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Control of renin gene expression in 2 kidney-1 clip rats.

This study was done to investigate the mechanisms that underly the changes of renal renin gene expression upon hypoperfusion of one kidney. To this end the left renal arteries of male Sprague-Dawley rats were clipped with 0.2 mm silver clips and renal renin mRNA levels were assayed by RNase protection during the first ten days after clipping. Unilateral reduction of renal blood flow led to transient maximal fivefold increases of renin mRNA levels in the clipped kidneys and to sustained suppression of renin gene expression to 20% of the control value in the contralateral intact kidneys. Inhibition of prostaglandin (PG) formation by meclofenamate or EDRF synthesis by L-NAME markedly attenuated the increase of renin mRNA levels in response to clipping, and a combination of PG/EDRF inhibition almost abolished the increase of renin mRNA levels. Inhibition of PG/EDRF formation did not change the suppression of renin mRNA levels in the contralateral intact kidneys. Neither did renal denervation nor inhibition of macula densa function by furosemide prevent the suppression of renin gene expression in response to unilateral renal artery clipping. Only converting enzyme inhibition by ramipril and blockade of Ang II-AT1 receptors by losartan attenuated the decrease of renin mRNA levels in the contralaterals to clipped kidneys. These findings suggest that intact PG and EDRF synthesis represent stimulatory signals for renin gene expression that are required for the elevation of renin mRNA levels upon unilateral renal hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Exchangeable sodium in rats with Goldblatt two-kidney one-clip hypertension.

1. Exchangeable sodium (NaE) was measured serially in rats given a sodium-free diet to eat with sodium chloride solution (85 mmol/l) containing 22Na to drink. 2. After 15 days, nine rats had a left renal artery clip applied; nine had a sham operation. 3. There was no significant difference in NaE between the two groups during the 6 week period after clipping, at the end of which blood pressure was 189 +/- 8 mmHg (mean +/- SEM) in the clipped group and 150 +/- 2 mmHg in the sham-operated group (P less than 0.001). 4. When the clips were removed blood pressure in the hypertensive group fell to 144 +/- 4 mmHg. 5. On the first day after removal of the clip NaE was significantly lower in the clipped group than in the sham-operated group, but there were no significant differences thereafter. 6. Total body sodium (TBNa), measured at death, was consistently higher than NaE by a mean of 1.25 +/- 0.08 mmol, in hypertensive and control rats alike. 7. We conclude that changes in sodium balance are not a necessary accompaniment of of the development of hypertension in this two-kidney one-clip rat model.

Animals↗

Exchangeable sodium in Goldblatt one-kidney one-clip hypertension in the rat.

Exchangeable sodium (NaE), plasma active renin concentration and blood pressure were measured in rats with a sole remaining kidney before and after the development of hypertension induced by clipping of the single renal artery and again after unclipping. Control observations were made in sham-clipped and sham-unclipped uninephrectomized rats. Renal artery clipping caused hypertension and expansion of NaE, the latter being sustained throughout the 6 weeks during which the renal artery was constricted. Hypertension in the clipped rats was progressive over 6 weeks, whereas the expansion of NaE was not; thus the two measurements were not significantly correlated. Two rats which remained normotensive after clipping did not show expansion of NaE. Plasma active renin was elevated in comparison with the sham-clipped controls on the day after clipping, but not thereafter. Unclipping in hypertensive rats was followed by a return of NaE and blood pressure to control values. Both the sustained expansion of NaE and the transient rise in active renin probably contribute to the development of hypertension in this model, but neither alone nor together do they provide a full satisfactory explanation.

Animals↗

[Reliable fixation of cochlear implant electrode mountings in children and adults--initial experiences with a new titanium clip].

BACKGROUND: There is a reported 1% incidence of delayed migration of extrusions of the electrode arrays out of the cochlea. METHODS: A titanium clip to fix the electrode array of the MED EL Combi 40 Cochlear Implant System is described. The clip is designed and shaped in a double U configuration. The clip material allows easy adaption to the individual anatomical situation. The clip is fixed to a bony bridge at the incus bar and fixes the electrode in a plane parallel to the chorda facial angle. It is closed around the electrode similarly to a stapes piston around the incus. Additional tests which examined the possible risk of damaging the electrode carrier and clinical findings are described. RESULTS: The clip was used in 23 cases with a follow-up period up to 1 year. No signs for dislocation of the electrode were found. In one revision case the clip was covered with a thin mucosal layer. The electrode array showed no signs of damage. Intraoperative findings confirmed the experimental tests on the electrode fixation. CONCLUSION: The titanium clip facilitates safe and quick fixation of the electrode array and prevents dislocation. its flexibility and shape minimizes the risk of damage.

Adult↗

Facilitated coronary anastomosis using a nitinol U-Clip device: bovine model.

OBJECTIVE: The coronary anastomosis is the most difficult part of the coronary bypass procedure, particularly when using a minimally invasive technique. Methods to facilitate coronary anastomosis will make the minimally invasive approach to coronary bypass feasible. We sought preclinical validation and testing of the design and efficacy of a self-closing penetrating clip that can be used to facilitate the creation of graft-to-coronary end-to-side anastomosis. METHODS: The nitinol U-Clip device (Coalescent Surgical, Inc, Sunnyvale, Calif) was used in 13 consecutive calves (63-118 kg). In each animal, the device was (1) used to create an anastomosis of the right internal thoracic artery to a coronary artery with the heart beating and (2) compared to polypropylene suture when used to repair two carotid arteriotomies. Intraoperative, 1-week, 8-week, and 26-week postoperative angiograms and detailed histopathologic examinations were used to evaluate anastomotic patency and healing characteristics. RESULTS: The nitinol U-Clip device successfully created right internal thoracic artery-coronary artery anastomoses and repaired carotid arteriotomy sites in 13 consecutive calves. The clip was precisely placed by means of the integrated suture and needle in a fashion similar to that used for conventional suture. The clip met design specifications by reliable release and automatic closure, thereby eliminating knot tying and assisted suture management. At the time of harvest, angiography showed widely patent coronary anastomoses (FitzGibbon grade A criteria, n = 13) and carotid arteriotomy repair sites (n = 13). Histopathologic evaluation confirmed normal healing with smooth circumferential neointimal resurfacing at the anastomotic and repair sites. CONCLUSIONS: The nitinol U-Clip design and function was validated in the formation of bovine coronary anastomoses on the beating bovine heart with excellent graft patency and healing characteristics. The nitinol U-Clip device tests favorably when compared with conventional sutures in carotid artery repair.

Alloys↗

A comparison of para-anastomotic compliance profiles after vascular anastomosis: nonpenetrating clips versus standard sutures.

PURPOSE: Anastomotic compliance is an important predictive factor for long-term patency of small diameter vascular reconstruction. In this experimental study we compare the compliance of continuous and interrupted sutured vascular anastomoses with those using nonpenetrating clips. METHODS: Both common carotid arteries in nine goats (average weight, 57 +/- 5.7 kg) were transected, and end-to-end anastomoses were constructed with nonpenetrating clips or polypropylene sutures. The latter were applied with both interrupted and continuous techniques. Intraluminal pressure was measured with a Millar Mikro-tip transducer, and vessel wall motion was determined with duplex ultrasound equipped with an echo-locked wall-tracking system. Diametrical compliance was determined. Environmental scanning electron microscopy was performed on explanted anastomoses. RESULTS: There was a reduction in anastomotic compliance and associated proximal and distal para-anastomotic hypercompliant zones with the use of all techniques. However, compliance loss was significantly less in those anastomoses with clips and interrupted sutures when compared with continuous suture (P <.001). Furthermore, the total compliance mismatch across anastomoses with continuous sutures was significantly greater than those with clips or interrupted sutures (P <.05). The mean time for constructing clipped anastomoses was 5.7 +/- 1.4 minutes, which was significantly less than either continuous (P <.0001) or interrupted sutures (P <.0001). Furthermore, environmental scanning electron microscopy demonstrated minimal intimal damage with good intimal apposition in the clip group. CONCLUSION: Anastomoses performed with nonpenetrating clips resulted in improved para-anastomotic compliance profiles and reduced intimal damage when compared with those with polypropylene sutures. These benefits may enhance long-term graft patency by reducing the risk of anastomotic intimal hyperplasia.

Anastomosis, Surgical↗

Binding of an invariant-chain peptide, CLIP, to I-A major histocompatibility complex class II molecules.

Invariant chain (Ii) associates with major histocompatibility complex (MHC) class II molecules and is crucial for antigen presentation by class II molecules. The exact nature of Ii interaction with MHC class II molecules remains undefined. A nested set of Ii peptides, CLIPs (class II-associated Ii peptides), have been eluted from various MHC class II molecules, suggesting that CLIPs correspond, at least in part, to the Ii motif which blocks the conventional peptide binding site in MHC class II molecules. Here we report how CLIPs interact with class II MHC molecules, I-A. We have identified regions critical for binding of CLIPs and I-A class II molecules. In most cases, the binding of CLIPs to a number of I-A molecules is modulated by the steric bulk of methionine residues at positions 93 and 99. In addition, the binding of CLIPs to an I-A molecule, I-Au, is sensitive to substitutions at aspartic acid-59 in the alpha chain and threonine-86 in the beta chain, whereas the binding of an antigen-derived peptide is not. Taken together, these results provide an insight as to how CLIPs bind to MHC class II heterodimers.

Animals↗

Endovascular coil embolization of residual or recurrent aneurysms after surgical clipping.

PURPOSE: Treatment of residual or recurrent aneurysms after surgical clipping is a challenge and most surgeons prefer to avoid a second surgical attempt. We present treatment of 4 residual or recurrent aneurysms after surgical clipping with electrolytically detachable coils. MATERIAL AND METHODS: In 3 of 4 patients, recurrent aneurysms were diagnosed with angiography 2 months, 5 years and 14 years after surgery, although the domes of the aneurysms were opened following clipping during the surgery. In the 4th patient, an early postoperative angiogram revealed filling of a residual aneurysm secondary to the incomplete neck clipping. Guglielmi detachable coils were used to occlude the residual or recurrent aneurysm. RESULTS: The endovascular approach was successful in all patients and the control angiograms showed complete obliteration of the aneurysms with no recanalization. CONCLUSION: The endovascular approach is a good treatment option for patients in whom complete obliteration of the aneurysm cannot be achieved by surgical clipping. Opening of the aneurysm sac after clipping does not necessarily preclude aneurysm regrowth from a neck remnant proximal to the clip.

Adult↗

Dynamic localization of CLIP-170 to microtubule plus ends is coupled to microtubule assembly.

CLIP-170 is a cytoplasmic linker protein that localizes to plus ends of microtubules in vivo. In this study, we have characterized the microtubule-binding properties of CLIP-170, to understand the mechanism of its plus end targeting. We show that the NH2-terminal microtubule-interacting domain of CLIP-170 alone localizes to microtubule plus ends when transfected into cells. Association of CLIP-170 with newly-formed microtubules was observed in cells microinjected with biotinylated tubulin, used as a tracer for growing microtubules. Using in vitro assays, association of CLIP-170 with recently polymerized tubulin is also seen. Cross-linking and sedimentation velocity experiments suggest association of CLIP-170 with nonpolymerized tubulin. We conclude from these experiments that the microtubule end targeting of CLIP-170 is closely linked to tubulin polymerization.

Centrosome↗

Autonomic dysreflexia and primary afferent sprouting after clip-compression injury of the rat spinal cord.

Spinal cord injury leads to many forms of autonomic dysfunction including autonomic dysreflexia, a condition involving recurrent episodes of paroxysmal hypertension and associated bradycardia. This hypertension may reach intensities that are life-threatening. We investigated autonomic dysreflexia and the sprouting of central processes of primary afferent neurons (a potential mechanism for autonomic dysreflexia) in a clinically-relevant calibrated clip-compression model of spinal cord injury in the rat. Autonomic dysreflexia was induced by colon distension in the conscious rats 2 weeks after severe (50-g) clip compression injury of the spinal cord at the 4th thoracic segment. The central arbor of small-diameter primary afferent fibers in laminae III-VII of the spinal cord dorsal horn was also assessed at 2 weeks after cord injury by quantitative morphometry, using calcitonin gene-related peptide as a marker. In response to colon distension, arterial pressure increased by 41 +/- 3 mmHg from a resting value of 109 +/- 4 mmHg, and heart rate decreased by 124 +/- 13 beats/min from a value of 515 +/- 16 beats/min (n = 7). Minimal locomotor function was recovered by these rats: by 2 weeks after injury they attained scores of only 3.1 +/- 1.3 on the Basso, Beattie and Bresnahan scale. Histopathology of the clip-compression lesion site in the cord consisted of extensive central necrosis extending several segments rostral and caudal to the lesion. Quantitative measures of the small-diameter afferent arbors revealed significant increases in area ranging from 20-27% in thoracolumbar segments caudal to the injury (n = 5) in comparison to sham-injured rats (n = 6). A second study was done to assess the impact of severity of injury on the relationship between the size of the primary afferent arbors and autonomic dysreflexia. At 2 weeks after milder (20-g) clip injury at T4, rats exhibited responses to colon distension that were not those associated with autonomic dysreflexia (n = 5). Arterial pressure increased by only 16 +/- 3 mmHg and heart rate tended to increase (+19 +/- 12 beats/min). These rats attained a locomotor score of 7.1 +/- 0.4 by 2 weeks. The lesions at the injury site also contained necrosis and mild cavitation within the gray matter. No change in the small-diameter afferent arbor was detected at 2 weeks after the 20-g clip injury at T4 (n = 6 rats). These findings suggest that after severe but not mild clip compression injury of the spinal cord, sprouting of the afferent component of the spinal reflex are contributes to the development of autonomic dysreflexia. Neither dysreflexia, nor changes in the afferent arbor size occurred after mild cord injury. This clinically relevant clip compression cord injury model, studied more frequently for locomotor function, is excellent for investigating mechanisms for the development of autonomic dysreflexia and strategies for its prevention.

Animals↗

Blunted renal responses to atrial natriuretic peptide and its reversal by unclipping in one-kidney, one clip Goldblatt hypertensive rats.

OBJECTIVE: To evaluate the hypotensive and renal effects of atrial natriuretic peptide (ANP) in one-kidney, one clip Goldblatt hypertensive rats with and without renal arterial stenosis. METHODS: The one-kidney, one clip hypertensive rats were divided into four groups: untreated time control, ANP-infused, unclipped and unclipped plus ANP-infused. The changes in blood pressure, glomerular filtration rate and renal excretory function were determined during intravenous vehicle and ANP infusions while the renal arterial clip was in place or removed acutely. One-kidney normotensive rats infused with ANP were used for comparison. RESULTS: In one-kidney control rats, ANP infusion at doses of 0.15, 0.30 and 0.45 microg/kg per min decreased the mean blood pressure from 121 +/- 4 to 108 +/- 5 (9%, P < 0.05), 104 +/- 5 (17%, P < 0.05) and 89 +/- 4 mmHg (25%, P < 0.05), respectively. There was no significant change in glomerular filtration rate. However, the absolute sodium excretion rate increased significantly, by 343 +/- 66, 770 +/- 91 and 786 +/- 78%, respectively. A comparable magnitude of increase in the fractional sodium excretion was noted. In one-kidney, one clip hypertensive rats, the similar three doses of ANP infusion reduced blood pressure from 179 +/- 7 to 162 +/- 8 (8%, P < 0.05), 146 +/- 9 (17%, P < 0.05) and 138 +/- 8 mmHg (22%, P < 0.05), respectively. A slight but insignificant increase in renal function was observed during ANP infusion. Removal of the renal arterial clip reduced blood pressure rapidly and caused a transient increase in renal function. Subsequent infusion of ANF further reduced blood pressure but increased sodium and water excretion markedly. CONCLUSION: There is a blunted natriuresis and diuresis in response to ANP infusion in one-kidney, one clip hypertensive rats. Surgical removal of the clip from the renal artery restores the natriuretic and diuretic effects of ANP.

Animals↗

Surgical and electrophysiological observations during clipping of 134 aneurysms with evoked potential monitoring.

Somatosensory evoked potentials (SEPs) were monitored during 113 operations for the clipping of 134 cerebral aneurysms. Changes in peak latency and amplitude of early cortical SEP as well as central conduction time were evaluated. In 58 cases surgical occlusion of arterial vessels or other events occurred, and in 17 of these cases such events were associated with SEP changes or loss. Arterial occlusions resulted from temporary clipping of a feeding blood vessel (22), accidental clipping of a vessel (12), and intentional permanent vessel occlusion (8). A total SEP loss was seen in 2 cases of accidental vessel occlusion and in 6 cases of temporary vessel clipping. Significant SEP changes were found in 6 patients with temporary clipping, and once each with retraction of the cerebellum, retraction of the middle cerebral artery, and after intentional permanent vessel occlusion. Response to these changes included reapplication of aneurysm clips, repositioning of retractors, or removal of temporary clips. Stable SEP signals during 13 cases allowed the surgeon to proceed with the surgical course. Despite the limitations of SEP monitoring in certain anatomical locations, it has been found to be helpful in the operative management of some cases such as multilobed aneurysms of the middle cerebral artery, giant aneurysms, trapping procedures, and procedures requiring temporary vessel occlusion.

Adolescent↗

A comparative study in opening and closing pressures of cerebral aneurysm clips.

Modern aneurysm clips with newer metallurgic properties and state-of-the-art designs have evolved through the years. Regretfully, manufacturers are still not required to provide product information regarding clip strength, and when such information is supplied, there is no interbrand consistency to how it is obtained. This experiment compares the closing pressures of 5 commonly used brands of aneurysm clips: Yasargil, Sugita, Sundt-Kees, Vari-Angle McFadden, and Heifetz. Interclip comparison is also made of opening pressures, that is, the arterial pressure required to open an aneurysm clip. Findings show a distinct difference in closing forces among these brands of aneurysm clips. The study of opening forces indicates that the important factors determining clip release or displacement were the failure of the clip to cross the vessel completely and intrinsic characteristics of the vascular wall.

Constriction↗

Interlocking-clipping technique for giant aneurysms of the internal carotid artery: technical case report.

OBJECTIVE AND IMPORTANCE: Direct clipping of giant intracranial aneurysms is sometimes difficult. A unique technique using multiple fenestrated clips for closing a giant aneurysm is described. CLINICAL PRESENTATION: A 65-year-old woman presented with a 10-month history of headache and gait disturbance. Cerebral angiography disclosed an unruptured giant aneurysm of the right internal carotid artery. INTERVENTION: Surgical exposure confirmed the presence of a giant aneurysm with the splaying and incorporation of the parent artery and a number of perforating arteries originating from the dome. Four angled and three straight fenestrated clips were applied in tandem to the aneurysm to reconstruct the parent artery and preserve the perforating vessels. Through their blades and heads, the closely arranged clips were successfully interlocked. CONCLUSION: This "interlocking-clipping" technique is a modification of the tandem clipping technique. The aim of this approach is to enhance closing pressure and allow a more stable "seating" of the clips in giant cerebral aneurysms.

Aged↗

Angioscopy-assisted aneurysm clipping.

OBJECTIVE: To test the concept that endovascular angioscopy can assist surgical intracranial aneurysm clipping by providing an endoluminal view of the aneurysm-parent vessel complex. METHODS: A carotid bifurcation aneurysm was surgically created in a dog at the lingual artery origin. A balloon catheter was inflated proximal to the aneurysm to block proximal blood flow and allow endoluminal visualization. A flexible angioscope connected to a video monitoring system and to a high-intensity light source was then advanced within the catheter lumen and positioned immediately distal to the catheter tip. The aneurysm neck was clipped, and the clip was repositioned several times along the neck, with or without distal parent vessel compromise. Each time, the endovascular image on the monitor was interpreted by an observer blinded to the position of the clip. Clip position and image interpretation were communicated independently to a third person, who analyzed the correlation between them. RESULTS: Angioscopy allowed clear visualization of the extent of aneurysm neck occlusion (complete, incomplete, residual "dog ear") after clip application, as well as the presence or absence of distal parent vessel compromise. Aneurysm neck configuration, size, presence of thrombus, and suture line definition were depicted. Critical structures external to the aneurysm-parent vessel complex were transilluminated by the high-intensity lamp. CONCLUSION: Although acknowledged as the treatment of choice for intracranial aneurysms, surgical exclusion can be accompanied by significant morbidity related to perforator occlusion, parent artery compromise, and/or persistent residual aneurysm. The availability of a device allowing visualization of an aneurysm from an endoluminal perspective theoretically could reduce the incidence of these complications. Angioscopy has the potential to become a useful adjunct during intracranial aneurysm clipping because it provides real-time endoluminal viewing of the aneurysm-distal parent vessel complex, which is sometimes obscured to the surgeon.

Angioscopy↗

The effect of coat clipping on thermoregulation during intense exercise in trotters.

The aim of this study was to study the physiological, especially thermoregulatory, responses during intense exercise in the clipped horse compared to the horse with winter coat. Six Standardbred trotters were studied before and after clipping. They performed an inclined incremental high intensity treadmill exercise test and were monitored during recovery. The clipped horse differed significantly (ANOVA) during exercise as compare to coated: less increase in central venous blood temperature, higher skin surface temperature, greater difference skin to ambient temperature and higher rate of nonevaporative heat loss. The clipped horse had significantly lower total cutaneous evaporative heat loss from walk to end of peak exercise and a shorter time for recovery for the respiratory rate using a paired t test. The clipped horse showed a tendency (P = 0.059) to decreased oxygen uptake during the stepwise increase in workload. We concluded that the clipped horse experienced less strain on the thermoregulatory system due to an enhanced heat loss. Some clipped horses in the study showed a more efficient power output; future studies with emphasis on respiration and oxygen demand are needed to explain this.

Analysis of Variance↗

Quality ratings for frequency-shaped peak-clipped speech.

Peak clipping is a common form of distortion in hearing aids and can reduce the subjective quality of the amplified speech. In a typical hearing aid, frequency-response shaping precedes symmetric peak clipping. The effect of peak clipping on speech quality ratings was therefore studied using sentence test materials that were processed using different frequency response contours and then clipped at different clipping thresholds. The quality of each processed sentence was rated on a ten-point scale by normal-hearing subjects. The experimental results indicate that the clipping threshold, and the interaction of the frequency-response shaping with the clipping threshold, significantly affect speech quality. It is also shown that the distortion effects on speech quality can be modeled by a distortion index computed from the magnitude-squared coherence of the speech-processing system in response to a shaped-noise input signal.

Acoustic Stimulation↗

Pathogenesis of one-kidney, one-clip hypertension in rats after renal denervation.

This study examines the role of the renal nerves in the chronic and early developmental stages of one-kidney, one-clip (1K-1C) Goldblatt hypertension. Groups of uninephrectomized Sprague-Dawley rats underwent renal artery constriction with a clip of an internal diameter of 0.23 mm (groups 1 and 3) or 0.40 mm (groups 2 and 4) to produce severe or moderate hypertension. Two weeks later, groups 1 and 2 were subjected to renal denervation and groups 3 and 4 were denervated 6 and 7 wk after clipping, respectively. In all four groups, hypertension remained unchanged during the subsequent 2 wk after denervation. To study further the effects of renal denervation during the early onset of hypertension, groups 5, 6, and 7 received the smaller (0.23 mm) clip after uninephrectomy. Groups 5 and 6 were renal denervated immediately before clipping; group 7 was not denervated. In groups 6 and 7 the renin-angiotensin system was blocked with a continuous infusion of the converting-enzyme inhibitor captopril for 24 h before and 15 days after clipping. In group 5, renal denervation did not prevent a prompt and severe rise in the systolic blood pressure. In groups 6 and 7, infusion of captopril prevented the hypertension only during the first 4 days after clipping; at no time was there a difference in the systolic blood pressure curves of groups 6 and 7 during or after captopril infusion. These data demonstrate that regardless of the severity and duration of hypertension, renal denervation failed to attenuate either the development or the maintenance of 1K-1C Goldblatt hypertension in the rat. Thus the present results fail to provide support for the concept that the renal nerves modulate the hypertension in this experimental model.

Animals↗