Constriction Of Blood Vessels Research Articles

EFEKTIFITAS KOMPRES HANGAT BASAH DAN KERING TERHADAP NYERI PUNGGUNG BAWAH PADA LANSIA DI WILAYAH KERJA PUSKESMAS TELEN KUTAI TIMUR KALIMANTAN TIMUR

Latar belakang: lansia yang ada di wilayah puskesmas Talen berjumlah 229 orang, terdapat 75 (32,75%) lansia mengalami nyeri punggung bawah. Kompres hangat basah dan kering merupakan salah satu terapi nonfarmakologi dalam mengurangi nyeri namun belum diketahui efektivitas diantara dua terapi tersebut.Tujuan: untuk mengetahui efektivitas antara kompres hangat basah dan kering terhadap nyeri punggung bawah pada lansia di wilayah kerja Puskesmas Telen. Metode penelitian: Quasy eksperiment denganpre and post test without control. Pengambilan sampel dilakukan dengan tehnik Quota Sampling, jumlah sampel sebanyak 32 responden yang dibagi menjadi 2 kelompok. Instrumen Numeric Rating Scale. Uji statistik Mann Whitney. Hasil: Rata-rata penurunan skala nyeri kompres hangat kering 1,94 dan basah 0,19 dengan P value 0,000 ≤ 0,05. Uji beda kompres hangat kering dan basah P value 0,48. Kesimpulan: Tidak ada perbedaan efektivitas kompres hangat basah dan kering terhadap nyeri punggung bawah pada lansia di wilayah kerja Puskesmas Telen. Saran: Untuk peneliti selanjutnya teknik pengambilan sampel menggunakan random agar memberi kesempatan yang sama.Kata kunci : Nyeri Punggung Bawah - Lansia - Kompres hangat basah dan kering

Transient Increase in Sympathetic Constriction of Mesenteric Arteries from High Fat Diet‐Fed Dahl Salt‐sensitive Female Rats

Obesity (BMI ≥ 30) is a risk factor for hypertension. Obesity‐associated hypertension is a risk factor for cardiovascular disease, stroke, type 2 diabetes and kidney failure. Hypertension is less common in premenopausal women compared to age‐matched men. This disparity fades away after the onset of menopause. Increased sympathoexcitation in the neuroeffector junction leads to increase in constriction of blood vessels. Differences in the mechanism/s neurogenic arterial constriction in male and female are not well understood. We hypothesized that sympathetic nerve activity in high fat diet‐induced hypertension is greater in male than female rat mesenteric arteries (MA). Rats were fed either control (C) or high fat (HF) diet beginning at 3 weeks of age, and used at 10, 17 and 24 weeks on diet. Body weight and systolic blood pressure (SBP) were measured weekly. HF males gained more weight than HF females at all time points. SBP was higher in HF rats compared to C rats in both sexes and across all time points. The estrus cycle stage was determined cytologically by vaginal lavage prior to euthanasia. Mesenteric arteries (Inner diameter; male=275–350 μm, female=245–315 μm) were harvested and mounted in a pressure (60 mmHg) myograph and inner diameter was measured continuously. MA contractile responses to electrical field stimulation (30 stimuli at 0.2–30 Hz) and drug applications were measured. Neurogenic constriction of MA from HF females was greater than HF males at 5 and 10 Hz at 10 wks, and at 5–30 Hz at 17 wks. At 24 wks the difference disappears. Constrictions caused by norepinephrine (NE) and ATP were similar in MA from HF male and female rats. Immunostaining for tyrosine hydroxylase (sympathetic nerve marker) and vesicular nucleotide transporter (ATP marker) revealed greater sympathetic nerve intensity in HF male than female rats at 10 and 24 wks. There was also greater intensity in MA from HF males than HF females at 10 and 17 wks. Moreover, HF males have higher NE and ATP nerve density than HF females at 10 and 17 but not for ATP at 24 wks. MA NE levels were similar in male and female rats. Prejunctional α2‐AR and NE transporter functions were not impaired in MA from HF Dahl salt‐sensitive rats. Taken together, despite sex differences in sympathetic nerve density in MA, we detected only transient sex differences in sympathetic neurogenic arterial constrictions. Contrary to our hypothesis, we found that HF females transiently have an upregulation of neurogenic sympathetic activity and this warrants further investigation into the mechanism.Support or Funding InformationResearch supported by PPG NIH Grant P01HL070687This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Angiotensin‐II‐Induced Increase in Blood Pressure in Female and Male Mice

The kidney regulates blood pressure by controlling urinary salt and water excretion. Angiotensin II (AngII), a key player in controlling blood pressure, constricts blood vessels, stimulates vasopressin and aldosterone release, stimulates thirst, and increases sodium absorption from the proximal tubule. All effects cause increased blood pressure. Sex differences in the regulation of arterial blood pressure involve events surrounding the renin‐angiotensin‐aldosterone system. Evidence generally supports a protective mechanism for females with AngII‐induced hypertension; although, conflicting evidence exists. The purpose of this study was to investigate sex differences in CD‐1 mice under AngII administration for a period of 10 days. We hypothesized that female mice would be protected from AngII‐induced increase in mean arterial pressure (MAP) compared to male mice and that the renal handling of salt and water contributes to this protection. Four‐week old CD‐1 mice were obtained from Envigo, Inc. (Indianapolis, IN). Two studies, one with females and one with males, were conducted. Mice were placed in metabolic cages and consumed normal diet and water, ad libitum, for 15 days. After the first 5 days, an Alzet™ minipump containing either AngII (n=5) or vehicle (n=5) was implanted subcutaneously in each mouse to ensure continuous AngII infusion (1 mg/kg/min). Daily measurements included MAP via the tail‐cuff method (Kent Scientific, CODA System), urinary output, and urinary sodium excretion. MAP (mmHg) was not different between females and males in the 5‐day control period (85.1 ± 3.7 vs 81.7 ± 4.0, respectively). AngII‐treatment increased MAP in both females and males (110.3 ± 4.4 and 105.8 ± 3.0, p<0.001, compared to respective control period). Interestingly, AngII‐treated females showed higher urine output than AngII‐treated males (9.7 ± 0.8 vs 7.4 ± 0.4 ml/day, p<0.05) and also had higher sodium excretion (242 mEq/day vs 166 mEq/day, p<0.01). Absolute food intake in females and males was not different, however, females consumed more food per body weight. We conclude that female mice are not protected from AngII‐induced increase in MAP compared to male mice for a 10‐day AngII infusion period. However, based on the sodium excretion data, protection may be observed later from increased urine and sodium output in females. Results suggest that the renal handling of salt and water could be an important determinant of sex differences in blood pressure regulation.Support or Funding InformationNational Institute of General Medical Sciences of National Institutes of Health through Grant Number 8P20GM103447This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Increased permeability of blood vessels after reversible electroporation is facilitated by alterations in endothelial cell-to-cell junctions

Delivery of electric field pulses, i.e. electroporation (EP), to tissues has been shown to have a blood flow modifying effect. Indeed, the diameter of blood vessels exposed to EP is immediately reduced resulting in blood flow abrogation, followed by an increase in vascular permeability. The main cause of the increased permeability remains unknown. The aim of this study was to determine whether the in vivo effects of EP on permeability of blood vessels are linked to the permeabilization of endothelial cells' membrane (EC) and/or disruption of cell-to-cell junctions. We used a dorsal window chamber model in C57Bl/6 mice coupled with multiphoton microscopy and fluorescently labelled antibodies against PECAM-1 (CD31) to visualize endothelial cell-to-cell junctions. Clinically validated EP parameters were used and behavior of cell-to-cell junctions, in combination with leakage of 70 kDa fluorescein isothiocyanate labelled dextran (FD), was followed in time. After EP, a constriction of blood vessels was observed and correlated with the change in the shape of ECs. This was followed by an increase in permeability of blood vessels for 70 kDa FD and a decrease in the volume of labelled cell-to-cell junctions. Both parameters returned to pre-treatment values in 50% of mice. For the remaining 50%, we hypothesize that disruption of cell-to-cell junctions after EP may trigger the platelet activation cascade. Our findings show for the first time in vivo that alterations in cell-to-cell junctions play an important role in the response of blood vessels to EP and explain their efficient permeabilization.

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Possible erythrocyte contributions to and exacerbation of the post-thrombolytic no-reflow phenomenon.

Reperfusion injury often occurs with therapeutic intervention addressing the arterial occlusions causing acute myocardial infarction and stroke. The no-reflow phenomenon has been ascribed to leukocyte plugging and blood vessel constriction in the microcirculation. To assess possible red cell contributions to post-thrombolytic no-reflow phenomenon. Blood clots were formed by recalcifying 1ml of citrated fresh human venous blood and then lysed by adding 1,000 units of streptokinase (SK) at several intervals within 1 hour. Red cell deformability was tested by both a microscopic photometric and a filtration technique, viscosity by a cone and plate viscometer, and erythrocyte aggregation by an optical aggregometer. Two sampling methods were devised for the microscopic photometric test, both of which indicated increases of erythrocyte stiffness after being lysed from the clot by SK. In accompanying experiments, the viscosity, aggregation and filterability of the post-lytic erythrocytes were assessed. Results indicated increased viscosity in Ringer's, decreased aggregation index and filterability through a 5 μm pore size Nuclepore membrane. Findings demonstrated that post-lytic changes in red cell deformability do occur which could contribute to the no-reflow phenomenon.

Muscle Contraction.

Muscle cells are designed to generate force and movement. There are three types of mammalian muscles-skeletal, cardiac, and smooth. Skeletal muscles are attached to bones and move them relative to each other. Cardiac muscle comprises the heart, which pumps blood through the vasculature. Skeletal and cardiac muscles are known as striated muscles, because the filaments of actin and myosin that power their contraction are organized into repeating arrays, called sarcomeres, that have a striated microscopic appearance. Smooth muscle does not contain sarcomeres but uses the contraction of filaments of actin and myosin to constrict blood vessels and move the contents of hollow organs in the body. Here, we review the principal molecular organization of the three types of muscle and their contractile regulation through signaling mechanisms and discuss their major structural and functional similarities that hint at the possible evolutionary relationships between the cell types.

Regulation, signalling and functions of hormonal peptides in pulmonary vascular remodelling during hypoxia.

Hypoxic state affects organism primarily by decreasing the amount of oxygen reaching the cells and tissues. To adjust with changing environment organism undergoes mechanisms which are necessary for acclimatization to hypoxic stress. Pulmonary vascular remodelling is one such mechanism controlled by hormonal peptides present in blood circulation for acclimatization. Activation of peptides regulates constriction and relaxation of blood vessels of pulmonary and systemic circulation. Thus, understanding of vascular tone maintenance and hypoxic pulmonary vasoconstriction like pathophysiological condition during hypoxia is of prime importance. Endothelin-1 (ET-1), atrial natriuretic peptide (ANP), and renin angiotensin system (RAS) function, their receptor functioning and signalling during hypoxia in different body parts point them as disease markers. In vivo and in vitro studies have helped understanding the mechanism of hormonal peptides for better acclimatization to hypoxic stress and interventions for better management of vascular remodelling in different models like cell, rat, and human is discussed in this review.

Gold nanospheres enhanced photothermal therapy in a rat model.

Efficient photothermal conversion of gold nanoparticles with strong light absorption suggests their wide use as selective photothermal agents in biomedical fields. The aim of this study is to investigate the use of gold nanospheres (GNPs) as exogenous visible light absorbers to improve laser treatment of port-wine stains. Thiol-terminated methoxypolyethylene glycol modified GNPs (PEG-GNPs) with peak extinction matching the visible light wavelength of the laser being used were synthesized. An in vitro capillary experiment was prepared to investigate the thermal response of blood vessels with and without injection of 4.54 mg PEG-GNPs in mice prior to irradiation by a frequency-doubled Nd:YAG laser at a wavelength of 532 nm. The in vitro results demonstrated that the photocoagulation size in blood vessels after exposed to laser light increased with the increment of concentration of PEG-GNPs in blood within a certain range. However, the unwanted thermal response (i.e., cavitation) occurred when the concentration of PEG-GNPs in blood was larger than 2.5 mg/ml. The in vivo results suggested that more obvious blood thermal response can be induced by laser light after injection of PEG-GNPs. After injection of 4.54 mg PEG-GNPs, laser radiant exposure required for thread-like constriction of blood vessels decreased from 12.5 to 9.8 J/cm2 with the pulse duration of 10 ms, from 15 to 11.85 J/cm2 with the pulse duration of 30 ms, respectively. This in vitro and in vivo experimental results show that PEG-GNPs combined with laser light could be a promising modality to reduce the radiant exposure required for obvious blood thermal response, thereby providing a potential strategy for improving the laser treatment of cutaneous vascular lesions. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

PEMBERIAN MILKSHAKE PISANG SEBELUM LATIHAN TERHADAP KELELAHAN DAN TEKANAN DARAH ATLET SEPAK BOLA

Background : Fatigue is affected by decreased muscle glycogen and decreased blood flow to muscle. In addition, dilation and constriction of blood vessels during exercise also affects blood pressure. Bananas are a source of carbohydrates and potassium. Carbohydrates are used to energy and potassium are used to regulate heart rate and maintain fluid and electrolyte balance. Calcium in milk can help muscle contraction during exercise.Objective : to determine the effect of banana milkshake on fatigue and blood pressure in football athletes.Methods : true experiment study with pre and post only control group design. Subjects of this study is 14 football athletes were randomly divided into 2 groups: the control group given banana and the treatment group given the banana milkshake. Fatigue at soccer athletes in PS Undip was measured with a harvard step test by calculating the Body efficiency index and blood pressure measured before and after the test. Data were analyzed by independent t-test and paired t-test.Results : Mean Body Efficiency Index (VO2max) before treatment in treatment group 89.85 ± 8.46 and after treatment 92.41 ± 9.813 and in control group before treatment 94.45 ± 11.596 and after treatment 99.01 ± 8.325. The difference of systolic and diastolic blood pressure in treatment group before treatment was 19.43 ± 22.44 and 0.00 ± 7.68 while in control group 19.28 ± 14.96 and 2.71 ± 10.68. After treatment in treatment group 30.57 ± 18.88 and 2.143 ± 10,023 while control group 13.43 ± 18.15 and 6.28 ± 18.98.Conclusion : There is no effect of banana milkshake on fatigue and blood pressure. Bananas are more effective than banana milkshakes.

Non-adrenergic vasoconstriction and vasodilatation of guinea-pig aorta by β-phenylethylamine and amphetamine – Role of nitric oxide determined with L-NAME and NO scavengers

Sympathomimetic and trace amines, including β-phenylethylamine (PEA) and amphetamine, increase blood pressure and constrict isolated blood vessels. By convention this is regarded as a sympathomimetic response, however, recent studies suggest trace amine-associated receptor (TAAR) involvement. There is also uncertainty whether these amines also release nitric oxide (NO) causing opposing vasodilatation. These questions were addressed in guinea-pig isolated aorta, a species not previously examined. Guinea-pig aortic rings were set up to measure contractile tension. Cumulative concentration-response curves were constructed for the reference α-adrenoceptor agonist, phenylephrine, PEA or d-amphetamine before and in the presence of vehicles, the α1-adrenoceptor antagonist, prazosin (1µM), the nitric oxide synthase inhibitor, Nω-nitro-L-arginine (L-NAME), or NO scavengers, curcumin and astaxanthin. Prazosin inhibited phenylephrine contractions with low affinity consistent with α1L-adrenoceptors. However, PEA and amphetamine were not antagonised, indicating non-adrenergic responses probably via TAARs. L-NAME potentiated contractions to PEA both in the absence and presence of prazosin, indicating that PEA releases NO to cause underlying opposing vasodilatation, independent of α1-adrenoceptors. L-NAME also potentiated amphetamine and phenylephrine. PEA was potentiated by the NO scavenger astaxanthin but less effectively. Curcumin, an active component of turmeric, however, inhibited PEA. Trace amines therefore constrict blood vessels non-adrenergically with an underlying NO-mediated non-adrenergic vasodilatation. This has implications in the pressor actions of these amines when NO is compromised.

Transfer-molded wrappable microneedle meshes for perivascular drug delivery

After surgical procedures such as coronary/peripheral bypass grafting or endarterectomy for the treatment of organ ischemia derived from atherosclerosis, intimal hyperplasia (IH) which leads to restenosis or occlusion at the site of graft anastomosis frequently occurs. In order to inhibit IH caused by abnormal growth of smooth muscle cells (SMCs) in tunica media, various perivascular drug delivery devices are reported for delivery of anti-proliferation drugs into vascular tissue. However, there still remain conflicting requirements such as local and unidirectional delivery vs device porosity, and conformal tight device installation vs pulsatile expansion and constriction of blood vessels. In this study, a biodegradable microneedle (MN) array is developed on a flexible woven surgical mesh using a transfer molding method. Mechanical properties of ‘wrappable’ MN meshes are investigated and compared to the properties of blood vessels. Ex vivo and in vivo animal studies demonstrate enhanced drug delivery efficiency, efficacy for IH reduction, and safety of MN mesh. In particular, MN mesh showed significantly reduced neointiamal formation (11.1%) compared to other competitive groups (23.7 and 22.2%) after 4-week in vivo animal study. Additionally, wrappable MN meshes effectively suppressed side effects such as IH due to mechanical constriction, loss of toxic drug to the surroundings, and cell death that were frequently observed with other previous perivascular drug delivery devices.

Chemotherapy without the hair loss

Injections of a hair-promoting protein may be enough to prevent people undergoing chemotherapy from losing their hair. Hair loss is one of the most feared side effects of chemotherapy. In one study, around B per cent of women said they had considered refusing treatment to save their locks. There are few options available. Scalp-cooling caps freeze and constrict blood vessels to stop chemo drugs from flowing into hair follicles. But they are expensive, work for only 50 per cent of people, extend treatment by two hours and cause discomfort and headaches.

A Two-Layer Mathematical Model of Blood Flow in Porous Constricted Blood Vessels

In this paper, we discussed a mathematical model for two-layered non-Newtonian blood flow through porous constricted blood vessels. The core region of blood flow contains the suspension of erythrocytes as non-Newtonian Casson fluid and the peripheral region contains the plasma flow as Newtonian fluid. The wall of porous constricted blood vessel configured as thin transition Brinkman layer over layered by Darcy region. The boundary of fluid layer is defined as stress jump condition of Ocha-Tapiya and Beavers–Joseph. In this paper, we obtained an analytic expression for velocity, flow rate, wall shear stress. The effect of permeability, plasma layer thickness, yield stress and shape of the constriction on velocity in core & peripheral region, wall shear stress and flow rate is discussed graphically. This is found throughout the discussion that permeability and plasma layer thickness have accountable effect on various flow parameters which gives an important observation for diseased blood vessels.

Levamisole-Adulterated Cocaine Leading to Fatal Vasculitis: A Case Report

Cocaine is often "cut" with various additives to increase the profitability of the drug. One of the most common additives on today's market is levamisole, an anthelmintic medication used to destroy and expel parasitic worms in animals. The use of levamisole-contaminated cocaine can result in agranulocytosis and vasculitis (inflammation and constriction of small blood vessels). The resulting clotting and decrease in peripheral blood flow lead to cutaneous lesions, particularly on the ears, face, hands, and feet, and in severe cases can cause generalized tissue necrosis throughout the entire body. Treatment is generally supportive, and symptoms typically abate with complete cessation of cocaine use. However, symptoms may recur with subsequent cocaine use and, as this case illustrates, severe neutropenia and extensive vasculitis may lead to overwhelming sepsis and death.

Terlipressin versus placebo or no intervention for people with cirrhosis and hepatorenal syndrome.

Hepatorenal syndrome is a potentially reversible renal failure associated with severe liver disease. The disease is relatively common among people with decompensated cirrhosis. Terlipressin is a drug that increases the blood flow to the kidneys by constricting blood vessels. The previous version of this systematic review found a potential beneficial effect of terlipressin on mortality and renal function in people with cirrhosis and hepatorenal syndrome. To assess the beneficial and harmful effects of terlipressin versus placebo/no intervention for people with cirrhosis and hepatorenal syndrome. We identified eligible trials through searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, and Science Citation Index Expanded, and manual searches until 21 November 2016. Randomised clinical trials (RCTs) involving participants with cirrhosis and type 1 or type 2 hepatorenal syndrome allocated to terlipressin versus placebo or no intervention. We allowed co-administration with albumin administered to both comparison groups. Two review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcomes were mortality, hepatorenal syndrome, and serious adverse events. We conducted sensitivity analyses of RCTs in which participants received albumin, subgroup analyses of participants with type 1 or type 2 hepatorenal syndrome, and Trial Sequential Analyses to control random errors. We reported random-effects meta-analyses with risk ratios (RR) and 95% confidence intervals (CI). We assessed the risk of bias based on the Cochrane Hepato-Biliary Group domains. We graded the quality of the evidence using GRADE. We included nine RCTs with a total of 534 participants with cirrhosis and ascites. One RCT had a low risk of bias for mortality and a high risk of bias for the remaining outcomes. All included trials had a high risk of bias for non-mortality outcomes. In total, 473 participants had type 1 hepatorenal syndrome. Seven RCTs specifically evaluated terlipressin and albumin. Terlipressin was associated with a beneficial effect on mortality when including all RCTs (RR 0.85, 95% CI 0.73 to 0.98; 534 participants; number needed to treat for an additional beneficial outcome (NNTB) 10.3 people; low-quality evidence). Trial Sequential Analysis including all RCTs also found a beneficial effect of terlipressin. Additional analyses showed a beneficial effect of terlipressin and albumin on reversal of hepatorenal syndrome (RR 0.63, 95% CI 0.48 to 0.82; 510 participants; 8 RCTs; NNTB 4 people; low-quality evidence). Terlipressin increased the risk of serious cardiovascular adverse events (RR 7.26, 95% CI 1.70 to 31.05; 234 participants; 4 RCTs), but it had no effect on the risk of serious adverse events when analysed as a composite outcome (RR 0.91, 95% CI 0.68 to 1.21; 534 participants; 9 RCTs; number needed to treat for an additional harmful outcome 24.5 people; low-quality evidence). Non-serious adverse events were mainly gastrointestinal, including diarrhoea (RR 5.76, 95% CI 2.19 to 15.15; 240 participants; low-quality evidence) and abdominal pain (RR 1.54, 95% CI 0.97 to 2.43; 294 participants; low-quality evidence).We identified one ongoing trial on terlipressin versus placebo in participants with cirrhosis, ascites, and hepatorenal syndrome type 1.Three RCTs reported funding from a pharmaceutical company. The remaining trials did not report funding or did not receive funding from pharmaceutical companies. This review suggests that terlipressin may be associated with beneficial effects on mortality and renal function in people with cirrhosis and type 1 hepatorenal syndrome, but it is also associated with serious adverse effects. We downgraded the strength of the evidence due to methodological issues including bias control, clinical heterogeneity, and imprecision. Consequently, additional evidence is needed.

Chronic cocaine induces HIF-VEGF pathway activation along with angiogenesis in the brain.

Cocaine induces vasoconstriction in cerebral vessels, which with repeated use can result in transient ischemic attacks and cerebral strokes. However, the neuroadaptations that follow cocaine’s vasoconstricting effects are not well understood. Here, we investigated the effects of chronic cocaine exposure (2 and 4 weeks) on markers of vascular function and morphology in the rat brain. For this purpose we measured nitric oxide (NO) concentration in plasma, brain neuronal nitric oxide synthase (nNOS or NOS1), HIF-1α, and VEGF expression in different brain regions, i.e., middle prefrontal cortex, somatosensory cortex, nucleus accumbens, and dorsal striatum, using ELISA or Western blot. Additionally, microvascular density in these brain regions was measured using immunofluorescence microscopy. We showed that chronic cocaine significantly affected NOS1, HIF-1α and VEGF expression, in a region- and cocaine treatment-time- dependent manner. Cerebral microvascular density increased significantly in parallel to these neurochemical changes. Furthermore, significant correlations were detected between VEGF expression and microvascular density in cortical regions (middle prefrontal cortex and somatosensory cortex), but not in striatal regions (nucleus accumbens and dorsal striatum). These results suggest that following chronic cocaine use, as cerebral ischemia developed, NOS1, the regulatory protein to counteract blood vessel constriction, was upregulated; meanwhile, the HIF-VEGF pathway was activated to increase microvascular density (i.e., angiogenesis) and thus restore local blood flow and oxygen supply. These physiological responses were triggered presumably as an adaptation to minimize ischemic injury caused by cocaine. Therefore, effectively promoting such physiological responses may provide novel and effective therapeutic solutions to treat cocaine-induced cerebral ischemia and stroke.

Diving Mice vs. Torpid Mice: A Comparison of Cardiovascular Regulation

The diving response is a coordinated physiological response to submersion into water, and is used widely amongst mammals. The physiological response is composed of three primary effects: an immediate drop in heart rate, a reduced drive to breathe, and constriction of peripheral blood vessels. The diving response is important, not only because of its dramatic influence of the autonomic nervous system, but also because it inhibits or alters normal homeostatic reflexes such as the drive to breathe. We hypothesized that the cardiovascular effects and neural circuitry involved in the murine dive response are similar to those used in daily torpor. In this study, telemeters that measure arterial pressure and body temperature were implanted into female C57Bl/6J mice. These mice were trained to swim then voluntarily dive underwater for a distance of 60 cm over a 5 second period. After a recovery period, the same mice were calorically restricted to induce a bout of torpor. Just before the dive, the interbeat interval (IBI) was 87±3 msec and diastolic pressure was 100±8 mmHg. Diving caused a dramatic bradycardia immediately at the onset of each dive (IBI increased to 464±60 msec) and diastolic pressure dropped to 56±9 mmHg, that coincided with elevated peripheral resistance. Mice experienced a short bout (~5 sec) hypertension (diastolic pressure rose to 133±9 mmHg) upon emergence. The bradycardia and hypotension were dependent on vagal influence, as pre‐treatment with atropine blocked these responses. The same absolute changes to heart rate, blood pressure, and total peripheral resistance were observed in the torpid mouse, albeit at a different time scale. These data suggest that the drivers of the cardiovascular changes during a bout of torpor and during the diving response are likely shared.Support or Funding InformationSupported by 1R15HL120072‐01A1 to SJS

IRAP inhibition using HFI419 prevents moderate to severe acetylcholine mediated vasoconstriction in a rabbit model

Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by the neurotransmitter acetylcholine, leads to paradoxical vasoconstriction as it binds to smooth muscle cell M3 receptors. Thus, inhibition of coronary artery vasospasm will improve clinical outcomes. Inhibition of insulin regulated aminopeptidase has been shown to improve vessel function, thus we tested the hypothesis that HFI419, an inhibitor of insulin regulated aminopeptidase, could reduce blood vessel constriction to acetylcholine. The abdominal aorta was excised from New Zealand white rabbits (n=15) and incubated with 3mM Hcy to induce vascular dysfunction in vitro for 1h. HFI419 was added 5min prior to assessment of vascular function by cumulative doses of acetylcholine. In some rings, vasoconstriction to acetylcholine was observed in aortic rings after pre-incubation with 3mM homocysteine. Incubation with HFI419 inhibited the vasoconstrictive response to acetylcholine, thus improving, but not normalizing, vascular function (11.5±8.9% relaxation vs 79.2±37% constriction, p<0.05). Similarly, in another group with mild vasoconstriction, HFI419 inhibited this effect (34.9±4.6% relaxation vs 11.1±5.2%, constriction, p<0.05). HFI419 had no effect on control aorta or aorta with mild aortic dysfunction. The present study shows that HFI419 prevents acetylcholine mediated vasoconstriction in dysfunctional blood vessels. HFI419 had no effect on normal vasodilation. Our results indicate a therapeutic potential of HFI419 in reducing coronary artery vasospasm.

Mixed vascular nevus syndrome: a report of four new cases and a literature review.

Mixed vascular nevus (or nevus vascularis mixtus) represents an admixture of cutaneous vascular malformations of the telangiectatic type and angiospastic spots of nevus anemicus. It can occur as an purely cutaneous trait or as a hallmark of a neurocutaneous phenotype (mixed vascular nevus syndrome) characterised by the combination of: (I) paired vascular (telangiectatic and anemic) twin nevi and brain abnormalities of the Dyke-Davidoff-Masson type (i.e., crossed cerebral/cerebellar hemiatrophy with hypoplasia of the ipsilateral cerebral vessels and homolateral hypertrophy of the skull and sinuses (hyperpneumatisation) with contralateral hemispheric hypertrophy); or (II) paired vascular twin nevi and brain malformations of the Dyke-Davidoff-Masson type in association with systemic abnormalities consisting in facial asymmetry, skeletal anomalies (i.e., Legg-Calvé-Perthes-like disease) and disorders of autoimmunity (i.e., diabetes, thyroiditis). In 2014, Happle proposed to name the syndrome with the eponym Ruggieri-Leech syndrome. Review of the existing literature on nevus vascularis mixtus and information on our personal experience on new cases and follow-up of previously reported cases by some of us. The existing literature revealed 4 previous studies including 33 cases with an inferred purely cutaneous trait and 3 cases with a combination of paired vascular twin nevi and brain malformation of the Dyke-Davidoff-Masson type. Our personal experience includes 4 unpublished patients (1 female and 3 males; currently aged 2 to 34 years) seen and followed-up at our Institutions in Italy who had: paired vascular nevi involving either the face (n=2) or the face and parts of the body (n=2); facial asymmetry (n=4); mild to moderate facial dysmorphic features (n=2); developmental delay (n=3); seizures/stroke-like episodes and associated hemiplegia (n=4); muscular hypotrophy (n=2); mild to moderate hemispheric atrophy (n=4); skull osseous hypertrophy (n=4); hyperpneumatisation of the sinuses (n=2); hypoplastic brain vessels (n=4); colpocephaly and malformation of cortical development (n=2). Follow-up data on our previous 2 cases revealed that the vascular abnormalities in the skin and nervous system were stable over years without neurological progression or deterioration. Pathogenically, this complex phenotype suggests that embryonic pairing and somatic recombination of recessive (didymotic) alleles controlling the balance between constriction (i.e., nevus anemicus) and dilatation (i.e., nevus telangiectaticus) of blood vessels could be the primary event causing the phenomena of cutaneous and brain vascular twin spotting and the paired phenomena of skull hyperpneumatisation vs. hypertrophy and brain megalencephaly/colpocephaly vs. cortical dysplasia. This association is likely more frequent than previously thought and should be investigated by means of: (I) brain and spinal cord imaging (combination of CT and MRI studies); (II) skeletal X-ray studies (when dictated by clinical findings); (III) systemic ultrasound studies; (IV) neurophysiologic studies (EEG); (V) psychomotor testing; (VI) and laboratory investigation (including immune-mediated dysfunction).