Investigation of Zinc on hemorheological parameters in a rat model of diabetes.

Diabetes mellitus (DM) is a complex, chronic metabolic disorder characterized by impaired regulation of blood glucose levels. Zinc (Zn) is an essential trace elements that plays a role in various physiological processes within the body, including those related to diabetes. The current study was investigated the effect of Zn supplementation on hemorheological parameters in a rat model of DM. After induction of DM, 32 male Wistar albino rats were divided into four groups: control, Zn, DM, and Zn+DM. Whole blood viscosity (WBV) was determined by using digital cone and plate viscometer and plasma viscosity (PV) was determined by a Coulter Harkness capillary viscometer. The rats in the DM Group showed a decrease in both Zn levels and body weight, as well as an increase in glucose levels when compared to the control group. Diabetic rats supplemented with Zn displayed lower blood glucose levels and higher concentrations of Zn compared to the DM Group. The higher PV and lower hematocrit level were measured in DM Group than control group and lower PV, higher hematocrit level were measured in Zn+DM group than DM Group. The WBV was measured at four different shear rates (57.6-115.2 - 172.8-230.4 s -1). A statistically significant increase was observed in the DM group compared to the control group. Additionally, a statistically significant decrease was observed in the Zn+DM Group compared to the DM Group at a shear rate of 230.4 s-1. Erythrocyte rigidity index (Tk) and oxygen delivery index (ODI) were computed under conditions of high shear rate. The rats in the DM group exhibited a reduction in ODI and an elevation in Tk in comparison to the control group. Conversely, the diabetic rats supplemented with Zn exhibited decreased Tk and increased ODI compared to the DM Group. Zn supplementation seems to have a potential beneficial effect for protecting adverse affect of diabetes on hemorheogical parameters and for maintaining vascular health.

Investigating the blood rheology in the first trimester pregnancies with high risk for preeclampsia.

BACKGROUND: Pregnancy is a dynamic process associated with changes in vascular and rheological resistance. Maternal maladaptation to these changes is the leading cause of pregnancy complications such as preeclampsia. OBJECTIVE: This study aimed to assess the hemorheological alterations in pregnancies with a high risk for preeclampsia in the first trimester. METHODS: Ninety-two pregnant women were allocated into the high preeclampsia risk group (37 cases) and control groups (55 cases). Plasma and whole blood viscosity and red blood cell morphodynamic properties, including deformability and aggregation were assessed by Brookfield viscometer and laser-assisted optical rotational cell analyzer (LORRCA) at 11-14 gestational weeks. RESULTS: Whole blood viscosity was significantly higher in the high-risk group at all shear rates. Plasma viscosity and hematologic factors showed no differences between the groups. Hematocrit levels positively correlated with high blood viscosity only in the high-risk group. There were no significant changes in the other deformability and aggregation parameters. CONCLUSIONS: Changes in the whole blood viscosity of pregnant women with high preeclampsia risk refer to impaired microcirculation beginning from the early weeks of gestation. We suggest that the whole blood viscosity is consistent with the preeclampsia risk assessment in the first trimester, and its measurement might be promising for identifying high-preeclampsia-risk pregnancies.

Whole Blood Viscosity Reference Intervals and Its Correlation with Hematology and Serum Chemistry in Cats Using Scanning Capillary Method.

Whole blood viscosity, a hemorheological factor, is currently used for diagnosis, as it is correlated with various vascular diseases that are difficult to diagnose early with a general blood test. It was determined that it was necessary to set reference intervals for further studies and utilization of whole blood viscosity in cats, a representative companion animal, and this study was conducted. Fifty healthy cats were recruited for the study, and whole blood viscosity, complete blood count, and serum chemistry tests were performed. The reference intervals of whole blood viscosity were 15.169 to 43.684 cP at a shear rate of 1 s-1 reflecting diastole, and 3.524 to 5.544 cP at a shear rate of 300 s-1 reflecting systole. Red blood cells, hematocrit, hemoglobin, white blood cells, and neutrophils in the complete blood count, and total protein, albumin, globulin, and cholesterol in the serum chemistry were significantly correlated with whole blood viscosity. The results of this study set the reference intervals of whole blood viscosity for healthy cats in a wide shear rate range that has not yet been fully established, and its correlation with other blood indicators investigated.

Increased whole blood viscosity is associated with primary idiopathic complete atrioventricular block and poor clinical outcomes in these patients.

BACKGROUND: Complete atrioventricular block is most commonly caused by age-related degeneration and fibrosis in the cardiac conduction system and is called primary idiopathic complete atrioventricular (iCAVB). Although many factors affect this situation, which increases with age in the cardiac conduction system, the relationship between whole blood viscosity (WBV) and iCAVB has not been clarified until now. In this study, we aim to reveal the relationship between iCAVB and WBV. METHODS AND RESULTS: 141 patients with dual-chamber permanent pacemaker implanted for iCAVB and 140 age- and sex-matched subjects were included in this study. The WBV values of the study groups were compared in both high shear rate (HSR) and low shear rate (LSR). Both WBV at HSR and WBV at LSR were significantly higher in the iCAVB group compared to the control group (16.11 [15.14-16.89] vs 14.40 [13.62-15.58]; 39.82 [17.43-55.23] vs 1.38 [-13.14-26.73]; p < 0.001, respectively). The patient population was followed up for an median of 38 months for all-cause mortality. Higher mortality rates were found in higher WBV at HSR and WBV at LSR (p < 0.001,for both). CONCLUSIONS: In this study, WBV was found to be an independent predictor for iCAVB, and in these patients WBV was associated with poor clinical outcomes.

Effects of sarpogrelate on blood viscosity.

The objective of the present study was to evaluate the effects and safety of sarpogrelate hydrochloride (sarpogrelate) in patients with elevated blood viscosity (BV), after 12 and 24 weeks of twice (BID) or thrice (TID) daily administrations of sarpogrelate (100 mg). The participants received oral sarpogrelate administration for 24 weeks and visited the hospital every 12 ± 2 week for blood viscosity measurements at shear rates of 5 and 300 s-1. The BV measured at shear rate of 5 s-1 in male patients decreased significantly from 18.91 cP at the baseline to 16.3 cP after 24 weeks of sarpogrelate administration (13.6 % drop, p < 0.001). The BV measured at 5 s-1 in female decreased more significantly from 17.5 cP at the baseline to 13.4 cP after 24 weeks of sarpogrelate administration (23.0 % drop, p < 0.001). In summary, sarpogrelate may be considered as a possible therapeutic option for improving BV in patients with elevated blood viscosity. In particular, the reduction of the low-shear BV with the help of a viscosity-reducing drug such as sarpogrelate may be considered as a potentially new pharmacological tool for microvascular disease.

Lipoprotein-X and Lipoprotein-Z Induced Hyperviscosity Syndrome in the Setting of Cholestatic Liver Failure.

We describe a case referred for worsening hypercholesterolemia in the setting of atorvastatin and fenofibrate-induced liver injury. The patient reported neurological complaints attributed to hyperviscosity syndrome (induced by lipoprotein-X and lipoprotein-Z). Hepatic recovery was associated with reduction of whole blood viscosity and amelioration of neurological symptoms. (Level of Difficulty: Advanced.).

Another possible determinant for ischemic stroke with nonvalvular atrial fibrillation other than conventional oral anticoagulant treatment: The relationship between whole blood viscosity and stroke☆.

OBJECTIVES: Patients with nonvalvular atrial fibrillation (NVAF) still experience ischemic stroke despite recommended medications and this could be the consequence of increased whole blood viscosity (WBV). We evaluated the predictive value of WBV for stroke in patients with NVFA despite receiving oral anticoagulant (OAC) therapy. METHODS: One thousand and forty-three NVAF patients on OAC medication were followed up for median 36.13 ± 18.31 months. WBV was calculated according to the validated de Simone's formula. RESULTS: WBV was significantly higher in stroke group when compared to non-stroke group at both low shear rate (LSR) and high shear rate (HSR). Multiple regression analysis demonstrated an independent association between WBV and stroke when adjusted for other risk factors. CONCLUSIONS: WBV appears to be a profitable predictor of ischemic stroke in patients with NVAF receiving OAC.

Hemorheological and microvascular disturbances in patients with type 2 diabetes mellitus.

BACKGROUND: In the blood vessels the impaired hemorheological parameters in patients with type 2 diabetes mellitus (T2DM) could lead to elevated flow resistance, increased forces at the endothelial wall and to microvascular disturbances. OBJECTIVE: The aim of the study is to investigate the hemorheological variables and the changes of the skin blood flow responses to cold stress in T2DM patients. METHODS: The basic hemorheological parameters: hematocrit (Ht), fibrinogen (Fib), whole blood viscosity (WBV) and plasma viscosity (PV) were examined in 20 patients with T2DM and a control group of 10 healthy age and sex matched controls. The mechanisms of vascular tone regulation were investigated using the wavelet analysis of the skin temperature oscillations (WAST). The degrees of the microvascular tone changes were determined during a cold test in the endothelial (0.02-0.0095 Hz), neurogenic (0.05- 0.02 Hz) and myogenic (0.05- 0.14 Hz) frequency ranges. RESULTS: Significant increase of Fib and WBV in the patients in comparison to controls was found. The mean values of the amplitudes of the skin temperature (ST) pulsations decreased significantly during the cold stress only in the endothelial frequency range for the diabetic patients. CONCLUSIONS: The results of our study reveal parallel impairment of the blood rheological parameters and the cutaneous microcirculation in T2DM patients.

Sex-differential downregulation of methotrexate on plasma viscosity and whole blood viscosity in psoriasis.

BACKGROUND: Psoriasis is associated with an increased risk for cardiovascular disease (CVD). Methotrexate (MTX) is often used as a first-line system therapy and there is a need to determine its effect on whole blood viscosity (WBV) and plasma viscosity (PV) in psoriasis.METHODSA prospective, single-center, interventional study with a total of 111 psoriatic patients who received MTX therapy from October 22, 2018, to December 28, 2019, and 111 age- and sex-matched healthy controls. Changes in WBV, PV, blood counts, liver and renal function were evaluated.RESULTSPsoriatic patients had significantly higher levels of WBV and relative viscosity (RV) at low shear rate (LSR), erythrocyte aggregation index (EAI), and PV than sex and age-matched healthy controls. PV was positively correlated with erythrocyte sedimentation rate (ESR), ESR was positively correlated with high sensitive C-reactive protein (hCRP). But only hCRP was positively associated with psoriasis area severity index (PASI) score. MTX significantly decreased the levels of PV, ESR, hCRP, and blood pressure (BP) in male patients, and the level of WBV in female patients. CONCLUSION: Sex-specific downregulation of MTX on WBV, PV, hCRP, and BP, indicating that the effect of MTX on the risk of cardiovascular disease was related with sex.

The association between whole blood viscosity and high thrombus burden in patients with non-ST elevation myocardial infarction.

BACKGROUND: Prior studies showed that patients with elevated whole blood viscosity (WBV) had a higher risk of arterial thrombosis, acute stent thrombosis, and left ventricular apical thrombus presence after acute coronary syndrome. This investigation aimed to determine the association between WBV and high thrombus burden (HTB) in non-ST elevation myocardial infarction (NSTEMI) patients treated with percutaneous coronary intervention (PCI). METHODS: This retrospective cohort investigation included data from consecutive 290 NSTEMI patients who received PCI at a tertiary institution. Patients with grade 1-3 thrombus burden were categorized as having low thrombus burden (LTB) (n = 178), whereas those with grade 4-5 thrombus burden were classified as having HTB (n = 112). WBV at high shear rate (HSR) and low shear rate (LSR) were estimated using hematocrit (HTC) and total protein levels. RESULTS: Patients with HTB had higher WBV at both LSR and HSR. In HTB patients, the frequency of infarct-related artery (IRA) reference vessel diameter, distal embolization, and no-reflow was also higher. Multivariable logistic regression models indicated that WBV at LSR (odds ratio [OR], 1.028; 95% confidence interval [CI], 1.014-1.043; P < 0.001) and HSR (OR, 1.606; 95% CI, 1.334-1.953; P < 0.001) were independent predictors of HTB in NSTEMI patients. Notably, the area under the curve value of WBV at both shear rates was greater than that of its components, including total protein and HTC. CONCLUSION: This is the first study showing that WBV at both shear rates is a significant predictor of HTB in NSTEMI patients.

Whole blood viscosity is an independent early predictor for metabolic syndrome and its components in men: A prospective cohort study in Northern Chinese population.

The association between whole blood viscosity (WBV) and metabolic syndrome (MetS) is still scarcely investigated in the population-based prospective cohort. We aim to explore the longitudinal effect of WBV on MetS, and to verify whether WBV measures can be used as early predictors for MetS. The longitudinal cohort consisted of 3,508 adults (2,350 males and 1,158 females) who visited the health check-up system twice. WBV were measured at four shear rate (200, 50, 10 and 1 s-1), and their values were classified into quartiles. Multivariate Cox models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women, respectively. A total of 444 (12.66%) incident MetS were observed at follow-up period. The incidences of MetS significantly increased with increasing quartiles of WBVs at all of the shear rate in men. After adjusting for baseline age, smoking, obesity, hypertension, hyperglycemia, and hyperlipidemia status, all of the WBV measures were significantly associated with incident MetS in men, and the HRs showed clear increasing trend across the quartiles of baseline WBVs. There were no significant association between WBVs and incident MetS in women. These findings suggest that MetS has a hemodynamic basis, and WBVs could be used as independent early predictor for MetS in men.

Whole blood viscosity is associated with baseline cerebral perfusion in acute ischemic stroke.

Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk factor for stroke. Poor microcirculation due to elevated WBV can prevent adequate perfusion of the brain and might act as an important secondary factor for hypoperfusion in acute ischaemic stroke. In the present study, we examined the association of WBV with basal cerebral perfusion assessed by CT perfusion in acute ischaemic stroke. Confirmed acute ischemic stroke patients (n = 82) presenting in hours were recruited from the single centre. Patients underwent baseline multimodal CT (non-contrast CT, CT angiography and CT perfusion). Where clinically warranted, patients also underwent follow-up DWI. WBV was measured in duplicate within 2 h after sampling from 5-mL EDTA blood sample. WBV was significantly correlated with CT perfusion parameters such as perfusion lesion volume, ischemic core volume and mismatch ratio; DWI volume and baseline NIHSS. In a multivariate linear regression model, WBV significantly predicted acute perfusion lesion volume, core volume and mismatch ratio after adjusting for the effect of occlusion site and collateral status. Association of WBV with hypoperfusion (increased perfusion lesion volume, ischaemic core volume and mismatch ratio) suggest the role of erythrocyte rheology in cerebral haemodynamic of acute ischemic stroke. The present findings open new possibilities for therapeutic strategies targeting erythrocyte rheology to improve cerebral microcirculation in stroke.

Association of whole blood viscosity with thrombus presence in patients undergoing transoesophageal echocardiography.

Whole blood viscosity (WBV) is considered as a reasonable proxy measure of blood flow, and it has been investigated in different cohort settings, including in patients with deep venous thrombosis, arterial thrombosis, acute stent thrombosis, and left ventricular apical thrombus formation following acute coronary syndrome. To determine the association between WBV and the presence of thrombus in the left atrium (LA) or left atrial appendage (LAA) in individuals who had transoesophageal echocardiography (TEE). The clinical data from 262 consecutive patients who had TEE at our facility were included in this retrospective cohort study. WBV was determined at both a high shear rate (HSR) and low shear rate (LSR) using hematocrit and total protein levels. In 22 cases (8.3%), the thrombus was detected. According to multivariable analyses, WBV at HSR and LSR were independently linked with thrombus detection in TEE. In a receiver operating characteristic (ROC) analysis, the area under curve (AUC) values of WBV at HSR and LSR were 0.77 and 0.76, respectively. To predict the presence of thrombus in TEE; the ideal value of WBV at HSR was > 16.6 with 81% sensitivity and 69% specificity and the ideal value of WBV at LSR was > 51.4 with 81% sensitivity and 70% specificity. This was the first study to indicate that significantly higher levels of WBV at both the HSR and LSR were linked to the presence of thrombus in the LA and LAA in cases who underwent TEE.

Comparison between whole blood viscosity measured and calculated in subjects with monoclonal gammopathy of undetermined significance and in patients with multiple myeloma: Re-evaluation of our survey.

BACKGROUND: in this study, with a re-evaluation of the hemorheological determinants previously described in MGUS subjects and in MM patients, we have detected the calculated whole blood viscosity, according whether to the hematocrit and total plasma protein concentration (de Simone formula) or to the haematocrit and plasma fibrinogen level (Merrill formula), and a marker of the erythrocyte aggregation (albumin/fibrinogen level). METHODS: data were expressed as means±standard deviation. Student's t test for unpaired data was used to compare MGUS subjects and MM patients. The correlation coefficient between mean erythrocyte aggregation (MEA) and hematocrit (Ht) was evaluated in MGUS, MM and MGUS + MM groups using the Spearman test. RESULTS: the comparison between MGUS and MM shows that the measured blood viscosity and calculated blood viscosity based on hematocrit and total plasma protein, but not which estimated in relation to the hematocrit and plasma fibrinogen, differentiate the two groups. A difference between the two groups also regards the measured erythrocyte aggregation and its surrogate marker. In addition, the measured plasma viscosity at low shear rate (0.51 s-1) and, in particular, the ratio between plasma viscosity at low (0.51 s-1) and high (450 s-1) shear rates distinguish MGUS and MM. CONCLUSIONS: calculated blood viscosity (de Simone formula and other formulas) and the surrogate marker of erythrocyte aggregation disclose an alike trend with the corresponding hemorheological determinants obtained by using their direct measurement.

Relationship between Whole Blood Viscosity and Lesion Severity in Coronary Artery Disease.

Objective This article investigates the relationship of fractional flow reserve (FFR) with whole blood viscosity (WBV) in patients who were diagnosed with chronic coronary syndrome and significant stenosis in the major coronary arteries and underwent the measurement of FFR. Material and Method In the FFR measurements performed to evaluate the severity of coronary artery stenosis, 160 patients were included in the study and divided into two groups as follows: 80 with significant stenosis and 80 with nonsignificant stenosis. WBVs at low shear rate (LSR) and high shear rate (HSR) were compared between the patients in the significant and nonsignificant coronary artery stenosis groups. Results In the group with FFR < 0.80 and significant coronary artery stenosis, WBV was significantly higher compared with the group with nonsignificant coronary artery stenosis in terms of both HSR (19.33 ± 0.84) and LSR (81.19 ± 14.20) ( p < 0.001). In the multivariate logistic regression analysis, HSR and LSR were independent predictors of significant coronary artery stenosis (HSR: odds ratio: 1.67, 95% confidence interval: 1.17-2.64; LSR: odds ratio: 2.46, 95% confidence interval: 2.19-2.78). In the receiver operating characteristic (ROC) curve analysis, when the cutoff value of WBV at LSR was taken as 79.23, it had 58.42% sensitivity and 62.13% specificity for the prediction of significant coronary artery stenosis (area under the ROC curve: 0.628, p < 0.001). Conclusion WBV, an inexpensive biomarker that can be easily calculated prior to coronary angiography, was higher in patients with functionally severe coronary artery stenosis, and thus could be a useful marker in predicting the hemodynamic severity of coronary artery stenosis in patients with chronic coronary syndrome.

Relationship between blood viscosity and no-reflow phenomenon in ST-segment elevation myocardial infarction performed in primary percutaneous coronary interventions.

Background: This study aimed to analyze the associations between no-reflow (NR) phenomenon development and whole-blood viscosity in patients with ST-elevated myocardial infarction. Methods: A total of 217 patients with ST-elevated myocardial infarction were included. whole-blood viscosity values were assessed using hematocrit and total protein values, and low shear rate (LSR) and high shear rate (HSR) were calculated. Results: The average LSR and HSR values of the study group were significantly higher than the control group (p < 0.001). Multivariate logistic regression analysis showed that both HSR (odds ratio: 4.957; p < 0.001) and LSR (odds ratio: 1.114; p < 0.001) were independent predictors for NR development. Conclusion: This study found that increased blood viscosity was an independent predictor for NR development.

Lay abstract Following a heart attack, surgeons can attempt to repair the damage using a procedure called a percutaneous coronary intervention. In some cases, blood flow does not return to the heart tissue as expected ('failure of reperfusion') after this procedure, which is known as the no-reflow (NR) phenomenon. In this study, the researchers investigated whether there was a link between patients who had experienced a type of heart attack called an ST-elevated myocardial infarction (STEMI) and developed NR, and the viscosity (thickness) of their blood. The researchers looked at the viscosity of whole-blood samples from 98 STEMI patients with NR and 119 control individuals matched for age and gender. They found that whole-blood samples could be used to predict the likelihood of a STEMI patient experiencing NR.

Whole blood viscosity in the evaluation of thrombogenic milieu in mitral stenosis.

Aim: We aimed to assess the association of whole blood with thromboembolic milieu in significant mitral stenosis patients. Methodology & results: We included 122 patients and classified patients into two groups as having thrombogenic milieu, thrombogenic milieu (+), otherwise patients without thrombogenic milieu, thrombogenic milieu (-). Whole blood viscosity (WBV) in both shear rates were higher in thrombogenic milieu (+) group comparing with thrombogenic milieu (-). WBV at high shear rate and WBV at low shear rate parameters were moderately correlated with grade of spontaneous echo contrast. Adjusted with other parameters, WBV parameters at both shear rates were associated with presence of thrombogenic milieu. Discussion & conclusion: We found that extrapolated WBV at both shear rates was significantly associated with the thrombogenic milieu in mitral stenosis. This easily available parameter may provide additional perspective about thrombogenic diathesis.

Blood Rheology Alterations in Patients with Cardiovascular Diseases.

Blood rheology is an important determinant of blood flow but is probably one of the most neglected areas in clinical literature and practice. Blood viscosity changes according to shear rates and depends on cellular and plasma factors. RBCs' aggregability and deformability are the main determinants of local flow characteristics in areas with lower and higher shear rates, but plasma viscosity is the main regulatory factor of flow resistance in the microcirculation. In individuals with altered blood rheology, the mechanical stress to vascular walls induces endothelial injury and vascular remodelling, and promotes atherosclerosis. Increased values of whole blood viscosity and plasma viscosity are correlated with cardiovascular risk factors and adverse cardiovascular events. The long-term effects of physical exercise can produce a hemorheological fitness that protects against cardiovascular diseases.

Whole blood viscosity predicts nondipping circadian pattern in essential hypertension.

Aim: We aimed to investigate the association between whole blood viscosity (WBV) and nondipping pattern in patients with essential hypertension. Materials & methods: A total of consecutive 530 patients who had been evaluated by ambulatory blood pressure monitoring were included. WBV was estimated by using hematocrit and plasma total protein levels for both WBV in low shear rate (0.5 s-1) and WBV in high shear rate (208 s-1) according to the de Simone's formula. Results: In the multivariate analysis, low shear rate and high shear rate of WBV were associated independently with nondipping pattern in patients with essential hypertension. Conclusion: As a simple, inexpensive and noninvasive tool, WBV seems to be a significant predictor of nondipping hypertension.

Relationship between apical thrombus formation and blood viscosity in acute anterior myocardial infarction patients.

Aim: This study sought to investigate the predictive value of whole blood viscosity (WBV) to identify high-risk patients who will develop an apical thrombus during the acute phase of anterior transmural infarction. Materials & methods: Consecutive 1726 patients with first acute anterior myocardial infarction were evaluated. WBV was calculated according to the Simone's formula. Results: Patients with an apical thrombus had prolonged pain to balloon time, higher rate of post-PCI thrombolysis in myocardial infarction flow ≤1 and significantly higher mean WBV values at both shear rates than those without an apical thrombus. Conclusion: WBV values at both shear rates were found to be significant and independent predictors for early LV apical thrombus formation complicating a first-ever anterior wall myocardial infarction.