Vascular Conduction Research Articles

AGR - 1 A Case Study of Cognitive Reserve and Wernicke's Aphasia Status-Post Insular Stroke.

The case is an 88-year-old, woman, formerly a successful surgeon for decades, with Wernicke's aphasia due to dominant insular stroke. Our evaluation explored her deficits in the context of the heterogeneous presentations of insular strokes and how speech rehabilitation has impacted her language abilities given her cognitive reserve prior to her stroke. The patient sustained a left MCA embolic stroke in 2020. Neurodiagnostics revealed an infarct in the insula, dominant temporal, frontal, and parietal lobes. Baseline language assessment was completed. Results included moderate-severe receptive language impairment; intact fluency; deficits in writing and repetition; and significant paraphasias. Neuropsychological assessment demonstrated prominent deficits in repetition with paraphasias and irritability. Auditory learning, attention, and working memory were invalid due to deficits in repetition. She was diagnosed with mild vascular neurocognitive disorder and conduction aphasia. Despite comprehension having improved, the patient's paraphasias resemble the presentation of Wernicke's aphasia. Interestingly, there were some consistencies in paraphasic errors, such as consistently swapping certain words or letters, demonstrating diminished but not absent volition of speech. Story memory was the most effective measure of auditory memory given repetition deficits. Despite repetition deficits commonly localizing to the supramarginal gyrus, her repetition difficulty is likely related to language network disruption due to her insular infarct. Rehabilitation for comprehension was successful despite age at time of injury. Consistent with previous research, results suggest despite cognitive reserve, repetition is resistant to rehabilitation; however, in this case, paraphasic errors were also resistant. Rehabilitation should include a behavioral component for insular stroke patients.

An alternative water transport system in land plants.

The evolution of vascular tissue is a key innovation enabling plants to inhabit terrestrial environments. Here, we demonstrate extra-vascular water transport in a giant, prop-rooted monocot from Lord Howe Island. Pandanus forsteri (Pandanaceae) produces gutter-like leaves that capture rainwater, which is then couriered along a network of channels to the tips of aerial roots, where it is stored by absorptive tissue. This passive mechanism of water acquisition, transport and storage is critical to the growth of aerial prop roots that cannot yet attain water via vascular conduction. This species therefore sheds light on the elaborate means by which plants have evolved to attain water.

Effect of Sacubitril/Valsartan vs. Valsartan on Vascular and Neural Complications in Type 2 Diabetic Rats

Previously we had shown that a vasopeptidase inhibitor, combination drug containing angiotensin converting enzyme and neprilysin inhibitors, was an effective treatment for diabetes vascular and neural complications. However, once in clinical trials, side effects prevented further development of this class of drugs. This lead to development of sacubitril/valsartan, combination drug similar to vasopeptidase inhibitors containing angiotensin II receptor blocker and neprilysin inhibitor that we hypothesized would be also an effective treatment for diabetic peripheral neuropathy. Using a rat model of type 2 diabetes, early and late intervention protocols, 4 and 12 weeks post hyperglycemia, respectively, rats were treated daily by gavage with valsartan or sacubitril/valsartan for 12 weeks followed by an extensive evaluation of vascular and neural endpoints. The results demonstrated that efficacy of sacubitril/valsartan in improving vascular and neural function was superior to valsartan alone. In the late intervention protocol, treatment of the diabetic rats was initiated well after the appearance of vascular and neural complications. Sacubitril/valsartan treatment was found to not only slow progression of vascular and neural deficits but also stimulate restoration of vascular reactivity, motor and sensory nerve conduction velocities and sensitivity/regeneration of sensory nerves of the skin and cornea. These studies suggest that sacubitril/valsartan may be an effective treatment for diabetic peripheral neuropathy and since it already has FDA approval for treatment of heart failure advancing this drug to clinical trials could proceed quickly. Disclosure M.A. Yorek: None.

The influence of connexin 45 on renal autoregulation

The kidney maintains constant renal blood flow and glomerular filtration rate despite acute changes in renal perfusion pressure (RPP) via renal autoregulation. Renal autoregulation is made up of the myogenic response and the tubuloglomerular feedback (TGF) mechanism, both acting on the afferent arteriole. Both mechanisms have a conducted component, believed to proceed via gap junctions (GJ). These fluid‐filled pores are made up of two connexons, one from each cell, with connexins (Cx) as building blocks. Several Cx isoforms are expressed in the renal vessel wall, including connexin 45 (Cx45), making it a functional syncytium. Disruption of Cx expression and function in the vasculature reduces myogenic response and causes TGF dysregulation, and is associated with hypertension development. The aim of the study was to explore the influence Cx45 has on renal autoregulation.To investigate the TGF mechanism, experiments were performed using the isolated perfused juxtamedullary nephron preparation. Kidneys were isolated from wild type (WT) and smooth muscle cell knockout (KO) Cx45 mice and perfused with a Tyrode's buffer containing BSA and amino acids mixture, at pH 7.4. Local afferent vasoconstriction was induced by electrical pulse stimulation administered via microelectrode, at the glomerular entrance. RPP was kept constant at 95 mmHg and inner afferent arteriolar diameter was measured locally and at upstream sites to evaluate vascular conduction. Responses between WT and KO were compared.To investigate the myogenic response, arteriolar diameter was measured in response to changes in RPP. Experiments were performed in the same setup as previously mentioned, using a stepwise increase in RPP. Perfusion was initiated at 95 mmHg and increased in steps of 20 mmHg until 195 mmHg is reached. Inner afferent arteriolar diameter was measured 100 μm upstream from the glomerulus, and responses between WT and KO were compared. To eliminate the TGF mechanism and isolate only the myogenic response in the kidneys, papillectomy were performed before repeating the same experimental protocol. Responses between WT and KO were compared.To further investigate the influence of Cx45 in the renal vascular function, interlobar arteries from WT and KO mice were isolated and mounted in a pressure myograph. An experimental protocol consisted of stepwise pressure increases of 25 mmHg, starting at 25 mmHg until 175 mmHg is reached. Inner diameter from both WT and KO were measured and compared. In this set‐up no TGF is present.In both WT and KO mice, electrical stimulation at the glomerular pole of the afferent arteriole reduces the diameter at the local site. The conducted vasoconstriction at upstream sites was attenuated in KO mice. The conducted response is observed at 400 μm in the WT mice and 250 μm in the KO. Preliminary myogenic data shows that pressure increases induce a greater afferent vasoconstriction in WT mice and less so in the Cx45 KO. These results suggest that Cx45 may play a role in TGF signaling and myogenic response in the preglomerular vasculature and thus renal autoregulation.Support or Funding InformationThe work is part of the Dynamical Systems Interdisciplinary Network, University of CopenhagenThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Quantitative analysis of vascular colonisation and angio-conduction in porous silicon-substituted hydroxyapatite with various pore shapes in a chick chorioallantoic membrane (CAM) model

The development of scaffolds for bone filling of large defects requires an understanding of angiogenesis and vascular guidance, which are crucial processes for bone formation and healing. There are few investigations on the ability of a scaffold to support blood vessel guidance and it this is of great importance because it relates to the quality and dispersion of the blood vessel network. This work reports an analysis of vascularisation of porous silicon-substituted hydroxyapatite (SiHA) bioceramics and the effects of pore shape on vascular guidance using an expedient ex ovo model, the chick embryo chorioallantoic membrane (CAM) assay. Image analysis of vascularised implants assessed the vascular density, fractal dimension and diameter of blood vessels at two different scales (the whole ceramic and pores alone) and was performed on model SiHA ceramics harbouring pores of various cross-sectional geometries (circles, square, rhombus, triangles and stars). SiHA is a biocompatible material which allows the conduction of blood vessels on its surface. The presence of pores did not influence angiogenesis related-parameters (arborisation, fractal dimension) but pore geometry affected the blood vessel guidance and angio-conductive potential (diameter and number of the blood vessels converging toward the pores). The measured angles of pore cross-section modulated the number and diameter of blood vessels converging to pores, with triangular pores appearing of particular interest. This result will be used for shaping ceramic scaffolds with specific porous architecture to promote vascular colonisation and osteointegration. Statement of SignificanceAn expedient and efficient method, using chick embryo chorioallantoic membrane (CAM) assays, has been set up to characterise quantitatively the angiogenesis and the vascular conduction in scaffolds. This approach complements the usual cell culture assays and could replace to a certain extent in vivo experiments. It was applied to silicon-substituted hydroxyapatite porous bioceramics with various pore shapes. The material was found to be biocompatible, allowing the conduction of blood vessels on its surface. The presence of pores does not influence the angiogenesis but the pore shape affects the blood vessel guidance and angio-conductive potential. Pores with triangular cross-section appear particularly attractive for the further design of scaffolds in order to promote their vascular colonisation and osteointegration and improve their performances.

High intensity one‐legged cycling improves functional sympatholysis and aerobic fitness in chronic heart failure

Exercise intolerance and fatigue during daily activities are primary symptoms in patients with chronic heart failure (CHF). The poor correlation between the hemodynamic parameters of left ventricular performance and perceived symptoms suggests that other factors such as muscle mal perfusion plays a role in determining exercise capacity. The purpose of this study was to investigate the peripheral hemodynamic response to high intense one‐legged cycling. Leg hemodynamics were measured before and after 6 weeks of high intensity interval one‐legged cycling (90% one‐legged cycling max 4×4 min intervals with each leg, 3 times per week) in seven heart failure patients (age: 58±4 years; LVEF 34±5%; BMI 25.8±1.8 kg/m2; VO2 peak: 2.1±0.2 l/min) at rest and during one‐legged knee extensions with without arterial tyramine infusion. Data were analyzed by repeated measures two‐way ANOVA and Tuckey's honestly significant difference (HSD) post hoc procedure. Exercise training increased VO2 peak (2.2±0.2 vs. 2.5±0.3 l/min: P<0.05), Wattmax during two‐legged cycling (153±14 vs. 163±24 Watt; P<0.05), Wattmax during one‐legged knee extensor exercise (36±10 vs. 52±9 Watt; P<0.05) and 6 min walking distance (553±48 vs. 595±59 m; P<0.05). Arterial tyramine infusion lowered leg blood flow and leg vascular conduction at rest (P<0.05) with no difference before and after the training intervention. Arterial tyramine infusion during one‐legged knee extensions, lowered leg blood flow before the training intervention (P<0.05), whereas tyramine did not lower leg blood flow after the training intervention. These results suggest that high intensity one‐legged cycling improves functional sympatholysis during exercise and is beneficial for patients with chronic heart failure in regards to exercise capacity and functionality.

The aortic valve: structure, complications and implications for transcatheter aortic valve replacement

The aortic valve operates in a complex haemodynamic environment, opening and closing over 100,000 times a day. When complications arise, such as aortic stenosis, prognosis can be very poor, leading to death within the first few years. Surgical valve replacement is currently the standard treatment for aortic stenosis. A thorough understanding of the anatomy and function of the native valve is imperative when developing a prosthetic replacement that can withstand the complex demands of the heart. This review focuses on the anatomy, structure and disease of the aortic valve and the implications for a transcatheter aortic valve replacement (TAVR). Current complications with TAVR, such as major vascular bleeding, conduction disturbances and patient-prosthesis mismatch (PPM), can be overcome by reducing the delivery profile and through the use of more accurate imaging technologies to work towards a fully functional and durable prosthesis.

Lipopolysaccharide effects on the proliferation of NRK52E cells via alternations in gap-junction function

Gap junctions regulate proper kidney function by facilitating intercellular communication, vascular conduction, and tubular purinergic signaling. However, no clear relationship has been described between gap-junction function and acute kidney injury induced by the endotoxin lipopolysaccharide (LPS). Normal rat kidney epithelial cells (NRK52E cells) were seeded at high and low densities to promote or impede gap-junction formation, respectively, and establish distinctive levels of intercellular communication in culture. Cells were then challenged with LPS at various concentrations (10-1,000 ng/mL). LPS-induced formation and function of gap junctions were assessed by measuring changes in cell proliferation and colony-forming rates, fluorescent dye transmission to adjacent cells, expression levels of connexin43, and repositioning of confluent cells in response to the gap junction inhibitor oleamide or agonist retinoic acid. The cell proliferation rate and colony-forming rate of high- and low-density NRK52E cells were decreased upon LPS challenge, in a dose-dependent manner. The colony-forming rate of confluent high-density cells was significantly lower than that of low-density cells. Oleamide treatment raised the LPS-induced colony-forming rate of high-density cells, whereas retinoic acid decreased the rate. Neither oleamide nor retinoic acid significantly affected the LPS-induced colony-forming rate of low-density cells. Fluorescence transmission of high-density cells was reduced by LPS challenge, in a dose-dependent manner, but inclusion of retinoic acid increased the LPS-induced transmission of fluorescence. LPS challenge of either high- or low-density NRK52E cells resulted in down-regulated connexin43 expression. Gap-junction function plays an important role in concentration-dependent cytotoxic effect of LPS on normal rat kidney cells in vitro.

Cell–Cell Communication in the Kidney Microcirculation

In the renal vasculature of humans, rats, and mice, at least four isoforms of Cx, Cxs 37, 40, 43, and 45 are expressed. In the ECs, Cx40 is the predominantly expressed Cx, whereas Cx45 is suggested to be expressed in the VSMCs. The preglomerular vasculature has a higher expression of Cxs than the postglomerular vasculature. Cxs form gap junctions between neighboring cells, and as in other organ systems, the major function of Cxs in the kidney appears to be mediation of intercellular communication. Cxs may also form hemichannels that allow cellular secretion of signaling molecules like ATP, and thereby mediate paracrine signaling. Renal Cxs facilitate vascular conduction, juxtaglomerlar apparatus calcium signaling, and enable ECs and VSMCs to communicate. Thus, current research suggests multiple roles for Cxs in important regulatory mechanisms within the kidney, including the renin-angiotensin system, TGF, and salt and water homeostasis. Interestingly, changes in the activity of the renin-angiotensin system or changes in blood pressure seem to affect the expression of the renal vascular Cxs. At the systemic level, renal Cxs may be involved in blood pressure regulation, and possibly in the pathogenesis of hypertension and diabetes.

Resistance exercise training improves age-related declines in leg vascular conductance and rejuvenates acute leg blood flow responses to feeding and exercise

One manifestation of age-related declines in vascular function is reduced peripheral (limb) blood flow and vascular conduction at rest and in response to vasodilatory stimuli such as exercise and feeding. Since, even in older age, resistance exercise training (RET) represents an efficacious strategy for increasing muscle mass and function, we hypothesized that likewise RET would improve age-related declines in leg blood flow (LBF) and vascular conductance (LVC). We studied three mixed-sex age groups (young: 18-28 yr, n = 14; middle aged: 45-55 yr, n = 20; older: 65-75 yr, n = 17) before and after 20 wk of whole body RET in the postabsorptive state (BASAL) and after unilateral leg extensions (6 × 8 repetitions; 75% 1 repetition maximum) followed by intermittent mixed-nutrient liquid feeds (∼6.5 kJ·kg(-1)·30 min(-1)), which allowed us to discern the acute effects of feeding (nonexercised leg; FED) and exercise plus feeding (exercised leg; FEDEX) on vascular function. We measured LBF using Doppler ultrasound and recorded mean arterial pressure (MAP) to calculate LVC. Our results reveal that although neither age nor RET influenced BASAL LBF, age-related declines in LBF responses to FED were eradicated by RET. Moreover, increases in LBF after FEDEX, which occurred only in young and middle-aged groups before RET (+73 ± 9%, and +90 ± 13%, P < 0.001, respectively), increased in all groups after RET (young +78 ± 10%, middle-aged +96 ± 15%, older +80 ± 19%, P < 0.001). Finally, RET robustly improved LVC under FASTED, FED, and FEDEX conditions in the older group. These data provide novel information that supports the premise that RET represents a valuable strategy to counter age-related impairments in LBF/LVC.

Connexins and the kidney

Connexins (Cxs) are widely-expressed proteins that form gap junctions in most organs, including the kidney. In the renal vasculature, Cx37, Cx40, Cx43, and Cx45 are expressed, with predominant expression of Cx40 in the endothelial cells and Cx45 in the vascular smooth muscle cells. In the tubules, there is morphological evidence for the presence of gap junction plaques only in the proximal tubules. In the distal nephron, Cx30, Cx30.3, and Cx37 are expressed, but it is not known whether they form gap junctions connecting neighboring cells or whether they primarily act as hemichannels. As in other systems, the major function of Cxs in the kidney appears to be intercellular communication, although they may also form hemichannels that allow cellular secretion of large signaling molecules. Renal Cxs facilitate vascular conduction, juxtaglomerular apparatus calcium signaling, and tubular purinergic signaling. Accordingly, current evidence points to roles for these Cxs in several important regulatory mechanisms in the kidney, including the renin angiotensin system, tubuloglomerular feedback, and salt and water reabsorption. At the systemic level, renal Cxs may help regulate blood pressure and may be involved in hypertension and diabetes.

Electrotonic vascular signal conduction and nephron synchronization

Tubuloglomerular feedback (TGF) and the myogenic mechanism control afferent arteriolar diameter in each nephron and regulate blood flow. Both mechanisms generate self-sustained oscillations, the oscillations interact, TGF modulates the frequency and amplitude of the myogenic oscillation, and the oscillations synchronize; a 5:1 frequency ratio is the most frequent. TGF oscillations synchronize in nephron pairs supplied from a common cortical radial artery, as do myogenic oscillations. We propose that electrotonic vascular signal propagation from one juxtaglomerular apparatus interacts with similar signals from other nephrons to produce synchronization. We tested this idea in tubular-vascular preparations from mice. Vascular smooth muscle cells were loaded with a fluorescent voltage-sensitive dye; fluorescence intensity was measured with confocal microscopy. Perfusion of the thick ascending limb activated TGF and depolarized afferent arteriolar smooth muscle cells. The depolarization spread to the cortical radial artery and other afferent arterioles and declined with distance from the perfused juxtaglomerular apparatus, consistent with electrotonic vascular signal propagation. With a mathematical model of two coupled nephrons, we estimated the conductance of nephron coupling by fitting simulated vessel diameters to experimental data. With this value, we simulated nephron pairs to test for synchronization. In single-nephron simulations, the frequency of the TGF oscillation varied with nephron length. Coupling nephrons of different lengths forced TGF frequencies of both pair members to converge to a common value. The myogenic oscillations also synchronized, and the synchronization between the TGF and the myogenic oscillations showed an increased stability against parameter perturbations. Electronic vascular signal propagation is a plausible mechanism for nephron synchronization. Coupling increased the stability of the various oscillations.

Connexin Expression in pial and penetrating cerebral arterioles of the rat

Intracerebral, penetrating arterioles provide a conduit by which parenchymal dilator signals are relayed to upstream cerebral arteries. Vascular conduction likely is regulated by the expression of gap junctions, which provide the most direct pathway for intercellular coupling. However, little is known regarding gap junctional connexin expression in penetrating arterioles. In this study, we compared the expression of connexin (Cx) 37, 40, 43 and 45 in penetrating arterioles with that in pial arterioles. Arterioles were isolated from the cortices of Sprague Dawley rats; connexin expression was determined by immunofluorescence staining and confocal laser microscopy. In both types of vessels, Cx37 immunostaining was observed mainly in smooth muscle, whereas Cx40 was found in both smooth muscle and endothelium. Cx43 staining appeared to be restricted adventitially to leptomeningeal tissue, but was absent in vascular cells. In penetrating arterioles, Cx43 punctate labeling was associated with aquaporin‐4 positive processes that envelop the vessels, suggesting the presence of astrocytic end‐feet. Aquaporin‐4 staining was also found in leptomeningeal tissue associated with pial arterioles. There was no evidence of Cx45 expression in these vessels. We conclude that both pial and penetrating cerebral arterioles have a similar distribution of vascular connexin expression. Funded by AHA 0755770Z.

Cortical Spreading Depression—Better Understanding and More Questions. Focus on “Distinct Vascular Conduction With Cortical Spreading Depression”

In this issue of the Journal of Neurophysiology Brennan et al. (p. 4143–4151) present a provocative, carefully conducted series of studies that challenge a very tightly held belief about cortical spreading depression (CSD) showing propagation of the dilation of cortical surface arterioles at a

Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans

We tested the hypothesis that cyclooxygenases (COXs) or COX products inhibit nitric oxide (NO) synthesis and thereby mask potential effects of NO on reactive hyperemia in the cutaneous circulation. We performed laser-Doppler flowmetry (LDF) with intradermal microdialysis in 12 healthy volunteers aged 19-25 yr. LDF was expressed as the percent cutaneous vascular conduction (%CVC) or as the maximum %CVC (%CVC(max)) where CVC is LDF/mean arterial pressure. We tested the effects of the nonisoform-specific NO synthase inhibitor nitro-L-arginine (NLA, 10 mM), the nonspecific COX inhibitor ketorolac (Keto, 10 mM), combined NLA + Keto, and NLA + sodium nitroprusside (SNP, 28 mM) on baseline and reactive hyperemia flow parameters. We also examined the effects of isoproterenol, a beta-adrenergic agonist that causes prostaglandin-independent vasodilation to correct for the increase in baseline flow caused by Keto. When delivered directly into the intradermal space, Keto greatly augments all aspects of the laser-Doppler flow response to reactive hyperemia: peak reactive hyperemic flow increased from 41 +/- 5 to 77 +/- 7%CVC(max), time to peak flow increased from 17 +/- 3 to 56 +/- 24 s, the area under the reactive hyperemic curve increased from 1,417 +/- 326 to 3,376 +/- 876%CVC(max).s, and the time constant for the decay of peak flow increased from 100 +/- 23 to 821 +/- 311 s. NLA greatly attenuates the Keto response despite exerting no effects on baseline LDF or on reactive hyperemia when given alone. Low-dose NLA + SNP duplicates the Keto response. Isoproterenol increased baseline and peak reactive flow. These results suggest that COX inhibition unmasks NO dependence of reactive hyperemia in human cutaneous circulation.

Distinct Vascular Conduction With Cortical Spreading Depression

Cortical spreading depression (CSD) is associated with significant vasodilatation and vasoconstriction, but the relationship between the cortical parenchymal and vascular phenomena remains poorly understood. We used optical intrinsic signal (OIS) imaging and electrophysiology to simultaneously examine the vascular and parenchymal changes that occur with CSD in anesthetized mice and rats. CSD was associated with a propagated multiphasic change in optical reflectance, with correlated negative DC shift in field potential. Dilatation of cortical surface arterioles propagated with a significantly greater intrinsic velocity than the parenchymal CSD wavefront measured by OIS and electrophysiology. Dilatation traveled in a circuitous pattern along individual arterioles, indicating specific vascular conduction as opposed to concentric propagation of a parenchymal signal. Arteriolar dilatation propagated into areas beyond the spread of parenchymal OIS and electrophysiological changes of CSD. Conversely, vasomotor activity could be experimentally dissociated from the parenchymal CSD wave. Frequent repetitive CSD evoked by continuous stimulation was associated with a reduced or absent arteriolar response despite preserved parenchymal OIS and electrophysiological changes. Similarly, dimethylsulfoxide at high concentrations (10%) inhibited arteriolar reactivity despite preserved parenchymal OIS and electrophysiological changes. These results suggest a mechanism, intrinsic to the vasculature, for propagation of vasodilatation associated with CSD. Distinct vascular conduction could be important for the pathogenesis of conditions that involve CSD, including migraine, stroke, and traumatic brain injury.

Postischemic Augmentation of Conducted Dilation in Cerebral Arterioles

Conducted vasomotor responses likely play an important role in cerebrovascular regulation, but it is unclear how these responses may be affected by ischemia. The purpose of this study was to evaluate the hypothesis that cerebral ischemia and reperfusion (I/R) alters vascular conduction in cerebral arterioles. Middle cerebral artery occlusion (MCAO) was induced by an intraluminal filament technique in 4 groups of rats: (A) 2-hour MCAO/24-hour reperfusion (n=14); (B) 2-hour MCAO/1-hour reperfusion (n=7); (C) 1-hour MCAO/24-hour reperfusion (n=6); and (D) 1-hour MCAO/1-hour reperfusion (n=5). Neurological status and infarction (2,3,5-triphenyltetrazolium chloride staining) were evaluated after I/R. Conducted vasomotor responses were assessed in intracerebral branches of the MCA, by following the longitudinal spread of vasodilation or vasoconstriction to localized microapplication of ATP or adenosine. Local microapplication of ATP evoked a biphasic constriction (17+/-3%) and dilation (7+/-2%) response, whereas adenosine elicited only dilation (11+/-2%). These local responses spread longitudinally along sham-control arterioles (1 mm conduction distance) with rapid spatial decay. Ischemia followed by 24-hour reperfusion (groups A and C) led to a marked potentiation of conducted dilation responses: dilation to ATP conducted with virtually no decay in I/R arterioles. Augmentation of conductivity was not observed in the 1-hour reperfusion groups (B and D). Moreover, I/R did not alter conducted constriction. Ischemia-reperfusion led to a specific augmentation of conducted vasodilation in cerebral arterioles. Presumably, enhanced conductivity may improve cerebral perfusion after ischemia.

Dissection of Metabolic, Vascular, and Nerve Conduction Interrelationships in Experimental Diabetic Neuropathy by Cyclooxygenase Inhibition and Acetyl-l-Carnitine Administration

Alterations in cyclooxygenase (COX) pathway activity have been implicated in the pathogenesis of experimental diabetic neuropathy (EDN). These studies explore the relationships between COX-mediated and acetyl-L-carnitine (ALC)-sensitive defects that contribute to functional, metabolic, and vascular abnormalities of EDN. The effects of nonselective COX inhibition with flurbiprofen were contrasted with selective COX-2 inhibition with meloxicam, administered alone and in combination with ALC in nondiabetic (ND) and streptozotocin-induced diabetic (STZ-D) rats. Flurbiprofen treatment of ND rats replicated many of the biochemical and physiological abnormalities of EDN, i.e., reduced motor nerve conduction velocity (MNCV), total and endoneurial nerve blood flow (NBF), Na,K-ATPase activity, and myo-inositol (MI) and taurine content. In STZ-D rats, however, flurbiprofen paradoxically prevented endoneurial NBF deficits but not MNCV slowing. Coadministration of 50 mg x kg(-1) x day(-1) ALC prevented reductions in MNCV, Na,K-ATPase activity, and endoneurial NBF in flurbiprofen-treated ND and STZ-D rats. In contrast, selective COX-2 inhibition with meloxicam was without effect on MNCV, NBF, or MI content in ND rats and prevented MNCV slowing and NBF deficits in STZ-D rats. Western blot analysis showed unchanged sciatic nerve COX-1 protein but increased COX-2 protein abundance in STZ-D versus ND rats. These results imply 1) a tonic role of the COX-1 pathway in the regulation of nerve osmolytes and Na,K-ATPase activity and the maintenance of NBF in ND animals and 2) activation of the COX-2 pathway as an important mediator of NBF and MNCV deficits in EDN.

Seedlessness and Parthenocarpy inPistacia veraL. (Anacardiaceae): Temporal Changes in Patterns of Vascular Transport to Ovules

Pistacia vera‘Kerman’ (pistachio nut) typically produces high numbers of seedless or blank fruits. Patterns of vascular transport into fruits and ovules were studied over 3 years by following the movement of disodium fluorescein solution from cut branches into developing fruitlets. Early in the season, vascular conductivity is intact through to the chalazal end of the ovule. Soon afterwards, the percentage of ovules with vascular conductivity through to the chalaza declines, and in a variable fraction of fruits, movement of the fluorochrome solution becomes blocked either at the placenta or in the funiculus. Six to 9 weeks after anthesis there is blockage in 90 (1 year) to 100% (2 years) of fruits. Subsequently, vascular conductivity resumes in 83.3% (3 year mean) of ovules, a percentage that correlates well with the mean percentage of seeded nuts at harvest (77.5%). Ovules from fruits with dysfunctional vascular conduction early in the season are smaller than those with fully functional vascular tissue. At the time conductivity declines, a high percentage of those ovules with blocked vascular movement lack endosperm and appear to be unfertilized; none of the ovules that retain full vascular flow lack endosperm. Pollination using gamma-irradiated pollen (60Co, 1.0 kGy) led to a nearly three-fold increase in the production of blank nuts. The results indicate that fluorescein transport may be a valuable tool to predict the fate of ovules, and are consistent with the hypothesis that parthenocarpic fruit set may be an important factor in blank nut production in pistachio.

Guidelines for Perioperative Cardiovascular Evaluation for Noncardiac Surgery: An Abridged Version of the Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Guidelines for Perioperative Cardiovascular Evaluation for Noncardiac Surgery: An Abridged Version of the Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines