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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

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↗
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↗
PubMed1986

Preservation of endothelium-dependent vascular relaxation in cholesterol-fed rabbit by treatment with the calcium blocker PN 200110.

We tested the effects of low doses of a dihydropyridine calcium antagonist, PN 200110, on endothelium-dependent vascular relaxation in rabbits fed a 1% cholesterol diet. The drug was given orally, 1 mg/day, and control rabbits received placebo. Plasma total cholesterol after 10 weeks, was similar in the placebo- and PN 200110-treated groups. The respective values averaged 2140 +/- 116 (n = 14; mean +/- SEM) and 2012 +/- 115 mg/dl (n = 13). In placebo-treated rabbits, sudanophilic aortic lesions covered 52 +/- 5% of the intimal surface, and the aortic cholesterol concentration was 72 +/- 6 mg/g protein. Corresponding values in aortas from PN 200110-treated rabbits were significantly lower [36 +/- 5% (P less than 0.03) and 52 +/- 3 mg/g protein (P less than 0.03)]. Maximal endothelium-dependent cholinergic relaxation of aortic strips in untreated (n = 14) and treated cholesterol-fed rabbits (n = 13) differed significantly (P less than 0.01) and averaged 31 +/- 4% and 61 +/- 7% of the value in normocholesterolemic controls (n = 13). We conclude that cholesterol feeding suppresses endothelium-dependent relaxation evoked by acetylcholine, and that PN 200110 reduces the severity of atherosclerosis and impairment of endothelium-dependent relaxation.

Animals↗
PubMed1979

Nifedipine: a myocardial protective agent.

The effectiveness of the calcium antagonist nifedipine in preserving postischemic myocardial function and structural integrity was experimentally demonstrated in isolated rabbit hearts, in conscious dogs subjected to myocardial infarction, in open chest anesthetized dogs with normothermic regional ischemia induced for 1 to 2 hours and in dogs undergoing hypothermic global ischemia for 2 hours followed by 2 hours of reperfusion. Nifedipine had a beneficial effect on postischemic myocardial stiffness and mitochondrial calcium accumulation, which were correlated. Administration of nifedipine at the onset of myocardial infarction increased blood flow to ischemic zones of myocardial infarction and resulted in less loss of creatine kinase. It reduced by two- to three-fold the volume of the ischemia-reperfusion injury induced by left anterior descending coronary arterial occlusion and release and preserved indexes of hemodynamic function. Nifedipine was found effective in protecting myocardial performance and structure after 2 hours of global ischemia during hypothermic cardiopulmonary bypass. It is suggested that this agent may be useful as an adjunct to cold cardioplegia in man for enhanced myocardial protection during cardiac surgery.

Animals↗
PubMed1979

Sensitization of isolated canine coronary arteries to calcium ions after exposure to cholesterol.

The abundance of membrane cholesterol is an important determinant of the functional properties of biomembranes. To determine whether arterial smooth muscle acquires altered contractile properties in a high cholesterol environment, isolated canine coronary arteries were exposed to cholesterol in stable aqueous solution. Cholesterol, 10(-12) to 10(-10) M, was an efficacious vasoconstrictor, as maximum contractions equaled those obtained with 15 mM KCl. Antiadrenergic interventions, including chemical sympathectomy in vivo with 6-hydroxydopamine and alpha- and beta-adrenergic blockade with phentolamine and L-propranolol (both 10(-6 M), did not significantly attenuate the contractions. However, responses to cholesterol were abolished completely by (+/-)-verapamil (10(-6) M). Cholesterol in picomolar concentration enhanced the constrictor effects of CaCl2 and KCl, both in the presence and absence of alpha- and beta-adrenergic blockade. Increases in tone in response to graded elevations in the CaCl2 concentration (0-2 mM) were augmented up to 1.5-fold by 10(-12) M cholesterol (P less than 0.01). Results indicate that cholesterol sensitizes isolated coronary arteries to external Ca2+ by a nonadrenergic mechanism. The findings are consistent with the hypothesis that acquisition of membrane cholesterol may alter the contractile properties of coronary arterial smooth muscle, a phenomenon that could play a role in the pathophysiology of atherosclerotic heart disease.

Animals↗