Changes In Microvascular Perfusion Research Articles

Rethinking Tako-tsubo Cardiomyopathy: The Contribution of Myocardial Pathology and Molecular Imaging.

Despite substantial research, the mechanisms behind stress Tako-tsubo cardiomyopathy (TTC) remain rather elusive. The purpose of this paper was to provide a detailed review of the mainstream factors underlying the pathophysiology of TTC, highlighting the novel contributions of molecular pathology and in-vivo molecular imaging. A careful literature review selected all papers discussing TTC, specifically those providing novel insights from myocardial pathology and cardiac molecular imaging. Results concerning myocardial pathology, defect extension, sites and relationships between functional parameters underline the existence of a causal relationship between a determinant (e.g., the release of catecholamines induced by stress) and an outcome for TTC, which is not limited to a reversible contractile cardiomyopathy, but it includes reversible changes in myocardial perfusion and a long-lasting residual deficit in sympathetic function. Besides, they reinforce the hypothesis that sympathetic nerves may exert a complex control on cardiac contractile function, which is likely to be direct or indirect through metabolism and microvascular perfusion changes during anaerobic and aerobic conditions. TTC is characterized by acute transient left ventricular systolic dysfunction, which can be challenging to distinguish from myocardial infarction at presentation. Catecholamineinduced myocardial injury is the most established theory, but other factors, including myocardial metabolism and perfusion, should be considered of utmost importance. Each effort to clarify the numerous pathways and emerging abnormalities may provide novel approaches to treat the acute episode, avoid recurrences, and prevent major adverse cardiovascular events.

BIO2: Microcirculation Perfusion is Impaired up to 24 Hours after Veno-arterial Extracorporeal Circulation.

Extracorporeal circulation (ECC) procedures, such as extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass (CPB), are used to replace the function of the heart and lung, but they induce complications in the form of acute kidney failure, bleeding, heart arrhythmias or thromboembolic complications. This study aimed to quantify the changes in microvascular perfusion and oxygenation that occur after veno-arterial ECC (VA-ECC). Male Golden Syrian hamsters were instrumented with a dorsal window chamber to study their microcirculation and an exteriorized carotid artery catheter for blood pressure and blood gas measurements. After baseline (BL) measurements were taken, the hamster underwent surgery under isoflurane to insert a drainage catheter into the jugular vein. A heparin bolus (0.05 IU/g) was then provided, and the animal was connected to the VA-ECC circuit, which consists of a peristaltic pump and bubble trap. The VA-ECC circuit was primed with either lactated ringers (LR) or 5% human serum albumin in saline (HSA). Blood flow was ramped up over 15 minutes, maintained at 15% of the animal’s cardiac output for 60 minutes, then ramped down over 15 minutes. Sham animals underwent cannulation surgery and heparinization but were not connected to the VA-ECC circuit. The animals were surgically closed, placed on a heating pad, and allowed at least 30 minutes to wake up from the anesthetic plane before taking measurements at 1, 2, and 24 hours after VA-ECC. Results show that flow in arterioles and venules (Figure 1) at all post-ECC timepoints statistically decreased in LR and HSA groups compared to Sham. LR and HSA failed to recover flow in arterioles and venules back to BL levels post-ECC. Interestingly, venule perfusion statistically increased at 1 and 2 hrs in the HSA group compared to the LR group. Functional capillary density (FCD, Figure 2) showed a statistical reduction in capillary perfusion for both ECC groups, with the HSA group maintaining higher levels compared to the LR group. Microvascular hemoglobin (Hb) oxygen (O2) saturation (Figure 3), in venules was statistically reduced post-ECC for both LR and HSA compared to Sham and BL. The microvascular perfusion results, combined with the consistent drop in hematocrit (Hct) post-ECC suggest an imbalance in oncotic pressure that slowly rectifies after ECC. Via Starling’s law of filtration, the priming volume dilutes protein content within the blood, causing the intravascular oncotic pressure to drop, resulting in ultrafiltration at the capillary level. Additionally, the drop in venule Hb O2 saturation and the reduced microvascular perfusion suggest a reduced O2 delivery and potentially a repayment of an O2 debt post-ECC. This study shows that microvascular sequelae could potentially cause ischemic injury in ECC procedures, which can lead to organ damage and inflammation.Figure 1. Microcirculatory hemodynamics. Diameter, velocity, and volumetric blood flow are shown from top to bottom, while arterioles (Sham: n = 38, LR: n = 33; HSA: n = 33) and venules (Sham: n = 38, LR: n = 30, HSA: n = 33) are shown from the left to right columns. All values are normalized to baseline (BL, before ECC) measurements for each vessel. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 between groups at each timepoint. † P<0.05 compared to BL, within each group.Figure 2. Functional capillary density (FCD). * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 between groups. † P<0.05 compared to baseline (BL). N = 6 for all groups.Figure 3. Microvascular Hemoglobin Oxygen Saturation Changes. The top row shows arterioles (Sham: n = 19, LR: n = 13, HSA: n = 16), while the bottom row shows venules (Sham: n = 21, LR: n = 19, HSA: n = 22). * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 between groups. † P<0.05 compared to baseline (BL).

Changes in microvascular perfusion of heart and skeletal muscle in sheep around the time of birth.

What is the central question of this study? How does the microvascular perfusion of striated muscle change during the dynamic developmental period between the late gestation fetus and early neonate? What is the main finding and its importance? In both myocardium and skeletal muscle, perfusion of striated muscle is significantly reduced in the neonate compared to the late term fetus, but flow reserve is unchanged. The results suggest striated muscle capillary networks grow more slowly relative to the myofibres they nourish during the perinatal period. Microvascular perfusion of striated muscle is an important determinant of health throughout life. Birth is a transition with profound effects on the growth and function of striated muscle, but the regulation of microvascular perfusion around this transition is poorly understood. We used contrast-enhanced ultrasound perfusion imaging (CEUS) to study the perfusion of left ventricular myocardium and hindlimb biceps femoris, which are populations of muscle with different degrees of change in pre- to postnatal workloads and different capacities for postnatal proliferative growth. We studied separate groups of lambs in late gestation (135days' gestational age; 92% of term) and shortly after birth (5days' postnatal age). We used CEUS to quantify baseline perfusion, perfusion during hyperaemia induced by adenosine infusion (myocardium) or electrically stimulated unloaded exercise (skeletal muscle), flow reserve and oxygen delivery. We found heart-to-body weight ratio was greater in neonates than fetuses. Microvascular volume and overall perfusion were lower in neonates than fetuses in both muscle groups at baseline and with hyperaemia. Flux rate differed with muscle group, with myocardial flux being faster in neonates than fetuses, but skeletal muscle flux being slower. Oxygen delivery to skeletal muscle at baseline was lower in neonates than fetuses, but was not significantly different in myocardium. Flow reserve was not different between ages. Given the significant somatic growth, and the transition from hyperplastic to hypertrophic myocyte growth occurring in the perinatal period, we postulate that the primary driver of lower neonatal striated muscle perfusion is faster growth of myofibres than their associated capillary networks.

Assessment of Renal Transplant Perfusion by Contrast-Enhanced Ultrasound after Switch from Calcineurin Inhibitor to Belatacept: A Pilot Study.

Calcineurin inhibitors (CNIs) have improved short-term kidney allograft survival but are nephrotoxic and vasoconstrictive. Vasoconstriction is potentially reversible after switching from CNIs to belatacept. The kidney allograft shows optimal requirements for dynamic perfusion imaging using contrast-enhanced ultrasound (CEUS). We performed standardized CEUS in patients after switching from CNIs to belatacept for clinical indication to study the suitability of CEUS, in order to assess the effects of CNI cessation on kidney allograft perfusion. Eleven kidney transplant patients were enrolled from February 2020 until November 2020. Demographic, clinical, and laboratory parameters, as well as perfusion imaging, were assessed at baseline and 6 months after switching immunosuppression. Quantification of perfusion imaging on CEUS was performed using a post-processing software tool on uncompressed DICOM cine loops. After CNI cessation, estimated glomerular filtration rate increased by 4.8 mL/min/1.73 m2 (16%). Despite good quality of fit and comparable regions of interest in baseline and follow-up CEUS examinations, quantification of perfusion imaging showed a slightly improved cortical perfusion without reaching statistical significance after CNI cessation. This is the first study that systematically investigates the suitability of CEUS to detect changes of microvascular perfusion in kidney transplant recipients in vivo. No significant differences could be detected in perfusion measurements before and after CNI cessation.

Application of contrast-enhanced ultrasound in minimally invasive ablation of benign thyroid nodules

ObjectiveThis study aimed to investigate the application value of contrast-enhanced ultrasound (CEUS) before and after minimally invasive ablation procedures for benign thyroid nodule(s) (BTN). MethodsThis prospective study included patients with BTNs scheduled to undergo ultrasound-guided minimally invasive ablation treatment. CEUS was performed before and after ablation (at 1 day, and 1, 6, and 12 months after ablation). Changes in microvascular perfusion and the volume of BTNs were noted and assessed. ResultsSixty-two patients (62 BTNs), who underwent ablation procedures between June 2016 and August 2020, were included. All lesions were confirmed by biopsy, and histopathological results were obtained before ablation treatment. On preoperative CEUS, the lesions exhibited hyperenhancement (53.23%) or iso-enhancement (46.77%) during the arterial phase, and all lesions exhibited iso-enhancement in the venous and late phases. One day after ablation, none of the BTNs exhibited obvious enhancement on CEUS. One (1.61%) lesion was re-treated due to a nodule-like enhancement area detected by CEUS at the 6-month follow-up. The mean nodular volume reduction rate (VRR) at 1, 6, and 12 months follow-up demonstrated no significant difference between the two ablation groups (microwave ablation versus radiofrequency ablation). Twelve months after ablation, the mean (±SD) VRR of all BTNs was 60.3 ​± ​10.3%. ConclusionCEUS helped guide treatment decisions for BTNs before ablation treatment. Moreover, it could also be used to accurately and noninvasively evaluate treatment efficacy.

Transpelvic Magnetic Stimulation Enhances Penile Microvascular Perfusion in a Rat Model: A Novel Interventional Strategy to Prevent Penile Fibrosis after Cavernosal Nerve Injury.

PurposePenile microvascular dysfunction is a known contributor to erectile dysfunction (ED) and penile fibrosis has been shown to impair microvascular perfusion (MVP). Our objectives were to: (i) determine beneficial effects of TPMS to modulate penile MVP, (ii) determine its mechanism, (iii) evaluate impact of cavernosal nerve injury (CNI) on penile MVP, and (iv) determine time-course of cavernosal tissue elastin changes after CNI in rats.Materials and MethodsAdult male rats (n=5) were anesthetized and subjected to TPMS (13%, 15%, and 17%) and MVP changes were recorded using laser speckle contrast imaging (LSCI). Another group of male rats were subjected to either bilateral cavernosal nerve injury (CNI; n=7) or sham surgery (n=7). After recovery, animals were monitored for MVP using LSCI before and after TPMS. Rat penile tissues were harvested and analyzed for fibrosis using a marker for elastin.ResultsRat TPMS resulted in a stimulus dependent increase in MVP; maximal perfusion was observed at 17%. L-N(G)-Nitroarginine methyl ester (L-NAME) resulted in a marked decrease in TPMS induced MVP increase (393.33 AU vs. 210.67 AU). CNI resulted in 40% to 50% decrease in MVP. CNI produced a remarkable increase in elastin deposits that are noticeable throughout the cavernosal tissues post injury.ConclusionsTPMS is a novel and non-invasive intervention to improve penile MVP after CNI. Potential application includes treatment of ED and sexual function preservation following cancer treatment, possibly through improved penile hemodynamics that might help prevent penile hypoxia and fibrosis.

Evaluation of Retinal Microvascular Perfusion Changes in Patients with Celiac Disease

ABSTRACT Purpose We aimed to determine whether there are retinal microvascular changes in patients with celiac disease (CD). Methods A total of 30 patients with CD (group 1) and 30 healthy controls (group 2) were included in this study. AngioVue optical coherence tomography angiography (OCTA) device was used to evaluate the retinal microvascular structure. Results Some of the values of both optic nerve head (ONH) vessel density (VD) and radial peripapillary capillary VDs were found to be significantly lower in group 1 than in group 2. These 2 groups were similar except for one of the parameters of superficial capillary plexus VD (SCP-VD), whereas it was found that deep capillary plexus VD (DCP-VD) was lower in group 1 than in group 2 except for the foveal area. Conclusion It was determined that some VDs obtained from the ONH and DCP-VD obtained from most areas of the macular region were significantly lower.

The Clinical Value of Extracorporeal Shock Wave Therapy Evaluated by Contrast-Enhanced Ultrasound for Noninfectious Nonunion

Objectives: The aim of this study was to investigate the clinical value of Contrast-enhanced ultrasound (CEUS) in evaluating Extracorporeal shock wave therapy (ESWT) for noninfectious nonunion.Methods: Thirty-eight patients with long bone nonunion fractures whose were treated in our hospital from October 2016 to October 2019 were included (20 males and 18 females). The patients received ESWT once a week for 12 consecutive weeks. CEUS was performed before and after the first ESWT session. According to the ratio of the perfusion area to the callus area, neovascular blood flow observed in CEUS was divided into 4 grades: grade 0 = 0%, grade 1 = 0–30%, grade 2 = 30–70% and grade 3 = 70–100%. The peak values of microbubbles perfusion in the callus area were recorded before and after ESWT. Each patient was followed up for 12 months to record the healing time. Nonunion over 12 months was considered a nonhealing fracture. To compare the ultrasonic data before and after ESWT, pairedTtest was used and the correlation between the ultrasonic data and the nonunion healing time, the pearson analysis was used.Results: Of the 38 patients, 35 patients achieved nonunion healing. The healing time ranged from 5 months to 12 months. Among the 38 patients, 24 patients had a microvascular health score of 0 points and 14 patients had a score of 1 point before treatment. After therapy, the neovascular health score was 0, 1, 2 and 3 in 5, 10, 15 and 8 patients, respectively. There was a statistically significant difference before and after treatment (P&lt; 0.05). The peak value of microbubbles perfusion in the fracture site after ESWT was significantly higher than that before ESWT (P&lt; 0.05). The greater of difference, the shorter of healing time.Conclusion: Under the supervision of CEUS, the changes in microvascular perfusion of noninfectious nonunion patients before and after ESWT effectively reflected the therapeutic effect. CEUS could predict the ESWT on bone nonunion at an early stage.Level of evidence: Level III.

Heterogeneity of Tau Deposition and Microvascular Involvement in MCI and AD.

BackgroundReduced cerebrovascular function and accumulation of tau pathology are key components of cognitive decline in Alzheimer’s disease (AD). Recent multimodal neuroimaging studies show a correlation between cortical tau accumulation and reduced cerebral perfusion. However, animal models predict that tau exerts capillary-level changes that may not be fully captured by standard imaging protocols.ObjectiveUsing newly-developed magnetic resonance imaging (MRI) technology to measure capillary-specific perfusion parameters, we examined a series of mild cognitive impairment (MCI) and AD patients with tau positron emission tomography (PET) to observe whole-brain capillary perfusion alterations and their association with tau deposition.MethodsSeven subjects with MCI or AD received Flortaucipir PET to measure tau deposition and spin-echo dynamic susceptibility contrast (SE-DSC) MRI to measure microvascular perfusion (<10μm radius vessels). Gradient-echo (GE) DSC and pseudocontinuous arterial spin labeling (PCASL) MRI were also acquired to assess macrovascular perfusion. Tau PET, microvascular perfusion, and cortical thickness maps were visually inspected in volumetric slices and on cortical surface projections.ResultsHigh tau PET signal was generally observed in the lateral temporal and parietal cortices, with uptake in the occipital cortex in one subject. Global blood flow measured by PCASL was reduced with increasing tau burden, which was consistent with previous studies. Tau accumulation was spatially associated with variable patterns of microvascular cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in the cortex and with increased capillary transit heterogeneity (CTH) in adjacent periventricular white matter, independent of amyloid-β status.ConclusionAlthough macrovascular perfusion generally correlated with tau deposition at the whole-cortex level, regional changes in microvascular perfusion were not uniformly associated with either tau pathology or cortical atrophy. This work highlights the heterogeneity of AD-related brain changes and the challenges of implementing therapeutic interventions to improve cerebrovascular function.

Early evaluation of treatment response to transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The role of dynamic three-dimensional contrast-enhanced ultrasound.

Dynamic three-dimensional contrast-enhanced ultrasound (3D-CEUS) with quantitative analysis is available in recent years. It can reduce the quantitative sampling error caused by the inconsistency of different sections in order to evaluate local treatment response of hepatocellular carcinoma (HCC) accurately. To investigate the value of dynamic 3D-CEUS in evaluating the early response to transarterial chemoembolization (TACE) treatment in patients with advanced HCC lesions. In this prospective study, both two-dimensional (2D) CEUS and dynamic 3D-CEUS were performed on 40 HCC patients who scheduled for TACE at baseline (T0) and 1-3 days (T1) after treatment. Tumor microvascular perfusion changes were assessed by CEUS time-intensity curve (TIC) and quantitative parameters. According to contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging 1 month after treatment results, patients were divided into responders and non-responders groups. The changes of perfusion parameters of both 2D-CEUS and 3D-CEUS were compared between responders and non-responders groups before and after TACE treatment. Before and after TACE treatment, no significant difference in maximum diameter of HCC lesions between the two groups could be found. There were more significant differences and ratios of perfusion parameters in 3D-CEUS quantitative analysis than in 2D-CEUS. The mutual significant differences and ratios of 2D-CEUS and 3D-CEUS included peak intensity (PI) difference, PI ratio, ratio of area under the curve (A), ratio of area under the wash-out part (AWO) and slope (S) difference. The former 4 corresponding parameters were better on 3D-CEUS than on 2D-CEUS. Dynamic 3D-CEUS can be used as a potential imaging method to evaluate early treatment response to TACE in advanced HCC patients.

Changes in the sublingual microcirculation following aortic surgery under balanced or total intravenous anaesthesia: a prospective observational study

BackgroundIn vascular surgery with aortic cross-clamping, ischemia/reperfusion injury induces systemic haemodynamic and microcirculatory disturbances. Different anaesthetic regimens may have a varying impact on tissue perfusion. The aim of this study was to explore changes in microvascular perfusion in patients undergoing elective open abdominal aortic aneurysm repair under balanced or total intravenous anaesthesia.MethodsProspective observational study. Patients undergoing elective open infrarenal abdominal aortic aneurysm repair received balanced (desflurane + remifentanil, n = 20) or total intravenous anaesthesia (TIVA, propofol + remifentanil using target-controlled infusion, n = 20) according to the clinician’s decision. A goal-directed haemodynamic management was applied in all patients. Measurements were obtained before anaesthesia induction (baseline) and at end-surgery and included haemodynamics, arterial/venous blood gases, sublingual microvascular flow and density (incident dark field illumination imaging), peripheral muscle tissue oxygenation and microcirculatory reactivity (thenar near infrared spectroscopy with a vascular occlusion test).ResultsThe two groups did not differ for baseline characteristics, mean aortic-clamping time and requirement of vasoactive agents during surgery. Changes in mean arterial pressure, systemic vascular resistance index, haemoglobin and blood lactate levels were similar between the two groups, while the cardiac index increased at end-surgery in patients undergoing balanced anaesthesia. The sublingual microcirculation was globally unaltered in the TIVA group at end-surgery, while patients undergoing balanced anaesthesia showed an increase in the total and perfused small vessel densities (from 16.6 ± 4.2 to 19.1 ± 5.4 mm/mm2, p < 0.05). Changes in microvascular density were negatively correlated with changes in the systemic vascular resistance index. The area of reactive hyperaemia during the VOT increased in the balanced anaesthesia group (from 14.8 ± 8.1 to 25.6 ± 14.8%*min, p < 0.05). At end-surgery, the tissue haemoglobin index in the TIVA group was lower than that in the balanced anaesthesia group.ConclusionsIn patients undergoing elective open abdominal aortic aneurysm repair with a goal-directed hemodynamic management, indices of sublingual or peripheral microvascular perfusion/oxygenation were globally preserved with both balanced anaesthesia and TIVA. Patients undergoing balanced anaesthesia showed microvascular recruitment at end-surgery.Trial registrationNCT03510793, https://www.clinicaltrials.gov, date of registration April 27th 2018, retrospectively registered.

Automated quantification of microvascular perfusion.

Changes in microvascular perfusion have been reported in many diseases, yet the functional significance of altered perfusion is often difficult to determine. This is partly because commonly used techniques for perfusion measurement often rely on either indirect or by-hand approaches. We developed and validated a fully automated software technique to measure microvascular perfusion in videos acquired by fluorescence microscopy in the mouse gastrocnemius. Acute perfusion responses were recorded following intravenous injections with phenylephrine, SNP, or saline. Software-measured capillary flow velocity closely correlated with by-hand measured flow velocity (R2 =0.91, P<0.0001). Software estimates of capillary hematocrit also generally agreed with by-hand measurements (R2 =0.64, P<0.0001). Detection limits range from 0 to 2000μm/s, as compared to an average flow velocity of 326±102μm/s (mean±SD) at rest. SNP injection transiently increased capillary flow velocity and hematocrit and made capillary perfusion more steady and homogenous. Phenylephrine injection had the opposite effect in all metrics. Saline injection transiently decreased capillary flow velocity and hematocrit without influencing flow distribution or stability. All perfusion metrics were temporally stable without intervention. These results demonstrate a novel and sensitive technique for reproducible, user-independent quantification of microvascular perfusion.

The role of thrombectomy and diffusion-weighted imaging with MRI in post-transplant renal vein thrombosis: a case report

BackgroundSurgical thrombectomy in the context of acute renal vein thrombosis (RVT) post-transplantation has had limited success, with considerable variation in the surgical techniques used. Unfortunately, it is usually followed by allograft nephrectomy within a few days if rapid allograft recovery does not ensue. We report a case of acute RVT in which nephrectomy was not performed despite a prolonged requirement for dialysis post-thrombectomy, but with recovery of renal function 2 weeks later. We also report the findings of serial MRI with diffusion-weighted imaging (DW-MRI) throughout the patient’s recovery, which provided novel insights into allograft microvascular perfusion changes post-thrombectomy.Case presentationA 65-year old patient underwent living-unrelated kidney transplantation complicated by acute RVT. Surgical thrombectomy and irrigation led to a delayed, but significant, recovery of renal function. Serial non-contrast DW-MRI scanning was used to non-invasively assess microvascular renal blood flow post-operatively. Unlike standard Doppler ultrasonography, DW-MRI documented reduced microvascular perfusion initially, with gradual but incomplete recovery that mirrored the partial improvement in renal function.ConclusionsOur findings suggest that surgical thrombectomy may be more effective than previously described if followed by careful patient observation. Moreover, diffusion-weighted MRI appears to provide important insights into the pathophysiology of delayed graft function and deserves further investigation.

Changes in skin microcirculation during radiation therapy for breast cancer

Background: The majority of breast cancer patients who receive radiation treatment are affected by acute radiation-induced skin changes. The assessment of these changes is usually done by subjective methods, which complicates the comparison between different treatments or patient groups. This study investigates the feasibility of new robust methods for monitoring skin microcirculation to objectively assess and quantify acute skin reactions during radiation treatment.Material and methods: Laser Doppler flowmetry, laser speckle contrast imaging, and polarized light spectroscopy imaging were used to measure radiation-induced changes in microvascular perfusion and red blood cell concentration (RBC) in the skin of 15 patients undergoing adjuvant radiation therapy for breast cancer. Measurements were made before treatment, once a week during treatment, and directly after the last fraction.Results: In the treated breast, perfusion and RBC concentration were increased after 1–5 fractions (2.66–13.3 Gy) compared to baseline. The largest effects were seen in the areola and the medial area. No changes in perfusion and RBC concentration were seen in the untreated breast. In contrast, Radiation Therapy Oncology Group (RTOG) scores were increased only after 2 weeks of treatment, which demonstrates the potential of the proposed methods for early assessment of skin changes. Also, there was a moderate to good correlation between the perfusion (r = 0.52) and RBC concentration (r = 0.59) and the RTOG score given a week later.Conclusion: We conclude that radiation-induced microvascular changes in the skin can be objectively measured using novel camera-based techniques before visual changes in the skin are apparent. Objective measurement of microvascular changes in the skin may be valuable in the comparison of skin reactions between different radiation treatments and possibly in predicting acute skin effects at an earlier stage.

Systemic application of carbon monoxide-releasing molecule 3 protects skeletal muscle from ischemia-reperfusion injury

ObjectiveIschemia-reperfusion (IR) is a limb- and life-threatening complication of acute limb ischemia and musculoskeletal trauma. Carbon monoxide-releasing molecules (CORMs) have recently been shown to protect microvascular perfusion and to reduce inflammation and injury in various ischemic animal models. The purpose of this study was to examine the effects of water-soluble CORM-3 on the extent of IR-induced muscle injury. MethodsWistar rats were randomized into three groups: sham (no ischemia), IR + CORM-3 (10 mg/kg intraperitoneally), and IR + inactive CORM-3 (iCORM-3; 10 mg/kg intraperitoneally). No-flow ischemia was induced by the application of a tourniquet to the hind limb for 2 hours; tourniquet release commenced the reperfusion phase. Both CORM-3 and iCORM-3 were injected immediately after tourniquet release. Temporal changes in microvascular perfusion, cellular tissue injury (ethidium bromide and bisbenzimide staining), and inflammatory response (leukocyte recruitment) within the extensor digitorum longus muscle were assessed using intravital video microscopy every 15 minutes for a total of 90 minutes after initiation of reperfusion. Systemic levels of tumor necrosis factor-α were also measured. ResultsHind limb IR resulted in (1) a significant no-reflow phenomenon followed by progressive increase in microvascular perfusion deficit (21% ± 2% continuously perfused capillaries in IR vs 76% ± 4% in sham [P < .001]; 52% ± 8% nonperfused capillaries in IR vs 13% ± 2% in sham at 90 minutes of reperfusion [P < .001]), (2) tissue injury (ethidium bromide and bisbenzimide staining of 0.52 ± 0.07 in IR vs 0.05 ± 0.03 in sham at 90 minutes of reperfusion [P < .001]), (3) leukocyte recruitment (13.7 ± 0.9 adherent leukocytes/30 seconds/1000 μm2 in IR vs 1.8 ± 0.5 adherent leukocytes/30 seconds/1000 μm2 in sham at 90 minutes of reperfusion [P < .001]), and (4) an increase in circulating tumor necrosis factor-α levels. Systemic administration of CORM-3 (but not of iCORM-3) effectively reduced the IR-associated skeletal muscle perfusion deficits, tissue injury, and inflammatory activation. ConclusionsCORM-3 displays potent protective and anti-inflammatory effects in an experimental model of hind limb IR, suggesting a potential therapeutic application of CORMs in treatment of ischemic conditions.

Effect of RBC Transfusion on Sublingual Microcirculation in Hemorrhagic Shock Patients: A Pilot Study.

The effects of RBC transfusion on microvascular perfusion are not well documented. We investigated the effect of RBC transfusion on sublingual microcirculation in hemorrhagic shock patients. Prospective, preliminary observational study. A 28-bed, surgical ICU in a university hospital. Fifteen hemorrhagic shock patients requiring RBC transfusion. Transfusion of one unit of RBCs. The sublingual microcirculation was assessed with a Sidestream Dark Field imaging device before and after RBC transfusion. After transfusion of one unit of RBC, hemoglobin concentration increased from 8.5 g/dL (7.6-9.5 g/dL) to 9.6 g/dL (9.1-10.3 g/dL) g/dL (p = 0.02) but no effect on macrocirculatory parameters (arterial pressure, cardiac index, heart rate, and pulse pressure variations) was observed. Transfusion of RBC significantly increased microcirculatory flow index (from 2.3 [1.6-2.5] to 2.7 [2.6-2.9]; p < 0.003), the proportion of perfused vessels (from 79% [57-88%] to 92% [88-97%]; p < 0.004), and the functional capillary density (from 21 [19-22] to 24 [22-26] mm/mm; p = 0.003). Transfusion of RBC significantly decreased the flow heterogeneity index (from 0.51 [0.34-0.62] to 0.16 [0.04-0.29]; p < 0.001). No correlations were observed between other macrovascular parameters and microvascular changes after transfusion. The change in microvascular perfusion after transfusion correlated negatively with baseline microvascular perfusion. RBC transfusion improves sublingual microcirculation independently of macrocirculation and the hemoglobin level in hemorrhagic shock patients. The change in microvascular perfusion after transfusion correlated negatively with baseline microvascular perfusion. Evaluation of microcirculation perfusion is critical for optimization of microvascular perfusion and to define which patients can benefit from RBC transfusion during cardiovascular resuscitation.

Microcirculatory perfusion shows wide inter-individual variation and is important in determining shock reversal during resuscitation in a porcine experimental model of complex traumatic hemorrhagic shock.

BackgroundTraumatic hemorrhagic shock (THS) is a leading cause of preventable death following severe traumatic injury. Resuscitation of THS is typically targeted at blood pressure, but the effects of such a strategy on systemic and microcirculatory flow remains unclear. Failure to restore microcirculatory perfusion has been shown to lead to poor outcomes in experimental and clinical studies. Systemic and microcirculatory variables were examined in a porcine model of complex THS, in order to investigate inter-individual variations in flow and the effect of microcirculatory perfusion on reversal of the shock state.MethodsBaseline standard microcirculatory variables were obtained for 22 large white pigs using sublingual incident dark field (IDF) video-microscopy. All animals were subjected to a standardised hind-limb injury followed by a controlled haemorrhage of approximately 35 % of blood volume (shock phase). This was followed by 60 min of fluid resuscitation with either 0.9 % saline or component blood products and a target SBP of 80 mmHg (early resuscitation phase). All animals were then given blood products to a target SBP of 110 mmHg for 120 min (mid-resuscitation phase), and a further 100 min (late resuscitation phase). IDF readings were obtained at the midpoint of each of these phases. Cardiac output was measured using a pulmonary artery catheter. Animals were divided into above average (A) and below average (B) perfused vessel density (PVD) groups based on the lowest recorded PVD measurement taken during the shock and early resuscitation phases.ResultsThere was minimal inter-individual variation in blood pressure but wide variation of both systemic and microcirculatory flow variables during resuscitation. During shock and early resuscitation, group A (n = 10) had a mean PVD of 10.5 (SD ± 2.5) mm/mm2 and group B (n = 12) 5.5 (SD ± 4.1) mm/mm2. During the later resuscitation phases, group A maintained a significantly higher PVD than group B. Group A initially had a higher cardiac output, but the difference between the groups narrowed as resuscitation progressed. At the end of resuscitation, group A had significantly lower plasma lactate, higher lactate clearance, lower standard base deficit and smaller mixed venous-arterial CO2 gradient. There was no significant difference in blood pressure between the two groups at any stage.ConclusionThere was a wide variation in both macro- and microcirculatory flow variables in this pressure-targeted experimental model of THS resuscitation. Early changes in microvascular perfusion appear to be key determinants in the reversal of the shock state during resuscitation. Microcirculatory flow parameters may be more reliable markers of physiological insult than pressure-based parameters and are potential targets for goal-directed resuscitation.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-016-0088-z) contains supplementary material, which is available to authorized users.

Visualization of perfusion changes with laser speckle contrast imaging using the method of motion history image

Laser speckle contrast imaging (LSCI) is a real-time imaging modality reflecting microvascular perfusion. We report on the application of the motion history image (MHI) method on LSCI data obtained from the two hemispheres of a mouse. Through the generation of a single image, MHI stresses the microvascular perfusion changes. Our experimental results performed during a pinprick-triggered spreading depolarization demonstrate the effectiveness of MHI: MHI allows the visualization of perfusion changes without loss of resolution and definition. Moreover, MHI provides close results to the ones given by the generalized differences (GD) algorithm. However, MHI has the advantage of giving information on the temporal evolution of the perfusion variations, which GD does not.

16 The cardiac toxicity CMR study in patients with lung cancer treated with chemo-radiotherapy: The cart study- a semi quantitative analysis of the myocardial perfusion index

Background There are limited data on the cardiac effects of radiotherapy and chemo-radiotherapy on the heart in patients with non-small cell lung cancer (NSCLC). CART is a pilot study designed to investigate change in myocardial function and tissue properties where Patients will undergo cardiac magnetic resonance (CMR) at baseline, during treatment, at 6 weeks and at 6 months after treatment completion. Here we report our preliminary findings related to temporal changes in myocardial perfusion index (MPI). Methods CMR was performed on a Siemens MAGNETOM Verio (Erlangen, Germany) 3.0 Tesla scanner. First-pass myocardial perfusion was assessed by saturation recovery prepared dynamic contrast enhanced sequence during administration of 0.1 mmol/kg of gadoterate meglumine (Dotarem). Semiquantitative analysis was performed on segmented basal and mid-LV short axis slices to derive normalised upslopes of myocardial signal intensity profiles (myocardial perfusion index, MPI). The change in MPI over time was analysed statistically using a linear mixed effects model. Results 13 patients currently have undergone CMR at baseline and during treatment (mean age 66 years, SD: 9; 71% male), 8 patients have undergone CMR at 6 weeks post treatment initiation (5 patients lost to follow-up/ died), and 6 patients have undergone CMR at 6 months from baseline (n = 2 lost to follow-up/ died). Perfusion index (Figure 1) varies significantly with time (p = 0.0015). After adjustment for multiple testing, the increase from baseline is statistically significant at 6 weeks (p = 0.014) and approaches significance at 6 months (p = 0.074) post treatment. Conclusion Change in microvascular perfusion is most pronounced 6 weeks following the completion of treatment. This finding will be used in the design of future clinical studies, where measurement of MPI will provide a robust comparison of different existing and emerging treatment protocols for NSCLC with regard to their effects on myocardial physiology. Funding Beatson Oncology Centre Fund

Deleterious Effects of Intra-arterial Administration of Particulate Steroids on Microvascular Perfusion in a Mouse Model

Purpose To determine the in vivo effects of several particulate steroids on microvascular perfusion by using intravital microscopy in a mice model and to investigate the in vitro interactions between these particulate steroids and red blood cells (RBCs). Materials and Methods The study was conducted in agreement with the guidelines of the National Committee of Ethic Reflection on Animal Experimentation. By using intravital microscopy of mouse cremaster muscle, the in vivo effects of several particulate steroids on microvascular perfusion were assessed. Four to five mice were allocated to each of the following treatment groups: saline solution, dexamethasone sodium phosphate, a nonparticulate steroid, and the particulate steroids cortivazol, methylprednisolone, triamcinolone, and prednisolone. By using in vitro blood microcinematography and electron microscopy, the interactions between these steroids and human RBCs were studied. All results were analyzed by using nonparametric tests. Results With prednisolone, methylprednisolone, or triamcinolone, blood flow was rapidly and completely stopped in all the arterioles and venules (median RBC velocity in first-order arterioles, 5 minutes after administration was zero for these three groups) compared with a limited effect in mice treated with saline, dexamethasone, and cortivazol (20.3, 21.3, and 27.5 mm/sec, respectively; P < .003). This effect was associated with a large decrease in the functional capillary density (4.21, 0, and 0 capillaries per millimeter for methylprednisolone, triamcinolone, or prednisolone, respectively, vs 21.0, 21.4, and 19.1 capillaries per millimeter in mice treated with saline, dexamethasone, and cortivazol, respectively; P < .003). This was because of the rapid formation of RBC aggregates. However, no change in microvascular perfusion was associated with administration of cortivazol or dexamethasone. In vitro experiments confirmed the formation of RBC aggregates associated with the transformation of RBCs into spiculated RBCs with the same steroids. Conclusion Several particulate steroids have an immediate and massive effect on microvascular perfusion because of formation of RBC aggregates associated with the transformation of RBCs into spiculated RBCs. (©) RSNA, 2016 Online supplemental material is available for this article.