Myocardial Demands of Atrial-Triggered Versus Fixed-Rate Ventricular Pacing in Patients with Complete Heart Block

Hemodynamics, myocardial oxygen consumption, and lactate concentration were determined by cardiac catheterization at rest and during exercise in eight patients treated with AV universal pacemakers (DDD) for high degree AV block. The pulse generator was alternately programmed in ventricular inhibited (VVI) or atrial synchronous (VAT) mode. During VVI pacing, the cardiac output rose between rest and exercise (4.3-7.6 L/min) due to increased stroke volume. VAT pacing gave significantly greater increase (4.5-8.8 L/min) which, as the stroke volume was unchanged, resulted from accelerated heart rate. The myocardial oxygen consumption and the coronary blood flow did not differ between VVI and VAT mode at rest or during exercise, nor did the modes make a difference in arterial systolic and pulmonary wedge pressures. These observations suggested that VAT pacing offers higher cardiac output than VVI pacing, but with similar demands on myocardial oxygen consumption.     

Coronary circulation in acute hypoxia

Summary. Healthy young men were subjected to different degrees of hypoxia at rest and during increased levels of cardiac work induced by atrial pacing and physical exercise at submaximal and maximal loads. Coronary sinus (cs) blood flow was measured by thermodilution and a-cs differences of O₂ and lactate were obtained. At low cardiac power output (rest, pacing) the reduction in arterial oxygen content was compensated for mainly by a more complete myocardial oxygen extraction producing lowered cs O₂ saturation and tension, while at higher cardiac power (exercise) the compensatory mechanism was entirely an increased coronary blood flow. It was possible to compensate fully for a reduction in arterial O₂ saturation of 9% even during maximal physical exercise. With a reduction in arterial oxygen content of more than 20–25% the flow increase was sufficient to supply the heart with enough O₂ during submaximal (heart rate 157 beats min^-1) but not maximal exercise, in which case anaerobic glycolysis contributed significantly to the myocardial energy metabolism. It is concluded that the normal heart has a ‘coronary flow reserve’ of about 33% above the flow prevailing during maximal physical exercise under air breathing.     

Myoglobin release in patients with angina pectoris following short-term ischaemia by pacing to angina

Summary. Thirteen patients with severe stable angina pectoris were studied by coronary sinus catheterization. In all patients, severe chest pains were produced by atrial pacing. The chest pains had disappeared within 10 min after pacing. Simultaneous arterial (a) and coronary sinus (cs) blood samples were taken before, during and after pacing and analyzed for myoglobin and lactate. The a-cs difference of myoglobin tended to become more negative after pacing, although the change was not significant. However, the change in negative direction post-pacing of the a-cs myoglobin difference was quantitatively correlated with the change in negative direction of the a-cs lactate difference during pacing in the individual patients. This suggests that short-term myocardial ischaemia without signs of established myocardial infarction may provoke myocardial myoglobin release.     

Effects of Increasing Heart Rate Induced by Efferent Sympathetic Neuronal Stimulation, Isoproterenol or Cardiac Pacing on Myocardial Function and Oxygen Utilization

The effects of increasing heart rate by six different methods on cardiac /unction were investigated in 17 open-chest anesthetized dogs. Heart rate was increased approximately 30% by (1) right interganglionic nerve stimulation, (2) atrial pacing, (3) ventricular pacing, (4) atriovenfricular sequential pacing, (5) right stellate ganglion stimulntion, and (6) isoproterenoi administration. During heart rate increases induced by atrial pacing left ventricular intramyocardial pressure, coronary Wood flow, oxygen delivery per unit of myocardial oxygen consumption, and myocardial efficiency were unchanged. Ventricular pacing reduced left ventricular cavity and septal intramyocardial pressure, while circumflex coronary flow increased, resulting in reduced oxygen delivery relative to myocardial oxygen consumption. Similarly, atrioventricu-lar sequential pacing increased circumflex coronary artery flow and myocardial oxygen consumption, and decreased septal intramyocardial pressure and oxygen delivery per unit of myocardial oxygen consumption. Right stellate ganglion stimulation and isoproterenol increased left anterior descending and circumflex coronary artery blood flow, intramyocardial pressure, and myocardial oxygen consumption. Estimated myocardial efficiency (left ventricle) was decreased by ventricular pacing and isoproterenol, and was unchanged by atrial pacing and right interganglionic nerve stimulation. Increases in heart rate induced by right interganglionic nerve stimulation did not alter myocardial oxygen consumption, or the index of cardiac efficiency. It is concluded that augmentation of heart rate by either ventricular or atrioventricular pacing impairs myocardial function so that there is a decrease of left ventricular efficiency, and isoproterenol augments chronotropism and myocardial force relative to cardiac external work so there is a reduction in cardiac efficiency. In contrast, atrial pacing or right interganglionic nerve stimulation augments chronotropism such that myocardial oxygen consumption and efficiency are unchanged.     

Differences in the effects of alpha-1 adrenergic blockade with prazosin and indoramin on coronary blood flow during exercise

This study compared the effects of two selective alpha-1 adrenergic blockers, prazosin and indoramin, on the response of coronary blood flow and myocardial oxygen consumption during treadmill exercise in chronically instrumented dogs. Left circumflex coronary artery blood flow was measured with an electromagnetic flowmeter, whereas myocardial arteriovenous oxygen difference was determined with indwelling aortic and coronary sinus catheters. During control conditions, coronary blood flow, arteriovenous oxygen extraction and myocardial oxygen consumption increased regularly with exercise. Both prazosin and indoramin decreased arterial pressure at rest and during exercise, but during heavier levels of exercise blood pressure was lower and heart rates were higher after prazosin. Prazosin did not alter myocardial oxygen consumption, whereas indoramin tended to decrease oxygen consumption; myocardial oxygen consumption was significantly less after indoramin than after prazosin during the heaviest levels of exercise. Prazosin, but not indoramin, significantly decreased coronary vascular resistance both at rest and during exercise, and blunted the decrease in coronary sinus oxygen tension which occurred during exercise. In comparison with prazosin, during heavy exercise coronary blood flow was significantly decreased, myocardial oxygen extraction significantly increased and myocardial oxygen consumption significantly decreased after indoramin.     

The Reliability of Rate-Pressure Product as an Index of Myocardial Oxygen Consumption in Atrial Synchronized Versus Fixed Rate Ventricular Pacing

The product of heart rate and blood pressure was tested as an index of myocardial oxygen consumption (MVO2) and compared with directly determined MVO2 during ventricular demand (VVI) fixed rate pacing and atrial synchronized (VAT) pacing at rest and during exercise. Systolic brachial artery pressure, pulmonary wedge pressure and MVO2 were similar in the two pacing modes and showed similar response to exercise. The correlation between rate-pressure product and MVO2 was closer with VAT than with VVI pacing (r = 0.74 and r = 0.64, respectively), and the latter value was not improved by using the product of atrial rate and systolic pressure (r = 0.61). The rate-pressure product was significantly higher during VAT pacing compared to VVI during exercise, although MVO2 was similar. The similarity of MVO2 during exercise indicated some other contributory factor than heart rate in VVI pacing, probably increase of contractility and/or volume. Because such factors are not included in currently used indices of MVO2 assessments must be interpreted cautiously, particularly in cases of complete heart block with VVI pacing.     

Is DDD Pacing Superior to VVI,R? A Study on Cardiac Sympathetic Nerve Activity and Myocardial Oxygen Consumption at Rest and During Exercise

Rate responsive ventricular pacing (VVI,R) has been demonstrated to equal atrial synchronous ventricular pacing (DDD) with regard to hemodynamics and exercise tolerance. Whether the two modes are also comparable, with regard to cardiac metabolic effects, is not yet dear. We assessed central hemodynamics, cardiac sympathetic nerve activity fcardiac norepinephrine overflow), and myocardial oxygen consumption in 16 patients treated with rate responsive atrial synchronous ventricular pacemakers (DDD,R), due to high degree AV block. The study was performed at rest and during supine exercise at two workloads (30 ± 12 and 68 ± 24 watts, respectively) during VDD and rate matched VVI pacing (VVI_m). Ventricular rates at rest and during both workloads were almost identical. Cardiac output at rest tended to be higher in the VDD mode, due to a slightly higher stroke volume. Central pressures including right atrial pressure and pulmonary capillary wedge pressure were similar in the pacing modes. The coronary sinus blood flow, the coronary sinus arteriovenous oxygen difference, and the myocardial oxygen consumption did not differ between the two pacing modes. Cardiac norepinephrine overflow was similar in the two pacing modes, at rest or during exercise. Thus, we found no significant differences between VDD and VVI_m pacing with regard to central hemodynamics, cardiac sympathetic nerve activity (cardiac norepinephrine overflow), or myocardial oxygen consumption either at rest or during moderate exercise.     

Conditioning Effects of Chronic Infusions of Dobutamine: COMPARISON WITH EXERCISE TRAINING

We studied the conditioning effects of chronic infusion of dobutamine and exercise training in three groups of chronically instrumented dogs. One group was infused with normal saline, a second group was infused with dobutamine (40 mug/kg per min), and the third group was exercised on a treadmill at 4 mph, up a 10 degrees incline. Each group was either infused or exercised for 2 h a day, 5 d a week for 5 consecutive wk. Resting heart rate and arterial blood lactate concentration, measured at weekly intervals, decreased progressively in the dobutamine and exercise groups, but not in the group that received normal saline infusion. Cardiovascular responses to submaximal treadmill exercise were not changed by 5 wk of normal saline infusion. However, the increases in heart rate, cardiac output, mean aortic blood pressure, arterial blood lactate, plasma renin activity, and norepinephrine concentration during exercise were significantly smaller after 5 wk of conditioning with either dobutamine or exercise training. After conditioning, the increases in arteriovenous oxygen difference during exercise were larger in the latter two groups, but the increases in total body oxygen consumption did not differ before and after conditioning.To assess ventricular function, we intravenously infused methoxamine both before and after conditioning. The slope of the line that related systolic aortic blood pressure and mean left atrial pressure increased in the animals conditioned with either dobutamine or exercise, indicating enhanced myocardial contractility. Left ventricular blood flow was lower in these two groups of animals than it was in the normal saline group. Left ventricular weight did not differ among the three groups.Our results show that chronic infusion of dobutamine produced cardiovascular and metabolic conditioning effects like those produced by exercise training, and further suggest that sympathetic stimulation during exercise plays a role in physical conditioning.     

Effects of heart rate reduction with ivabradine on exercise-induced myocardial ischemia and stunning.

We investigated the effects of the selective bradycardic agent ivabradine, an I(f) channel inhibitor, on exercise-induced ischemia and resulting myocardial stunning. Seven dogs were chronically instrumented to measure left ventricular (LV) wall thickening (Wth), aortic pressure and coronary blood flow (CBFv) (Doppler). Circumflex coronary artery stenosis was set up to suppress the increase in CBFv during a 10 min treadmill exercise. During exercise under saline, LVWth in the ischemic zone was depressed (-70 +/- 4%) and a prolonged myocardial stunning was subsequently observed. Infusion of ivabradine started before exercise significantly reduced heart rate (HR) at rest (-22 +/- 7%), during exercise (-33 +/- 4%) and throughout the recovery period (-21 +/- 2%). By reducing HR during exercise, ivabradine simultaneously improved LVWth compared with saline (14 +/- 1% versus 7 +/- 1%, respectively) and subendocardial perfusion (microspheres). This anti-ischemic effect was subsequently responsible for a strong decrease in the intensity and severity of myocardial stunning. All these beneficial effects were abolished when HR reduction during exercise was suppressed by atrial pacing. Interestingly, when ivabradine infusion was started after exercise, LVWth was still significantly enhanced and myocardial stunning strongly attenuated. This direct effect of ivabradine on the stunned myocardium disappeared when HR reduction was suppressed by atrial pacing at rest. In conclusion, this study demonstrates that ivabradine exerts an anti-ischemic effect that is responsible for subsequent protection against myocardial stunning. Furthermore, administration of ivabradine after the ischemic insult still improves LVWth of the stunned myocardium.     

Influence of Body Position on the Anginal Threshold during Leg Exercise

Abstract. The circulatory adaptation to leg exercise in the supine and sitting positions with stepwise increased work loads was studied in twelve patients with signs of coronary heart disease. In four patients right heart catheterization was performed. Anginal pain appeared during exercise in both body positions in all patients, but at a lower work load and lower pulmonary oxygen uptake during supine exercise. Heart rate and systolic blood pressure were lower and the systolic ejection period was longer at the occurrence of angina during supine exercise. The calculated pressure-time per minute was significantly lower during exercise in the supine position. Catheterization data suggested a greater rise in left ventricular filling pressure with supine exercise. It is concluded that the differences in work tolerance for the two positions are partly due to a lower mechanical efficiency and may partly be secondary to the augmented venous return and increased left ventricular filling pressure observed during supine exercise. The augmented filling pressure will tend both to increase heart volume–and thereby augment myocardial oxygen requirements–and to compromise coronary perfusion and thus reduce myocardial oxygen supply during supine exercise.     

Influence of body position on the anginal threshold during leg exercise

Abstract. The circulatory adaptation to leg exercise in the supine and sitting positions with stepwise increased work loads was studied in twelve patients with signs of coronary heart disease. In four patients right heart catheterization was performed. Anginal pain appeared during exercise in both body positions in all patients, but at a lower work load and lower pulmonary oxygen uptake during supine exercise. Heart rate and systolic blood pressure were lower and the systolic ejection period was longer at the occurrence of angina during supine exercise. The calculated pressure-time per minute was significantly lower during exercise in the supine position. Catheterization data suggested a greater rise in left ventricular filling pressure with supine exercise. It is concluded that the differences in work tolerance for the two positions are partly due to a lower mechanical efficiency and may partly be secondary to the augmented venous return and increased left ventricular filling pressure observed during supine exercise. The augmented filling pressure will tend both to increase heart volume—and thereby augment myocardial oxygen requirements—and to compromise coronary perfusion and thus reduce myocardial oxygen supply during supine exercise.     

Soluble L-selectin and neutrophil derived oxidative stress after pacing induced myocardial ischemia in chronic stable coronary artery disease

We studied the effect of atrial pacing induced myocardial ischemia on levels of soluble L-selectin (sL-selectin) and generation of neutrophil derived reactive oxygen species (ROS) in 10 patients with coronary artery disease (CAD) and stable angina and in six individuals without CAD. Myocardial ischemia was measured metabolically by lactate sampling from the coronary sinus (CS) and arterial blood at each pacing step. Before each pacing step, at peak pacing and shortly after cessation, plasma concentrations of sL-selectin and generation of ROS using the chemiluminescence method were measured in CS and femoral artery blood. Baseline sL-selectin levels in CS samples were significantly lower in the CAD compared to the control group (547 +/- 80 vs 836 +/- 82 ng/mL, P = 0.03). At peak pacing, nine of ten patients with CAD developed myocardial ischemia (lactate extraction ratio at rest 28% +/- 7%, at peak pacing -16% +/- 6%). In these patients, luminol-enhanced chemiluminescence (CL, 0.88 +/- 0.45 vs 1.9 +/- 0.9 cpm x 10(5), P = 0.09) and levels of sL-selectin (547 +/- 80 vs 764 +/- 86 ng/mL, P = 0.03) from naive neutrophils increased significantly in CS blood suggesting a potent in vivo activation of neutrophils. In control patients, incremental pacing caused neither myocardial ischemia nor a significant change of chemiluminescence or of sL-selectin levels. In conclusion, myocardial ischemia induced by pacing tachycardia is able to activate neutrophils in patients with chronic stable coronary artery disease leading to increased generation of ROS and shedding of L-selectin into the coronary circulation.     

Myocardial insulin resistance in patients with syndrome X.

Insulin resistance is common in patients with angina pectoris, a positive exercise electrocardiogram, and normal coronary angiograms (syndrome X). It is still not known whether insulin resistance affects the cardiac muscle itself and, if so, whether insulin resistance involves myocardial hemodynamics and energy metabolism. We investigated hemodynamics as well as metabolite exchanges across the heart and the forearm in eight patients with syndrome X and eight control subjects during a baseline period after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Myocardial hemodynamics and metabolism were studied at rest, during pace stress, and in the recovery period after pacing. Neither coronary sinus blood flow nor forearm blood flow differed between the groups before and during the clamp. Whole body insulin-stimulated glucose uptake was decreased in the patients (15.6+/-2.1 vs. 23.1+/-2.0 micromol x kg-1 x min-1). Insulin-stimulated glucose uptake in the forearm and the cardiac muscle was equally reduced in the patients (46+/-5 and 48+/-5%). Myocardial glucose uptake correlated with total arterial delivery in the control subjects (r = 0.63, P < 0.01), but not in patients (r = 0.22, P = 0.13). Carbohydrate and lipid oxidation was similar in the two groups at rest, and changes during the clamp were not different in control subjects and patients either at rest, during pacing, or in the recovery period. Patients with syndrome X exhibit myocardial insulin resistance, but cardiac energy metabolism remains unaffected. In patients with syndrome X, insulin-stimulated glucose uptake is independent from myocardial blood flow.     

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.     

Effect of nicotine on coronary blood-flow in man

Summary. The effect of 4 mg nicotine administered in a chewing gum on coronary haemodynamics and oxygen transport, was studied by coronary sinus catheterization in eight healthy non-smoking men. Measurements were made of coronary sinus blood-flow (CSF) by thermodilution and arterial-coronary sinus (a-cs) O₂-difference together with heart rate and intra-arterial pressure both at rest, and during, atrial pacing with and without nicotine. Nicotine increased myocardial oxygen consumption (MVO₂) more than expected from the increase in the rate-pressure product. The increased MVO₂ was covered only partly by increased coronary blood-flow; especially during and after pacing an increased a-cs O₂-difference contributed significantly. This differed from the response when MVO₂ was increased by atrial pacing alone, in which case the whole increase in MVO₂ was covered by increased flow. The results suggest that nicotine affects coronary vascular resistance and blood-flow indirectly through a vasodilatory effect, by mechanisms related to the increased cardiac work, and directly through a vasoconstrictory effect. The suggested vasoconstrictor component is moderate in the non-ischaemic human heart.     

Rate Adaptive Atrial Pacing in the Bradycardia Tachycardia Syndrome

In 42 patients (26 men, 16 women; mean age 69 ± 10 years), who were paced and medicated with antiarrhythmic drugs for the bradycardia tachycardia syndrome, chronotropic response and AV conduction with rapid atrial pacing during exercise were studied. Patients were included if they had no second- or third-degree AV block, no complete bundle branch or bifascicular block, and a PQ interval ≤ 240 ms during sinus rhythm at rest. The interval between the atrial spike and the following Q wave (SQ) was measured in the supine position at rest with an AAI pacing rate of 5 beats/min above the sinus rate (SQ-R+5), and at the end of exercise with 110 beats/min (SQ-E110). Bicycle ergometry was performed using the Chronotropic Assessment Exercise Protocol with the pacemakers being programmed to AAI with a fixed rate of 60 beats/min. Chronotropic incompetence was defined as peak exercise heart rate: (1) < 100 beats/min; (2) < 75% of the maximum predicted heart rate; or (3) the heart rate at half the maximum workload < 60 + 2 beats/min per mL O₂/kg per minute (calculated O₂ consumption). During exercise, one patient developed atrial fibrillation. Chronotropic incompetence was present in 71 % (29/41) of the patients according to definition 2, and in 76% (31/41) according to definition 1 or 3. Ten out of 41 patients (24%) exhibited a second-degree AV block with atrial pacing at 110 beats/min at the end of exercise. Only 9 out of the remaining 31 patients (29%) showed a physiological adaptation of the SQ-E110, and 21 patients (68%) exhibited a paradoxical increase of the SQ interval with rapid atrial pacing at the end of exercise as compared to the SQ-R+5. These observations indicate that the pacing system to be used in most patients paced and medicated for the bradycardia tachycardia syndrome should be dual chamber, and the option of rate adaptation should be considered.     

A clinical course of coronary heart disease after pacemaker implantation and optimization of the pacing regime

AIM: To study effects of pacemaker implantation on the course of coronary heart disease (CHD) with stable angina pectoris and choice of optimal regimen of pacing. MATERIAL AND METHODS: A total of 154 CHD patients with a pacemaker were examined. All the patients had angina of effort of functional class II-IV. RESULTS: The symptoms of the disease improved in 72 (46.8%) patients (group 1): the number of anginal attacks decreased, exercise tolerance increased, the dose of antianginal medicines went down. Pain attacks became more frequent, response to nitroglycerin changed in 30 (19.5%) patients of group 2. This was explained by 1.5-2-fold enhancement of heart rate by pacemaker raising myocardial oxygen consumption and psychocardial syndrome. In 52 (33.8%) patients of group 3 anginal attacks characteristics did not change. CONCLUSION: To optimize coronary reserve, frequency of electroimpulses must be reprogrammed to adjust to a functional class of angina and chronic cardiac failure as well as pacing regime. In particular, low coronary reserve demands optimal frequency of 55-65 imp/min while congenital cardiac failure--75-85 imp/min.     

Comparison of atrial pacing and the cold pressor test in patients with angina pectoris

A haemodynamic and myocardial metabolic study was performed to compare effects of maximal atrial pacing and the cold pressor test (CPT) in patients with angina pectoris. Twelve patients (group I) had angiographically severe coronary artery disease, while 16 patients (group II) had normal coronary angiograms. At maximal pacing, angina developed in all patients in group I, and myocardial lactate production was found in eight of 12 patients. In group II, 12 out of 16 patients experienced chest pain, but only two patients had myocardial lactate production. Neither angina nor myocardial lactate production was present in any patient in either group during CPT. Coronary sinus flow increased and coronary vascular resistance decreased significantly in both groups at maximal pacing (P less than 0.001). At CPT, coronary flow decreased (P less than 0.05) and coronary resistance increased (P less than 0.001) in group I, while individual response was more variable in group II. In conclusion, maximal pacing was a more effective method of provocation of angina pectoris than CPT. The reactions of coronary sinus flow and coronary vascular resistance were different in group I than in group II. However, because of the variability of response in patients with normal coronary arteries, CPT cannot be used to distinguish patients with coronary artery disease from patients with no such disease.     

Effect of Ventricular Pacing on Coronary Blood Flow in Patients with Normal Coronary Arteries

Although ventricular pacing is thought to produce impairment of left ventricular function by altering the sequence of ventricular activation and AV dyssynchrony, little is known about the effect of ventricular pacing on coronary blood flow. We measured coronary blood flow and coronary flow reserve in the left anterior descending coronary artery during sinus rhythm, and during both atrial and ventricular pacing at a rate of 100 ppm in 14 patients with normal coronary arteries. The double product increased significantly during both types of pacing. Coronary arterial diameter during ventricular pacing significantly increased compared to that during both sinus rhythm and atrial pacing. Coronary flow velocity during ventricular pacing was significantly lower compared to that during both sinus rhythm and atrial pacing. Coronary blood flow increased significantly during atriai pacing (30.7%± 12.1%; P < 0.001), but not significantly during ventricular pacing (23.6%± 47.0%; P = ns). While coronary flow re-serve during both atrial (3.9 ± 1.3) and ventricular pacing (3.8 ± 0.9) was lower compared to its value during sinus rhythm (4,5 ± 1.5), the difference was not significant. There was a significant positive correlation between the coronary flow reserve during sinus rhythm and the increase of coronary blood flow during ventricular pacing (R²= 0.78; P < 0.001). We concluded that an increase in coronary blood flow during ventricular pacing is not a common finding regardless of the increase in metabolic demand. The increase of coronary blood flow during ventricular pacing was less in patients with a reduced coronary flow reserve. These findings suggest that preservation of AV synchrony and the presence of a normal sequence of ventricular activation may play an important role in preserving coranary blaod flow in this subset of patients.     

Release of Adenosine from Human Hearts during Angina Induced by Rapid Atrial Pacing

This study was designed to determine whether human hearts release adenosine, a possible regulator of coronary flow, during temporary myocardial ischemia and, if so, to examine the mechanisms involved. Release of adenosine from canine hearts had been reported during reactive hyperemia following brief coronary occlusion, and we initially confirmed this observation in six dogs hearts. Angina was then produced in 15 patients with anginal syndrome and severe coronary atherosclerosis by rapid atrial pacing during diagnostic studies. In 13 of these patients, adenosine appeared in coronary sinus blood, at a mean level of 40 nmol/100 ml blood (SE = +/-9). In 11 of these 13, adenosine was not detectable in control or recovery samples; when measured, there was concomitant production of lactate and minimal leakage of K(+), but no significant release of creatine phosphokinase, lactic acid dehydrogenase, creatine, or Na(+).THERE WAS NO DETECTABLE RELEASE OF ADENOSINE BY HEARTS DURING PACING OR EXERCISE IN THREE CONTROL GROUPS OF PATIENTS: nine with anginal syndrome and severe coronary atherosclerosis who did not develop angina or produce lactate during rapid pacing, five with normal coronaries and no myocardial disease, and three with normal coronaries but with left ventricular failure.The results indicate that human hearts release significant amounts of adenosine during severe regional myocardial ischemia and anaerobic metabolism. Adenosine release might provide a useful supplementary index of the early effects of ischemia on myocardial metabolism, and might influence regional coronary flow during or after angina pectoris.