Microvascular Tissue Perfusion Research Articles

Intestinal mucosal perfusion and integrity are maintained in hypotensive brain dead mice.

Brain death (BD) leads to complex hemodynamic and inflammatory alterations which may compromise organ perfusion and induce morphologic and functional damage in various organs. The intestine is particularly sensitive to hypoperfusion and donor hypotension usually precludes intestinal donation. Previous studies reported inflammatory intestinal changes following BD but information on mucosal integrity and perfusion are lacking. BD was induced in mice by inflating an epidural balloon catheter. Controls underwent only anesthesia and tracheostomy. Intestinal perfusion was assessed using laser Doppler flowmetry (LDF). Intestinal injury was assessed after 2h of BD by the Chiu-Park score and morphometry. Intestinal tight junction (TJ) proteins (claudin-1, claudin-3, occludin, tricellulin) as well as inflammatory activation (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-6) were also analysed and compared with a sham group. Although blood pressure decreased in BD mice, intestinal perfusion remained similar between BD and sham mice. Histologically, mucosal injury was absent/minimal and TJs appeared well maintained in both groups. BD may trigger intrinsic, autoregulatory mechanisms to preserve microvascular tissue perfusion and mucosal integrity in spite of mild hypotension.

Poster 225: Acetabular Labral Blood Flow Using Laser Doppler Flowmetry Before & After All- Arthroscopic Capsular Autograft Labral Reconstruction

Objectives: All-arthroscopic capsular autograft labral reconstruction has been proposed to repair complex or irreparable tears without the downside of autograft related donor-site morbidity. Cadaveric studies have suggested that the acetabular labrum receives its blood supply from radial branches of the periacetabular periosteal vascular ring that penetrate the hip capsule, with perfusion remaining intact in most hips exhibiting labral tears. Despite this, little is known about the exact course of blood flow to labral tissue or how surgical reconstruction of this region affects microvasculature during hip arthroscopy. The purpose of this study was to examine the effects of all-arthroscopic capsular autograft labral reconstruction on labral blood flow in vivo using laser doppler flowmetry (LDF) to measure microvascular perfusion. Methods: After obtaining institutional review board approval, patients ≥18 years old undergoing arthroscopic repair of the acetabular labrum by a single surgeon were consented between 2018-2022. Labral repair was performed via a previously published capsular autograft labral reconstruction technique. An LDF probe (Moor Instruments) continuously measured microvascular blood flow flux (perfusion units [PU]) within 1mm3 of surrounding labral tissue (Figure 1). LDF measurements were taken medial and lateral to the region of the tear before/after labral reconstruction and before/after labral elevation from the acetabular rim. The mean of flux measurements was expressed as a percent change from each patient’s baseline measurements. The percent change in labral perfusion was analyzed using student t-tests and one-way ANOVA using Tukey’s method for multiple comparisons. Associations between preoperative demographics and labral perfusion were analyzed using multiple regression analyses. Lending from previous literature, flux decreases ≥50% were considered clinically significant. Results: This study included 41 patients [24 males (58.5%) and 17 females (41.5%)] undergoing arthroscopic labral repair with capsular autograft reconstruction with mean [SD] age 31.3 [8.4] years, BMI 24.8 [3.3] kg/m2, lateral center edge angle (LCEA) 35.3 [4.9] degrees, Tönnis angle 5.8 [5.8] degrees, and mean arterial pressure 96.0 [10.9] mmHg. The mean [95% CI] percent change in blood flow following labral elevation was -9.24% [(-0.04) to (-18.1)]. Following labral reconstruction, the mean [95% CI] percent change in blood flow medially was -22.3% [(-11.9) to (-32.7)] and laterally -32.5% [(-23.6) to (-41.5)]. There was no significant difference between the changes in medial versus lateral perfusion (p=0.136) following repair. Unadjusted analyses stratifying for age, BMI, sex, type of impingement, Tönnis/Outerbridge class, amount of capsule used for augmentation, and suture technique revealed that none of these factors were correlated with significant differences in labral perfusion medially or laterally (p>0.05; Table 1). Multiple regression analyses controlling for demographic and intra-operative variables demonstrated that BMI, LCEA, suture technique, age, mean arterial pressure were not significantly associated with changes in medial or lateral labral perfusion (p>0.05; Table 2). Finally, all changes in flux were found to be significantly less than the 50% threshold, when comparing decreases following labral elevation (p<0.001) and labral reconstruction medially (p<0.001) and laterally (p<0.001). Conclusions: While the vascular nature of the acetabular labrum has been described in literature, preservation of labral blood flow following arthroscopic labral repair has not yet been objectively reported. This study found that techniques to preserve native hip anatomy and vascular supply may adequately maintain perfusion to labral tissue and promote healing. While laser doppler flowmetry may be affected by secondary operative factors, careful measures were taken to standardize the in vivo environment during each measurement. Additionally, blood flow measurements are only limited time assessments with no ability to speculate if observed changes are permanent or temporary. Although this study cannot be generalized to all variations of labral repair/reconstruction, these results suggest that surgeons can employ techniques that preserve microvascular tissue perfusion. The use of capsular augmentation enables preservation of the donor-tissue blood supply with local tissue transfer, suggesting that current labral repair techniques can preserve labral perfusion. [Table: see text] [Table: see text]

Magnetic Resonance Imaging Techniques in Peripheral Arterial Disease.

Significance: Peripheral arterial disease (PAD) leads to a significant burden of morbidity and impaired quality of life globally. Diabetes is a significant risk factor accelerating the development of PAD with an associated increase in the risk of chronic wounds, tissue, and limb loss. Various magnetic resonance imaging (MRI) techniques are being increasingly acknowledged as useful methods of accurately assessing PAD. Recent Advances: Conventionally utilized MRI techniques for assessing macrovascular disease have included contrast enhanced magnetic resonance angiography (MRA), noncontrast time of flight MRA, and phase contrast MRI, but have significant limitations. In recent years, novel noncontrast MRI methods assessing skeletal muscle perfusion and metabolism such as arterial spin labeling (ASL), blood-oxygen-level dependent (BOLD) imaging, and chemical exchange saturation transfer (CEST) have emerged. Critical Issues: Conventional non-MRI (such as ankle-brachial index, arterial duplex ultrasonography, and computed tomographic angiography) and MRI based modalities image the macrovasculature. The underlying mechanisms of PAD that result in clinical manifestations are, however, complex, and imaging modalities that can assess the interaction between impaired blood flow, microvascular tissue perfusion, and muscular metabolism are necessary. Future Directions: Further development and clinical validation of noncontrast MRI methods assessing skeletal muscle perfusion and metabolism, such as ASL, BOLD, CEST, intravoxel incoherent motion microperfusion, and techniques that assess plaque composition, are advancing this field. These modalities can provide useful prognostic data and help in reliable surveillance of outcomes after interventions.

Microvascular tissue perfusion after postcatheterization pseudoaneurysm treatment.

Femoral pseudoaneurysm (PSA) is a severe complication after endovascular procedures. Ultrasound-guided manual compression (MC) and percutaneous thrombin injection (TI) are frequently used treatments. MC is less effective, TI may cause thromboembolic events. Up to date, there is no data regarding impairment of microvascular tissue perfusion after PSA treatment. In this single-center, prospective study 22 patients with PSA were included. We compared macro- and microcirculatory perfusion in the treated and untreated leg at baseline before, after and one day after treatment. Leg perfusion was assessed with ultrasound and ankle-brachial index (ABI). Microcirculatory perfusion of the feet was measured with a near-infrared spectroscopy (NIRS) camera generating StO2-tissue-maps. Successful PSA thrombosis was achieved in 16 (100%) patients in TI group and in 4 (66.7%) patients in MC group. There was no evidence of arterial thrombi on ultrasound and the ABI did not differ between groups. NIRS StO2-tissue-maps of the feet showed no significant difference in both groups concerning the treated (p = 0.121) or the untreated (p = 0.198) leg during follow up. In this small exploratory study, there was no evidence of micro- and macrovascular tissue perfusion impairment after treatment of postcatheterization femoral pseudoaneurysm with thrombin injection underscoring the safety of this approach.

Vitamin C improves microvascular reactivity and peripheral tissue perfusion in septic shock patients

BackgroundVitamin C has potential protective effects through antioxidant and anti-inflammatory properties. However, the effect of vitamin C supplementation on microvascular function and peripheral tissue perfusion in human sepsis remains unknown. We aimed to determine vitamin C effect on microvascular endothelial dysfunction and peripheral tissue perfusion in septic shock patients.MethodsPatients with septic shock were prospectively included after initial resuscitation. Bedside peripheral tissue perfusion and skin microvascular reactivity in response to acetylcholine iontophoresis in the forearm area were measured before and 1 h after intravenous vitamin C supplementation (40 mg/kg). Norepinephrine dose was not modified during the studied period.ResultsWe included 30 patients with septic shock. SOFA score was 11 [8–14], SAPS II was 66 [54–79], and in-hospital mortality was 33%. Half of these patients had vitamin C deficiency at inclusion. Vitamin C supplementation strongly improved microvascular reactivity (AUC 2263 [430–4246] vs 5362 [1744–10585] UI, p = 0.0004). In addition, vitamin C supplementation improved mottling score (p = 0.06), finger-tip (p = 0.0003) and knee capillary refill time (3.7 [2.6–5.5] vs 2.9 [1.9–4.7] s, p < 0.0001), as well as and central-to-periphery temperature gradient (6.1 [4.9–7.4] vs 4.6 [3.4–7.0] °C, p < 0.0001). The beneficial effects of vitamin C were observed both in patients with or without vitamin C deficiency.ConclusionIn septic shock patients being resuscitated, vitamin C supplementation improved peripheral tissue perfusion and microvascular reactivity whatever plasma levels of vitamin C.ClinicalTrials.gov Identifier: NCT04778605 registered 26 January 2021.

Evaluation of Tissue Perfusion by Wound Blush and 2D Color-Coded Digital Subtraction Angiography During Endovascular Intervention and Its Impact on Limb Salvage in Critical Limb Ischemia

Purpose: Critical limb ischemia (CLI) is an entity with high mortality if not properly treated. The primary aim of CLI revascularization is to enhance wound healing, which greatly depends on microvascular circulation. The available tools for assessment of revascularization success are deficient in the evaluation of local microvascular tissue perfusion, that wound blush (WB) reflects. A reliable technique that assesses capillary flow to foot lesions is needed. This study aims to assess WB angiographically at sites of interest in the foot after revascularization and its impact on limb salvage in CLI. Materials and Methods: 198 CLI patients (Rutherford category 5/6) with infrainguinal atherosclerotic lesions amenable for endovascular revascularization (EVR) were included. Limbs were directly or indirectly revascularized by EVR. Direct revascularization meant that successful revascularization of the area of interest according to the angiosome concept was achieved. A completion angiographic run was taken to assess WB. Patients were divided into 2 groups; positive and negative WB groups. In the event of a disagreement between the observational investigators, the digital subtraction angiography (DSA) series was analyzed for hemodynamic changes with a computerized 2D color-coded DSA (Syngo iFlow). Results: 176 limbs had successful revascularization in 157 patients. The successful revascularization rate was 88.9% (176/198), with technical failure encountered in 22 limbs. 121 patients had positive WB and 55 patients had negative WB. Direct revascularization of target areas was obtained in 98 limbs (55.7%). There was a significant difference in the rate of achieving direct flow to the lesion between the positive WB and negative WB groups (36.4% vs 19.3%, p≤0.001). We noticed a nonsignificant difference between patients who had direct revascularization of the foot lesion(s) and those who had indirect revascularization as regards limb salvage. Patients were followed up for 25.2 ± 12.7 months. By the end of the first year, limb salvage rate was significantly higher in patients who had positive WB (98% vs 63%, p<0.001, after 2 years (97% vs 58%, p<0.001) and after 3 years (94% vs 51.5%, p<0.001). Conclusions: WB is an important predictor and a prognostic factor for wound healing in CLI patients with soft tissue lesions.

Deterioration of peripheral microvascular tissue perfusion after transcatheter aortic valve implantation (TAVI) measured by 2D near-infrared spectroscopy (NIRS)

Abstract Background The data on the effect of transcatheter aortic valve implantation (TAVI) on peripheral microcirculation is scarce. Therefore, in this study, we investigate the changes of peripheral microvascular tissue perfusion before and after TAVI measured by a 2D near-infrared spectroscopy (NIRS) camera. NIRS allows measurement of hemoglobin oxygen saturation (StO2) in the blood perfusing the volume tissue under scrutiny. Methods In this prospective, single center study, patients with symptomatic, severe aortic stenosis either planned for elective TAVI procedure or elective cardiac catheterization were included. 2-D StO2 maps of all distal extremities (i.e. hand/foot) were acquired before and after TAVI by using a NIRS camera; macrovascular function of the tibial and forearm arteries was assessed by Doppler ultrasound with spectral analysis including ankle-brachial index (ABI) and applanation tonometry. Results 26 subjects (19 male, age 83±6 years) undergoing TAVI procedure and 5 subjects (4 male, age 76±10) undergoing cardiac catheterization were included in this trial. In the group undergoing TAVI procedure, 5 patients had diabetes mellitus (19%), one of whom was insulin-dependent, 3 patients had a history of peripheral artery disease (12%) and 1 patient had a history of smoking (4%). TAVI procedure was successful without major complications in all cases.Mean peripheral StO2 decreased significantly on all extremities after TAVI, i.e. right hand (from 71±14% to 61±16%; p=0.01), left hand (from 70±12 to 62±16%; p=0.03), right foot (from 70±11% to 61±15%; p&amp;lt;0.01) and left foot (from 66±15% to 58±14%; p=0.03). ABI did not change after TAVI (right ABI baseline mean 1.08±0.2; Δ0.06; left ABI baseline 1.05; Δ0.05). Macrovascular function of the forearm and tibial arteries did not deteriorate as measured by Doppler ultrasound. Furthermore, aortic mean pressure (from 108±21 mmHg to 87±13 mmHg; p=0.002) and augmentation index (from 34±8 mmHg to 24±8 mmHg; p&amp;lt;0.001) decreased significantly while subendocardial viability ratio (from 128±22 to 147±7; p&amp;lt;0.001), a marker for coronary microvascular function, improved significantly after TAVI. In the group undergoing cardiac catheterization, there were no statistically significant changes in macro- or microvascular function. Conclusion This is, to our knowledge, the first study investigating the effect of peripheral microvascular tissue perfusion measured by NIRS after TAVI. Our results show that peripheral microvascular tissue perfusion was significantly deteriorated after TAVI procedure. StO2 before and after TAVI procedure Funding Acknowledgement Type of funding source: None

Current Perspectives in Facilitated Angioplasty.

Ischemic heart disease represents the most important cause of mortality worldwide, and the management of patients with ST-elevation myocardial infarction (STEMI) still remains a great challenge. For a great number of patients who do not have immediate access to primary percutaneous coronary intervention (PCI), facilitated angioplasty may be a reasonable therapeutic option. The goal of reperfusion therapy is achieving repermeabilization of the infarct-related artery. However, the restoration of normal epicardial flow is not always followed by microvascular tissue perfusion and the presence of myocardial blush. Early studies assessing the benefits of facilitated angioplasty over primary PCI encountered disappointing results, with an increased number of bleeding complications. The invasive strategy following fibrinolysis mainly consists in angiography and PCI of the infarct-related artery between 2 and 24 hours after successful fibrinolysis or rescue PCI in failed fibrinolysis, hemodynamic, electrical instability, or worsening ischemia. Currently, a strategy of routine early angiography after fibrinolysis is recommended, taking into account studies that have demonstrated a reduced rate of reinfarction and recurrent ischemia, without an increased risk of stroke or major bleeding complications. After evaluating 1892 patients with STEMI within 3 hours after the onset of symptoms and revealing, beyond clear benefit of fibrinolysis, an increased risk of bleeding complications, the STREAM trial was the one that led to halving the tenecteplase dose for patients aged >75 years. A safety profile of adjusted-dose fibrinolytic therapy in elderly patients with STEMI will be further investigated by the ongoing STREAM-2 trial. With the current increased burden of acute coronary syndromes and the lack of immediate primary PCI facilities for all patients with STEMI, facilitated angioplasty seems a feasible therapeutic option. Another benefit of facilitated angioplasty may be represented by a major contribution of thrombolytic therapy in re-establishing microvascular myocardial blood flow.

500.08 Adverse Events and Modes of Failure Associated with the Filterwire EZ Embolic Protection System; The Utility of the FDA MAUDE Database

Embolic protection devices (EPDs) prevent distal embolization of atherothrombotic material during percutaneous interventions resulting in reduced microvascular obstruction, improved microcirculation, and tissue perfusion. The FilterWire EZ Embolic Protection System (Boston Scientific, Natick, MA) is

Interrelations of Hemorheological Parameters and Microcirculation in Subjects with an Increased Blood Pressure

Vascular resistance and blood pressure (BP) have known effects on blood viscosity. Therefore, the purpose of this study was to investigate the interrelation between the set of rheological characteristics and the parameters of microcirculation in patients with moderately increased blood pressure. We measured the hemorheological characteristics, including blood viscosity (BV) at high and low shear rates, plasma viscosity (PV), the viscosity of erythrocyte suspension, hematocrit (Hct), and erythrocyte aggregation and deformability. We also evaluated the efficacy of the transport function of blood. We determined the functional capillary density (FCD) using the method of microscopy and recorded the value of microvascular perfusion in patients with elevated blood pressure (mean blood pressure above 97 mmHg) and a group of subjects with normal blood pressure (control group, mean blood pressure of 87 mmHg) using laser Doppler imaging (LDI). We studied the changes in microrheological characteristics of red blood cells during their incubation in the presence of compounds with vasoactive properties: spermine (a donor of nitric oxide), ADP, and adenosine. Subjects with high blood pressure had a higher BP than the controls. This was due to an increase in PV, Hct, and erythrocyte aggregation with a decrease in their deformability. The ATP content of red blood cells was measured in patients with elevated blood pressure; it was found to be lower by 25% (p < 0.01) than in the control group. It was found that the content of ATP in erythrocytes was significantly negatively correlated with the values of blood pressure (systolic and diastolic blood pressures); the correlation was stronger in patients with a high blood pressure. These findings suggest that the characteristics of the hemorheological profile and the parameters of microcirculation in patients with moderately elevated blood pressure were significantly different from those in subjects with normal blood pressure. This indicates a reduction of the effectiveness of microvascular tissue perfusion.

Hyperspectral imaging for monitoring of perfusion failure upon microvascular anastomosis in the rat hind limb

Background/purposeObjective, reliable and easy monitoring of microvascular tissue perfusion is a goal that was achieved for many years with limited success. Therefore, a new non-invasive hyperspectral camera system (TIVITA™) was tested for this purpose in an in vivo animal model. MethodsEvaluation of tissue oxygenation during ischemia and upon reperfusion was performed in left hind limb in a rat model (n=20). Ischemia was induced by clamping and dissection of the superficial femoral artery. Reperfusion of the limb was achieved by microsurgical anastomosis of the dissected artery. Oxygenation parameters of the hind limb were assessed via TIVITA™ before and immediately after clamping and dissection of the artery, 3 and 30min after reperfusion as well as on postoperative days 1 and 2. Thereby, the non-operated hind limb served as control. As clinical parameters, the refill of the anastomosis as well as the progress of the affected leg were assessed. ResultsIn 12 from 20 cases, TIVITA™ recorded a sufficient reperfusion with oxygenation parameters comparable to baseline or control condition. However, in 8 from 20 cases oxygenation was found impaired after reperfusion causing a re-assessment of the microvascular anastomosis. Thereby, technical problems like stenosis or local thrombosis were found in all cases and were surgically treated leading to an increased tissue oxygenation. ConclusionsThe TIVITA™ camera system is a valid non-invasive tool to assess tissue perfusion after microvascular anastomosis. As it safely shows problems in oxygenation, it allows the clinician a determined revision of the site in time in order to prevent prolonged ischemia.

Autodigestion by migrated trypsin is a major factor in small intestinal ischemia-reperfusion injury

BackgroundThe pathophysiological role of pancreatic digestive hydrolases in intestinal ischemia-reperfusion (I/R) injury is still not clear. Here, we studied whether ischemia-induced injury to the small intestine can be explained by the autodigestion hypothesis. Materials and methodsMesenteric I/R was induced in rats by superior mesenteric artery occlusion (90 min) and reopening (120 min). Thirty minutes before superior mesenteric artery occlusion, aprotinin (14.7 mg/kg), orlistat (5 mg/kg), and their combination or α1-proteinase inhibitor (60 mg/kg) were injected into the lumen of the small intestine. Systemic and vital parameters, intestinal microcirculation, and mucosal barrier function were monitored during the observation phase; markers of small intestinal injury, as well as trypsin-, chymotrypsin-, elastase-, and lipase-like activities in intestinal effluates were assessed at the end. ResultsThe pattern of small intestinal injury correlated inversely with the local alterations in microvascular tissue perfusion and corresponded with the intestinal distribution of trypsin-like activity. Aprotinin almost completely inhibited trypsin-like activity (P < 0.05) and significantly reduced intestinal tissue injury. Combined with orlistat, it also increased the postischemic blood pressure (P < 0.05) but not the intestinal barrier function. Macroscopic as well as the histologic alterations were decreased by α1-proteinase inhibitor, which significantly improved postischemic blood pressure (P < 0.05). ConclusionsThe I/R-induced pattern of small intestinal injury is likely to result from both local differences in tissue ischemia and the digestive activity of migrated pancreatic trypsin. Therefore, administration of aprotinin and orlistat into ischemic small intestines may be a therapeutic option in patients with a poor diagnosis.

Microcirculation and Hemorheology: points of interaction

Transport of respiratory gases and the entire spectrum of substances for the metabolism of cells is carried out by coordinated work of circulation and blood. The review considers the main theoretical and experimental studies on microcirculation and hemorheology with an emphasis on the mechanisms of their interrelation and on the influence of individual hemorheological characteristics on the regulation of microvascular tissue perfusion. The analysis of the leading microrheological characteristics of erythrocytes - deformability is performed, the signal molecular mechanisms associated with the change of this cell parameter are shown. Data on the role of erythrocytes in the regulation of arteriolar tonus and functional density of capillaries are given. The mechanism of this regulation by exocytosis with erythrocytes adenosine triphosphate (ATP) and its stimulation of nitric oxide synthesis by endothelial cells is discussed. The review performed a comprehensive analysis of the participation of major hemorheological characteristics in the regulation of microvascular perfusion, including the role of the optimal viscosity of whole blood and the viscosity of plasma for effective tissue perfusion and oxygenation.

131-02: Laser Doppler Perfusion Monitoring reliably detects acute haemodynamic changes associated with VF

Purpose: The incidence of inappropriate shocks would be expected to be reduced if ICD's had a reliable method for assessing hemodynamic status. Laser Doppler Perfusion Monitoring (LDPM) measures microvascular tissue perfusion. In this study we aim to assess whether LDPM reliably detects hemodynamic changes associated with VF. Methods: 18 consecutive patients referred for ICD implantation were recruited. During VF induction continuous non-invasive: beat-by-beat blood pressure, Doppler blood flow to the brain and non- invasive laser Doppler signals (with probes positioned on the chest and finger) were recorded. Summary of Results: During VF the laser Doppler signals were markedly reduced, the timing of the changes in signal matched those observed in blood pressure and transcranial Doppler flow. In order to minimize the effect of noise we calculated the oscillatory power of the LDPM signal. In all patients during VF the signal always fell to a value less than 2% of the absolute value. We did not observe values below 2% in any of the baseline recordings made during sinus rhythm.

When is contrast-enhanced sonography preferable over conventional ultrasound combined with Doppler imaging in renal transplantation?

Conventional ultrasound in combination with colour Doppler imaging is still the standard diagnostic procedure for patients after renal transplantation. However, while conventional ultrasound in combination with Doppler imaging can diagnose renal artery stenosis and vein thrombosis, it is not possible to display subtle microvascular tissue perfusion, which is crucial for the evaluation of acute and chronic allograft dysfunctions. In contrast, real-time contrast-enhanced sonography (CES) uses gas-filled microbubbles not only to visualize but also to quantify renal blood flow and perfusion even in the small renal arterioles and capillaries. It is an easy to perform and non-invasive imaging technique that augments diagnostic capabilities in patients after renal transplantation. Specifically in the postoperative setting, CES has been shown to be superior to conventional ultrasound in combination with Doppler imaging in uncovering even subtle microvascular disturbances in the allograft perfusion. In addition, quantitative perfusion parameters derived from CES show predictive capability regarding long-term kidney function.

Contrast-Enhanced Ultrasound Detects Differences in Microvascular Blood Flow in Adults with Sickle Cell Disease Administered Regadenoson

Background: Outcome measures for therapeutic studies in patients with sickle cell disease (SCD) are poor.Abnormal microvascular blood flow (MBF), the basis for tissue ischemia and injury associated with vaso-occlusion, would be an optimal outcome measure for SCD studies. Ideally, a modality to measure blood flow in SCD would non-invasively quantify microvascular tissue perfusion rather than assess conduit arterial flow through large vessels. Limitations of existing techniques to measure blood flow prevent their widespread use in clinical trials of patients with SCD. Contrast-enhanced ultrasound (CEU) is a non-invasive and portable technique that uses standard ultrasound equipment to measure microvascular perfusion and functional capillary patency. The primary objective of this study was to determine whether CEU is able to detect differences in the MBF of skeletal muscle: 1) before and after infusion with the adenosine A2A receptor (A2AR) agonist regadenoson, and 2) between steady state and vaso-occlusive crisis (VOC).Methods: CEU measurements were obtained in forearm skeletal muscle in adult HbSS patients. Two measures are used to calculate MBF: 1) velocity of RBCs through capillaries and 2) volume of blood perfused in an area of tissue. MBF is the product of RBC velocity and volume of blood. In one study cohort, MBF was measured in steady-state patients during a 24-hour infusion of regadenoson (1.44 µg/kg/hour). CEU perfusion imaging was obtained at baseline, 6 and 24 hours after initiation of regadenoson. In the second study cohort, CEU measurements were obtained within the same patient during a hospital admission for VOC and at steady state. MBF was expressed in terms of a ratio to baseline flow (pre-regadenoson) in cohort 1 and as a ratio of VOC to steady-state flow for cohort 2.Results: CEU measurements were obtained in13 patients administered regadenoson, and 7 patients at steady state and during VOC. Median age (range) of all patients studied was 24 years (20-45) and 55% were female. During regadenoson infusion, there was a median increase in skeletal muscle MBF of 29% at 6 hours (ratio 1.29, IQR 0.81) and 9% at 24 hours (ratio 1.09, IQR 1.40). Increase in MBF during regadenoson administration was largely due to higher RBC velocity (6 hours ratio: 1.24, IQR 0.88; 24 hours: ratio 1.12 IQR 0.85). There was a median decrease of 40% in skeletal muscle blood flow during VOC compared to steady state (ratio 0.60, IQR 0.27). Similarly, a decrease in RBC velocity accounted for most of the reduction in MBF in VOC compared to steady state (ratio 0.63, IQR 0.35).Conclusion: CEU measures of skeletal muscle MBF increased during a 24-hour infusion of regadenoson and decreased in VOC compared to steady state. Changes in RBC velocity, as opposed to the volume of blood perfused, accounted for most of the differences in MBF seen during regadenoson infusion and VOC. Alterations in rheology or vascular tone could explain these changes. These data provide additional evidence for the A2AR agonist regadenoson as a therapeutic modality for patients with SCD and suggest that CEU is a valid measure of blood flow in VOC. Taken together, the findings of this preliminary study demonstrate that CEU, a non-invasive, portable technique to measure MBF, could be used as an objective outcome measure for therapeutic studies in SCD. DisclosuresField:NKTT: Consultancy, Research Funding. Off Label Use: IND for regadenoson for treatment of VOC in sickle cell disease.

Contrast-Enhanced Ultrasonography in the Early Period After Kidney Transplantation Predicts Long-Term Allograft Function

IntroductionReal-time contrast-enhanced sonography (CES) can assess microvascular tissue perfusion using gas-filled microbubbles. The purpose of the study was to evaluate the feasibility of early CES in predicting long-term kidney allograft function in comparison to color Doppler ultrasonography (CDUS). MethodsWe prospectively studied 68 consecutive kidney transplant recipients using CES and conventional CDUS investigation 1 week after transplantation. Transplant tissue perfusion imaging was performed by low-power imaging during intravenous administration of the sonocontrast SonoVue. Renal tissue perfusion was assessed quantitatively using flash replenishment kinetics of microbubbles to estimate renal blood flow (RBF). The obtained sonography values were correlated with clinical data 1 week up to 1 year after transplantation. ResultsIn contrast with conventional CDUS resistive indices, RBF estimated by CES 1 week posttransplantation significantly correlated with kidney function after 1 year (r = 0.67; P < .001). Determination of RBF by CES revealed a significant correlation with donor age but not recipient age, whereas conventional CDUS resistive index was significantly correlated to recipient age (r = 0.54; P < .001) but not donor age. Furthermore RBF was associated with vascular fibrosis and intimal thickening of the engraftment biopsies. ConclusionThis is the first prospective study demonstrating the prognostic value of CES early after kidney transplantation. In contrast with CDUS, CES reveals information about kidney allograft perfusion independent of recipient vascular compliance.

Erratum to: Impact of rapid ventricular pacing during TAVI on microvascular tissue perfusion

Patient characteristics Age (years ± SD) 81.21 ± 8.44 Male, n (%) 18/26 AVA (cm ± SD) 0.64 ± 0.17 cm Vmax (m/s ± SD) 4.58 ± 0.66 m/s Mean pressure gradient (mmHg ± SD) 48.79 ± 16.73 mmHg Ejection fraction (EF ± SD) 55.93 ± 15.89 % log EuroScore 28.89 ± 14.07 Comorbidities Arterial hypertension n (%) 42 (100) CAD n (%) 32 (76.2) Diabetes mellitus n (%) 19 (45.2) Atrial fibrillation n (%) 11 (26.2) Renal insufficiency n (%) 10 (23.8) Peripheral vascular disease n (%) 9 (21.4) Previous myocardial infarction n (%) 7 (16.67) Pulmonary hypertension n (%) 5 (11.9) Previous stroke n (%) 3 (7.14)

Impact of rapid ventricular pacing during TAVI on microvascular tissue perfusion

Rapid ventricular pacing (RVP) is an established technique to temporarily reduce left ventricular output during transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the impact of RVP on microvascular tissue perfusion (MTP) in patients undergoing TAVI. We studied 42 patients (mean age 81.8±6.9years, n=18 females. EuroSCORE 33±12%) during TAVI. MTP was analyzed using Sidestream-Darkfield imaging, of the sublingual microvasculature. Microvascular flow index (MFI) was continuously measured in small (10-25μm)- and medium (26-50μm)-sized vessels, starting 10s before and ending 12s after RVP. Further, perfused capillary density, total vessel density and the proportion of perfused vessels were assessed. After a mean RVP duration of 14.3s (range 6-29), mean arterial pressure decreased from 68±05 to 40±7mmHg (p<0.001). This was associated with a significant decrease of MFI in small- and medium-sized vessels from 2.29±0.64 and 2.36±0.6 to 0.87±0.66 (p<0.001) and 1.0±0.83 (p<0.001), respectively. MFI remained significantly below baseline values (small: 1.75±0.8, p=0.001 vs. baseline; medium: 1.77±0.85; p=0.005 vs. baseline) at 12s after end of RVP. The study demonstrates a time-dependent effect of RVP on microflow, leading to 50 and 25% of baseline at 8 and 18s of RVP, respectively. In a substantial proportion of patients, RVP is associated with microcirculatory arrest and a delayed recovery of microflow. Although the impact of these findings on outcome is yet unclear, TAVI operators should be aware of the potentially adverse effects of even short periods of RVP.

Acute Effects of Calcineurin Inhibitors on Kidney Allograft Microperfusion Visualized by Contrast-Enhanced Sonography

Calcineurin inhibitors induce detrimental vascular remodeling, which may be one cause of chronic allograft failure. Real-time contrast-enhanced sonography (CES) is a relatively new technique in providing quantitative information on microvascular tissue perfusion in kidney allografts in more detail. The purpose of the study was to explore whether acute changes of kidney allograft microperfusion due to the administration of cyclosporine A (CsA) and tacrolimus (Tac) can be evidenced using real-time CES. In an explorative single-center clinical trial, renal parenchymal tissue perfusion of 32 stable kidney allograft recipients was evaluated with CES before and 2 hr after the intake of CsA or Tac. In addition to laboratory and clinical parameters, Doppler indices and estimated glomerular filtration rate were measured. Although systolic and diastolic blood pressure and color Doppler indices did not significantly differ, there was a significant decrease of renal blood flow 2 hr after the intake of CsA compared with baseline (4.78±2.31 dB/s, 49%, respectively). In contrast, kidney allograft microperfusion was neither significantly reduced in patients receiving CsA paralleled by calcium channel blockers nor significantly reduced in patients receiving Tac. Furthermore, there was a significant correlation between renal blood flow obtained before drug administration and kidney function. CES revealed a 49% reduction of kidney allograft microperfusion 2 hr after the intake of CsA, which might be abrogated by calcium channel blockers. In comparison to CsA, Tac did not result in a significant decrease of kidney blood flow.