Role of K+ ATP channels and adenosine in the regulation of coronary blood flow during exercise with normal and restricted coronary blood flow.

Regulation of coronary vasomotor tone during exercise is incompletely understood. We investigated the contributions of K+ ATP channels and adenosine to the coronary vasodilation that occurs during exercise in the normal heart and in the presence of a coronary artery stenosis. Dogs that were chronically instrumented with a Doppler flow probe, hydraulic occluder, and indwelling catheter on the left anterior descending coronary artery were exercised on a treadmill to produce heart rates of approximately 200 beats/min. By graded inflation of the occluder to produce a wide range of coronary stenosis severities, we determined the coronary pressure-flow relation. K+ atp channel blockade with intracoronary glibenclamide (10-50 microgram/kg per min) decreased coronary blood flow during exercise at coronary pressures within and below the autoregulatory range, indicating that coronary K+ ATP channel activation is critical for producing coronary vasodilation with either normal arterial inflow or when flow is restricted by a coronary artery stenosis. Adenosine receptor blockade with intravenous 8-phenyltheophylline (5 mg/kg) had no effect on coronary flow at pressures within the autoregulatory range but decreased flow at pressures < 55 mmHg. In contrast, in the presence of K+ ATP channel blockade, the addition of adenosine receptor blockade further decreased coronary flow even at coronary pressures in the autoregulatory range, indicating increased importance of the vasodilator influence of endogenous adenosine during exercise when K+ atp channels are blocked. Intracoronary adenosine (50 microgram/kg per min) increased coronary flow at perfusion pressures both within and below the autoregulatory range. In contrast, selective K+ ATP channel activation with intracoronary pinacidil (0.2-5.0 microgram/kg per min) increased flow at normal but not at lower coronary pressures (< 55 mmHg). This finding demonstrates that not all K+ ATP channels are activated during exercise at pressures in the autoregulatory range, but that most K+ ATP channels are recruited as pressures approach the lower end of the autoregulatory plateau. Thus, K+ ATP channels and endogenous adenosine play a synergistic role in maintaining vasodilation during exercise in normal hearts and distal to a coronary artery stenosis that results in myocardial hypoperfusion during exercise.     

Assessment of transmural coronary blood flow with intraoperative transesophageal color Doppler echocardiography during coronary revascularization.

Intraoperative color Doppler transesophageal echocardiography with a 4- to 7-MHz transducer was performed on 28 consecutive patients who underwent coronary artery bypass grafting to image and evaluate the transmural coronary blood flow before and after cardiopulmonary bypass. The transmural coronary flow was visualized in 26 (92.8%) of 28 patients in the inferior wall and in 13 (46.4%) of 28 patients in the lateral wall. The peak diastolic flow velocity of the transmural coronary artery in the inferior and lateral wall was significantly increased after coronary revascularization in patients with a successful bypass graft to the right coronary artery (from 34.0 +/- 19.7 to 64.9 +/- 30.9 cm/s, P <.001, n = 10) and to the left circumflex coronary artery (from 35.1 +/- 18.6 to 62.1 +/- 21.1 cm/s, P <.001, n = 10). No significant changes were observed in patients with no bypass graft to the right or left circumflex coronary artery. Coronary blood flow can be mapped and the velocity measured with Doppler transesophageal echocardiography with a high-frequency (4- to 7-MHz) transducer. Assessment of the transmural coronary flow may provide valuable information and aid in decision making during surgical revascularization.     

Distribution of coronary blood flow during acute coronary occlusion in dogs. Effect of nicotinic acid and sodium salicylate

The effects of the antilipolytic agents nicotinic acid (NA) and sodium salicylate (SS) on the distribution of coronary blood flow during acute myocardial ischaemia were studied in open chest dogs. Fifteen min following experimental coronary artery occlusion, blood flow in the ischaemic myocardium was on average 28% of flow in the non-ischaemic myocardium. The reduction in blood flow in the ischaemic mycardium was more pronounced in the endocardial than in epicardial halves of the myocardium. No significant change in blood flow was observed after administration of NA or SS in either the ischemic or nonischemic part of the myocardium. Both drugs reduced the extent of myocardial ischaemic injury as shown by reduced epicardial ST-segment elevations. Arterial concentrations of fatty acids were lowered by NA or SS, whereas the mechanical activity of the heart remained unchanged. It is concluded that the reduction of acute myocardial ischaemic injury effected by NA or SS is not due to changes in myocardial blood flow, but more likely to lower myocardial oxygen demand related to reduced fatty acid utilization.     

Distribution of coronary blood flow during acute coronary occlusion in dogs. Effect of nicotinic acid and sodium salicylate

The effects of the antilipolytic agents nicotinic acid (NA) and sodium salicylate (SS) on the distribution of coronary blood flow during acute myocardial ischaemia were studied in open chest dogs. Fifteen min following experimental coronary artery occlusion, blood flow in the ischaemic myocardium was on average 28% of flow in the non-ischaemic myocardium. The reduction in blood flow in the ischaemic mycardium was more pronounced in the endocardial than in epicardial halves of the myocardium. No significant change in blood flow was observed after administration of NA or SS in either the ischemic or nonischemic part of the myocardium. Both drugs reduced the extent of myocardial ischaemic injury as shown by reduced epicardial ST-segment elevations. Arterial concentrations of fatty acids were lowered by NA or SS, whereas the mechanical activity of the heart remained unchanged. It is concluded that the reduction of acute myocardial ischaemic injury effected by NA or SS is not due to changes in myocardial blood flow, but more likely to lower myocardial oxygen demand related to reduced fatty acid utilization.     

Transthoracic echocardiographic visualization of coronary artery blood flow and assessment of coronary flow reserve in the right coronary artery: a first report of 3 patients.

Assessment of coronary flow reserve (CFR) has proven to be an important diagnostic tool providing useful clinical and physiologic information about coronary artery function. In several studies, the transthoracic echocardiographic assessment of CFR, defined as a ratio of hyperemic to basal coronary flow velocity, was validated in the left anterior descending artery. But so far, the visualization of coronary flow and the measurement of CFR were limited to the mid and distal portion of the left anterior descending artery. Introduction of a modified 2-chamber view enables the recording of coronary blood flow and the assessment of CFR in the posterior descending branch of the right coronary artery in selected patients. This report of 3 cases describes for the first time a method to visualize and measure coronary blood flow in the distal right coronary artery by precordial Doppler echocardiography.     

Total and effective coronary blood flow in coronary and noncoronary heart disease

There are no data available concerning total coronary blood flow to the whole heart (CBF) in man. "Effective" or "nutrient" coronary blood flow to the whole heart (MBF), supposedly a measure of flow through exchanging channels of the coronary circulation, has been measured but its validity has not been established. Accordingly, CBF and MBF were measured in 9 normal subjects, 26 patients with coronary heart disease (CHD), and 19 with noncoronary, mostly valvular heart disease (NCHD), by coincidence counting 84Rb technique. Two methods were used: single bolus (24 cases) and continuous infusion (30 cases). Various other parameters including myocardial oxygen utilization (MVO2) and lactate extraction ratio were determined. In the normal subjects CBF (386 +/- 77 ml/min) was significantly higher (P < 0.05) than in CHD (288 +/- 124 ml/min) and NCHD (292 +/- 111 ml/min). Likewise the normal MBF (380 +/- 81 ml/min) was significantly higher (P < 0.01) than in CHD (251 +/- 105 ml/min) as well as NCHD (258 +/- 104 ml/min). The myocardial Rb extraction ratio epsilon Rb) was significantly lower in normal subjects (39 +/- 9%) than in CHD (50 +/- 7%) and NCHD (52 +/- 11%) and this supports the view that epsilon Rb is flow-dependent. In both CHD and NCHD there was significant diminution of MVO2 as well as CBF. In CHD this was accompanied by a significant anaerobic trend but in NCHD it was not. It might therefore appear that in CHD, MVO2 is determined by perfusion whereas in NCHD, perfusion is determined by MVO2. In comparing CBF with MBF by paired observation testing, there was no significant difference in the normals (P > 0.3), whereas the differences were significant in CHD (P < 0.01) and NCHD (P < 0.02). This was merely a reflection of a reduced ratio of myocardial to total body epsilon Rb in CHD and NCHD, and available evidence indicates that this may be an expression of depressed transport of Rb+ rather than true shunting.     

Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions.

Smooth muscle contraction is initiated primarily by an increase in intracellular Ca2+, Ca(2+)-dependent activation of myosin light chain kinase, and phosphorylation of myosin light chain. In this investigation, we identified pregnancy-associated alterations in myosin light chain phosphorylation, force of contraction, and content of contractile proteins in human myometrium. Steady-state levels of myosin light chain phosphorylation and contractile stress were correlated positively in both tissues, but the myometrial strips from pregnant women developed more stress at any given level of myosin light chain phosphorylation. During spontaneous contractions and during conditions that favor maximal generation of stress, the rate and extent of myosin light chain phosphorylation were attenuated in myometrial strips from pregnant women. The content of myosin and actin per milligram of protein and per tissue cross-sectional area was similar between myometrium of nonpregnant and pregnant women. Although cell size was significantly increased in tissues obtained from pregnant women, the amounts of contractile proteins per cellular cross-sectional area were similar. In addition, myosin light chain kinase and phosphatase activities were similar in the two tissues. The content of caldesmon was significantly increased in myometrium of pregnant women, whereas that of calponin (a smooth muscle-specific protein associated with the thin filaments) was not different. We conclude that adaptations of human myometrium during pregnancy include (a) cellular mechanisms that preclude the development of high levels of myosin light chain phosphorylation during contraction and (b) an increase in the stress generating capacity for any given level of myosin light chain phosphorylation.     

Elevated blood cholesterol. A risk factor for coronary heart disease

1. The Report of the Adult Treatment Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults is designed to provide guidance to healthcare professionals in the detection, evaluation, and treatment of adult hypercholesterolemic patients. 2. Dietary intervention, an essential part of every treatment plan, is highlighted followed by the introduction of drug treatment if the dietary intervention fails to achieve the desired results. 3. Guidelines for intervention at the worksite, including those using community resources, are discussed.     

Lipid peroxides in blood from patients with atherosclerosis of coronary and peripheral arteries.

Lipid peroxides in plasma were determined in 100 patients with coronary artery disease, in 100 patients with peripheral artery disease and in 100 persons without any clinical symptoms of coronary or peripheral artery disease. The concentrations of lipid peroxides were significantly higher in patients with atherosclerosis (both coronary and peripheral arteries) than in controls. There was no difference between lipid peroxides in patients with coronary and peripheral artery disease. Lipid peroxides in plasma were similar in subgroups of patients with coronary artery disease without a history of myocardial infarct and those who had had myocardial infarct. In subgroups of patients with peripheral artery disease divided according to the severity of peripheral atherosclerosis a positive association between the concentration of lipid peroxides in plasma and the severity of disease was observed. In all groups there was a significant correlation between the age of examined persons and lipid peroxides in plasma; however, the concentration of lipid peroxides in plasma was statistically higher in patients with atherosclerosis than in the control age matched group. The correlation between lipid peroxides and total cholesterol as well as triglycerides were weak and not statistically significant in most of the examined groups. The results of this study provide clinical support for experimental data indicating that peroxidation of lipids is an important factor in the formation of atherosclerotic changes. They also indicate that determination of plasma lipid peroxides may give important supplementary information in monitoring patients with clinical symptoms of atherosclerosis.     

Treadmill exercise promotes cyclic alterations in coronary blood flow in dogs with coronary artery stenoses and endothelial injury.

We have previously shown in anesthetized, open-chest dogs with coronary stenosis and endothelial injury that serotonin and/or thromboxane A2 (TXA2) receptor activation play a major role in the mediation of platelet-dependent, intermittent coronary occlusion. Using a similar model in awake, closed-chest dogs, we tested the following hypotheses: (a) treadmill exercise promotes the development of cyclic flow variations in dogs with coronary stenoses and endothelial injury; (b) ventricular pacing does not induce cyclic flow variations in the same dogs; and (c) TXA2 and/or serotonin are important mediators of exercise-induced cyclic flow variations in this model. The surgical preparation consisted of the application of a hard, flow-limiting constrictor and a Doppler ultrasonic flow probe around the left coronary artery of 11 dogs. Treadmill exercise resulted in the prompt development of cyclic flow variations in all 11 dogs. Ventricular pacing at rates as high as 170 beats/min induced cyclic flow variations in only one of five dogs. Exercise-induced cyclic flow variations were abolished by TXA2 and/or serotonin receptor antagonists in all but one dog. Thus, (a) treadmill exercise promotes the development of cyclic flow variations in dogs with coronary stenoses and endothelial injury; (b) ventricular pacing does not induce cyclic flow variations in most dogs in the same model; and (c) TXA2 and/or serotonin are important mediators of cyclic flow variations in this model.     

Regional atrial blood flow in dogs. Effect of hypertrophy on coronary flow reserve.

Little is known regarding regional atrial blood flow responses during varying hemodynamic states in both the normal and hypertrophied atria. This study was undertaken to develop a canine model of chronic atrial hypertrophy and to define in both this group and in normal dogs the regional blood flow response to acute atrial fibrillation and to measure coronary flow reserve. In the 12 dogs with atrial but not ventricular hypertrophy the mean left and right atrial weights were 75 and 47% respectively greater than in the normal group. Blood flow in the normal dogs was less in the appendage than in the non-appendage region for both atria and increased significantly during atrial fibrillation. Similar findings were noted in the hypertrophy group except that during control conditions the left atrial appendage flow was similar to the nonappendage flow. Minimal vascular resistance for the hypertrophy group, 39 +/- 3 was significantly (P less than 0.05) greater when compared to the normal group 28 +/- 2 mmHg/cm3 per min per g. Thus, significant regional blood flow differences occur in both the normal and hypertrophied atria. In addition, atrial hypertrophy does not alter the autoregulatory capacity to the hemodynamic stress of atrial fibrillation but does reduce coronary flow reserve.     

Improvement of coronary morphology and blood flow after stenting

Intravascular ultrasound (IVUS) and intracoronary Doppler (ICD) were performed in eight patients (54.3±6.5 years, 6 male) immediately after PTCA and after stenting. ICD was also performed before PTCA. After PTCA, IVUS has demonstrated intimal rupture in all patients. After stenting, IVUS revealed wall wrapping of the intimal flap with a free lumen in all patients. The lumen diameter was 2.42±0.55 mm after PTCA and was 2.74±0.49 mm after stenting (p<0.001). The cross-sectional area increased from 4.70±1.99 mm² post-PTCA to 6.40±2.15 mm² post-stent (p<0.005). Coronary flow velocity reserve, calculated by the ratio of mean flow velocity at rest and after intracoronary papaverine administration, increased from 2.05±1.01 to 2.99±1.14 after PTCA (p = 0.015); and increased to 4.51±1.33 after stenting (p<0.001). The morphological data derived from IVUS correlated with the functional information obtained with ICD. In addition to its established role in bail out situations, stent implantation may be considered when a suboptimal morphological and functional result has been demonstrated.     

Percutaneous assessment of coronary blood flow and cardiac biomarkers

The aim of this study was to compare blood flow determined by coloured microspheres vs. Doppler intravascular ultrasound (US) combined with angiography. A second endpoint was to assess cardiac troponin I (cTnI) as a marker of myocardial injury. Doppler and microspheres were compared in 11 closed chest pigs. Blood flow was measured by catheter-based percutaneous technique in the left circumflex artery (LCx) and compared with coloured microspheres injected in the left ventricle. cTnI was measured in all pigs (73). The mean blood flow (mL/min-1) was 23.3 +/- 8.7 vs. 21.9 +/- 12.1 by Doppler vs. microspheres (p = 0.156), correlation coefficient r = 0.90, p = 0.006. The mean coronary flow with Doppler technique and microspheres in the middle LCx was 22.9 +/- 7.6 vs. 21.2 +/- 6.2 (p = 0.077), and distal 23.9 +/- 10.9 vs. 23.1 +/- 12.1 (p = 0.698). Coronary blood flow measured by Doppler and angiography was comparable to myocardial blood flow measured by coloured microspheres injected in the left atrium or the left ventricle. cTnI was more sensitive to ischaemia than CK-MB mass.     

冠状动脉病变与动态血压的相关性研究

目的探讨24 h动态血压与冠状动脉病变严重程度的相关性.方法 194例行冠状动脉造影的患者同时进行24 h动态血压监测.冠状动脉病变的严重程度用冠状动脉病变的血管支数表示.结果合并高血压组冠状动脉双支和三支血管病变的患病率显著高于未合并高血压组（P＜0.001）;与脉压＜60 mm Hg的患者相比,脉压≥60 mm Hg的患者冠状动脉双支和三支血管病变的患病率显著增高（P＜0.001）.结论脉压与冠状动脉病变严重程度密切相关,最高收缩压是预测冠状动脉病变与否的最佳参数.     

Coronary blood flow reserve response to left anterior descending coronary artery stenting and its value in predicting coronary restenosis.

BACKGROUND: Heterogeneous results of coronary flow velocity reserve (CFVR) to percutaneous procedures have been reported and the impact of transesophageal echocardiographic evaluation of CFVR in predicting restenosis has not been completely established. Methods and results: We studied 20 control volunteers and 51 patients with left anterior descending coronary artery stenosis to determine the CFVR response to left anterior descending coronary artery stenting, the clinical markers of persistent CFVR impairment, and its value in predicting restenosis. Prestent CFVR was lower in the stenosis group than in control volunteers (1.89 +/- 0.66 vs 3.82 +/- 1.15; P <.001). Although there was a significant increase of CFVR after stenting (2.58 +/- 0.76; P <.001 vs prestent), it remained depressed in 53% of patients and was independently related to multivessel disease (odds ratio, 0.14; 95% confidence interval 0.03-0.55; P =.005), age (odds ratio, 1.07; 95% confidence interval 0.99-1.15; P =.056), and prestent CFVR (odds ratio, 3.78; 95% confidence interval 0.99-14.42; P =.051). CFVR measured both before and early after stenting did not differ between patients with and without restenosis. CONCLUSIONS: CFVR impairment occurs in a large proportion of patients despite successful stenting and appears to be consequent of the extent of atherosclerotic coronary disease. Periprocedural CFVR conferred no predictive value for subsequent intrastent restenosis.