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Biomedical subjects

M L Armstrong

Publications and source records attributed to M L Armstrong.

At least 91 records · Page 5Linked to original sources

Effects of chronic hypertension on vasa vasorum in the thoracic aorta.

The outer layers of the thoracic aorta receive substantial blood flow through vasa vasorum within the aortic wall. Flow delivered via these channels is functionally important because medial necrosis occurs when vasa vasorum are ligated. If flow through vasa vasorum is limited in chronic hypertension, this could contribute to medial necrosis and, perhaps, aortic dissection. In these experiments, flow and conductance in vasa vasorum were assessed in twelve awake dogs with renal hypertension (arterial pressure = 127 +/- 4 mmHg [mean +/- SE]) and nine normotensive controls (arterial pressure = 100 +/- 3 mmHg [P less than 0.001]). At rest, blood flow delivered via vasa vasorum to the thoracic aorta was similar in hypertensive and normotensive dogs (5.2 +/- 0.9 and 4.8 +/- 0.4 ml . min-1 X 100 g-1 respectively). Thus, in hypertensive dogs, conductance of the vasa vasorum decreased to maintain flow constant. During maximal dilatation induced by iv adenosine (4.7 mumol . kg-1 per min) flow delivered via vasa vasorum increased by 100% in both hypertensive and normotensive dogs. Calculations of maximum conductance indicate that vasodilator capacity was decreased by 67% in vasa vasorum of hypertensive dogs. These data suggest that vasodilator capacity of vasa vasorum in the thoracic aorta is limited in chronic hypertension. This abnormality could contribute to the pathogenesis of medial necrosis and aortic dissection in hypertensive patients.

Adenosine↗

Transluminal, subselective measurement of coronary artery blood flow velocity and vasodilator reserve in man.

Assessment of coronary blood flow and the vasodilator reserve capacity of individual coronary arteries in the catheterization laboratory has been hampered by methodologic limitations. We have developed and validated a small Doppler catheter that can subselectively measure phasic coronary blood flow velocity (CBFV). In seven anesthetized calves, CBFV was varied from 0.1 to 5.7 times control CBFV. Changes in mean CBFV measured intraluminally by catheter in the left anterior descending and left circumflex arteries were similar to those measured simultaneously with an epicardial Doppler probe on the surface of the same vessel (n = 85, r = .95, slope = 1.04) and to changes in coronary sinus flow (n = 69, r = .97, slope = 1.06) measured with timed venous collections. Identical maximal coronary reactive hyperemic responses with the catheter present and absent in the artery being studied demonstrated that coronary obstruction by the catheter was minimal. Safety studies in six additional calves demonstrated that the catheter caused small changes in coronary endothelial permeability. Histologic studies revealed no endothelial denudation or thrombus formation. Stable phasic recordings of coronary blood flow velocity have been obtained in 58 of 70 patients studied. One of the 70 patients studied had abrupt coronary occlusion probably related to catheter-induced vasospasm. In 10 normal patients, intracoronary meglumine diatrizoate increased CBFV to 3.5 times that at rest (range 2.8 to 5.0). CBFV rose 5.0-fold after an intravenous infusion of dipyridamole (range 3.8 to 7.0). In each patient, dipyridamole produced greater vasodilation than meglumine diatrizoate. The time- and dose-response characteristics to dipyridamole infusion were heterogeneous, underscoring the advantage of continuous on-line measurement of CBFV in the measurement of vasodilator reserve. This method of measuring CBFV and assessing vasodilator reserve in the catheterization laboratory should facilitate studies of the coronary circulation in man.

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Techniques of networking in the computer world.

Networks can play an important role for nurses in user-to-user communication because they can be used both within and outside the health care delivery system. The choices include an information exchange, which can be an effective strategy for sharing personal concerns, problems, and achievements about the computer; commercial data bases with their vast sources of information and research data; or local area networks, effective in an office or campus setting. All of these networks can put worlds of information and services just a few words or keyboard strokes away, because they offer, outside of your own computer, a whole new dimension of retrieval, storage, reference, and communication capabilities. These networks can significantly enhance computing potential by providing an overall expansion of information.

Commerce↗

Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys.

We examined effects of hypercholesterolemia and atherosclerosis on vasoconstrictor responses to norepinephrine and serotonin. Responses were compared in normal, atherosclerotic, and hypercholesterolemic but non-atherosclerotic cynomolgus monkeys. The hindlimb was perfused at constant flow so that changes in perfusion pressure indicated changes in vascular resistance. We measured the pressure gradient from the iliac to the dorsal pedal artery so that responses of the large artery segment could be determined. Serotonin decreased total hindlimb resistance in normal and hypercholesterolemic 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 monkeys, compared with normal and hypercholesterolemic monkeys. In contrast, we found that vasoconstrictor responses to norepinephrine are normal in atherosclerotic monkeys and increased in hypercholesterolemic monkeys prior to development of atherosclerosis. Hypercholesterolemia augmented responses of small vessels to norepinephrine. We conclude that, during early stages of hypercholesterolemia in cynomolgus monkeys, vasoconstrictor responses to norepinephrine are increased in small vessels. At a later stage, as atherosclerosis develops, responses to norepinephrine return to normal, but vasoconstrictor effects of large arteries to serotonin are greatly potentiated.

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The effect of diet on plasma carnitine, triglyceride, cholesterol and arterial carnitine levels in cynomolgus monkeys.

Plasma carnitine, cholesterol, and triglycerides were measured over a 13-week period in male cynomolgus monkeys (M. fascicularis) that were fed a control diet (Purina Monkey Chow, n = 5) and a semisynthetic hypercholesterolemic diet (n = 15). Plasma cholesterol levels rose from 100 +/- 5 to 743 +/- 50 mg/dl in the cholesterol-fed group during the 13-week period but remained below 133 +/- 13 mg/dl in the control group. Plasma triglyceride levels tended to be lower in the cholesterol-fed group, particularly at 4 week (28 +/- 3 vs 42 +/- 7 mg/dl, P less than 0.05). Plasma carnitine levels rose from 43 +/- 4 to 53 +/- 5 nmol/ml within two weeks in the cholesterol-fed group and remained above control values for the duration of the study. Carnitine levels were significantly higher in the carotid arteries of cholesterol-fed animals relative to control (224 +/- 25 vs 109 +/- 15 pmol/mm in situ length, P less than 0.01). Higher mean values of carnitine were also found in iliac, subclavian, and coronary arteries of cholesterol-fed animals but not in femoral arteries.

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Hemodynamic sequelae of regression of experimental atherosclerosis.

Regression of experimental atherosclerosis is characterized by decreased intimal thickness and luminal enlargement, but intimal fibrosis becomes more dense. We tested the hypothesis that fibrosis of arteries during regression might limit vasodilator capacity and restrict hemodynamic improvement despite luminal improvement. We studied limb, coronary, and cerebral hemodynamics in 11 normal cynomolgus monkeys, 10 monkeys given an atherogenic diet for 20 mo and 8 monkeys given a regression diet for an additional 18 mo. The atherogenic diet induced lesions of moderate severity (50-60% stenosis); owing to characteristic vessel growth during the atherogenic period, luminal size did not decrease correspondingly. Regression monkeys showed typical changes of regression with luminal enlargement but increased fibrosis. The iliac artery was perfused at constant blood flow and maximal vasodilatation was produced with papaverine. Blood flow was measured with microspheres during maximal vasodilatation in the coronary bed (adenosine) and cerebral bed (hypercapnia). In normal monkeys, minimal vascular resistances were 1.95 +/- 0.19 mm Hg/ml/min X 100 g (mean +/- SE) (limb), 0.13 +/- 0.01 (coronary), and 0.44 +/- 0.02 (cerebral). In atherosclerotic monkeys minimal resistance increased (P less than 0.05) 108, 62, and 166% in the limb, coronary, and cerebral beds, respectively. In regression monkeys, minimal resistance increased from values found in atherosclerotic animals in the limb (+22%), decreased inconsistently in the coronary bed (-19%), and decreased significantly in the cerebral bed (-44%, P less than 0.05). Thus morphologic regression was accompanied by significant hemodynamic improvement during maximal dilatation only in cerebral vessels. We conclude that increases in luminal size during regression of atherosclerotic lesions may not be associated with increases in vasodilator capacity, as intimal fibrosis may limit physiologically important hemodynamic improvement.

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Role of vasa vasorum in nourishment of the aortic wall.

Vasa vasorum are present in the middle and outer layers of media in the thoracic aorta of dogs and humans. To examine the role of vasa vasorum in nourishment of the aorta, we ligated four contiguous pairs of intercostal arteries in anesthetized dogs. These arteries are the source of vasa to the descending aorta but not the aortic arch. Blood flow through vasa vasorum was measured with microspheres. Acute intercostal ligation did not reduce conductance in the aortic arch but reduced conductance in the middle third of the descending aorta from 7 +/- 1 to 3 +/- 0.7 (SE) ml.min-1.100 g-1.mmHg-1 (P less than 0.05). After intercostal ligation, infusion of adenosine (5 mumol.kg-1.min-1 iv) increased conductance in the aortic arch 3- to 4-fold but did not increase conductance in the descending aorta. Six to ten days after intercostal ligation, conductance in the middle third of the descending aorta remained low. Vasodilator capacity was partially restored in outer layers of the descending aorta, probably by collateral vessels or formation of new vessels. Morphological changes ranged from broad bands of necrosis to patchy areas of cell loss, primarily in middle layers of descending aorta. We conclude that vasa vasorum are critical in nourishment of aortic media.

Adenosine↗

Hyperemia of the aortic wall in atherosclerotic monkeys.

The aortic wall is nourished by diffusion from the aortic lumen and from vasa vasorum in the adventitia and outer layers of media. Intimal proliferation in atherosclerosis might be expected to reduce the effectiveness of diffusion from the lumen and increase dependence on nourishment by vasa. This study was performed to determine whether there is increased perfusion of the aortic wall by vasa vasorum in atherosclerosis. We used microspheres to measure flow through vasa in normal and atherosclerotic cynomolgus monkeys. Blood flow to inner layers of the thoracic and abdominal aorta was less than 1 ml/min X 100 g in normal monkeys, and there was a minimal increase in atherosclerotic monkeys. Flow to the outer layers of the thoracic and abdominal aorta was 1.3 +/- 0.9 and 2.2 +/- 0.8 ml/min per 100 g in normal monkeys. Flow to outer layers of the thoracic and abdominal aorta was increased in atherosclerotic monkeys to 17 +/- 8.9 and 31 +/- 12 ml/min per 100 g (P less than 0.05 vs. normal). Thus there is increased perfusion of the atherosclerotic aorta, particularly in the outer layers. During maximal vasodilation induced by infusion of adenosine, flow through vasa was 3- to 8-fold greater in atherosclerotic than in normal monkeys. This finding suggests that proliferation of new vessels, rather than dilation of existing vessels, accounts for the increase in blood flow through vasa. We speculate that hyperemia of the aortic wall in atherosclerosis may be in part a compensatory response to increased oxygen requirements and possibly to ischemia produced by intimal proliferation and a resulting increase in diffusion distance.

Adenosine↗

Hepatic acylcoenzyme A: cholesterol acyltransferase activity during diet-induced hypercholesterolemia in cynomolgus monkeys.

Acylcoenzyme A: cholesterol acyltransferase (ACAT) activity was studied in hepatic microsomes of cynomolgus monkeys fed either commercial chow or an atherogenic diet of high cholesterol and saturated fat content. ACAT activity (pmol/min per mg protein) was 35 in liver microsomes from control monkeys, and 142 and 161 at 10 and 100 days, respectively, after starting the high cholesterol diet. The cholesterol-fed monkeys had about 1.5-fold increase in cholesterol content of hepatic microsome was compared to control monkeys (94 nmol/mg protein in controls versus 142 nmol/mg protein in the cholesterol fed group). There was no difference between the two groups in microsomal fatty acids in saturated, monoenoic, or polyenoic acid classes. However, the cholesterol-fed monkeys had relatively lower amounts of linoleic acid and higher amounts of arachidonic acid in the microsomes. To determine whether the increased microsomal cholesterol content might be responsible for the increase in ACAT activity, liver microsomes from control monkeys were incubated for 15-120 min with liposomes composed of cholesterol and dipalmitoyl phosphatidylcholine, 2:1 (mol/mol). The microsomal cholesterol content increased from 90 to 128 nmol/mg protein as the incubation progressed. There was a corresponding increase in ACAT activity from 80 to 240 pml/min per mg protein. This observation is consistent with the view that the high hepatic ACAT activity in the cholesterol-fed monkeys is due to the larger amount of cholesterol contained in the microsomes. The increase in hepatic ACAT activity occurs soon after cholesterol feeding is started; this response may be involved in the production of cholesteryl ester-rich lipoprotein by the liver, and thereby may be related to the atherogenic process in these primates.

Acyltransferases↗

Arterial platelet accumulation in experimental hypercholesterolemia.

Accumulation of arterial platelets was calculated from 51Cr radioactivity in the intima-inner media of flushed, perfuse-fixed aortas and branch vessels of cynomolgus monkeys 48 hours after labeling of the blood platelets. In normo-cholesterolemic controls the radioactivity per square centimeter of tissue was consistently higher in aortic branching sites (circumostial aorta) than in the remainder of the aorta. In monkeys given 10 and 100 days of hypercholesterolemic diet radioactivity rose in circumostial aorta in proportion to increases in streaks and in areas of Evans blue uptake. In branch artery inner wall, where intimal changes were minimal and usually absent, counts were significantly greater in animals given 100 days of hypercholesterolemic diet than in controls. After 10 days of hypercholesterolemic diet the mean radioactivity in aortic branch artery inner wall uniformly exceeded control values, but usually nonsignificantly, permitting the speculation that changes in platelet-intima interactions may occur in widespread fashion throughout the arterial tree very early in hypercholesterolemia when lesion formation is incipient or absent.

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The relation of hypercholesterolemic fatty streaks to intimal permeability changes shown by Evans blue.

The aortic localization of diet-induced fatty streaks in relation to focal increases in intimal permeability was evaluated in cynomoglus monkeys. Animals fed a hypercholesterolemic diet and studied at 10, 15, and 100 days had increasing intensity of Evans blue dye uptake. The overlap of fatty streaks with areas of dye intake increased as the areas of dye uptake enlarged, but all hypercholesterolemic groups showed some fatty streaks not topographically related to areas of dye uptake or flow instability. Because the upper thoracic aorta tended to show more advanced fatty streak formation dissociated from evident permeability change or hydraulic instability, it is suggested that mechanical factors associated with the geometric configuration of the descending thoracic aorta may have a significant role in the localization of some hypercholesterolemic fatty streaks.

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Regulation of blood flow to the aortic media in dogs.

Morphologic observations suggest that the inner layers of the thoracic aorta in man and dog are avascular and the outer layers have vasa vasorum. It appears that vasa vasorum are essential in the thoracic aorta because their interruption produces medial necrosis. These experiments provide the first measurements of blood flow through aortic vasa vasorum and examine physiologic regulation of that flow. During control conditions the outer two-thirds of the media of the thoracic aorta received 10 ml/min per 100 g blood flow through vasa vasorum. Flow to the inner third of the aorta was 1 ml/min per 100 g. Flow to both the inner and outer media of the abdominal aorta was less than 1 ml/min per 100 g. Adenosine increased blood flow to vasa vasorum in the outer media of the thoracic aorta from 7 to 18 ml/min per 100 g, but did not increase flow to the inner layers of the aorta. Hemorrhagic hypotension decreased flow in the outer media of the thoracic aorta from 14 to 2 ml/min per 100 g. Acute hypertension failed to increase blood flow through vasa vasorum, as conductance decreased significantly. These studies indicate that vasa vasorum provide a considerable amount of blood flow to the outer layers of the thoracic aorta. The vessels are responsive to physiologic stimuli because they dilate during infusion of adenosine and constrict during both hemorrhagic hypotension and acute hypertension. We speculate that the failure of blood flow to the aortic wall to increase during acute hypertension might, if it were sustained, contribute to aortic medial necrosis.

Adenosine↗

Ectopic pregnancy in 2 guinea-pigs.

The foetuses were completely developed and were found in the peritoneal cavities of strain 13/N guinea-pigs in their 3rd pregnancies. One foetal placenta was attached to the left side of the peritoneal wall, the other adhered to the pyloric region of the stomach.

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