Potassium exchange in the human heart during atrial pacing and myocardial ischaemia

Potassium homoeostasis in the heart was studied during atrial pacing in 20 patients undergoing diagnostic coronary angiography. The potassium concentrations in the coronary sinus and a systemic artery were recorded continuously by means of catheter tip potassium electrodes. Ten patients with coronary artery disease and a positive exercise test developed chest pain and ST segment depression on the electrocardiogram during atrial pacing. Potassium concentrations in the coronary sinus rose initially and increased further when myocardial ischaemia developed. Ten patients including five with normal coronary arteries remained symptom free during atrial pacing with no electrocardiographic changes. In these patients coronary sinus potassium concentration increased at the onset of pacing, but returned to near control values despite continued pacing. In both groups arterial potassium concentration remained constant. Immediately after the end of pacing there was an abrupt transient fall in potassium concentrations in the coronary sinus to below control values. These results indicate that in man, as in other species, an increase in heart rate causes the transient movement of potassium out of the cell into the extracellular space. The onset of myocardial ischaemia is associated with a further loss of potassium from the cell. The end of pacing or ischaemia is accompanied by a re-uptake of potassium by heart muscle.     

Potassium exchange in the human heart during atrial pacing and myocardial ischaemia.

Potassium homoeostasis in the heart was studied during atrial pacing in 20 patients undergoing diagnostic coronary angiography. The potassium concentrations in the coronary sinus and a systemic artery were recorded continuously by means of catheter tip potassium electrodes. Ten patients with coronary artery disease and a positive exercise test developed chest pain and ST segment depression on the electrocardiogram during atrial pacing. Potassium concentrations in the coronary sinus rose initially and increased further when myocardial ischaemia developed. Ten patients including five with normal coronary arteries remained symptom free during atrial pacing with no electrocardiographic changes. In these patients coronary sinus potassium concentration increased at the onset of pacing, but returned to near control values despite continued pacing. In both groups arterial potassium concentration remained constant. Immediately after the end of pacing there was an abrupt transient fall in potassium concentrations in the coronary sinus to below control values. These results indicate that in man, as in other species, an increase in heart rate causes the transient movement of potassium out of the cell into the extracellular space. The onset of myocardial ischaemia is associated with a further loss of potassium from the cell. The end of pacing or ischaemia is accompanied by a re-uptake of potassium by heart muscle.     

Effects of Acute Myocardial Ischaemia on Platelet Aggregation in the Coronary Sinus and Aorta in Dogs

The effect of an acute myocardial ischaemia on circulating platelet aggregates (CPA) in the coronary sinus and aorta was studied in open chest dogs. Even before induction of myocardial ischaemia significantly more CPA were found in the coronary sinus than in the aorta. Acute myocardial ischaemia produced by a non-thrombotic coronary artery occlusion increased CPA in coronary sinus, but not in aorta. Administration of acetylsalicylic acid (ASA) reduced the extent of the myocardial ischaemia as evidenced by reduced ST-segment elevations in epicardial ECG. Before induction of myocardial ischaemia, ASA significantly reduced CPA in coronary sinus, but no significant effect was observed during myocardial ischaemia. In the aorta no effect of ASA on CPA was found.     

Lipid peroxidation during myocardial ischaemia induced by pacing

Oxygen derived free radical generation can be shown in experimental models of myocardial ischaemia and reperfusion and may cause cellular damage by peroxidizing polyunsaturated membrane phospholipids. An attempt was made to quantify human intracardiac lipid peroxidation during transient myocardial ischaemia by measuring the aortic and coronary sinus concentrations of malondialdehyde (a marker of lipid peroxidation) before, during, and after incremental pacing. Twenty six patients were paced until they had severe chest pain or 2 mm ST segment depression or they reached a paced rate of 180 beats/min. They were divided into two groups according to whether or not lactate was produced during pacing. Twelve patients (group 1), all with coronary artery disease, produced myocardial lactate during pacing. None of the other 14 patients (group 2), half of whom had coronary disease, produced lactate during pacing. Concentrations of malondialdehyde in the aorta and coronary sinus were significantly higher in group 1 than in group 2. Five minutes after the end of pacing coronary sinus malondialdehyde concentrations in group 1 had increased significantly from baseline values. There were no changes with time in the coronary sinus concentration of malondialdehyde in group 2 or in the aorta in either group. The negative malondialdehyde extraction ratio in group 1 suggests that intracardiac lipid peroxidation occurs during transient human myocardial ischaemia.     

Lipid peroxidation during myocardial ischaemia induced by pacing.

Oxygen derived free radical generation can be shown in experimental models of myocardial ischaemia and reperfusion and may cause cellular damage by peroxidizing polyunsaturated membrane phospholipids. An attempt was made to quantify human intracardiac lipid peroxidation during transient myocardial ischaemia by measuring the aortic and coronary sinus concentrations of malondialdehyde (a marker of lipid peroxidation) before, during, and after incremental pacing. Twenty six patients were paced until they had severe chest pain or 2 mm ST segment depression or they reached a paced rate of 180 beats/min. They were divided into two groups according to whether or not lactate was produced during pacing. Twelve patients (group 1), all with coronary artery disease, produced myocardial lactate during pacing. None of the other 14 patients (group 2), half of whom had coronary disease, produced lactate during pacing. Concentrations of malondialdehyde in the aorta and coronary sinus were significantly higher in group 1 than in group 2. Five minutes after the end of pacing coronary sinus malondialdehyde concentrations in group 1 had increased significantly from baseline values. There were no changes with time in the coronary sinus concentration of malondialdehyde in group 2 or in the aorta in either group. The negative malondialdehyde extraction ratio in group 1 suggests that intracardiac lipid peroxidation occurs during transient human myocardial ischaemia.     

Sympathetically induced myocardial ischaemia causes the heart to release plasma kinin

A recently developed highly sensitive radioimmunoassay method for detecting plasma kinin was used to re-evaluate the results of previous studies, in which plasma kinin had been measured with a bioassay method. To clarify the mechanism of plasma kinin release in global myocardial ischaemia the left main coronary artery was cannulated using a Griggs type autoperfusing cannula after pentobarbital anaesthesia in open chest dogs. The animals were divided into a non-coronary constricted group (n = 4) and a moderately coronary constricted group (n = 7). Cardiac sympathetic nerve stimulation (10 V, 4 Hz, 2 ms duration) was given to both groups. Haemodynamic recordings and blood samples were taken before and after coronary constriction as well as after sympathetic nerve stimulation. The arterial and coronary sinus plasma kinin concentrations were determined with the new radioimmunoassay method. After sympathetic nerve stimulation apparent myocardial ischaemia occurred and the plasma kinin concentration in coronary sinus blood increased significantly in the constricted group. In the non-constricted group, however, myocardial ischaemia did not appear and no significant change in coronary sinus plasma kinin concentrations was seen. These findings show that there was a pronounced release of plasma kinin from the heart when apparent myocardial ischaemia occurred.     

Lack of platelet-activating factor release during reversible myocardial ischaemia.

Platelet-activating factor (PAF) is involved in experimental models of myocardial ischaemia, and PAF infusion can cause thromboxane release. Thromboxane is produced during brief episodes of reversible myocardial ischaemia in patients with coronary heart disease. To learn whether PAF synthesis is associated with thromboxane production in mild myocardial ischaemia, we performed rapid atrial pacing in four patients with angina pectoris which caused chest pain, ST segment depression (delta ST = -1.8 +/- 0.2 mm) and lactate excretion in the coronary sinus (percent lactate extraction decreased from 20 +/- 6% to -15 +/- 9%). Thromboxane B2 was produced causing a positive transmyocardial gradient (from 88 +/- 154 pg.ml-1 baseline to 1770 +/- 1407 pg.ml-1 at the peak) but there was no PAF release into coronary sinus blood. In four other patients we determined whether more pronounced ischaemia could be associated with PAF synthesis. Coronary sinus blood was sampled before and during balloon occlusion of a major coronary artery: PAF was not detected in coronary sinus, whereas percent lactate extraction decreased from 24 +/- 6% to -63 +/- 22% (n = 4). We conclude that PAF plays a minor role in short episodes of reversible ischaemia and does not participate in thromboxane production.     

Intravascular detection of myocardial ischemia by spectrometry in the near infrared spectrum in experimental animals

Interruption of oxygen supply in acute myocardial ischaemia reduces venous return of oxygen at the coronary sinus. In this study, the oxygen content of venous return in the coronary sinus was measured by using spectrometry in the near infrared spectrum. The authors developed a new intravascular catheter made of fibre optics. After in vitro calibration by blood flow based on a standard gas mixture used in in vitro experiment, an in vivo application in 12 domestic pigs was undertaken. The catheter was positioned in the coronary sinus and ischaemia induced by temporary occlusion of the left anterior descending artery. Recordings of the near infrared spectrum and haemodynamic data were obtained during 90 minutes' ischaemia followed by 90 minutes reperfusion. Spectrometry in the near infrared range detected a marked difference between oxyhaemoglobin and deoxyhaemoglobin, especially when the oxygen concentration was less than 30%. The near infrared spectrum of liaison between haemoglobin and oxygen in the coronary sinus shows significant and reproducible differences between pre-ischaemia occlusion of the left anterior descending artery and reperfusion. The recordings of the near infrared also show variation in CO2, pH and temperature. The authors conclude that the use of intravascular spectrometry of the near infrared spectrum could be a permanent reliable tool for detection and follow-up of acute myocardial ischaemia.     

Myocardial potassium loss after acute coronary occlusion in humans

Animal studies have established that there is a rapid increase in extracellular potassium concentration in myocardial tissue after the onset of ischemia. To study this phenomenon in humans, coronary sinus plasma potassium concentration was measured in five patients undergoing therapeutic coronary angioplasty. Recordings were obtained during a total of 22 coronary artery occlusions lasting between 5 and 50 seconds. Though little change was observed during angioplasty balloon inflation, all occlusions that lasted more than 15 seconds were followed by a transient elevation in coronary sinus potassium concentration of between 0.18 and 1.55 mmol X liter-1. The majority of occlusions (n = 17) were not accompanied by chest pain, electrocardiographic (ECG) changes or alteration of heart rate. The increase in coronary sinus potassium concentration after angioplasty balloon deflation is attributable to a washout of accumulated extracellular potassium during reperfusion. Redistribution of human myocardial potassium occurs within 15 seconds of the onset of myocardial ischemia and may be an important factor accounting for early electrophysiologic changes.     

Coronary haemodynamic effects of nifedipine. Comparison with glyceryl trinitrate.

The coronary haemodynamic effects of nifedipine and glyceryl trinitrate were compared in 22 patients undergoing investigations for suspected coronary artery disease. Myocardial blood flow was estimated by the coronary sinus thermodilution technique. In sinus rhythm nifedipine increased mean coronary sinus flow from 135 ml/min to 152 ml/min, and reduced arterio-coronary sinus oxygen difference from 12.4 to 10.96 ml/100 ml without causing a significant change in coronary vascular resistance or in myocardial oxygen consumption. Glyceryl trinitrate reduced mean coronary sinus flow from 165 to 111 ml/min, myocardial oxygen consumption from 19.2 to 11.9 ml/min, and arterio-coronary sinus oxygen difference from 11.7 to 10.9 ml/100 ml. There was a rise in coronary vascular resistance from 54 355 to 74 364 dynes s cm-5. During atrial pacing nifedipine reduced the arterio-coronary sinus oxygen difference from 11.99 to 11.0 ml/100 ml but had no significant effect on the other variables measured. Glyceryl trinitrate caused a fall in mean coronary sinus flow from 207 ml/min to 168 ml/min; myocardial oxygen consumption fell from 24 ml/min to 18 ml/min, while coronary vascular resistance rose from 41 714 to 51 234 dynes s cm-5. Direct comparison of the two drugs showed a significant difference in effects on coronary sinus flow and coronary vascular resistance in sinus rhythm. Both drugs appeared effective in relieving ischaemia as judged by a reduction of the incidence of pacing induced angina and an improvement in lactate status.     

Unusual congenital coronary anomaly and myocardial ischaemia

Angiography was used to diagnose a rare congenital coronary anomaly with myocardial ischaemia in a woman with typical angina. All three coronary arteries arose from a solitary coronary ostium in the right aortic sinus; the left anterior descending coronary artery followed a septal course, the circumflex coronary artery ran behind the ascending aorta, and the right coronary artery followed a normal course. No significant coronary lumen narrowing was found. Transoesophageal echocardiography confirmed the anomalous origin and course of the aberrant coronary arteries. An exercise test reproduced angina, and ECG changes and myocardial perfusion study showed an anterior reversible defect. In contrast to previous reports, myocardial ischaemia was associated with the septal (intramuscular) course of the left anterior descending coronary artery; there was no other significant coronary artery disease.


Keywords: congenital heart defects; myocardial ischaemia; angiography; echocardiography     

Cardiac release of chemoattractants after ischaemia induced by coronary balloon angioplasty.

OBJECTIVE--To investigate the release of chemoattractants after myocardial ischaemia during balloon angioplasty. DESIGN--Sampling of femoral arterial and coronary sinus blood before and immediately after the first balloon inflation during angioplasty. In a study group of 16 patients the balloon was kept expanded for two minutes, whereas in a control group of eight patients the first balloon inflation was brief (< 10 s). MAIN OUTCOME MEASURES--Chemotaxis of neutrophils from healthy donors towards patient plasma (Boyden chamber), superoxide anion production by normal neutrophils after incubation with patient plasma (cytochrome C reduction). RESULTS--In the study group, coronary sinus plasma after balloon deflation was more chemoattractive to normal neutrophils (median relative increase 24% (quartiles: 4%, 45%), p = 0.008) and induced a higher superoxide anion production in normal neutrophils (44% (10%, 97%), p = 0.013) than arterial plasma. Concomitantly, the degree of activation of patient neutrophils was increased in coronary sinus blood compared with arterial blood, as shown by an increased proportion of neutrophils reducing nitro-blue tetrazolium (21% (9%, 38%), p = 0.006) and a decreased neutrophil filter-ability (-16%(-3%, -40%), p = 0.003) in coronary sinus blood. In the study group before balloon inflation and in the control group before and after balloon inflation differences between arterial and coronary sinus blood were not significant. Signs of ischaemia (lactate release, ST segment changes) were only detected in the study group. CONCLUSION--After transient myocardial ischaemia during balloon angioplasty there is a local release of chemoattractants, associated with neutrophil activation.     

Increased coronary sinus lactate concentration during pacing induced angina pectoris after clinical improvement by glyceryl trinitrate.

Ten patients with stable angina pectoris and obstructed coronary arteries (greater than 75% reduction in diameter) were studied before and during two periods of pacing, the second of which was preceded by sublingual administration of glyceryl trinitrate (mean dose 0.78 mg). Coronary sinus blood flow measurements and aortocoronary sinus blood sampling for metabolite determinations were carried out. Although the rate of pacing was increased by 10 beats/minute after glyceryl trinitrate administration, the onset of angina was delayed in eight patients during pacing. Drug administration decreased coronary sinus blood flow by 42% and myocardial oxygen uptake by 41% during pacing and induced a shift in mean lactate extraction towards a net release (from 3.1% to -12.6%). It increased the number of patients producing lactate from three to five. Glyceryl trinitrate administration decreased myocardial glucose uptake throughout the study, decreased lactate extraction during recovery, and increased the aortocoronary sinus citrate gradient at rest and during recovery, while the exchange of free fatty acids remained unchanged. A decrease in aortocoronary sinus lactate difference during pacing after glyceryl trinitrate administration correlated positively with the fall in coronary sinus blood flow. The metabolic data do not indicate an augmented myocardial lactate production after glyceryl trinitrate administration. A decrease in coronary sinus blood flow seems, therefore, to be of primary importance in explaining the elevated coronary sinus lactate concentration. Our finding that coronary sinus lactate concentration increased during pacing after glyceryl trinitrate administration despite clinical improvement questions the validity of its use as a quantitative index of ischaemia.     

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.     

Extracellular potassium activity changes in the canine myocardium after acute coronary occlusion and the influence of beta-blockade.

Extracellular potassium activity before and after coronary occlusion was measured in the canine heart by means of potassium-selective surface electrodes. In the ischaemic myocardium potassium activity rapidly increased from a preocclusion value of 3.2 +/- 0.3 mmol.litre-1 to 10 +/- 0.6 mmol.litre-1 within the first 5 min and to about 11.3 +/- 0.5 mmol.litre-1 after 10 min of ischaemia (range from 9.5 to 14.5 mmol.litre-1). Following the initial 10 min of ischaemia no further increase was measured. In the non-ischaemic area potassium activity remained constant. Acute beta-blockade significantly attenuated the initial rate of increase in potassium activity; however, beta-blockade did not influence maximal values of extracellular potassium activity measured after occlusion. Lowering of heart rate by vagal stimulation did not modify the pattern of increase in potassium during acute ischaemia. Following ventricular fibrillation, a slow but continuous rise in potassium activity was found. These results demonstrate that extracellular potassium activity in the acutely ischaemic myocardium is considerably higher than indicated by the technique of coronary vein sampling and is in the range necessary for the development of re-entrant arrhythmias in the early phase after coronary occlusion.     

Rate dependence of ischaemic myocardial depolarisation: evidence for a novel membrane current

Depolarisation of ischaemic myocardial cells is at least partly due to loss of cellular potassium. Whereas most manifestations of ischaemia vary with heart rate potassium loss, however, reportedly does not. Cellular depolarisation was therefore correlated with extracellular potassium activity during serial coronary artery occlusions in Langendorff perfused canine hearts. Occlusions in sinus rhythm (92(11) beats X min-1) were alternated with rapidly paced occlusions (180 beats X min-1). For each occlusion cellular depolarisation was estimated from TQ depression and compared with the simultaneous increase in potassium electrode potential, delta EK. Although potassium accumulation accounted for most of the estimated depolarisation at slow heart rates, a potassium independent mechanism predominated during rapid pacing. The potassium independent mechanism was especially important in the first minute of ischaemia when pacing increased depolarisation by 324%, with little increase in delta EK. It appears that ischaemia induces a rate sensitive depolarising membrane current, which worsens conduction and promotes arrhythmias.     

Transcardiac serotonin concentration is increased in selected patients with limiting angina and complex coronary lesion morphology

Serotonin is released by activated platelets and may act as a mediator to initiate or sustain certain unstable syndromes of ischemic heart disease in humans. To determine whether or not serotonin concentration increases across the coronary bed in patients with severe, limiting angina, we measured central aortic and coronary sinus serotonin concentrations by a sensitive radioenzymatic assay in 39 patients with coronary artery disease and 13 patients with minimal or no coronary artery lesions as detected by arteriography. Although no difference existed in the mean aortic or coronary sinus serotonin concentrations between these two groups, elevated coronary sinus serotonin concentrations were detected in 23% of those with coronary artery disease. The coronary sinus and aortic serotonin concentration difference was greater in patients with significant coronary artery disease (0.6 +/- 6.62 ng/ml) compared with patients without significant coronary artery disease (-5.6 +/- 10.32 ng/ml) (mean +/- SD) (p less than 0.05). Further analysis revealed that patients with eccentric, irregular coronary artery lesions or intraluminal filling defects had a significantly elevated coronary sinus and aortic serotonin difference (3.1 +/- 5.54 ng/ml) compared with those with smooth concentric lesions (-1.9 +/- 6.61 ng/ml) (p less than 0.02). These data suggest that serotonin is released into the coronary circulation of some patients with coronary artery disease, especially those with frequent angina and complex coronary lesions. Although serotonin may be released in some patients with coronary artery disease, the specific pathophysiologic role of serotonin in the development or perpetuation of certain coronary syndromes in humans remains to be determined.     

Changes in coronary sinus pH during dipyridamole stress in patients with hypertrophic cardiomyopathy.

OBJECTIVES: The presence of angina pectoris and myocardial scarring in patients with hypertrophic cardiomyopathy (HCM) suggests that myocardial ischemia is a factor in the pathophysiology of the disease. The clinical evaluation of ischaemia is problematic in HCM as baseline electrocardiographic abnormalities are frequent and thallium-201 perfusion abnormalities correlate poorly with anginal symptoms. Coronary sinus pH measurement using a catheter mounted pH electrode is a validated sensitive technique for the detection of myocardial ischaemia. METHODS AND RESULTS: 11 patients with HCM and chest pain (eight men; mean (SD) (range) age 36 (11) (19-53) years) and six controls (two men; mean (SD) (range) age 49 (11) (31-62) years) with atypical pain and normal coronary angiograms were studied. Eight patients with HCM had baseline ST segment depression of > or = 1 mm and four had reversible perfusion defects during stress 201TI scintigraphy. A catheter mounted hydrogen ion sensitive electrode was introduced into the coronary sinus and pH monitored continuously during dipyridamole infusion (0.56 mg/kg over four min). The maximal change in coronary sinus pH during dipyridamole stress was greater in patients with HCM than in controls (0.082 (0.083) (0 to -0.275) v 0.005 (0.006) (0 to -0.012), P = 0.02). In six patients (four men; mean (SD) (range) age 29 (9) (19-40 years) the development of chest pain was associated with a gradual decline in coronary sinus pH (mean 0.123 (0.089)), peaking at 442 (106) s. There were no relations among left ventricular dimensions, maximal wall thickness, and maximum pH change. In patients with HCM there was a correlation between maximum pH change and maximum heart rate during dipyridamole infusion (r = 0.70, P = 0.02). CONCLUSION: This study provides further evidence that chest pain in patients with HCM is caused by myocardial ischaemia. The role of myocardial ischaemia in the pathophysiology of the disease remains to be determined but coronary sinus pH monitoring provides a method for quantifying and prospectively assessing its effects on clinical presentation and prognosis.     

Continuous recording of coronary sinus oxygen saturation during atrial pacing in patients with coronary artery disease or with syndrome X

Coronary sinus oxygen saturation was measured continuously during incremental atrial pacing in 34 patients undergoing cardiac catheterisation. In eleven patients with normal coronary arteriograms, negative exercise tests, and no ST segment depression on the electrocardiogram, an increase in the rate of atrial pacing transiently decreased coronary sinus oxygen saturation but within 20 s oxygen saturation returned to the control value. In six patients with coronary artery disease ST segment depression developed during atrial pacing. The coronary sinus oxygen saturation fell and remained reduced until pacing was discontinued. The size of the fall of coronary sinus oxygen saturation increased with increasing heart rate. In seven patients with coronary artery disease the ST segments were unaltered during atrial pacing and coronary sinus oxygen saturation did not fall. Ten patients with syndrome X were studied. In six ST segment depression developed on atrial pacing. In five, three of whom developed ST segment depression, the changes in coronary sinus oxygen saturation during atrial pacing were similar to those observed in patients without any evidence of coronary artery disease. In three, all of whom developed ST segment depression, coronary sinus oxygen saturation gradually increased throughout the period of atrial pacing. In two patients coronary sinus oxygen saturation fell in a manner similar to that observed in patients with obstructive coronary artery disease who developed ST segment depression on pacing. Thus regulation of coronary blood flow in normal persons in response to an increase of heart rate is rapid. Oxygen extraction across the coronary bed can increase by up to 30% and a persistent increase in oxygen extraction is an indicator of myocardial ischaemia. The term "syndrome X" does not describe a homogeneous group of patients but in the majority coronary sinus oxygen saturation does not fall despite symptoms and changes on the electrocardiogram, indicating that inadequate coronary blood flow is not the dominant mechanism.     

Continuous recording of coronary sinus oxygen saturation during atrial pacing in patients with coronary artery disease or with syndrome X.

Coronary sinus oxygen saturation was measured continuously during incremental atrial pacing in 34 patients undergoing cardiac catheterisation. In eleven patients with normal coronary arteriograms, negative exercise tests, and no ST segment depression on the electrocardiogram, an increase in the rate of atrial pacing transiently decreased coronary sinus oxygen saturation but within 20 s oxygen saturation returned to the control value. In six patients with coronary artery disease ST segment depression developed during atrial pacing. The coronary sinus oxygen saturation fell and remained reduced until pacing was discontinued. The size of the fall of coronary sinus oxygen saturation increased with increasing heart rate. In seven patients with coronary artery disease the ST segments were unaltered during atrial pacing and coronary sinus oxygen saturation did not fall. Ten patients with syndrome X were studied. In six ST segment depression developed on atrial pacing. In five, three of whom developed ST segment depression, the changes in coronary sinus oxygen saturation during atrial pacing were similar to those observed in patients without any evidence of coronary artery disease. In three, all of whom developed ST segment depression, coronary sinus oxygen saturation gradually increased throughout the period of atrial pacing. In two patients coronary sinus oxygen saturation fell in a manner similar to that observed in patients with obstructive coronary artery disease who developed ST segment depression on pacing. Thus regulation of coronary blood flow in normal persons in response to an increase of heart rate is rapid. Oxygen extraction across the coronary bed can increase by up to 30% and a persistent increase in oxygen extraction is an indicator of myocardial ischaemia. The term "syndrome X" does not describe a homogeneous group of patients but in the majority coronary sinus oxygen saturation does not fall despite symptoms and changes on the electrocardiogram, indicating that inadequate coronary blood flow is not the dominant mechanism.