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Role of protons in activation of cardiac sympathetic C-fibre afferents during ischaemia in cats

JOURNAL OF PHYSIOLOGY-LONDON 1999年第3期518卷 857-866页

作者： Pan, HL Longhurst, JC Eisenach, JC Chen, SR Wake Forest Univ Sch Med Dept Anesthesiol Winston Salem NC 27157 USA Wake Forest Univ Sch Med Dept Physiol & Pharmacol Winston Salem NC 27157 USA Univ Calif Davis Sch Med Dept Internal Med Div Cardiovasc Med Davis CA 95616 USA

1. Chest pain caused by myocardial ischaemia is mediated by cardiac sympathetic afferents. The mechanisms of activation of cardiac afferents during ischaemia remain poorly understood. Increased lactic acid production is associated closely with myocardial ischaemia. The present study examined the role of protons generated during ischaemia in activation of cardiac sympathetic C-fibre afferents. 2. Single-unit activity of cardiac afferents innervating both ventricles was recorded from the left sympathetic chain in anaesthetized cats. Epicardial tissue pH was measured within 1-1.5 mm of the surface by a pH-sensitive needle electrode. Responses of cardiac afferents to myocardial ischaemia, lactic acid, sodium lactate, acidic phosphate buffer and hypercapnia were determined. 3. Occlusion of the coronary artery for 5 min decreased epicardial tissue pH from 7.35 +/- 0.21 to 6.98 +/- 0.22 (P < 0.05). Epicardial placement of isotonic neutral phosphate buffer, but not saline, prevented the ischaernia-induced decrease in epicardial pH. This manoeuvre;significantly attenuated the response of 16 afferents to 5 min of ischaemia (1.56 +/- 0.23 pre treatment vs. 0.67 +/- 0.18 impulses s(-1)). Topical application of 10-100 mu g ml-l of lactic acid, but not sodium lactate, concentration-dependently stimulated 18 cardiac afferents. Inhalation with high-CO2, gas failed to activate 12 separate cardiac afferents. Furthermore, lactic acid stimulated cardiac afferents to a greater extent than acidic phosphate buffer solution, applied at a similar pH to the same afferents. ***, this study provides important in vivo evidence that protons contribute to activation/sensitization of cardiac sympathetic C-fibre afferents during myocardial ischaemia.

关键词：酸碱平衡/生理学肾上腺素能纤维/代谢肾上腺素能纤维/生理学缓冲剂胸痛/病理生理学冠状血管/生理学电极高碳酸血/代谢乳酸/代谢心肌缺血/代谢心肌缺血/病理生理学神经纤维/代谢神经纤维/生理学神经元传入/代谢神经元传入/生理学质子动物猫女(雌)性男(雄)性

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Role of incremental doses of intracoronary adenosine for fractional flow reserve assessment

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AMERICAN HEART JOURNAL 2003年第1期146卷 99-105页

作者： Murtagh, B Higano, S Lennon, R Mathew, V Holmes, DR Lerman, A Mayo Clin & Mayo Fdn Ctr Coronary Physiol & Imaging Div Cardiovasc Dis Rochester MN 55905 USA Mayo Clin & Mayo Fdn Dept Internal Med Rochester MN 55905 USA Mayo Clin & Mayo Fdn Div Biostat Rochester MN 55905 USA

Background The achievement of maximal vasodilatation of the coronary microvessels is mandatory for the accurate determination of fractional flow reserve (FFR);the optimal dosing to achieve maximal vasodilation is unclear. This study was designed to address the hypothesis that incremental doses of intracoronary adenosine are necessary to ensure complete vasodilatation of the coronary microcirculation and accurate assessment of FFR. We also examined the relationship between FFR and coronary artery disease risk factors. Methods A total of 191 patients (215 vessels) with intermediate coronary lesions were examined. FFR was measured during cardiac catheterization with a pressure monitoring wire. Incremental doses of intracoronary adenosine (12-42 mug, left coronary artery;12-48 mug, right coronary artery) were administered. Results Diabetes mellitus was present in 23% of patients, hypertension was present in 65% of patients, and prior myocardial infarction had occurred in 25% of patients. The average percent stenosis in vessels was 57% +/- 15%. Vessels were subdivided on the basis of initial FFR (group I, <0.75;group II, 0.75-0.79;group III, 0.80-0.89;group IV, 0.9). Five of the 24 (21%) vessels with an initial FFR in the 0.75 to 0.80 range had a subsequent FFR of <075. There was no difference in FFR or doses of adenosine in the patients with coronary artery disease risk factors. The average adenosine dose given at the achievement of minimal FFR was 26 mug in the right coronary artery (RCA) and 34 mug in the left coronary artery (LCA). The average maximum dose of intracoronary,adenosine administered was 29 mug for the RCA and 37 mug for the LCA. The maximum dose of adenosine ever required to achieve minimum FFR was 42 mug in both the LCA and RCA. Conclusion This study suggests that a single high dose of 42 mug of intracoronary adenosine for both the RCA and LCA is sufficient to achieve maximum hyperemia and accurate FFR in most patients, independent of risk factors. Alte

关键词：腺苷/投药和剂量方差分析血流速度/药物作用血流速度/生理学冠状动脉循环/药物作用冠状动脉循环/生理学冠状动脉狭窄/药物疗法冠状动脉狭窄/病理生理学冠状血管/药物作用冠状血管/生理学充血/化学诱导充血/病理生理学注射动脉内微循环/药物作用微循环/生理学血管舒张血管舒张药/投药和剂量老年人女(雌)性人类男(雄)性中年人

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EXPERIMENTAL-OBSERVATIONS OF CORONARY BLOOD-FLOW USING THE THERMOGRAPHIC CAMERA

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ANGIOLOGY 1978年第12期29卷 911-918页

作者： ROBICSEK, F MASTERS, TN SVENSON, RH DANIEL, WG CHARLOTTE MEM HOSP DEPT CARDIOLCHARLOTTENC 28201 CHARLOTTE MEM HOSP DEPT THORAC & CARDIOVASC SURGCHARLOTTENC 28201 UNIV HANOVER SCH MEDDEPT CARDIOLHANOVERFED REP GER

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Simulation of circular array ultrasound transducers for intravascular applications

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JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA 2000年第2期108卷 827-835页

作者： Borsboom, JMG Céspedes, EI van der Steen, AFW Lancèe, CT Deprettere, EF Erasmus Univ Thoraxctr NL-3000 DR Rotterdam Netherlands Delft Univ Technol Dept Elect Engn Circuits & Syst Lab Delft Netherlands Endoson Corp Rancho Cordova CA 95670 USA Delft Univ Technol Dept Elect Engn Circuits & Syst Lab Delft Netherlands

The beam shape of a circular array transducer that is commonly used in intravascular ultrasound catheters was investigated in linear mode of operation. For this use, a simulation program which can simulate the radio frequency (rf)-response of a number of scatterers has been developed. The program is based on the impulse response method, which is implemented in the frequency domain, Due to the unusual geometry of the transducer, the far field gets peculiarly shaped for large apertures, instead of having a far field with its maximum intensity in a single lobe on the acoustical axis, the far field splits up into a dual-lobe far field with maximum intensity in two lobes off the acoustical axis. A formula is derived that predicts the occurrence of these beam shapes. (C) 2000 Acoustical Society of America. [S0001-4966(00)00108-9].

关键词：冠状血管/生理学模型生物学换能器超声学人类

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Numerical simulation of pulsatile flow in a compliant curved tube model of a coronary artery

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JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME 2000年第1期122卷 77-85页

作者： Qiu, YC Tarbell, JM Penn State Univ Dept Chem Engn University Pk PA 16802 USA Penn State Univ Bioengn Program University Pk PA 16802 USA

The endothelial cells (ECs) lining a blood vessel wall are exposed to both the wall shear stress (WSS) of blood flow and the circumferential strain (CS) of pulsing artery wall motion. These two forces and their interaction are believed to play a role in determining remodeling of the vessel wall and development of arterial disease (atherosclerosis). This study focused on the WSS and CS dynamic behavior in a compliant model of a coronary artery taking into account the curvature of the bending artery and physiological radial wall motion. A three-dimensional finite element model with transient flow and moving boundaries was set up to simulate pulsatile flow with physiological pressure and flow wave forms characteristic of the coronary arteries. The characteristic coronary artery curvature and flow conditions applied to the simulation were: aspect ration (lambda) = 10, diameter variation (DV) = 6 percent, mean Reynolds number (Re) = 150, and unsteadiness parameter (alpha) = 3. The result show that mean WSS is about 50 percent lower on the inside wall than the outside wall while WSS oscillation is stronger on the inside wall. The stress phase angle (SPA) between CS and WSS, which characterized the dynamics of the mechanical force pattern applied to the endothelial cell layer, shows that CS and WSS are more out of phase in the coronaries than in any other region of the circulation (-220 deg on the outside wall, -250 deg on the inside wall). The suggests that in addition to WSS, SPA may play a role in localization of coronary atherosclerosis. [S0148-0731(00)01201-2].

关键词：血压顺应性冠状动脉疾病/病因学冠状动脉疾病/病理生理学冠状血管/生理学冠状血管/超微结构疾病模型动物内皮血管/损伤有限元分析血液流变学模型心血管数值分析计算机辅助搏动血流结果可重复性应力物理动物狗

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Usefulness of an echo-contrast agent for assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery with transthoracic Doppler scan echocardiography

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AMERICAN HEART JOURNAL 2002年第4期143卷 668-675页

作者： Okayama, H Sumimoto, T Hiasa, G Morioka, N Yamamoto, K Kawada, H Kitasihikai Hosp Dept Cardiol Ozu Ehime 7950061 Japan

Background This study assessed the feasibility of transthoracic Doppler scan echocardiography (TTDE) combined with echo-contrast agent in measuring coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) in the left anterior descending artery. Methods In 68 consecutive patients who underwent cardiac angiography, TTDE was recorded before and after induction of a hyperemic condition with intravenous administration of adenosine triphosphate (0.14 mg/kg/min), After CFV values returned to baseline, the same measurements were repeated while an echo-contrast agent was continuously infused. CFVR was assessed as the ratio of hyperemic to basal CFV. The pulsed wave Doppler scan quality was graded from I to 3 (TTDE score: 1, no signal detection;2, poor definition of outline;3, optimal outline definition). Results Before enhancement, CFVR could not be measured in 20 patients. Prevalence of delayed stenosis (Thrombolysis In Myocardial Infarction [TIMI] 11 grade flow) in these patients (30%) was significantly greater than in those whose CFVRs could be measured without enhancement (2%;P <.01). TTDE scores both of baseline and after hyperemia were significantly improved with contrast enhancement (before, 2.8 +/- 0.6;after, 3.0 +/- 0.3;P <.01;before, 2.6 +/- 0.7;after, 3.0 +/- 0.3;P <.01;respectively). Overall contrast enhancement increased the rate of successful CFVR measurement from 70% to 97% (P <.01). Sensitivity and specificity of significant left anterior descending artery stenosis detection with CFVR of <2.0 were 94.4% and 87.8%, respectively. Conclusion These data suggest that administration of echo-contrast agent improves pulse wave Doppler scan quality and thus the feasibility of measuring CFVR.

关键词：血量造影剂冠状动脉循环冠状血管/生理学冠状血管/超声检查心舒期/生理学超声心动描记术可行性研究观察者偏差多糖类/诊断应用局部血流回归分析敏感性与特异性心缩期/生理学老年人女(雌)性人类男(雄)性

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Velocity and wall shear stress patterns in the human right coronary artery

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JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME 1999年第4期121卷 370-375页

作者： Kirpalani, A Park, H Butany, J Johnston, KW Ojha, M Univ Toronto Inst Biomed Engn Toronto ON Canada Univ Toronto Dept Pathol Toronto ON Canada Univ Toronto Dept Surg Toronto ON Canada

Blood flow dynamics ia the human right coronary artery have not been adequately quantified despite the clinical significance of coronary atherosclerosis. In this study a technique was developed to construct a rigid flow model from a cast of a human right coronary artery A laser photochromic method was used to characterize the velocity and wall shear stress patterns. The flow conditions include steady flow at Reynolds numbers of 500 and 1000 as well as unsteady flow with Womersley parameter and peak Reynolds number of 1.82 and 750, respectively. Characterization of the three-dimensional geometry of the artery revealed that the largest spatial variation in curvature occurred within the almost branch-free proximal region, with the greatest curvature existing along the acute margin of the heart. In the proximal segment, high shear stresses were observed on the outer wail and lower, but not negative, stresses along the inner wall. Low shear stress on the inner wall may be related to the preferential localization of atherosclerosis in the proximal segment of the right coronary artery. However it is possible that the large difference between the outer and inner wall shear stresses may also be involved.

关键词：血流速度冠状血管/生理学激光多普勒流量测定模型心血管搏动血流/生理学应力物理人类

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Effects of cocaine on the coronary arteries

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AMERICAN HEART JOURNAL 2001年第3期142卷 402-410页

作者： Benzaquen, BS Cohen, V Eisenberg, MJ McGill Univ Jewish Gen Hosp Div Cardiol Montreal PQ H3T 1E2 Canada

Background A number of studies have documented myocardial ischemia and infarction associated with cocaine use. Mismatch between myocardial oxygen supply and demand from cocaine-induced vasoconstriction and increased myocardial workload are often invoked as the major postulated mechanism by which cocaine induces myocardial ischemia. This article reviews the literature studying the effects produced by cocaine on the coronary arteries to provide insight into the various pathophysiologic mechanisms by which cocaine triggers acute cardiac ischemic or infarction. Methods We reviewed the published literature describing the effects of cocaine on the coronary arteries. A MEDLINE search of English language articles published between 1985 and 2000 was performed. Key words included coronary arteries, coronary vasoconstriction, vasospasm, coronary vasodilation, cardiac vasculature, myocardial ischemia, platelets, thrombosis, and cocaine. Both animal and human studies were included. The bibliographies of identified articles were also explored for additional sources of information. Results A recreational dose of cocaine increases the heart rate by approximately 30 beats/min. It also increases the blood pressure by 20/10 mm Hg. These increases are modest, are equivalent to mild exercise, and are not believed to be sufficient to result in myocardial ischemia in the majority of cases. Animal and human studies have documented cocaine-induced early coronary artery vasodilation as shown by a decrease in coronary perfusion pressure ranging from 13% to 68%. This was followed by a more sustained vasoconstriction demonstrated by a decrease in epicardial coronary artery diameter ranging from 5% to 30% with various doses of cocaine by various methods of administration. These changes alone are also an unlikely explanation for cocaine-induced myocardial ischemia. Therefore neither increases in myocardial workload nor hemodynamic changes are sufficient to explain cocaine-induced myocardial ische

关键词：动脉硬化/化学诱导血压/药物作用可卡因/药理学冠状血管/药物作用冠状血管/生理学心率/药物作用心肌梗死/化学诱导心肌梗死/病理生理学心肌缺血/化学诱导心肌缺血/病理生理学血栓形成/化学诱导血管收缩/药物作用血管舒张/药物作用动物人类

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FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium

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CELL 2000年第7期101卷 729-739页

作者： Tevosian, SG Deconinck, AE Tanaka, M Schinke, M Litovsky, SH Izumo, S Fujiwara, Y Orkin, SH Childrens Hosp Div Hematol Oncol Boston MA 02115 USA Childrens Hosp Dept Pediat Boston MA 02115 USA Childrens Hosp Dept Pathol Boston MA 02115 USA Dana Farber Canc Inst Boston MA 02115 USA Harvard Univ Sch Med Beth Israel Deaconess Med Ctr Dept MedDiv Cardiol Boston MA 02115 USA Howard Hughes Med Inst Boston MA 02115 USA

We disrupted the FOG-2 gene in mice to define its requirement in vivo. FOG-2(-/-) embryos die at midgestation with a cardiac defect characterized by a thin ventricular myocardium, common atrioventricular canal, and the tetralogy of Fallot malformation. Remarkably, coronary vasculature is absent in FOG-2(-/-) hearts. Despite formation of an intact epicardial layer and expression of epicardium-specific genes, markers of cardiac vessel development (ICAM-2 and FLK-1) are not detected, indicative of failure to activate their expression and/or to initiate the epithelial to mesenchymal transformation of epicardial cells. Transgenic reexpression of FOG-2 in cardiomyocytes rescues the FOG-2(-/-) vascular phenotype, demonstrating that FOG-2 function in myocardium is required and sufficient for coronary vessel development. Our findings provide the molecular inroad into the induction of coronary vasculature by myocardium in the developing heart.

关键词：冠状血管/胚胎学冠状血管/生理学 DNA结合蛋白质类/生理学胚胎和胎儿发育基因表达调控发育期/生理学心脏/胚胎学心脏/生理学小鼠转基因形态发生心包/胚胎学转录因子/生理学锌指动物小鼠

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Acute effects of urinary bladder distention on the coronary circulation in patients with early atherosclerosis

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第2期36卷 453-460页

作者： Lee, TM Su, SF Chen, NF Tsai, CH Natl Taiwan Univ Hosp Dept Surg Cardiol Sect Taipei 10002 Taiwan Natl Taiwan Univ Hosp Dept Internal Med Taipei 10002 Taiwan Natl Cheng Kung Univ Coll Med Tainan 70101 Taiwan

OBJECTIVES We sought to examine whether distention of the urinary bladder, a physiologic stimulus, could induce impaired coronary circulation in patients with early atherosclerosis. BACKGROUND Distention of the urinary bladder reflexively causes an increase in sympathetic activity. The effect of such distention on the coronary circulation in patients with early atherosclerosis remains unknown. METHODS To assess the effect of bladder distention on coronary dynamic forces, epicardial and microvascular responses were measured with an intracoronary Doppler how wire in 40 patients with early atherosclerosis (<50% diameter stenosis). Patients were randomized into two groups according to whether they did not (group 1, n = 20) or did have (group 2, n = 20) pretreatment with an alpha(1)-adrenergic receptor blocker (oral doxazosin, 2 mg). Coronary flow velocity was monitored by quantitative coronary angiography at baseline, during urinary bladder distention and after intracoronary nitroglycerin injection. METHODS Bladder distention significantly decreased the coronary diameter in the stenotic segments (p < 0.001), decreased coronary blood flow (p < 0.001) and increased coronary resistance (p < 0.001), as compared with baseline values, in group 1 patients. In group 2 patients with bladder distention, the angiographic variables did not show significant changes, as compared with baseline values. No significant differences were noted between the groups in the responses of the angiographic Variables after nitroglycerin administration. CONCLUSIONS The present study shows, for the first time, that urinary bladder distention caused vasoconstriction of coronary conduit and resistance vessels involved mechanisms related to alpha, adrenoceptors. Pretreated administration of doxazosin reversed the changes toward baseline. Vasoconstriction during bladder distention can be relieved after nitroglycerin administration, suggesting an unchanged responsiveness of vascular smooth muscle cells to

关键词：血流速度/生理学冠状动脉疾病/病理生理学冠状动脉循环/生理学冠状血管/生理学多沙唑嗪/药理学血流动力学前瞻性研究受体肾上腺素能/生理学抗交感神经药/药理学膀胱/生理学血管阻力血管收缩/生理学女(雌)性人类男(雄)性中年人

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