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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary vasomotion is an important determinant of myocardial perfusion in patients with angina pectoris, and it influences not only normal but also stenotic coronary arteries. The ability of a stenotic coronary artery to change its size is dependent on the presence of a normal musculo-elastic wall segment within the stenosis (i.e., eccentric stenosis). Coronary vasoconstriction of normal and stenotic coronary arteries has been reported by Brown and coworkers (Circulation 1984; 70: 18-24) during isometric exercise. The effect of dynamic exercise on coronary vasomotion was evaluated in one group of 13 patients with ischaemia-like symptoms and normal coronary arteries (group 1) and in a second group of 12 patients with coronary artery disease with exercise-induced angina pectoris (group 2). Luminal area of a normal and a stenotic vessel segment was determined by biplane quantitative coronary arteriography at rest, during supine bicycle exercise and 5 min after administration of 1.6 mg sublingual nitroglycerin. Coronary sinus blood flow was measured in group 1 at rest and after 0.5 mg kg-1 intravenous dipyridamole using coronary sinus thermodilution. Coronary flow reserve was calculated from coronary sinus flow after dipyridamole divided by coronary sinus flow at rest. In group 1, coronary vasodilation of the large (i.e., proximal) and the small (i.e., distal) coronary arteries was observed during exercise in seven patients (subgroup A). However, in the remaining six patients (subgroup B) coronary vasoconstriction of the small arteries (-24%, P less than 0.001) was found during exercise, whereas the large vessels showed coronary vasodilation (+26%, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coronary vasomotor tone during static and dynamic exercise. 251 65

Recently, we showed that supplementation with nitric oxide (NO) via donor nitroglycerin (NG) alleviated the ovariectomy and corticosteroid-induced bone loss in rats. In humans, high doses or frequent applications of NG (i.e., for angina) lead to rapid loss of its efficacy in relieving angina. To examine whether there is a similar effect on the loss of efficacy of NG on bone, we examined the frequency-dependent effects of NG on bone mineral density (BMD), bone mass, trabecular bone volumes (BV/TV), and blood pressure in rats. Thirty 7-month-old female Brown Norway rats underwent ovariectomy, and an additional six rats were sham-operated. The ovariectomized rats were treated either with vehicle (ovariectomized control), 17beta-estradiol (E2; positive control), or 0.2 mg NG (via dermal application) once, twice, or three times a day. Before and at the end of the 10-week treatment period, BMD of the lumbar spine was measured by dual-energy X-ray absorptiometric (DXA) scanning and expressed as a percentage change. BMD in ovariectomized rats was significantly lower (-2.5 +/- 2.0%) compared with the sham-operated rats (+6.3 +/- 5.3%; p < 0.01). Estrogen therapy completely abolished the ovariectomy-induced potential bone loss (+5.9 +/- 3.4%). Application of NG once daily also completely prevented (+6.2 +/- 2.8%; p < 0.01) the ovariectomy-induced bone loss (i.e., it was as effective as estrogen). However, the beneficial effects of NG on BMD were significantly reduced with increased frequency of application of NG (+1.9 +/- 2.1%, twice a day and -0.2 +/- 3.3% three times a day). Estrogen or once daily administration of NG preserved femur weights, BV/TV, and decreased urinary deoxypyridinoline levels as expected. However, a higher level of serum osteocalcin and bone-specific alkaline phosphatase levels were maintained only with once daily administration of NG. There were no adverse effects of these doses of NG on blood pressure, but a tendency to lower blood pressure was noticed with increased frequency of NG. These results confirmed our previous findings that NO donors counteract the bone loss associated with estrogen deficiency. However, these beneficial effects of maintaining BMD are lost with increased frequency of NG application.
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PMID:Frequency-dependent effect of nitric oxide donor nitroglycerin on bone. 1084 Nov 80

Considering the morphological findings in egyptian mummies at the beginning of the 20th century, atherosclerotic lesions were also apparent in pharaoh mummies more than 3500 years ago. Hippokrates (469-377 b.c.) described the sudden (cardiac) death, whereas Erasistratos had documented the typical claudication intermittens symptoms of peripheral arterial disease approximately 300 b.c. Later on in 1575, Fallopius observed severe pathological findings in arteries which he has characterized as a 'degeneration to bones', suggesting the presence of calcified atherosclerotic lesions. The relation between coronary lesions and the symptoms of angina pectoris was postulated in 1799 by Parry, however, only more than 80 years later angina pectoris was interpreted as a result of myocardial ischemia by Potain. During that time, the term 'arteriosclerosis' was firstly created by Lobstein in his 'Lehrbuch der pathologischen Anatomie', published in 1835. With the beginning of the last century, the pathophysiological aspects of plaque development were investigated in more detail by a number of researchers. In this context, people such as Saltykow, Chalatow and Anitschkow are important to notice. In 1914, Anitschkow firstly described the role of cholesterol accumulation in the vessel wall for the development of atherosclerosis. He used a cholesterol-fed rabbit model, which is the most important model of experimental atherosclerosis up to now. He also firstly described the 'Cholesterinesterphagozyten', which today commonly are known as foam cells, derived from macrophages. Using the cholesterol-fed rabbit model as well, already in 1942, Ludden et al. could demonstrate the atheroprotective effect of estrogen experimentally, a finding, which got later confirmed in the primate model and epidemiological studies. In the last three decades our knowledge has expanded by a large number of findings, based on morphological, immunohistological and molecular methods. In this context, one major contribution was the discovery of the LDL-receptor and its importance for the development of atherosclerosis by Brown and Goldstein, and the setting up of the 'response to injury hypothesis' by Ross and Glomset. At the present, we understand atherosclerosis as a complex (and at least in part as a physiological) phenomenon, beginning in the early childhood. The pathological aspect, making it to a disease, is depending on individual growth dynamics and plaque localization. The following key processes during the development of atherosclerosis are identified: 1) Endothelial injury, 2) intimal cholesterol accumulation and monocyte invasion with subsequent foam cell formation, 3) migration and proliferation of smooth muscle cells with expression of extracellular matrix 4) local thrombus formation with secondary organization 5) calcification and/or plaque rupture 6) final occlusion due to plaque rupture/thrombus formation. The classical concept of cardiovascular risk factors does only partially explain the origin of atherosclerosis. For the future, further mechanism(s) need to be identified and studied (genomic pathways, hormonal aspects, infective components, etc.) probably opening an effective therapeutical strategy to prevent and treat atherosclerotic diseases.
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PMID:The discovery of the pathophysiological aspects of atherosclerosis--a review. 1168 58

To evaluate the local hemodynamics in flow limiting coronary lesions, computational hemodynamics was applied to a group of patients previously reported by Wilson et al. (1988) with representative pre-angioplasty stenosis geometry (minimal lesion size d(m)=0.95 mm; 68% mean diameter stenosis) and with measured values of coronary flow reserve (CFR) in the abnormal range (2.3+/-0.1). The computations were at mean flow rates (Q) of 50, 75 and 100 ml/min (the limit of our converged calculations). Computed mean pressure drops Deltap were approximately 9 mmHg for basal flow (50 ml/min), approximately 27 mmHg for elevated flow (100 ml/min) and increased to an extrapolated value of approximately 34 mmHg for hyperemic flow (115 ml/min), which led to a distal mean coronary pressure p(rh) of approximately 55 mmHg, a level known to cause ischemia in the subendocardium (Brown et al., 1984), and consistent with the occurrence of angina in the patients. Relatively high levels of wall shear stress were computed in the narrow throat region and ranged from about 600 to 1500 dyn/cm(2), with periodic (phase shifted) peak systolic values of about 3500 dyn/cm(2). In the distal vessel, the interaction between the separated shear layer wave, convected downstream by the core flow, and the wall shear layer flow, led to the formation of vortical flow cells along the distal vessel wall during the systolic phase where Reynolds numbers Re(e)(t) were higher. During the phasic vortical mode observed at both basal and elevated mean flow rates, wide variations in distal wall shear stress occurred, distal transmural pressures were depressed below throat levels, and pressure recovery was larger farther along the distal vessel. Along the constriction (convergent) and throat segments of the lesion the pulsatile flow field was principally quasi-steady before flow separation occurred. The flow regimes were complex in the narrow mean flow Reynolds number range Re(e)=100-230 and a frequency parameter of alphae=2.25. The shear layer flow disturbances diminished in strength due to viscous damping along the distal vessel at these relatively low values of Re(e), typical of flow through diseased epicardial coronary vessels. The distal hyperemic flow field was likely to be in an early stage of turbulent flow development during the peak systolic phase.
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PMID:Physiological flow analysis in significant human coronary artery stenoses. 1277 11

This study gains insight on the nature of flow blockage effects of small guidewire catheter sensors in measuring mean trans-stenotic pressure gradients Deltap across significant coronary artery stenoses. Detailed pulsatile hemodynamic computations were made in conjunction with previously reported clinical data in a group of patients with clinically significant coronary lesions before angioplasty. Results of this study ascertain changes in hemodynamic conditions due to the insertion of a guidewire catheter (di=0.46 mm) across the lesions used to directly determine the mean pressure gradient (Deltap) and fall in distal mean coronary pressure (pr). For the 32 patient group of Wilson et al. [1988] (minimal lesion diameter dm=0.95 mm; 90% mean area stenosis; proximal measured coronary flow reserve (CFR) of 2.3 in the abnormal range) the diameter ratio of guidewire catheter to minimal lesion was 0.48, causing a tighter "artifactual" mean area stenosis of 92.1%. The results of the computations indicated a significant shift in the Deltap-Q relation due to guidewire induced increases in flow resistances (R=Deltap/Q) of 110% for hyperemic flow, a 35% blockage in hyperemic flow (Qh) and a phase shift of the coronary flow waveform to systolic predominance. These alterations in flow resulted in a fall in distal mean coronary pressure (at lower mean flow rates) below the patho-physiological range of prh approximately 55 mmHg, which is known to cause ischemia in the subendocardium (Brown et al. [1984]) and coincides with symptomatic angina. Transient wall shear stress levels in the narrow throat region (with flow blockage) were of the order of levels during hyperemic conditions for patho-physiological flow. In the separated flow region along the distal vessel wall, vortical flow cells formed periodically during the systolic phase when instantaneous Reynolds numbers Ree(t) exceeded about 110. For patho-physiological flow without the presence of the guidewire these vortical flow cells were much stronger than in the more viscous flow regime with the guidewire present. The non-dimensional pressure data given in tabular form may be useful in interpretation of guidewire measurements done clinically for lesions of similar geometry and severity.
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PMID:Effects of diagnostic guidewire catheter presence on translesional hemodynamic measurements across significant coronary artery stenoses. 1461 Mar 12

Since its first description in 1979 (Brown et al., 1979. Nature 280, 235-236), extensive work on the I(f) current has amply demonstrated its role in the generation and neurotransmitter-induced modulation of pacemaker activity in heart (DiFrancesco, 1993. Annual Review of Physiology 55, 455-472). At pacemaker voltages, I(f) is an inward current activated by negative voltage and by intracellular cAMP. Moderate beta-receptor stimulation accelerates, and vagal stimulation slows, cardiac rate by increasing and decreasing, respectively, I(f) at diastolic potentials via changes in cAMP level. Cloning of four isoforms of hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channels in the late 1990s has shown their correlation to native f-channels. Comparison of the properties of native pacemaker channels with those of HCN channels has provided information concerning the composition and molecular features of native channels in different cardiac regions. The relevance of I(f) to pacemaker generation and modulation makes f-channels a natural target of drugs aiming to control pharmacologically heart rate. Agents selectively reducing heart rate have been developed which act by specific inhibition of I(f), such as ivabradine; these drugs have a high potential for treatment of diseases where heart rate reduction is beneficial, such as angina and heart failure. Knowledge of the molecular properties of HCN clones will help the development of drugs specifically interacting with cardiac, rather than neuronal pacemaker channels. Devices able to replace electronic pacemakers and based on the delivery of a cellular source of pacemaker channels to non-pacing tissue (biological pacemakers) are likely to be developed in the near future for use in therapies for diseases of heart rhythm.
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PMID:Serious workings of the funny current. 1597 37

"Funny" (f) channels underlie the cardiac "pacemaker"I(f) current, originally described as an inward current activated on hyperpolarization to the diastolic range of voltages in sino-atrial node myocytes [Brown, HF, DiFrancesco, D, Noble, SJ. How does adrenaline accelerate the heart? Nature 1979;280:235-236]. The involvement of funny channels in the generation and modulation of cardiac pacemaker activity has been amply demonstrated by thorough analysis since its discovery. The degree of funny current activation upon termination of an action potential determines the slope of diastolic depolarization, and hence pacemaker frequency; furthermore, I(f) is under cAMP-mediated control by beta-adrenergic and muscarinic stimulation and underlies the modulation of cardiac rate by the autonomous nervous system: it therefore represents a mechanism of fundamental physiological relevance. Their function in pacemaking makes funny channels an obvious target for drugs aiming at regulation of spontaneous activity and cardiac rate. This explains the recent development of "heart rate-reducing" drugs which act as selective f-channel inhibitors, and as such are capable of specifically slow cardiac frequency by decreasing the rate of diastolic depolarization. These substances will be useful in treating diseases such as chronic angina and heart failure. Furthermore, in situ delivery of funny channels, or of a cellular source of funny channels, is a promising new technique for the development of biological pacemakers which may in a near future replace electronic devices. Finally, a channel mutation responsible for one type of a relatively common rhythm disturbance, sinus bradycardia, has been recently identified, highlighting the clinical relevance of funny channels in the pacemaker function.
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PMID:Funny channels in the control of cardiac rhythm and mode of action of selective blockers. 1663 40