Significant Decrease In Blood Flow Research Articles

Testicular torsion in vivo models: Mechanisms and treatments.

Testicular torsion is a condition in which a testis rotates around its longitudinal axis and twists the spermatic cord. This in turn results in a significant decrease in blood flow and perfusion of testicular tissue. During Testicular torsion, the testicular tissue is affected by ischemia, heat stress, hypoxia, and oxidative and nitrosative stress. The testicular torsion should be considered an emergency condition and surgical intervention (testicular detorsion ) as the sole treatment option in viable cases involves counter-rotation on twisted testes associated, when possible, to orchipexy, in order to avoid recurrence. Possible testicular detorsion side-effects occur due to reperfusion and endothelial cells injury, microcirculation disturbances, and intense germ cells loss. To discuss testicular torsion surgery-based methods, different time frames for testicular torsion induction, and the associated pathophysiology by emphasizing cellular and molecular events as well as different therapeutic agent applications for testicular torsion. We reviewed all original research and epidemiological papers related to testicular torsion condition. Testicular torsion causes germ cell necrosis, arrested spermatogenesis, and diminished testosterone levels, with consequent infertility. Among different involved pathophysiological impacts, testicular torsion/detorsion-induced ischemia seems to play the key role by leading the tissue toward other series of events in testis. Numerous studies have used adjuvant antioxidants, calcium channel blockers, anti-inflammatory agents, or vasodilating agents in order to decrease these effects. To the best of our knowledge, no previously conducted study examined therapeutical agents' beneficial effects post clinical I/R condition in humans. Different agents targeting different pathophysiological conditions were used to ameliorate the ischemia/reperfusion-induced condition in animal models, however, none of the administrated agents were tested in human cases. Although considering testicular detorsion surgery is still the golden method to reverse the testicular torsion condition and the surgical approach is undeniable, the evaluated agents with beneficial effects, need to be investigated furthermore in clinical conditions. Thus, furthermore clinical studies and case reports are required to approve the animal models proposed agents' beneficial impacts.

Some Features of the Development of AMD and Other Diseases of the Posterior Pole Associated with the Virus Carrier and the Novel Coronavirus Disease COVID-19

This article highlights main aspects of pathogenesis of age-related macular degeneration (AMD) and the connection between SARS-CoV-2 and diseases of the posterior pole of the eyes. Background: A novel coronavirus disease COVID-19 is actual nowadays due to its multiple organ damage, including eye tissues. Retina is also a target organ. AMD is the most common cause of central vision loss and its development is connected not only with ageing, but also with some other factors. Last years ophthalmological community considers virus infection to be a predictor and trigger for developing of AMD. Objective: Several theories have been proposed for the development of AMD. The most common theories are vascular due to pathogenetically significant decrease in blood flow in the pool of the carotid arteries; metabolic disorders (systemic and local); oxidative stress in endothelial cells; hereditary predisposition. Inflammation as a pathogenetic mechanism appeared in a novel light of discoveries in developing of not only AMD, but also some other eye diseases. The connection between SARS-CoV-2 and diseases of the posterior pole known nowadays are conjunctivitis, central retinal vein occlusion, isolated inflammatory optic neuritis, acute bilateral demyelinating optic neuritis. Thus, the question is still open. Conclusion: no single theory of the development of AMD can absolutely explain the diversity of pathological changes in of the retina and choroid tissues. Further study of the role of each factor of pathogenesis– from molecular to tissue will allow the development of fundamentally novel and perspective directions of AMD therapy.

Changes in microcirculation and structural components of the skin under photodynamic effects

Introduction . Distinctive features of microcirculation and their connection with structural disorders in the skin during photodynamic exposure using various photosensitizers (PS) are not well understood. Objective . Comparative analysis of the relationship between morphological abnormalities and changes in blood flow in the skin during photoactivation of PS, taking into consideration the influence on mast cells (MC), structural elements of the dermis and underlying muscle tissue. Materials and methods . In this work were used male Wistar rats (n=46). PS were administered intravenously: Radachlorin (RDC) (5 mg/kg) 3 hours, Coproporphyrin III (CPP) (10 mg/kg) 24 hours before irradiation. To control the accumulation of PS in the skin, methods of fluorescence videodermatoscopy and confocal scanning laser microscopy (CSLM) were used. Laser irradiation (662 and 635 nm) was performed with an energy density of 50 Jcm –2 , the irradiated surface area was 0,78 cm 2 . Laser Doppler flowmetry was used to assess microcirculation in the skin. Results . According to videodermatoscopy, fluorescence maximum values in the R channel were recorded 6-8 hours after administration, and amounted to 4901 [4190; 6732] a. u. for RDC and 2997 [2678; 3351] a. u. for CPP. Using the CSLM method, it was shown that CPP is poorly visualized in the walls of blood vessels. In experiments with RDC, the structures of areolar tissue of the hypodermis are determined. An hour after laser irradiation, in experiments with RDC, as well as with CPP, a significant decrease in blood flow was noted compared with the control to 3,61±0,7 and 4,27±1,4 PU, respectively. Structural changes when using both PS showed endothelial swelling, vasodilation and congestion, hemorrhages in the dermis, and underlying muscle tissue. The amount of MC was reduced. Conclusions . Laser irradiation with the parameters used in the work leads to a significant decrease in blood flow in the skin in experimental animals as a result of photoactivation of PS. CPP requires a higher radiation energy density. Morphological changes were revealed not only at the level of the epidermis, dermis and hypodermis, but also the underlying striated muscle tissue. In the early stages after exposure, massive degranulation of MC is noted with a decrease in their number.

Effect of “Dry” Immersion on Blood Flow in Jugular Veins and Cerebral Venous Sinus Characterized by Ultrasonic Methods of Investigation

Venous circulation in the brain was investigated in a three-day “dry” immersion experiment. The aim of the study was to estimate the influence of microgravity factors on venous drainage from the cranial cavity. Duplex scanning and Doppler ultrasound were used to record hemodynamic parameters of the cervical main veins and orbital and cerebral venous sinuses. A significant decrease in blood flow along the jugular pathway with the activation of additional pathways of both the extra- and intracranial divisions of the venous system of the brain was detected. These results suggest that microgravity triggers the mechanisms capable of compensating the increasing intracranial venous pressure. The fact that in some volunteers the intracranial venous blood flow did not accelerate may reflect anatomical features and require a more scrupulous investigation of their venous systems.

Efficacy evaluation of reteplase in a novel canine acute pulmonary thromboembolism model developed by minimally invasive surgery and digital subtraction angiography.

PurposeIn order to evaluate the thrombolytic effects of reteplase in pulmonary thromboembolism (PTE), we developed a novel canine PTE model. The efficacy of reteplase against PTE in comparison to alteplase was clarified for the first time, and this PTE model could be further applied to studies of novel thrombolytic therapies.Patients and methodsTwenty-four dogs were divided into four groups: sham operation, vehicle, alteplase, and reteplase. Autologous thrombi/saline were injected into the pulmonary artery, and thrombolytic agents were administrated. Thrombus formation and dissolution were monitored by real-time digital subtraction angiography (DSA), and pulmonary pressures were measured simultaneously. Blood coagulation, blood gas, hematology, and histopathologic examinations were used as subsidiary methods.ResultsThe canine PTE model was established with a significant decrease of blood flow and ~75% blocking area. Administration of reteplase (0.6 mg/kg) resulted in effective thrombus dissolution with a recovery of over 80% blood flow, as effective as alteplase (1.6 mg/kg). Correspondingly, the elevated pulmonary systolic, diastolic, and mean arterial pressures declined to the normal level. Blood coagulation was changed by reteplase, with a dramatic elongation of prothrombin time, activated partial thromboplastin time, and thrombin time, even longer than alteplase. In contrast to the vehicle group, no obvious pathological changes were found in the two thrombolytic groups. Hematological, blood biochemical, and blood gas results also indicated that reteplase had no adverse reactions in this PTE model.ConclusionReteplase proved to be an effective and safe therapy for PTE for the first time, and a small dosage of reteplase exerted an efficacy comparable to the routine dosage of alteplase. Our findings indicated the potential of reteplase as clinical treatment against PTE. This technically innovative, stability- and validity-proved canine PTE model developed by minimally invasive surgery and DSA resembled major clinical features. This may further facilitate our understanding of thrombotic disorders and development of prophylactic and therapeutic approaches.

Использование ультразвуковой допплерографии для объективной оценки изменений пенильной гемодинамики в генезе эректильной дисфункции у больных рассеянным склерозом

In order to assess the incidence and nature of violations of penile hemodynamics in the genesis of erectile dysfunction in patients with multiple sclerosis, data on pharmacodopplerometry of penile vessels in 151 men divided into 3 groups (patients with multiple sclerosis divided into 2 groups by severity and control group of healthy juniper) we are studied. On the basis of ultrasound dopplerography and spectral analysis, a significant decrease in blood flow along the arteries of the penis was found in patients with severe neurological disorders in 22.5% of cases with preserved functional capabilities of cavernous bodies. With a slight degree of neurological deficit in most patients, disorders of arterial blood supply and functional ability of cavernous bodies were not detected.

Effects of dobutamine, dopamine, phenylephrine and noradrenaline on systemic haemodynamics and intestinal perfusion in isoflurane anaesthetised horses.

In the horse, effects of cardiovascular-active drugs on local perfusion of the gastrointestinal tract are poorly understood. To determine the effect of drugs commonly used to support blood pressure, on local intestinal blood flow and tissue oxygenation under isoflurane anaesthesia. In vivo randomised crossover experiment. Ten horses were anaesthetised with isoflurane. After 90 min of equilibration three doses (μg/kg bwt/min) of dobutamine (DOB 0.5/1/3), dopamine (DA 1/2/5), noradrenaline (NA 0.1/0.2/0.5) and phenylephrine (PHE 0.5/1/3) were infused for 15 min, in a randomised order, with a 45 min washout-period. Blood flow and tissue oxygenation (sO2 ) of jejunum, colon and stomach were measured using white light remission spectrophotometry and laser doppler flowmetry; heart rate (HR), mean arterial blood pressure (MAP), cardiac output (CO) were measured and systemic vascular resistance (SVR) calculated. Compared to baseline high dose dobutamine significantly increased CO, HR, MAP (P<0.001) and blood flow to the jejunum (+47 ± 26%, P = 0.001) and colon (+29 ± 15%, P<0.001) (mean ± s.d.). Dopamine (DA5) increased CO but decreased colonic blood flow (-39 ± 21% from baseline, P<0.001), as well as SVR and MAP compared to baseline (P<0.001). Noradrenaline had no significant influence on intestinal perfusion, but increased MAP and SVR from baseline (P<0.001). Phenylephrine (PHE3) caused a significant decrease in blood flow and sO2 , most profoundly at the colon compared to baseline (flow -44 ± 21%; sO2 -16 ± 3%, P<0.001), while MAP and SVR increased and CO and HR decreased (P<0.001). The measurement technique only allows for flow measurements in arbitrary units, which can limit comparability to other techniques. At the investigated doses dobutamine improved systemic and peripheral haemodynamics, while dopamine decreased MAP and peripheral perfusion. Noradrenaline increased MAP and SVR while peripheral blood flow was maintained, phenylephrine increased MAP, but reduced both local and systemic perfusion.

Infusion of Coagulation Factor VIII-Containing Induced Pluripotent Stem Cell (iPSC)-Derived Megakaryocytes (iMks) Shows Potential As Hemophilia a Treatment

Ectopically expressed factor VIII (FVIII) in megakaryocytes (MKs) and platelets (pFVIII) is stored in a-granules and released at sites of vascular injury by activated platelets (Plts), restoring hemostasis in FVIIInull mice, even in the presence of neutralizing inhibitors. These studies support the idea that unlike therapies that correct plasma levels of FVIII, pFVIII may be a useful therapy in patients with hemophilia A who have intractable inhibitors and significant bleeds. Expressing FVIII in Plts, however, has limitations that make pFVIII gene therapy through bone marrow transplantation (BMT) problematic: 1) pFVIII expressed during megakaryopoiesis can injure the Mks, potentially exacerbating post-BMT thrombocytopenia, and 2) pFVIII’s efficacy in joint and intracranial bleeds has yet to be shown, especially in the presence of inhibitors. Due to these limitations we propose an alternative strategy: infusing patient-specific iMks derived from personalized iPSCs and expressing either human B-domain-deleted (BDD) FVIII or variants of FVIII that have greater stability and longer half-lives. Our group has shown that infusing in vitro-grown Mks into mice releases functional Plts in the recipient animals. iPSCs are a renewable source of stem cells that can be pre-screened to select clones that both express high levels of pFVIII and also release high numbers of Plts after differentiation into iMks. As proof-of-principle, iMks were transfected with a self-inactivating lentivirus containing cDNA for 1 of 3 FVIII variants: wildtype BDD FVIII (WT FVIII), a PACE/furin cleavage site FVIII (FVIIIR1645H) variant, and an amino acid 1645 to 1648 deletion FVIII (FVIIIΔ) variant that removes the entire PACE/furin cleavage site. FVIIIR1645H and FVIIIΔ showed greater stability and consequently greater specific activity with no increase in injuring Mks. We previously published that hemophilia A mice expressing pFVIIIR1645H were more hemostatically corrected than comparable mice expressing WT pFVIII. All of the FVIII variant iMks expressed at least a 40-fold higher level of mRNA compared to the non-transduced control (N=6) and integration levels show the same number of viral copies between the groups (N=6). All variants expressed >550 pg FVIII/106 CD42b+ iMKs (N=6). Upon activation with thrombin, transduced Mks released the FVIII into the supernatant. To examine whether this pFVIII injured the developing Mks, baseline PAC-1 binding for Mk activation in culture (N=3), TUNEL staining and Annexin-5 binding for apoptosis (N=4) were analyzed with no differences observed with WT Mks not expressing pFVIII. To test the ability of FVIII-expressing iMks to correct the coagulopathy in hemophilia A, 5x105 iMks were added to FVIIInull murine whole blood (0.11 ml) and evaluated for clot formation using rotational thromboelastometry (ROTEM). Each pFVIII iMk variant showed a decrease in clotting time, clot formation time, and an increase in maximum clot firmness when compared to the non-transduced control (p<0.007 for each, N=4). These FVIII expressing iMks were also tested in vivo in a FeCl3 carotid artery injury murine model. 24 hours prior to infusion, recipient hemophilia A mice were treated with clodronate liposomes to eliminate circulating monocytes and to improve the survival of infused human iMks and their released Plts. Immediately post iMks (5x106)infusion, a 20% FeCl3 solution was applied to the carotid artery for 3 mins and flow rate through the injured vessel was measured for 30 mins. Both WT FVIII and FVIIIR1645H showed a significant decrease in blood flow through the injured vessel from 1.2 ml/min seen in FVIIInull mice receiving control iMks to 0.4 ml/min (p<0.05, N=10). Wild-type mice had a flow rate of 0.13 ml/min. These data indicate that pFVIII within iMKs or their derived Plts expressing FVIII can improve hemostasis in vitro and in vivo. These studies provide the groundwork to examine whether infused iMks pFVIII can improve hemostasis in the setting of inhibitors. DisclosuresArruda:Pfizer: Patents & Royalties, Research Funding. Sabatino:Spark Therapeutics: Research Funding. Camire:Bayer: Consultancy; Spark Therapeutics: Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties; Pfizer: Consultancy, Patents & Royalties, Research Funding; Novo Nordisk: Research Funding.

Abstract: A Prospective Randomized Trial to Assess Perfusion and Patient Satisfaction in Nipple-Areola Skin Sparing Mastectomy with Immediate Reconstruction

BACKGROUND: Nipple-areola and skin sparing mastectomy (NASSM) is an accepted and sought after option for eligible patients, and the rate of women undergoing this operation continues to climb. The main advantage of the procedure is the ability utilize existing skin envelope and NAC for improved shape, fewer operations, and less psychological impact on patients. There are many possible incisions, each providing its own advantage from an oncologic or reconstructive perspective. Studies suggest that perfusion is received primarily from superior, medial, and lateral contributions. Therefore the lateral radial (LR) incision may lead to improved perfusion, however the mastectomy is more difficult via an inframammary (IMF) incision and this could lead to a higher complication rate. We aim to assess perfusion to nipple-areola complex in these two incision patterns and determine the impact of the incision type on overall outcomes, complications, and patient satisfaction. METHODS: Patients with age >18 with BMI 18–35, with estimated breast size 100-800g were included in this prospective study. Patients were randomized to receive either an IMF or LR incision unless one was given a strong preference by patient or surgeon. A BreastQ survey was administered preoperatively, and three-dimensional images of both breasts were captured. Mastectomies were performed by experienced breast surgical oncologists. Laser angiography (SPY system, Lifecell) was performed at 3 distinct time points: pre-operatively, post-NASSM, and post-reconstruction. Blood pressure was monitored closely throughout the operation. Patients were followed for at least 3 months after their permanent implant placement for complications. Three months post-operatively, the BreastQ survey was again administered and three-dimensional images were captured to measure aesthetic landmarks. Two-tailed Mann-Whitney U and Chi-squared tests were used to compare group medians and proportions with P<0.05 indicating significance. RESULTS: Fifty-five received an IMF incision, and twenty-four a LR incision. There was no difference in demographics, comorbidities, specimen weight, initial implant volume, or intraoperative blood pressure between groups. Similarly, there was no there a difference in distribution of breast perfusion pattern. The LR group did have a longer operative time (155 min vs 177 min, p=0.02). The decrease in perfusion to the whole breast did not differ between groups at each surgical stage. Patients with an IMF incision had significantly lower remaining perfusion to the inferior (21.94% vs 36.89%, p=0.001) and lateral portions of the flap (23.08% vs 40.70%, p=0.003) after reconstruction. Perfusion to the nipple was not significantly different (29.87% vs 40.03%, p=0.15) when adjusting for covariates. Rates of complications, including necrosis, infection, implant exposure or malposition, and explant did not differ between incision types. There was no difference in patient satisfaction based on BreastQ scores between incision types. Finally, there was no significant difference in mammographic measurements on three-dimensional imagining between groups. CONCLUSIONS: There is a significant decrease in blood flow to the inferior and lateral portions of the skin envelope using the IMF incision when compared to the LR incision, possibly due to differences in retraction and difficulty in technique. Despite this, there is no difference in complications, outcomes, or patient satisfaction with their surgical reconstruction over a 3 month period.

Photodynamic Therapy-Induced Microvascular Changes in a Nonmelanoma Skin Cancer Model Assessed by Photoacoustic Microscopy and Diffuse Correlation Spectroscopy

One of the main mechanisms of action for photodynamic therapy (PDT) is the destruction of tumor vasculature. We observed the PDT-induced vasculature destruction in a mouse model of skin cancer using two techniques: Photoacoustic microscopy (PAM) and diffuse correlation spectroscopy (DCS). PAM showed high-resolution images of the abnormal microvasculature near the establishing tumor area at pre-PDT, as well as the subsequent destruction of those vessels post-PDT. DCS indicated a significant blood flow decrease after PDT, confirming the vascular destruction. Noninvasive assessment of vascular changes may be indicative of therapy response.

A non-invasive method to produce pressure ulcers of varying severity in a spinal cord-injured rat model

Experimental study. The objective of this study was to establish a non-invasive model to produce pressure ulcers of varying severity in animals with spinal cord injury (SCI). The study was conducted at the Johns Hopkins Hospital in Baltimore, Maryland, USA. A mid-thoracic (T7-T9) left hemisection was performed on Sprague-Dawley rats. At 7 days post SCI, rats received varying degrees of pressure on the left posterior thigh region. Laser Doppler Flowmetry was used to record blood flow. Animals were killed 12 days after SCI. A cardiac puncture was performed for blood chemistry, and full-thickness tissue was harvested for histology. Doppler blood flow after SCI prior to pressure application was 237.808±16.175 PFUs at day 7. Following pressure application, there was a statistically significant decrease in blood flow in all pressure-applied groups in comparison with controls with a mean perfusion of 118.361±18.223 (P<0.001). White blood cell counts and creatine kinase for each group were statistically significant from the control group (P=0.0107 and P=0.0028, respectively). We have created a novel animal model of pressure ulcer formation in the setting of a SCI. Histological analysis revealed different stages of injury corresponding to the amount of pressure the animals were exposed to with decreased blood flow immediately after the insult along with a subsequent marked increase in blood flow the next day, conducive to an ischemia-reperfusion injury (IRI) and a possible inflammatory response following tissue injury. Following ischemia and hypoxia secondary to microcirculation impairment, free radicals generate lipid peroxidation, leading to ischemic tissue damage. Future studies should be aimed at measuring free radicals during this period of increased blood flow, following tissue ischemia.

Effects of cryotherapy methods on circulatory, metabolic, inflammatory and neural properties: a systematic review

Abstract Introduction: The cooling therapy (cryotherapy) is commonly used in clinical environmental for the injuries treatment according to its beneficial effects on pain, local inflammation and the recovery time of patients. However, there is no consensus in the literature about the effects of cryotherapy in the physiological reactions of affected tissues after an injury. Objective: To realize a systematic review to analyze the cryotherapy effects on circulatory, metabolic, inflammatory and neural parameters. Materials and methods: A search was performed in PubMed, SciELO, PEDro and Scopus databases following the eligibility criteria. Included studies were methodologically assessed by PEDro scale. Results: 13 original studies were selected and presented high methodological quality. Discussion: The cryotherapy promotes a significant decrease in blood flow, in venous capillary pressure, oxygen saturation and hemoglobin (only for superficial tissues) and nerve conduction velocity. However, the effect of cryotherapy on the concentration of inflammatory substances induced by exercise, as the creatine kinase enzyme and myoglobin, remains unclear. Conclusion: The physiological reactions to the cryotherapy application are favorable to the use of this therapeutic tool in inflammatory treatment and pain decrease, and demonstrate its importance in the neuromuscular system injuries rehabilitation.

Ocular hemodynamics in patients with rhegmatogenous retinal detachment

Aim. In case of retinal detachment atrophic processes lead to irreversible loss of functions within 4–6 days, it happens on underlying low ocular blood flow. In order to evaluate the degree of violation of regional hemodynamics in patients with retinal detachment two groups of patients were examined: the main group (52 patients with rhegmatogenous retinal detachment) and the control group (24 myopic patients with lattice form of peripheral chorioretinal dystrophy). Methods and results. Doppler and reography results had been compared, significant decrease of blood flow in patients with retinal detachment was found. No differences between affected and fellow eye in these patients, close negative correlation between the level of ocular blood flow and the degree of myopia in the control group. Conclusion. This demonstrates the feasibility of actions to improve regional blood flow in patients operated on for retinal detachment.

Decision-making deficit of a patient with axonal damage after traumatic brain injury

Patients with traumatic brain injury (TBI) were reported to have difficulty making advantageous decisions, but the underlying deficits of the network of brain areas involved in this process were not directly examined. We report a patient with TBI who demonstrated problematic behavior in situations of risk and complexity after cerebral injury from a traffic accident. The Iowa gambling task (IGT) was used to reveal his deficits in the decision-making process. To examine underlying deficits of the network of brain areas, we examined T1-weighted structural MRI, diffusion tensor imaging (DTI) and Tc-ECD SPECT in this patient. The patient showed abnormality in IGT. DTI-MRI results showed a significant decrease in fractional anisotropy (FA) in the fasciculus between the brain stem and cortical regions via the thalamus. He showed significant decrease in gray matter volumes in the bilateral insular cortex, hypothalamus, and posterior cingulate cortex, possibly reflecting Wallerian degeneration secondary to the fasciculus abnormalities. SPECT showed significant blood flow decrease in the broad cortical areas including the ventromedial prefrontal cortex (VM). Our study showed that the patient had dysfunctional decision-making process. Microstructural abnormality in the fasciculus, likely from the traffic accident, caused reduced afferent feedback to the brain, resulting in less efficient decision-making. Our findings support the somatic-marker hypothesis (SMH), where somatic feedback to the brain influences the decision-making process.

Submucosal implantation of soft tissue expanders does not affect microcirculation

To investigate the effect of submucosal implantation of self-filling osmotic tissue expanders on mucosal microcirculation. In ten beagle dogs, all premolars were extracted on both sides of the mandible. Tooth-supporting bone and excess soft tissue were removed to mimic a severely resorbed edentulous ridge. Six weeks later, tissue expanders with 0.7ml final volume were implanted into a submucosal pouch at randomly selected test sites, while contralateral sites served as untreated controls. Microcirculation was assessed in perfusion units (PU) before surgery, after local anaesthesia, directly after surgery, and after 1 and 3days, using Laser Doppler flowmetry. Local anaesthesia caused a significant decrease of blood flow from baseline (zero) to -6.4 PU (median; Q1 -10.5; Q3 -0.9; P=0.006); however, no additional significant decrease was recorded after completion of surgery. Blood flow showed significant increases to -3.6 PU (median; Q1 -11.3, Q3 2.1; P=0.02) and -4.0 PU (median; Q1 -9.2, Q3 1.1; P=0.013) after 1 and 3days, respectively, when compared to the measurements obtained after application of local anaesthesia and completion of surgery. Blood flow had returned to unimpaired baseline levels 1day after surgery (P>0.05). Submucosal implantation of self-filling osmotic tissue expanders results in only momentary disturbance of microcirculation. The minor impairment of perfusion may explain the consistently good outcomes of submucosal implantation of these tissue expanders.

The effect of negative wound pressure therapy on haemodynamics in a laparostomy wound model

We have recently shown that negative pressure wound therapy (NPWT) induces a decrease in microvascular blood flow in the small intestinal loop close to the dressing. The effect of NPWT is thus thought to be local. In this study, we investigate whether the application of NPWT in laparostomy affects the haemodynamics. Midline incisions were made in six pigs followed by NPWT at -120 mmHg for 20 minutes. The cardiac output, mean systemic arterial pressure, mean pulmonary artery pressu re, central venous pressure, left atrial pressure and superior mesenteric artery blood flow were recorded. The blood flow in a small branch of the superior mesenteric artery was then recorded under NPWT between -50 and -175 mmHg. Cardiac output was not affected by NPWT [P = not significant (n.s.)]. Neither the mean arterial pressure nor the mean pulmonary artery pressure was affected by NPWT (P = n.s.). Negative pressures of -50, -75, -100 and -125 mmHg did not alter the blood flow in the small branch of the superior mesenteric artery (P = n.s.). After application of -150 mmHg, a significant decrease in blood flow was seen (P < 0·01), while the application of -175 mmHg resulted in only a slight decrease in blood flow (P = n.s.). The effect of NPWT in laparotomy seems to be local and to have no influence on central haemodynamics or the blood flow to the superior mesenteric artery.

In vivo, label-free, three-dimensional quantitative imaging of kidney microcirculation using Doppler optical coherence tomography

Doppler optical coherence tomography (DOCT) is a functional extension of optical coherence tomography (OCT) and is currently being employed in several clinical arenas to quantify blood flow in vivo. In this study, the objective was to investigate the feasibility of DOCT to image kidney microcirculation, specifically, glomerular blood flow. DOCT is able to capture three-dimensional (3D) data sets consisting of a series of cross-sectional images in real time, which enables label-free and non-destructive quantification of glomerular blood flow. The kidneys of adult, male Munich–Wistar rats were exposed through laparotomy procedure after being anesthetized. Following exposure of the kidney beneath the DOCT microscope, glomerular blood flow was observed. The effects of acute mannitol and angiotensin II infusion were also observed. Glomerular blood flow was quantified for the induced physiological states and compared with baseline measurements. Glomerular volume, cumulative Doppler volume, and Doppler flow range parameters were computed from 3D OCT/DOCT data sets. Glomerular size was determined from OCT, and DOCT readily revealed glomerular blood flow. After infusion of mannitol, a significant increase in blood flow was observed and quantified, and following infusion of angiontensin II, a significant decrease in blood flow was observed and quantified. Also, blood flow histograms were produced to illustrate differences in blood flow rate and blood volume among the induced physiological states. We demonstrated 3D DOCT imaging of rat kidney microcirculation in the glomerulus in vivo. Dynamic changes in blood flow were detected under altered physiological conditions demonstrating the real-time imaging capability of DOCT. This method holds promise to allow non-invasive imaging of kidney blood flow for transplant graft evaluation or monitoring of altered-renal hemodynamics related to disease progression.

Olfactory function improves following hemodialysis

Olfactory function has been shown to be affected in chronic kidney disease; however, studies are contradictory and little is known on the effects of dialysis. To resolve these issues we tested olfactory function in 24 healthy controls and in 28 patients with chronic kidney disease receiving hemodialysis (20 patients) or peritoneal dialysis (the other 8). As assays for olfactory function we measured smell identification, n-butanol and acetic acid thresholds, Kt/V urea, percentage reduced urea, and weights before and after dialysis. Olfactory function was also self-rated by the participants. Compared to healthy controls, predialysis olfactory function was moderately but significantly decreased in the two dialysis groups, with hemodialysis patients being more affected. Patients self-rated olfactory function similar to that of healthy controls, suggesting that patients are unaware of the olfactory decrease. Olfactory function was significantly improved by one hemodialysis session. Neither body mass index, total volume loss, nor any other dialysis parameter correlated with olfactory function or its restitution following hemodialysis. The observed pattern of improvement suggests underlying mixed peripheral and central mechanisms. Thus, olfactory dysfunction in patients with chronic kidney disease is readily reversible by hemodialysis.

The effect of a cryotherapy gel wrap on the microcirculation of skin affected by chronic venous disorders

The aim of this randomized clinical trial was to investigate a cryotherapy (cooling) gel wrap applied to lower leg skin affected by chronic venous disorders to determine whether therapeutic cooling improves skin microcirculation. Chronic venous disorders are under-recognized vascular health problems that result in severe skin damage and ulcerations of the lower legs. Impaired skin microcirculation contributes to venous leg ulcer development, thus new prevention therapies should address the microcirculation to prevent venous leg ulcers. Sixty participants (n = 30 per group) were randomized to receive one of two daily 30-minute interventions for four weeks. The treatment group applied the cryotherapy gel wrap around the affected lower leg skin, or compression and elevated the legs on a special pillow each evening at bedtime. The standard care group wore compression and elevated the legs only. Laboratory pre- and post-measures included microcirculation measures of skin temperature with a thermistor, blood flow with a laser Doppler flowmeter, and venous refill time with a photoplethysmograph. Data were collected between 2008 2009 and analysed using descriptive statistics, paired t-tests or Wilcoxon signed ranks tests, logistic regression analyses, and mixed model analyses. Fifty-seven participants (treatment = 28; standard care = 29) completed the study. The mean age was 62 years, 70% female, 50% African American. In the final adjusted model, there was a statistically significant decrease in blood flow between the two groups (-6.2[-11.8; -0.6], P = 0.03). No statistically significant differences were noted in temperature or venous refill time. Study findings suggest that cryotherapy improves blood flow by slowing movement within the microcirculation and thus might potentially provide a therapeutic benefit to prevent leg ulcers.

Anterior knee pain after total knee arthroplasty: does it correlate with patellar blood flow?

Total knee arthroplasty (TKA) disturbs patellar blood flow, an unintended accompaniment to TKA that may be a cause of postoperative anterior knee pain. We examine whether disrupted patellar blood flow correlates with anterior knee pain following TKA. In 50 patients (21 men, 29 women) undergoing TKA, we compared patellar blood flow at flexions 0° to 30°, 60°, 90°, and 110° before and after medial parapatellar arthrotomy to pre- and postoperative anterior knee pain scores by means of a laser Doppler flowmeter (LDF) probe. Anterior knee pain was assessed using the pain intensity numeric rating scale (NRS) of 0-10 (0-no, 10-worst pain). Based on the NRS pain values, patients were divided into two main groups: group A (n = 34) with no pain or discomfort (NRS range 0-4) and group B (n = 16) with anterior knee pain (NRS range 5-10). Patients of group B demonstrated a significant decrease in blood flow before arthrotomy at flexions from 0° to 90°, and 110° and from 0° to 60°, 90°, and 110° after arthrotomy. For group A, a significant decrease in blood flow was detected at flexions from 0° to 90°, and 110° before and after arthrotomy. For both groups, medial arthrotomy did not have a statistically significant influence on patellar blood flow (margin of significance P < 0.05). Prior to TKA, 16 of the 50 patients of group B (32%) complained of anterior knee pain (mean NRS 7.1 ± 1.7). At 2-year follow-up, pain significantly decreased (NRS 3.1 ± 2.1) and only 4 of the 16 patients (25%) complained of moderate anterior pain (average NRS 5.7 ± 0.5), while 8 of 16 (50%) patients reported discomfort (mean NRS 3.5 ± 1.8) around the patella. Patients in group A also demonstrated a significant decrease in pain intensity (from NRS 1.5 ± 1.4 preoperatively to NRS 0.4 ± 1.5 at 2-year follow-up). Statistical analysis demonstrated no statistically significant correlation between pre-arthrotomy/post-arthrotomy patellar blood flow and the presence of preoperative and postoperative anterior knee pain. Only the degree of flexion had an influence on patellar blood flow. Medial arthrotomy had no direct significant effect on patellar blood flow, and the diminished blood flow did not correlate with postoperative anterior knee pain. However, a significant correlation was revealed between patellar blood flow and the degree of flexion: in almost a quarter of patients, blood flow dropped to zero at flexions of 100° and above.