral internal carotid artery blood flow (ICBF) using a flow probe placed on the common carotid artery after ligation of the ipsilateral external carotid circulation. Progressive inhibition of EDRF was achieved by continuous infusion of the substituted L-arginine analog N-nitro-L-arginine (NNLA). Hemodynamic observations were compared at 0, 0.1, 1.0, 10, 30, and 80 mg/kg cumulative dose of NNLA. RESULTS: At all NNLA doses > or = 1 mg/kg, both systemic blood pressure and systemic vascular resistance were elevated. At all NNLA doses > or = 10 mg/kg, systemic cardiac output was reduced. At all NNLA doses > or = 10 mg/kg, pulmonary artery pressure and pulmonary vascular resistance were elevated. Although cerebral vascular resistance was elevated at all NNLA doses > or = 10 mg/kg, ICBF was maintained at or near baseline values up to a dose of 80 mg/kg. At all levels of EDRF inhibition, both the pulmonary and systemic circulations demonstrated approximately equal magnitudes of vasoconstriction. In contrast, at 30 and 80 mg/kg cumulative dose of NNLA, the cerebral circulation was relatively less constricted by NNLA than was the systemic circulation. Systemic VO2 was significantly reduced at 30 mg/kg and 80 mg/kg cumulative NNLA dose, while cerebral VO2 was preserved at both NNLA doses. CONCLUSIONS: EDRF contributes to resting vasodilator tone in the systemic, pulmonary, and cerebral circulations in piglets. Progressive inhibition of EDRF constricts the systemic and pulmonary circulation equally. Inhibition of EDRF does not impair the ability of the brain to vary cerebral vascular resistance in order to redistribute blood flow towards itself during a period of reduced cardiac output.

Animals↗
PubMed1978

[Coronary collateral circulation in coronary atherosclerosis (author's transl)].

The coronary collateral circulation of 162 patients suffering from atherosclerosis and coronary insufficiency (coronary artery disease) was studied. It was found to be present in 44 patients, or 27.1%; homocoronary in 9%, intercoronary in 90.9%. As other Authors have previously reported, anastomotic circulation is more developed when the coronary occlusion exceeds 75%. Not one of the 44 cases with normal coronary arteries or occlusion inferior to 75% presented collateral circulation. In addition, it was found to be present more frequently in cases with three branch lesions. The time of insurgence of coronary insufficiency seems to condition the development of anastomotic circulation which appears more frequently when the symptoms have been present for more than 5 years (43.9%). Anastomotic circulation is also found more frequently (48.4%) in patients who have suffered myocardial infarction and who have angina. Collateral circulation was not found in any of the 46 patients with unstable isolated angina; this seems to show the importance, in its pathogenesis, of the functional factor (spasm). In conclusion, we may say that anastomotic circulation is more developed: 1) in cases of severe occlusive lesions (in severe coronary occlusive disease/atherosclerosis) (85%);2) in three branch lesions; 3) in cases of long standing symptomatology; 4) in stable angina and in angina t infarction.

Angina Pectoris↗
PubMed1998

[Collateral circulation and the coronary reserve].

The mechanisms regulating coronary collateral circulation are largely unknown owing to both the complex and variable nature of clinical models and the difficulty to obtain quantitative and differentiated flow measurements within the various coronary tree portions. With the aim of assessing collateral flow reserve, we studied 19 patients with effort angina, without myocardial infarction and with isolated occlusion of either the left anterior descending coronary artery (n = 14) or the circumflex coronary artery (n = 5). Flow values were measured basally, during atrial pacing induced tachycardia and following ev dipyridamole infusion (0.56 mg/kg of body weight in 4 min), by means of positron emission tomography and nitrogen-13 ammonia as flow tracer, within both regions depending on collateral circulation and the remote ones. Results have been compared with those obtained in 13 normal subjects. Basal flow values in regions depending on collateral circulation and in the remote regions (0.61 +/- 0.11 vs 0.63 +/- 0.17 ml/min/g) were found to be similar, but lower than in normal subjects (1.00 +/- 0.20 ml/min/g, p < 0.01). During atrial pacing, flow increased to 0.83 +/- 0.25 and to 1.11 +/- 0.39 ml/min/g, in the regions depending on collateral circulation and in the remote regions, respectively (p < 0.05 as compared to baseline); again, values were lower than in normal subjects (1.86 +/- 0.61 ml/min/g, p < 0.01). Dipyridamole infusion further increased flow in the remote regions (1.36 +/- 0.57 ml/min/g, p < 0.01 as compared to atrial pacing) but it did not in the regions depending on collateral circulation (0.94 +/- 0.37 ml/min/g, NS as compared to atrial pacing); both values were lower than in normal subjects (3.46 +/- 0.78 ml/min/g, p < 0.01). Flow reserve in the regions depending on collateral circulation was found to have a direct linear correlation with the one in the remote regions (r = 0.83; p < 0.01). In conclusion, in spite of basal hypoperfusion, collateral circulation maintains a flow reserve which, even if reduced, is able to cope with moderate increments in oxygen consumption. An analogous flow reduction can be observed in the remote regions, suggesting that the entire coronary tree is involved, beyond the obstructive lesions of the main arterial branches.

Adult↗
PubMed1999

Major organ function under mechanical support: comparative studies of pulsatile and nonpulsatile circulation.

We examined a major organ function during 3 h biventricular assisted circulation after acute myocardial infarction model in the pig. In left ventricular circulation, the outflow cannula was placed in the ascending aorta and an inflow cannula through the mitral valve in the left ventricle. A pump (pulsatile group, Zeon Medical, Inc., Tokyo, Japan and nonpulsatile group, Nikkiso HPM-15, Nikkiso, Inc., Tokyo, Japan) was connected to each cannula. In right ventricular circulation, the outflow cannula was placed in the pulmonary artery and an inflow cannula in the right ventricle. The right ventricular circulation was supported by a nonpulsatile pump (Nikkiso HPM-15). The items measured were the regional blood flows of the cortex and medulla in the kidney, white matter and gray mater in brain, and liver; renal arterial flow; carotid arterial flow; portal vein flow; common hepatic arterial flow; arterial ketone body ratio (AKBR); and lactate/pyrubic acid (L/P). In the pulsatile group, the renal cortical blood flow increased, and the medulla blood flow decreased. On the other hand, in the nonpulsatile group, both regional blood flows decreased. That means that in the pulsatile assisted group intrarenal redistribution improved rather than in the nonpulsatile assisted group. In addition the liver regional blood flow, AKBR, and L/P showed significant differences between the pulsatile and nonpulsatile groups. On the other hand, the white matter and gray matter regional blood flows and carotid arterial flow did not show significant differences between the groups. The results of our study indicated that pulsatile circulation produced superior circulation in the kidney and liver, and microcirculation on the cell level was superior as well in early treatment of acute heart failure.

Animals↗
PubMed2026

Translational Gap in Biomarker Discovery: Tumor Surface Markers Rarely Mirror Circulating Levels.

BACKGROUND: Tumor-associated cell surface proteins are frequently proposed as circulating biomarkers for colorectal cancer (CRC) based on their high tumor expression. However, many candidates identified through tissue-based analyses fail to translate into clinically useful biomarkers. We investigated the translational gap between tissue-level expression and circulating detectability in CRC, focusing on molecular subtypes defined by caudal-type homeobox&#xa0;2 (CDX2) expression. METHODS: Transcriptomic data from The Cancer Genome Atlas (TCGA) were analyzed to identify cell surface markers differentially expressed between CDX2-Low and CDX2-High CRCs. A clinical cohort of right-sided CRC patients was evaluated using paired tumor tissue and preoperative plasma samples. CDX2 expression was assessed by immunohistochemistry, and circulating concentrations of selected cell surface proteins were quantified using a multiplex ELISA platform. RESULTS: Several tumor-associated cell surface markers exhibited marked CDX2-dependent differences in tissue expression. However, for most markers, circulating plasma levels did not mirror tissue-level patterns. CEACAM1 was the sole marker demonstrating concordant CDX2-dependent differences in both tumor tissue and plasma, with significantly lower levels in CDX2-Low CRCs. In contrast, CEACAM5 showed a dissociation between tissue expression and circulating levels, despite analytical validation against serum carcinoembryonic antigen (CEA). CONCLUSIONS: Our findings demonstrate that tumor overexpression of cell surface markers does not necessarily translate into detectable circulating biomarkers. This translational disconnect underscores limitations of biomarker selection strategies based solely on tissue expression and highlights the importance of integrating systemic biology into biomarker development. While some tumor-associated proteins may lack utility as circulating biomarkers, they may still represent viable therapeutic targets in CRC.

CDX2↗
PubMed2001

Decrease in circulating tumor cells as an early marker of therapy effectiveness.

As melanoma cells are present in the circulation of many patients with this cancer, decreases in their number could provide an early indication of therapy effectiveness. To evaluate this possibility, we examined the effect of treatment with a melanoma vaccine on the number of melanoma cells present in the circulation. PCR was used to detect melanoma cells that expressed the melanoma-associated antigens MART-1, MAGE-3, tyrosinase and/or gp100 in 91 patients with melanoma. Melanoma cells that expressed one or more of these markers were present more often in advanced disease, i.e. in 80% of patients with advanced stage IV compared to in less than one-third of patients with less advanced disease. We then measured circulating melanoma cells in a subset of 43 of these patients who were treated with a polyvalent, shed antigen, melanoma vaccine. The vaccine contains multiple melanoma-associated antigens including MART-1, MAGE-3, tyrosinase and gp100. Immunizations were given intradermally q2-3 weeks x4 and then monthly x3. Prior to vaccine treatment, circulating melanoma cells were detected in 14 (32%) patients. Following 4 and 7 months of vaccine treatment, melanoma cells that expressed any of these markers were present in only nine (21%) and three (7%) of patients, respectively. Thus, vaccine therapy was associated with clearance of melanoma cells from the circulation in 78% of initially positive patients. As the number of these cells declined steadily with increasing length of therapy, it is unlikely that this was due to a random change in their number. Rather it suggests that the decline was a result of the therapy. These observations suggest that the presence of melanoma cells in the circulation is related to the extent of the melanoma, and that their disappearance may provide an early marker of the efficacy of therapy. However, the practical utility of assaying circulating tumor cells as a guide to the effectiveness of therapy or of prognosis will need to be confirmed by correlations with clinical outcome.

Biomarkers, Tumor↗
PubMed2005

Detection of circulating cancer cells after a gastrectomy for gastric cancer.

PURPOSE: In this study, we evaluated the correlation between the postoperative detection of circulating cancer cells and the risk of recurrence in patients with gastric cancer. METHODS: Total RNA was extracted from 1.5 ml of peripheral blood from 59 patients with gastric cancer and 15 patients with cholecystolithiasis (control) before and after operation. Carcinoembryonic antigen (CEA) messenger RNA (mRNA) was used as a probe to detect gastric cancer cells in samples using a real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Carcinoembryonic antigen mRNA-positive cells were not found in the peripheral blood of the control patients either before or after operation, nor in the peripheral blood of the gastric cancer patients before operation. However, CEA and mRNA-positive cells were detected in 46% of the patients just after a gastrectomy, though these circulating cancer cells disappeared from peripheral blood within 2 postoperative days. In 55 patients who underwent a curative operation, the risk for cancer recurrence (10/30; 33%) in 30 patients who did not show circulating cancer cells postoperatively was higher than that for cancer recurrence (3/25; 12%) in 25 patients with positive for circulating cancer cells (P = 0.064). As a result, the presence of blood circulating tumor cells just after surgery tends to correlate with a low rate of tumor recurrence in patients operated on for gastric cancer. CONCLUSION: These findings indicate that a gastrectomy may spread gastric cancer cells into the peripheral blood from primary tumors; however, such circulating cancer cells may be destroyed within a short time. The detection of circulating cancer cells may therefore be a marker for a possibly better prognosis in patients with gastric cancer.

Adult↗
PubMed2003

Preoperative detection of peripherally circulating cancer cells and its prognostic significance in ovarian cancer.

OBJECTIVES: Studies in several solid tumors have shown that the presence of occult metastasis in the bone marrow or peripheral blood is highly predictive of decreased disease-free and overall survival. Our objective was to determine the incidence of circulating ovarian or primary peritoneal cancer cells in the peripheral blood at the time of disease diagnosis, or recurrence, and to determine the prognostic significance of these occult metastasis. METHODS: Peripheral blood was drawn preoperatively from 91 women thought to have newly diagnosed or recurrent epithelial ovarian or primary peritoneal carcinoma. All samples underwent a tumor-enriched immunocytochemical assay. RESULTS: Sixty-four women were found to have epithelial ovarian or primary peritoneal cancer. Of the 64 women with cancer, 12 had evidence of circulating cancer cells in their peripheral blood (18.7%). Characteristics were compared between those with circulating cancer cells and those without, using Fisher's exact test or the Wilcoxon-Mann-Whitney test, as appropriate. Women with circulating cancer cells had statistically more grade 3 tumors than women without. At a mean follow-up of 18.7 months (SD 6.7 months), analysis using Kaplan-Meier estimation and the log-rank test indicated that survival curves did not differ between patients with and without circulating cancer cells. CONCLUSIONS: Ovarian and primary peritoneal cancer, which historically has been thought to spread primarily by direct cell seeding throughout the abdominal cavity, can have circulating cancer cells in the peripheral blood. The clinical utility of identifying circulating cancer cells is yet to be defined.

Disease-Free Survival↗
PubMed2005

Circulating tumor cells in patients with breast cancer: possible predictor of micro-metastasis in bone marrow but not in sentinel lymph nodes.

BACKGROUND: Blood and lymphatic circulation are the major routes during metastatic spread of breast cancer cells. Despite the predictive and prognostic value of bone marrow (BM) micro-metastasis, repeated and frequent BM aspirations may not be easily accepted by patients. We try to establish the role of circulating tumor cells as a predictor for micro-metastasis in BM and sentinel lymph node (SLN) as well as to identify the association between micro-metastasis in blood and lymphatic circulation. We prospectively studied 47 breast cancer patients without overt metastasis. Bilateral BM samples and blood samples were obtained before surgery and subsequently handled using magnetic-activated cell separation (MACS) followed by immunocytochemistry (ICC). SLN was examined by hematoxylin and eosin (H and E) staining and ICC. RESULTS: Blood and BM micro-metastasis were detected in 16 (35%) and 25 (54%) of 47 patients. SLN micro-metastasis were detected in 13 (27.7%) and 22 (46.8%) patients using H and E and ICC, respectively. All the patients with circulating tumor cells had micro-metastasis in BM, whereas 9 of 25 (36%) patients with micro-metastasis in BM had no circulating tumor cells (P < 0.001). On the other hand, there is no correlation between circulating tumor cells and micro-metastasis in SLNs detected by either H and E (P = 0.52) or ICC (P = 0.36). We found that the presence of circulating tumor cells might predict BM micro-metastasis but not SLN micro-metastasis. It is also interesting to find that the presence of SLN micro-metastasis does not necessarily correlate with the presence of micro-metastasis in BM and blood.

Adult↗
PubMed1990

Renal medullary circulation: hormonal control.

It is now becoming apparent that the medullary circulation in the kidney can be regulated separately from overall renal blood flow. This characteristic of the medullary circulation plays an important role in the kidney's ability to excrete a dilute or concentrated urine in concert with changes in water and sodium transport in the distal nephron secondary to the action of vasopressin, prostaglandins, the renal nerves, and other hormones without significant other renal hemodynamic changes. There is strong evidence that renal autocoids such as angiotensin II and prostaglandins uniquely affect regional blood flow in the inner medulla because of the special structure and organization of the microvasculature in this region. There is also evidence that this regional blood flow is in part regulated by circulating hormones, such as vasopressin and atrial natriuretic peptide, which are released in response to changes in extracellular fluid volume or osmolality. In addition, data are emerging to suggest that the kallikrein-kinin system, acetylcholine, the renal nerves and adenosine participate in this regulation. In addition to the role of the medullary circulation in the urinary concentrating operation, there are data to suggest that the medullary circulation either directly (by changes in physical forces) or indirectly (by regulating medullary toxicity) may influence sodium excretion in a variety of conditions. In this regard, activation of the renin-angiotensin system locally reduces blood flow in the papilla which may be necessary before sodium retention is fully expressed in salt retaining states. Future research looking at the microvasculature of the medulla and papilla and those factors that control the contractility of these vessels are necessary before a clearer picture emerges. Nevertheless, from the data already available it seems reasonable to suggest that the medullary circulation may be as important to kidney function during physiological and pathophysiological states as is the cortical circulation.

Acetylcholine↗
PubMed2004

Circulating tumor cells, disease progression, and survival in metastatic breast cancer.

BACKGROUND: We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer. METHODS: In a prospective, multicenter study, we tested 177 patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit. The progression of the disease or the response to treatment was determined with the use of standard imaging studies at the participating centers. RESULTS: Outcomes were assessed according to levels of circulating tumor cells at baseline, before the patients started a new treatment for metastatic disease. Patients in a training set with levels of circulating tumor cells equal to or higher than 5 per 7.5 ml of whole blood, as compared with the group with fewer than 5 circulating tumor cells per 7.5 ml, had a shorter median progression-free survival (2.7 months vs. 7.0 months, P<0.001) and shorter overall survival (10.1 months vs. >18 months, P<0.001). At the first follow-up visit after the initiation of therapy, this difference between the groups persisted (progression-free survival, 2.1 months vs. 7.0 months; P<0.001; overall survival, 8.2 months vs. >18 months; P<0.001), and the reduced proportion of patients (from 49 percent to 30 percent) in the group with an unfavorable prognosis suggested that there was a benefit from therapy. The multivariate Cox proportional-hazards regression showed that, of all the variables in the statistical model, the levels of circulating tumor cells at baseline and at the first follow-up visit were the most significant predictors of progression-free and overall survival. CONCLUSIONS: The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer.

Breast Neoplasms↗
PubMed2003

Nuclear factor kappaB mediates a procoagulant response in monocytes during extracorporeal circulation.

OBJECTIVE: The objective of this study was to examine the mechanism of procoagulant activity and inhibition in whole blood during extracorporeal circulation. METHODS: In this study we examine the development of procoagulant activity and monocyte activation in heparinized whole blood passing through a closed circuit consisting of a pump and silicone envelope membrane oxygenator for 6 hours. RESULTS: Anaphylatoxins, C3a and C5a, determined by means of enzyme-linked immunosorbant assay, appeared in the blood within 30 minutes of circulation. Circulated blood developed a marked potential for coagulation demonstrated in a 1-step clotting assay that reached maximal activity by 4 hours of circulation. This procoagulant activity was neutralized by anti-tissue factor antibody, suggesting a prominent role for the extrinsic pathway in pump-induced intravascular coagulation. Isolation of monocytes from circulated blood revealed that tissue factor expression is upregulated on the cell surface. Furthermore, we observed nuclear factor kappaB nuclear translocation in monocytes from blood passing through the circuit, suggesting that tissue factor expression was due to monocyte stimulation and transcriptional activation of the tissue factor gene. Tissue factor expression resulted in an approximately 30-fold increase in thrombin generation. Monocyte nuclear factor kappaB activation, monocyte tissue factor expression, thrombin generation, and the procoagulant activity of blood in extracorporeal circulation were all blocked by the proteasome inhibitor MG132. CONCLUSIONS: We conclude that intravascular tissue factor expression during extracorporeal circulation of blood is due to nuclear factor kappaB-mediated activation of monocytes (possibly by complement), which can be controlled pharmacologically.

Blood Coagulation↗
PubMedDate not supplied

Comparative studies of glycoprotein Ib in heparin coated and nonheparin coated extracorporeal circulation circuits.

Contact between blood and artificial materials has various effects on blood. Impairment of platelet function is an especially important and well known effect, but its precise mechanism is not clearly understood. The authors constructed a circulation model to investigate the effect of extracorporeal circulation on platelet membrane glycoproteins (GPs), especially GP Ib, and to compare the changes in GP Ib in heparin coated (group C) and nonheparin coated (group N) circuits. As determined by flow cytometry, GP Ib in both groups decreased on initiating circulation, but the decrease in group N was significantly larger than that in group C. There was no observed change in GP IIb/IIIa levels in either group. The extent of shear stress induced platelet aggregation significantly decreased during circulation in both groups. Decreases in the extent of shear stress induced platelet aggregation were significantly less with the use of heparin coated circuits. In addition, the amount of GP Ib in the high speed pellet decreased progressively during circulation in both groups. In contrast, the amount of GP Ib in the Triton insoluble (low speed) pellet increased dramatically during circulation. However, expression of GP Ib in the Triton soluble platelet fraction was low in both groups. From the results, it was concluded that the cause of the decrease in platelet function during extracorporeal circulation is attributable to the internalization of GP Ib from the platelet surface inside the platelet. It also can be said that a heparin coated circuit is one effective means of controlling this change.

Blood Platelets↗