Peripheral Arterial Blood Research Articles

The Virtual Coronary Angiography Method

This article is devoted to the development of a virtual coronary angiography method, a noninvasive method of evaluation of the state of the human coronary artery. Registration and processing of the signal of peripheral arterial blood pulsation against the background of a functional test with controlled respiration form the basis of the method. A mathematical model of the relationship between relative change in spectral evaluations of the variability of the cardiac rhythm and the degree of coronary-artery stenosis was developed. Clinical testing, which demonstrated the high efficiency of the proposed virtual coronary angiography method when examining patients with different states of coronary arteries, was conducted.

Correlation of Myeloperoxidase Levels in Coronary and Peripheral Arterial Blood With Plaque Morphology by Optical Coherence Tomography in Acute Coronary Syndrome

Background: Circulating myeloperoxidase (MPO) correlates with the presence and severity of coronary artery disease. It is unclear whether MPO is released in acute coronary syndromes (ACS) directly from unstable plaques or as part of systemic inflammation.

Evaluation of the reduction in central and peripheral arterial blood pressure following an oral glucose load.

The clinical significance of measuring central arterial blood pressure has been recently discussed. Although the postprandial reduction in blood pressure is well known, postprandial changes in central blood pressure have not been intensively studied. The present study investigated differences in the reduction of central and peripheral arterial blood pressure after administration of an oral glucose load.An oral glucose tolerance test (75 g) was performed in 360 participants in our physical checkup program. Brachial and central systolic blood pressures were assessed before and after the glucose load. Central arterial blood pressure was measured noninvasively using an automated device.The mean age was 53.6 ± 8.2 years. Both brachial (127.9 ± 17.7 to 125.0 ± 16.3 mm Hg) and central arterial blood pressures were significantly decreased after an oral glucose load (118.9 ± 17.9 to 112.8 ± 16.8 mm Hg). The reduction in blood pressure was greater in central (7.3 ± 11.5 mm Hg) than in brachial blood pressure measurements (3.4 ± 11.3 mm Hg, P < .001). Extreme blood pressure reduction (>20 mm Hg) was recorded more frequently in central (n = 43, 12.3%) than brachial blood pressure measurements (n = 20, 5.6%).An oral glucose load decreases both central and brachial systolic blood pressure, with more pronounced effects on central blood pressure. Postprandial reductions in blood perfusion of the important organs such as the brain may be underestimated when postprandial BP reduction is assessed using brachial BP measurements.

Intra- and Inter-rater Reliability of Peripheral Arterial Blood Flow Velocity by Means of Doppler Ultrasound

ObjectiveAlthough it is possible to find studies that analyze the velocity of blood flow in different arteries, the reliability of Doppler ultrasound on peripheral arteries has not yet been completely established. Our objective was to evaluate intra- and inter-rater reliability of the measurement of blood flow velocity by Doppler ultrasound of brachial, radial, popliteal, and posterior tibial arteries. MethodsFifty healthy individuals of both genders, aged between 18 and 45 years, were included in the study. For the evaluation of arterial blood flow velocity, a portable Doppler ultrasound device was used to measure the mean and maximum blood flow velocity of posterior tibial, popliteal, brachial, and radial arteries. Two examiners performed assessments of the same volunteers independently and twice, with an interval of 1 week between them. ResultsWe found good to very good reliability for measuring the mean and maximum blood flow velocity of the arteries evaluated. The intraclass correlation coefficients ranged between 0.501 and 0.866, standard error of measurement ranged between 0.81 and 9.45 cm/s, and minimum detectable change ranged between 2.25 and 26.13 cm/s. ConclusionThe assessment of mean and maximum blood flow velocity of the brachial, radial, popliteal, and posterior tibial arteries by means of Doppler ultrasound presents acceptable reliability values, which supports the use of this evaluation method in research and clinical practice.

Stretching Exercises Improve Vascular Endothelial Dysfunction Through Attenuation of Oxidative Stress in Chronic Heart Failure Patients With an Implantable Cardioverter Defibrillator.

Endurance training improves oxidative stress and vascular endothelial dysfunction in patients with chronic heart failure (CHF). However, patients with CHF and an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) often avoid endurance training for fear of ICD shock. Recent studies have reported that stretching exercises enhance antioxidant activity and improve vascular responses. Therefore, we aimed to assess the effects of 4 weeks of stretching exercises on oxidative stress and vascular endothelial function in patients with CHF with an ICD or CRT-D. Fifty sedentary patients with CHF (78% males; mean age = 70 ± 9 years; left ventricular ejection fraction = 26% ± 8%) with an ICD or CRT-D were randomly divided into a group that performed 4 weeks of stretching exercises (stretching group) and a group that continued a sedentary lifestyle (control group). We compared the reactive hyperemia peripheral arterial tonometry (RH-PAT) index and blood parameters, such as von Willebrand factor (vWF), malondialdehyde-modified low-density lipoprotein cholesterol (MDA-LDL), reactive oxygen species (ROS), high-sensitivity C-reactive protein, pentraxin 3, and fibrinogen between the 2 groups before and after the 4-week study period. In the stretching group, a significant increase in the RH-PAT index and significant decreases in vWF, MDA-LDL, ROS, and fibrinogen concentrations were observed after the study compared with before (all P < .05). No significant changes were observed in the control group. Four weeks of stretching exercises improved vascular endothelial dysfunction through attenuation of oxidative stress in sedentary patients with CHF with an ICD or CRT-D.

Peripheral arterial blood pressure versus central crterial blood pressure monitoring in critically ill patients after Cardio-pulmonary Bypass.

Objective:To determine the accuracy of peripheral (radial) arterial access as compared to central (femoral) arterial access for measurement of invasive blood pressure (IBP) in critically ill patients after cardiopulmonary bypass.Methods:Sixty patients (60) who required high inotropic/vasopressor support on weaning from cardio-pulmonary bypass and weaned off in 2nd attempt were included in this study. The duration of this study was from June 2015 to August 2016. Radial and femoral arterial access was achieved in all patients for simultaneous measurement of blood pressure. Arterial pressures were noted after 5, 15 and 30 minutes of weaning from cardiopulmonary bypass for both radial and femoral artery simultaneously.Results:Mean age of study patients was 56.48±11.17 years. 85% patients were male. There was significant difference in systolic blood pressure, diastolic blood pressure and mean arterial pressures between the radial artery and femoral artery cannulation. Mean arterial pressures were significantly high in femoral artery as compared to the radial artery. The mean arterial pressures after five minutes of weaning using central access were 76.28±10.21 mmHg versus 64.15±6.76 mmHg in peripheral arterial access (p-value <0.001). Similarly we also found significant difference in mean arterial pressures after 15 minutes of weaning from cardiopulmonary bypass 78.70±10.12 mmHg in central access versus 72.03±6.76 mmHg using peripheral arterial access (p-value <0.001). The difference in arterial pressures were less marked as compared to the previous differences after 30 minutes of weaning from cardiopulmonary bypass as compared to the earlier readings (p-value 0.001).Conclusion:Peripheral arterial pressures are unreliable in critically ill patients after cardiopulmonary bypass receiving high dose of inotropic drugs. Central arterial access should be used in these patients to get accurate estimates of patients’ blood pressure in early periods after cardiopulmonary bypass.

Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock.

Animal studies and human case reports show promise in using lipid rescue to treat refractory calcium channel antagonist toxicity. However, the majority of research and clinical experience has focused on non-dihydropyridine agents. Thus, we sought to investigate the value of lipid emulsion (ILE) therapy for dihydropyridine-induced shock. This IACUC-approved study utilized seven swine that were sedated with alpha-chloralose, mechanically ventilated, and instrumented for drug delivery and hemodynamic measures. After stabilization and basal measures, nifedipine (0.01875 mg/kg/min) was infused until imminent cardiac arrest (seizure, end tidal CO2 < 10 mmHg, bradydysrhythmia, or pulseless electrical activity). Animals then received a 7mL/kg bolus of 20% lipid emulsion via central catheter. Lipid circulation was visually confirmed by the presence of fat in peripheral arterial blood. Hemodynamics were continuously monitored until 10 min after lipid bolus. Surviving animals were euthanized. Pre- and post-lipid treatment parameters were analyzed using the Wilxocon signed rank test (p <0.05 significant). Nifedipine toxicity was characterized by vasodilatory hypotension, impaired vascular contractility, and tachycardia with terminal bradycardia. The median time to imminent cardiac arrest from start of nifedipine infusion was 218 min. Lipid treatment did not improve hemodynamics or restore circulation in any animal. There was no benefit from lipid rescue in this model of nifedipine toxicity. Further study of ILE for dihydropyridine toxicity is warranted but initial animal model results are not promising.

Front cover: 2D‐DIGE‐based proteomic analysis of intracoronary versus peripheral arterial blood platelets from acute myocardial infarction patients: Upregulation of platelet activation biomarkers at the culprit site

Front cover: 2D‐DIGE‐based proteomic analysis of intracoronary versus peripheral arterial blood platelets from acute myocardial infarction patients: Upregulation of platelet activation biomarkers at the culprit site

Circulating non-hematological cells during cardiopulmonary bypass: new findings in cardiac surgery procedures.

Several factors have been historically advocated to explain the coagulative and inflammatory disorders following cardiopulmonary bypass (CPB). In this paper, we describe the presence of circulating non-hematological cells, introduced within the bloodstream during CPB. We defined the origin of the cells and tested their impact on coagulation. We collected peripheral arterial blood samples in twenty consecutive coronary artery bypass graft cases at four different surgical moments and assessed the presence and nature of circulating cells with the use of the CELLSEARCH® Test, immunocytochemistry and immunofluorescence, evaluating the expression of cytokeratin and calretinin. The effect of the circulating non-hematological cells on coagulation was tested in vitro, using the ROTEM assay. A mean of 263.85 ± 57.5 (median 258.5) cells were present in the samples following the suction of blood from the surgical field while all the other samples were negative (zero cells) (p<0.00001). Immunologic tests confirmed the mesothelial origin of the cells. The ROTEM® assay of the blood samples contaminated by the mesothelial cells presented longer clotting times (53.4 ± 8.2 secs 48.3 ± 8.9 sec, p=0.05), longer clot formation times (137.1 ± 31.5 sec vs 111.9 ± 25.2 sec, p=0.009), smaller alfa angle amplitudes (66.7 ± 9.1° vs 71.1 ± 5.1°, p=0.04) and maximum clot firmness times (59.0 ± 5.4 sec vs 61.9 ±4.6 sec, p=0.004) than the controls. The presence of circulating non-hematological cells during CPB with a mesothelial immunophenotype alters in vitro coagulation assays. This finding can help to further understand the pathophysiology of CPB.

Peripheral artery disease and blood pressure profile abnormalities in hemodialysis patients.

Patients undergoing chronic hemodialysis (HD) are at increased risk for peripheral artery disease (PAD). Both ankle-brachial index (ABI) and ambulatory blood pressure monitoring (ABPM) in the interdialytic period have been shown to be strong predictors of all-cause mortality. This cross-sectional study investigated the relationship between ABPM profile and ABI in 81 HD patients. ABPM was measured throughout a 44-h midweek interdialytic period. Pre-dialysis ABI was evaluated with a BOSO ABI device. An ABI value <0.9 or ≥1.3 was defined as abnormal. In the whole study group (72% males, mean age 67±14years), there was an increase in BP (p<0.05) and in systolic BP night/day ratio (n/dSR, p=0.01) during the interdialytic period. Patients with abnormal ABI (n=29) more frequently had a positive history for cerebrovascular accident and PAD and higher proBNP values than those with normal ABI (n=52). No difference was detected among ABPM-derived components except for the n/dSR (p=0.02). Patients with abnormal ABI showed a significantly increased n/dSR (p=0.02) and ambulatory arterial stiffness index (AASI) (p=0.006) on the second day compared to the first. Patients with n/dSR >1 during day 2 (n=34) were older, showed significantly higher proBNP and AASI and were more likely to reveal abnormal ABI compared to those with a lower n/dSR (p=0.006). Abnormal ABI in HD patients is associated to changes in interdialytic ABPM pattern, namely higher n/dSR on day 2. These data may indicate the pathophysiological mechanisms underlying the worse outcome observed in HD patients.

Evaluating Approaches for the Diagnosis of Hemodialysis Catheter-Related Bloodstream Infections.

Guideline-recommended diagnostic criteria for hemodialysis (HD) catheter-related bloodstream infections (CRBSIs) are based on data from indwelling central catheters in patients not on HD and non-HD situations, and upon which peripheral vein cultures are the gold standard. We aimed to examine the validity of these criteria in patients on HD. Adult patients on in-center HD using catheters were prospectively followed from 2011 to 2014 at a large academic-based HD facility (Toronto, Canada). When a CRBSI was suspected, blood culture sets were obtained from four sites (peripheral vein, both catheter hubs, and HD circuit) to determine the guideline-recommended differential time to positivity (DTTP). DTTP criteria were met when catheter hub cultures turned positive ≥120 minutes before peripheral vein cultures. The sensitivity, specificity, and accuracy were first calculated using peripheral vein cultures as the gold standard and then these same calculations were repeated with additional information, including exit site/catheter tip and HD circuit cultures, as the true gold standard. The feasibility of obtaining peripheral vein cultures was determined. Of 178 suspected CRBSIs, 100 had peripheral vein blood cultures. Using the true gold standard, sensitivity, specificity, and accuracy of blood culture results were highest in samples from the HD circuit (93.5%, 100%, and 95%, respectively). The guideline recommended combination of peripheral vein and arterial hub blood cultures was the least sensitive, specific, and accurate (91.7%, 93.1%, and 92.7%, respectively). The diagnostic criteria using measured DTTP were met in less than one third of events. In patients on HD, blood culture results are the most sensitive, specific, and accurate for diagnosing CRBSIs when taken from the HD circuit and the venous catheter hub, and blood culture results are the least sensitive, specific, and accurate in any combination with peripheral vein cultures. The DTTP does not increase diagnostic accuracy, reducing the necessity for venipuncture and its potential vein damage. Future guidelines should consider the applicability of criterion on specific patient populations and tailor them accordingly.

(186) Relationship between central pain mechanisms and arterial blood pressure in pain free subjects

Studies in humans suggest an interrelationship between blood pressure and pain regulation, where elevated resting blood pressure is associated with decreased pain sensitivity in pain free normotensives. However, it is still unclear whether: 1) this interrelationship involves peripheral and central arterial blood pressure, or 2) central pain mechanisms are involved. We classified 13 pain-free subjects (mean age = 47.46; SD= 7.32) as normotensive (n = 6) or prehypertensive (n = 7) using a systolic blood pressure >135 mm Hg as the cutoff. Heart rate (HR) and peripheral and central blood pressures were measured non-invasively before, during and after experimental pain procedures. Suprathreshold heat pain responses (SHPR) were generated with repeated thermal stimuli, and conditioned pain modulation (CPM) was assessed using SHPR as the experimental stimulus and cold pressor task (7 °C) as the conditioning stimulus. Repeated measures ANOVA showed significant increases (pre, during and post pain) in all measures of peripheral and central blood pressure; however, the time*group (normotensive vs prehypertensive) interaction was significant only for peripheral systolic pressure (F (2,18)=6.07, p=0.01) and central systolic pressure (F(2,18)=3.84, p=0.04). Significant positive associations were found between SHPR and arterial blood pressure (peripheral and central, p< 0.01) only in prehypertensive subjects. There was a significant positive association between the magnitude of CPM and HR difference in all subjects. These preliminary results imply that: 1) the acute response of peripheral and central systolic pressure differs between normotensive and prehypertensive individuals, where normotensives have a more pronounced response to pain induction, and 2) inhibitory (CPM) and facilitatory (SHPR) central pain mechanisms are related to different cardiovascular mechanisms in response to acute pain induction. Further analyses in a larger sample and in chronic pain patients will provide stronger evidence about the interrelationship between blood pressure and central pain mechanisms. Supported by Charlotte Zietlow Research Grant, Indiana State University.

Perioperative circulating tumor cells in surgical patients with non-small cell lung cancer: does surgical manipulation dislodge cancer cells thus allowing them to pass into the peripheral blood?

We herein evaluated the status of circulating tumor cells (CTC) dislodged from the tumor during surgery in patients who underwent pulmonary resection for non-small cell lung cancer (NSCLC) to assess the clinical implications. Tumor cells in the peripheral arterial blood before surgery (Before) and immediately after lung resection (After) and in the blood from the pulmonary vein of the resected lung were detected using a size selective method. The clinicopathological characteristics and the prognosis were then analyzed according to the CTC status: no tumor cells detected (N), single tumor cell or total number less than 4 cells (S), and existence of clustered cells (C). According to the CTC status, the patients were classified into the following three groups: Before-C and After-C, Group I (n=6); Before-S or N and After-C, Group II (n=9); and Before-S or N and After-S or N, Group III (n=8). Group III showed a high rate of p-stage IA, smaller tumor size, lower CEA level, lower SUVmax level, and a higher relapse-free survival rate than the other groups. CTCs were detected in patients after undergoing lung resection, some of which may have been dislodged by the surgical procedure. The presence of clustered CTCs after the operation indicated an unfavorable outcome.

Lymphocyte subpopulations in myocardial infarction: a comparison between peripheral and intracoronary blood.

The frequency and profile of lymphocyte subsets within the culprit coronary artery were investigated in 33 patients with myocardial infarction and compared to their systemic circulating counterparts. T cell subsets including CD4+CD28null, activated and regulatory T-cells, TH1/TH2/TH17 phenotypes, NK and B-cells were studied in intracoronary (IC) and arterial peripheral blood (PB) samples. CD4+CD28null T-lymphocytes were significantly increased in IC compared to PB (3.7 vs. 2.9 %, p < 0.0001). Moreover, patients with more than 6 h of evolution of STEMI exhibited higher levels of CD4+CD28null T-cells suggesting that this subset may be associated with more intense myocardial damage. The rare NK subpopulation CD3−CD16+CD56− was also increased in IC samples (5.6 vs. 3.9 %, p = 0.006). CD4+CD28null T-cells and CD3−CD16+CD56− NK subpopulations were also associated with higher CK levels. Additionally, IFN-γ and IL10 were significantly higher in IC CD4+ lymphocytes. Particular immune cell populations with a pro-inflammatory profile at the site of onset were increased relative to their circulating counterparts suggesting a pathophysiological role of these cells in plaque instability, thrombi and myocardial damage.

Plasma levels of carboxypeptidase U (CPU, CPB2 or TAFIa) are elevated in patients with acute myocardial infarction

Two decades after its discovery, carboxypeptidase U (CPU, CPB2 or TAFIa) has become a compelling drug target in thrombosis research. However, given the difficulty of measuring CPU in the blood circulation and the demanding sample collecton requirements, previous clinical studies focused mainly on measuring its inactive precursor, proCPU (proCPB2 or TAFI). Using a sensitive and specific enzymatic assay, we investigated plasma CPU levels in patients presenting with acute myocardial infarction (AMI) and in controls. In this case-control study, peripheral arterial blood samples were collected from 45 patients with AMI (25 with ST segment elevation myocardial infarction [STEMI], 20 with non-ST segment elevation myocardial infarction [NSTEMI]) and 42 controls. Additionally, intracoronary blood samples were collected from 11 STEMI patients during thrombus aspiration. Subsequently, proCPU and CPU plasma concentrations in all samples were measured by means of an activity-based assay, using Bz-o-cyano-Phe-Arg as a selective substrate. CPU activity levels were higher in patients with AMI (median LOD-LOQ, range 0-1277 mU L(-1) ) than in controls (median < LOD, range 0-128 mU L(-1) ). No correlation was found between CPU levels and AMI type (NSTEMI [median between LOD-LOQ, range 0-465 mU L(-1) ] vs. STEMI [median between LOD-LOQ, range 0-1277 mU L(-1) ]). Intracoronary samples (median 109 mU L(-1) , range 0-759 mU L(-1) ) contained higher CPU levels than did peripheral samples (median between LOD-LOQ, range 0-107 mU L(-1) ), indicating increased local CPU generation. With regard to proCPU, we found lower levels in AMI patients (median 910 U L(-1) , range 706-1224 U L(-1) ) than in controls (median 1010 U L(-1) , range 753-1396 U L(-1) ). AMI patients have higher plasma CPU levels and lower proCPU levels than controls. This finding indicates in vivo generation of functional active CPU in patients with AMI.

Growing thrombi release increased levels of CD235a+ microparticles and decreased levels of activated platelet‐derived microparticles. Validation in ST‐elevation myocardial infarction patients

Local fluid dynamics and exposed atherosclerotic lesions regulate thrombus formation. Activated cells in the attached thrombi release microparticles to the circulation (circulating microparticles [cMPs]); however, their phenotype is unknown. To investigate the specific phenotype of the cMPs released by growing thrombi. cMPs released by thrombi growing in different well-characterized thrombogenic conditions were investigated. cMP contents just before and immediately after perfusion of the thrombogenic surfaces were analyzed by triple-labeling flow cytometry. cMPs were tested for their thrombin-generating capacity. The cMPs identified in the exvivo perfusion experiments were validated in blood of ST-elevation myocardial infarction (STEMI) patients undergoing thrombectomy and percutaneous coronary intervention. Culprit coronary blood (STEMI-CCB) and peripheral artery blood (STEMI-PAB) were simultaneously analyzed and compared with peripheral artery blood from age-matched controls (C-PAB) and peripheral artery blood from patients who had recovered from acute coronary syndrome (ACS) (pSTEMI-PAB). The levels of annexinV(+) cMPs significantly increased in blood collected after perfusion of the exposed thrombogenic surfaces. cMP release was directly related to the formed thrombus mass and the plasma procoagulant activity. Post-thrombus blood showed higher thrombin generation potential and contained higher levels of cMPs carrying glycophorin-A (CD235a(+) ; erythrocyte-derived microparticles [ErMPs]) than preperfusion blood (P<0.05), whereas the levels of cMPs carrying activated and adhesion platelet markers were decreased. STEMI-CCB and STEMI-PAB had significantly higher ErMP levels than control blood (P<0.005). ErMP levels were also significantly higher in STEMI-PAB than in pSTEMI-PAB, validating the experimental mechanistic studies and suggesting that ErMPs are markers of ongoing coronary thrombosis (C-statistics: 0.950; 95% confidence interval0.889-1.000; P<0.001). Glycophorin-A-rich microparticles are released from evolving growing thrombi into the distal perfusing blood, and can be measured in peripheral blood. CD235a(+) cMPs may constitute a novel systemic biomarker of ongoing thrombosis.

Borderline hypotension: how does it influence cerebral regional tissue oxygenation in preterm infants?

Aim: To monitor cerebral regional tissue oxygenation (crSO2) of preterm infants continuously and to analyze the influence of arterial hypotension on crSO2. Methods: In this prospective, observational study crSO2, peripheral oxygen saturation (SpO2), heart rate (HR) and mean arterial blood pressure (MABP) were monitored continuously for 24 h, starting within the first 6 h after birth. Furthermore, cerebral fractional tissue oxygen extraction (cFTOE) was calculated. Preterm neonates with and without arterial hypotension (MABP below the gestational age in weeks) were compared to each other. Results: Forty-six preterm infants could be analyzed, 17 with (33.4 ± 1.9 weeks, 2016.5 ± 548.5 g) and 29 without arterial hypotension (33.3 ± 1.3 weeks, 1924.7 ± 451.9 g). Altogether, we detected 30 episodes of hypotension, with a mean duration of 1.6 ± 1.2 h per infant and a mean decrease in MABP of 2.2 ± 0.9 mmHg. During hypotension mean crSO2 was 7 5 ± 11%, 2 h prior to that 76 ± 10% and 2 h after the hypotension 7 7 ± 10%, therefore no significant alterations could be observed. Moreover, there was no significant difference in mean 24-h crSO2, SpO2 and cFTOE between the two groups. Conclusion: Mild short-term hypotensive episodes in preterm infants did not affect crSO2. This suggests that cerebral autoregulation is maintained in case of borderline-hypotension and may protect infants from cerebral injury.

Arterial Blood, Rather Than Venous Blood, is a Better Source for Circulating Melanoma Cells

BackgroundCTCs provide prognostic information and their application is under investigation in multiple tumor types. Of the multiple variables inherent in any such process, none is more important to outcome than the appropriateness of the sample source. To address this question, we investigated CTCs in paired peripheral venous and arterial blood specimens obtained from stage IV uveal melanoma patients.MethodsBlood specimens were obtained from both common femoral arteries and antecubital veins in 17 uveal melanoma patients with multiple hepatic metastases for CTC measurements.FindingCTCs were detectable with greater frequency (100%) and in larger numbers (median 5, range 1 to 168) in all arterial blood specimens than in venous samples (52.9%; median 1, range 0 to 8). Patients with hepatic as well as extra-hepatic metastasis showed higher number of arterial CTCs, compared to patients with liver-only metastasis (p = 0.003). There was no significant association between the number of arterial CTCs and the tumor burden within the liver in patients who had liver-only metastases.InterpretationOur data indicate that arterial blood specimens might be a better source of circulating uveal melanoma cells. Although less conveniently processed, perhaps arterial blood should be evaluated as sample source for measurement of CTCs.

Simulation of Generation of Peripheral Arterial Blood Pulsation

A mathematical model for the signal formation process of peripheral arterial blood pulsation in vessels of upper limbs is discussed. Formation of peripheral arterial blood pulsations is represented as a composition of forward and reflected pulse waves propagating through the arterial system. The study proposes a system of analogies between the propagation of pulse wave in the human arterial system and propagation of electrical oscillations in lines with distributed parameters. Dependences of pulse wave propagation in the arterial system were obtained by solving the one-dimensional Navier–Stokes equations for several special cases.

Abstract 384: Detection of circulating melanoma cells in paired arterial and venous specimens from uveal melanoma patients with hepatic metastatic

Abstract Background: Circulating tumor cells (CTCs) represent a surrogate biomarker for hematogenous metastases. The detection of CTCs has gained increasing interest for prediction of clinical outcome. However, it remains to be determined whether uveal melanoma cells circulating in a peripheral vein predict systemic recurrence and poorer overall prognosis. Uveal melanoma, the most common primary cancer of the eye in adults, is unique in that the uveal tract is devoid of lymphatics. Since systemic recurrence develops exclusively via hematogenous spread, patients with uveal melanomas present a special opportunity to explore the prognostic potential of CTCs. Although the lung is the first organ through which venous drainage from the affected eye passes and indeed the only organ through which all venous blood must pass, 80-95% of systemic metastases are found first in the liver without development of lung metastases. To address these issues, we investigated the numbers of CTCs in paired arterial (femoral) and venous (antecubital) blood specimens obtained from uveal melanoma patients with hepatic metastases. Methods: CTCs in blood specimens were measured in 17 uveal melanoma patients with multiple hepatic metastases, including 10 patients with liver-only metastases and 7 patients with hepatic and extra-hepatic metastases. Peripheral arterial and venous blood specimens were collected at the same time prior to liver directed treatment. CTCs were analyzed using CellTracks Circulating melanoma Cell Kit by CellSearch System. The clinical information and sources of blood specimens were blinded when CTCs were analyzed. Result: CTCs were detectable from all 17 arterial blood specimens (100%) (median 5, range 1 to 168). In contrast, much smaller numbers of CTCs were detectable in 52.9% (9/17) of venous blood specimens (median 1, range 0 to 8) from the same patients. In terms of degree of tumor burden, patients who have hepatic as well as extra-hepatic metastasis showed higher numbers of arterial CTCs (median 12, range 5 to 168), compared to patients who have liver-only metastasis (median 4, range 1 to 11). More importantly, there is no significant correlation between numbers of arterial CTCs and the degree of tumor volume in the liver in patients who have liver-only metastases. Conclusions: Using this technology, the detection of uveal melanoma cells in peripheral blood is feasible. Peripheral capillary beds effectively filter CTCs from venous blood; thus venous blood might not be the best source for measurement of CTCs in patients with metastatic uveal melanoma. The paucity of clinically evident non-hepatic metastases despite the effective filtration by peripheral capillary beds remains unexplained and may be a demonstration of the “seed and soil” hypothesis. CTCs are a non-invasive source of uveal melanoma cells for evaluating tumor biology. Further investigation is warranted. Citation Format: Mizue Terai, Zhaomei Mu, David Eschelman, Carin Gonsalves, Ken Kageyama, Michael J. Mastrangelo, Marlana Orloff, Ryan Weight, Massimo Cristofanilli, Takami Sato. Detection of circulating melanoma cells in paired arterial and venous specimens from uveal melanoma patients with hepatic metastatic. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 384. doi:10.1158/1538-7445.AM2015-384