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[Less invasive establishment of the Fontan circulation in terms of earlier farewell to a cyanotic circulation].

To promote further improvement of surgical results in the longer terms after the Fontan procedure, we have paid attention to age at operation. Establishment of a non-cyanotic circulation at younger stage, for example around 1 year of age, could have potential advantages in postoperative cardiac performance and functional status. In order to commence the Fontan circulation safe and sound, in turn, the surgical intervention ought to be arranged in a less invasive fashion. In this respect, we introduced off-pump Fontan procedure. Since April 1996, 77 patients have undergone the off-pump Fontan procedure. Its less invasive nature was demonstrated in terms of inflammatory reaction immediately after the operation. Further devices are being sought. These include an alternative off-pump procedure even without a temporary bypass for drainage through the inferior caval vein, which has been thus far applied in 14 patients. This option proved to provide readily an excellent surgical field when an extracardiac conduit is to be anastomosed to the orifice of the inferior caval vein. Another device can be a cordial preparation of the extracardiac channel at the time of the bidirectional Glenn procedure when the staged approach is chosen.

Age Factors↗

[Regional liver circulation and scintigraphic imaging of portal circulation with 133Xe].

Regional hepatic blood flow has been determined by 4 methods with the aid of the 133Xe washout technique: scintisplenoportography (direct application of 133Xe into the spleen by means of a thin needle); arterial method (133Xe is injected into the A. hepatica by means of a catheter); retrograde-venous method (133Xe administered by an occluding hepatic vein catheter); percutaneous intrahepatic method (133Xe administered directly into the parenchyma by means of a Chiba needle). Ad 1.: Scintisplenoportography (SSP) was executed with 97 patients: 8 patients with a healthy liver presented a hepatic blood flow of 103.37 +/- 11.5 ml/100 g/min. 4 patients with a chronic hepatitis showed a hepatic blood flow of 105.67 +/- 10.2 ml/100 g/min. In 38 patients with compensated cirrhosis, hepatic blood flow was determined with 58.15 +/- 11.5 ml/100 g/min and 19 patients with decompensated cirrhosis showed a blood flow of 34.54 +/- 7.2 ml/100 g/min. Of the 19 patients, who did not present any liver image, 2 patients suffered from a prehepatic block, 1 patient (female) from a posthepatic block, the rest were decompensated cirrhoses. In 5 patients suffering from steatosis only collateral circulation was determined and in 4 patients the spleen could not be punctured. In the patients with compensated and decompensated cirrhosis of the liver, hepatic blood flow differentiated significantly (p less than 0.001) from patients with healthy livers and chronic hepatitis. In the patients with bioptically assured steatosis only the washout constant was determined. Reproducibility of this method was tested in 4 patients and no statistical difference of hepatic blood flow values could be found and the correlation coefficient amounted to 0.9856. The advantage of SSP lies in the possibility of recording the portal vein circulation: cranial collaterals were found in 33 patients, 2 patients had caudal collaterals exclusively and 29 patients cranial and caudal collaterals. 33 cirrhosis patients presented evidence of hepatic shunts. In nearly all patients hepatic blood flow was higher in the right lobe than in the left. Ad 2.: Arterial method was executed in 26 patients: 2 patients with healthy livers had a hepatic blood flow of 89.85 +/- 2.9 ml/100 g/min, 19 compensated cirrhoses with 49.28 +/- 11 ml/100 g/min and 3 decompensated cirrhoses with 36.43 +/- 3.4 ml/100 g/min. Patients suffering from cirrhosis demonstrated significantly lower hepatic blood flow than patients with healthy livers (p less than 0.001). In arterial application also, with the exception of a single patient, the values for hepatic blood flow were higher for the right than the left lobe of the liver.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Evidence that circulating immune complexes remove transfused platelets from the circulation.

Fifteen recently diagnosed patients with acute leukemias admitted for induction chemotherapy were selected for study. When thrombocytopenic (venous platelet count less than 20 X 10(9)/l) these patients received prophylactic platelet transfusions. A total of 67 platelet transfusion therapies were administered and evaluated. Using the Raji cell radioimmunoassay, the serum concentrations of circulating immune complexes (CIC) were measured immediately before and 10-12 hr after each platelet transfusion. In 36 instances, elevated values of CIC were present in the recipient's pretransfusion samples. The corresponding posttransfusion values being significantly lower (P less than 0.05). Furthermore, in those 36 instances the mean percentage for the posttransfusion platelet increment was significantly lower (P less than 0.001) than in the remaining 31 instances in which normal pretransfusion values of CIC were measured. We conclude that CIC were an important factor in rapidly removing transfused platelets from the circulation, thereby, adversely affecting the benefit of platelet transfusions.

Acute Disease↗

Infarction and circulation in cerebrum. Effect of recanalization and/or collateral circulation on the lesion and prognosis.

Findings of computed tomography (CT) and angiography in supratentorial cerebral infarction associated with complete stroke were compared with regard to prognosis. It was found that the extent of low-density areas on CT was perfectly in accordance with the areas of occluded arteries on angiograms. However, the low-density areas on CT were always smaller than the areas involved angiographically when early recanalization and/or collateral circulation were carried out within 2 to 3 days of onset. It was also found that smaller low-density areas only had favorable effect. We concluded that the prognosis was better with early recanalization and/or collateral circulation, despite the general acceptance of its poor prognostic implication.

Adult↗

A simple neonatal mock circulation enabling pulsatility and different hemodynamical states for neonatal ECMO research: application to assess the effect of a centrifugal pump operated neonatal ECMO system on the circulation.

In neonates, extracorporeal membrane oxygenation (ECMO) is increasingly used for circulatory support, e.g., after cardiac surgery. For training purposes and for research, animal experiments are usually required, complicated by increasing social issues, high costs, and limited reproducibility. Therefore, we designed a mechanical neonatal mock circulation (NMC) model enabling pulsatility and various hemodynamic conditions commonly occurring in neonates. Connected to a flow and pressure reading interface, a computer assisted data management system was installed. A nonocclusive roller pump combined with stiff and elastic tubing segments (for aortic pressure regulation and venous capacity) as well as constant and variable resistance (and optionally a patent duct) are essential features of the NMC system. To show the investigational potential, we studied the influence of venoarterial and venovenous ECMO on the NMC performance during normal circulation, hypovolemia, high arterial resistance, the combination of both, and in low cardiac output. By assessing the significant effects of ECMO on the circulatory function of the NMC, its feasibility and investigational properties could be demonstrated.

Blood Pressure↗

Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor.

Endothelin releases prostacyclin and thromboxane A2 from guinea pig or rat isolated lungs and endothelium-derived relaxing factor in the perfused mesentery of the rat. Endothelin is also substantially removed by the pulmonary circulation of the rat in vitro and in vivo and by guinea pig lungs in vitro. In the rat, the effects of endothelin on the blood pressure vary from pressor (in pithed rats) to purely depressor in anesthetized rats where the resting blood pressure is high. It therefore has the characteristics of a local pressor hormone, rather than a circulating one.

Animals↗

Autoregulation of portal circulation: a correlative study of circulation and vascular morphology.

To investigate the mechanism of portal circulation and the genesis of portal hypertension, an in vivo model was made to increase portal venous flow (PVF) by forming a bypass shunt between the femoral artery to the splenic venous branch in pigs and dogs via a regulatable pump. Using this model, an autoregulatory hemodynamics of the portal circulation and corresponding morphological changes of the intrahepatic vascular system were determined. Immediately after blood flow increase (100 mL/min) to the portal vein, PVF increased to the baseline level plus bypass shunt flow. But, PVF returned to the baseline level within 1 h for both animals. Portal venous resistance (PVR) at 1 h was significantly higher than the baseline level (P < 0.05). By histometric analysis of the cross-sectional area of the portal and hepatic venous branches (CSA-PV, CSA-HV) using the biopsized liver, CSA-HV at 1 h was 27.6% of the CSA-HV of the baseline level in dog, which showed narrowing and contractive changes of the hepatic venous branches, and CSA-PV at 1 h was 36.4% of the CSA-PV of the baseline level in pig, which showed narrowing and contractive changes of the portal venous branches. It is suggested that a tone of the intrahepatic vascular system has an important role in the portal autoregulatory hemodynamics.

Animals↗

Posterior circulation infarcts simulating anterior circulation stroke. Perspective of the acute phase.

BACKGROUND AND PURPOSE: Ischemic stroke patients whose initial clinical presentation suggests an involvement of the anterior circulation (AC) are sometimes found to have a posterior circulation (PC) infarct, a fact that may generate erroneous decisions in clinical management. We investigated the prevalence of this misdiagnosis in the first few hours after stroke onset. METHODS: We performed a cohort study of 158 patients hospitalized within 5 hours of onset of a presumed AC ischemic stroke, as diagnosed on clinical grounds. RESULTS: Final CT or pathology diagnosis was AC infarct in 128 patients (81%), a repeatedly negative CT in 14 (9%), PC infarct (5 pons, 1 midbrain and cerebellum, 6 supratentorial territory of the posterior cerebral artery) in 12 (8%), and other or undiagnosed lesions in 4 (3%). AC and PC stroke patients did not differ in terms of age, vascular risk factors, and initial severity, but the latter were more frequently men (83% versus 53%; P = .04), were hospitalized later (mean +/- SD, 168 +/- 86 versus 109 +/- 55 minutes; P = .001), and presented a pure motor hemiparesis or a sensorimotor stroke (50% versus 33%) more often than their counterparts. At baseline CT, PC stroke patients never exhibited an early parenchymal hypodensity in the carotid territory or a hyperdense middle cerebral artery, which were instead found in 59% (P = .0003) and 31% (P = .02) of AC stroke patients, respectively. Early neurological deterioration, 1 month case-fatality rate, and disablement in survivors were comparable in the two groups. CONCLUSIONS: Shortly after onset the clinical discrimination between AC and nontypical PC infarcts is not reliable, which explains the frequent occurrence of this misdiagnosis. Emergency CT scan helps in the differential diagnosis only when it demonstrates an early focal hypodensity within the carotid territory.

Acute Disease↗

Comparison of conventional extracorporeal circulation and minimal extracorporeal circulation with respect to microbubbles and microembolic signals.

The intention of minimal extracorporeal circulation (MECC) is to reduce priming volume and minimize contact of blood with polymers and air in a closed system. In contrast to conventional extracorporeal circulation (ECC), a venous reservoir is missing. Thus, air trapping is limited and avoidance of bubble embolism is a major concern. This study investigates microbubbles (MBB) number and size in the venous and arterial lines of ECC and MECC compared to the number of microembolic signals (MES) in the right and left middle cerebral artery (MCA). Twenty patients undergoing coronary surgery were operated either with conventional ECC (cardiotomy reservoir, Rotaflow pump, Quadrox oxygenator, Quart filter) or MECC (Quart filter, Rotaflow pump, Quadrox oxygenator). Number and size of MBB were monitored in the venous and arterial lines with an ultrasound Doppler system. MES in right and left MCAs were measured by transcranial Doppler (TCD) monitoring. Patients undergoing MECC had additional sealing of the venous cannula by a ligature at the site of its insertion into the right atrium. There were no significant differences between groups with respect to age, X-clamping, bypass time and number of distal anastomoses. The number of MES and MBB in the arterial line was comparable between the groups. On the venous side, MECC-perfusion shows a significantly lower number of MBB. This could be explained with the additional sealing of the venous cannula. Furthermore, our data indicate that the MBB-volume reaching the pump will also appear in the arterial outflow and into the patient's MCA. For this reason, the avoidance of air contamination is a major concern for surgeons, anaesthesiologists and perfusionists.

Aged↗

Differential CD146 expression on circulating versus tissue endothelial cells in rectal cancer patients: implications for circulating endothelial and progenitor cells as biomarkers for antiangiogenic therapy.

PURPOSE: Circulating endothelial cells (CECs) and progenitor cells are currently evaluated as potential biomarkers of antiangiogenic therapy. CD146 is considered a panendothelial-specific marker, but its utility as a CEC marker in cancer patients remains unclear. PATIENTS AND METHODS: We analyzed the expression of CD146 on mononuclear blood cells, primary tissue endothelial cells, and malignant and normal tissues by flow cytometric and immunohistochemical analyses. Furthermore, we measured the circulation kinetics of CD146+ cells before, and then 3 and 12 days after vascular endothelial growth factor (VEGF) antibody blockade by bevacizumab infusion in rectal cancer patients enrolled in a phase I trial. RESULTS: In the peripheral blood of these cancer patients, over 90% of the CD146+ cells were CD45+ hematopoietic cells. CD146 expression was primarily detected on a subset of CD3+CD4+ lymphocytes, and was undetectable on CD34+CD133+CD45(dim) progenitor cells or CD31(bright)CD45- viable CECs. In contradistinction, CD146 was detectable in tissues on both cellular components of tumor vessel wall: CD31(bright)CD45- endothelial cells and alpha-SMA+ pericytes. Unlike viable CECs and progenitor cells, CD146+ cell concentration in the peripheral blood of cancer patients did not decrease during VEGF blockade. CONCLUSION: CD146 is fairly homogeneously expressed on vascular endothelium but not on viable CECs or progenitor cells. The vast majority of CD146+ blood cells are lymphocytes, and VEGF blockade by bevacizumab did not significantly change their number in rectal cancer patients. These results underscore the need for further characterization and identification of new markers for CEC subpopulations for their development as biomarkers of antiangiogenic therapy.

Angiogenesis Inhibitors↗

[Effects of ATP on cerebral circulation--morphological observation of cerebral circulation and cerebral vasculature].

Review was made on the effect of adenosine triphosphate, 1.0-3.0 mg/kg intravenously, on the cerebral circulation and the presence of the dilating action on the cerebral blood-vessels in cats. 1. The group of the normal intra-cranial pressure showed, as reported previously, the transient hypotension and its complicated decrease of cerebral blood-circulation at the initial period for 30-100 check, then demonstrating the increase of cerebral blood-flow for 200-1000 check. Its increased volume and duration were dose-dependent. 2. The group of the loaded intracranial pressure of 20-30 mmHg (slightly elevated group) showed the increase of cerebral blood-flow, like the group of the normal intracranial pressure. However, the effect of ATP showed the decrease or disappearance in accordance with the elevation of the loaded pressure. 3. Cerebral vasodilating effect of ATP was promptly observed after the administration, and its degree was 30-50% in photographical observation. 4. Increasing effect on cerebral blood-flow and cerebral vasodilating action of ATP were similar in the pattern to that of vasodilators such as papaverine hydrochloride.

Adenosine Triphosphate↗

The 1653 English edition of De motu cordis, shown to be Harvey's vernacular original and revealing crucial aspects of his pre-circulation theory and its connection to the discovery of the circulation of the blood.

From a comparative study of the first Latin edition of William Harvey's De motu cordis published in 1628, and the first English edition published in 1653, it is argued that the latter is the printed copy of Harvey's original manuscript written in the vernacular. It will also be shown that Harvey's pre-circulation theory described the heart as an impulsor of blood for several years before his discovery of the circulation of the blood. The crucial aspect of his description was a new explanation of the cause of the arterial pulse as felt at the extremities.

Blood Circulation↗

[Regional liver circulation and the scintigraphic representation of the portal circulation with 133Xe].

Regional hepatic blood flow has been determined by 4 methods with the aid of the 133Xe washout technique: scintisplenoportography (direct application of 133Xe into the spleen by means of a thin needle); arterial method (133Xe is injected into the A. hepatica by means of a catheter); retrograde-venous method (133Xe administered by an occluding hepatic vein catheter); percutaneous intrahepatic method (133Xe administered directly into the parenchyma by means of a Chiba needle). Ad 1.: Scintisplenoportography (SSP) was executed with 97 patients: 8 patients with a healthy liver presented a hepatic blood flow of 103.37 +/- 11.5 ml/100 g/min. 4 patients with a chronic hepatitis showed a hepatic blood flow of 105.67 +/- 10.2 ml/100 g/min. In 38 patients with compensated cirrhosis, hepatic blood flow was determined with 58.15 +/- 11.5 ml/100 g/min and 19 patients with decompensated cirrhosis showed a blood flow of 34.54 +/- 7.2 ml/100 g/min. Of the 19 patients, who did not present any liver image, 2 patients suffered from a prehepatic block, 1 patient (female) from a posthepatic block, the rest were decompensated cirrhoses. In 5 patients suffering from steatosis only collateral circulation was determined and in 4 patients the spleen could not be punctured. In the patients with compensated and decompensated cirrhosis of the liver, hepatic blood flow differentiated significantly (p less than 0.001) from patients with healthy livers and chronic hepatitis. In the patients with bioptically assured steatosis only the washout constant was determined. Reproducibility of this method was tested in 4 patients and no statistical difference of hepatic blood flow values could be found and the correlation coefficient amounted to 0.9856. The advantage of SSP lies in the possibility of recording the portal vein circulation: cranial collaterals were found in 33 patients, 2 patients had caudal collaterals exclusively and 29 patients cranial and caudal collaterals. 33 cirrhosis patients presented evidence of hepatic shunts. In nearly all patients hepatic blood flow was higher in the right lobe than in the left. Ad 2.: Arterial method was executed in 26 patients: 2 patients with healthy livers had a hepatic blood flow of 89.85 +/- 2.9 ml/100 g/min, 19 compensated cirrhoses with 49.28 +/- 11 ml/100 g/min and 3 decompensated cirrhoses with 36.43 +/- 3.4 ml/100 g/min.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Changes in autonomic response of the cerebral circulation after normothermic extracorporeal circulation.

Patients who undergo cardiopulmonary bypass frequently have neuropsychologic dysfunction. This study was undertaken to determine whether altered cerebral perfusion and vascular responses may in part lead to these neuropsychologic changes. Pigs were placed on normothermic cardiopulmonary bypass for 2 hours. Basal cerebral blood flow and in vivo responses to administration by internal carotid artery of neuronally released vasoactive substances were evaluated before and 5 to 15 minutes after termination of cardiopulmonary bypass. Another group of pigs were placed on cardiopulmonary bypass for 2 hours and then perfused off bypass for 1 additional hour. In vitro responses of cerebral arterial microvessels (100 to 175 microns) from both groups were examined in a pressurized (40 mm Hg) no-flow state with videomicroscopy. Vessels from uninstrumented pigs served as control preparations for in vitro studies. Cerebrovascular resistance and cerebral perfusion were maintained constant during cardiopulmonary bypass and after separation from bypass. The internal carotid artery infusion of acetylcholine (cholinergic agonist) caused increased internal carotid artery blood flow before cardiopulmonary bypass but decreased blood flow after cardiopulmonary bypass. After 2 hours of cardiopulmonary bypass, the increase in internal carotid artery blood flow induced by isoproterenol (a beta-adrenoceptor agonist) was reduced, whereas the response to sodium nitroprusside (a guanylate cyclase activator) was unchanged. In vitro acetylcholine-induced microvascular vasodilation was converted to a contractile response and isoproterenol elicited less relaxation after 2 hours of cardiopulmonary bypass. One hour of cerebral perfusion after cardiopulmonary bypass caused a further reduction in isoproterenol-induced relaxation but had no further effect on the cholinergically mediated response. In vitro relaxation responses to sodium nitroprusside and forskolin (an adenylate cyclase activator) were similar in all experimental groups, suggesting that second-messenger mechanisms remain intact after normothermic cardiopulmonary bypass. In conclusion, basal cerebrovascular resistance and internal carotid artery blood flow are maintained if the systemic circulation and pressure are supported with fluid administration after cardiopulmonary bypass. Agonist-induced vasodilation of cerebral microvessels to cholinergic and beta-adrenoceptor stimulation are selectively impaired after normothermic cardiopulmonary bypass, whereas second-messenger mechanisms remain intact.

Acetylcholine↗

Surface receptors and immune activity of purified human circulating mononuclear cells. V. Circulating null cells and a factor secreted by the null cells inhibit the synthesis of receptors for Fc mu by T cells in culture.

Receptors for Fc mu (Fc mu R) were not detected on freshly isolated unfractionated circulating human mononuclear cells (MNC) or purified T cells. However, a significant percentage of the T cells (20% to 40%), but not of the unfractionated MNC, exhibited Fc mu receptors following culture for 24 h at 37 degrees C in medium enriched with fetal calf serum. These receptors were newly synthesized by the T cells since they were not detected on T cells cultured for 24 h with cycloheximide in a non-cytotoxic concentration. The absence of Fc mu R on the cultured unfractionated MNC (of which 70% are T cells) suggested that non-T cells within the MNC-B cells and/or null cells and/or monocytes suppressed the synthesis of Fc mu R by the T cells. These cells were individually assayed for their capacity to suppress Fc mu R synthesis by co-cultured T cells. The null cells were able to totally suppress Fc mu R synthesis whereas the B cells and monocytes exhibited no suppressive activity. Null cells cultured for 24 h at 37 degrees C secreted a factor which inhibited the synthesis of receptors for Fc mu by the cultured T cells. This factor is referred to as receptor synthesis suppressor factor or RSSF. On the basis of these findings, it is concluded that (a) the circulating T cells do not possess Fc mu R; these receptors are synthesized de novo by the T cells in culture, (b) the null cells, but neither the B cells nor the monocytes, suppress the synthesis of the Fc mu R by the T cells and (c) the null cells, but neither the B cells nor the monocytes, secrete a factor, receptor synthesis suppressor factor, which can suppress the synthesis of Fc mu R by the T cells.

Cells, Cultured↗

Serum levels of circulating anodic antigen and circulating cathodic antigen detected in mice infected with Schistosoma japonicum or S. mansoni.

Serum concentrations of circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were studied in mice infected with either Schistosoma japonicum or S. mansoni cercariae. Sera from uninfected mice were negative for both antigens. CAA was detectable in the S. japonicum-infected mice as early as at 2 weeks post-infection (p.i.), and levels were higher in these animals than in the S. mansoni-infected group during the full study period. At the moment of perfusion, 10 weeks p.i., a median of 9 and 29 worms, respectively, were recovered from the S. japonicum- and S. mansoni-infected mice, and the median CAA levels were 326 and 27 ng/ml, respectively. In contrast, CCA levels were much lower in the S. japonicum-infected group (27 ng/ml) as compared with the S. mansoni-infected mice (282 ng/ml). These results suggest an important difference between S. japonicum and S. mansoni infections in CAA and CCA production and/or clearance and indicate a significant role for CAA in the diagnosis of human schistosomiasis japonicum.

Animals↗

Circulating soluble adhesion molecules in patients with systemic sclerosis: correlation between circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) and impaired left ventricular diastolic function.

The objective of this paper is to investigate the relation between circulating soluble adhesion molecules and cardiac involvement, as assessed by echocardiography in patients with systemic sclerosis (SSc). Nineteen patients with SSc were submitted for assessment of serum levels of circulating soluble intercellular adhesion molecules (sICAM-1), and soluble vascular cell adhesion molecules-1 (sVCAM-1), and echocardiography. Abnormal left ventricular filling patterns (down E/A ratio) were detected in ten patients (52.6%) with significant negative correlation with sVCAM-1 (r = -0.484, P < 0.05). It was also significantly correlated with age (r = -0.791, P < 0.01), age of onset (r = -0.468, P < 0.05), degree of dyspnea (r = -0.687, P < 0.01), and erythrocyte sedimentation rate (ESR) (r = -0.489, P < 0.05). Our findings suggest an important role for sVCAM-1 as a marker of disease severity and impaired left ventricular filling pattern in SSc.

Activities of Daily Living↗