Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Collateral sensitivity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed2006

Elevated levels of C-reactive protein are associated with impaired coronary collateral development.

BACKGROUND: In vitro studies have shown that C-reactive protein (CRP) attenuates nitric oxide production and inhibits angiogenesis, which may result in impaired collateral development. The aim of this study was to investigate the association between high sensitivity CRP (hsCRP) levels and the extent of coronary collaterals. MATERIALS AND METHODS: We investigated the association between hsCRP levels and the extent of coronary collaterals according to the Rentrop classification in a cohort of 185 patients who had high-grade coronary stenosis or occlusion on their angiograms. RESULTS: Mean age was 62 years and 80% were males. Subjects with a higher grade of collaterals were significantly less likely to have diabetes mellitus (OR; 0.48, 95% and CI; 0.28, 0.83) or acute coronary syndrome (OR; 0.58, 95% and CI; 0.33, 0.99), but they were more likely to have higher number of vessels with significant stenosis (OR; 1.41, 95% and CI; 1.03, 1.93) and to have received statins (OR; 1.84, 1.09, 3.13). The mean hsCRP values reduced significantly as the Rentrop grades increased (trend, P = 0.0006). After adjusting for age, gender, statin use, clinical presentation with acute coronary syndrome, diabetes mellitus and the number of vessels with significant stenosis, each 10-unit increase in hsCRP values corresponded to a 31% reduced odds of having a higher collateral score (OR; 0.69, 95% and CI; 0.53, 0.90). CONCLUSIONS: Our findings indicate that elevated hsCRP levels are associated with a significant impairment in coronary collateralization. These data suggest a previously unrecognized mechanism through which inflammation may worsen cardiovascular outcomes.

Aged↗
PubMed1993

Transcranial Doppler validation pilot study.

The use of transcranial Doppler sonography (TCD) for the evaluation of patients with ischemic cerebrovascular disease remains controversial. This study was organized to gather preliminary data regarding the sensitivity and specificity of TCD when compared to cerebral angiography in detecting stenosing lesions and collateral flow patterns of the anterior cerebral circulation. Forty-two patients from six medical centers were prospectively enrolled. Each received cerebral angiography and TCD testing within 24 hours of each other. Based on TCD criteria established a priori, the results were first analyzed by a blinded investigator and then by computer. Computerized analyses were then repeated with modified criteria. Collateral flow through the anterior communicating and ophthalmic arteries was detected with sensitivities of 62% and 100%, and specificities of 98% and 92%, respectively. Internal carotid artery proximal and distal severe ( greater than 70%) stenoses were detected with sensitivities of 79% and 100% and specificities of 88% and 97%. Middle and anterior cerebral artery stenoses and middle cerebral artery occlusion were detected with specificities exceeding 98%; however, the data were insufficient to determine sensitivity. Computerized analyses did not permit improvement of sensitivity and specificity of the baseline criteria. The selected TCD criteria are highly specific in detecting intracranial stenoses and collateral flow patterns of the anterior circulation. The criteria have limited but acceptable sensitivity and specificity in detecting internal carotid artery origin severe stenoses, and are highly sensitive in detecting ophthalmic artery retrograde flow. A study with a larger sample is necessary to provide definitive guidelines for diagnosis.

Adult↗
PubMed1994

Regulation of native collateral vessel dilation after coronary occlusion in the dog.

The purpose of this study was to examine mechanisms involved in the response of native collaterals to coronary occlusion. In anesthetized dogs native collaterals were identified as vessels coursing between the left anterior descending and left circumflex arteries using fluorescence angiography. After a left anterior descending occlusion in 12 dogs, collaterals < 100 microns in diameter progressively dilated by 21 +/- 4% (n = 12) 1 min after occlusion and by 39 +/- 6% 15 min after occlusion. Collaterals > 100 microns in diameter did not dilate after coronary occlusion. NG-nitro-L-arginine (1 mg/min intracoronary) caused constriction under basal conditions in collaterals < 100 microns but did not prevent the dilation of collaterals after occlusion. In contrast, glibenclamide (10(-5) M), an inhibitor of ATP-sensitive potassium channels, had no effect on baseline diameter of collaterals < 100 microns diameter but completely prevented dilation of collaterals after occlusion. We conclude that collaterals are not maximally dilated immediately after a coronary occlusion but rather progressively dilate for at least 15 min after an occlusion. This dilation of native collaterals after an occlusion is not mediated by release of an endothelium-derived relaxing factor derived from L-arginine but is mediated by activation of ATP-sensitive K+ channels.

Acetylcholine↗
PubMed1995

Modulation of coronary collateral angiogenesis: a canine model of neovascularization induced by chronic ischemia.

Coronary collateral development in response to chronic myocardial ischemia is modulated by the integrated release of a variety of growth factors. Protamine, a specific inhibitor of angiogenesis in vitro and in vivo, may attenuate coronary collateral development. The purpose of this investigation was to characterize a model of canine coronary collateral development and to ascertain the effects of protamine on collateral perfusion in response to chronic myocardial ischemia. Ischemia-induced coronary collateral enhancement in response to daily, repetitive, 2-minute left anterior descending (LAD) coronary artery occlusions over 22 consecutive days was demonstrated in control (saline treated) dogs by time dependent, significant (p < 0.05) increases in collateral blood flow to ischemic myocardium. Concomitant with increases in collateral perfusion, myocardial contractile function during LAD occlusion was progressively normalized, and percent coronary flow repayment was reduced successively. These indicators of collateral development were attenuated significantly by administration of subcutaneous protamine. The present findings demonstrate that a model of brief, repetitive, coronary artery occlusion in chronically instrumented dogs sensitively elicits extensive enhancement of the coronary collateral circulation in response to chronic myocardial ischemia. In contrast, protamine attenuates coronary collateral development through its actions as an inhibitor of angiogenesis.

Animals↗
PubMed1998

[Detection of coronary artery disease by adenosine triphosphate stress echocardiography: comparison with adenosine triphosphate stress thallium myocardial scintigraphy and coronary angiography].

The clinical feasibility and usefulness of adenosine triphosphate-2Na (ATP) stress echocardiography for the detection of coronary artery disease (CAD) were assessed. Two-dimensional echocardiography and thallium-201 single photon emission computed tomography (SPECT) during ATP infusion were performed simultaneously in 58 consecutive patients (41 men and 17 women; mean age 66 +/- 12 years) with suspected CAD. ATP was infused intravenously at 0.16 mg/kg/min for 5 min and thallium was injected at 4 min. All patients underwent coronary angiography within 2 weeks of ATP echocardiography and ATP SPECT. An ischemic response during ATP infusion was detected by echocardiography as the development or worsening of a wall motion abnormality compared with the baseline and by SPECT as a perfusion defect that filled totally or partially during redistribution. Significant coronary artery stenosis was defined as > or = 75% diameter stenosis in a major epicardial vessel. The severity of the stenosis was classified as follows: Group A, lesions with significant coronary artery stenosis (> or = 75%, < 90%); Group B, lesions with severe coronary artery stenosis (> or = 90%) without collateral circulation; Group C, lesions with severe coronary artery stenosis (> or = 90%) with collateral circulation. Significant CAD was present in 43 of 58 patients. The overall sensitivity, specificity and accuracy of ATP echocardiography for detecting significant CAD were 70%, 100% and 78%, respectively, and those of ATP SPECT were 98%, 87% and 95%, respectively. In patients without previous myocardial infarction, the sensitivity of ATP echocardiography was 67%. The sensitivity of ATP echocardiography and ATP SPECT for detecting myocardial ischemia were 59% and 95% in patients with 1-vessel disease, 75% and 100% in those with 2-vessel disease, and 88% and 100% in those with 3-vessel disease, respectively. The induction of wall motion abnormality by ATP echocardiography was highly concordant with ATP SPECT imaging in patients with multivessel disease. Although the sensitivity of ATP echocardiography improved in patients with multivessel disease more than in those with single-vessel disease, detection of all diseased vessels was achieved in only 10% of patients with multivessel disease. The sensitivity of ATP echocardiography and ATP SPECT for detecting myocardial ischemia in individual vessels were: right coronary artery, 58% and 74%; left anterior descending artery, 59% and 97%; left circumflex artery, 27% and 68%. ATP-induced transient perfusion defects were associated with transient wall motion abnormality in only 57% of segments. The sensitivity of ATP echocardiography and ATP SPECT for detecting myocardial ischemia in patients with severe coronary stenosis were: Group A, 32% and 66%; Group B, 60% and 93%; Group C, 80% and 95%. The sensitivity of ATP echocardiography was significantly higher in the lesions with collateral circulation than in those without collateral circulation. ATP stress echocardiography is useful for detecting myocardial ischemia in patients with multivessel disease and in patients with severe coronary artery stenosis (> or = 90%). In particular, transient wall motion abnormality tends to be detected in the segments perfused by collateral circulation.

Adenosine Triphosphate↗
PubMedDate not supplied

Selective MR angiography and intracranial collateral blood flow.

This study evaluates the usefulness of MR angiography (MRA) in analyzing the individual collateral flow dynamics and anatomy of the circle of Willis in patients with high-grade extracranial carotid stenosis or occlusion. Selective MRA of the carotid or vertebrobasilar territory was performed by means of presaturation of up to three of the brain-supplying arteries at the level of the middle or lower neck (angled presaturation slabs). Results obtained with selective and nonselective arterial MRA in 45 consecutive patients were compared with findings at transcranial Doppler ultrasonography and intraarterial angiography, the latter serving as the "gold standard." Sensitivity of selective MRA in detecting intracranial collateral circulation via the anterior and posterior communicating artery was 95 and 97%, respectively; sensitivity in depicting extracranial to intracranial transorbital flow was lower (67%). Nonselective arterial MRA was 100% sensitive in detecting a nonfilling of the horizontal (A1) segment of the anterior cerebral artery and in identifying an origin of the posterior cerebral artery from the intracranial carotid artery. Visibility of the posterior communicating artery at MRA predicted for pathological collateral flow via this vessel in all cases. We conclude that selective and nonselective MRA of the cerebral arteries as used here is the most powerful noninvasive method to demonstrate collateral circulation via the basal communicating arteries and to identify hemodynamically relevant anatomic variants of the circle of Willis.

Adult↗
PubMed2001

Echo-enhanced transcranial color-coded duplexsonography to study collateral blood flow in patients with symptomatic obstructions of the internal carotid artery and limited acoustic bone windows.

We prospectively evaluated 30 consecutive patients with echo-enhanced transcranial color-coded duplexsonography (TCCD) and correlative transfemoral digital subtraction angiography to assess the diagnostic efficacy of echo-enhanced TCCD for evaluation of collateral pathways through the circle of Willis in patients with limited acoustic bone windows and critical symptomatic carotid disease. Echo-enhanced TCCD detected collateral blood flow through the anterior communicating artery in 16 of 18 patients (sensitivity 89%, 95% CI 65-99%) and was false positive in one out of 12 patients without collateral flow (specificity 92%, 95% CI 59-100%). For the posterior communicating artery, sensitivity was 11/14 (79%, 95% CI 49-95%) and specificity was 15/16 (94%, 95% CI 70-100%). Echo-enhanced TCCD enables to study collateral blood flow through the communicating arteries of the circle of Willis with high sensitivity and specificity in patients with obstructions of the internal carotid artery and limited acoustic bone windows.

Aged↗
PubMed2005

Exercise training increases basal tone in arterioles distal to chronic coronary occlusion.

Endurance exercise training increases basal active tone in coronary arteries and enhances myogenic tone in coronary arterioles of control animals. Paradoxically, exercise training has also been shown to augment nitric oxide production and nitric oxide-mediated relaxation in coronary arterioles. The purpose of the present study was to examine the effect of exercise training on basal active tone of arterioles (approximately 150 microm ID) isolated from the collateral-dependent region of hearts exposed to chronic coronary occlusion. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery of miniature swine. Arterioles were isolated from both the collateral-dependent and nonoccluded myocardial regions of sedentary (pen confined) and exercise-trained (treadmill run; 14 wk) pigs. Coronary tone was studied in isolated arterioles using microvessel myographs and standard isometric techniques. Exposure to nominally Ca2+-free external solution reduced resting tension in all arterioles; decreases were most profound (P < 0.05) in arterioles from the collateral-dependent region of exercise-trained animals. Furthermore, nitric oxide synthase (NOS) inhibition (N(omega)-nitro-L-arginine methyl ester; 100 microM) unmasked markedly increased nitric oxide-sensitive tone in arterioles from the collateral-dependent region of exercise-trained swine. Blockade of K+ channels revealed significantly enhanced K+ channel contribution to basal tone in collateral-dependent arterioles of exercise-trained pigs. Protein content of endothelial NOS (eNOS) and phosphorylated eNOS (pS1179), determined by immunoblot, was elevated in arterioles from exercise-trained animals with the greatest effect in collateral-dependent vasculature. Taken together, we demonstrate the interaction of opposing exercise training-enhanced arteriolar basal active tone, nitric oxide production, and K+ channel activity in chronic coronary occlusion, potentially enhancing the capacity to regulate blood flow to collateral-dependent myocardium.

Animals↗
PubMed2002

Collateral circulation in internal carotid artery occlusion. A study by duplex scan and magnetic resonance angiography.

BACKGROUND: Clinical effects of internal carotid artery (ICA) occlusion may range from the absolute absence of symptoms to lethal hemispheric stroke. In this paper symptoms of patients with ICA occlusion have been related to the development of collateral circulation, different types of developed collateral circulation have been assessed, and the degree of sensitivity and specificity of duplex scan has been appraised. METHODS: Forty-eight patients with ICA occlusion or subocclusion, 24 males and 24 females, aged between 50 and 83 years (67.7+/-7.15), underwent duplex scan and magnetic resonance (MR) angiography. Nineteen patients were completely asymptomatic, 20 patients showed permanent neurological symptoms and 9 patients had shown transient symptoms. RESULTS: Twelve patients (25%) did not show any collateral circulation, 29 patients (60%) showed collateral circulation through homolateral external carotid artery branches and 7 patients (15%) showed collateral circulation through other circuits. Of the 20 patients with permanent symptoms only 8 showed collateral circulation. On the contrary, all the 19 asymptomatic patients and the 9 patients with transient symptoms showed collateral circulation. Eventually, duplex scan showed 78% sensitivity, 100%, specificity and 83% diagnostic accuracy. CONCLUSIONS: Our data show: 1) a clear-cut prevalence of collateral circulation through homolateral external carotid artery branches with respect to other possible collateral circulation; 2) an inverse relationship between the development of collateral circulation and the appearance of permanent symptoms; 3) a good diagnostic accuracy of duplex scan in revealing collateral circulation in the case of ICA occlusion.

Aged↗
PubMed1980

[Criteria of myocardial ischemia in bicycle ergometry of patients with stenosing arteriosclerosis of the cardiac coronary arteries depending on the initial ECG at rest].

The sensitivity of various criteria of the physical exercise test in revealing myocardial ischemia was studied in 2 groups of patients with ischemic heart disease: 1st group of 64 patients with normal ECG at rest, 2nd group of 96 patients with cicatricial changes in the myocardium. Selective coronography demonstrated atherosclerotic narrowing (stenosis of more than 70%) of one or more coronary arteries of the heart in all patients. During physical exercise an attack of angina pectoris without "ischemic" changes on the ECG occurred in 36.1% of patients of the 1st group and in 22.4% of patients of the 2nd group. The frequency of other clinical signs of cessation of the exercise (dyspnoea, change of arterial pressure, extrasystole and others) was three and a half times higher in patients with cicatricial changes in the myocardium. It is concluded that the frequency with which signs of myocardial ischemia are revealed during physical exercise depends not only on the pronounced character of the pathological coronary condition and the development of collateral circulation but also by the sensitivity of the separate ECG leads and the presence and localization of cicatricial changes in the myocardium.

Adult↗
PubMedDate not supplied

Enterocyte response to ischemia is dependent on differentiation state.

Enterocytes at the tips of microvilli are more sensitive to an ischemic insult than those cells residing in the crypts, an effect thought to be due to a relative lack of collateral flow. We speculated that this increased cellular sensitivity to ischemia might be an intrinsic feature of the cells related to their differentiated phenotype. To test this hypothesis, enterocyte response to ischemia was determined using both in vivo and in vitro models. For the in vivo studies, male Sprague-Dawley rats underwent laparotomy, and small intestinal ischemia was induced by clamping the superior mesenteric artery for 30 or 60 minutes, after which reperfusion was allowed for various time points up to 4 days. Injury was assessed histologically, as well as with Northern blots, probing for the enterocyte differentiation markers intestinal alkaline phosphatase and lactase, as well as the gut-epithelial marker villin. Mucosal changes consistent with ischemia/reperfusion injury were evident--that is, a rapid inflammatory response followed by progressive villus cell loss beginning at the tips and progressing to the crypts, depending on the degree of insult, with an eventual return to normal microanatomy. Intestinal alkaline phosphatase and lactase were lost immediately after ischemia and returned with reperfusion, confirming that the differentiated cells are particularly sensitive to ischemic injury. The in vitro studies employed two separate models of enterocyte differentiation: sodium butyrate-treated HT-29 cells and Caco-2 cells maintained for 7 days after confluence. In both models, undifferentiated and differentiated cells were subjected to treatment with 2-deoxyglucose and oligomycin-A (in vitro model of ischemia) and apoptosis was assessed by fluorescence-activated cell sorting analysis. Differentiation of both cell lines resulted in a significantly greater apoptotic response to ischemia compared to undifferentiated cells exposed to an identical insult. We conclude that differentiated enterocytes may be inherently more sensitive to ischemia-induced injury than their undifferentiated counterparts. These findings call into question the popularly held belief that villus tip cells are more susceptible to ischemia because of their location relative to the microvascular anatomy.

Animals↗
PubMed2006

Granulocyte-macrophage colony-stimulating factor stimulates arteriogenesis in a pig model of peripheral artery disease using clinically applicable infusion pumps.

BACKGROUND: A growing number of patients suffer from peripheral artery disease (PAD). Current therapies are often limited by the extent of vascular pathology and the occurrence of restenosis after angioplasty. The stimulatory effect of growth factor administration on collateral vessel formation (arteriogenesis) has evolved as a potential new treatment for this patient group. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to stimulate arteriogenesis in small-animal models and in a pilot study in patients with coronary artery disease. Although a recent clinical study demonstrated disappointing results after subcutaneous GM-CSF application in patients with PAD, we hypothesized that intra-arterial cytokine application using implantable infusion pumps might well stimulate arteriogenesis in a large-species model of peripheral vascular disease. We also aimed to compare continuous and intermittent infusion regimens and to validate experimental and clinically available measurements of collateral artery growth. METHODS: Twenty-four pigs underwent unilateral occlusion of the right femoral artery and received either GM-CSF continuously, GM-CSF intermittently, or phosphate-buffered saline (PBS). After 1 week, collateral conductance was determined under maximal vasodilatation with adenosine and by using a pump-driven extracorporal shunt system. RESULTS: Conductance showed a significant stimulatory effect of GM-CSF on arteriogenesis (collateral conductance [mL/min/mm Hg]: PBS, 37.7 +/- 5.4; GM-CSF continuous, 69.2 +/- 12.5; GM-CSF intermittent, 71.5 +/- 11.1). Flow measurements under reactive hyperemia were consistent with these results (flow occluded/non-occluded hind limb: PBS, 40.5% +/- 9.1%; GM-CSF continuous, 48.9% +/- 3.9%; GM-CSF intermittent, 48.7% +/- 4.4%). Measurements of ankle/brachial indices were not sensitive enough to detect the differences in collateral growth between the three groups. CONCLUSION: These results demonstrate the proarteriogenic properties of GM-CSF in larger animal species, revealing comparable efficacy of continuous and intermittent intra-arterial infusion. Furthermore, we provide evidence that implantable pumps offer a possible means for the intra-arterial application of growth factors. Intra-arterial application of GM-CSF might be a future treatment option for vascular occlusive disease. Finally, we show that in the peripheral circulation, pressure measurements alone have a low sensitivity to determine the effects of proarteriogenic therapy compared with flow or combined flow-pressure measurements.

Analysis of Variance↗
PubMed1997

Migration and healing of ligament cells under inflammatory conditions.

It is well documented that the adult human medial collateral ligament has a functional healing response, whereas the anterior cruciate ligament does not. The differential healing responses of the medial collateral and anterior cruciate ligaments could be due to factors caused by different biological conditions and locations in vivo. In addition, different intrinsic properties of the constituent cells of these ligaments may contribute to their different healing abilities. Ligament healing follows an orderly process of hemorrhage, inflammation, proliferation, and remodeling. At the cellular level, healing involves a cell's detachment from and attachment to the matrix adjacent to the wound area, migration, and proliferation. This study sought to investigate whether, during migration, the responses of the medial collateral and anterior cruciate ligament fibroblasts are intrinsically different under the same inflammatory conditions. Human medial collateral and anterior cruciate ligament fibroblast cells were cultured, and in vitro wounds were simulated by streaking the cells with an inoculating loop, creating a cell-free area. The migration of the cells into this gap, thus filling the cell-free area, was observed. Two sets of experiments were conducted; one varied the wound width and the other added the inflammatory factors tumor necrosis factor-alpha, complement C5a, and lipopolysaccharide. As the width of the wound increased, the rate of recovery decreased for both types of ligament cells (slope: anterior cruciate ligament, 0.13 hour/micron and medial collateral ligament, 0.10 hour/micron). Also, the three inflammatory factors used all inhibited the recovery rates of both ligaments to ones that were 1.4-2.3 times slower than controls. However, in both sets of experiments, the anterior cruciate ligament fibroblasts were more sensitive to inflammatory factors, and the medial collateral ligament fibroblasts had faster recovery rates (anterior cruciate ligament, 1.2-3.4 times slower than rates for medial collateral ligament fibroblasts, excluding those under lipopolysaccharide treatment). The results showed that medial collateral and anterior cruciate ligament fibroblasts responded differently under the same inflammatory conditions. This may suggest that these differences in intrinsic properties contribute to their different healing responses and abilities.

Anterior Cruciate Ligament↗
PubMed1998

[The significance of magnetic resonance venography in the pre-interventional clarification of a malignant superior venous obstruction].

PURPOSE: Comparison between peripheral digital subtraction venography (DSV) and magnetic resonance venography (MRV) in planning for stent placement in malignant superior central venous obstruction. METHOD: 19 patients with malignant central vein obstruction were examined by DSV (n = 19) and MRV (n = 19). For each patient 12 segment-vessel evaluation was performed to review for obstruction and then compared with the gold standard--selective catheter phlebography--performed at the time of stent insertion. Additionally, tumor extension and collateral venous outflow was noted. RESULTS: Sensitivity, specificity, and accuracy amounted to 92%, 96%, and 95% for DSV and 98%, 100%, and 100%, respectively for MRV. The McNemar test revealed a significance between MR venography and DSV. CONCLUSIONS: With regard to planning of stent placement, a more exact evaluation was possible with MR venography than with DSV. Thus, MR venography can replace DSV as the method of choice for clarifying malignant superior central vein obstructions prior to stent placement.

Adult↗
PubMed1999

Body-rocking and other habits of college students and persons with mental retardation.

Prevalence of body-rocking in college students was assessed, and the characteristics of body-rocking of college students were compared to those of individuals with mental retardation. For college students, the prevalence depended on the restrictiveness of the method used and varied between 3% and 25%. Video samples showed that when compared with college students, a greater proportion of people with mental retardation engage in body-rocking, seem less sensitive to situational factors, demonstrate atypical collateral behaviors, engage in less leg-kicking, and execute their body-rocking with larger amplitudes. There were no differences in duration or number of individual rocks or bouts of body-rocking. We conclude that body-rocking is a "normal" behavior whose form of expression may become atypical.

Adolescent↗
PubMed2005

Nitric oxide (NO)- and nitroxyl (HNO)-generating diazeniumdiolates (NONOates): emerging commercial opportunities.

Diazeniumdiolate ions are convenient and, for a variety of applications, uniquely advantageous nitric oxide (NO) dosage forms. Ionic diazeniumdiolates generate bioactive NO in physiological fluids truly spontaneously (i. e., without metabolism or redox activation), with reliable half-lives ranging from 2 seconds to 20 hours depending on the ion's structure. They are generally simple-to-prepare solids with excellent shelf life and high NO content - up to 40% by weight. Very importantly from the pharmaceutical point of view, the ionic diazeniumdiolates can be easily derivatized to prodrug forms that can be activated for NO release enzymatically, photolytically, or by slowed hydrolysis, allowing for rational design of strategies for targeting pharmacological delivery of NO to sites of need without unwanted collateral exposure of other NO-sensitive compartments. In addition to their world-wide sale for use in probing the chemical biology of NO, published proof-of-concept studies with diazeniumdiolates suggest several more lucrative applications. These include: converting existing drugs and biologicals to NO-releasing form to improve performance and/or extend patent life; diazeniumdiolating medical devices for improved biocompatibility; anticancer drug discovery; use as surgical aids and for wound repair; field generation of NO gas; and non-medical uses such as extending the post-harvest life of cut flowers. Future work aimed at exploiting the full clinical potential of diazeniumdiolate technology will be pursued in this laboratory and strongly encouraged in others, with a concurrent fundamental research effort to broaden the knowledge base from which further opportunities can be inferred [e. g., exploiting the very recent finding that some diazeniumdiolates appear to offer a versatile platform from which nitroxyl (HNO)-generating prodrugs can be developed].

Animals↗
PubMed1989

Normal numbers of retinotectal synapses during the activity-sensitive period of optic regeneration in goldfish: HRP-EM evidence implicating synapse rearrangement and collateral elimination during map refinement.

Optic and nonoptic fibers and synapses were counted in the primary optic innervation layer (S-SO-SFGS) in anteromedial tectum in normal goldfish and in fish 30, 60, and 240 d after the optic nerve was crushed. A newly developed "cold-fill" HRP-labeling protocol was used to label optic afferents for electron microscopy, and counts were then made on EM photomontages of columns through the HRP-labeled S-SO-SFGS. Normal numbers of retinotectal synapses were present at 30 d regeneration, at a time when activity-dependent refinement of the optic projection is incomplete. Normal numbers were also found at 60 and 240 d, when refinement is largely completed. In contrast to this constancy in optic synapse numbers, there was nearly 10 times the normal number of optic fibers in the SFGS at 30 d, and these were reduced by 50% at 60 d, remaining over 4 times normal at 240 d. These findings imply extensive rearrangement of optic synapses during map refinement. They also indicate that synapse rearrangement is associated with the elimination of optic collaterals.

Animals↗
PubMed1995

Color Doppler sonography of the thoracic inlet veins.

Color duplex sonography of the thoracic inlet veins produces a spectrum of normal and abnormal findings. These vessels include the internal jugular, innominate, subclavian, and axillary veins. Although venography is the traditional means of imaging these veins, ultrasound lends itself to assessment of these vessels by providing anatomic and hemodynamic information. Advances in gray-scale resolution and color Doppler technology permit direct visualization of thrombus, stenosis, collateral vessels, catheters, and stents, as well as sensitive spectral waveform analysis. Abnormal findings in the thoracic inlet veins include locally elevated velocities at stenoses with low velocities peripherally. Thrombus, extrinsic compression, and collateral vessels may also produce abnormal findings. Common interpretive pitfalls are caused by transducer pressure, deep inspiration, slow flow, collateral veins, large-bore catheters, and hemodialysis fistulas. A thorough knowledge of the regional anatomy, normal and abnormal waveforms, and commonly encountered pitfalls will optimize the accuracy of color duplex sonography of the thoracic inlet veins.

Axillary Vein↗