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Baroreceptor dysfunction induced by nitric oxide synthase inhibition in humans

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第1期36卷 213-218页

作者： Spieker, LE Corti, R Binggeli, C Lüscher, TF Noll, G Univ Zurich Hosp Dept Cardiol CH-8091 Zurich Switzerland

OBJECTIVES We sought to investigate baroreceptor regulation of sympathetic nerve activity and hemodynamics after inhibition of nitric oxide (NO) synthesis. BACKGROUND Both the sympathetic nervous system and endothelium-derived substances play essential roles in cardiovascular homeostasis and diseases. Little is known about their interactions. METHODS In healthy volunteers, we recorded muscle sympathetic nerve activity (MSA) with microneurography acid central hemodynamics measured at different levels of central venous pressure induced by lower body negative pressure. RESULTS After administration of the NO synthase inhibitor N-G-monomethyl-L-arginine (L-NMMA, 1 mg/kg/min), systolic blood pressure increased by 24 mm Hg (p = 0.01) and diastolic blood pressure by 12 mm Hg (p = 0.009), while stroke volume index (measured by thermodilution) fell from 53 to 38 mL/min/m(2) (p < 0.002). Administration of L-NMMA prevented the compensatory increase of heart rate, but not MSA, to orthostatic stress. The altered response of heart rate was not due to higher blood pressure, because heart rate responses were not altered during infusion of the alpha-1-adrenoceptor agonist phenylephrine (titrated to an equal increase of systolic blood pressure). In the presence of equal systolic blood pressure and central venous pressure, we found no difference in MSA during phenylephrine and L-NMMA infusion. CONCLUSIONS This study demonstrates a highly specific alteration of baroreceptor regulation of heart rate but not muscle sympathetic activity after inhibition of NO synthesis in healthy volunteers. This suggests an important role of NO in reflex-mediated heart rate regulation in humans. (C) 2000 by the American College of Cardiology.

关键词：肾上腺素能α激动剂/药理学血压/药物作用血压/生理学酶抑制剂/药理学心率/药物作用心率/生理学输注静脉内下身负压肌骨骼/神经支配一氧化氮合酶/拮抗剂和抑制剂苯福林/药理学压力感受器/药物作用压力感受器/病理生理学受体肾上腺素能α1/代谢参考值交感神经系统/药物作用交感神经系统/病理生理学 ωN-甲基精氨酸/药理学成年人女(雌)性人类男(雄)性

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Decreased baroreflex sensitivity assessed from phase IV of Valsalva maneuver in mild congestive heart failure

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ANGIOLOGY 1999年第8期50卷 655-664页

作者： Rostagno, C Felici, M Caciolli, S Olivo, G Comeglio, M Galanti, G Serneri, GGN Univ Florence Ist Clin Med Gen & Cardiol I-50134 Florence Italy

Decreased sensitivity of cardiopulmonary and arterial baroreceptors has been hypothesized to sustain sympathetic activation in patients with heart failure. In the present investigation the relationship between the impairment of baroreflex sensitivity and clinical severity of congestive heart failure was investigated. The authors studied 58 patients with heart failure (14 in NYHA class I, 22 in NYHA class II, and 22 in NYHA class III), 38 women and 20 men, age range 28-65 years. Thirty-two patients suffered from idiopathic dilated cardiomyopathy and 26 from coronary heart disease. As control group they examined 21 age-matched subjects. Baroreceptor sensitivity was studied by using the Valsalva maneuver as stimulus. Arterial pressure and heart rate were measured noninvasively by Finapres instrument (Ohmeda) and signals were recorded and elaborated with a personal computer. A decrease of baroreflex sensitivity was already demonstrable in NYHA class I patients (4.72 +/- 3.31 vs 9.25 +/- 5.05 msec/mm Hg in control group) (p < 0.005). 14 further impairment of baroreceptor response was found in patients in NYHA class II (1.94 +/- 2.88 msec/mm Hg, p < 0.001) and class III (1.78 +/- 1.52 msec/mm Hg, p < 0.001). Baroreceptor response showed a significant correlation with functional NYHA class (r = 0.61, p < 0.001) and anaerobic threshold (r = 0.57, p < 0.001) while the correlation was less tight with left ventricular end-diastolic diameter, fractional shortening, left ventricular ejection fraction, pulmonary mean arterial blood pressure, cardiac index, distance at 6 minutes walk corridor test, and maximal oxygen consumption ((V) over dot o(2)max). These results suggest that baroreceptor function may be impaired early in the clinical course of heart failure and may contribute to sympathetic activation.

关键词：压力感受器反射/生理学血压超声心动描记术多普勒运动试验心率氧耗量压力感受器/病理生理学预后疾病严重程度指数每搏输出量 Valsalva动作成年人老年人女(雌)性人类男(雄)性中年人

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ORTHOSTATIC HYPOTENSION - MECHANISMS AND MANAGEMENT

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AMERICAN HEART JOURNAL 1975年第4期90卷 513-520页

作者： IBRAHIM, MM TARAZI, RC DUSTAN, HP CLEVELAND CLIN EDUC FDN CLEVELAND OH 44106 USA CLEVELAND CLIN FDN RES DIV CLEVELAND OH 44106 USA

There is no single drug that proved effective in the treatment of orthostatic hypotension. Oral sympathomimetics like ephedrine, wyamine, aramine, and similar drugs are generally prescribed but, in our experience, their effectiveness is unpredictable; however they should be given a trial. Mineralocorticoids have already been referred to, 9 α fluorohydrocortisone (Florinef) is the one we use. Besides producing salt and water retention and expanding the blood volume, an effect which helps venous filling of the heart, it may increase the responsiveness of arterioles to the neurotransmitter. Recently there are claims that tyramine rich foods combined with monoamine oxidase inhibitors are effective in the treatment of resistant cases of IOH, but results were not encouraging when this regimen was tried in two of our patients. All kinds of drug therapy carry the danger of precipitating hypertension. Frequent observation of arterial pressure at weekly intervals is recommended. When Florinef is prescribed one should start with a small dose (0.1 mg. per day) which can be increased gradually according to therapeutic response. In conclusion the treatment of orthostatic hypotension still presents a challenging problem. The aim should be to keep the patient active and ambulatory as long as possible.

关键词：自主神经系统血压血量缓激肽/血液用力氟氢可的松/治疗应用低血压直立性/药物疗法低血压直立性/病理生理学神经系统疾病/并发症体位压力感受器/病理生理学氯化钠/治疗应用血管阻力血管舒缩系统/病理生理学人类

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ANTI-DIURETIC HORMONE EXCESS

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JOURNAL OF PEDIATRICS 1979年第4期94卷 521-526页

作者： FRIEDMAN, AL SEGAR, WE Department of Pediatrics University ofWisconsin Center for Health Sciences Madison Wis. USA

An extensive review of human antidiuretic hormone (ADH) synthesis, secretion and localized action is presented. Syndromes of inappropriate ADH secretion are described resulting in hyponatremia, serum hypoosmolality, urine hyperosmolality, regional hypovolemia, right-sided heart failure and generalized antidiuresis. Frequent causes of ADH excess are proposed including tumors, Guillain-Barre syndrome, hypothalamic lesions, hydrocephalus, skull fractures, hematomas and systemic lupus erythematosus. Fluid restriction, lithium chloride and demethylchlortetracycline are suggested to prevent fluid pooling and suppress ADH release.

关键词：血液地美环素/治疗应用呋塞米/治疗应用低钠血症/并发症 ADH分泌不当综合征/药物疗法 ADH分泌不当综合征/病理生理学锂/治疗应用容积渗克分子浓度压力感受器/病理生理学盐水高渗/治疗应用血管升压素类/代谢人类

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Cardiac positron emission tomography imaging with [¹¹C]hydroxyephedrine, a specific tracer for sympathetic nerve endings, and its functional correlates in congestive heart failure

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第5期84卷 568-574页

作者： Vesalainen, RK Pietilä, M Tahvanainen, KUO Jartti, T Teräs, M Någren, K Lehikoinen, P Huupponen, R Ukkonen, H Saraste, M Knuuti, J Voipio-Pulkki, LM Univ Turku Dept Med Turku Finland Univ Turku Dept Clin Pharmacol Turku Finland Univ Turku Dept Clin Physiol Turku Finland Turku PET Ctr Turku Finland Tampere Univ Hosp Dept Clin Physiol Tampere Finland

The integrative mechanisms of autonomic dysfunction in congestive heart failure (CHF) remain poorly understood. We sought to study cardiac retention of [C-11]hydroxyephedrine (HED), a specific tracer for sympathetic presynaptic innervation, and its functional correlates in CHF. Thirty patients with mild to moderate heart failure underwent resting cardiac HED positron emission tomography imaging, spectrum analysis testing of systolic pressure and heart rate variability in the resting supine and 70 degrees head-up tilt positions, and testing of baroreflex sensitivity. Compared with control subjects, global myocardial HED retention index was reduced by 30% (p <0.01) in patients with CHF. The HED retention index did not correlate significantly with heart rate variability. However, it correlated with baroreflex sensitivity at rest (r = 0.43, p = 0.05) and with systolic pressure low-frequency (0.03 to 0.15 Hz) variability at head up tilt (r = 0.76, p <0.01), as well as with low-frequency systolic pressure variability response from baseline to tilt (r = 0.75, p <0.01). We conclude that cardiac HED retention is reduced in patients with CHF. This correlates with blunted vascular sympathetic effector responses during posture-induced reflex activation and baroreflex control of heart rate, suggesting an interdependence between cardiac presynaptic innervation abnormalities and neural mechanisms important to blood pressure maintenance in CHF. (C) 1999 by Excerpta Medica, Inc.

关键词：血压/生理学碳放射性同位素/诊断应用冠状动脉循环/生理学麻黄碱/类似物和衍生物麻黄碱/诊断应用心脏/神经支配心脏/放射性核素显像心率/生理学图像处理计算机辅助神经末梢/病理生理学神经末梢/放射性核素显像去甲肾上腺素/类似物和衍生物去甲肾上腺素/诊断应用压力感受器/病理生理学参考值反射/生理学交感神经系统/病理生理学交感神经系统/放射性核素显像拟交感神经药/诊断应用体层摄影术发射型计算机女(雌)性人类男(雄)性中年人

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Neurohumoral activations in congestive heart failure: Correlations with cardiac function, heart rate variability, and baroreceptor sensitivity

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AMERICAN HEART JOURNAL 1999年第4期137卷 666-671页

作者： Yoshikawa, T Baba, A Akaishi, M Mitamura, H Ogawa, S Suzuki, M Negishi, K Takahashi, T Murayama, A Keio Univ Sch Med Dept Med Cardiopulm DivShinjuku Ku Tokyo 1608582 Japan Yokohama Municipal Hosp Tokyo Japan Natl Saitama Hosp Tokyo Japan Urawa Municipal Hosp Tokyo Japan

Background The clinical significance of the determination of heart rate variability and baroreceptor sensitivity relating to cardiac function and neurohumoral factors remains to be established, Methods and Results we investigated the relation between conventional clinical variables and frequency domain analysis of heart rate variability and baroreceptor sensitivity in 146 patients with heart failure. Cardiac function including left ventricular ejection fraction, left ventricular dimensions, and left atrial size was different by the plasma atrial natriuretic peptide level but not by the norepinephrine level. The total power and low-frequency power were correlated with plasma norepinephrine, whereas baroreceptor sensitivity was correlated with plasma atrial natriuretic peptide. None of the frequency domain variables and baroreceptor sensitivity was correlated with cardiac function. There was a positive correlation between the low-frequency power and baroreceptor sensitivity. Conclusions Heart rate variability and baroreceptor sensitivity, which reflect autonomic regulation, may be an indicator independent from cardiac function in patients with heart Failure.

关键词：心钠素/血液心脏功能试验心率去甲肾上腺素/血液压力感受器/病理生理学女(雌)性人类男(雄)性中年人

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Association of depressive symptoms with reduced baroreflex cardiac control in coronary artery disease

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AMERICAN HEART JOURNAL 1999年第3期137卷 453-457页

作者： Watkins, LL Grossman, P Duke Univ Med Ctr Dept Psychiat & Behav Sci Durham NC 27710 USA Hebrew Rehabil Ctr Aged Brookline MA USA

Background Although depression has been associated with cardiac death in coronary artery disease (CAD), little is known about the effects of depression on autonomic nervous system control of heart rate. This study evaluated whether depressive symptomatology is associated with impaired baroreflex sensitivity (BRS) in patients with CAD. Methods and Results BRS was assessed in 66 patients with stable CAD by using cross-spectral analysis to measure baroreceptor-mediated R-R interval oscillations. Depressive symptomatology was determined with the Beck Depression Inventory, with lower (scores <3, n = 14) and upper (scores >9, n = 16) quartiles of scores used to define groups with low and high depressive symptomatology, respectively. Comparison of the two groups showed that age-adjusted BRS was reduced in the patients with high depressive symptomatology when compared with patients with low depressive symptomatology (4.5 +/- 2.7 vs 6.5 +/- 2.8 ms/mm Hg;P < .05). Conclusions The current findings show that patients with CAD and depressive symptomatology have reduced BRS. Future studies are needed to examine whether reduced baroreflex cardiac control predicts cardiac risk in patients with CAD and depressive symptomatology.

关键词：年龄因素方差分析自主神经系统/病理生理学压力感受器反射/生理学血压/生理学卡方分布冠心病/病理生理学冠心病/心理学抑郁/病理生理学心电描记术傅里叶分析心率/生理学压力感受器/病理生理学危险因素信号处理计算机辅助每搏输出量/生理学心室功能左/生理学女(雌)性人类男(雄)性中年人

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Baroreflex and non-baroreflex modulation of vagal cardiac control after myocardial infarction

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第5期84卷 525-529页

作者： Grassi, G Seravalle, G Giannattasio, C Saino, A Turri, C Mancia, G Univ Milan Osped S Gerardo Cattedra Med Interna I-20052 Monza Italy Osped Maggiore Ctr Fisiol Clin & Ipertens IRCCS I-20122 Milan Italy Inst Auxol Italiano Milan Italy

Vagal control of sinus node exerted by arterial baroreceptors is markedly impaired 48 hours after acute myocardial infarction (AMI), but it recovers 10 days later. However, it is unknown whether this recovery is peculiar to baroreceptor vagal control or reflects normalization of the overall vagal modulation of heart rate, In 21 untreated patients (aged 51 +/- 3 years, mean a SEM) studied 10 +/- 1 and 21 +/- 1 days after an AMI and in 13 healthy controls (aged 47 +/- 2 years), we examined the increases in RR interval (electrocardiogram) induced by carotid baroreceptor stimulation via a neck chamber and by immersion of the face in iced water for 15 seconds (diving reflex). Both 10 and 21 days after AMI, baseline blood pressure and RR interval values were superimposable to those obtained in controls. Ten days after AMI, the bradycardic responses to carotid baroreceptor stimulation were similar to those seen in controls (maximal RR interval lengthenings: 248 +/- 34 vs 270 +/- 31 ms, respectively, p = NS) and remained virtually unchanged later. In contrast, the bradycardic response to diving was reduced in patients after AMI compared with controls (maximal RR interval lenghtenings: 203 +/- 43 vs 325 +/- 52 ms, respectively, p <0.05) and did not improve later. Thus, in AMI recovery of the early impairment of baroreceptor- heart rate control does not reflect normalization of vagal cardiac control, which remains lower than normal values at a time when the baroreflex is restored. (C) 1999 by Excerpta Medica, Inc.

关键词：血压/生理学颈动脉体/病理生理学心电描记术心脏/神经支配心率/生理学浸渍/病理生理学心肌梗死/病理生理学压力感受器/病理生理学参考值反射/生理学窦房结/病理生理学迷走神经/病理生理学女(雌)性人类男(雄)性中年人

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The effect of variations in arterial blood pressure and baroreceptor reflexes on pulpal blood flow in dogs

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Archives of Oral Biology 1975年第5-6期20卷 345-349页

作者： Tønder, K.Heyeraas Institute of Physiology University of Bergen N-5000 Bergen Norway

Pulpal blood flow (PBF) of the canine teeth in dogs was estimated by measuring local H2 gas clearance during: (1) reduced arterial perfusion pressure, (2) increased sympathetic vasoconstrictor tone. Local arterial per... 详细信息

Pulpal blood flow (PBF) of the canine teeth in dogs was estimated by measuring local H₂ gas clearance during: (1) reduced arterial perfusion pressure, (2) increased sympathetic vasoconstrictor tone. Local arterial perfusion pressure (LAP) was measured in the lateral nasal or middle mental artery. External carotid occlusion caused a proportionately greater fall in PBF than in LAP, indicating no autoregulation of PBF,-but on the contrary, an increase in vascular resistance at lowered perfusion pressure. This increased resistance is presumably due to lowered transmural pressure and passive reduction of the diameter of the pulpal resistance vessels. Increased sympathetic vasoconstrictor tone owing to reduced pressure at the baroreceptor site in the carotid sinus induced by common carotid occlusion increased systemic arterial blood pressure by an average of 20 per cent. LAP fell in some experiments, and increased slightly in others -but in every case PBF fell markedly, by an average of 40 per cent of control. Thus pulpal sympathetic vasoconstrictor fibres are activated through the carotid baroreceptor reflex. © 1975.

关键词：动脉闭塞性疾病/病理生理学血压颈动脉/生理学颈外动脉/生理学颈动脉窦/神经支配牙髓/血液供给压力感受器/生理学压力感受器/病理生理学反射局部血流血管阻力动物狗女(雌)性男(雄)性

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Carotid sinus hypersensitivity - a modifiable risk factor for fractured neck of femur

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AGE AND AGEING 2000年第1期29卷 85-85页

作者： Horan, MA Clague, JE Univ Manchester Hope Hosp Fac Med Clin Gerontol GrpClin Div 1 Salford M6 8HD Lancs England

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