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P Whittaker

Publications and source records attributed to P Whittaker.

At least 37 records · Page 2Linked to original sources
PubMed1999

Success of transmyocardial laser revascularization is determined by the amount and organization of scar tissue produced in response to initial injury: results of ultraviolet laser treatment.

BACKGROUND AND OBJECTIVE: Previous studies of transmyocardial laser revascularization have reported open channels after ultraviolet laser treatment and closed channels with infrared lasers. We speculated that differences in long-term channel patency were determined by the healing response to injury. METHODS: Channels were made in rat hearts with a frequency-tripled neodymium:YAG laser, at 5 and 10 mJ per pulse, by advancing an optic fiber through the myocardium, from the epicardium to the ventricular cavity. Several months later, we challenged the ability of the channel to supply blood by arterial occlusion and examined the channel structure with polarized light microscopy. RESULTS: Low-pulse energy was associated with lower patency, more fibrosis, and larger infarcts than was the higher energy. Open channels were surrounded by collagen fibers aligned parallel to the channel; in closed channels, fibers were aligned perpendicular to the original channel direction. CONCLUSION: The amount of initial injury and its repair determine channel patency and function.

Animals↗
PubMed1999

Laser-mediated reversal of cardiac expansion after myocardial infarction.

BACKGROUND AND OBJECTIVES: A complication of transmural myocardial infarction is infarct expansion, which can lead to the development of heart failure. However, the necrotic muscle is replaced by collagen, a material known to shrink when heated. Thus, the hypothesis was that thermally-induced scar shrinkage could reverse infarct expansion. STUDY DESIGN/MATERIALS AND METHODS: Four weeks after transmural infarcts were produced by coronary occlusion, rats were randomized to control or treatment with a neodymium:yttrium-aluminum-garnet laser. The epicardial scar surface was irradiated until shrinkage was observed. Thirty minutes later, hearts were excised and fixed at a distending pressure of 15 mm Hg, left ventricular cavity volume was measured, and histologic analysis was performed. RESULTS: Cavity volume was reduced by laser treatment (0.72 +/- 0.07 ml vs. 0.54 +/- 0.05 ml; P= 0.044). In addition, treatment resulted in thicker scars, a leftward shift of the heart's electrical axis, and straightening of collagen fibers. CONCLUSION: Laser treatment resulted in thermally-mediated scar shrinkage, which reversed infarct expansion and reduced cavity volume.

Animals↗
PubMed1999

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Journal Article↗
PubMed1999

Genotoxicity of iron compounds in Salmonella typhimurium and L5178Y mouse lymphoma cells.

The mutagenic activity of elemental and salt forms of iron (Fe), including compounds currently being used in dietary supplements and for food fortification, were evaluated for mutagenicity in Salmonella typhimurium and L5178Y mouse lymphoma cells. Except for the weak response obtained with ferrous fumarate, none of the compounds induced a mutagenic response in Salmonella. In the mouse lymphoma assay, responses were related to the Fe compound and/or reduction of ferric (Fe+3) to ferrous (Fe+2). Responses with the elemental forms of Fe were divergent. Electrolytic Fe with a relatively larger particle size and irregular shape was negative. The smaller-sized carbonyl Fe, which after 4 hr attached to and was taken up by the cells, induced mutagenic responses both with and without S9. With ferric chloride (FeCl3) and ferric phosphate (FePO4), there was an increase in mutant frequency only with S9. With the Fe+2 compounds, ferrous sulfate (FeSO4) and ferrous fumarate (FeC4H2O4), positive responses were observed without S9. The Fe chelate, sodium Fe(III)EDTA was positive in both the presence and absence of S9. The lowest effective doses (LED) for induction of mutagenicity were identified for these compounds and an LED ratio calculated. The LED ratio ranges from 1 for FeSO4 to 30 for carbonyl Fe, which are similar to oral LD50 values obtained in animal studies.

Animals↗
PubMed1999

Transmyocardial revascularization: the fate of myocardial channels.

Attempted cardiac revascularization through laser-made channels has gained considerable recent notoriety. Although the treatment reduces angina, its ability to enhance perfusion is unclear, and the mechanism of action unknown. The fate of the channels appears an obvious place to look for insight. Therefore, this review focuses on temporal and spatial changes in channel morphology. An appreciation of the natural history of the channels not only has potential to elucidate mechanisms, but also to provide the basis for optimization of channel-making.

Animals↗
PubMed1998

Brief antecedent ischemia attenuates platelet-mediated thrombosis in damaged and stenotic canine coronary arteries: role of adenosine.

BACKGROUND: Recent studies suggest that patients with angina before myocardial infarction exhibit improved recovery of coronary perfusion after thrombolysis by an as-yet-unknown mechanism. We therefore proposed that brief antecedent ischemia/reperfusion may, via release of adenosine, improve vessel patency in damaged and stenotic coronary arteries. METHODS AND RESULTS: Anesthetized dogs underwent coronary injury + stenosis, resulting in repeated cyclic variations in coronary blood flow (CFVs) caused by the formation/dislodgment of platelet-rich thrombi. Vessel patency was assessed for 3 hours after stenosis by quantification of the nadir of the CFVs, duration of total thrombotic occlusion (flow=0), and area of the flow-time profile (expressed as percent of baseline flow x 180 minutes). In protocol 1, dogs received 10 minutes of coronary occlusion + 10 minutes of reflow or a comparable 20-minute control period before injury + stenosis. The median nadir of the CFVs was higher (4.0 versus 0.3 mL/min), median zero flow duration per 30-minute time interval was shorter (0.4 versus 15.1 minutes), and mean percent flow-time area was greater (54+/-8% versus 28+/-9%) in dogs that received antecedent ischemia versus controls (P<.05). These benefits of antecedent ischemia/reperfusion were largely mimicked by a 10-minute intracoronary adenosine infusion (400 microg/min) in lieu of brief ischemia (protocol 2) and were abolished by administration of the adenosine A1/A2 receptor antagonist PD 115,199 (3 mg/kg i.v.) before brief antecedent coronary occlusion (protocol 3). CONCLUSIONS: Brief antecedent ischemia attenuates subsequent platelet-mediated thrombosis in damaged and stenotic canine coronary arteries, due, in large part, to an adenosine-mediated mechanism.

Adenosine↗
PubMed1998

Collagen organization in wound healing after myocardial injury.

Our understanding of what constitutes "normal" collagen organization in wound healing after myocardial injury and how such organization is achieved is still in its infancy. However, once this knowledge has been obtained, it may suggest methods of enhancing or even optimizing healing, and thus provide us with the possibility of modifying the structural problems responsible for infarct expansion and rupture.

Animals↗
PubMed1998

Iron and zinc interactions in humans.

Iron deficiency is the most common nutritional deficiency in the world; zinc deficiency is associated with poor growth and development and impaired immune response. Several Third World countries are taking measures to increase the dietary intake of iron and zinc with fortification of foods or dietary supplements. Several studies showed that high iron concentrations can negatively affect zinc absorption in adults when these trace minerals are given in solution. However, when iron and zinc are given in a meal, this effect is not observed. Solomons (J Nutr 1986;116:927-35) postulated that the total amount of ionic species affects the absorption of zinc and that a total dose of >25 mg Fe may produce a measurable effect on zinc absorption. This could occur if iron supplements are taken with a meal, and iron experts recommend that iron supplements be taken between meals. Recent studies using stable isotopes showed that fortifying foods with iron at current fortification amounts has no adverse effect on zinc absorption. There are 5 zinc salts listed as generally recommended as safe (GRAS) by the US Food and Drug Administration for food fortification. From 1970 to 1987, the total amount of zinc salts used in food continually increased, with zinc oxide and zinc sulfate showing the largest increases. Twelve iron sources are listed as GRAS; elemental iron has become the source of choice because it is less expensive to produce and has fewer organoleptic problems. Use of ferrous fumarate is also increasing.

Absorption↗
PubMed1998

Collagen organization in the branching region of human brain arteries.

BACKGROUND AND PURPOSE: Unruptured saccular aneurysms are relatively common, occurring in 4% to 9% of autopsies. Their development at the apex region of brain artery bifurcations is attributed to a combination of structural factors and the effect of blood pressure. Collagen is a primary tension-bearing fabric of the vessel wall, and our purpose was to examine its 3-dimensional alignment at arterial branches. METHODS: Sixteen segments of arteries from the circle of Willis, including bifurcations, were pressure distended, fixed, and sectioned in 1 of 3 orthogonal planes. We measured the 3-dimensional organization of collagen at the flow divider by using the polarized light microscope. An electron microscopy study performed in tandem provided measurements on the collagen fibril diameters and packing density. RESULTS: Orientation data of the collagen fabric were obtained from sections from 3 different cutting planes. The tunica media of all bifurcations had an alignment that was primarily circumferential, and the medial gap (medial defect) was distinguishable at the apex of all bifurcations. The subendothelial layer was thin at the apex but thicker and more disorganized distally. Adventitial collagen showed little organization except for a high degree of alignment along the apex. Results from the electron microscopy study showed densely packed collagen fibrils of uniform diameter at the apex, compared with slightly smaller and less densely packed fibrils nearby. CONCLUSIONS: In the region of the medial gap, a narrow band of highly aligned tendonlike collagen running in the direction of the ridge of the flow divider was a consistent finding. This structure would provide strength and stability to the vessel and is inconsistent with the concept of an inherent defect in the structure of bifurcations.

Adult↗
PubMed1997

Percutaneous treatment of abdominal aortic aneurysm in a swine model: understanding the behavior of aortic aneurysm closure through a serial histopathological analysis.

BACKGROUND: Previous studies used covered stent grafts to treat abdominal aortic aneurysms; however, such devices block flow into aortic side branches. We used uncovered stents with and without additional embolization coils to treat abdominal aortic aneurysm in a swine model and examined serial histological changes in the aneurysms over a 6-month period. METHODS AND RESULTS: We examined aneurysms in 9 control and 9 treated pigs (5 received stents alone and 4 received stents and coils). Aneurysms were surgically created with abdominal fascia. Three days later, we percutaneously placed a self-expandable uncovered stent across the aneurysm. Coils were implanted through the stent into the aneurysm lumen. An aortogram immediately after stent placement showed no significant change in aneurysm lumen; however, in pigs that had aortograms between 6 weeks and 6 months after treatment, the diameter decreased (28% to 65%) in 4 of 5 pigs, and 1 had no discernible aneurysm. Three treated pigs died, but only 1 from rupture. In contrast, 7 untreated aneurysms ruptured (2 pigs died of other causes). Histological examination revealed that the aneurysm lumen was reduced after treatment by collagen production. This healing process was accelerated in aneurysms treated with both stents and coils. In contrast, only limited amounts of new collagen were found in untreated, ruptured aneurysms. Instead, the fascia was disrupted and there was evidence of collagen degradation. CONCLUSIONS: We found that uncovered stents reduce the likelihood of aneurysm rupture in a swine model without blocking arterial branches. The presence of coils enhanced filling of the lumen by collagen.

Aneurysm, Ruptured↗
PubMed1997

Collagen content is significantly lower in restenotic versus nonrestenotic vessels after balloon angioplasty in the atherosclerotic rabbit model.

BACKGROUND: It is recognized that restenosis is primarily due to alterations in geometric remodeling of the extracellular matrix rather than intimal hyperplasia. Prior studies have shown that angioplasty stimulates an increase in both synthesis and degradation of collagen in the atherosclerotic vessel. However, differences in collagen content and metabolism between restenotic and nonrestenotic vessels have not been examined. METHODS AND RESULTS: Four weeks after angioplasty in an atherosclerotic rabbit model, collagen content in restenotic and nonrestenotic vessels was measured both biochemically by hydroxyproline quantitation and histologically by a digital subtraction method with the use of circularly polarized images of picrosirius red-stained sections. Collagenase and gelatinase activity also were measured in the same restenotic and nonrestenotic vessels by use of a radiosubstrate assay. Collagen content was found to be significantly lower in restenotic vessels than in nonrestenotic vessels both biochemically (127.0 +/- 32.6 versus 212.6 +/- 84.3 micrograms/mg tissue; n = 11 vessels; P < .05) and histologically (67.3 +/- 7.9% versus 76.3 +/- 11.8% area fraction; n = 20 sections from 6 vessels; P = .05). There was a significant inverse correlation between biochemically determined collagen content and gelatinase activity (P = .02) and a significant correlation between histologically determined lumen are and percent collagen content (P = .0071). CONCLUSIONS: Collagen content is significantly decreased in restenotic versus nonrestenotic vessels after angioplasty in the atherosclerotic rabbit model. The increased collagen content in nonrestenotic vessels was associated with preserved lumen area and may play a role in geometric remodeling after angioplasty.

Angioplasty, Balloon↗
PubMed1997

Characterization of collagen by high-frequency ultrasound: evidence for different acoustic properties based on collagen fiber morphologic characteristics.

Fibrous tissue on conventional ultrasound images appears as an echo-bright area. We have observed that on high-frequency ultrasonography images of thin sections of myocardium, fibrous tissue may appear as either a dark or light area. This study was designed to test the hypothesis that echo characteristics of fibrous tissue on high-frequency ultrasonography are determined by collagen fiber morphologic characteristics. We examined 16 tissue specimens from human beings and rats containing different forms of fibrosis. The specimens were sectioned at 5 microns, placed on a glass slide, and imaged with a 600 MHz transducer. On ultrasound images, collagen appeared either as a dark amorphous area or a light area that had a fibrillar pattern. The same specimens were then stained with picrosirius red and examined with polarized light. When viewed with polarized light microscopy, thick collagen fibers appear red or orange and thin fibers appear green or yellow. Polarized light microscopy revealed that dark areas on ultrasound images corresponded to thick collagen fibers that were predominantly longitudinally sectioned. In contrast, light areas corresponded to regions of thin, loosely packed fibers, or to thick collagen fibers that were obliquely sectioned. Collagen has different appearances on high-frequency ultrasound images depending on collagen fiber morphologic characteristics. If such variation in echo intensity also occurs with lower frequency transducers used in clinical echocardiography, the differentiation between normal myocardium and immature scar may be difficult.

Acoustics↗
PubMed1997

The effects of topical calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis.

BACKGROUND: Calcipotriol is an effective treatment of chronic plaque psoriasis. We have previously demonstrated that it has a small effect on systemic calcium homeostasis even at recommended doses. OBJECTIVE: We attempted to determine the mechanism of the effect of calcipotriol on systemic calcium homeostasis so we could assess the possible consequences of long-term use. METHODS: Sixteen patients with extensive chronic plaque psoriasis were hospitalized and treated with high-dose topical calcipotriol. Up to 360 gm of calcipotriol (50 micrograms/gm) ointment was applied per week for 2 weeks under controlled conditions. RESULTS: There was a dose-dependent rise in intestinal absorption of calcium. No effect on bone turnover was demonstrated over this short period. Five patients became hypercalcemic, and there was a dose-dependent rise in serum total adjusted calcium, serum ionized calcium, serum phosphate, urine calcium, and urine phosphate. There was a dose-dependent fall in serum parathyroid hormone and serum 1,25 dihydroxyvitamin D3. CONCLUSION: Calcipotriol exerts its effects on systemic calcium homeostasis by increasing intestinal absorption of calcium and probably phosphate. This results in suppression of parathyroid hormone and 1,25 dihydroxyvitamin D3.

Administration, Cutaneous↗
PubMed1997

The physics of transmyocardial laser revascularization.

Lasers create channels through the myocardium by ablating the tissue and tissue ablation is achieved by breaking the molecular bonds of the organic constituents of the myocardium. Lasers provide the energy required to dissociate these molecular bonds by the interaction of laser photons with the tissue. However, the energy supplied to the electrons within the bonds must match specific allowed energy levels. Such energy matching is accomplished through different mechanisms by different laser wavelengths. Infrared laser photons are strongly absorbed by water in the tissue and it is the subsequent vaporization of the water that provides the energy necessary to break the bonds. In contrast, ultraviolet laser photons are not absorbed by water and have energies that can match those required for bond dissociation. Thus, ablation by ultraviolet lasers is achieved primarily by direct bond absorption of the photons. Both of these ablation mechanisms produce secondary effects that can cause injury to tissue surrounding the channels. The generation of steam or the gaseous breakdown products of tissue proteins can cause thermal injury in addition to the mechanical injury produced by escape of these gases into the tissue. Furthermore, shock waves generated by ablation are also a possible source of mechanical injury, while free radical molecules capable of cell injury are known to be formed after breaking chemical bonds. The variety of tissue interactions provided by the different lasers should enable the optimal laser treatment to be applied once the optimal channel configuration has been determined.

Biophysical Phenomena↗
PubMed1997

Detection and assessment of laser-mediated injury in transmyocardial revascularization.

When channels are made through the myocardium with a laser, tissue surrounding the channels is injured. Thus, methods of examining and quantifying the histologic changes caused by laser-mediated injury are required both for comparison of different channel making protocols and also to help understand the mechanisms of transmyocardial revascularization. The two principal components of the myocardium, collagen and muscle, are both normally birefringent. This optical property can be exploited with the use of polarized light microscopy to assess tissue structure at the cellular and subcellular levels allowing several different types of injury to be detected. Increases in tissue temperature above 60 degrees C for muscle and 70 degrees C for collagen decrease their birefringence and, hence, result in decreased brightness when viewed with polarized light. Lower temperatures may cause cell membrane injury, calcium overload, and the formation of contraction bands, which appear as areas of increased birefringence. In this way, the extent of thermal injury can be assessed. The same optical properties can be used to measure cell and fiber orientation and, hence, enable assessment of mechanical disruption of the tissue after ablation. Long-term remodeling of the myocardium in the form of scar formation, increased interstitial fibrosis, and muscle disarray can also be quantified. The ability to measure the acute injury and the long-term structural consequences of that injury with the use of polarized light microscopy should prove vital in determining the optimal laser "dose" required and may also reveal information on the mechanism(s) of benefit found with transmyocardial revascularization.

Animals↗