Angina pectoris with normal coronary arteriograms: hemodynamic and metabolic response to atrial pacing.

Seventeen subjects ranging from 36 to 58 years of age presented with chest pain suggestive of myocardial ischemia. Each patient had a positive double Master's two-step test with ST segment depression of 0.5 mm. or more in the postexercise ECG. In each case coronary angiography and left ventriculography were normal. Hemodynamic and metabolic investigations were carried out during sinus rhythm and atrial pacing. Thirteen patients experienced pain during pacing but only one showed an abnormal hemodynamic response. Two patients showed abnormal myocardial lactate metabolism during the control period and four during pacing-induced tachycardia. The increase in ejection fractions in this group suggests hyperdynamic ventricular contraction which could result in increased oxygen requirements and thus induce ischemic pain in the absence of arteriographically demonstrable coronary artery disease.     

The response of the myocardial metabolism to atrial pacing in patients with coronary slow flow

The pathophysiology of angina pectoris is not precisely known yet in patients who have no coronary lesion but slow coronary flow by angiography. In this study we aim to display metabolic ischemia via atrial pacing to determine the difference of lactate production and arterio-venous O2 content difference (AVO2). Thirty-four patients with slow coronary flow detected by coronary angiography via the TIMI 'frame count' method were included in this study. The resting and stress images from the patients undergoing myocardial perfusion tomography were recorded, pre and postpacing lactate extraction and AVO2 content difference values were calculated. Patients were classified according to their metabolic responses to atrial pacing stress. Group I consisted of 28 patients (18 male, 10 female, mean age 54.42 +/- 9.61) who did not demonstrate metabolic ischemia and group II consisted of six patients (four male, two female, mean age 60 +/- 5.76) who had metabolic ischemia after the procedure. There was no statistically significant difference between prepacing AVO2 content difference in group I (57.38+/-2.05%) and group II (58.23 +/- 2.11%) (P = NS). However postpacing AVO2 content difference of group I and group II was statistically significant (respectively, 57.96+/-2.65 vs. 68.35 +/- 2.15%, P < 0.001). In other words, postpacing AVO2 content difference was unchanged from the basal AVO2 content difference level in group I (respectively, 57.38 +/- 2.05 vs. 57.96 +/- 2.65%; P = NS) in contrast to the postpacing AVO2 content difference which increased significantly in group II (58.23 +/- 2.11 vs. 68.35 +/- 2.15%; P < 0.028). Although basal lactate extraction rates were similar in groups I and II (respectively, 0.24 +/- 0.1 vs. 0.23 +/- 0.18; P = NS), postpacing lactate extraction rates were decreased significantly in the two groups, prominently in group II (0.154 +/- 0.15 vs. -0.471 +/- 0.27; P < 0.0001) which indicated that lactate extraction converted to lactate production. Metabolic ischemia was detected in only 17.6% of patients included in this study and 83.4% of these six patients with proven metabolic ischemia had perfusion defects in scintigraphy. Our data confirmed that angina pectoris was not originated from myocardial ischemia in most of the patients with slow coronary flow. We conclude that perfusion scintigraphy is a reliable and accurate method for detection of true ischemia in this group of patients.     

Effects of atrial pacing on coronary sinus endothelin-1 and nitric oxide levels in patients with myocardial bridging

Myocardial bridging (MB) is associated with clinical and metabolic evidence of ischaemia. In the present study, we aimed to evaluate the extent of atherosclerosis and endothelial dysfunction in patients with MB. The study population consisted of 15 patients with MB [9 women (60%), aged 56 +/- 9 years] and 14 control subjects [8 women (57%), aged 54 +/- 10 years]. All patients underwent coronary angiography. The femoral artery and coronary sinus endothelin-1 (ET-1) and nitric oxide (NOx) plasma levels were measured before and after right atrial pacing in all subjects. Also, intravascular ultrasonography was performed in 13 patients with MB. With right atrial pacing, coronary sinus ET-1 levels increased significantly in patients with MB compared with baseline levels (5.77 +/- 6.76 versus 11.32 +/- 9.40 pg/ml, p < 0.05). The coronary sinus ET-1 levels remained unchanged in controls with pacing (3.99 +/- 4.00 versus 4.19 +/- 7.15 pg/ml, p > 0.05). There was no significant difference between the two groups according to the increase in NOx levels with atrial pacing. Ten (77%) of the 13 patients had plaque formation in the segments proximal to the bridge with an area stenosis of 37 +/- 21% (12% to 75%). In patients with MB, post-pacing levels of coronary sinus ET-1 correlated significantly with the cross-sectional area of the plaque (r = 0.65, p = 0,04). Increased ET-1 levels and the pathological data of intravascular ultrasonography may be associated with endothelial dysfunction and atherosclerosis development in patients with MB. The presence of atherosclerosis in the proximal segments to the bridge may contribute to the myocardial ischaemia detected in these patients.     

Effects of propranolol on coronary hemodynamic and metabolic responses to tachycardia stress in patients with and without coronary disease

To clarify the influence of propranolol—and particularly its heart-rate effects—on myocardial ischemia, coronary hemodynamics and metabolism were studied in 15 patients utilizing a protocol to control heart rate. Ten patients had significant coronary narrowing (CAD) and 5 were normal. Systemic pressure, coronary sinus blood flow (CSBF), left ventricular oxygen utilization (LVV?O₂), ST Segment depression, and myocardial lactate extraction were measured before and after propranolol (10 mg IV), at rest, and during pacing-induced tachycardia stress. Propranolol-related reduction in CSBF and LVV?O₂ at rest was reversed when heart rate was controlled in both patient groups. Propranolol failed to alter heart-rate threshold, tension-time index (TTI), CSBF, or LVV?O₂ at angina in the CAD patients. Likewise, ischemic-type ST depression, decreases in lactate extraction, and coronary resistance were unchanged compared to values observed during tachycardia stress before propranolol. In normal coronary patients, propranolol also produced no significant change in LVV?O₂ or coronary resistance when its heart rate effects were controlled. These data imply that a major coronary and metabolic influence of propranolol relates to changes occurring secondary to its influence on heart rate. Furthermore, this agent's anti-ischemic effect is not prominent during tachycardia stress suggesting that this stress test may be clinically useful in patients taking propranolol.     

Effects of isosorbide dinitrate on the response to atrial pacing in coronary heart disease.

To study the efficacy of isosorbide dinitrate in prevention of myocardial ischemia, 20 patients with angiographically proved coronary artery disease underwent atrial pacing (mean rate 138/min) before (P1), 10 minutes after (P2) and 65 minutes after (P3) sublingual administration of 5 mg of isosorbide dinitrate. The symptomatic, hemodynamic and metabolic responses were evaluated at rest and during each pacing period. Angina occurred in all subjects during P1. Angina did not recur or was less severe in 17 of 19 patients during P2 and in 19 of 20 patients during P3. Resting left ventricular end-diastolic pressure for the group was normal at 11 plus or minus 4 mm Hg (mean plus or minus standard deviation). On interruption of pacing at 4.5 minutes during P1, average end-diastolic pressure during sinus rhythm was abnormal (18 plus or minus 6 mm Hg). After administration of isosorbide dinitrate mean left ventricular end-diastolic pressure was significantly decreased at rest and remained normal when pacing was interrupted during P2 and P3. Brachial arterial pressure, cardiac index, tension-time index, left ventricular stroke work index and maximal rate of rise of left ventricular pressure were all diminished at rest before and during P2 and P3. S-T segment depression was less during P2 and P3 than during P1. Before isosorbide dinitrate was given, resting myocardial lactate extraction was 15 plus or minus 11 percent during P1 lactate extraction decreased to minus2 plus or minus 25 percent. Lactate extraction was significantly greater during P2 and P3 than during P1. This study demonstrates that sublingual administration of 5 mg of isosorbide dinitrate has a significant protective effect against pacing-induced myocardial ischemia at 10 and 65 minutes after administration.     

The effect of nitroglycerin on coronary blood flow and the hemodynamic response to exercise in coronary artery disease

Hemodynamic indexes and coronary blood flow were measured at rest and during exercise before and after nitroglycerin in 15 patients with coronary artery disease. Angina developed in 7 of these patients during the initial exercise period and was associated with an increase in left ventricular end-diastolic pressure to 32.9 mm Hg without an appropriate increase in left ventricular stroke work. During exercise after nitroglycerin only 2 of these patients experienced angina and the hemodynamic response to exercise was normal. In the patients without angina minor alterations in ventricular performance occurred during the initial exercise period, and these were similarly reversed with nitroglycerin. Coronary blood flow measured by the ⁸⁵krypton technique was normal at rest and during exercise in both groups of patients before and after the administration of nitroglycerin. Since there was no demonstrable effect on coronary blood flow, we conclude that nitroglycerin acts primarily by reducing left ventricular oxygen requirements and that this reduction is effected primarily through a reduction in left ventricular volume.     

Effects of atrial pacing on arterial and coronary sinus endothelin-1 levels in syndrome X

Syndrome X may be caused by a coronary microvascular dysfunction, possibly due to abnormalities in coronary endothelial function. Previous studies suggested that endothelin-1 (ET-1) might be involved in the pathogenesis of syndrome X. Baseline arterial and coronary sinus ET-1 levels were measured in 13 patients with syndrome X (10 women, 52+/-7 years) and in 8 control patients (5 women, 46+/-11 years). ET-1 was also measured after atrial pacing in 12 patients with syndrome X and all controls. To simultaneously assess the activity of nitric oxide, guanosine 3'-5'-cyclic monophosphate (cGMP) was also measured in 11 patients with syndrome X and 7 controls. Baseline arterial (2.27+/-0.46 vs. 1.90+/-0.22 pg/ml, p<0.05) and coronary sinus (2.03+/-0.43 vs. 1.68+/-0.28 pg/ml, p = 0.06) ET-1 plasma levels were higher in patients than in controls. After pacing, arterial ET-1 levels did not change in either group and coronary sinus ET-1 levels were also unchanged in controls. In contrast, coronary sinus ET-increased significantly in response to atrial pacing in patients with syndrome X (p = 0.023), and differences between coronary sinus ET-1 levels of patients with syndrome X and controls after pacing became highly significant (2.22+/-0.45 vs. 1.69+/-0.20 pg/ml, respectively, p = 0.006). No significant differences in arterial and coronary sinus cGMP concentrations were found between the 2 groups, both at baseline and after pacing. Our findings suggest that an increased vasoconstrictor activity of microvascular endothelium is present in at least some patients with syndrome X and may be involved in the pathogenesis of the syndrome.     

Characteristics of right atrial activation during coronary sinus pacing

INTRODUCTION: Anatomic and electrical connections between the left atrium and right atrium (RA) have been described. The relationship between coronary sinus (CS) pacing site and RA activation has not been examined. METHODS AND RESULTS: Fifteen anesthetized swine underwent high-density noncontact mapping of the RA during pacing from up to five different sites within the CS. Isopotential mapping identified the site of earliest RA depolarization and the pattern of subsequent activation. Hearts were excised and endocardial dissection performed. Earliest RA activation occurred at the CS os with proximal CS pacing sites and at Bachmann's bundle at distal pacing sites. The mean depth at which a shift in earliest RA activation site occurred was 46 +/- 13 mm (range 21 to 63 mm). RA activation times following earliest activation at the CS and Bachmann's bundle were 40 +/- 4 msec and 51 +/- 6 msec (P < 0.002). Conduction delay or block was recorded at the lateral cavotricuspid isthmus, terminal crest, and tendon of Todaro. Latest RA activation always occurred in the high anterolateral atrium after ascending the anterolateral wall. The lateral RA was activated by the wavefront that traversed the posterior wall rather than by the wavefront crossing the cavotricuspid isthmus, even with earliest RA activation at the CS os. CONCLUSION: The site of earliest RA activation during CS pacing is dependent upon the pacing depth within the CS. In the porcine heart, areas of conduction delay influence RA activation patterns and timings. These findings may have implications for patients undergoing assessment of radiofrequency ablation of atrial flutter.     

冠状静脉窦起搏治疗阵发性心房颤动

心房颤动 (房颤 )的治疗一直是临床难点 ,起搏治疗是临床的选择之一。 1997年 ,Papageorgiou等[1] 的电生理研究表明冠状静脉窦起搏能有效防止房颤发生 ,但冠状静脉窦起搏治疗阵发房颤的长期临床应用尚未见报道。资料和方法患者 6例 ,男性 ,年龄 6 4～ 79(平均 6 9 2 )岁。 6例均为病态窦房结综合征 (病窦 )患者 ,其中 3例合并高血压性心脏病。超声心动图测定左心房直径为 2 7 3～ 37 5 (平均33 7)mm ,其中 3例左心房增大。 6例患者均反复发生阵发性房颤 ,其中 2例合并心房扑动、1例合并二度房室阻滞 ,5例窦性心律时体表心电图P波时限≥ 0 …     

Long-term hemodynamic benefit of biventricular pacing depending on coronary sinus lead position

Summary Background Acute studies in cardiac resynchronization therapy (CRT) showed that hemodynamic effects may depend on the coronary sinus (CS) lead position. However, there are no data on the longterm effect of CS lead position. Methods In 45 heart failure patients with left bundle branch block and QRS >150 ms (age 59±10 years, 17 dilative cardiomyopathy, 23 ischemic, 5 valvular), biventricular pacemakers were implanted. CS leads were positioned in posterior (P, n=15), lateral (L, n=19) or, if no other option available, anterior (A, n=11) side branches. Before and 6 months after implantation, clinical state, echocardiography, brain natriuretic peptide (BNP) and right heart catheterization were evaluated. Results Baseline parameters were similar between groups. After 6 months, there were 32/34 responders in groups P and L compared to 7/11 responders in group A (94 vs roups P and L: Arterial pressure +8 and +9% vs +2%; PCWP –23 and –15% vs –4%, pulmonary pressure –18 and –12% vs –3% (p<0.01 for A vs P+L); cardiac index +21 and +12% vs +11% (p=0.03 for A vs P). BNP was reduced by 55, 35, and 27% (p=0.05 for A vs P). Ejection fraction increased in P and L by 40 and 41%, respectively, but only by +19% in A (p<0.03 for A vs P+L). Conclusion Chronic CRT improves ejection fraction, BNP and hemodynamic measurements predominantely in patients with lateral and posterior CS lead positions. Anterior lead positions should be avoided.      

Cardiovascular dynamics during coronary sinus, right atrial, and right ventricular pacing

Permanent pervenous right atrial pacing has not been widely used to date. The coronary sinus may provide a site from where reliable permanent pacing can be performed so as to preserve atrial contribution in patients with intact A-V conduction who require pacing, as in sinus bradycardia, sinus arrest, and recurrent tachyarrhythmias.     

冠状静脉窦口起搏对心房激动时间影响及方法学探讨

目的观察冠状静脉窦口起搏对心房激动时间的影响，并探讨该部位起搏的方法学。方法包括两部分，首先对20例射频消融的患者行心内电生理检查，术中分别给予高位右心房（HRA）、冠状静脉窦口（CS9-10）、左心房游离壁（CS1-2）起搏，记录刺激信号至腔内电图最远A波为心房激动时间；HRA至CS1-2的AA间期作为左、右心房间激动时间差，同时测量体表心电图最长P波时限。第二部分研究在可控弯导丝系统的辅助下将心房主动电极导线固定在冠状静脉窦口，比较冠状静脉窦口起搏与HRA起搏的起搏参数及起搏后体表心电图P波时限。结果冠状静脉窦口起搏时P波时限、心房激动时间及左、右心房激动时间差较窦性心律下、高位右心房及左心房游离壁起搏时均明显缩短。两组患者术中及术后起搏参数差异无统计学意义，冠状静脉窦口起搏患者体表心电图P波宽度明显缩短。结论冠状静脉窦口起搏时心房激动时间明显缩短，左、右心房间激动时间差最短。采用可控弯导丝系统的辅助可实现冠状静脉窦口起搏。     

Increased myocardial microvascular utilisation and flow during atrial pacing

To determine the influence of heart rate on regional coronary flow, the coronary vascular and microvascular responses to increased heart rate were examined in anaesthetised open chest New Zealand white rabbits. Coronary blood flow was measured with labelled microspheres. Fluorescein isothiocyanate (FITC)-dextran (150 mg.kg-1) was given to mark the perfused microvessels. The FITC-dextran was given at various intervals before removal of the heart. Alkaline phosphatase stain was used to locate the total microvasculature. Increase in heart rate from 272(SD23) to 339(13) beats.min-1 increased the coronary blood flow from 198(56) to 288(82) ml.min-1.100 g-1. The subendocardial/subepicardial flow ratio was not altered by pacing. Total capillary density averaged 2508(363).mm-2 and arteriolar density was 1.74(4.1).mm-2. There were no significant regional or treatment differences in these values. The increase in blood flow with pacing was accompanied by a uniform increase in the percentage of the microvasculature perfused in the subepicardial and the subendocardial layers of the left ventricular free wall, from 58(6)% to 75(10)% for capillaries and from 54(17)% to 81(19)% for arterioles. These results show that enhanced heart rate increases the coronary blood flow and the density of the perfused microvessels uniformly across the ventricular wall. Thus both the coronary vascular and microvascular reserves are used in the rabbit heart during tachycardia.     

Effects of posture on metabolic and hemodynamic predischarge exercise response after acute myocardial infarction

Predischarge exercise testing after acute myocardial infarction (AMI) is an important noninvasive modality for risk stratification. To study the impact of position on cardiopulmonary exercise response, 30 patients performed symptom-limited upright treadmill and supine bicycle ergometry exercise an average of 8 days after an AMI. The exercise sequence was randomly assigned with a minimum 4-hour interval between tests. Exercise time and peak oxygen consumption were significantly greater in the upright position (7.0 +/- 2.0 vs 5.6 +/- 2.0 minutes; p less than 0.001 and 14.9 vs 12.0 ml/min/kg; p less than 0.001, respectively). Compared to the supine position, exercise in the upright position was associated with a significant increased incidence of ischemic exercise-induced ST-segment depression (33 vs 20%; p less than 0.03), and chest pain (20 vs 10%; p less than 0.04). Thus, position is an important determinant of myocardial ischemic response and exercise tolerance in patients who perform symptom-limited exercise tests early after AMI.     

Consequences of reperfusion after coronary occlusion. Effects on hemodynamic and regional myocardial metabolic function

Hemodynamic and regional metabolic measurements were obtained in seven closed chest dogs during a control period, 3 hours of coronary occlusion and 5 hours of reperfusion. Reperfusion resulted in intermittent ectopic arrhythmias in five dogs and severe shock in two. It usually caused increases in heart rate, coronary sinus flow and maximal isovolumetric rate of rise in left ventricular pressure (dP/dt), which were associated with a decrease in systemic pressure, left ventricular end-diastolic pressure, systemic vascular resistance and stroke work. A transitory increase in cardiac output occurred. Global myocardial oxygen consumption, which was reduced during occlusion, increased with reperfusion. Reperfusion induced abnormal lactate metabolism and myocardial potassium loss in the previously occluded area and often in the nonoccluded segment as well. Histopathologic changes of accelerated necrosis, reactive hyperemia and hemorrhage were often noted after reperfusion.These studies indicate that reperfusion after 3 hours of occlusion caused serious abnormalities in hemodynamic states, metabolic function and morphologic features of the heart.