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Biomedical subjects

M L Armstrong

Publications and source records attributed to M L Armstrong.

At least 73 records · Page 4Linked to original sources
PubMed1988

Responsiveness of iliac collateral vessels to constrictor stimuli in atherosclerotic primates.

This study was performed to examine, first, the protective effects and responses of collateral vessels of the hind limb in normal and atherosclerotic monkeys and, second, the effects of chronic arterial occlusion on the development of atherosclerosis. The iliac artery was ligated on one side in cynomolgus monkeys. Sixteen months later, we recorded the pressure gradient across the limb collaterals and measured blood flow with microspheres. Collateral conductance was fivefold greater after chronic ligation of the iliac artery than after acute ligation. Despite dilatation or growth of collateral vessels after chronic ligation, iliac pressure was reduced distal to the ligation. Blood flow to the limb was normal after chronic ligation in both normal and atherosclerotic monkeys. Collateral vessels constricted in response to infusion of phenylephrine and serotonin in normal and atherosclerotic monkeys. Thus, one conclusion of this study is that collateral vessels restore limb blood flow to normal after chronic vascular occlusion in both normal and atherosclerotic monkeys, but the protective effects of collateral vessels may be compromised by vasoconstrictor stimuli. Morphometric measurements indicated that occlusion of the iliac artery reduced proliferation of atherosclerotic intima distal to the occlusion in the cholesterol-fed monkeys. Thus, a second conclusion of this study is that atherosclerosis is attenuated below an arterial occlusion.

Animals↗
PubMed1987

Diffusional support of the thoracic aorta in atherosclerotic monkeys.

We have demonstrated previously that there is increased blood flow through vasa vasorum in the aorta of atherosclerotic monkeys. In this study, a new method was used to examine diffusional support to the wall of blood vessels. Our goal was to determine whether proliferation of vasa vasorum in the outer media contributes to increased diffusional support of the atherosclerotic aorta and whether there are focal or homogeneous increases in diffusion to the aortic wall. Cynomolgus monkeys were fed normal or atherogenic diet for 1.5 or 4 years. Diffusional support of the thoracic aorta was determined by measuring the concentration of iodo[14C]antipyrine in the aortic media. The findings suggest that: 1) vasa vasorum provide only minimal nutritional support to the thoracic aorta of normal monkeys and monkeys with moderately severe atherosclerosis, and 2) in monkeys with severe atherosclerosis, diffusional support to the thoracic aorta is strikingly heterogeneous, ranging from minimal to large. We speculate that minimal diffusional support to the outer layers of the thickened atherosclerotic aorta may contribute to development of focal medial necrosis.

Animals↗
PubMed1987

Serotonin and experimental vascular disease.

We have examined effects of atherosclerosis on constrictor responses to serotonin in several vascular beds. In normal monkeys, serotonin produces modest constriction of large arteries. In atherosclerotic monkeys, vasoconstrictor responses to serotonin are greatly potentiated in the limb, cerebral, and mesenteric circulation. The findings may be pertinent to the pathogenesis of vasospasm, which is an important complication of atherosclerosis. Platelets release serotonin when they aggregate. If platelets aggregate at atherosclerotic lesions and release serotonin, and vasoconstrictor responses to serotonin are greatly potentiated in atherosclerotic arteries, serotonin may be an important mediator of vasospasm. To determine whether treatment of atherosclerosis alters vascular responses, atherosclerotic monkeys were fed a low-cholesterol diet for 18 months. This treatment produced marked improvement in vascular lesions, but maximal vasodilator responses were not consistently improved by treatment of atherosclerosis. We speculated that fibrosis of the vessel may prevent improvement of vasodilator responses in vessels with fixed lesions. In contrast, we have found recently that dietary treatment of atherosclerosis abolishes hyperresponsiveness to serotonin in the limb. We conclude that atherosclerosis potentiates vasoconstrictor responses to serotonin and these abnormalities are reversible by dietary treatment of atherosclerosis.

Animals↗
PubMed1987

Arterial uptake indices of low density lipoproteins after fatty streak formation in Cynomolgus monkeys.

To evaluate changes in arterial wall uptake of an atherogenic lipoprotein in early atherogenesis the uptake of labelled low density lipoprotein was measured in four segments of aorta in Cynomolgus monkeys with diet induced fatty streaks. The influx rate of low density lipoprotein was estimated from a simple kinetic model. The mean influx rate, expressed as plasma equivalents of tracer, was 69 nl.cm-2 per hour in fatty streak monkeys and 28 nl.cm-2 per hour in controls (p less than 0.001). Using additional assumptions, provisional estimates of the rates of apparent efflux were calculated. In fatty streak monkeys the mean apparent efflux rate, relative to the accumulation of tracer in the wall, did not differ significantly from the efflux rate in controls (8.7% per hour vs 7.9% per hour, p greater than 0.05). Thus intimal permeability to low density lipoprotein is increased at the fatty streak stage of lesion formation but apparent efflux may not be changed. The data fit the hypothesis that relative failure of efflux is a major cause of excess low density lipoprotein accumulation in the vessel wall in hypercholesterolaemia.

Animals↗
PubMed1987

Dietary treatment of atherosclerosis abolishes hyperresponsiveness to serotonin: implications for vasospasm.

Diet-induced atherosclerosis in primates impairs vasodilator responses and greatly potentiates vasoconstrictor responses to serotonin. Serotonin may play an important role in the pathogenesis of vasospasm. In diet-induced regression of atherosclerosis, intimal lesions are reduced, but maximal vasodilator responses do not improve, perhaps because of vascular fibrosis. Our goal was to determine whether dietary treatment of atherosclerosis reverses the augmented vasoconstrictor responses to serotonin and thus might reduce susceptibility to vasospasm. Normal cynomolgus monkeys, atherosclerotic monkeys, and atherosclerotic monkeys that were given a normal (regression) diet for 18 months were studied. Morphometric studies indicated that the regression diet reduced lesions in the iliac and femoral artery since intimal area was reduced by about 50%. In the hind limb perfused at constant flow, residual resistance during maximal vasodilatation produced by infusion of adenosine tended to be greater in atherosclerotic monkeys than in normals and failed to improve in regression monkeys. In contrast, vasoconstrictor responses to serotonin were greatly potentiated in atherosclerotic monkeys and were restored to normal in regression monkeys. Serotonin (20 micrograms i.a.) decreased hind limb resistance (in mm Hg/ml/min) 0.34 +/- 0.06 (mean +/- SE) in normal monkeys, increased resistance 0.58 +/- 0.17 in atherosclerotic monkeys (p less than 0.05 vs. normal), and decreased resistance 0.70 +/- 0.15 in regression monkeys (p less than 0.05 vs. atherosclerotic). Thus, dietary treatment of atherosclerosis abolishes augmented vasoconstrictor responses to serotonin. It is proposed that treatment of atherosclerosis may be beneficial, even when vasodilator responses fail to improve, by reducing susceptibility to serotonin-induced vasospasm.

Animals↗
PubMed1987

Restoration of endothelium-dependent relaxation by dietary treatment of atherosclerosis.

Atherosclerosis results in impaired relaxation to acetylcholine, thrombin, and the calcium ionophore A23187, all agents that require the presence of endothelium. We now report that dietary treatment of atherosclerosis in monkeys not only produces morphological improvement of the atherosclerotic lesion but restores endothelium-dependent vascular relaxation to normal. Because the intima remains thickened after regression of atherosclerosis, these studies suggest that intimal thickening which is present in both atherosclerotic vessels and after regression of atherosclerosis does not prevent the endothelium-derived relaxing factor from reaching the underlying vascular smooth muscle.

Animals↗
PubMed1987

Alterations of vascular reactivity in atherosclerosis.

We have previously found that vascular relaxation to acetylcholine and thrombin is markedly impaired in vessels from monkeys with diet-induced atherosclerosis. In the present study, we found that both normal and atherosclerotic vessels relaxed completely to the calcium ionophore A23187, which stimulates release of the endothelium-derived relaxing factor by nonreceptor-mediated mechanisms. Atherosclerotic vessels, however, were less sensitive to this agent. The finding that responses to the calcium ionophore were impaired in atherosclerosis suggests that abnormal endothelium-dependent relaxation in atherosclerotic vessels is not related entirely to alterations of thrombin and muscarinic receptors but may also be due to abnormal endothelium-derived relaxing factor production or transfer from the endothelium to the underlying vascular smooth muscle. Neither normal nor atherosclerotic iliac arteries constricted in response to acetylcholine when studied in the nonpreconstricted state. Constriction to acetylcholine in these vessels was not unmasked by removal of the endothelium. Thus, the smooth muscle of iliac vessels from monkeys contains few functioning muscarinic receptors. Impaired relaxation of atherosclerotic vessels to acetylcholine is not due to enhanced muscarinic-mediated constriction or to production of an endothelium-derived constricting factor. In vivo studies were performed to determine if alpha-adrenergic coronary vascular constriction is enhanced in the presence of atherosclerosis. In anesthetized monkeys, myocardial oxygen consumption was increased by two mechanisms, aortic occlusion and phenylephrine infusion. During both aortic occlusion and phenylephrine infusion, decreases in coronary vascular resistance were similar in control and atherosclerotic monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1986

Blood flow through vasa vasorum in arteries and veins: effects of luminal PO2.

We have examined effects of chronic reduction of intraluminal PO2 on blood flow through vasa vasorum, by comparing large arteries and veins, and effects of acute hypoxia on flow through vasa. Microspheres were used to measure flow in anesthetized dogs. Values obtained with different sizes of microspheres suggest that spheres 9 and 15 micron in diam, but not 50 micron, are appropriate for measurement of blood flow through vasa vasorum. Flow [expressed as ml X min-1 X 100 g-1 (SE)] through medial vasa was similar in the aorta (9.0 +/- 2.1) and pulmonary artery (9.3 +/- 1.1) although, on the basis of wall thickness and number of lamellae, one would predict much higher levels of flow to aortic media. Two veins that we studied have a thick muscular wall. Both veins had high levels of flow through medial vasa: 33 +/- 4.4 to the subdiaphragmatic inferior vena cava and 18 +/- 5.4 to the portal vein. Two other veins are apparently conduit vessels, with dense connective tissue and minimal smooth muscle. Both veins had minimal flow through medial vasa: 2.4 +/- 1.0 to superior vena cava, and 1.9 +/- 0.8 to supradiaphragmatic inferior vena cava. Thus, because flow through vasa differs greatly in different veins, structure of the vessel (as well as intraluminal PO2) is an important determinant of flow through vasa. Acute hypoxia increased conductance of medial vasa vasorum of arteries and veins when neurohumoral constrictor effects were blocked by phenoxybenzamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1986

Intraoperative evaluation of coronary artery bypass graft anastomoses with high-frequency epicardial echocardiography: experimental validation and initial patient studies.

There is currently no accepted approach for intraoperative evaluation of the technical adequacy of coronary artery bypass graft anastomoses. High-frequency epicardial echocardiography performed intraoperatively could assess coronary artery bypass graft anastomoses by providing on-line short-axis (cross-sectional) and longitudinal two-dimensional images of the vessels. To validate measurements of anastomoses with high-frequency epicardial echocardiography, luminal diameter determined by high-frequency epicardial echocardiography was compared with that determined histologically after perfusion fixation in 12 dogs studied after coronary artery bypass grafting. Technical errors were deliberately created in some grafts. The results of these animal validation studies showed that maximum luminal diameter of the anastomosis by high-frequency epicardial echocardiography correlated well with histologic measurements (r = .92; high-frequency epicardial echocardiography = 0.8 histology + 0.3). All deliberately created technical errors were detected by an independent observer using high-frequency epicardial echocardiography. After completion of the animal studies, we demonstrated the clinical applicability of this approach in 12 patients. Fifteen coronary artery bypass graft anastomoses were examined intraoperatively with high-frequency epicardial echocardiography. The measured maximum luminal diameter of the anastomosis was greater than the maximum luminal diameter of the native artery, as expected, in all end-to-side anastomoses. However, the maximum luminal diameter of the side-to-side anastomoses was equal to or slightly less than that of the native artery. In this initial patient group, minor technical errors were noted in two of 15 graft anastomoses. In conclusion, high-frequency epicardial echocardiography can accurately measure coronary arterial bypass graft anastomoses and has potential for intraoperative detection of technical errors and inadequacies.

Animals↗
PubMed1986

Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates.

To test the hypothesis that atherosclerosis impairs endothelium-dependent vascular relaxation, we examined the effect of the endothelium-dependent vasodilators acetylcholine and thrombin and the endothelium-independent vasodilator nitroglycerin on iliac arteries from normal cynomolgus monkeys and cynomolgus monkeys with diet-induced atherosclerosis. Rings of iliac artery were suspended in organ chambers at their optimal length for generating tension. After preconstriction with prostaglandin F2 alpha, cumulative concentration-response curves to acetylcholine, thrombin, and nitroglycerin were examined. The presence of endothelium was confirmed in each vessel by scanning electron microscopy. Atherosclerotic vessels showed morphologic evidence of moderate to severe atherosclerosis. Acetylcholine produced a maximal relaxation of 65 +/- 10% in the normal group and 27 +/- 10% in atherosclerotic vessels (P less than 0.05). Thrombin (10.0 U/ml) produced relaxation of 39 +/- 9% in the normal group and 13 +/- 7% in atherosclerotic iliac arteries (P less than 0.05). Nitroglycerin relaxed both normal and atherosclerotic blood vessels to an equal extent; maximal relaxation was 92 +/- 4% in normal vessels and 98 +/- 2% in atherosclerotic vessels. To determine if hypercholesterolemia alone produces an abnormality in endothelium-dependent relaxation, we performed two additional studies. First, because veins are exposed to hypercholesterolemia, but do not develop atherosclerosis, we studied relaxation responses to acetylcholine and thrombin in veins from normal monkeys and monkeys with diet-induced atherosclerosis. Veins from normal and atherosclerotic monkeys relaxed to a similar extent upon exposure to the endothelium-dependent vasodilators acetylcholine and thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1986

Lipid metabolism in xanthomatous skin of hypercholesterolemic rabbits.

The authors studied xanthomatous skin in cholesterol-fed rabbits for changes in lipid content and in activities of enzymes regulating intracellular lipid content. After 80 days of hypercholesterolemic diet, xanthomas were widespread and changes in lipid metabolism were marked. In both tissue homogenates and cell membrane pellets, unesterified cholesterol and phospholipids increased 2-fold to 6-fold, and cholesteryl esters increased about 30-fold. Tissue triglycerides, however, decreased to half the levels found in control skin. Cholesterol esterification rates, measured by activity of acyl coenzyme A: cholesterol acyltransferase, increased moderately to markedly; hydrolase activity against 4-methylumbelliferyl oleate also increased at both acid and neutral pH, but hydrolase activity against cholesterol oleate increased only at acid pH. Thus, hypercholesterolemia caused striking increases in intracellular cholesterol esterification rates, increases in lipase activity at both neutral and acid pH, and increases in cholesteryl ester hydrolase activity at acid pH. Increases in cholesterol-esterifying activity uniformly exceeded increases in cholesteryl ester hydrolytic activity in congruence with net accumulation of cholesteryl ester. Skin xanthoma grade, however, had no consistent relation to the cholesterol esterification rates. Instead, the enzyme data suggested that marked abnormalities of lipid metabolism are diffusely distributed through dermal tissue as a precondition for the focal emergence of xanthomas.

Animals↗
PubMed1986

Potentiation of vasoconstrictor responses to serotonin in the limb of atherosclerotic monkeys.

Vasoconstrictor responses to serotonin and norepinephrine were examined in: normal cynomolgus monkeys, atherosclerotic monkeys that were fed atherogenic diet for 3-5 years and hypercholesterolaemic but non-atherosclerotic monkeys that were fed atherogenic diet for 4-5 months. Serotonin decreased total hindlimb resistance in normal and hypercholesterolaemic monkeys, but increased total resistance in atherosclerotic monkeys. There was a greater than 10-fold increase in constrictor responses of large arteries to serotonin in atherosclerotic compared with normal and hypercholesterolaemic monkeys. In contrast, responses to norepinephrine were not increased in atherosclerotic monkeys. Thus, atherosclerosis greatly potentiates constrictor responses to serotonin in large arteries of the limb. This potentiation appears to be somewhat selective for serotonin, as it is not observed with norepinephrine.

Animals↗
PubMed1986

Whither CAI?

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Computer-Assisted Instruction↗
PubMed1985

Increased production of lipoxygenase products by cholesterol-rich mouse macrophages.

The metabolism of arachidonic acid by cholesterol-enriched resident mouse peritoneal macrophages was investigated. The amounts of monohydroxyeicosatetraenoic acid (mono-HETE) produced by the cholesterol-rich macrophages were 2.5-fold greater when compared to control macrophages. The major lipoxygenase product, identified by high-performance liquid chromatography in both macrophages was 12-HETE. Since macrophages are important participants in the formation of atheromatous lesions, the increased metabolism of arachidonic acid to HETE products by cholesterol-rich macrophages could contribute to the initiation and progression of the atherosclerotic process.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1985

A defect in mobilization of cholesteryl esters in rabbit macrophages.

Macrophages provide an important way for cholesteryl esters to accumulate in tissues in pathologic amounts. We studied cholesteryl ester metabolism in thioglycollate-induced peritoneal macrophages obtained from normocholesterolemic and hypercholesterolemic rabbits. The macrophage preparations from normocholesterolemic rabbit (MN cells) had 26 nmol esterified cholesterol/mg cellular protein, incorporated 1 nmol of labeled oleate into cholesteryloleate/2 h per mg cellular protein and had an acyl-coenzyme A:cholesterol acyltransferase activity of 22 pmol cholesterylpalmitate formed/min per mg protein in isolated membranes. The macrophage preparations from hypercholesterolemic rabbits (MHC cells) contained a 12-fold greater mass of cholesteryl ester, had an 8-times higher rate of formation of cholesteryloleate, and had 3-times more acyl-coenzyme A:cholesterol acyltransferase activity in the isolated membranes. When a cholesterol acceptor (10% fetal bovine serum or 10 mg of lipid-free fetal bovine serum protein) was added to the culture medium of rabbit MHC cells, the MHC cells retained more than 70% of their cholesteryl esters after 48 h of incubation. In contrast, when a cholesterol acceptor (10% fetal bovine serum) was added to the medium of thioglycollate-induced, cholesterol-enriched macrophages from mice, the mice macrophages retained only 19% of their cholesteryl esters after 48 h of incubation. The limited capacity of rabbit macrophages to release unesterified cholesterol from stored cytoplasmic cholesteryl esters to an exogenous acceptor may be related to the propensity of rabbits to develop atherosclerotic lesions.

Animals↗