Prolonged Constriction Research Articles

Penile Entrapment by Metal Ring: A Video Guide to Surgical Removal

ABSTRACT Introduction Penile rings may be used to enhance sexual function. Prolonged constriction greater than 30 minutes may lead to pain, edema and ultimately ischemic end organ damage. Failure to remove the ring warrants prompt evaluation and can be a surgical emergency. Objective The purpose of this video abstract is to review and demonstrate the management strategies to remove a constricting penile ring. Methods Conservative interventions which can be attempted at the bedside are reviewed. These include but are not limited to sliding the penile ring off of the penis using available lubrication as well as cutting the rings using pliers or bolt cutters. Interventions performed under general anesthesia include repeated attempts at sliding off or cutting the ring, and when these maneuvers fail, utilization of mechanical drills or saws may be indicated. Results The case presented is a 41 year old gentleman who presented with a thick silver metallic ring placed on the base of his penis. The penis had been entrapped for greater than 24 hours. Conservative measures at the bedside were not successful and the ring was ultimately removed in the operating room using a microsurgical saw. The patient experienced a complete cosmetic recovery and did not experience any long-term detriment to his voiding habits. Conclusions Prolonged penile entrapment by placement of a constricting ring risks ischemic end organ damage and is a rare surgical emergency. The conservative and more invasive management approaches are demonstrated in this video. Disclosure No

Caffeine Delays Retinal Neurovascular Coupling during Dark to Light Adaptation in Healthy Eyes Revealed by Optical Coherence Tomography Angiography.

PurposeThe purpose of this study was to investigate the acute effects of caffeine on retinal hemodynamics during dark to light adaptation using optical coherence tomography angiography (OCTA).MethodsThirteen healthy individuals (13 eyes) underwent OCTA imaging after dark adaptation and at repeated intervals during the transition to ambient light in two imaging sessions: control and after ingesting 200 mg of caffeine. We analyzed the parafoveal vessel density (VD) and adjusted flow index (AFI) of the superficial capillary plexus (SCP), middle capillary plexus (MCP), and deep capillary plexus (DCP), as well as the vessel length density (VLD) of the SCP. After adjusting for age, refractive error, and scan quality, we compared parameters between control and caffeine conditions.ResultsIn the dark, MCP VD decreased significantly after caffeine (−2.63 ± 1.28%). During the transition to light, initially, DCP VD increased (12.55 ± 2.52%), whereas SCP VD decreased (−2.09 ± 0.91%) significantly with caffeine compared to control. By 15 minutes in light, DCP VD reversed and was significantly decreased (−5.45 ± 2.62%), whereas MCP VD increased (4.65 ± 1.74%). There were no differences in AFI or VLD.ConclusionsWe show that, overall, caffeine causes a trend of delayed vascular response in all three macular capillary plexuses in response to ambient light. Whereas the MCP is constricted in the dark, during the transition from dark to light, there is initially delay followed by prolonged constriction of the DCP and constriction followed by slow dilation of the SCP. We posit that these delayed vascular responses may present potential risk of capillary ischemia.

Development of a UV-Stabilized Topical Formulation of Nifedipine for the Treatment of Raynaud Phenomenon and Chilblains.

Raynaud’s Phenomenon is a vascular affliction resulting in pain and blanching of the skin caused by excessive and prolonged constriction of arterioles, usually due to cold exposure. Nifedipine is a vasodilatory calcium channel antagonist, which is used orally as the first-line pharmacological treatment to reduce the incidence and severity of attacks when other interventions fail to alleviate the condition and there is danger of tissue injury. Oral administration of nifedipine, however, is associated with systemic adverse effects, and thus topical administration with nifedipine locally to the extremities would be advantageous. However, nifedipine is subject to rapid photodegradation, which is problematic for exposed skin such as the hands. The goal of this project was to analyze the photostability of a novel topical nifedipine cream to UVA light. The effect of incorporating the photoprotectants rutin, quercetin, and/or avobenzone (BMDBM) into the nifedipine cream on the stability of nifedipine to UVA light exposure and the appearance of degradation products of nifedipine was determined. Rutin and quercetin are flavonoids with antioxidant activity. Both have the potential to improve the photostability of nifedipine by a number of mechanisms that either quench the intermolecular electron transfer of the singlet excited dihydropyridine to the nitrobenzene group or by preventing photoexcitation of nifedipine. Rutin at either 0.1% or 0.5% (w/w) did not improve the stability of nifedipine 2% (w/w) in the cream after UVA exposure up to 3 h. Incorporation of quercetin at 0.5% (w/w) did improve nifedipine stability from 40% (no quercetin) to 77% (with quercetin) of original drug concentration after 3 h UVA exposure. A combination of BMDBM and quercetin was the most effective photoprotectant for maintaining nifedipine concentration following up to 8 h UVA exposure.

CSD-Induced Arterial Dilatation and Plasma Protein Extravasation Are Unaffected by Fremanezumab: Implications for CGRP's Role in Migraine with Aura.

Cortical spreading depression (CSD) is a wave of neuronal depolarization thought to underlie migraine aura. Calcitonin gene-related peptide (CGRP) is a potent vasodilator involved in migraine pathophysiology. Evidence for functional connectivity between CSD and CGRP has triggered scientific interest in the possibility that CGRP antagonism may disrupt vascular responses to CSD and the ensuing plasma protein extravasation (PPE). Using imaging tools that allow us to generate continuous, live, high-resolution views of spatial and temporal changes that affect arteries and veins in the dura and pia, we determined the extent to which CGRP contributes to the induction of arterial dilatation or PPE by CSD in female rats, and how these events are affected by the anti-CGRP monoclonal antibody (anti-CGRP-mAb) fremanezumab. We found that the CSD-induced brief dilatation and prolonged constriction of pial arteries, prolonged dilatation of dural arteries and PPE are all unaffected by fremanezumab, whereas the brief constriction and prolonged dilatation of pial veins are affected. In comparison, although CGRP infusion gave rise to the expected dilatation of dural arteries, which was effectively blocked by fremanezumab, it did not induce dilatation in pial arteries, pial veins, or dural veins. It also failed to induce PPE. Regardless of whether the nociceptors become active before or after the induction of arterial dilatation or PPE by CSD, the inability of fremanezumab to prevent them suggests that these events are not mediated by CGRP, a conclusion with important implications for our understanding of the mechanism of action of anti-CGRP-mAbs in migraine prevention.SIGNIFICANCE STATEMENT The current study identifies fundamental differences between two commonly used models of migraine, CSD induction and systemic CGRP infusion. It raises the possibility that conclusions drawn from one model may not be true or relevant to the other. It sharpens the need to accept the view that there is more than one truth to migraine pathophysiology and that it is unlikely that one theory will explain all types of migraine headache or the mechanisms of action of drugs that prevent it. Regarding the latter, it is concluded that not all vascular responses in the meninges are born alike and, consequently, that drugs that prevent vascular dilatation through different molecular pathways may have different therapeutic outcomes in different types of migraine.

Assessment of Basilar Artery Reactivity in Stroke and Subarachnoid Hemorrhage Using Wire Myograph.

Blood flow regulation of normal cerebral arteries is a critical and important factor to supply the brain tissue with nutrients and oxygen. Stroke insult results in a disruption or reduction in cerebral arteries' blood flow with subsequent brain tissue damage. Hemorrhagic stroke is one type of stroke and accounts for about 13 % of all of stroke insults. In this type of stroke, the cerebral artery breaks open and causes bleeding in or surrounding the brain. Subsequently, this bleeding causes blood vessels to constrict in a process called vasospasm, in which the vessels narrow and impede the blood flow to brain tissue. Hemorrhagic stroke is the major cause of prolonged constriction of cerebral arteries. This leads to partial brain damage and sometimes death in patients with aneurysmal subarachnoid hemorrhage. Among the key delicate techniques to assess small blood vessel functionality is the wire myograph, which can be utilized in several cerebral injury models including stroke. The wire myograph is a device that provides information about the reactivity, stiffness, and elasticity of small blood vessels under isometric conditions. In this book chapter, we describe the techniques involved in wire myography assessment and the different measures and parameters recorded; we describe the utility of this technique in evaluating the effects of subarachnoid hemorrhage on basilar artery sensitivity to different agonists.

DESIGN AND CONSTRUCTION OF RH2000 CYBERNATICS HAND

Recently, the number of patients with wrist and forearm amputations increased tremendously due to trauma, prolonged constriction, or surgery. The amputees experienced lots of problems, especially in dealings with their daily life activities. Thus, as a solution, a prototype called as RH2000 Cybernetics Hand is designed. Early design of bionic hand comprises of 14 motors with 14 degree of freedom which caused the bionic hand to be costly and complex to control. In this research, design of a bionic hand that has 10 degrees of freedom with 5 motors attached to mechanical linkages is proposed. The bionic hand designs in SolidWorks that resembled the function and size of an actual human hand. It is fabricated using aluminum 6061 as it is light in weight and durable. As for the sensor, V3 muscle sensor is utilized to identify a signal generated from the human muscle and amplified it as the primary control signal to control the movement of the bionic hand. The performance of bionic hand is tested in terms of repeatability and accuracy. Repeatability accuracy test is divided into two phases, the first test is constructed to analyze the repeatability of angular movement for each finger while the second test is constructed to analyze the repeatability of wrist movement. Similarly, the accuracy test is also divided into two phases where the first test is conducted to analyze the accuracy of finger press while the second test is to analyze the accuracy of hand grasp. The results are compared with the natural human force and yielded acceptable results. Finally, the hand is tested in term of canonical hand posture and manage to emulate actual human hand.

Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn

Although past studies demonstrate that altered serotonin (5-HT) signaling is present in adults with idiopathic pulmonary arterial hypertension, whether serotonin contributes to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) is unknown. We hypothesized that 5-HT contributes to increased pulmonary vascular resistance (PVR) in a sheep model of PPHN and that selective 5-HT reuptake inhibitor (SSRI) treatment increases PVR in this model. We studied the hemodynamic effects of 5-HT, ketanserin (5-HT2A receptor antagonist), and sertraline, an SSRI, on pulmonary hemodynamics of the late gestation fetal sheep with PPHN caused by prolonged constriction of the ductus arteriosis. Brief intrapulmonary infusions of 5-HT increased PVR from 1.0 ± 0.07 (baseline) to 1.4 ± 0.22 mmHg/ml per minute of treatment (P < 0.05). Ketanserin decreased PVR from 1.1 ± 0.15 (baseline) to 0.82 ± 0.09 mmHg/ml per minute of treatment (P < 0.05). Sertraline increased PVR from 1.1 ± 0.17 (baseline) to 1.4 ± 0.17 mmHg/ml per minute of treatment (P = 0.01). In addition, we studied 5-HT production and activity in vitro in experimental PPHN. Compared with controls, pulmonary artery endothelial cells from fetal sheep with PPHN exhibited increased expression of tryptophan hydroxylase 1 and 5-HT production by twofold and 56%, respectively. Compared with controls, 5-HT2A R expression was increased in lung homogenates and pulmonary artery smooth muscle cell lysates by 35% and 32%, respectively. We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT2A receptor and that SSRI infusion further increases PVR in this model.

NADPH oxidase and angiogenesis following endothelin-1 induced stroke in rats: role for nox2 in brain repair.

NADPH oxidases contribute to brain injury, yet they may also have a role in brain repair, particularly in vascular signaling and angiogenesis. This study determined the temporal and spatial profile of NADPH oxidase subunit expression/activity concurrently with angiogenesis in the brain following transient ischemic stroke induced by prolonged constriction of the middle cerebral artery by perivascular injection of endothelin-1 in conscious Hooded Wistar rats (n = 47). VEGF mRNA expression was increased in the ipsilateral cortex and striatum between 6 h and 28 days post-stroke concurrently with a marked increase in Nox2 mRNA expression up to 7 days, and increased Nox4 mRNA expression detected between 7 and 28 days. Point counting of blood vessels using Metamorph imaging software showed increased vascular sprouting between 3 and 7 days after stroke with new vascular networks detected in the core infarct region by 14 days. Angiogenic blood vessels 3 and 7 days post-stroke were observed to co-localise with both Nox2 antibody and dihydroethidium fluorescence suggesting a role for Nox2 generated superoxide during the phase of vascular remodeling, whilst Nox4 expression was detected once new cerebral vessels had formed. These results indicate for the first time that ROS signaling through a cerebrovascular Nox2 NADPH oxidase may be important in initiating brain angiogenesis.

Tenascin-C induces prolonged constriction of cerebral arteries in rats

Tenascin-C (TNC), a matricellular protein, is induced in association with cerebral vasospasm after subarachnoid hemorrhage. The aim of this study was to assess the vasoconstrictive effects of TNC and its mechanisms of action on cerebral arteries in vivo. Two dosages (1 and 10μg) of TNC were administered intracisternally to healthy rats, and the effects were evaluated by neurobehavioral tests and India-ink angiography at 24, 48, and 72h after the administration. Western blotting and immunohistochemistry were performed to explore the underlying mechanisms on constricted cerebral arteries after 24h. The effects of toll-like receptor 4 (TLR4) antagonists (LPS-RS), c-Jun N-terminal kinase (JNK), and p38 inhibitors (SP600125 and SB203580) on TNC-induced vasoconstriction were evaluated at 24h. Higher dosages of TNC induced more severe cerebral arterial constriction, which continued for more than 72h. TNC administration also upregulated TLR4, and activated JNK and p38 in the smooth muscle cell layer of the constricted cerebral artery. LPS-RS blocked TNC-induced TLR4 upregulation, JNK and p38 activation, and vasoconstrictive effects. SP600125 and SB203580 abolished TNC-induced TLR4 upregulation and vasoconstrictive effects. TNC may cause prolonged cerebral arterial constriction via TLR4 and activation of JNK and p38, which may upregulate TLR4. These findings suggest that TNC causes cerebral vasospasm and provides a novel therapeutic approach against it.

Penultimate devoicing in Chaha: phonetic enhancement rather than devoicing

Two of the most well-cited phonological processes in Chaha, ‘devoicing’ (i.e., voiceless consonants alternating with voiced counterparts in the penultimate) and degemination, are reinvestigated to provide a uniform account for laryngeal representations in obstruents within the framework of Dimensional Theory (Avery and Idsardi 2001). In this approach, different from Banksira (2000) and O’Bryan and Rose (2004), devoicing is viewed as articulatory enhancement which assigns [stiff] to Glottal Tension, not a process which deletes the underlying specified feature [voice]. This is drawn from Ohala and Ridordan’ (1979) finding that vocal fold vibration resulting from a prolonged constriction (i.e. geminate consonants) is articulatorily effortable; the phonetic change to [tt] from /dd/ is motivated. Furthermore, Vaux’s Law and the special status of /t/ in Chaha are introduced to account for devoicing in Chaha since devoicing applies when the final consonant is either a sonorant or /t/, which is assumed to be not specified for the Laryngeal articulator (Banksira 2000).

Constrictive pericarditis, still a diagnostic challenge: comprehensive review of clinical management

The diagnosis of constrictive pericarditis (CP) continues to be a challenge in the modern era. Understanding the pathophysiology and integrating the results of invasive and non-invasive techniques are important in the differential diagnosis of CP and e.g. restrictive cardiomyopathy. New echocardiographic techniques such as tissue Doppler imaging (TDI) and 2D-speckle tracking, dual-source CT (computed tomographic imaging) and especially tagged cine-MRI (magnetic resonance imaging) with the analysis of phase contrast angiography sequences are promising novel approaches. Pericardiectomy in experienced centers with complete decortication (if technically feasible) is the treatment of choice for CP and it results in symptomatic relief in most patients. However, some patients may not benefit from pericardiectomy and this may be due to myocardial compliance abnormalities, myocardial atrophy after prolonged constriction, residual constriction or other myocardial processes. An important predictor of long-term outcome after pericardiectomy is the etiology of the pericardial disease. The overall mortality in the current literature is nearly 5-6%. Survival with post-surgical CP is worse than with idiopathic CP, but significantly better than with post-radiation CP.

Mechanism of hypoxia/reoxygenation damage in rat cerebral arterioles

Background: It is not known if Ischemia/Reperfusion (I/R) directly impairs cerebral microvascular regulation. Such impairment could contribute to regional hypoperfusion as observed after I/R. Methods: Cerebral arterioles were isolated, cannulated and their internal diameter monitored with a video microscope. Vasomotor responses to adenosine tri-phosphate (ATP) were obtained before and/or after 60 to 120 min. of hypoxia (PO2< 5 mmHg) with rapid normoxic reoxygenation (H/RO) in the presence or absence of inhibitors. Results: Arterioles significantly constricted during hypoxia. Reoxygenation resulted in a transient dilation followed by a significant vasoconstriction which lasted more than 120 min. Dilation to ATP was significantly decreased. Application of oxygen radial scavenger MnTBAP or calcium sensitive potassium channel activators restored dilation to ATP but not inhibition of nitric oxide synthase. Conclusions: H/RO directly impairs cerebral arteriolar regulation causing prolonged constriction and reduced dilation which could contribute to the hypoperfusion observed after ischemia/reperfusion and promote neuronal damage. possibly via production of reactive oxygen species (ROS) and subsequent inhibition of calcium activated potassium channels. ROS scavenging or potassium channel openers rescued the vessel response. NIH HL57540 (HHD) and NS30555 (RGD and HHD).

Role of transmural pressure and α‐adrenoceptors in acute mechanoadaptive remodeling in mouse tail resistance arteries

After prolonged constriction to norepinephrine, vascular smooth muscle cells (VSMs) undergo a mechanoadaptation process resulting in incomplete relaxation upon removal of the agonist. Experiments were performed to determine the role of transmural pressure (PTM) and α-adrenergic activation in this remodeling. Mouse tail resistance arteries were isolated and exposed to PTMs of 10 or 60 mmHg. A PTM of 60 but not 10 mmHg evoked a robust and prolonged myogenic constriction. Mechanoadaptation and remodeling of VSMs was assessed by recording pressure-diameter relationships in Ca2+-free Krebs solution before and after interventions. Exposure of arterioles to PTMs of 10 or 60 mmHg for 5 min or 4 hrs did not alter the pressure-diameter curves. Arterioles were constricted with norepinephrine (10−6 M, ~50% constriction) for 5 min or 4 hrs at a PTM of 60 mmHg. Constriction to norepinephrine for 5 min did not change the pressure-diameter curves. However, constriction to norepinephrine (10−6 M) for 4 hrs at a PTM of 60 mmHg depressed pressure-diameter curves, and significantly decreased arterial diameter compared with pre-exposure controls (p<0.05). Therefore, α-adrenoceptor stimulation but not the PTM-induced myogenic response causes mechanoadaptive remodeling in mouse tail resistance arteries.

Haptoglobin and the development of cerebral artery vasospasm after subarachnoid hemorrhage

Vasospasm is a prolonged constriction of a cerebral artery that is induced by hemoglobin after subarachnoid hemorrhage (SAH). The subarachnoid blood clot also contains the protein haptoglobin, which acts to neutralize hemoglobin. Because the haptoglobin alpha gene is dimorphic, a person can expresses only one of three types of haptoglobin (alpha1-alpha1, alpha1-alpha2, or alpha2-alpha2) depending on the alpha subunit genes he or she inherits. Each of these three haptoglobin types has different antihemoglobin activities; therefore, haptoglobin may influence the development of vasospasm differently in various patients with SAH. To determine whether SAH patients who have haptoglobin containing the alpha2 subunit would be more likely to develop vasospasm than would be SAH patients who have haptoglobin alpha1-alpha1. A total of 32 patients with Fisher Grade 3 SAH were enrolled in this study. Haptoglobin type was determined by polyacrylamide gel electrophoresis. The primary measure for vasospasm was increased blood flow velocities as detected by daily transcranial Doppler ultrasonography (TCD). The authors found that only 2 of 9 patients with haptoglobin alpha1-alpha1 (22%) had development of "possible" vasospasm as measured by TCD, whereas 20 of 23 patients with the haptoglobin alpha2 subunit (either the alpha1-alpha2 or alpha2-alpha2 haptoglobin types) had development of "possible" vasospasm (87%). The secondary measure for vasospasm was cerebral angiography performed between 3 and 14 days after SAH. Similar results (17% vs 56%) were seen between these groups in those patients who underwent cerebral angiography, although its inconsistent use limited the strength of the statistical comparison. Haptoglobins containing the alpha2 subunit seem to be associated with a higher rate of vasospasm than is haptoglobin alpha1-alpha1.

Autoimmune Retinopathy with RPE Hypersensitivity and ‘Negative ERG’ in X-Linked Hyper-IgM Syndrome

Purpose: To report the clinical, electrophysiological, and immunological features of a patient with X-linked hyper-IgM immunodeficiency syndrome type 1 (HIGM1) accompanied by a novel type of autoimmune retinopathy, including retinal pigment epithelium (RPE) hypersensitivity. Methods: Comprehensive ophthalmological examinations, electrophysiological function testing, and inquiries into the immunological status of a 13-year-old presenting with subacute loss of vision in association with a molecularly confirmed diagnosis of HIGM1 were performed. The patient was genotyped by a PCR-based sequence tag content mapping strategy to define the genetic defect within the causative X-HIM gene TNFSF5. Since conventional allogenic bone marrow transplantation has been reported to cure HIGM1, a peripheral blood stem-cell transplantation was performed. Results: (1) The patient's reduced visual acuity included prolonged dark adaptation and visual field constriction. Electrophysiology revealed a ‘negative ERG’ indicating post-receptoral dysfunction. (2) Initial immunological examination of the patient's serum identified abnormal antibody activity with components of the photoreceptors and the inner nuclear layer. The patient later developed indications of RPE hypersensitivity. A massively reduced light-peak to dark-trough ratio of the EOG slow oscillations (L/D ratio) corresponded to impaired RPE-photoreceptor complex function. (3) Molecular genetic analyses revealed the patient to be nullizygous for the tumor necrosis factor ligand member 5 gene (TNFSF5; CD40LG). A large chromosomal deletion of ∼27.6–32.3 kb in size was identified in Xq26. (4) The transplant with its associated immunomodulation appeared to worsen rather than improve the patient's condition. Conclusions: The fundus appearance and electrophysiological function testing revealed indications of atypical retinal degeneration. However, the clinical course and the serological findings were consistent with those of ocular autoimmunity involving both antiretinal activity and RPE hypersensitivity. In this case, peripheral stem-cell transfusion with its associated chemotherapy failed to benefit the patient's vision; indications of autoimmunity appeared to increase following this treatment.

Acute mechanoadaptation of vascular smooth muscle cells in response to continuous arteriolar vasoconstriction: implications for functional remodeling.

Arterioles exposed to norepinephrine (NE) for 4 h exhibit incomplete relaxation on removal of the agonist. We hypothesized that this is due to a mechanoadaptation process associated with active repositioning of vascular smooth muscle cells (VSMCs) within the vascular wall. Isolated arterioles were exposed to NE (10(-5.5) M) for either 5 min (n = 7) or 4 h (n = 13). During the 5-min exposure, vessel diameter was reduced to 61 +/- 2.6%, and cells shortened to 76.3 +/- 3.8% of control. After NE removal, vessel diameter and cell length returned to control values, which indicated that during acute vasoconstriction cells shorten and relengthen in a reversible fashion. In contrast, when NE exposure lasted 4 h, vessels did not return to control diameter, but VSMCs returned to control length after NE removal. During the 4-h constriction, 56% of the VSMCs began returning to control length, and the overlap between VSMCs increased, which indicated that cellular repositioning had occurred in the presence of the maintained constriction. Thus, in response to prolonged constriction, VSMCs undergo a mechanoadaptation process involving "length autoregulation" that would be energetically favorable for maintenance of a reduced diameter and may provide a mechanism for the development of eutrophic remodeling of the vascular wall.

Endothelin Modulation of Choroidal Blood Flow in the Rabbit

Based on the previous finding that locally produced nitric oxide (NO) and endothelin (ET) exert competing effects on choroidal resistance vessels, the present study sought to further characterize the pharmacology of ET in the choroid. The specific goal was to quantify the choroidal blood flow responses to acute changes in perfusion pressure before and after administering endothelin 1 (ET1), a non-selective ET antagonist, and selective antagonists for the endothelin A (ETA) and endothelin B (ETB) receptor subtypes. Anesthetized rabbits were instrumented with an ear artery cannula to measure mean arterial pressure (MAP), occluders on the aorta and vena cava to control MAP, and a vitreous cannula to measure intraocular pressure (IOP). Choroidal blood flow was measured by laser Doppler flowmetry with a vitreous fiber optic probe. The protocol entailed changing the ocular perfusion pressure by varying MAP before and after ET1 (0.9μ gkg−1, i.v.,n=14), non-selective ET blockade (A-182086, 3mgkg−1, i.v., n=10), selective ETA blockade (FR-139317, 3mgkg−1, i.v., n=12), and selective ETB blockade (A-192621, 3mgkg−1, i.v., n=14). ET1 and ETB blockade shifted the choroidal pressure-flow relation downward, while the non-selective antagonist and the selective ETA antagonist had no effect. The choroid had a biphasic response to exogenous ET1 as seen in other tissues (i.e. initial brief dilation followed by prolonged constriction) that was blocked by the non-selective antagonist whereas the ETA antagonist enhanced the dilation and blocked the constriction, and the ETB antagonist blocked the dilation and enhanced the constriction. These results indicate that ETA and ETB receptors are present and mediate opposing effects on choroidal vascular resistance. The results also suggest that endogenous ET preferentially elicits ETB vasodilation, most likely by stimulating endothelial nitric oxide release.

Reversal of hypercapnia induces K ATP channel and NO-independent constriction of basilar artery in rabbits with acute metabolic alkalosis

The mechanism of hypocapnic constriction of the cerebral vasculature under conditions of altered acid–base balance has not been investigated. As K ATP channels and NO have been implicated in hypocapnic constriction, this study investigated their roles in the constriction due to lowered pCO 2 in hypercapnic rabbits with acute metabolic alkalosis. Metabolic alkalosis was induced acutely following ketamine/xylazine injection. Lowering blood pCO 2 from initial baseline hypercapnic levels to near normocapnic and hypocapnic levels constricted basilar artery by 10.2±0.8% (4) and 16.2±0.6% (44), respectively (means±S.E., n), as determined in an in situ cranial window preparation. The constrictions were maintained for 4–5 h and return of pCO 2 to hypercapnic levels relaxed the constriction. Changing the suffusate pH to either the pH of the cerebral spinal fluid observed during initial baseline hypercapnia or following lowered pCO 2 did not alter the magnitude of constriction due to lowered pCO 2. Neither 0.3 mM N G-monomethyl- l-arginine monoacetate, an NO synthase inhibitor, nor 10 μM glibenclamide, a K ATP channel blocker, altered the magnitude of hypocapnic constriction. These results demonstrated that under conditions of acute metabolic alkalosis and accompanying compensatory hypercapnia, subsequent pCO 2 reduction induces prolonged constriction of the basilar artery that is independent of (1) cerebral spinal fluid pH over a physiologic range, and (2) NO and K ATP channels.

Active Regulation of Insect Respiration

Neurohormonal regulation of insect breathing has been studied in the pupae of Lepidoptera, Coleoptera, and Diptera and in the adults of Hymenoptera. The measurements were obtained by a combination of several electronic methods (barographic, anemometric, respirographic, gravimetric, thermographic, infra-red radiation). It has been found that (in contrast to general theories that claim that insect respiration is based on passive physical diffusion) insects can actively breathe through individual spiracles. A lepidopteran pupa, for instance, is able to inspire simultaneously through both the contralateral spiracles of a given segment, but it can also use only 1 of them or, eventually, it can exhibit a concert of perfectly coordinated spiracular functions across different segments as well as across different sides of the body. This type of active breathing is regulated by the autonomic nervous system (coelopulse) by means of periodically repeated extracardiac pulsations in hemocoelic pressure. The valves of the selected spiracles pulsate in synchrony with the frequency of extracardiac pulsations, which produce a unidirectional ventilatory stream of air. Active, neurohormonal regulation has been also determined for the release of CO 2 from internal carbonate buffers. The pupae of Galleria mellonella (L. ), for instance, actively produce gaseous CO 2 only in special, newly identified organs, from which the concentrated CO 2 is rapidly expelled through just 1 or a few selected spiracles. The discontinuous ventilation cycles are usually very simple. The prolonged constriction of spiracles after the CO 2 burst occurs only in certain lepidopteran pupae, whereas the mysterious fluttering phase does not exist at all. A possibility that insects favor active regulation of breathing to minimize respiratory water loss and avoid respiratory acidaemia is discussed.

Antioxidant therapy against cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

1. Approximately one-third of the morbidity and mortality due to aneurysmal subarachnoid hemorrhage (SAH) is caused by delayed ischemic neurological deficit (DIND) due to cerebral vasospasm. 2. Compared to prolonged arterial constriction in other parts of the body, cerebral vasospasm is characterized by its long duration and refractoriness to vasodilators such as calcium antagonists. 3. Whereas oxyhemoglobin (oxyHb) liberated into the CSF from the subarachnoid clot has been deemed the causative agent of vasoconstriction, the biochemical mechanisms whereby oxyHb elicits prolonged constriction of the cerebral arteries has remained elusive. Here, we suggest that oxyHb triggers the generation of reactive oxygen intermediates (ROI) within the CSF. 4. Multiple lines of evidence indicate that the occurrence of vasospasm, namely, prolonged smooth muscle contraction, is due to the following intracellular events. 5. First, hydroxyl radicals (OH*), the most reactive species of ROI, are generated within the cerebral arterial wall via the Fenton and Haber-Weiss reactions catalyzed by oxyHb. Second, subsequent peroxidative membrane damage in the arterial smooth muscle cell enhances the metabolism of phosphatidylcholine and phosphatidylethanolamine, leading to a rise in the intracellular level of diacylglycerol, an endogenous activator of protein kinase C. 6. The prolonged arterial contraction that occurs during vasospasm is attributable primarily to the activation of protein kinase C, not to the Ca2+/calmodulin system. In this article, literature relevant to the above thesis is reviewed, and the rationale for the antioxidant therapy against cerebral vasospasm is discussed.