The effects of atrial fibrillation on coronary blood flow and performance of ischaemic myocardium in dogs with coronary artery stenosis

1. Atrial fibrillation may impair coronary blood flow by tachycardia and reflex vasoconstriction. It has not been documented, however, whether in the presence of coronary stenosis atrial fibrillation exceeds the effects of rhythmic atrial tachycardia. 2. The effects of experimentally induced atrial fibrillation compared with atrial tachycardia, therefore, were tested in 22 anaesthetized dogs. Stenosis of the left anterior descending coronary artery was induced to reduce coronary blood flow by about 40%. 3. In the presence of coronary stenosis, atrial fibrillation (ventricular rate: 234 +/- 21 beats/min) reduced coronary blood flow from 58 +/- 7 to 44 +/- 8 ml min-1 100 g-1 (P less than 0.001, mean +/- SEM) and subendocardial segment shortening (ultrasonic crystals) from 12 +/- 2 to 4 +/- 2% (P less than 0.0025), and resulted in a lactate production of 30 +/- 11% (P less than 0.005 vs sinus rhythm). 4. Atrial tachycardia (heart rate: 216 +/- 21 beats/min, NS vs atrial fibrillation) did not significantly change coronary blood flow and reduced segment shortening to 7 +/- 3% (P less than 0.05 vs atrial fibrillation). Significant lactate production did not occur. 5. Since mean arterial pressure fell from 100 +/- 4 mmHg at sinus rhythm to 89 +/- 3 mmHg (P less than 0.01) during atrial fibrillation but not during atrial tachycardia, it was held constant in 13 dogs by a pressurized blood reservoir. Coronary blood flow, however, fell from 43 +/- 6 to 36 +/- 5 ml min-1 100 g-1 (P less than 0.0025). 6. Thus atrial fibrillation may reduce coronary blood flow and induce myocardial ischaemia in the presence of coronary stenosis in excess of atrial tachycardia.     

Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs.

The time relationship for recovery of mechanical function, the intramyocardial electrogram and coronary flow after brief periods of regional myocardial ischemia, was studied in conscious dogs. Total left vemtricular (LV) function was assessed with measurements of LV systolic and diastolic pressures, rate of change of LV pressure (dP/dt), and dP/dt/P. Regional LV function was assessed with measurements of regional segment length and velocity of shortening. An implanted hydraulic occluder on either the left anterior descending or circumflex coronary artery was inflated for 5- and 15-min periods on separate days. A 5-min occlusion depressed overall LV function transiently, but just before release of occlusion overall function had nearly returned to control. At this time regional function in the ischemic zone was still depressed to the point of absent shorteining or paradoxical motion during systole and was associated with marked ST segment elevation (+ 10 +/- 2.2 mV) at the site where function was measured. With release of occlusion and reperfusion the intramyocardial electrogram returned to normal within 1 min, and reactive hyperemia subsided by 5-10 min. In contrast to the rapid return to preocclusion levels for coronary flow and the electrogram, regional mechanical function remained depressed for over 3 h. A 15-min coronary occlusion resulted in an even more prolonged (greater than 6 h) derangement of function in the ischemic zone. Thus, brief periods of coronary occlusion result in prolonged impairement of regional myocardial function which could not have been predicted from the rapid return of the electrogram and coronary flow. These observations indicate that brief interruptions of coronary flow result either in a prolonged period of local ischemia or that alterations of mechanical induced by ischemia far outlast the repayment of the oxygen debt.     

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.     

Effect of exercise on perfusion of collateral-dependent myocardium in dogs with chronic coronary artery occlusion.

Since the ability of mature intercoronary collateral channels to increase myocardial blood flow in response to drug-induced coronary vasodilation has been questioned, the present study was undertaken to evaluate the response of coronary collateral circulation to the stress of exercise. Studies were performed at rest and during two levels of treadmill exercise in six dogs a minimum of 6 mo after placement of an Ameroid constrictor on the left circumflex coronary artery. Regional myocardial blood flow was estimated in normally perfused anterior and predominantly collateral-dependent posterior left ventricular wall with left atrial injections of radio-nuclide-labeled microscheres 7-10 mum in diameter. At rest, heart rate was 87 +/- 7 beats/min and mean myocardial blood flow was comparable in control and collateral-dependent regions (0.96 +/- 0.13 and 0.97 +/- 0.14 ml/min-g, respectively). During exercise, heart rates increased to 180 +/- 13 and 228 +/- 14 beats/min and myocardial blood flow (MBF) in the anterior control region increased linearly with heart rate (HR), (MBF = 0.133 HR - 0.202, r = 0.88). MBF to the posterior collateral-dependent region was similarly augmented during exercise (MBF = 0.140 HR - 0.252, r = 0.89), so that the linear correlation between HR and MBF was similar for the control and collateral-dependent regions. In addition, the transmural distribution of MBF was uniform at rest and during exercise in both the anterior control and posterior collateral-dependent regions. Thus, not only could the mature intercoronary collateral vasculature supply adequate flow at rest, but when subjected to the natural stress of exercise, the increase in flow to the predominantly collateral-dependent area was similar to that in the normally perfused area.     

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.     

慢性冠脉狭窄时局部心肌收缩功能与心肌血流的关系

目的评价慢性冠脉狭窄时心肌收缩功能与心肌血流（MBF）的关系,以探讨慢性可逆性左室收缩功能低下的发生机制。方法于左前降支（LAD）和左回旋支（LCX）近端以安放“水膨胀”式缩窄器的方法,建立13只慢性多支冠脉狭窄犬模型。二维超声评价室壁增厚率（%WT）,放射性微球定量心肌血流量（MBF）。结果术后第7dLAD和LCX供血区的平均%WT较术前均已降低（P<0.05）,但MBF在术后第21d才出现降低（P<0.05）。术后第7d26个（26/50）心肌节段表现为局部室壁运动异常（RWMA）;在15对配对的RWMA和非RWMA中,两者的MBF差异无显著性意义（P>0.05）;MBF与%WT间无明显相关（P>0.05）。然而术后第42d,在13对配对的RWMA和非RWMA中,RWMA的MBF均明显低于非RWMA（P<0.05）,且36个RWMA的MBF均与%WT有良好的相关性（P<0.0001）。结论慢性冠脉狭窄时,存活而收缩功能低下的心肌可伴或不伴MBF的降低,表明反复性心肌顿抑和心肌冬眠均在慢性可逆性左室收缩功能低下的发生中起作用。     

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.     

运动训练对冠心病患者血浆同型半胱氨酸水平的影响

目的探讨运动训练对冠心病患者血浆同型半胱氨酸（Hey）水平的影响。方法将148例冠心病患者分为康复组81例及药物组67例，均给予基础药物治疗和冠心病饮食指导，康复组患者增加运动训练；药物组同时应用叶酸、维生素B。：治疗。结果经12周的治疗，2组Hey水平均明显低于治疗前（P〈0．05）；组间比较，差异无统计学意义（P〉0．05）。康复组心功能及生活质量方面较药物组有明显改善（P〈0．05）。结论心脏康复治疗可明显降低冠心病患者Hey水平，改善心功能状态，提高患者生活质量。     

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.     

Accuracy and rate of coronary artery segment visualization with CT angiography for the non-invasive detection of coronary artery stenoses

Objectives To evaluate CT coronary angiography (CTA) when compared with catheter coronary angiography (CCA), for the detection of coronary artery stenoses and rate of optimal coronary artery segment visualization. Method Retrospective, two-center study enrolling 26 patients who underwent CCA and ECG-gated 16-detector CTA (slice thickness 0.6 mm; rotation 500 ms). Results and conclusion 283 segments were available for postprocessing. Sensitivity, specificity, and positive predictive value were, respectively, 80, 100, and 100%, for detecting more than 50% luminal stenoses, when optimally visualized segments were considered, in comparison to CCA. Negative predictive value was excellent (98%). Rate of non-optimally visualized coronary segments was 26%. Most clinical benefits of coronary CT angiography should probably be obtained when it is performed to exclude significant stenoses on selected populations of patients with a low pre-test probability of severe coronary artery disease, and under optimal conditions of controlled heart rate and minimal presence of calcium.     

Alpha-adrenoceptor subtypes and regional myocardial blood flow distribution during coronary occlusion in dogs

The involvement of postsynaptic alpha-adrenoceptors in the distribution of regional myocardial blood flows (RMBFs, microsphere technique) within the left ventricle has been investigated during intermittent coronary artery occlusion in open-chest anesthetized dogs. Two types of RMBFs distribution were assessed: (1) between endocardial (endo) and epicardial (epi) layers (endo/epi ratio) and (2) between nonischemic (NIZ) and ischemic zones (IZ) (IZ/NIZ ratio). Equipressor does of selective alpha 1-(cirazoline after rauwolscine) and alpha 2-(UK-14,304 after prazosin) adrenoceptor agonists were infused in dogs previously submitted to ganglionic and muscarinic blockade. In a control group, aortic pressure was mechanically raised by aortic stenosis to levels similar to those reached with both alpha-adrenoceptor agonists. Cirazoline and aortic stenosis increased RMBFs in IZ and NIZ but did not alter the calculated coronary resistance in NIZ and did not affect endo/epi and IZ/NIZ ratios. In contrast, UK-14,304 preferentially augmented coronary resistance in NIZ, increased IZ/NIZ ratio (both P less than 0.05) but did not affect endo/epi ratio in IZ and NIZ. Thus, we conclude that if transmural distribution of RMBFs (endo/epi ratio) is not preferentially controlled by any alpha-adrenoceptor subtype, postsynaptic alpha 2-adrenoceptors are of importance during coronary occlusion in promoting a favorable redistribution of RMBFs from NIZ towards IZ by inducing a selective NIZ coronary vasoconstriction (ie a "reverse coronary steal").     

Alpha adrenoceptor regulation of coronary artery blood flow in normal and stenotic canine coronary arteries

The response of systemic blood pressure, heart rate, lead II ECG and left circumflex (LCX) coronary artery blood flow to left cardiac sympathetic nerve stimulation was measured in pentobarbital-anesthetized, open chest, spinal transected and vagotomized dogs. After beta adrenoceptor blockade, left cardiac sympathetic nerve stimulation produced frequency dependent decreases in LCX blood flow. Selective alpha-2 adrenoceptor blockade with idazoxan produced a greater inhibition of this decrease in LCX blood flow than did selective alpha-1 adrenoceptor blockade with prazosin. In an additional population of dogs which were similarly prepared but were not spinally transectioned or pretreated with a beta adrenoceptor antagonist, left cardiac sympathetic nerve stimulation produced an increase in LCX blood flow in all animals which reached a maximum within 40 sec, and then began to decline slowly. However, after beta adrenoceptor blockade, identical stimulation parameters produced only a decline in LCX blood flow which returned to the level of control resting blood flow by the end of the stimulation period. Both selective alpha-2 adrenoceptor blockade with idazoxan and selective alpha-1 adrenoceptor blockade with prazosin produced an inhibition of the LCX blood flow decrease provoked by left cardiac sympathetic nerve stimulation in dogs pretreated with beta adrenoceptor antagonists. Idazoxan produced a slightly greater inhibition of the LCX blood flow decrease than did prazosin, suggesting a greater role for postjunctional vascular alpha-2 adrenoceptors in LCX blood flow regulation during cardiac sympathetic nerve stimulation. The presence of a severe coronary artery stenosis reduced, but did not inhibit, the increase in LCX blood flow in response to cardiac sympathetic nerve stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between geometric dimensions of coronary artery stenoses and myocardial perfusion reserve in man.

To determine the relation between stenosis anatomy and perfusion in man, 31 patients had quantitative coronary arteriography and positron imaging (PET) with Rb-82 or N-13 ammonia at rest and after dipyridamole-handgrip stress. 10 patients were also studied after angioplasty (total stenoses = 41). Percent narrowing and absolute cross-sectional luminal area were related through a quadratic function to myocardial perfusion reserve determined with PET. Arteriographically determined coronary flow reserve was linearly related to relative myocardial perfusion reserve as expected, based on the derivation of equations for stenosis flow reserve. All of the correlations had considerable scatter, indicating that no single measurement derived by coronary arteriography was a good indicator of perfusion reserve by PET in individual patients. This study provides the relation between all anatomic dimensions of coronary artery stenoses and myocardial perfusion reserve in man, and suggests that PET indicates the functional significance of coronary artery stenoses for clinical purposes.     

Abnormal coronary vascular response to exercise in dogs with severe right ventricular hypertrophy.

Measurements of right coronary artery blood flow, aortic and right ventricular (RV) pressures and heart rate were radiotelemetered during strenuous, spontaneous exercise in normal dogs and dogs with severe RV hypertrophy induced by chronic (5-6 mo) pulmonary artery stenosis. With fixed pulmonic stenosis, dogs with RV hypertrophy exhibited a decrease (P less than 0.01) in arterial pressure during exercise. Under these conditions, exercise increased right coronary artery blood flow and decreased right coronary vascular resistance less (P less than 0.05) in dogs with RV hypertrophy compared with normal. This attenuated response of right coronary artery blood flow of dogs with RV hypertrophy was not observed when arterial pressures remained at preexercise values during exercise. However, regardless of changes in arterial pressures during exercise, all dogs with RV hypertrophy demonstrated a striking postexercise coronary hyperemia (P less than 0.01), suggesting a perfusion deficit of the hypertrophied right ventricle during exercise. These results imply a fundamental defect in the ability of the coronary circulation of the severely hypertrophied right ventricle to provide sufficient nutrient supply in the face of elevated metabolic demands of exercise.     

Tachycardia and coronary blood flow: non-invasive estimation during Valsalva manoeuvre and exercise

Summary. Simultaneous changes in cycle length and coronary blood flow were studied during Valsalva manoeuvre and supine cycloergometer exercise test in 10 male patients (mean age 4812 years) who had successfully undergone myocardial revascularization by surgical anastomosis of the left internal mammary artery on the left anterior descending coronary artery. Blood velocity curves in the left internal mammary artery were obtained by a non-invasive continuous-wave Doppler probe at rest, in the last phase of the expiratory effort of the Valsalva manoeuvre and at the maximum load attained during the exercise test. Mean arterial pressure by sphygmomanometer, and cardiac cycle length on the basis of Doppler recording were measured. Mean blood velocity, the length of the blood column entering the coronary bed at each cycle (cardiac cycle times mean velocity), an index of blood cell acceleration (the ratio of mean velocity to cardiac cycle), and an index of coronary resistance (the ratio of mean pressure to mean velocity), were calculated. For approximately the same change in cycle length, coronary resistance decreased in exercise, with an increased mean velocity, but increased in Valsalva, with no changes in mean velocity. The length of the blood column entering the coronary bed at each cycle was unchanged in exercise, with a marked increase in the acceleration index, while it decreased in Valsalva. Therefore, we hypothesize that tachycardia has a limiting effect on sympathetic coronary constriction in Valsalva when cardiac external work is decreased, and an additional vasodilatory effect on coronary bed in exercise when external work is increased.,     

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.     

Duplex sonographic determination of blood pressure gradient in iliac artery stenoses. Comparison with invasive measurement]

The present study investigates the validity and accuracy of the simplified Bernoulli equation in the duplex-derived determination of pressure gradients across iliac artery stenoses. 28 patients presenting with iliac artery stenoses were examined by both duplex scanning and intraarterial catheter pressure measurement. The catheter-determined and duplex-derived mean pressure gradient was 16 +/- 7 and 14 +/- 7 mmHg, respectively. There was a fairly good correlation between the mean pressure gradients assessed nonsimultaneously by both methods (r = 0.77). The catheter-determined and duplex-derived maximum instantaneous pressure gradient was 53 +/- 16 and 52 +/- 21 mmHg, respectively. The correlation coefficient (r) for the maximum instantaneous pressure drop values determined by the two methods was r = 0.79. The results show that duplex ultrasound predicts mean and maximal-instantaneous pressure gradients with acceptable approximation in patients with iliac artery stenoses.