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Extracorporeal circulation for the removal of serum myoglobin in experimentally induced myonephropathic metabolic syndrome in dogs.

The removal of serum myoglobin with extracorporeal circulation using a column filled with methylmethacrylate-divinylbenzene (MMA-DVB) was studied in experimentally induced myonephropathic metabolic syndrome in the dog. All animals showed marked edema in the hind limbs and degeneration or necrosis of the adductor muscle 5 hours after the reestablishment of arterial flow. The serum levels of myoglobin, creatinine phosphokinase, glutamic oxaloacetic transaminase and aldolase increased linearly after the reperfusion of blood in the group of animals which received no extracorporeal circulation (group 1). Sediments of numerous myoglobin casts in the renal tubules and immunoreactive myoglobin in the renal epithelium of almost all the tubules were seen in 4 out of 5 cases. In the group of animals reperfused with extracorporeal circulation using the MMA-DVB column, serum myoglobin was adsorbed selectively by the column and showed a significantly lower value at 0.5, 1, 2 and 3 hours than that of the group 1 animals. Concomitantly, the immunoreactive myoglobin was absent or scant in the renal epithelium of the proximal convoluted tubule. The present study therefore indicates that extracorporeal circulation using the MMA-DVB column is useful for the removal of serum myoglobin from experimentally induced myonephropathic metabolic syndrome.

Animals↗

Collateral circulation in stenosis or occlusion of the renal artery.

The abdominal angiograms of 381 patients were critically reexamined for the existence of collateral circulation in cases of renal artery stenosis or occlusion. Typical renal artery stenosis was found in 39 patients; among these, 17 had a collateral circulation, which was extrarenal in 15 and intrarenal in two. Collateral circulation involving the lumbar arteries was most common. In two patients a collateral circulation was established via the inferior mesenteric artery.

Adolescent↗

Combined use of positive and negative immunomagnetic isolation followed by real-time RT-PCR for detection of the circulating tumor cells in patients with colorectal cancers.

To establish a novel molecular diagnostic method of detecting circulating tumor cells (CTCs) LS174T colon cancer cells were serially diluted with normal blood. Additional peripheral blood samples were collected from 25 patients with colorectal carcinoma. Mononuclear cells (MNCs) were collected, equally divided into four parts, and then cancer cells were enriched by four methods: method A, nonimmunobead method; method B, negative immunobead method: CD45 immunomagnetic beads were used to deplete the leukocytes; method C, positive immunobead method: Ber-EP4 immunomagnetic beads were used to enrich cancer cells; method D, negative-and-positive immunobead method: CD45 immunomagnetic beads were first used to deplete the leukocytes from MNC and then Ber-EP4 immunomagnetic beads were used to enrich cancer cells. Finally, real-time quantitative RT-PCR was used to monitor mRNA expression of beta2-mircoglobulin (beta2M) and carcinoembryonic antigen (CEA). The relative CEA mRNA values were corrected with reference to beta2M mRNA, to CEA mRNA/beta2M mRNA ratios according to a CEA mRNA external standards prepared with tenfold serial dilutions (1-10(4) IS174T cells) of cDNA and beta2M mRNA external standards prepared with tenfold serial dilutions (10(2)-10(7) leukocytes) of cDNA. In recovery experiments a significant correlation between the number of cancer cells and CEA mRNA expression was found when CD45 or Ber-EP4 immunomagnetic beads were used alone. A highly significant correlation was found when CD45 and Ber-EP4 immunomagnetic beads were used successively. The sensitivity of method D was one cancer cell per milliliter of blood. Circulating cancer cells were detected in 19 of 25 patients with colorectal cancers. The relative CEA mRNA value obtained by method D was the smallest. The positive detection rate of circulating cancer cells in patients at Dukes' B, C, and D stages were 25.0% (1/4), 83.3% (10/12), and 88.9% (8/9). Combinative use of immunomagnetic isolation followed by real-time RT-PCR is a useful technique to detect circulating tumor cells in patients with colorectal carcinomas. Applying negative and positive immunomagnetic beads successively yields the highest correlation with amount of tumor cells.

Aged↗

Assessment of changes in cerebral circulation time due to vasospasm in a specific arterial territory: effect of angioplasty.

This study demonstrates that in experienced hands, intracranial angioplasty is a feasible and safe option in a selected group of patients with severe (>50% stenosis) symptomatic vasospasm following subarachnoid hemorrhage. Cerebral circulation time is a surrogate parameter closely linked to cerebral perfusion. The study presented shows that not only stenosis but also changes in circulation time are obtained by angioplasty. Twenty angioplasties of one or two vessel segments were performed over 2 years in 18 consecutive patients with posthemorrhagic vasospasm fulfilling criteria for invasive treatment. In all patients, degree of stenosis and circulation time could be reduced by angioplasty. Clinical results were ranked according to Glasgow Outcome Scale. Imaging after 15/20 angioplasties showed no additional infarction. In 4/20 cases, CT showed demarcation of infarction after angioplasty. In 1/20 cases of posterior circulation angioplasty, CT is not sensitive enough to exclude smaller infarctions. Imaging and clinical outcome reveal a definite benefit.

Adolescent↗

Plasma endothelin-1 levels depress optic nerve head circulation detected during the glucose tolerance test.

PURPOSE: To determine the relationship between the changes in optic nerve head (ONH) circulation and the level of plasma endothelin-1 (ET-1) during the glucose tolerance test (GTT). METHODS: Twenty-six healthy volunteers with normal GTT and 15 patients with mild hyperglycemia and abnormal GTT were studied. The ONH circulation [square blur rate (SBR) value], blood pressure, intraocular pressure (IOP), blood glucose, blood insulin and plasma ET-1 were determined before and every hour up to 3 h after an oral intake of 75 g of glucose. RESULTS: The SBR increased in the normal glucose tolerance group at all times during the GTT, but it decreased significantly in the abnormal glucose tolerance group (P < 0.05). Before the GTT, the plasma ET-1 level was not significantly different in the two groups; however, the level increased 1 h after the oral GTT in the abnormal glucose tolerance group (P < 0.05). No significant changes were observed in mean blood pressure or IOP. CONCLUSIONS: ONH circulation increased after glucose intake in the normal glucose tolerance group and remained high even after the blood glucose level had returned to its baseline. The decrease in ONH circulation in the abnormal glucose tolerance group was attributed partly to the increased ET-1.

Adult↗

Effects of dexmedetomidine on cerebral circulation and systemic hemodynamics after cardiopulmonary resuscitation in dogs.

PURPOSE: Our purpose was to examine the effect of dexmedetomidine, when used with phenylephrine during cardiopulmonary resuscitation (CPR), on the cerebral and systemic circulations. METHODS: In pentobarbital-anesthetized, mechanically ventilated dogs, we evaluated pial vessel diameters, cerebral oxygen extraction, and systemic hemodynamics before and after cardiac arrest (5 min) and resuscitation, in the presence or absence of dexmedetomidine (n = 7 each; dexmedetomidine or control group). RESULTS: In both groups: (a) pial arterioles were dilated at 5 and 15 min after CPR, and had returned to baseline diameters at 30 min; (b) sagittal sinus pressure was significantly raised at 5 and 15 min after CPR; and (c) cerebral oxygen extraction was decreased at 5, 15, and 30 min after CPR, and had returned to baseline level at 60 min after CPR. We could find no differences between the two groups in the cerebral circulation after CPR. However, the number of defibrillation electric shocks required to restore spontaneous circulation (5.5 vs 3.6; P < 0.05), the dose of phenylephrine used for CPR (1193 microg vs 409 microg; P < 0.01), and the number of postresuscitation ventricular ectopic beats observed during the first 120 min after successful resuscitation (1606 vs 348; P < 0.05) were all significantly lower in the dexmedetomidine group. CONCLUSION: Although intravenous dexmedetomidine, as used for CPR, does not have a beneficial effect on either cerebral vessels or cerebral oxygen extraction, it may reduce the number of defibrillation shocks needed and the number of postresuscitation ventricular ectopic beats, and help to bring about stable systemic circulation after CPR.

Analgesics, Non-Narcotic↗

Cardiac hemodynamics, coronary circulation and interventional cardiology.

Microcirculation is the functional end of the coronary circulation and it plays a key role in the regulation of coronary blood flow, both on the local and global scales. A good understanding of its function under physiological and pathophysiological conditions is crucial but, because of its micro-scale, access to this part of the coronary circulation is extremely difficult and requires a considerable amount of innovation and new technologies. Dynamics of the coronary circulation provide the true vehicle by which blood supply reaches the myocardium- coronary vasculature is only the conducting component of that vehicle. It is highly unlikely that the pulsatile nature of the flow, the capacitance of the conducting vessels and the constant pounding of coronary vasculature by surrounding tissue are not part of the design, regulation, and function of the coronary circulation. Interventions, whether to assess or to correct coronary stenosis, continue to be the main clinical avenue to dealing with coronary heart disease. Clinical decisions rely heavily on the ability to determine the true morphology of an occlusive lesion, to predict the future course of that lesion and to assess the functional toll on coronary blood supply which it will inflict at each stage.

Animals↗

Detection of Survivin-expressing circulating cancer cells in the peripheral blood of breast cancer patients by a RT-PCR ELISA.

Survivin mRNA expression was detected in 69.2%-93.8% of primary breast carcinomas, but is rarely expressed in normal breast tissues and hematopoietic cells. The objective of this study was to investigate the significance that the detection of Survinin-expressing circulating breast cancer cells in the peripheral blood has on clinical outcomes. The detection method was based on a RT-PCR ELISA technique developed in our laboratory. Sixty-seven breast cancer patients in various stages and 135 normal healthy women were investigated. Survivin-expressing circulating cancer cells were detected in the peripheral blood samples from 34 (50.7%) out of 67 breast cancer patients, but not in the healthy women that were used as controls. The presence of Survivin-expressing circulating breast cancer cells was found to be significantly associated with various clinicopathological parameters such as vessel infiltration, histological grade, tumor size, nodal status, ER/PgR status, Her-2 status and clinical stages of the disease (P < 0.01). During a follow-up period of 36 months, 9 out of 11 (81.8%) breast cancer patients that had a positive Survivin-expressing at the time of the initial assay test suffered a relapse of the disease, whereas recurrence was only found in 2 out of 6 (33.3%) breast cancer patients that had a negative Survivin-expression. Thus, the detection of circulating cancer cells expressing Survivin mRNA could provide valuable information for the prediction of metastasis and recurrence of breast cancer.

Adult↗

Tumor cell and circulating markers in melanoma: diagnosis, prognosis, and management.

The search is on for biomarkers for use in the diagnosis, staging, prognosis, and management of patients with melanoma. As with many types of cancer, the hematogenous spread of melanoma is a bad prognostic sign, and many groups have attempted to detect circulating melanoma cells in patients with different stages of melanoma. Some studies have used direct extraction of intact tumor cells from the peripheral blood and others the detection of surrogate markers of circulating melanoma cells, such as tyrosinase or MART-1. However, a correlation between the detection of intact melanoma cells in the circulation and prognosis is controversial. Many other biomarkers have also been studied, including lactate dehydrogenase, S100, TA90, and C-reactive protein. Much progress has been made, and preliminary studies have shown promise with many of these markers. Finally, the detection of tumor-specific circulating DNA has shown promise as a prognostic and diagnostic marker of disease in melanoma as well. In this review we examine the most promising biomarkers for use in patients with cutaneous melanoma.

Antigens, Neoplasm↗

Importance of ischemic preconditioning and collateral circulation for left ventricular functional recovery in patients with successful intracoronary thrombolysis for acute myocardial infarction.

We studied the effects of myocardial ischemic preconditioning and preexistent collateral circulation on the preservation of left ventricular function in 30 patients who had successful intracoronary thrombolysis within 6 hours after the onset of a first acute anterior myocardial infarction. The existence of ischemic preconditioning was defined as the episode of recurrent ischemic chest pain within 4 hours before the onset of acute myocardial infarction. In 16 patients with ischemic preconditioning (group A), the left ventricular ejection fraction during the convalescence of myocardial infarction was 57% +/- 11% (mean +/- SD); regional wall motion in the infarct area was 13% +/- 9%. In 14 patients without ischemic preconditioning (group B), the left ventricular ejection fraction and regional wall motion in the infarct area were 46% +/- 9% and 5% +/- 9% (both p < 0.05 vs group A). Moreover, among group A patients, seven patients having a well-developed collateral circulation during the acute stage of myocardial infarction showed a more prominent improvement in regional wall motion in the infarct area compared with nine patients having poor or no collateral circulation (18% +/- 8% vs 9% +/- 7%, p < 0.05). These data indicate that ischemic preconditioning is effective for the preservation of left ventricular function in patients with successful intracoronary thrombolysis and that preexistent coronary collateral circulation potentiates this favorable effect of ischemic preconditioning.

Adult↗

Predictive criteria for the need of extracorporeal circulation in single-lung transplantation.

Use of extracorporeal circulation is mandatory in heart-lung and en bloc double-lung transplantation. However, no criteria exist to predict the necessity of its application during single-lung transplantation for parenchymal lung diseases. We therefore reviewed our experience in 23 patients undergoing single-lung transplantation for idiopathic pulmonary fibrosis. All patients were evaluated by preoperative right heart catheterization. For intraoperative monitoring, a pulmonary artery thermodilution catheter was placed in the contralateral lung to repeatedly assess pulmonary artery pressure, cardiac output, and pulmonary vascular resistance. Extracorporeal circulation was necessary during graft implantation in 4 patients, whereas 19 patients underwent operation without it. Preoperative demographic patient data, time of ischemia, and hemodynamic values obtained preoperatively and before the clamping of the pulmonary artery showed no significant differences between groups. In contrast, after the clamping of the pulmonary artery, a significant drop in cardiac index of about 1.5 L.min-1.m-2 (p less than 0.01) and a concomitant rise in pulmonary vascular resistance (p less than 0.01) was observed in the group requiring extracorporeal circulation, whereas these variables showed no significant changes in the other 19 patients. Pulmonary artery pressure rose significantly in both groups (p less than 0.05), without significant differences between them. It is concluded that intraoperative assessment of cardiac index and pulmonary vascular resistance is essential for estimation of cardiac performance during single-lung transplantation. A decrease in cardiac index of more than 1.5 L.min-1.m-2 after the clamping of the pulmonary artery rather than the degree of pulmonary hypertension is indicative of the need of extracorporeal circulation.

Adult↗

Relationship between regional pertechnetate cerebral circulation time and EEG in patients with cerebral infarction.

The qualitative and regional correlations between the EEG and the cerebral circulation time (CCT), obtained by using intravenously injected pertechnetate and a multidetector device, were studied in 75 patients with supratentorial cerebral infarction. Because bolus dispersion and changes in systemic circulation may distort absolute CCT values when intravenous injection of the isotope is used, the inter- and intrahemispheric relative CCT values were used as indices of CCT. Overall good correlations could be demonstrated between both inter- and intrahemispheric CCT abnormalities and the EEG, though not in all patients. The number of patients with pathological CCT findings showed a tendency to increase with increasing severity of the EEG abnormality. The number of abnormal CCT areas per patient (indicating the size of the circulation disturbance) also increased significantly with increasing severity of the EEG disturbance. Interestingly, relative 'hypervelocity' areas occurred in fewer patients with normal or clearly disturbed EEGs than in patients with mildly disturbed EEGs, perhaps due to differences in autoregulatory capacity and collateral circulation. Within the EEG focus the relative number of CCT abnormalities was greater than outside it. In spite of this fairly good overall correlation between the EEG focus and the CCT abnormality, more than 10% of the patients with an EEG focus showed no CCT abnormalities, thus indicating the complementary roles of these methods. The present study on cerebral infarction, though using intravenously injected pertechnetate for the CCT measurement, showed a reasonable correspondence with earlier reports on the relationship between the EEG and either the CBF or the CCT (obtained by intra-arterially injected isotope). This would seem to suggest that the used non-invasive method for regional CCT measurement has potential for evaluation of cerebral haemodynamics.

Adult↗

A nonlinear fluid model for pulmonary blood circulation.

In this paper, we apply a quasi-one-dimensional unsteady nonlinear fluid model to study human pulmonary circulation. Eighteen generations of blood vessels composed of the branching arterial, capillary and venous distensible vessel segments make up the complete pulmonary circulation. The numerical result gives satisfactory agreement with the physiological experimental data: a dramatic pressure drop occurs in the arterioles and postcapillaries, a negative transmural pressure is shown in the postcapillary and small venous segments, a large reverse flow occurs in the main pulmonary artery during the diastolic period, and the reverse flow decreases gradually along the pulmonary tree. In the microgravity case where g = 180 cm s-2, the computation illustrated the effect of gravity force on the blood distribution in the different parts of the pulmonary circulation. The effect of gravity on the total output is not obvious. The effect of local factors which initiate the variations of the geometrical or pulmonary circulation can be stimulated quantitatively by this model. The proposal model can be very useful for clinical practice and for studying the extreme cases which are very difficult to investigate by experiments.

Arteries↗

Vagal release of serotonin into gut lumen and portal circulation via separate control mechanisms.

The mechanisms controlling vagally induced serotonin-like immunoreactivity (5-HTLI) release into portal circulation and jejunal lumen were studied in individual cats. In control animals, electrical vagal nerve stimulation significantly enhanced both the endoluminal secretion rate of 5-HTLI and the release of 5-HTLI to the portal vein. The vagally induced release of 5-HTLI to the portal circulation was blocked by pretreatment with propranolol or phenoxybenzamine, or by prior removal of the superior cervical ganglia, but was not blocked by atropine or hexamethonium. On the contrary, the luminal secretion of 5-HTLI after vagal stimulation was not blocked by adrenoceptor blocking agents or ganglionectomy, but instead was inhibited by cholinoceptor antagonists. Thus, in the same experimental animal it was shown that vagally induced release of 5-HTLI to the portal circulation was mediated by adrenoceptor mechanisms, while the luminal release of 5-HTLI was regulated via cholinoceptors. Based on indirect estimations, the apical release of 5-HT seems to be qualitatively small in comparison with the release into the portal circulation.

Animals↗

Atrial natriuretic peptide increases adrenomedullin in the circulation of healthy humans.

Adrenomedullin (ADM) is a new 52 amino acid peptide originally isolated from extracts of human pheochromocytoma. ADM's biologic properties are nearly identical to those of atrial natriuretic peptides. Thus, the 4 peptide hormones originating from amino acids 1-30 [long acting natriuretic peptide], 31-67 [vessel dilator], 79-98 [kaliuretic peptide] and 99-126 [atrial natriuretic factor; ANF] of the 126 amino acid ANF prohormone as well as ADM have blood pressure lowering and diuretic properties. The present investigation was designed to determine if one or more of these 4 atrial natriuretic peptides increase adrenomedullin within the circulation of healthy humans. Infusion of 100 ng/kg body weight/minute for 60 minutes of the respective atrial peptides resulted in a 4-fold (P < 0.001) increase in the circulating concentration of adrenomedullin secondary to the ANF infusion but no increase in adrenomedullin with the long acting natriuretic peptide, vessel dilator, or kaliuretic peptide infusions. The four-fold increase of adrenomedullin in the circulation persisted throughout the infusion of ANF, but returned to pre-infusion levels within 30 minutes of stopping the ANF infusion. Infusion of 10 pg/kg body weight/minute for 60 minutes of ANF resulted in a 2 1/2-fold increase (P < 0.05) in the circulating concentration of adrenomedullin. There was a significant (P < 0.01) diuresis and blood pressure lowering effect with each of the atrial natriuretic peptides in the present investigation. This investigation suggests that 1) atrial natriuretic factor increases the release of adrenomedullin and 2) that the diuretic and blood pressure lowering effects previously attributed to atrial natriuretic factor may be partially due to adrenomedullin since both increased during the ANF infusion and both have similar biologic effects. As opposed to atrial natriuretic factor, adrenomedullin was not increased by long acting natriuretic peptide, vessel dilator, or kaliuretic peptide suggesting that their biologic effects do not involve adrenomedullin.

Adrenomedullin↗

Cerebral circulation during diabetes mellitus.

Diabetes mellitus is characterized by hyperglycemia, a decrease in circulating insulin and the development of macro- and microvascular pathology. Hyperglycemia appears to be a primary determinant for the structural, biochemical and functional changes that occur in large and small blood vessels during diabetes mellitus. While much research has focused on the effects of diabetes mellitus on the peripheral circulation, it is clear that diabetes mellitus also has profound effects on the cerebral circulation. Thus, the focus of this review is to discuss morphological and functional alterations in the cerebral circulation during diabetes mellitus.

Animals↗

Effects of acute myocardial infarction on the circulation of the conscious rat.

This study was conducted to determine if experimental left coronary artery ligation resulting in a small myocardial infarction (MI, 15% of the left ventricle) affects the peripheral circulation in conscious rat during the first 48 h of recovery. At 24 or 48 h post-MI or sham surgery, animals were instrumented and evaluated using the radioactive microsphere technique. There were no overt central hemodynamic changes 24 h post-MI but at 48 h, left ventricular end diastolic pressure was significantly increased compared to the parallel control (MI: 5.9 +/- 0.6, sham 2.0 +/- 0.5 mm Hg, P less than 0.005). At 24 h post-MI, renal vascular resistance was increased and similar but non-significant changes occurred in the gut. At 48 h post-MI, vascular resistance in the skeletal muscle, spleen, gut and cutaneous circulations were significantly reduced compared to sham-operated rats. Similar changes at 24 h were seen in a separate group of conscious rats with MI which had previously undergone cardiac denervation suggesting that cardiac afferent activity was not directly responsible for the peripheral response to MI at 24 h. Denervation did eliminate the 48 h peripheral vasodilator response. In denervated animals, circulating renin levels were similar in MI and sham-operated rats and were unchanged between 24 and 48 h. Thus, small MI in conscious rat induces a sequela of effects on the peripheral circulation over 48 h. These changes are associated with cardiac afferent nerve activity but appear to be unrelated to plasma renin levels.

Animals↗

Evidence for an enterohepatic circulation of ochratoxin A in mice.

The distribution and elimination of [3H]ochratoxin A (OTA) from stomach content and tissue, intestine content and tissue, liver, bile, serum and urine of Swiss male mice which had received a single low dose of OTA by intubation was followed as a function of time. The profiles of radioactivity do not show a smooth decline after the absorption period, but an oscillating pattern with rapid declines followed by increases which favour the assumption of an enterohepatic circulation. Between 28% and 68% of conjugated OTA together with OTA cleavage products were found in bile giving evidence for biliary excretion of OTA and its metabolites in mice. When given i.m. to mice [3H]OTA is already found after 30 min in bile and intestine contents and its elimination patterns show several peaks confirming the biliary excretion and the enterohepatic circulation. Cholestyramine, which is known to prevent the enterohepatic circulation of drugs and toxins, changes the profile of elimination of OTA which no longer presents the cyclic pattern. This result is also in favour of an enterohepatic circulation of OTA. When phenylalanine is given together with OTA by oral gavage the toxicokinetics of the mycotoxin change completely in the different body fluids, in stomach and intestine content and tissues. Phenylalanine seems to facilitate the gastric absorption of OTA and the gastro-intestinal transit. It increases also its early excretion into urine and bile. However, its elimination pattern no longer shows the oscillating pattern. Thus phenylalanine seems to inhibit the intestinal reabsorption of OTA conjugates.

Animals↗