Clinical Hemorheology and Microcirculation - Volume Pre-press, issue Pre-press

Authors: Chung, Ju-Hyun | Lee, Kyung Eun | Park, Jai-Wun | Shin, Eun-Seok

Article Type: Research Article

Abstract: While fractional flow reserve (FFR) is a good diagnostic index to assess the myocardial ischemia, coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) can be used to address microvascular status without any significant epicardial disease. The independent predictors of for FFR and IMR are totally different and acts differently on the macro- and micro-vascular dysfunction. In high FFR patients, low CFR and high IMR which indicates the presence of overt microvascular disease demonstrated poor prognosis. Thus, comprehensive physiological assessments using FFR, CFR and IMR could improve the ability to discriminate patients at high risk of future events.

Keywords: Microvascular dysfunction, fractional flow reserve, coronary flow reserve, index of microcirculatory resistance

DOI: 10.3233/CH-189403

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-4, 2018

Authors: Horobin, Jarod T. | Watanabe, Nobuo | Hakozaki, Masaya | Sabapathy, Surendran | Simmonds, Michael J.

Article Type: Research Article

Abstract: BACKGROUND: Red blood cells (RBC) are exposed to varying shear stress while traversing the circulatory system; this shear initiates RBC-derived nitric oxide (NO) production. OBJECTIVE: The current study investigated the effect of varying shear stress dose on RBC-derived NO production. METHODS: Separated RBC were prepared with the molecular probe, diamino-fluoreoscein diacetate, for fluorometric detection of NO. Prepared RBC were exposed to discrete magnitudes of shear stress (1–100 Pa), and intracellular and extracellular fluorescence was quantified via fluorescence microscopy at baseline (0 min) and discrete time-points (1–30 min). RESULTS: Intracellular RBC-derived NO fluorescence was significantly increased (p  < … 0.05) following shear stress exposure when compared to baseline at: i) 1 min–100 Pa; ii) 5 min–1, 5 Pa; iii) 15 min–1, 5, 35 Pa; iv) 30 min–35 Pa. Extracellular RBC-derived NO fluorescence was significantly increased (p  <  0.05) following shear stress exposure when compared to baseline at: i) 5 min – 100 Pa; ii) 15 min–100 Pa; iii) 30 min–40, 100 Pa. CONCLUSIONS: These data indicate that: i) a dose-response exists for the RBC-derived production of NO via shear stress; and ii) exposure to supra-physiological shear stress allows for the leakage of RBC intracellular contents (e.g., RBC-derived NO). Show more

Keywords: Haemorheology, erythrocyte, mechanotransduction, vasodilation, biocompatibility

DOI: 10.3233/CH-189412

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2018

Authors: Mrowietz, C. | Franke, R.P. | Pindur, G. | Sternitzky, R. | Jung, F. | Wolf, U.

Article Type: Research Article

Abstract: BACKGROUND: The laser Doppler fluxmetry (LDF) is a non-invasive method to assess skin blood perfusion, measuring the flow of blood cells inside a tissue volume without harming the tissue. In the diagnosis of skin circulation disorders, the results of the LDF measurement are generally used in such a way that “normal” (or non-ill) or “pathological” values are achieved by comparison with a reference sample, for example of apparently healthy subjects. MATERIAL AND METHODS: In this study, the values of LDF for the diagnosis of microcirculatory disorders in patients with coronary artery disease (n  = 20) or in patients …with microcirculatory disorders, already diagnosed by capillary microscopy (n  = 46), were examined. RESULTS: The mean values of LD amplitudes in the four frequency windows for patients with coronary artery disease were in the reference range. However, some of the patients showed reduced LD values: in eleven of the twenty patients, one or more mean LD amplitudes were below the reference range. Four of the eleven patients had pathologically decreased capillary erythrocyte velocities of v ery  = 0.09–0.21 [mm/s], while the other seven patients had normal blood circulation at rest. For all patients with a proven cutaneous microcirculatory disorder, the mean LD amplitude in at least one of the frequency windows FF2 to FF4 was pathologically reduced. CONCLUSION: The Laser-Doppler fluxmetry method used in the study allows the reliable diagnosis of cutaneous microcirculatory disorders. Show more

Keywords: Laser-Doppler fluxmetry, cutaneous microcirculation, atherosclerosis

DOI: 10.3233/CH-189402

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2018

Authors: Negrão de Figueiredo, G. | Mueller-Peltzer, K. | Armbruster, M. | Rübenthaler, J. | Clevert, D.A.

Article Type: Research Article

Abstract: BACKGROUND: The first method of choice for gallbladder alteration detection is the conventional ultrasound. Due to some imaging limitations, contrast-enhanced ultrasound (CEUS) has been widely used in the last years. CEUS is an additional modality that is able to depict microvessels flow and elucidate suspicious findings. OBJECTIVE: The aim of this retrospective mono-center analysis study is to evaluate the performance of CEUS in gallbladder diseases and compare it to cross-sectional imaging modalities and histopathological results as gold standard. METHODS: The retrospective study analysed 37 patients with gallbladder diseases between 2009 and 2017. All patients underwent CEUS …examinations and additional cross-sectional imaging was also performed: CT imaging on 24 (64.9% ) patients, MRI imaging on 18 (48.6% ) patients, CT and MRI imaging on (28.7% ). CEUS images were performed and interpreted by a single physician. RESULTS: CEUS imaging results of the gallbladder showed a sensitivity and specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100%. CT imaging of the gallbladder showed a sensitivity of 100%, specificity of 75%, PPV of 100%, and NPV of 95%. MR imaging of the gallbladder showed a sensitivity of 100%, specificity of 93%, PPV of 75%, and NPV of 100%. CONCLUSION: Ultrasound imaging plays an essential role in the evaluation of gallbladder disease. Due to additional features of contrast-enhanced ultrasound, it is possible to differentiate gallbladder pathologic alterations by depicting its micro and macrocirculation and display important malignant features that recommends prompt management. Patients with contraindications to other cross-sectional imaging modalities benefit from this safe technique. Show more

Keywords: CEUS, gallbladder, cross-sectional imaging modalities, histopathological findings

DOI: 10.3233/CH-189404

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Ahmadizad, Sajad | Daraei, Ali | Bassami, Minoo | Rahmani, Hiwa

Article Type: Research Article

Abstract: BACKGROUND: L-Arginine, the precursor of NO might be involved in improving the cardiovascular disorders via regulation of functional properties of erythrocytes. OBJECTIVE: This study investigated the effects of L-Arginine supplementation on responses of red blood cell (RBC) properties to high intensity interval exercise (HIIE). METHODS: Ten overweight healthy men participated voluntarily in the study and performed two HIIE trials with and without L-Arginine in two separate weeks. The HIIE protocol included 12 intervals of 3-min encompassed 1-min running at 100% of vVO2 max and 2-min active recovery at 40% of vVO2 max. Three blood samples …were taken before and after supplementation, and immediately after exercise; and were used to measure red blood cell properties. RESULTS: The HIIE protocol increased hematocrit, hemoglobin and lactate significantly (P  <  0.05), but had no significant effect on RBC aggregation, RBC deformability, and fibrinogen concentration. When data were compared for two trials no significant differences between the responses of RBC properties to two HIIE protocols were detected (P  >  0.05), whereas the increases in lactate concentration following HIIE was significantly lower in L-Arginine than placebo trial (P  <  0.05). CONCLUSIONS: It is concluded that L-Arginine consumption prior to HIIE does not lead to any improvement in RBC properties during HIIE in overweight healthy men. Show more

Keywords: Intermittent exercise, nitric oxide, hemorheology, erythrocyte, blood flow

DOI: 10.3233/CH-189413

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Niessen, C. | Beyer, L.P. | Haimerl, M. | Schicho, A. | Stroszczynski, C. | Wiggermann, P. | Jung, E.M.

Article Type: Research Article

Abstract: PURPOSE: To assess the postprocedure findings after percutaneous irreversible electroporation (IRE) of hepatocellular carcinoma (HCC) in contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Percutaneous IRE was performed in a total of 22 patients with 24 HCC tumours following interdisciplinary tumour board review. The lesions were documented using CEUS before, immediately and within 24 hours after IRE. During follow-up CEUS was performed at 6 weeks and 3, 9, and 12 months after ablation. Two experienced radiologists evaluated the acquired CEUS image date in a consensus reading. RESULTS: Median tumour size before treatment was 13.7±4.8 mm (short axis) and 16.0±5.2 mm …(long axis). All HCC lesions showed arterial hyperenhancement in CEUS. Median size of the ablation defect after ablation was 29.3±5.2 mm (short axis) and 31.6±5.6 mm (long axis). After IRE all tumours showed complete devascularization. The size of the ablation defects showed significant shrinkage and reduced peripheral enhancement in the course of follow-up. At 12 months follow-up the ablation defect size decreased to 16.7±4.3 mm (short axis) and 18.3±4.1 mm (long axis). CONCLUSION: CEUS showed a complete devascularization of HCC tumours after IRE. Post-intervetional peripheral enhancement returned to normal during follow-up and may represent zones of reversible damage of cellular integrity through electroporation. A significant shrinkage of the ablation defects during 12 month of follow-up was seen in all cases. Show more

DOI: 10.3233/CH-180449

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Negrão de Figueiredo, G. | Mueller-Peltzer, K. | Zengel, P. | Armbruster, M. | Rübenthaler, J. | Clevert, D.A.

Article Type: Research Article

Abstract: BACKGROUND: Radiologic imaging, especially ultrasound has an important role in the assessment of gallbladder alteration. Contrast-enhanced ultrasound (CEUS) is an easy and fast imaging technique that overcomes the limitations of greyscale ultrasonography. It is a safe tool that can be used as an additional imaging modality in order to elucidate and differentiate gallbladder pathological findings. OBJECTIVE: The aim of this retrospective study analysis is to assess the diagnostic performance of CEUS in gallbladder alterations and compare the results to the histopathological findings. METHODS: A total of 17 patients between 2009 and 2017 with uncertain gallbladder …appearance were retrospectively analysed. A single experienced physician with more than fifteen years’ experience performed CEUS examinations by applying a second-generation blood pool agent (SonoVue ® , Bracco, Milan, Italy). Archived images were interpreted by the same physician and compared to the histopathological findings. RESULTS: CEUS results when correlated to the respectively pathologic findings presented a sensitivity of 100%, a specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100%. All patients were successfully examined without any adverse reaction. CONCLUSION: In conclusion, the excellent results in this study acknowledged that CEUS is a feasible alternative tool to differentiate gallbladder pathologic alterations. Show more

Keywords: CEUS, gallbladder, histopathological findings

DOI: 10.3233/CH-189405

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2018

Authors: Mueller-Peltzer, K. | Negrao de Figueiredo, G. | Graf, T. | Rübenthaler, J. | Clevert, D.-A.

Article Type: Research Article

Abstract: BACKGROUND: Renal cell carcinomas (RCC) represent a heterogeneous group of hypo- and hypervascularized malignancies. Using contrast-enhanced ultrasound (CEUS) specific imaging features of clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC) subtypes have been demonstrated. However, some RCCs show atypical imaging features making it difficult to distinguish between the subtypes. OBJECTIVE: This study was performed to evaluate the observed enhancement features of pRCC in CEUS and to assess the sensitivity in the diagnosis of suspected renal malignancies in a 10 year retrospective analysis at our institution. METHODS: The study population consisted of 60 …patients with histologically confirmed pRCC. All patients underwent CEUS imaging between 2005 and 2015 as part of their diagnostic workup. RESULTS: In 45 out of 60 (75%) cases the examined pRCC showed typical hypoenhancement and wash-out. 15 out of 60 (25%) pRCC showed atypical enhancement features; in 14 cases the contrast enhancement indicated a ccRCC. 1 complex cyst was falsely reported as IIF lesion. 59 out of 60 malignancies were reported as malignant using CEUS resulting in a sensitivity of 98.4%. CONCLUSIONS: CEUS is an eligible imaging technique to visualize the contrast enhancement features of pRCC. However, up to 25% of pRCCs show an atypical enhancement pattern making it difficult to distinguish it from other renal lesions. Show more

Keywords: Contrast-enhanced ultrasound, CEUS, renal cell carcinoma, RCC, enhancement features

DOI: 10.3233/CH-189406

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2018

Authors: Preuss, Stephanie | Rother, Charlotte | Renders, Lutz | Wagenpfeil, Stefan | Büttner-Herold, Maike | Slotta-Huspenina, Julia | Holtzmann, Christopher | Kuechle, Claudius | Heemann, Uwe | Stock, Konrad Friedrich

Article Type: Research Article

Abstract: Introduction: Allograft rejection (AR), chronic allograft injury (CAI) and acute tubular necrosis (ATN) can lead to renal allograft dysfunction after kidney transplantation. Interstitial fibrosis/tubular atrophy (Banff classification 2005) describes chronic allograft injury with no specific etiology, thus explaining the common final endpoint of various (immunologic and non immunologic) etiologies. The aim of this study was to evaluate correlations between the Doppler sonographic RI-values and histopathological changes of renal allografts biopsies during rejection, acute tubular necrosis and chronic allograft injury as well as the influence of donor and recipient features on the intrarenal RI-values. Methods: 102 allograft biopsies and …ultrasound reports of 69 patients with kidney transplantation performed at the hospital Klinikum rechts der Isar (Technische Universität München, Germany) between 2009 and 2013 were analyzed retrospectively (41 biopsies of living donors, 61 biopsies of deceased donors). Chronic allograft injury was described using the IFTA (interstitial fibrosis and tubular atrophy) or the ECAI score (extended chronic allograft injury score). The ECAI score was built out of the chronic histological lesions glomerulopathy, interstitial fibrosis, tubular atrophy and fibrous intimal thickening (cg + ci + ct + cv) of the BANFF scoring. Results: Intrarenal RI-values were significantly higher in patients with allograft rejection than without rejection (median 0,79 vs. 0,73; inter quartile range: 0,20 vs. 0,13; p  = 0,018). The same was found for T-and non-T cell mediated rejection (median 0,78 vs. 0,73; inter quartile range 0,20 vs. 0,13; p  = 0,039). There were no significant differences in the RI-values between the subtypes of T-cell mediated rejection (type IA-IIB). Furthermore, there were no significant differences of RI-values regarding antibody-mediated rejection (present vs. not present) or type of rejection (T-cell- vs. antibody mediated rejection). Patients with rejection and simultaneously chronic allograft injury showed significantly higher RI-values than patients with only chronic allograft injury. Analyses using the IFTA or the ECAI score showed comparable results (IFTA p  = 0,043; Score p  = 0,021). The intrarenal RI-value was neither able to detect chronic allograft injury nor to distinguish between acute tubular necrosis and rejection. The intrarenal RI-value showed a significant correlation with recipient age (p  <  0,001) but not with donor features. Conclusion: In summary, the intrarenal RI-value can indicate a rejection but gives no clear hint to acute tubular necrosis and cannot differentiate from it. Since patients with rejection can have normal RI-values, a biopsy should always be performed in case of suspected rejection. The intrarenal RI-value has no unambiguous validity to determine intrinsic values of the renal allograft, but should rather be understood and interpreted as a systemic parameter influenced by multiple factors. Show more

DOI: 10.3233/CH-189306

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Cheung, A.T.W. | Chen, P.C.Y. | Wong, K.Y. | Banerjee, A. | Tracy, B.D. | To, W.J.

Article Type: Research Article

Abstract: Orthokeratology (Ortho-K) is an over-night hard contact lens therapy, which physically reshapes the corneal curvature in order to stabilize or temporally eliminate myopia in patients. We hypothesize that the prolonged physical contact and mechanical pressure induced by the Ortho-K lenses may create lasting inadvertent effects and damages (microangiopathy), and may bring about unwanted changes in the microvasculature of the bulbar conjunctiva. Computer-assisted intravital microscopy (CAIM) was used to view, document (via videotaping) and objectively quantify (via computer-assisted image analysis) the real-time dynamic and morphometric characteristics of the conjunctival microcirculation in long-term (at least over one year) Ortho-K patients (n  = 11) …and matched non-user control subjects (n  = 8). Ortho-K patients were instructed to wear their lenses overnight following standard protocol. During the study, the conjunctival microcirculation of the left eye of all Ortho-K lens users was viewed, frequently re-focused and videotaped, without and with the lens in place, as outlined in METHODS. The matched control subjects (non-lens wearing) were videotaped and studied in like manner. The dynamic and morphometric characteristics of each user and control subject were analyzed, quantified and summated as a severity index (SI) collectively for comparison. SI of Ortho-K lens users (4.18±1.08) differed significantly from SI of control subjects (1.75±1.39, p ≤0.05). In addition, changes in the conjunctival microcirculation (e.g., flow velocity, vessel diameter, shape change, etc) were viewed and videotaped immediately after the myopic patients put on the Ortho-K lenses. Eight of the 11 Ortho-K lens users displayed significant percentage changes (p ≤0.05) in flow velocity and 10 of 11 displayed significant percentage changes (p ≤0.05) in vessel diameter, without and with the Ortho-K lenses. The results clearly indicated that significant microvascular changes via tissue remodeling occurred, and were caused directly by the physical presence of the Ortho-K lenses. Show more

DOI: 10.3233/CH-189908

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018