Perfusion Units Research Articles

Retinoprotective Effect of 2-Ethyl-3-hydroxy-6-methylpyridine Nicotinate

An important task of pharmacology is to find effective agents to improve retinal microcirculation and resistance to ischemia. The purpose of the study is to pharmacologically evaluate the retinoprotective effect of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate in a rat model of retinal ischemia–reperfusion. A retinal ischemia–reperfusion model was used, in which an increase in intraocular pressure (IOP) to 110 mmHg was carried out within 30 min. The retinoprotective effect of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate at a dose of 3.8 mg/kg, in comparison with nicotinic acid at a dose of 2 mg/kg and emoxipine at a dose of 2 mg/kg, was estimated by the changes in the eye fundus during ophthalmoscopy, the retinal microcirculation level with laser Doppler flowmetry (LDF), and electroretinography (ERG) after 72 h of reperfusion. The use of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate prevented the development of ischemic injuries in the fundus and led to an increase in the retinal microcirculation level to 747 (median) (lower and upper quartiles: 693;760) perfusion units (p = 0.0002) in comparison with the group that underwent no treatment. In the group with the studied substance, the b-wave amplitude increased significantly (p = 0.0022), and the b/a coefficient increased reliably (p = 0.0002) in comparison with the group with no treatment. Thus, 2-ethyl-3-hydroxy-6-methylpyridine nicotinate has established itself as a potential retinoprotector.

Two apples a day lower serum cholesterol and improve cardiometabolic biomarkers in mildly hypercholesterolemic adults: a randomized, controlled, crossover trial

ABSTRACTBACKGROUNDApples are rich in bioactive polyphenols and fiber. Evidence suggests that consumption of apples or their bioactive components is associated with beneficial effects on lipid metabolism and other markers of cardiovascular disease (CVD). However, adequately powered randomized controlled trials are necessary to confirm these data and explore the mechanisms.OBJECTIVEWe aimed to determine the effects of apple consumption on circulating lipids, vascular function, and other CVD risk markers.METHODSThe trial was a randomized, controlled, crossover, intervention study. Healthy mildly hypercholesterolemic volunteers (23 women, 17 men), with a mean ± SD BMI 25.3 ± 3.7 kg/m2 and age 51 ± 11 y, consumed 2 apples/d [Renetta Canada, rich in proanthocyanidins (PAs)] or a sugar- and energy-matched apple control beverage (CB) for 8 wk each, separated by a 4-wk washout period. Fasted blood was collected before and after each treatment. Serum lipids, glucose, insulin, bile acids, and endothelial and inflammation biomarkers were measured, in addition to microvascular reactivity, using laser Doppler imaging with iontophoresis, and arterial stiffness, using pulse wave analysis.RESULTSWhole apple (WA) consumption decreased serum total (WA: 5.89 mmol/L; CB: 6.11 mmol/L; P = 0.006) and LDL cholesterol (WA: 3.72 mmol/L; CB: 3.86 mmol/L; P = 0.031), triacylglycerol (WA: 1.17 mmol/L; CB: 1.30 mmol/L; P = 0.021), and intercellular cell adhesion molecule-1 (WA: 153.9 ng/mL; CB: 159.4 ng/mL; P = 0.028), and increased serum uric acid (WA: 341.4 μmol/L; CB: 330 μmol/L; P = 0.020) compared with the CB. The response to endothelium-dependent microvascular vasodilation was greater after the apples [WA: 853 perfusion units (PU), CB: 760 PU; P = 0.037] than after the CB. Apples had no effect on blood pressure or other CVD markers.ConclusionsThese data support beneficial hypocholesterolemic and vascular effects of the daily consumption of PA-rich apples by mildly hypercholesterolemic individuals.This trial was registered at clinicaltrials.gov as NCT01988389.

Evaluation of a replanted finger and measuring its perfusion changes to predict its viability by laser speckle contrast imaging

<p class="abstract"><strong>Background:</strong> This research aims to monitor the microcirculation of the replanted finger, which was entirely severed by using laser speckle contrast imaging (LSCI) for early detection and revision of vascular compromise for successful finger replantation.</p><p class="abstract"><strong>Methods:</strong> These six months of research was taken for a survey of 40 cases of replanted fingers of patients of distinct ages and sex. Scrutinizing was done postoperatively by LSCI, every hourly for seven days, to assess changes in blood perfusion both in replanted fingers and healthy ones and analyzed graphically. </p><p class="abstract"><strong>Results:</strong> Initially, from postoperative d=0 to d=2, the perfusion value was at baseline, which ranged 40±15 perfusion unit (PU), showing a wave-like curve, then gradually increased up to 350±50 PU or above in case of those which survived successfully, showing continuous peak slope. However, a gradual drop in perfusion, <35 PU from d=2 or d=3, was seen in those despite undergoing heparinized finger pin-prick bleeding therapy and failed to thrive, showing a downslope curve. Whereas some were under meticulous observation, which flourished lately. Concurrently, a comparison was made with the healthy fingers’ of the same patient, ranging from 200±50 to as high as 400±50 or above. Clinical correlation, as well as perfusion readings of LCSI, were done simultaneously.</p><p class="abstract"><strong>Conclusions:</strong> LSCI provides sensitive and reproducible finger microcirculation measurements and is reliable in predicting reductions in blood perfusion induced by venous or arterial occlusion. It is, therefore, an informative device to detect microvascular compromise during and after replantation surgery.</p>

Intraoperative Laser Speckle Contrast Imaging in DIEP Breast Reconstruction: A Prospective Case Series Study.

Introduction:Laser speckle contrast imaging (LSCI) is a laser-based perfusion imaging technique that recently has been shown to predict ischemic necrosis in an experimental flap model and predicting healing time of scald burns. The aims were to investigate perfusion in relation to the selected perforator during deep inferior epigastric artery perforator (DIEP) flap surgery, and to evaluate LSCI in assisting of prediction of postoperative complications.Methods:Twenty-three patients who underwent DIEP-procedures for breast reconstruction at 2 centers were included. Perfusion was measured in 4 zones at baseline, after raising, after anastomosis, and after shaping the flap. The perfusion in relation to the selected perforator and the accuracy of LSCI in predicting complications were analyzed.Results:After raising the flap, zone I showed the highest perfusion (65 ± 10 perfusion units, PU), followed by zone II (58 ± 12 PU), zone III (53 ± 10 PU), and zone IV (45 ± 10 PU). The perfusion in zone I was higher than zone III (P = 0.002) and zone IV (P < 0.001). After anastomosis, zone IV had lower perfusion than zone I (P < 0.001), zone II (P = 0.01), and zone III (P = 0.02). Flaps with areas <30 PU after surgery had partial necrosis postoperatively (n = 4).Conclusions:Perfusion is highest in zone I. No perfusion difference was found between zones II and III. Perfusion <30 PU after surgery was correlated with partial necrosis. LSCI is a promising tool for measurement of flap perfusion and assessment of risk of postoperative ischemic complications.

Quantitative indicators of microcirculation of the skin of the lower extremities

Purpose of the study. To study the quantitative indicators of microcirculation and perfusion of the skin of the lower extremities, taking into account the angiosomal theory.&#x0D; &#x0D; Materials and methods. We studied the microcirculation of the skin of the lower extremities in 31 people, taking into account the angiosomal approach without pathology of the cardiovascular system on the device Easy-LDI company AIMAGO SA (Switzerland).&#x0D; Results. We found that the highest rates of perfusion units on the thigh were found in the pool of the sciatic and posterior arteries, the lowest – in the pool of the deep femoral artery and popliteal artery. On the shin, the highest rates of microcirculation are found in the pool of the posterior tibial artery, the lowest – on the foot.&#x0D; Having such an objective quantitative perfusion index, it is easy to determine the occlusion of the arteries corresponding to the angiosomes, areas of the skin of the lower extremity and to quantify the results of the treatment.&#x0D; Conclusions. The developed indicators of skin perfusion of angiosomes of the lower extremities can normally form the basis for diagnosing the degree of stenosis of the main arteries, serve as an indication for direct and indirect methods of revascularization in obliterating diseases of the arteries of the lower extremities and quantify immediate and long-term treatment.

A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis

Increased cardiovascular (CV) morbidity and mortality have been found in rheumatoid arthritis (RA). Tumour necrosis factor α (TNF-α) inhibitors may improve vascular function. In the first part of this study, we determined microcirculation during postoocclusive reactive hyperemia (PORH) representing endothelial function. In a nonselected population (n = 46) we measured flow-mediated vasodilation (FMD) of the brachial artery and laser Doppler flow (LDF) by ultrasound. Among LDF parameters, we determined TH1 (time to half before hyperemia), TH2 (time to half after hyperemia), Tmax (time to maximum) and total hyperemic area (AH). We measured von Willebrand antigen (vWF:Ag) by ELISA. In the second part of the study, we assessed the effects of adalimumab treatment on microcirculatory parameters in 8 early RA patients at 0, 2, 4, 8 and 12 weeks. We found significant positive correlations between FMD and LDF Tmax (R = 0.456, p = 0.002), FMD and TH2 (R = 0.435, p = 0.004), and negative correlation between vWF:Ag and Tmax (R = − 0.4, p = 0.009) and between vWF:Ag and TH2 (R = − 0.446, p = 0.003). Upon adalimumab therapy in early RA, TH2 times improved in comparison to baseline (TH2baseline = 26.9 s vs. TH24weeks = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH28weeks = 40.5, p = 0.026; TH212weeks = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AHbaseline = 1599 Perfusion Units [PU] vs. AH8weeks = 2724 PU, p = 0.045). The PORH test carried out with LDF is a sensitive option to measure endothelial dysfunction. TH1 and TH2 may be acceptable and reproducible markers. In our pilot study, treatment with adalimumab exerted favorable effects on disease activity, endothelial dysfunction and microcirculation in early RA patients.

Improved endothelial-dependent and endothelial-independent skin vasodilator responses following remote ischemic preconditioning

One week of daily remote ischemic preconditioning (RIPC) improves cutaneous vasodilatory (VD) function. However, the underlying mechanisms and the number of sessions needed to optimize this adaptive response remain unclear. We hypothesized that the responses to localized heating of the skin will be greater after 2 wk as opposed to 1 wk of RIPC. Furthermore, 2 wk of repeated RIPC will augment cutaneous VD responses to thermal and pharmacological stimuli. In methods, twenty-four participants (24 ± 2 yr; 13 men, 11 women) performed repeated RIPC (7 daily sessions over 1 wk, n = 11; 12 sessions over 2 wk, n = 13), consisting of four repetitions of 5 min of arm blood flow occlusion separated by 5 min reperfusion. Laser speckle contrast imaging was used to measure skin blood flow responses, in perfusion units (PU), to local heating (Tloc = 42°C), acetylcholine (ACh), and sodium nitroprusside (SNP) before and after repeated RIPC. Data were expressed as cutaneous vascular conductance (CVC, in PU/mmHg). In results, the VD response to local heating increased after RIPC (∆CVC from baseline; 1 wk: 0.94 ± 0.11 to 1.19 ± 0.15, 2 wk: 1.18 ± 0.07 to 1.33 ± 0.10 PU/mmHg; P < 0.05) but the ∆CVC did not differ between weeks. SNP-induced VD increased after 2 wk of RIPC (∆CVC; 0.34 ± 0.07 to 0.63 ± 0.11 PU/mmHg; P < 0.05), but ACh-induced VD did not. In conclusion, repeated RIPC improves local heating- and SNP-mediated cutaneous VD. When compared with 1 wk of RIPC, 2 wk of RIPC does not induce further improvements in cutaneous VD function.NEW & NOTEWORTHY Repeated RIPC increases the cutaneous vasodilatory response to local heating and to sodium nitroprusside but not to acetylcholine. Thus, endothelial-independent and local heating-mediated cutaneous vasodilation are improved following RIPC. However, 2 wk of RIPC sessions are not more effective than 1 wk of RIPC sessions in enhancing local heating-mediated cutaneous vasodilation.

Visualizing and quantifying the impact of reactive hyperemia on cutaneous microvessels in humans.

The mechanisms underlying reactive hyperemia (RH) responses in microvessels are poorly understood. Previous assessment tools have not been capable of directly visualizing microvessels during physiological stimulation in humans. Optical coherence tomography (OCT) is capable of imaging and quantifying subcutaneous microvessels as small as ~30 µm. In this study we use OCT to visualize and quantify skin microvascular changes in response to RH for the first time in humans. We also assessed the reproducibility of this technique. OCT and laser Doppler flowmetry (LDF) were used simultaneously to scan cutaneous microvessels in 10 young healthy subjects on 2 days. We applied a speckle decorrelation algorithm to assess OCT images and calculated flow rate, speed, diameter, and density parameters. Measures were obtained at rest (baseline) and 30-s following a 5-min cuff inflation (RH). All data were compared between days. The RH stimulus significantly increased (P < 0.0001) OCT-derived microvascular diameter (37.6 ± 3.4 vs. 44.5 ± 5.2 µm), flow rate (82.4 ± 23.4 vs. 240.1 ± 58.6 pl/s), speed (48 ± 5.7 vs. 101.5 ± 17.1 µm/s), density (5.1 ± 1.7 vs. 14.6 ± 2.6%), and also LDF-derived flux (12.3 ± 5.7 vs. 31.6 ± 9.1 perfusion units). At baseline, OCT-derived diameter (r = 0.55), flow rate (r = 0.64), speed (r = 0.55), and density (r = 0.75) showed significant between-day correlations (P < 0.05), as did LDF results (r = 0.74). In response to RH, OCT-derived diameter (r = 0.63) and density (r = 0.64) showed significant correlations (P < 0.05), whereas flow rate (r = 0.45), speed (r = 0.43), and LDF (r = 0.26) were less reproducible. Our study is novel in that it establishes the feasibility of using OCT to visualize and quantify microvascular structure and function responses to RH in humans.NEW & NOTEWORTHY This study describes the first evidence in humans that optical coherence tomography provides direct visualization and comprehensive quantification of cutaneous microvascular hemodynamics as a response to reactive hyperemia. This imaging technique will greatly improve human cutaneous microvascular assessment in physiological and clinical settings.

Clinical efficacy of bowel perfusion assessment during laparoscopic colorectal resection using laser speckle contrast imaging: A matched case-control study.

Disadvantages of bowel perfusion assessment with indocyanine green fluorescence angiography include the need for a fluorophore and the subjective nature of the assessment. This study was performed to evaluate the clinical efficacy of bowel perfusion assessment using laser speckle contrast imaging (LSCI) during laparoscopic colorectal surgery. The study population comprised the first 27 consecutive patients who underwent laparoscopic left-sided colorectal resection with intraoperative perfusion assessment using LSCI. The operative outcomes of these patients were compared with those of a matched group of patients without perfusion assessment. We analyzed the flux data expressed in laser speckle perfusion units. After propensity score matching, we found no significant between-group differences in the patients' characteristics with the exception of the cancer stage. No patients undergoing LSCI perfusion assessment developed anastomotic leakage, but five (18.5%) patients in the control group did, at a significantly higher rate in male patients (P = .042). There were no significant differences in other operative outcomes. The laser speckle perfusion unit values after ligating marginal vessels were significantly lower than before ligation (P < .01). With respect to anastomotic leakage, LSCI may improve patient outcomes after colorectal surgery. This technique appears to be a superior tool with the advantages of measurement repeatability and quantitativity and no need for a fluorophore.

Evaluating the Far-Infrared Radiation Bioeffects on Micro Vascular Dysfunction, Nervous System, and Plantar Pressure in Diabetes Mellitus.

The most frequent clinical complication is diabetes. Diabetes is characterized by elevated blood glucose levels resulting in sensory nerve damage or lesions. Diabetic foot wounds are often slow to heal and require medical attention and monitoring. This study evaluates the effect of far-infrared radiation on the microcirculation and plantar pressure in the diabetic foot. Ten diabetics and 4 nondiabetics were recruited in this study. The diabetic group was examined before and after the intervention in each month for 3 consecutive months. Four nondiabetic groups were also measured before and after the intervention for 2 weeks in each month. The surface temperature and blood flow in the diabetic foot was significantly improved (temperature: 32.1 ± 2.3°C vs 33.5 ± 2.2°C, P < .05; blood flow image: 118.3 ± 58.1 PU [perfusion unit] vs 50.4 ± 4.3 PU, P < .05). The sympathetic nerve activity index LF also increased from 40.8 ± 18.6% to 61.8 ± 13.5% (P = .07) in the second month. Plantar pressure tended to increase in the third month. This might indicate that far-infrared radiation could affect the mechanical properties of the plantar foot soft tissue. These results indicated that the effects of far-infrared radiation would improve blood circulation and change the soft tissue properties in the diabetic foot.

A study of osteoprotective effect of l-arginine, l-norvaline and rosuvastatin on a model of hypoestrogen-induced osteoporosis in rats

Effect on the microcirculatory bed of the bony tissue is one of promising approaches to treatment of osteoporosis.&#x0D; Aim. To study anti-osteoporotic properties of endothelioprotectors: L-arginine, L-norvaline and rosuvastatin.&#x0D; Materials and Methods. Osteoprotective properties of L-arginine, L-norvaline and rosuvastatin, and also of a reference drug– strontium ranelate – were studied on 152 female rats of Wistar line using a model of hypoestrogen-induced osteoporosis. Anti-osteoporotic and endothelioprotective effect of the drugs were evaluated by laser dopplerflowmetry (LDF) of the proximal metaphysis of the femoral bone, morphometry of trabeculae of bone, and also by calculation of the coefficient of endothelial dysfunction.&#x0D; Results. LDF showed that maximal increase in microcirculation of the proximal metaphysis of the femoral bone, in comparison with animals with untreated osteoporosis (61.52±3.74 perfusion units, PU) was achieved with L-norvaline (115.25±5.36 PU, p&lt;0.001) and rosuvastatin (106.57±5.22 PU, p&lt;0.001), less expressed effect was demonstrated by L-arginine (98.10±4.48 PU, p&lt;0.001) and a reference drug – strontium ranelate (86.49±4.99 PU). A similar tendency was observed in morphometry of trabeculae of bone: in the group with untreated osteoporosis the diameter of trabeculae was 61.68±1.24 µm, in the group with use fL-norvaline – 91.86±1.8 µm (p&lt;0.001), in the group with use of L-arginine – 86.64±1.39 µm (p&lt;0.001) and in the group with use of strontium ranelate – 89.08±1.09 µm.&#x0D; Conclusion. L-arginine and L-norvaline and also rosuvastatin possess the property of improving a morphofunctional condition of bone tissue and may be recommended for further preclinical study.

Assessment of compromised parasternal skin perfusion after left internal mammary artery harvesting with a novel laser Doppler imaging.

Our aim was to investigate the impact of the non-skeletonized (pedicled) versus the skeletonized left internal mammary (LIMA) harvesting technique on the postoperative sternal and parasternal skin perfusion in patients undergoing coronary artery bypass grafting (CABG), as compared to patients undergoing non-CABG heart surgery. We included 142 patients who underwent non-bypass (N.=39) or CABG surgery (N.=103). CABG cases were differentiated according to the LIMA harvesting technique: skeletonized (N.=74) or non-skeletonized (N.=29). Parasternal and sternal skin perfusion measurements via a Laser Doppler Imaging tool were performed on the preoperative day and 5-7 days postoperatively, using a grid of 15 spatially segregated measurement points across the chest and normalization to a distinct reference point. Data were analyzed retrospectively. In the CABG group, the non-skeletonized LIMA harvesting resulted in a near-significant (P=0.057, two-sided Student t-test, 95% CI -[0.111, 0.002]), and the skeletonized LIMA harvesting in a significant (P< 0.001, 95% CI [-0.096, -0.032]) post-surgical decrease of left-sided parasternal skin perfusion in arbitrary perfusion units (APU), as compared to right-sided parasternal skin perfusion. No corresponding differences were found for the non-bypass group (P=0.5, 95% CI [-0.065, 0.033]). The harvesting techniques did not yield significantly different post-surgical parasternal skin perfusion measures in the CABG group (P=0.6). Measurement of parasternal skin perfusion using Laser Doppler Imaging is feasible. Both harvesting techniques resulted in a reduced parasternal/sternal skin perfusion upon removal of the internal mammary artery.

Chronic Hindlimb Ischemia Assessment; Quantitative Evaluation Using Laser Doppler in a Rodent Model of Surgically Induced Peripheral Arterial Occlusion.

Therapeutic neoangiogenesis (TNA) holds promise as a treatment for peripheral arterial disease. Nevertheless, proper tools for in vivo pre-clinical investigation of different TNA approaches and their effects are still lacking. Here we describe a chronic ischemic hindlimb model in rats using laser Doppler quantitative evaluation of tissue perfusion. Male Wistar rats (n = 20), aged between 6–8 months, with an average weight of 287 ± 26.74 g, were used. Animals were divided into two experimental groups: group A (n = 17; hindlimb chronic ischemia model) and group B (n = 3; control). Hindlimb ischemia was induced by concomitant ligation of the right femoral and popliteal artery. Evaluation of tissue perfusion was quantified in perfusion units (PU) on a scale from 0 to 500 (500 PU = maximal detectable perfusion) by laser Doppler analysis at day 0, day 15 and day 30 after induction of ischemia. Induction of chronic ischemia in the rat hindlimb by concomitant ligation of the femoral and popliteal artery can be readily obtained but requires basic microsurgical skills. Laser Doppler analysis has shown unaltered ischemia levels throughout the study (129,17 PU ± 3.13 day 0 vs. 130,33 PU day 30 ± 3,27, p = not significant (n.s.)). We demonstrate a simple and reproducible model of chronic hindlimb ischemia in rats, with stable tissue perfusion levels that are accurately quantified using laser Doppler technology. Hence, this model can represent a valid tool for further studies involving therapeutic neoangiogenesis.

Vascular endothelial function is improved after active mattress use.

Active mattresses are used to prevent, treat and relieve pressure ulcers (PU) by intermittent contact pressure/relief. However, no studies have directly assessed the vascular endothelial response to long-term active mattress use. This study investigated the hypothesis that eight weeks use of an active mattress would lead to improvements in vascular endothelial function in healthy participants. Physiological parameters of baseline skin temperature (BskT), resting blood flow (RBF) and endothelial function as measured using post-occlusive reactive hyperaemia (PORH), were assessed at baseline (week 0); following eight weeks of sleeping on an active mattress, and after an eight week washout period (at week 16). We recruited 10 healthy participants (four male, age 52.7±8.5 years, six female age 51.8±17.5 years). Following active mattress use RBF, PORH and BskT at the hallux pulp increased by 336%, 197% and 3.5ºC, respectively. Mean values increased from 24.3±38.3 perfusion units to 106.0±100.3 perfusion units (p=0.021) and from 13,456±10,225 to 40,252±23,995 perfusion units x seconds (p=0.003) and from 22.9±2.5ºC to 26.4±1.9ºC (p<0.001), respectively. Active mattress use for eight weeks leads to significant improvements in RBF, PORH, and BskT. These results suggest that active mattress use can improve endothelial function. Future research is required to explore the potential of active mattress use in the treatment and management of diseases and conditions that would benefit from an improved endothelial function.

Dexmedetomidine reduces norepinephrine requirements and preserves renal oxygenation and function in ovine septic acute kidney injury

Norepinephrine exacerbates renal medullary hypoxia in experimental septic acute kidney injury. Here we examined whether dexmedetomidine, an α2-adrenergic agonist, can restore vasopressor responsiveness, decrease the requirement for norepinephrine and attenuate medullary hypoxia in ovine gram-negative sepsis. Sheep were instrumented with pulmonary and renal artery flow probes, and laser Doppler and oxygen-sensing probes in the renal cortex and medulla. Conscious sheep received an infusion of live Escherichia coli for 30 hours. Eight sheep in each group were randomized to receive norepinephrine, norepinephrine with dexmedetomidine, dexmedetomidine alone or saline vehicle, from 24-30 hours of sepsis. Sepsis significantly reduced the average mean arterial pressure (84 to 67 mmHg), average renal medullary perfusion (1250 to 730 perfusion units), average medullary tissue pO2 (40 to 21 mmHg) and creatinine clearance (2.50 to 0.78 mL/Kg/min). Norepinephrine restored baseline mean arterial pressure (to 83 mmHg) but worsened medullary hypoperfusion (to 330 perfusion units) and medullary hypoxia (to 9 mmHg). Dexmedetomidine (0.5 μg/kg/h) co-administration significantly reduced the norepinephrine dose (0.8 to 0.4 μg/kg/min) required to restore baseline mean arterial pressure, attenuated medullary hypoperfusion (to 606 perfusion units), decreased medullary tissue hypoxia (to 29 mmHg), and progressively increased creatinine clearance (to 1.8 mL/Kg/min). Compared with vehicle time-control, dexmedetomidine given alone significantly prevented the temporal reduction in mean arterial pressure, but had no significant effects on medullary perfusion and oxygenation or creatinine clearance. Thus, in experimental septic acute kidney injury, dexmedetomidine reduced norepinephrine requirements, attenuated its adverse effects on the renal medulla, and maintained renal function.

SAT-143 MILD HYPERCAPNIA DURING MAJOR SURGERY, A POSSIBLE STRATEGY TO PREVENT RENAL MEDULLARY HYPOXIA AND THE DEVELOPMENT ACUTE KIDNEY INJURY

Acute kidney injury (AKI) is a common complication of major surgery that increases short- and long-term morbidity and mortality. There is emerging evidence that decreased renal medullary perfusion, resulting in hypoxia, contributes to the development of AKI during prolonged surgery. Since hypercapnia can provide a degree of organ protection, possibly due to its vasodilator effects, we investigated whether increases in arterial carbon dioxide level (PaCO2) improve global and regional kidney oxygenation in anesthetised sheep. In addition, positive end expiratory pressure (PEEP) is used to increase oxygenation, but it also decreases cardiac output and may therefore reduce renal perfusion and oxygenation. Thus, we determined the effects of PEEP (0, 5, 10, 15 and 20 cmH2O for 15 min), and PEEP with mild hypercapnia (PaCO2 45-55mmHg), on renal perfusion and oxygenation. In Merino ewes, surgery was performed to implant pulmonary and renal artery flow probes and laser-Doppler and oxygen-sensing probes in the renal medulla and cortex and to cannulate a renal vein. In anaesthetised sheep (isoflurane 2.5%), FiO2 was held at 0.4 and respiratory rate was changed to achieve target PaCO2 (normocapnia 35-45, mild hypercapnia 45-55 and severe hypercapnia 55-65 mmHg) for periods of 20 minutes, in random order. PEEP was held at (0, 5, 10, 15 and 20 cm H2O) for periods of 15 min during normocapnia and mild hypercapnia. Increases in PaCO2 from normocapnia, to mild and severe hypercapnia significantly increased medullary PO2 (39.1±5.5, 48.6±4.2 and 51.9±4.8 mmHg, respectively) and perfusion (336±66, 449±72 and 453±82 blood perfusion units, respectively). There were no changes in cortical perfusion or PO2, renal blood flow or renal oxygen delivery. During normocapnia, PEEP decreased cardiac output, renal blood flow, renal oxygen delivery, medullary perfusion (342±101 to 243±64 blood perfusion units (BPU)) and medullary PO2 (33.5±5.4 to 22.6±8.9 mmHg). Mild hypercapnia, for 30 min before and during PEEP, prevented the PEEP-induced decreases in medullary perfusion (586±165 to 491±93 BPU) and PO2 (54.6±7.8 to 57.4±7.6 mmHg), despite reductions in cardiac output and renal blood flow. Under volatile anaesthesia, increases in PaCO2 caused progressive increases in renal medullary perfusion and oxygenation. PEEP had detrimental effects on cardiac output, renal blood flow and medullary perfusion and PO2. Mild hypercapnia prevented the PEEP-induced decreases in medullary perfusion and PO2. During prolonged major surgery, increasing PaCO2 to prevent decreases in renal medullary PO2 may be a useful strategy to reduce the incidence of post-operative AKI.

EFFECTS OF THE CHRONIC INHIBITION OF TYPE 5 PHOSPHODIESTERASE ON PENILE MICROVASCULAR ENDOTHELIAL REACTIVITY AND BLOOD PRESSURE IN HYPERTENSIVE PATIENTS WITH ERECTILE DYSFUNCTION

Objective: The primary aim of this study was to test penile endothelial microvascular function and blood pressure in patients with treated primary arterial hypertension, before and after a chronic oral treatment with sildenafil citrate (SIL). Design and method: This was a prospective, randomized, double blinded and crossover study, controlled against placebo (PLA), with 30 day washout between treatments. Penile endothelial-dependent microvascular reactivity of hypertensive patients (aged 57.4 ± 5.6 years, n = 50) was evaluated using cutaneous laser speckle contrast imaging (LSCI) before and after chronic administration of placebo or sildenafil (50 mg twice daily during 30 days). LSCI was coupled with the cutaneous iontophoresis of acetylcholine (ACh) using increasing anodal microcurrents (30–180 μA). The measurements of skin blood flow (arbitrary perfusion units, APU) were divided by values of mean arterial pressure to give the cutaneous vascular conductance (CVC) in APU/mmHg. Erectile function was evaluated using the Simplified International Index of Erectile Function (IIEF-5) score. 24 hour ambulatory blood pressure monitoring (ABPM) was performed using oscillometric devices (Spacelabs). Results: IIEF-5 scores significantly increased after SIL [18(16–20) and 21.5(19.75–23); P < 0.0001] but not after PLA [18(14.75–19.25) and 17.84 ± 3.88; P = 0.16]. The basal values of CVC in the penis increased significantly after SIL (P = 0.004), but not after PLA (P = 0.86). Maximum CVC values after cutaneous ACh administration increased only with SIL treatment (P = 0.001); after PLA (P = 0.63). The area under the curve of penile microvascular vasodilation induced by ACh also significantly increased after SIL (P = 0.003) but not after PLA (P = 0.98). Finally, 24 hours diastolic arterial pressure significantly decreased after SIL (83.5 ± 8.9 and 79.9 ± 8.2; P = 0.0003) but not after PLA (P = 0.27). The decrease in 24-hour systolic blood pressure was not statistically significant after SIL or PLA, but it was significant in the office measurements after treatment with sildenafil [136(130–144.3) and 131.5 (119–139.3); P = 0.02] but not with placebo [136(130.8–145) and 134.7 ± 13;P = 0.23]. Conclusions: Penile endothelium-dependent microvascular reactivity and erectile function improved after chronic treatment with sildenafil. The treatment also reduced blood pressure suggesting that, in addition to the effects on erectile function, chronic treatment with sildenafil could improve blood pressure control.

Assessment of microcirculation in the diabetic foot with laser speckle contrast imaging

Objective: A major challenge for treating diabetic foot ulcers is estimating the severity of ischemia, as the currently used non-invasive diagnostic techniques provide relatively poor prognostic values. Laser speckle contrast imaging (LSCI) is a promising non-invasive technique to assess microcirculation. Our aim was to investigate the stability and reproducibility of LSCI for the assessment of microcirculation in the diabetic foot, the relation of LSCI results to currently used non-invasive blood pressure measurements, and the ability of LSCI to discriminate between the degrees of ischemia. Approach: Thirty-three participants with diabetic foot ulcers were included in this prospective, single centre, observational cohort study that was conducted in the Netherlands. They were classified as non-ischemic, ischemic or critical-ischemic based on criteria formulated in the international guidelines. Two clinicians performed LSCI scans of the foot, consisting of baseline measurements, followed by two stress tests (post-occlusion peak and elevation test). With three measurement conditions and five regions of interest of the foot per patient, a total of 15 measurements were available for analyses. Main results: The intra-observer agreement of LSCI was high (interclass correlation coefficient (ICC) = 0.711–0.950; p < 0.001) for all 15 measurements. The inter-observer agreement was high (ICC = 0.728–0.861; p ⩽ 0.001) for 10 measurements and moderate (ICC = 0.476–0.570; p ⩽ 0.005) for the remaining five measurements. The inter-assessor agreement was high and significant (ICC = 0.857–0.996; p ⩽ 0.001) for all measurements. Correlation between LSCI and non-invasive blood pressure measurements was low (ICC = −0.272–0.582). During both stress tests, microcirculation was significantly lower in critical-ischemic feet compared to non-ischemic feet (67.5 perfusion units (PU) versus 96.3 PU and 41.0 PU versus 63.9 PU; p < 0.05). Significance: LSCI is a stable and reproducible technique for assessment of microcirculation in people with diabetic foot ulcers and shows significant differences between non-ischemic, ischemic and critical-ischemic patient populations.

Furosemide reverses medullary tissue hypoxia in ovine septic acute kidney injury.

In experimental sepsis, the rapid development of renal medullary hypoxia precedes the development of acute kidney injury (AKI) and may contribute to its pathogenesis. We investigated whether inhibiting active sodium transport and oxygen consumption in the medullary thick ascending limb with furosemide attenuates the medullary hypoxia in experimental septic AKI. Sheep were instrumented with flow probes on the pulmonary and renal arteries and fiber optic probes to measure renal cortical and medullary perfusion and oxygen tension (Po2). Sepsis and AKI were induced by infusion of live Escherichia coli. At 24 h of sepsis there were significant decreases in renal medullary tissue perfusion (1,332 ± 233 to 698 ± 159 blood perfusion units) and Po2 (44 ± 6 to 19 ± 6 mmHg) (both P < 0.05). By 5 min after intravenous administration of furosemide (20 mg), renal medullary Po2 increased to 43 ± 6 mmHg and remained at this normal level for 8 h. Furosemide caused transient increases in fractional excretion of sodium and creatinine clearance, but medullary perfusion, renal blood flow, and renal oxygen delivery were unchanged. Urinary F2-isoprostanes, an index of oxidative stress, were not significantly changed at 24 h of sepsis but tended to transiently decrease after furosemide treatment. In septic AKI, furosemide rapidly restored medullary Po2 to preseptic levels. This effect was not accompanied by changes in medullary perfusion or renal oxygen delivery but was accompanied by a transient increase in fractional sodium excretion, implying decreased oxygen consumption as a mechanism.

Ghrelin regulates sepsis‑induced rat acute gastric injury

Ghrelin, a peptide expressed in the gastric mucosa, has an essential role in sustaining the normal function of the digestive system. Sepsis is one of the primary causes of mortality in intensive care units and can lead to multiple organ dysfunction, especially in the gastrointestinal system. The aim of the present study was to explore the effect of ghrelin on gastric blood flow in a rat model of sepsis, as well as the effect of ghrelin on the expression of the apoptotic markers, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax), in gastric tissues. The sepsis model was established using cecal ligation and puncture (CLP). The expression levels of apoptosis-related factors in gastric epithelial cell were determined by immunohistochemistry, reverse transcription quantitative-PCR and western blotting. Collectively, the present results suggested that ghrelin administration attenuated sepsis symptoms induced by CLP. Blood flow in the stomach greater curvature was significantly higher in the CLP-induced sepsis group rats (284.3±95.7 perfusion units) compared with the sham operation group (317.8±5.2 perfusion units; P<0.05), whereas there was no difference between the CLP group treated with ghrelin (377.8±99.0 perfusion units) and the sham rats. Ghrelin administration also reduced the secretion of pro-inflammatory cytokines compared with the CLP-induced sepsis group rats. In addition, CLP significantly reduced the expression of Bcl-2 and enhanced the expression of the pro-apoptotic proteins, Bax and cleaved caspase-3; whereas, ghrelin application reversed the effects of CLP on these apoptosis-associated proteins. In conclusion, the present study revealed that ghrelin has the ability to increase blood flow in the gastrointestinal tract in a sepsis model and can also regulate the expressions of apoptosis-associated factors in gastric tissues. These results suggest that ghrelin could be a novel treatment for sepsis-induced gastric injury.