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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sympathetic stimulation by cold-pressor testing induces a complex interplay between adrenergic receptor stimulation, humoral and local metabolic factors, and alterations in coronary perfusion pressure. Since the endothelium importantly modulates the effect of neurohumoral stimulation, we evaluated the coronary hemodynamic determinants of epicardial artery vasomotor responses to cold-pressor testing in 12 normal patients with intact endothelial function, and in 20 patients with early atherosclerosis, demonstrating a dysfunctional endothelium. Endothelial function was assessed by intracoronary infusion of the endothelium-dependent dilator acetylcholine. Vasomotor responses were examined by quantitative coronary angiography and continuous intracoronary flow velocity measurements using a Doppler catheter. All coronary artery segments demonstrating a dilator response to intracoronary acetylcholine also vasodilated in response to cold-pressor testing by 19.7 +/- 8.2% (mean +/- 1 SD). In contrast, all arteries with evidence of atherosclerosis demonstrated a vasoconstrictor response during cold pressor testing with an area reduction by 18.4 +/- 7.5%. The systemic hemodynamic variables heart rate and mean aortic pressure increased by comparable amounts in both groups of patients during cold pressor testing, indicating comparable increases in myocardial workloads. There was a significant positive relation between increases in blood flow and changes in arterial luminal area. Increases in blood flow were closely related to increases in mean aortic pressure in normal epicardial vessels, but this relation was blunted in vessels with a dysfunctional endothelium. Estimated shear stress changes within the epicardial conductance vessels were significantly lower in normal compared to atherosclerotic arteries. Thus, the increase in coronary blood flow is an important hemodynamic determinant of epicardial artery dilation in normal arteries during cold pressor testing. On the other hand, the vasodilator response limits increases in shear stress for a given increase in blood flow. In contrast, the failure of atherosclerotic arteries to dilate, despite increased myocardial demands, exaggerates increases in local shear stress in relation to changes in flow.
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PMID:Coronary hemodynamic determinants of epicardial artery vasomotor responses during sympathetic stimulation in humans. 195 12

Endothelial injury represents an important factor in the initiation of atherosclerosis and is associated with abnormal vasomotor responses (= dysfunctional endothelium) to a variety of stimuli. Therefore, the evaluation of endothelial function may provide a means to detect early vascular alteration preceding overt atherosclerotic lesions. To test this clinically important hypothesis, we studied the coronary vasomotor responses to three different endothelium-dependent stimuli in patients with different early stages of coronary artery disease: first, increasing doses of intracoronary infusion of acetylcholine (ACH) (10(-8), 10(-7), 10(-6) M); second, transient increases in coronary flow causing flow-dependent dilation by injection of papaverine into the midportion of the left descending artery (exposing the proximal segment of this vessel to increased flow, but not to papaverine); and third, sympathetic stimulation by cold pressor test. Coronary diameters were assessed by repeated coronary angiography and quantitative angiography, blood flow velocity (and subsequent calculation of blood flow) was obtained by intracoronary Doppler. In normal individuals, all three stimuli elicited epicardial artery dilation. In patients with smooth coronary arteries, but hypercholesterolemia, a substantial vasoconstriction was observed in response to ACH, whereas the response to cold pressor test and increases in flow was normal, that is, vasodilation occurred. In patients with angiographically visible atherosclerosis, acetylcholine and cold pressor test exerted coronary vasoconstriction. Moreover, flow-dependent, endothelium-mediated dilation was attenuated in those patients demonstrating visible luminal irregularities in the vessel under study. In patients with hypercholesterolemia, substantial endothelial dysfunction (as assessed by attenuated blood-flow increase in response to acetylcholine) was demonstrated in the coronary microcirculation. Thus, progression of endothelial dysfunction occurs during the early course of development of coronary atherosclerosis. Utilizing quantitative coronary angiography and the intracoronary Doppler technique, these early functional alterations can be identified safely at a stage when atherosclerotic lesions are not detectable by angiography. This may be useful in designing early effective interventions which restore endothelial function and prevent the occurrence of overt atherosclerosis.
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PMID:Progression of coronary endothelial dysfunction in man and its potential clinical significance. 195 14

From January, 1984 to May, 1990 eleven patients (men 9, women 2) underwent coronary artery bypass surgery for chronic total occlusion of the left main coronary artery by means of intermittent antegrade cold blood cardioplegia. The ages ranged from 33 to 74 (mean 56) years. The causes of the total occlusion of the left main coronary artery were atherosclerosis in 10 patients and aortitis syndrome in one. Four patients had history of a previous myocardial infarction. Preoperative selective coronary arteriography revealed well developed collateral vessels from the RCA to the LCA in all patients. One to five coronary arteries were bypassed. Myocardial protection was obtained in the usual fashion: antegrade intermittent cold blood cardioplegia with topical cardiac cooling. All patients were successfully weaned off from cardiopulmonary bypass without the need of IABP assist. No patient developed perioperative myocardial infarction. All grafts were patent postoperatively. Treadmill testing was negative in all patients. We believe that coronary artery bypass surgery for chronic total occlusion of the left main coronary artery can be performed safely with intermittent antegrade cold blood cardioplegia.
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PMID:[Coronary artery bypass surgery for chronic total occlusion of the left main coronary artery by means of intermittent antegrade cold blood cardioplegia]. 196 Apr 68

DNA samples from 53 unrelated Dutch patients with familial hypercholesterolemia (FH) were screened for rearrangements in the gene for the LDL receptor (LDLR) by Southern analysis. Four different mutations have been detected by hybridisation of BglII digested genomic DNA with an exon 10-14 containing cDNA probe. The mutations are defined by a 7 kb insertion near exon 11, a partial gene duplication encompassing exons 9-12, a 4 kb deletion of exons 7 and 8 and an 0.4 kb deletion comprising the 5'-part of exon 16. These four different rearrangements in the LDLR gene account for 17% of the mutations in the Dutch FH population sample. Interestingly, the 4 kb deletion was detected in 5 unrelated FH patients (9.5%) and appeared to be identical to the deletion previously described (Russell, D.W. et al., Arteriosclerosis, 9 (Suppl. I) (1989) I-8; Russell, D.W. et al., Cold Spring Harbor Symp. Quant. Biol., 51 (1987) 401). in an FH patient of Dutch origin. This suggests that the 4 kb deletion is a common mutation in the Dutch FH population.
Atherosclerosis 1990 Aug
PMID:Rearrangements in the LDL receptor gene in Dutch familial hypercholesterolemic patients and the presence of a common 4 kb deletion. 197 82

The endothelium plays a critical role in the control of vasomotor tone by the release of vasoactive substances. Because endothelial injury or dysfunction is considered important very early in atherogenesis, we hypothesized that abnormal endothelial function precedes the angiographic detection of coronary atherosclerosis in the human coronary circulation. The coronary vasomotor responses to three different endothelium-mediated stimuli (intracoronary infusion of acetylcholine 10(-8) to 10(-6) M, increase in blood flow to induce flow-dependent dilation, and sympathetic stimulation by cold pressor testing) were assessed by quantitative angiography and subselective intracoronary Doppler flow velocity measurements within the left anterior descending coronary artery in 38 patients. All three stimuli elicited epicardial artery dilation in all 11 patients with smooth coronary arteries and absence of risk factors for coronary artery disease (group 1). All nine patients with smooth coronary arteries but with hypercholesterolemia (group 2) demonstrated a selective impairment in endothelial function with vasoconstriction (35 +/- 12.7% decrease in mean luminal area) in response to acetylcholine but showed a preserved flow-dependent dilation (15.5 +/- 4.4% increase in mean luminal area) and vasodilation in response to cold pressor testing (14.2 +/- 4.6% increase in mean luminal area). In all nine patients with an angiographically defined smooth coronary artery segment but with evidence of atherosclerosis elsewhere in the coronary system (group 3), both acetylcholine and cold pressor testing induced vasoconstriction (26.2 +/- 8.7% and 18.7 +/- 7.9% decrease in mean luminal area, respectively), whereas flow-dependent dilation was preserved (20.4 +/- 8.7% increase in mean luminal area). In the nine patients with angiographic evidence of wall irregularities (group 4), flow-dependent dilation was also abolished and vasoconstriction occurred in response to acetylcholine and cold pressor testing (34.5 +/- 10.7% and 19.9 +/- 6.3% decrease in mean luminal area, respectively). All coronary artery segments dilated in response to nitroglycerin, suggesting preserved function of vascular smooth muscle. Despite similar reductions in coronary vascular resistance in response to the smooth muscle relaxant papaverin, patients with hypercholesterolemia demonstrated a selective impairment of vasodilation of the resistance vasculature in response to acetylcholine (p less than 0.05 versus groups 1, 3, and 4). Thus, there is a progressive impairment of endothelial vasoactive functioning in coronary arteries of patients with different early stages of atherosclerosis, beginning with a selective endothelial dysfunction in angiographically defined normal arteries in patients with hypercholesterolemia and progressively worsening to a complete loss of endothelium-mediated vasodilation in angiographically defined atherosclerotic coronary arteries.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. 199 63

Oxygen reactive species are normally formed in cells and play an essential part of the bactericidal activity of phagocytic cells. The damaging effect of these oxygen reactive species is prevented by the endogenous scavengers SOD, glutathione peroxidase, catalase, circulating transferrin, ascorbic acid, and membrane-bound alpha-tocopherol. However, when excess amounts of oxygen radicals and hydrogen peroxide are formed, as in reperfusion injury or trauma, the endogenous scavengers are insufficient to react with these active molecules. Lipid peroxidation is an important part of the formation of oxygen reactive species. Lipid peroxidation, especially peroxidation of LDL, may have a significant role in atherosclerosis. Thus dietary manipulation of PG and TX formation through either feeding cold water fish oils or plant oils containing high amounts of polyunsaturated fatty acids may be a two-edged sword. Also, the dietary manipulation of arachidonic acid through increasing its precursor linoleate may cause a decrease in the immune response as seen in animal experiments. The marine oils may be regarded as a natural aspirin in that formation of PGs of the bisenoic series will be replaced by the PGs of the trienoic series. This results in the formation of TXA3, which is biologically inactive, and PGI3, which is biologically active like PGI2. This may have no physiologic consequences but it is used to illustrate a possible mechanism for the postulated beneficial cardiovascular effects of these oils. The issues and the mechanisms are controversial and frequently highly speculative. The subject is a boon for the lipid biochemist and nutritionist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Free radicals, arachidonic acid metabolites, and nutrition. 212 35

Vasodilation in normal and vasoconstriction in atherosclerotic coronary arteries have been observed in response to complex stimuli such as exercise and the cold pressor test. To study a single parameter that changes during these activities, and to better understand the pathophysiology of ischemia associated with increases in heart rate, we studied coronary vasomotion and blood flow response to increasing heart rate alone, produced by atrial pacing, with quantitative angiographic and Doppler flow-velocity measurements in 15 patients. In five patients with angiographically smooth coronary arteries (group 1), tachycardia produced progressive dilation of the epicardial artery with increases in cross-sectional area (CSA) of +15.5 +/- 3.4%, +22.4 +/- 2.1%, +28.5 +/- 3.3%, and +30.6 +/- 2.2% at 90, 110, 130, and 150 beats/min, respectively. In contrast, in five patients with mild angiographic narrowings (group 2), coronary segments failed to dilate with progressive tachycardia (-6.3 +/- 2.0%, -8.3 +/- 2.0%, -12.5 +/- 2.0%, and -11.4% at 90, 110, 130, and 150 beats/min, respectively), and progressive loss of luminal area was observed in five patients with severe angiographic narrowings (group 3) (-34.4 +/- 3.4%, -49.6 +/- 2.2%, -59.2%, and -72.8% at 90, 110, 130, and 150 beats/min, respectively). Coronary blood flow increased significantly with tachycardia in group 1 (+44.5 +/- 10.2%, +86.0 +/- 24.6%, +105.8 +/- 29.3%, and +137.5 +/- 46.0%), increased slightly in group 2 (+7.8 +/- 3.2%, +9.4 +/- 4.4%, +8.4 +/- 3.9%, and +10.0%), and decreased significantly in group 3 (-31.8 +/- 6%, -42.6 +/- 10.7%, -61.0%, and -70.0%). We conclude that an isolated increase in heart rate in patients with normal coronary arteries results in a modest increase in flow and vasodilation. In early atherosclerosis, the flow increase is blunted and dilation is replaced with paradoxical loss in luminal size. In patients with stenoses, further loss in luminal size occurs accompanied by a decrease in coronary blood flow. Thus, increasing heart rate alone in the setting of coronary stenoses could produce myocardial ischemia by a reduction in coronary supply, as well as by an increase in oxygen demand.
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PMID:Paradoxical narrowing of atherosclerotic coronary arteries induced by increases in heart rate. 230 22

In 8 normotensive volunteers, digital blood pressure was determined, and the value was compared to direct brachial arterial pressure and to that measured by a conventional, indirect Korotkoff-method in the upper arm. The correlation coefficient was determined by changing blood pressure with intravenous administration of vasoconstrictors, sublingual nitroglycerin, and stress tests. Although the absolute value of the digital blood pressure was slightly lower than direct arterial pressure, the correlation between the two determinations was highly significant. The difference in readings between direct and digital arterial pressure was not significant even when the pressure was fluctuated with administration of vasoactive drugs and stress tests. In 2 of 6 volunteers the photosignals of the digital arterial pulses became too small to measure pressure 30 min after they entered in a cold room. However, the digital/brachial blood pressure difference did not alter even when the signals became small during the cold exposure in the remaining 4 subjects. Afterward, the subjects visited our outpatient clinic, where their digital blood pressure was taken. The value was compared with the indirect, contralateral brachial blood pressure. The absolute difference between the readings increased significantly when hypertension advanced. Among the patients (WHO, stage I) treated with antihypertensive drugs, the digital/arm pressure gap was the greatest in patients treated with beta-adrenergic blockers, diuretics and calcium channel blockers in decreasing order. These results indicate that digital blood pressure is influenced by the severity of hypertension and drugs; i.e., hypertensive vascular injury and/or atherosclerosis lowers the peripheral blood pressure leading to impaired peripheral tissue perfusion in the hypertensive patient, and beta-adrenergic blockers may deteriorate peripheral circulation in spite of their hypotensive effects.
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PMID:Measurement of digital arterial pressure in patients with essential hypertension. 236 7

When the local concentration of serotonin is raised during platelet aggregation, the direct effect of serotonin on vascular smooth muscle is to activate the contractile process. Serotonin also amplifies the constrictor responses to other neurohumoral mediators. Vascular smooth muscle can become hyperreactive to the vasoconstrictor effects of serotonin both acutely (e.g., local cold, hypoxia) and chronically (e.g., atherosclerosis, hypertension). Vasodilator responses to serotonin can be unmasked by blockade of its vasoconstrictor component. The inhibition by ketanserin of the various vasoconstrictor and platelet-aggregating effects of serotonin presumably contributes to the therapeutic effects of the compound.
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PMID:Serotonin and the blood vessel wall. 241 58

Experimental studies in chickens have shown a relationship of a herpesvirus to atherosclerosis. The hypothesis of an association in humans was tested by using data on the history of cold sores and other manifestations of herpes infections reported by 658 male and 919 female participants (ages 58 to 89) in the Framingham Heart Study from 1977 to 1979 and on the prevalence and subsequent 6-year incidence of coronary heart disease (CHD). Approximately 40% of the men and 52% of the women reported a history of ever having "fever blisters or cold sores." Overall, there was no association between a history of such oropharyngeal manifestations and prevalent CHD. Only in the subgroup of women with recurrent infections was there a suggestion of a possible relationship (relative risk = 1.5, 95% confidence interval 1.0 to 2.1). Among members of the cohort without CHD at baseline there was no association between the history of cold sores, chicken pox, shingles, or infectious mononucleosis and 6-year CHD incidence. However, a possible interaction among women with recurrent herpes, lower levels of serum cholesterol, and incidence of angina pectoris without myocardial infarction was suggested in post hoc analyses. These data from the Framingham cohort do not support the notion that any self-reported clinically manifest herpesvirus infection has a strong etiological role in older persons, but they do raise issues to be addressed in any further research.
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PMID:Unlikely association between clinically apparent herpesvirus infection and coronary incidence at older ages. The Framingham Heart Study. 255 99


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