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Biomedical subjects

P D Henry

Publications and source records attributed to P D Henry.

At least 19 recordsLinked to original sources
PubMed1992

XeCl laser ablation of atherosclerotic aorta: optical properties and energy pathways.

The energetics of 308-nm excimer laser irradiation of human aorta were studied. The heat generation that occurred during laser irradiation of atherosclerotic aorta equaled the absorbed laser energy minus the fraction of energy for escaping fluorescence (0.8-1.6%) and photochemical decomposition (2%). The absorbed laser energy is equal to the total delivered light energy minus the energy lost as specular reflectance (2.4%, air/tissue) and diffuse reflectance (11.5-15.5%). Overall, about 79-83.5% of the delivered light energy was converted to heat. We conclude that the mechanism of XeCl laser ablation of soft tissue involves thermal overheating of the irradiated volume with subsequent explosive vaporization. The optical properties of normal wall of human aorta and fibrous plaque, both native and denatured were determined. The light scattering was significant and sufficient to cause a subsurface fluence (J/cm2) in native aorta that equaled 1.8 times the broad-beam radiant exposure, phi o (2.7 phi o for denatured aorta). An optical fiber must have a diameter of at least 800 microns to achieve a maximum light penetration (approximately 200 microns for phi o/e) in the aorta along the central axis of the beam.

Aorta↗
PubMed1991

Antiperoxidative actions of calcium antagonists and atherogenesis.

Recent experimental and clinical studies suggest that structurally disparate calcium channel blockers retard the progression of atherosclerosis. However, mechanisms of action by which calcium blockers exert their antiatherosclerotic effects have not been completely elucidated. Formation of atherosclerotic lesions involves cells (macrophages, endothelial cells, and platelets) not expressing voltage-dependent (L-type) calcium channels, the major drug receptors for calcium channel blockers. Therefore, it is possible that these drugs act by non-L-type channel mechanisms. Recent reports indicate that nifedipine, verapamil, and diltiazem exert antiperoxidative effects on membrane lipids. It has been suggested that antiperoxidants such as probucol and butylated hydroxytoluene (BHT) exert antiatherosclerotic effects by preventing oxidation of low-density lipoprotein (LDL), a modification thought to confer atherogenic properties to the lipoprotein. Therefore, the beneficial effects of calcium channel blockers might be related to their antiperoxidative activity.

Animals↗
PubMed1990

Atherogenesis, calcium and calcium antagonists.

Hypercholesterolemia and arterial hypertension are highly interrelated risk factors of atherosclerosis. Early lesions in nonhuman primates with dietary hypercholesterolemia resemble atherosclerotic lesions demonstrable in the arteries of American children with comparably elevated plasma cholesterol levels. Lesion formation depends upon calcium-regulated cellular processes such as chemotaxis, adhesion, migration, proliferation, lipid uptake and necrosis. Interventions acting on cell calcium uptake including treatment with calcium chelating agents, lanthanum trichloride, and calcium antagonists may retard atherogenesis in fat-fed animals in the absence of hypolipidemic effects. Recent controlled coronary angiographic trials in patients with coronary artery disease suggest that calcium antagonists may retard the progression of coronary atherosclerosis in humans. Large-scale long-term studies are needed to determine the utility of these agents for the treatment of coronary artery disease.

Animals↗
PubMed1990

Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins.

Atherosclerosis in animals and humans is associated with an unresponsiveness of arteries and arterioles to endothelium-dependent vasodilators--agents acting on smooth muscle indirectly by stimulating the release from endothelial cells of a vasodilator principle (endothelium-derived relaxing factor). Altered vasomotor regulation in atherosclerosis could partly reflect an injurious action of abnormal lipoproteins on endothelium. Recently, 'cell-modified' or 'oxidized' low-density lipoprotein (EC-LDL) has received increasing attention because of its potential cytotoxic and atherogenic properties. We report here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries. Our results indicate that transfer of lysolecithin from EC-LDL to endothelial membranes produces a selective unresponsiveness to receptor-regulated endothelium-dependent vasodilators.

Acetylcholine↗
PubMed1990

Antiatherogenic effects of calcium-channel blockers: possible mechanisms of action.

Calcium-channel blockers (Ca blockers), such as nifedipine, verapamil, diltiazem, flunarizine, and their respective derivatives, have been reported to suppress the formation of arterial lesions in animals fed atherogenic diets. The fact that structurally unrelated Ca blockers exert similar antiatherogenic effects may suggest that the drugs act by a calcium-channel-dependent mechanism. However, in cell culture experiments in which putative antiatherosclerotic effects were observed only in the presence of a very high drug concentration (greater than 10 microM), calcium-channel-independent mechanisms are likely. It does not appear that Ca blockers act predominantly by altering coronary risk factors such as arterial pressure or hypercholesterolemia. On the other hand, current evidence is accumulating that Ca blockers may act by suppressing chemotaxis and the proliferation of cells involved in lesion formation. Recent reports indicate that relatively low concentrations (less than 1 microM) of nifedipine may promote the release of cholesterol from fat-laden smooth cells and macrophages. Controlled clinical trials are needed to determine whether Ca blockers have utility in the prevention of the progression of atherosclerosis in humans.

Animals↗
PubMed1990

Calcium channel blockers and atherosclerosis.

There is evidence that calcium antagonists (calcium channel blockers) may suppress atheroma formation in animals fed high-fat diets. Studies on the antiatherosclerotic effects of calcium blockers have suggested a variety of possible mechanisms: (a) lowering of arterial pressure, (b) decrease in atherogenic plasma lipoproteins, (c) suppression of accumulation of intracellular lipids, (d) suppression of atherogenic platelet dysfunction, (e) prevention of dyslipidemic endothelial injury, (f) inhibition of chemotaxis and cell migration, (g) inhibition of cell proliferation, (h) inhibition of deposition of matrix proteins, (i) suppression of tissue mineralization, and (j) retardation of cell necrosis. Although it is tempting to ascribe the antiatherosclerotic effects of calcium blockers to a blockade of calcium channels, other possible common mechanisms of action involving low-affinity drug-binding sites must be considered. Recently, two randomized, prospective clinical trials designed to determine the effects of calcium channel blockers on the progression of coronary artery disease have been completed. Results of the trials suggest that calcium channel blockers suppressed the progression of coronary atherosclerosis. The utility of calcium channel blockers for the treatment of atherosclerosis will require further evaluation.

Arteriosclerosis↗
PubMed1990

Endothelium-dependent relaxation in human saphenous vein grafts. Effects of preparation and clinicopathologic correlations.

Activity of endothelium-dependent relaxation factor (EDRF) was measured in 139 open ring preparations of fresh human saphenous vein from 85 patients undergoing coronary bypass grafting. The veins were constricted with phenylephrine and relaxed with the EDRF-dependent agents calcium ionophore A23187 or acetylcholine. EDRF activity produced a 36% +/- 4% relaxation of baseline contraction in response to calcium A23187. Vein graft preparation with room-temperature heparinized normal saline and pressurization to 400 mm Hg caused EDRF relaxation to fall to 10.6% +/- 2.0% versus 32.4% +/- 3.4% for control segments (p less than 0.05). Storage alone in room-temperature saline reduced EDRF response to 17.4% +/- 3.9% versus a control of 29.6% +/- 4.7% (p less than 0.05). Storage in heparinized room-temperature blood produced relaxation of 31.4% +/- 4.3% versus 34.1% +/- 5.7% (p less than 0.05). Storage in Plasma-Lyte solution (Travenol Laboratories, Inc., Deerfield, Ill), produced relaxation of 28.4% +/- 6.3% versus 30.1% +/- 5.3% (control) (p greater than 0.05). Veins stored at 2 degrees to 4 degrees C had severe depression of EDRF: 18.2% +/- 4.0% versus 34.0% +/- 5.4% for 37 degrees C storage (p less than 0.05). Pressurization to 400 mm Hg lessened EDRF relaxation: 20% +/- 3% versus 34% +/- 4% (control) (p less than 0.05), and use of nitroglycerin, papaverine, or verapamil produced no improvement. Twenty-eight vein grafts prepared with Plasma-Lyte solution were obtained from 12 patients who died 11.6 days (range up to 66 days) after operation. When compared with control veins prepared with saline and obtained at similar intervals, they had significantly more intact endothelium, less subintimal cellular infiltration, less fibrin deposition, fewer medial inflammatory changes, and less necrosis. Thus EDRF activity is significantly affected by vein graft preparation. Changes in technique to preserve EDRF produced better graft morphology early after operation.

Aged↗
PubMed1989

Stress fibers in endothelial cells overlying atherosclerotic lesions in rabbit aorta.

Endothelial injury or dysfunction has long been postulated to promote atherogenesis, but structural alterations of endothelium in atherosclerosis have remained obscure. We report the common occurrence of actin-containing stress fibers, stainable by rhodamine-phalloidin, in endothelium overlying atherosclerotic lesions in cholesterol-fed rabbits. Nonlesioned areas in the same aortas showed normal endothelium with minimal development of stress fibers, which was no different from the appearance of endothelium in chow-fed rabbits. Microtubule organization revealed by immunofluorescence appeared normal in all areas. The development of stress fibers may be related to an altered substratum for endothelial attachment. This study provided no evidence to relate stress fiber formation with lesion initiation, but an association with well-developed foam cell lesions was evident.

Animals↗
PubMed1988

Calcium antagonists as antiatherogenic agents.

Pharmacological manipulations of calcium metabolism in animals fed high-fat diets may slow the progression of atherosclerosis. Agents with calcium-chelating (diphosphonic acid and thiophene carboxylic acid derivatives) or calcium-channel-blocking properties (dihydropyridine derivatives, verapamil and its derivatives, diltiazem) have been demonstrated to suppress atherogenesis in rabbits and monkeys. The antiatherosclerotic effects appear to occur in the absence of hypolipidemic effects. The mechanisms of action of the structurally unrelated drugs remain to be elucidated.

Animals↗
PubMed1988

Laser-induced autofluorescence of human arteries.

A new technique for imaging the intimal surface of arteries through optic fibers has been devised. With the aid of an optical multichannel analyzer, we recorded in real time fluorescence spectra during excitation of the arterial surface with an argon ion laser. Spectral parameters were used to detect atherosclerotic plaques and to discriminate normal tissue from lipid rich and calcified atheromas. By digitizing relative intensity values and the ratios of the peak at 550 nm to that at 520 nm into a gray scale, we generated pseudocolor maps of the arterial wall of 10 human aortas. Specific color distributions were congruent with the distribution of calcified tissue visualized by soft x-ray radiography and the distribution of lipid delineated by staining with Sudan IV. Thus, bidimensional maps obtained by laser spectroscopy can be used to identify the presence and composition of atherosclerotic lesions. Fluorescence imaging may prove to be an important application of laser techniques for the diagnosis and treatment of atherosclerosis.

Adolescent↗
PubMed1988

Videomicroscopic demonstration of defective cholinergic arteriolar vasodilation in atherosclerotic rabbit.

In atherosclerotic rabbits (SCLER), decreases in vascular resistance in response to acetylcholine (ACH), an endothelium-dependent agent, are suppressed, whereas those to nitroprusside (NP), an endothelium-independent vasodilator, are preserved. To determine whether defective vasodilation in SCLER is related to altered reactivity of resistance vessels, we visualized arterioles of rabbit cremaster muscle by videomicroscopy. Arteriolar diameter was monitored during topical (superfusional) delivery of ACh and NO, interventions that did not affect systemic hemodynamics. Diameter changes in response to NP (0.01-100.0 microM) did not differ between SCLER and controls; maximal dilations amounted to 110 +/- 10% (mean +/- SE). In contrast, responses to ACH (0.001-100 microM) differed; maximal dilations averaged 54 +/- 4% in SCLER and 124 +/- 9% in controls (P less than 0.001). These differences persisted after blockade with phentolamine, propranolol, and indomethacin. Phenidone and hydroquinone blockers of endothelium-dependent vasodilation, inhibited arteriolar dilation to ACH without affecting that to NP. Microvascular responses to intra-arterial drug were similar to those elicited by topical drug. Thus, hypercholesterolemia and atherosclerosis in the rabbit appear to produce a microvascular defect characterized by an impaired endothelium-dependent dilation and a preserved endothelium-independent dilation. This defect could play a role in limiting vasodilator reserve in atherosclerosis.

Acetylcholine↗
PubMed1987

Tissue interactions and measurement of ablation rates with ultraviolet and visible lasers in canine and human arteries.

Ablation rates measured as the depth of tissue excavation per unit time were determined in human and canine aortas subjected to radiation with ultraviolet (UV) excimer (ArF 193 nm, KrF 248 nm, XeF 351 nm) and visible lasers [continuous wave (cw) and 50-ms chopped argon ion, 478 nm-514 nm; pulsed double-frequency Nd:YAG, 532 nm]. For UV and pulsed double-frequency Nd:YAG lasers ablation rates were constant in time and depended linearly on average laser power, but for cw and chopped argon lasers ablation rates varied with irradiation time and were nonlinearly dependent on laser power. In human aortas, atherosclerosis without gross calcification had no influence on ablation rates. Charring and tissue disruption were observed with cw and chopped argon ion, whereas excimer and pulsed Nd:YAG lasers produced only minimal injury to surrounding tissue. We conclude that the determination of ablation rates is useful for the selection of laser wavelengths and power densities applicable to angioplasty and that UV and pulsed visible laser permit a better control of ablation compared to continuous wave lasers.

Animals↗
PubMed1987

Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta.

The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it.

Acetylcholine↗