Reduction Of Arterial Blood Flow Research Articles

035. Short-Term Outcomes for Catheter-Directed Thrombolysis for Non-Threatening Acute Limb Ischaemia: A Systematic Review and Meta-Analysis

Background: Acute limb ischemia (ALI) is a rapid reduction in arterial blood flow to a limb, which may jeopardize its viability, particularly in sensory loss or motor impairment. Catheter-directed thrombolysis (CDT) is the preferred treatment in numerous centers for patients with marginally threatening acute limb ischemia (ALI). This meta-analysis examined the short-term effects of catheter-directed thrombolysis (CDT) for patients with non-imminent limb ischemia. Methods: We searched PubMed, ScienceDirect, and the Cochrane Library to locate observational papers and trials published from 2014 up to early 2024 that report on the outcomes of CDT in patients with ALI. The outcome of this study was mortality rate, amputation rate, and major bleeding. We utilized R Studio to perform the meta-analysis. Results: Nine trials were included, involving 1,067 patients receiving CDT for non-imminent acute limb ischemia. Our results indicate that the pooled mean short-term amputation rate was 10% (95% CI [0.06; 0.15], p < 0.01), the major bleeding rate was 5% (95% CI [0.00; 0.09], p = 0.03), and the short-term death rate was 4% (95% CI [0.03; 0.06], p = 0.08). Our findings indicate a low incidence of short-term death, amputation, and major bleeding in patients undergoing CDT. Conclusion: This meta-analysis reveals a low incidence of short-term mortality, amputation, and major bleeding in patients undergoing Catheter-directed thrombolysis. Further investigations are necessary to determine if CDT should be utilized for the revascularization of limbs with non-urgent ischemia.

Effect of arterial flow on muscle atrophy

This study analyzed the inherent relation between arterial blood mass flow and muscle atrophy of residual limb to provide some necessary information and theoretical support for the clinical rehabilitation of lower limb amputees. Three-dimensional arterial model reconstruction was performed on both intact side and residual limb of a unilateral transfemoral amputee who is the subject. Then hemodynamic calculation was carried out to comparatively analyze the mass flow state at each arterial outlet of both lower extremities. The muscle atrophy ratio of residual limb was calculated by measuring the cross-sectional area of bilateral muscles. Based on the blood supply relationship, the correlation between arterial blood flow reduction ratio and muscle atrophy ratio was discussed. The results showed that the mass flow of superficial femoral arteries and lateral circumflex femoral arteries severely reduced. Meanwhile rectus femoris, vastus lateralis and vastus medialis which were fed by these arteries showed great atrophy too. On the contrary, the mass flow of deep femoral arteries and medial femoral circumflex arteries slightly reduced. Meanwhile gracilis, adductor longus, long head of biceps which were fed by these arteries showed mild atrophy too. These results indicated that there might be a positive and promotion correlation between the muscle atrophy ratio and the blood mass flow reduction ratio of residual limb during rehabilitation.

Doppler-guided ligation of hemorrhoidal arteries with mucopexy: A technique for the future

The transanal hemorrhoidal de-arterialization (THD) procedure is an effective treatment of hemorrhoidal disease. The ligation of hemorrhoidal arteries ("de-arterialization") can provide a significant reduction of arterial blood flow to the hemorrhoidal tissues. Plication of redundant rectal mucosa/submucosa ("mucopexy") can reposition prolapsing tissue to its original anatomical site. In this paper the surgical technique using a specific device (THD(®) Doppler) and peri-operative patient management are illustrated. After appropriate clinical assessment, patients undergo the THD procedure under general or spinal anesthesia, in either the dorsal lithotomy or prone jackknife position. A specifically designed device is used. In all patients, THD is performed, consisting of selective ligation of hemorrhoidal arteries identified by Doppler and marked with a mucosal stitch overlying the artery. In patients with hemorrhoidal or mucosal prolapse, a mucopexy is also performed using continuous suture(s) that include the redundant prolapsing mucosa and submucosa. In long-term follow-up, THD results in resolution of symptoms in the majority of patients. The most common complication is transient but sometimes-painful tenesmus. Rectal bleeding occurs in only a very limited number of patients. There is little or no risk of fecal incontinence or chronic pain. Ano-rectal manometry and endo-anal ultrasound show no evidence of injury to physiologic sphincteric function. THD is a safe procedure and is, at present, one of the most effective treatments of hemorrhoidal disease.

Hemodynamic changes during balloon-occluded transarterial chemoembolization (B-TACE) of hepatocellular carcinoma observed by contrast-enhanced ultrasound.

Balloon-occluded transarterial chemoembolization (B-TACE) is able to achieve denser accumulation of Lipiodol emulsion (LE) in hepatocellular carcinoma (HCC) than conventional TACE. However, to maximize the therapeutic effect of B-TACE, it is imperative to understand the hemodynamic changes that occur during arterial occlusion. We here present two patients with HCC in whom the hemodynamic changes during arterial occlusion were depicted and evaluated by contrast-enhanced ultrasound (CEUS). Arterial flow beyond the catheter tip was observed by CEUS even after balloon occlusion. In one patient, a reduction in arterial blood flow in the HCC was observed by CEUS during balloon occlusion of the target area for embolization. After B-TACE, dense LE accumulation in the HCC nodule was confirmed by flat-panel detector CT, indicating an excellent therapeutic effect. In the other patient, no changes in arterial blood flow in the HCC nodule were observed by CEUS during balloon occlusion of the target area for embolization. After B-TACE, intermediate LE accumulation in the HCC nodule was confirmed by flat-panel detector CT, indicating an incomplete therapeutic effect. The findings obtained in the two patients presented here suggest that B-TACE can be performed more effectively and reliably by monitoring blood flow using CEUS.

Inferior mesenteric venous thrombosis and 18F-FDG PET/CT

The transanal hemorrhoidal de-arterialization (THD) procedure is an effective treatment of hemorrhoidal disease. The ligation of hemorrhoidal arteries (“de-arterialization”) can provide a significant reduction of arterial blood flow to the hemorrhoidal tissues. Plication of redundant rectal mucosa/submucosa (“mucopexy”) can reposition prolapsing tissue to its original anatomical site. In this paper the surgical technique using a specific device (THD® Doppler) and peri-operative patient management are illustrated.After appropriate clinical assessment, patients undergo the THD procedure under general or spinal anesthesia, in either the dorsal lithotomy or prone jackknife position. A specifically designed device is used. In all patients, THD is performed, consisting of selective ligation of hemorrhoidal arteries identified by Doppler and marked with a mucosal stitch overlying the artery. In patients with hemorrhoidal or mucosal prolapse, a mucopexy is also performed using continuous suture(s) that include the redundant prolapsing mucosa and submucosa.In long-term follow-up, THD results in resolution of symptoms in the majority of patients. The most common complication is transient but sometimes-painful tenesmus. Rectal bleeding occurs in only a very limited number of patients. There is little or no risk of fecal incontinence or chronic pain. Ano-rectal manometry and endo-anal ultrasound show no evidence of injury to physiologic sphincteric function.THD is a safe procedure and is, at present, one of the most effective treatments of hemorrhoidal disease.

Association between serum inhibin-B levels and coronary artery disease in aging males

IntroductionAtherosclerosis is a systemic disorder. It is a frequent leading cause of coronary artery disease (CAD). Similarly, atherosclerotic vascular alterations could lead to testicular arterial blood flow reduction and impairment of testicular function with age. Inhibin-B has been validated as a valuable serum marker of testicular functions and its correlation with testicular volume was shown in some studies done before. The purpose of this study is to investigate the association between serum inhibin-B levels and CAD in elderly men.Material and methodsBetween March 2009 and March 2010, fifty-two 50-80-year-old consecutive patients with Gensini score over 20 and ejection fraction (EF) > 50% were included in the study as the CAD group. Fifty healthy men without any cardiac disease history were recruited as the control group. All patients in the CAD group who had indications for coronary artery angiography underwent selective coronary artery angiography.ResultsInhibin-B, total testosterone and testicular volume levels were found to be significantly lower in the CAD group in comparison with the control group (p = 0.004, p < 0.0001, and p = 0.001 respectively).ConclusionsIn this study, although no correlation was found in CAD patients between Gensini score and inhibin-B or testicular volume, inhibin-B levels and testicular volume were significantly lower in patients with CAD than in healthy men. In order to fully assess the relationship between serum inhibin-B levels and CAD, multi-centered prospective and longitudinal studies must be done in elderly male patients.

Quintessential Risk Factors: Their Role in Promoting Cognitive Dysfunction and Alzheimer’s Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. The human brain is extremely sensitive to hypoxia, ischemia, and glucose depletion. Impaired delivery of oxygen in obstructive sleep apnea (OSA) alters neuronal homeostasis, induces pathology, and triggers neuronal degeneration/death. This article systematically delineates the steps in the complex cascade leading to AD, focusing on pathology caused by chronic intermittent hypoxia, hypertension, brain hypoperfusion, glucose dysmetabolism, and endothelial dysfunction. Hypoxia/hypoxemia underpins several pathological processes including sympathetic activation, chemoreflex activity, neuroinflammation, oxidative stress, and a host of perturbations leading to neurodegeneration. The arterial blood flow reduction in OSA is profound, being about 76 % in obstructive hypopneas and 80 % in obstructive apneas; this leads to cerebral ischemia promoting neuronal apoptosis in neocortex and brainstem. OSA pathology also includes gray matter loss in the frontal, parietal, temporal, and occipital cortices, the thalamus, hippocampus, and key brainstem nuclei including the nucleus tractus solitarius. (18)F-FDG PET studies on OSA and AD patients, and animal models of AD, have shown reduced cerebral glucose metabolism in the above mentioned brain regions. Owing to the pathological impact of hypoxia, hypertension, hypoperfusion and impaired glucose metabolism, the adverse cardiovascular, neurocirculatory and metabolic consequences upregulate amyloid beta generation and tau phosphorylation, and lead to memory/cognitive impairment-culminating in AD. The framework encompassing these factors provides a pragmatic neuropathological approach to explain onset of Alzheimer's dementia. The basic tenets of the current paradigm should influence the design of therapeutic strategies to ameliorate AD.

Síndrome del dedo azul

Blue digit syndrome (or sign) is a cutaneous manifestation of multiple diseases that produce acute or subacute ischemic compromise in one or more fingers or toes. The most frequent cause of this syndrome is a reduction in arterial blood flow due to compromise or occlusion of small peripheral vessels, with preservation of the distal pulses. The reduction in blood flow may be caused by a variety of pathogenic mechanisms including thrombosis, embolism, severe vasoconstriction, or inflammatory or non-inflammatory lesions of the vascular wall. The finger or toe affected by ischemia turns blue or violet and may develop necrosis. Independently of the cause, blue digit syndrome is a medical emergency requiring rapid diagnosis and specific treatment, given the risk of progression to irreversible necrosis.

Bmx non‐receptor tyrosine kinase mediation of hypoxic signaling in the adult myocardium

Myocardial ischemia, a reduction in arterial blood flow to the heart muscle, often results in cell death and is critically mediated by both the angiogenic capacity of the myocardium and the ability of the target tissue itself to resist injury. Recent evidence has suggested a novel role for the non-receptor tyrosine kinase Bmx in growth factor dependent angiogenesis and response to ischemia. However, the role of this protein in myocardial injury is unknown. In the present study, we used CD31 and lectin staining of endothelial cells in the adult mouse to reveal capillary density in the normal and ischemic heart. To evaluate the role of Bmx in the myocardium, immunoblotting of whole heart lysates as well as of isolated myocytes was used to detect protein expression in the adult animal. Likewise, confocal imaging was used to detect the presence of Bmx within the anatomical context of the heart and to localize it with specific associating proteins. In the isolated myocyte setting, the effects of hypoxia/reoxygenation on mRNA expression, total protein expression and phosphorylation of Bmx and its associated family members was examined along with an evaluation of the involvement of potential regulatory proteins. Coupled with studies of cell viability, these data provide the first glimpse at the role of Bmx signaling in the normal and ischemic myocardium. These studies were supported by AHA and NIH/NHLBI grant funding.

Microcirculatory hemodynamics of the rat cremaster muscle flap in reduced blood flow states.

Recent studies revealed that muscle and musculocutaneous flaps have the lowest peripheral resistance and best flap survival. The critical values of flow rates responsible for this survival have not been established. The authors evaluated the effect of prolonged arterial flow reduction on flow hemodynamics and muscle flap survival, independent of neovascularization using the rat cremaster muscle island flap model for microcirculatory studies. Muscle flaps were implanted into a transparent Plexiglas chamber to allow prolonged observation of the microcirculation. Twenty-six male Sprague-Dawley rats were studied in three experimental groups. In group I (control; no occlusion), after flap isolation, the cremaster muscle was implanted into the tissue chamber and microcirculatory measurements were performed from day 0 to day 3. In group II, after flap isolation, flow in the main feeding artery (the iliac) was reduced with a silk suture loop between 47% and 62%. In group III, arterial flow was reduced between 63% and 80%. Vessel diameters, red blood cell velocities, number of perfused capillaries, and number of rolling, sticking, and transmigrating leukocytes were reduced daily for each rat. Immediately after flow reduction, mean arteriolar (A1) diameters were significantly smaller in group II (25%) and group III (29%) compared with the controls (p<0.05). This reduction was confirmed by a drop in red blood cell velocities of 37% and 58% in groups II and III respectively (p<0.05). At day 1, more than 60% of group III flaps had no arterial flow, whereas normal flow was observed in control flaps for as long as 3 days. In addition, the number of perfused capillaries dropped significantly (by 42%) in group II flaps after 3 days (p<0.05). The authors conclude that continuous arterial blood flow reduction exceeding 60% of the normal volume, independent of angiogenesis, is incompatible with flap viability in the rat cremaster muscle model.

Pharmacokinetics of intra-arterial mitomycin C in the chemoembolization treatment of liver metastases with polyvinylalcohol or degradable starch microspheres.

In cancer treatment, arterial blood flow reduction by embolization combined with intra-arterial chemotherapy may be advantageous by achieving high and prolonged drug concentrations in the tumor, and lower systemic drug exposure. The pharmacokinetics of intra-arterial mitomycin C (MMC) was investigated in patients with liver metastases undergoing chemoembolization treatment. The chemoembolization treatment consisted of the use of polyvinylalcohol microspheres (ITC-Contour, diameter 150-250 micro m, irreversible vessel occlusion, 20 mg MMC, 15 patients) followed by sealing of the supplying artery with Ethibloc. Alternatively, starch microspheres (Spherex, diameter 45 micro m, biologically degradable, 10 ml of suspension containing 60 mg starch/ml, 20 mg MMC in 7 patients, 15 mg/m2 body surface in 3 patients) were used. MMC was infused over 6 min into the artery supplying the tumor. Serum MMC concentrations were determined from peripheral venous blood samples [protein precipitation with acetonitrile, reverse-phase HPLC with ultraviolet detection (C18 column, elution with 0.01 M, pH 6.5 phosphate buffer/methanol, v/v 70:30, 365 nm)]. The pharmacokinetic parameters were computed assuming an open two-compartment model and linear kinetics. The disposition parameters for MMC in patients treated with polyvinylalcohol microspheres were comparable to data from the literature (C(max)=913+/-98 ng/ml, T(max)=7.7+/-0.3 min, V(c)=0.27+/-0.03 l/kg, V(ss)=0.59+/-0.07 l/kg, Cl=757+/-67 ml/min, T(1/2 alpha)=5.8+/-0.8 min, T(1/2 beta)=50.4+/-4.1 min). There was no significant difference in the disposition parameters for MMC between patients treated with polyvinylalcohol microspheres and those treated with starch microspheres ( P>0.05). In particular, there was no significant difference in the standardized AUC between the groups; this implies that the systemic toxicity of MMC is comparable when polyvinylalcohol microspheres and ethibloc (AUC 1472+/-123 microg min/l per 1 mg MMC) or starch microspheres (AUC: 1448+/-172 microg min/l per 1 mg MMC) are used. The AUC values found in this study do not indicate a reduction in the systemic toxicity of MMC if applied intra-arterially in combination with embolizing microspheres, when compared to the AUC values in the literature for intra-arterial application without embolization, or intravenous MMC application. The amount of starch microspheres may have been too small to cause marked effects. On the other hand, there is a very wide range of AUC values reported in the literature for different application modes, and the use of such historical controls is not adequate for detecting more subtle advantages of the chemoembolization procedure, which may, however, exist.

MR-guided interstitial laser-induced thermotherapy of hepatic metastasis combined with arterial blood flow reduction: technique and first clinical results in an open MR system.

The feasibility and safety of percutaneous laser-induced thermotherapy (LITT) of liver metastases in an open low-field magnetic resonance imaging (MRI) system combined with microsphere-modulated blood flow reduction were tested. Nd:YAG laser therapy with an internally cooled laser applicator was performed under local anesthesia on 20 patients with 34 liver metastases. To increase the effectiveness of LITT, degradable starch microspheres were injected into the proper hepatic artery through an MR-visible catheter initially inserted under fluoroscopy. Near real-time imaging was used for positioning the laser applicator. A T1-weighted gradient-echo breath-hold sequence was used for catheter localization and temperature monitoring. The volumes of the liver metastases and the thermonecroses were determined. MRI-guided LITT could be performed in all patients with no clinically relevant complications. Intraprocedural imaging underestimated the extent of thermonecrosis. In conclusion, percutaneous LITT of liver metastases after injection of starch microspheres is both technically feasible and safe in an open MRI system. J. Magn. Reson. Imaging 2001;13:31-36.

MR‐guided interstitial laser‐induced thermotherapy of hepatic metastasis combined with arterial blood flow reduction: Technique and first clinical results in an open MR system

MR‐guided interstitial laser‐induced thermotherapy of hepatic metastasis combined with arterial blood flow reduction: Technique and first clinical results in an open MR system

The in vivo pharmacological profile of eletriptan (UK-116,044): a potent and novel 5-HT 1B/1D receptor agonist

The anti-migraine drug, eletriptan [( R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl)ethyl]-1 H-indole; UK-116,044], is a novel 5-HT 1B/1D receptor agonist. In this paper, the regional vasoconstrictor profile of eletriptan, in comparison with sumatriptan, was examined in the anaesthetised dog. The inhibitory actions of eletriptan on neurogenic inflammation in rat dura mater were also assessed. In the anaesthetised dog, eletriptan (1–1000 μg kg −1 i.v.) produced a dose-dependent reduction of carotid arterial blood flow with a similar potency and maximum effect to sumatriptan (ED 50 values: eletriptan and sumatriptan, 12 and 9 μg kg −1, i.v., respectively). However, eletriptan exhibited a significantly lower potency than sumatriptan in reducing coronary artery diameter (ED 50 values: 63 and 19 μg kg −1, i.v., respectively, P<0.05). In the femoral circulation, sumatriptan caused a significant reduction in arterial blood flow (ED 50 35 μg kg −1 i.v.) whereas eletriptan (1–1000 μg kg −1 i.v.) had no significant effect upon femoral arterial blood flow when compared to vehicle-treated animals. In rats, eletriptan (30–300 μg kg −1 i.v.) administered prior to electrical stimulation of the trigeminal ganglion produced a dose-related and complete inhibition of plasma protein extravasation in the dura mater (mean extravasation ratio: control 1.9; eletriptan 1.0, minimum effective dose 100 μg kg −1, P<0.05). The potency and maximum effect of eletriptan was identical to that of sumatriptan in this model. When administered during a period of continual stimulation of the trigeminal nerve, eletriptan (100 μg kg −1 i.v.) produced a complete inhibition of plasma protein extravasation. The ability to reduce canine carotid arterial blood flow and inhibit neurogenic inflammation in rat dura mater suggests that vascular and neurogenic mechanisms may contribute to eletriptan's clinical efficacy in migraine patients. In addition, eletriptan exhibits some selectivity for reducing carotid arterial blood flow when compared with femoral arterial blood flow and coronary artery diameter, in the anaesthetised dog.

Misoprostol’s effect on uterine arterial blood flow and fetal heart rate in early pregnancy

Objective: To determine whether a single oral dose of misoprostol is associated with change in Doppler resistance indices (RIs) of the uterine artery in early pregnancy. Methods: Forty pregnant women seeking legal termination of pregnancy at 7–15 completed gestational weeks were each given a single oral dose of 200 μg misoprostol. Resistance indices (A/B ratio) and pulsatility index (PI) of the uterine arteries (UA) and fetal heart rate (FHR) were assessed by Doppler ultrasound before and 1 hour after administration of misoprostol. Results: Doppler RIs (UA-A/B and UA-PI) of the right and left uterine arteries increased significantly 1 hour after misoprostol administration. The right UA–A/B increased from 7.16 ± 1.09 (mean ± SEM) to 10.26 ± 0.67 ( P < .001), and the left UA–A/B increased from 7.40 ± 0.72 to 9.21 ± 0.82 ( P = .04). The right UA–PI increased from 2.38 ± 0.11 to 2.90 ± 0.12 ( P < .001), and the left UA–PI increased from 2.38 ± 0.17 to 2.70 ± 0.18 ( P = .03). No significant changes in FHR were noted 1 hour after misoprostol administration. None of the fetuses died during that time. Conclusion: Doppler RIs of the uterine arteries increased significantly after single oral doses of misoprostol during the first trimester, implying a reduction in arterial blood flow. Those changes were not associated with fetal death, possibly explaining congenital abnormalities associated with misoprostol in early pregnancy.

Endotoxin and Cytokine Release in Strangulation Obstruction and in Partial Occlusion of the Mesenteric Artery in Pigs

Background: The study was performed to determine if endotoxin or the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) are liberated from strangulated or partially ischemic small bowel. Methods: Strangulation obstruction was induced by elevating pressure in a gasket placed around a loop of ileum until venous pressure reached 50 mm Hg. Low arterial flow in a loop of ileum was produced by arterial clamping reducing blood flow by 70%. A proximal bowel loop was used for control. Arterial blood flow was measured by transit time flowmetry. Blood samples were collected before and after 30, 90 and 180 min of strangulation or clamping. Plasma levels of endotoxin and cytokines (TNF, IL-1 and IL-6) were measured by limulus amebocyte lysate test and bioassays, respectively. Results: Strangulation obstruction caused more extensive mucosal damage than arterial clamping. Strangulation was followed by markedly increased venous concentration and release of IL-6 in the strangulated loop. Partial arterial occlusion did not cause increased release of IL-6. Strangulation or partial clamping did not influence the concentration of endotoxin, IL-1 or TNF in intestinal venous blood. Conclusions: Strangulation obstruction causes increased release of IL-6 to intestinal venous blood. IL-6 levels did not increase after 70% reduction of arterial blood flow. The early IL-6 increase was not detected in systemic blood. Strangulation did not cause early changes in plasma levels of endotoxin, TNF or IL-1.

Vanadate as factor of cardiovascular regulation by interactions with the catecholamine and nitric oxide systems.

The effects of 1 microgram/mL of vanadium, given for 12 mo as sodium metavanadate in drinking water, on cardiovascular and biochemical indices of male rabbits were investigated. At the end of the exposure period, vanadium was more accumulated in bones and kidneys than in spleen and liver; the cardiac ventricles and the aorta contained similar amounts of this element. Blood pressure and heart rate were unchanged in the vanadate-exposed animals since the observed decrease of both cardiac inotropism and stroke volume was counteracted by an increase of peripheral vascular resistance, with reduction of arterial blood flow. The arterial levels of sodium, potassium and aldosterone were unmodified by vanadate which, however, strongly raised those of noradrenaline, adrenaline, L-DOPA, and dopamine. Vanadate caused a marked increase of the activity of monoamine oxidase in renal tubules and liver (probably in relation to the increased plasma catecholamine levels) and a reduction of that of glucose-6-phosphate dehydrogenase in the kidney. There was also evidence that vanadium reduces synthesis and/or release of nitric oxide, the endothelium-derived vasodilating factor, likely through a reduced formation from bradykinin. It was concluded that vanadium may represent an environmental factor of altered cardiovascular homeostasis.

Methylene blue attenuates vasodilatation and enhances vasoconstriction in response to endothelin‐1 in the pig nasal mucosa

In thiopentone anaesthetized pigs (n = 10), simultaneous recordings of the vasomotor response to local intra-arterial infusion of endothelin-1 and -3 were performed in three different vascular compartments of the nasal mucosa. Sphenopalatine artery blood flow (reflecting nasal blood flow), nasal cavity volume (representing blood content in capacitance vessels) and laser Doppler flowmeter signal (reflecting superficial mucosal blood flow) increased in response to low doses (4 x 10(-9) to 4 x 10(-8) moles) of endothelin-1. In contrast, marked vasoconstriction (up to 50% of arterial blood flow reduction) occurred upon higher doses (4 x 10(-7) to 4 x 10(-6) moles). Endothelin-3 (4 x 10(-9) to 4 x 10(-6) moles) evoked at the highest dose a long-lasting increase of systemic arterial blood pressure resulting in a 22 +/- 4% increase in nasal vascular resistance. After local intra-arterial pretreatment with methylene blue (4 x 10(-4) mol), the vasodilatory responses to low doses of endothelin-1 were abolished for the three vascular parameters studied, whereas the vasoconstrictor responses in resistance and capacitance vessels evoked by higher doses of endothelin-1 were increased. In contrast, the laser Doppler flowmeter signal reduction in response to endothelin-1 was markedly attenuated. The vasodilatatory effect of substance P was abolished after methylene blue probably due to interference with effects of endothelium dependent relaxing factor (EDRF). These observations suggest that in the pig nasal mucosa in vivo, exogenous endothelin-1 induces a dose-dependent reduction of blood flow in resistance and capacitance vessels and in superficial mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Venous Incompetence and Arterial Insufficiency on Erectile Function: An Animal Model

We designed an animal model to elucidate the effect of venous leakage and arterial insufficiency on erectile function. In 10 dogs, electrodes were implanted around the cavernous nerves for electroerection and blood flow in the internal pudendal artery was recorded. Venous leakage was mimicked by inserting needles of varying gauges (30 to 16G) into the corpus cavernosum and the erectile response to neurostimulation was recorded before and after the creation of the leak. The relationship between the size and the amount of the venous leakage, the changes in the intracavernous pressure (peak and drop), and the changes in the peak and maintenance arterial blood flow were documented.Arterial blood flow was then reduced by 25 and 50 per cent by means of a screw clamp on the terminal aorta. The erectile response to neurostimulation was again determined, with the same electrical parameters, first with reduced blood flow alone, then in combination with leakage of varying size.Our results showed that minor cavernous vein leakage in the presence of normal arterial flow and a healthy sinusoidal system had a minimal effect on erectile function owing to a compensatory increase in penile blood flow. However, when reduction of arterial blood flow was superimposed on venous leakage, even of a minor degree, the erectile response to neurostimulation was markedly impaired.

Adrenergic and neuropeptide Y supersensitivity in denervated nasal mucosa vasculature of the pig

The effects of sympathetic denervation for 2 weeks on vasoconstrictor reactivity to α-adrenoceptor agonists, neuropeptide Y (NPY) and α,β-methylene adenosine triphosphate (mATP) were investigated in different vascular compartments of the nasal mucosa of pentobarbital-anesthetized pigs. Supersensitivity to the vasoconstrictor actions of noradrenaline (NA) was observed in the function of both resistance vessels (as revealed by a reduction in arterial blood flow) and capacitance vessels (reflected by a reduction in nasal mucosal volume). The NA supersensitivity was, to a large extent, of prejunctional type since inhibition of neuronal uptake by desipramine also markedly enhanced the NA response. Whereas the reduction in arterial blood flow and in mucosal volume induced by the α 1-agonist, phenylephrine, was not changed by denervation, the effects of the α 2-agonists UK 14.304 and oxymetazoline were enhanced and/or prolonged. Furthermore, the reduction in blood flow and volume induced by NPY was enhanced in both amplitude and duration. The effects of mATP on the amplitude of the volume response and the duration of the blood flow and volume changes were increased. The maximal reduction in superficial blood flow was larger, as revealed by the laser Doppler flowmetry signal, when NPY or adrenoceptor agonists were given to denervated animals. It is concluded that sympathetic denervation is associated with increased sensitivity and prolonged responses to a variety of vasoconstrictor agents in the pig nasal mucosa in vivo. However, α 2-adrenoceptor, NPY and mATP mechanisms seem to be influenced more by denervation than by α 1-adrenoceptor sensitivity.