Circulatory Changes Research Articles

Functional and circulatory renal changes in advanced heart failure

OBJECTIVES The aim of the study was to describe the relations between heart and renal functions and to investigate whether reduced glomerular filtration rate is influenced more by reduced perfusion or venous congestion. METHODS A prospective cohort study of 101 patients (69 men, 32 women) with chronic heart failure aged 52 (49-54) (median, 95 % confidence interval) years. We analyzed the blood samples, parameters of echocardiography and right heart catheterization. RESULTS Left ventricular ejection fraction correlated with the estimated glomerular filtration rate eGFR (r = 0.214, p = 0.036) in the whole sample of patients. We found a correlation between cardiac output and renal perfusion pressure in the whole sample (r = 0.232, p = 0.0225) and in patients with chronic heart failure (r = 0.254, p = 0.0278).In the whole sample the mean pulmonary artery pressure (PAP) correlated with the variables determining renal function: PAP and renal perfusion pressure (r = -0.345, p = 0.002),PAP and eGFR (r = -0.299, p = 0.009). In the other two studied groups these correlations were not significant. CONCLUSION In the group of heart failure patients left and right ventricular functions were the main determinants for renal function. Current cardiac output or right atrial pressure as markers of renal perfusion were not associated with renal functions in advanced but stable heart failure patients with low burden of extracardiac comorbidities (Tab. 1, Fig. 4, Ref. 13).

Identification of proteins of cardiovascular system in healthy subjects’ urine during “dry” immersion

We analyzed the urine proteome in 14 healthy volunteers who were subjected to 5-day dry immersion using proteomic analysis methods and bioinformatics approach. We identified nine proteins related to the cardiovascular system. It was shown that 5-day dry immersion modifies the urine proteomic profile, indicating renal, endocrine, circulatory, and metabolic changes. Most of these changes are characterized by both a very rapid development and very rapid restoration within return to normal conditions.

Circulatory changes of the novel adipokine adipolin/CTRP12 in response to metformin treatment and an oral glucose challenge in humans

Adipolin/CTRP12 is a novel adipokine with anti-inflammatory and glucose-lowering properties in rodents. We sought to investigate the effects of metformin treatment (850mg twice daily for 6months) and a 2h 75g oral glucose tolerance test (OGTT) on serum adipolin concentrations in humans. Cross-sectional study [PCOS (n=83) and control (n=39) subjects]. Serum adipolin was measured by ELISA. Metformin treatment (850mg twice daily for 6months) was offered to all women with PCOS, 34 women participated but 21 women completed 6months of metformin therapy. Reasons for subjects not completing the study were nausea and gastrointestinal side effects (n=4), pregnancies (n=5), noncompliance (n=2) and loss of contact (n=2). Metformin treatment (850mg twice daily for 6months) substantially increased serum adipolin concentrations (P<0·05) in women with polycystic ovary syndrome (PCOS), a pro-inflammatory state associated with obesity, diabetes, dyslipidaemia and atherosclerosis. Furthermore, changes in waist-hip ratio, glucose, triglycerides, CRP and carotid intima media thickness showed significant negative associations with changes in adipolin levels (P<0·05, P<0·01); in multiple regression analyses, only changes in glucose were predictive of changes in adipolin levels (β=-0·570, P=0·009). Serum adipolin decreased significantly in response to the OGTT in PCOS and control subjects at 90min (P<0·05) and 120min (P<0·01). Adipolin and/or novel pharmacologic agents that increase adipolin's circulating concentrations might constitute a novel approach in the treatment of insulin resistant states.

Abdominal Hypertension and Decompression: The Effect on Peritoneal Metabolism in an Experimental Porcine Study

The aim of this study was to investigate the abdominal metabolic response and circulatory changes after decompression of intra-abdominal hypertension in a porcine model. This was an experimental study with controls. Three-month-old domestic pigs of both sexes were anesthetized and ventilated. Nine animals had a pneumoperitoneum-induced IAH of 30mmHg for 6 hours. Twelve animals had the same IAH for 4 hours followed by decompression, and were monitored for another 2 hours. Hemodynamics, including laser Doppler-measured mucosal blood flow, urine output, and arterial blood samples were analyzed every hour along with glucose, glycerol, lactate and pyruvate concentrations, and lactate-pyruvate (l/p) ratio, measured by microdialysis. Laser Doppler-measured mucosal blood flow and urine output decreased with the induction of IAH and showed a statistically significant resolution after decompression. Both groups developed distinct metabolic changes intraperitoneally on induction of IAH, including an increased l/p ratio, as signs of organ hypoperfusion. In the decompression group the intraperitoneal l/p ratio normalized during the second decompression hour, indicating partially restored perfusion. Decompression after 4 hours of IAH results in an improved intestinal blood flow and a normalized intraperitoneal l/p ratio.

Spindle-like abdominal wall-lifting device in gasless laparoscopic surgery in animal experiments

Introduction: CO2 pneumoperitoneum has been used to establish an operation space in laparoscopic surgery. It may have some bad consequences, such as respiratory and circulatory system changes, hypotension and hypoxia in infants and the release of free tumor cells into the abdominal cavity. Gasless laparoscopic technique can avoid these adverse effects. But present gasless laparoscopic techniques have their own disadvantages. The main shortcoming of gasless laparoscopic techniques is inadequate operative space. Material and methods: We herein describe a new technique. We used a self-designed spindle-like abdominal wall-lifting device to perform gasless laparoscopic cholecystectomy in seven pigs, recording the operation time, bleeding volume and unexpected occurrences during the operation. Results: Seven pigs underwent laparoscopic cholecystectomy using this technique with no conversion to open operation. The operation time was between 21minutes and 65 minutes, with a mean operative time of 42.5 minutes. The range of bleeding volumes was 2 ml to 8 ml, with a mean operative bleeding volume of 4.3ml. There were no massive hemorrhages, internal organ injuries or other complications during the operation. Conclusions: These preliminary outcomes indicate that the spindle-like abdominal wall-lifting device is feasible and safe in gasless laparoscopic cholecystectomy, which can provide sufficient exposure of the operative filed.

Elderly bioheat modeling: changes in physiology, thermoregulation, and blood flow circulation

A bioheat model for the elderly was developed focusing on blood flow circulatory changes that influence their thermal response in warm and cold environments to predict skin and core temperatures for different segments of the body especially the fingers. The young adult model of Karaki et al. (Int J Therm Sci 67:41-51, 2013) was modified by incorporation of the physiological thermoregulatory and vasomotor changes based on literature observations of physiological changes in the elderly compared to young adults such as lower metabolism and vasoconstriction diminished ability, skin blood flow and its minimum and maximum values, the sweating values, skin fat thickness, as well as the change in threshold parameter related to core or skin temperatures which triggers thermoregulatory action for sweating, maximum dilatation, and maximum constriction. The developed model was validated with published experimental data for elderly exposure to transient and steady hot and cold environments. Predicted finger skin temperature, mean skin temperature, and core temperature were in agreement with published experimental data at a maximum error less than 0.5°C in the mean skin temperature. The elderly bioheat model showed an increase in finger skin temperature and a decrease in core temperature in cold exposure while it showed a decrease in finger skin temperature and an increase in core temperature in hot exposure.

LEDを利用した透過型光電脈波法（TLP）の歯髄診断への応用

Transmitted-light plethysmography (TLP) is an optical technique to detect circulatory changes in pulp tissue. It has been reported as overcoming the disadvantages of electrical pulp testing in terms of objectivity and invasiveness. In a previous study, we reported the applicability of the TLP system with a 525 nm light-emitting diode (LED) to traumatized young permanent and deciduous teeth. The system works by detecting the pulsation intensity of light transmitted through a tooth and visualizing the pulpal blood flow synchronized with the heartbeat. During the clinical follow-up, we found that TLP pulse amplitudes and pulse shape characteristics change gradually due to the pathological condition. However, the origins of tooth plethysmograms were not fully understood because of the structural specificity of teeth. In this study, multiwavelength optical plethysmography was used to examine the light transmission properties of teeth to clarify the effects of physiological parameters such as the blood volume and SO2 on the pulsation of TLP pulse waves. The results indicated that the optical process in teeth mainly depended on the blood cell concentration (Hctp), light attenuation by the hard tissues, and the light source wavelength. Clinically, it was assumed that the changes in blood vessel density, pulpal blood volume, and pulp chamber size associated with subjects' ages or pathological conditions might affect TLP pulse waves. We also demonstrated the applicability of pulse oximetry to dental pulp using an in vitro blood circulation model. The LEDs with 470 nm and 590 nm wavelengths showed high sensitivity to the blood SO2 level. R values calculated from pulsatile/nonpulsatile component ratios of two different wavelengths were significantly correlated with the pulpal SO2, indicating the possibility of pulpal blood SO2 measurement. The present results indicate that TLP pulse waves potentially provide additional information to diagnose the circulatory status of the pulp in relation to pathological conditions of the dental pulp.

Cardiovascular events in pregnancy with hypertrophic cardiomyopathy.

The influence of the physiological circulatory changes during pregnancy on hypertrophic cardiomyopathy (HCM) is unclear. There have been no comprehensive studies of pregnant women with HCM in the Japanese population. A total of 27 pregnancies (23 women with HCM) were retrospectively reviewed. A total of 18 cardiovascular events occurred in 13 of the 27 pregnancies (48%), and 13 of these events (76%) were related to arrhythmia. The cardiovascular events tended to occur in the early stage of pregnancy (≈30 gestational weeks) or postpartum. The events related to arrhythmia mainly occurred in the early stage of pregnancy or at approximately 30 gestational weeks. Four pregnancies were terminated because of cardiovascular events. Cardiovascular events occurred in 8 of 9 pregnancies in women on medication before pregnancy (88%), 7 of 10 pregnancies with high CARPREG score (70%), and in 9 of 12 pregnancies with high ZAHARA score (75%). Cardiovascular events occurred in more than half of the pregnant women complicated with HCM, and the arrhythmia is the most common cardiovascular event. Medication in the pre-pregnancy period, and CARPREG or ZAHARA score ≥1 were identified as risk factors of cardiac events during pregnancy or postpartum.

The semiology of tilt-induced reflex syncope in relation to electroencephalographic changes

Syncope is defined as transient loss of consciousness as a result of cerebral hypoperfusion. Electroencephalography during syncope shows either a 'slow-flat-slow' or a 'slow' pattern. The first is believed to denote more severe hypoperfusion. Although the diagnosis of vasovagal syncope relies primarily on history taking, there is limited evidence regarding the relative importance of various clinical features, and none that relate them to the severity of electroencephalographic changes. The aim of this investigation was to study symptoms, signs and electroencephalographic changes with a 1 s resolution using electroencephalography and video data in 69 cases of tilt-induced vasovagal syncope. The main finding was that flattening of the electroencephalograph indicated more profound circulatory changes: the 'slow-flat-slow' group had a lower minimum blood pressure, longer maximum RR-interval, contained more cases with asystole and had a longer duration of loss of consciousness than the 'slow' group. Second, we describe a range of signs, including some that have rarely been reported in syncope, e.g. oral automatisms. Third, signs occurred at different rates depending on electroencephalographic flattening, suggesting a classification of syncopal signs. Type A signs (e.g. loss of consciousness, eye opening and general stiffening) develop during the first slow phase, stay present during flattening and stop in the second slow phase. Type B (particularly myoclonic jerks) occur when the electroencephalograph is slow but not flat: their abolition with electroencephalographic flattening suggests dependence on cortical activity. Type C signs (making sounds, roving eye movements and stertorous breathing) occur only in the flat phase, whereas type D (dropping the jaw and snoring) may occur either in slow or flat phases. In conclusion, our findings provide a detailed assessment of clinical symptoms in relation to electroencephalographic (EEG) changes during tilt-induced syncope.

Increased Thrombin Generation and Fibrin Formation In Premature Aging BMAL1 Deficient Mice

IntroductionThe occurrence of venous thromboembolism is strongly age-dependent and has a substantial morbidity and mortality. While the incidence is<1 per 1000 per year up to an age of 50, it thereafter increases rapidly end exponentially. The cause of this increased risk is still unclear, however immobility, decreased muscular tone, aging of the veins and the presence of other or more risk factors and diseases than young individuals all contribute to this increased risk. Whether age-induced circulatory changes and/or increased levels of blood coagulation levels are responsible for the increased thrombogenicity remains unclear. We recently developed a method in which these problems were overcome enabling the measurement of thrombin generation (TG) in a small aliquot of blood. The advantage of the use of this whole blood assay is that the small volume enables us to apply this assay to mice and the use of whole blood enables us to include the effect of blood cells on TG. ObjectivesBy modifying the classic plasma Calibrated Automated Thrombogram (CAT) assay, we were able of measuring TG in whole blood in mice. The objective was to validate this assay in mice blood and to examine the rate and extent TG in a mouse model of premature aging. MethodsTG was assayed in 20- to 28-week-old brain and muscle ARNT-like protein-1 (Bmal1)-deficient (knockout, KO) mice and wild-type (WT) littermates. The Bmal1-KO mice have an impaired circadian behavior and demonstrate loss of rhythmicity in the expression of their target genes. They are known to have a reduced lifespan and display symptoms of premature aging. Mice blood samples were taken from the orbital sinus using a capillary anticoagulated with citrate (3.8%). Coagulation and therefore TG was initiated with a solution containing calcium, tissue factor (TF) and a thrombin specific substrate. Varying the TF concentration revealed an optimal of 0.5 pM. At the end of the TG assay, the samples were fixated, prepared for and analysed by scanning electron microscopy (SEM). ResultsThe intra-assay variations (CV%) in mice blood of the endogenous thrombin potential (ETP), peak height, lagtime, time-to-peak and velocity index were 10% or less (n=24). The whole blood TG test showed that Bmal1-KO mice have a significantly (p<0.001) higher ETP (437±7 nM.min; mean±SD, n=5) when compared with wild type mice (ETP=220±45 nM.min; mean±SD, n=5). The peak heights also differed significantly (p=0.027). However, differences in lagtime, TTP and velocity index were not significantly different (p-values were respectively 0.45, 0.15 and 0.74). Applying SEM we found that Bmal1 deficient mice display a more dense fibrin network with smaller pores compared to WT-mice. ConclusionsThe whole blood TG assay in mice blood revealed to be reproducible and we demonstrated that aging Bmal1-KO mice have a hypercoagulable state when compared with WT mice indicating that a higher thrombotic risk in elderly is partially due to a more procoagulation state. Disclosures:No relevant conflicts of interest to declare.

Complement C5A Antagonist Treatment Improves the Acute Circulatory and Inflammatory Consequences of Experimental Cardiac Tamponade

Cardiogenic shock often leads to splanchnic macro- and microcirculatory complications, and these events are linked to local and systemic inflammatory activation. Our aim was to investigate the consequences of complement C5a antagonist treatment on the early circulatory and inflammatory changes in a clinically relevant large animal model of cardiac tamponade. A randomized, controlled in vivo animal study in a university research laboratory. Anesthetized, ventilated, and thoracotomized Vietnamese mini pigs (24 ± 3 kg). Group 1 (n = 6) served as sham-operated control. In group 2 (n = 7), cardiac tamponade was induced for 60 minutes by the administration of intrapericardial fluid, while the mean arterial pressure was kept in the interval 40 to 45 mm Hg. Group 3 (n = 6) was treated with a complement C5a antagonist compound (the peptide acetyl-peptide-A, 4 mg/kg) after 45 minutes of tamponade. The macrohemodynamics, including the superior mesenteric artery flow, was monitored; the average red blood cell velocity in the small intestinal mucosa was determined by an intravital orthogonal polarization imaging technique. The whole blood superoxide production, the plasma level of high-mobility group box protein-1 and big-endothelin and the small intestinal myeloperoxidase activity were measured. One hundred eighty minutes after the relief of tamponade, the mean arterial pressure was decreased, while the plasma levels of superoxide, high-mobility group box protein-1, and big-endothelin, and the intestinal myeloperoxidase activity were increased. The administration of acetyl-peptide-A normalized the mean arterial pressure and preserved the cardiac output, while the superior mesenteric artery flow and mucosal average red blood cell velocity were increased significantly, and the plasma superoxide, high-mobility group box protein-1, big-endothelin, and intestinal myeloperoxidase levels were reduced. These results provide evidence that blockade of the C5a effects significantly influences the acute splanchnic macro- and microhemodynamic complications and decreases the potentially harmful inflammatory consequences of experimental cardiogenic shock.

Perfusion index in the very preterm infant

Perfusion Index (PI) is a quantifiable measurement of peripheral perfusion and may be a useful adjunct to the assessment of circulatory status in the newborn. (i) To assess reproducibility of PI and (ii) To determine whether there is a difference between simultaneously obtained limb measurements of PI in newborns <32 weeks GA in the transitional period. Perfusion Index was measured in newborns <32 weeks during the first 48 h of life. To examine reproducibility, the pulse oximetry probe was replaced on the same limb consecutively by the same operator. Upper and lower limbs were then simultaneously evaluated over a 5-min period. Heart rate, blood pressure, birth weight, ventilation requirement, inotrope use, lactate, PCO2 and CRIB-II score were also recorded. Thirty infants were assessed. Intraclass correlation coefficient for reproducibility in the same limb was high (r value = 0.982 p < 0.001). Measurements obtained in the right upper limb were consistently higher than either lower limb. The median (IQR) PI for the entire cohort was 0.70 (0.29-1.35). No correlation existed between gestational age, birth weight, CRIB scores, systolic and diastolic blood pressure, mean blood pressure and median PI values. Perfusion Index measurement is reproducible, and values are highest in the right upper limb. Wide differences between right upper and lower limb readings are most likely related to transitional circulatory changes.

Gasless Laparoscopic Cholecystectomy in a Pig Using a Self-Designed Umbrella-Like Abdominal Wall-Lifting Device

Abstract Introduction: In laparoscopic surgery with CO2 pneumoperitoneum, serious complications often occur for elderly patients and those who undergo long operations.1 These complications mainly include respiratory and circulatory system changes.2–4 In patients with tumors, release of free tumor cells into the abdominal cavity is believed to be possible.5 Gasless laparoscopic techniques can avoid these complications of CO2 pneumoperitoneum. Currently, the main shortcoming of gasless laparoscopic techniques is the inadequate operative space. Because of this shortcoming, gasless techniques have not been widely applied in clinical practice. Case Report: In the video, we describe a new technique of gasless laparoscopic cholecystectomy in a pig using a self-designed umbrella-like abdominal wall-lifting device. The umbrella was constructed from stainless steel and was 150 mm in diameter. Ten spokes formed an umbrella through a folding movement. This device lifted up the anterior abdominal wall by opening the u...

Monitoring microcirculatory blood flow with a new sublingual tonometer in a porcine model of haemorrhagic shock

Tissue capnometry may be suitable for the indirect evaluation of regional hypoperfusion. We tested the performance of a new sublingual capillary tonometer in experimental hemorrhage. Thirty-six anesthetized, ventilated mini pigs were divided into sham-operated (n = 9) and shock groups (n = 27). Hemorrhagic shock was induced by reducing mean arterial pressure (MAP) to 40 mmHg for 60 min, after which fluid resuscitation started aiming to increase MAP to 75% of the baseline value (60-180 min). Sublingual carbon-dioxide partial pressure was measured by tonometry, using a specially coiled silicone rubber tube. Mucosal red blood cell velocity (RBCV) and capillary perfusion rate (CPR) were assessed by orthogonal polarization spectral (OPS) imaging. In the 60 min shock phase a significant drop in cardiac index was accompanied by reduction in sublingual RBCV and CPR and significant increase in the sublingual mucosal-to-arterial PCO2 gap (PSLCO2 gap), which significantly improved during the 120 min resuscitation phase. There was significant correlation between PSLCO2 gap and sublingual RBCV (r = -0.65, p < 0.0001), CPR (r = -0.64, p < 0.0001), central venous oxygen saturation (r = -0.50, p < 0.0001), and central venous-to-arterial PCO2 difference (r = 0.62, p < 0.0001). This new sublingual tonometer may be an appropriate tool for the indirect evaluation of circulatory changes in shock.

RAISING THE ‘DEAD’ – REPERFUSION FROM TORPOR

> Kelly Drew discusses Paul Chatfield and Charles Lyman's classic paper ‘Circulatory changes during the process of arousal in the hibernating hamster’, published in the American Journal of Physiology in 1950. Over 60 years ago, Paul Chatfield and Charles Lyman described fundamental

Effect of task-related extracerebral circulation on diffuse optical tomography: experimental data and simulations on the forehead

The effect of task-related extracerebral circulatory changes on diffuse optical tomography (DOT) of brain activation was evaluated using experimental data from 14 healthy human subjects and computer simulations. Total hemoglobin responses to weekday-recitation, verbal-fluency, and hand-motor tasks were measured with a high-density optode grid placed on the forehead. The tasks caused varying levels of mental and physical stress, eliciting extracerebral circulatory changes that the reconstruction algorithm was unable to fully distinguish from cerebral hemodynamic changes, resulting in artifacts in the brain activation images. Crosstalk between intra- and extracranial layers was confirmed by the simulations. The extracerebral effects were attenuated by superficial signal regression and depended to some extent on the heart rate, thus allowing identification of hemodynamic changes related to brain activation during the verbal-fluency task. During the hand-motor task, the extracerebral component was stronger, making the separation less clear. DOT provides a tool for distinguishing extracerebral components from signals of cerebral origin. Especially in the case of strong task-related extracerebral circulatory changes, however, sophisticated reconstruction methods are needed to eliminate crosstalk artifacts.

Preliminary Study on the Application of an Umbrella-Like Abdominal Wall-Lifting Device in Gasless Laparoscopic Surgery

Abstract Background: In laparoscopic surgery with CO2 pneumoperitoneum, serious complications often occur for elderly patients and those who undergo long operations. These complications mainly include respiratory and circulatory system changes. In patients with tumors, release of free tumor cells into the abdominal cavity is believed to be possible. Gasless laparoscopic techniques can avoid these complications of CO2 pneumoperitoneum. Currently, the main shortcoming of gasless laparoscopic techniques is inadequate operative space. Because of this shortcoming, gasless techniques have not been widely applied in clinical practice. We herein describe a new technique of gasless laparoscopic cholecystectomy in pigs using a self-designed umbrella-like abdominal wall-lifting device. This device lifts up the anterior abdominal wall by opening the umbrella leaf in the abdominal cavity. Five pigs underwent laparoscopic cholecystectomy using this technique. The operation times were 85, 40, 28, 21, and 24 minutes. The corresponding bleeding volumes were 11, 20, 5, 2, and 8 mL. These preliminary outcomes suggest that the umbrella-like abdominal wall-lifting technique is safe and feasible in gasless laparoscopic surgery and can provide sufficient exposure of the operative field. Further study in the form of randomized controlled trials is needed to investigate the advantages of this new technique.

Pulmonary circulatory changes after bilateral total knee arthroplasty during regional anesthesia

Study ObjectiveTo monitor the pulmonary hemodynamics of patients undergoing bilateral total knee arthroplasty (BTKA) intraoperatively and up to 24 hours following surgery. DesignProspective observational study. SettingUniversity-affiliated teaching hospital. Patients30 ASA physical status 2 and 3 patients scheduled for single-stage, cemented BTKA during epidural anesthesia. InterventionsPulmonary artery catheters were in all patients. MeasurementsSystemic vascular resistance (SVR), pulmonary vascular resistance (PVR), the ratio of PVR to SVR at baseline, at the beginning of surgery, and after each knee implantation were recorded and compared with measurements taken one day postoperatively (POD 1). Main ResultsOn POD 1, PVR/SVR was increased by 30% compared with baseline (P < 0.0001) and by 20% versus the end of surgery (P < 0.0001). Systemic vascular resistance decreased during surgery and was significantly lower than baseline at 24 hours after surgery (P < 0.0001). No significant change in PVR was noted during surgery. ConclusionThe PVR/SVR ratio on the day following BTKA was increased. This change may represent the different effects of inflammatory perioperative stresses on the pulmonary and systemic vasculature.

Is classical pseudoxanthoma elasticum a consequence of hepatic ‘intoxication’ due to ABCC6 substrate accumulation in the liver?

Pseudoxanthoma elasticum (PXE) is a serious genetic disorder with ectopic mineralization affecting the skin, the eye and the cardiovascular system. The disease is predominantly caused by mutations in the transmembrane ABC protein ABCC6, a putative small substrate transporter. Interestingly, ABCC6 seems virtually absent in the affected organs, whereas a high expression is seen in hepatocytes. This and further published experimental evidence indicate that PXE is a systemic, metabolic liver disease where circulatory changes affect the peripheral mineralization process. Owing to the well-characterized transport of organic substrates by related ABC proteins, it has been proposed that PXE is caused by impaired export of an antimineralization compound to the blood. The authors here present an alternative hypothesis that explains ectopic mineralization in PXE as a consequence of hepatic accumulation of ABCC6 substrate(s) that via gene-regulating effects leads to altered hepatic secretion and activation of antimineralization/anticalcification proteins such as fetuin-A and Gla proteins.

Grand Challenge: Computational Models Validated Against Critical Experiments.

Grand Challenge: Computational Models Validated Against Critical Experiments.