Tachycardia Stress Research Articles

Syncope associated with supraventricular tachycardia: Diagnostic role of implantable loop recorders.

Syncope represents a relatively uncommon symptom of supraventricular tachycardia (SVT). It is likely that an impaired autonomic vasomotor response to the hemodynamic stress of tachycardia is the determinant of hemodynamic changes leading to cerebral hypoperfusion and syncope. In this regard, tilt‐table test may detect abnormalities in the autonomic nervous function and predict the occurrence of syncope during SVT. Electrophysiology studies may reproduce the SVT, distinguish it from other life‐threatening ventricular tachyarrhythmias, and exclude other causes of syncope. Not infrequently mixed syncope mechanisms are revealed during the above diagnostic workup raising doubts about the operating mechanism in the clinical setting. In such cases of uncertainty, an implantable loop recorder, providing long‐term cardiac monitoring, may play a pivotal role in the establishment of the diagnosis, confirming the association of an arrhythmic event with the symptom. Herein, we present four such cases with recurrent unexplained syncope finally attributed to paroxysmal SVT guiding them to a potentially radical treatment through radiofrequency catheter ablation.

Metabolic Response to Stress by the Immature Right Ventricle Exposed to Chronic Pressure Overload.

BackgroundThe right ventricle exposed to chronic pressure overload exhibits hypertrophy and decompensates when exposed to stress. We hypothesize that impaired ability to increase myocardial oxidative flux through pyruvate dehydrogenase leads to hypertrophied right ventricular (RV) dysfunction when exposed to hemodynamic stress, and pyruvate dehydrogenase stimulation can improve RV function.Methods and ResultsInfant male Yorkshire piglets (13.5±0.6 kg weight, n=19) were used to assess substrate fractional contribution to the citric acid cycle after sustained pulmonary artery banding (PAB). Carbon 13–labeled glucose, lactate, and leucine, oxidative substrate tracers for the citric acid cycle, were infused into the right coronary artery on 7 to 10 days after PAB. RV systolic pressure, RV free wall thickness, and individual cardiomyocyte cell size after PAB were significantly elevated compared with the sham group. Both fractional glucose and lactate oxidations in the PAB group were >2‐fold higher than in the sham group. Pigs with overdrive atrial pacing (≈80% increase in heart rate) stress after PAB showed only a 22% increase in rate‐pressure product from baseline before atrial pacing and limited carbohydrate oxidation rate in the right ventricle. Intracoronary infusion of dichloroacetate, a pyruvate dehydrogenase agonist, produced higher rate‐pressure product (59% increase) in response to increased workload by atrial pacing in association with a marked increase in lactate oxidation.ConclusionsThe immature hypertrophied right ventricle shows limited ability to increase carbohydrate oxidation in response to tachycardia stress leading to energy supply/utilization imbalance and decreased systolic function. Enhanced pyruvate dehydrogenase activation by dichloroacetate increases energy supply and preserves hypertrophied RV contractile function during hemodynamic stress.

Orthostatic intolerance in chronic fatigue syndrome

BackgroundOrthostatic intolerance (OI) is a significant problem for those with chronic fatigue syndrome (CFS). We aimed to characterize orthostatic intolerance in CFS and to study the effects of exercise on OI.MethodsCFS (n = 39) and control (n = 25) subjects had recumbent and standing symptoms assessed using the 20-point, anchored, ordinal Gracely Box Scale before and after submaximal exercise. The change in heart rate (ΔHR ≥ 30 bpm) identified Postural Orthostatic Tachycardia Syndrome (POTS) before and after exercise, and the transient, exercise-induced postural tachycardia Stress Test Activated Reversible Tachycardia (START) phenotype only after exercise.ResultsDizziness and lightheadedness were found in 41% of recumbent CFS subjects and in 72% of standing CFS subjects. Orthostatic tachycardia did not account for OI symptoms in CFS. ROC analysis with a threshold ≥ 2/20 on the Gracely Box Scale stratified CFS subjects into three groups: No OI (symptoms < 2), Postural OI (only standing symptoms ≥ 2), and Persistent OI (recumbent and standing symptoms ≥ 2).ConclusionsDizziness and Lightheadedness symptoms while recumbent are an underreported finding in CFS and should be measured when doing a clinical evaluation to diagnose orthostatic intolerance. POTS was found in 6 and START was found in 10 CFS subjects. Persistent OI had symptoms while recumbent and standing, highest symptom severity, and lability in symptoms after exercise.Trial registration The trial was registered at the following: https://clinicaltrials.gov/ct2/show/NCT03567811

Ischemic Heart Disease during Acute Exacerbations of COPD.

Patients with chronic obstructive pulmonary disease (COPD) have a higher risk of acute cardiovascular events, and around 30% die from cardiovascular diseases. Recent data suggest an increased risk of myocardial infarction in the following days of a severe exacerbation of COPD. Disruption in the balance during the exacerbation with tachycardia, increased inflammation and systemic oxidative stress as well as some other factors may confer an increased risk of subsequent cardiovascular events. A number of investigations may be useful to an early diagnosis, including electrocardiography, imaging techniques and blood test for biomarkers. Some drugs that have changed prognosis in the cardiovascular setting such as cardioselective beta-blockers may be underused in patients with COPD despite its demonstrated benefits. This review focuses on several aspects of exacerbation of COPD and cardiovascular events including epidemiology, possible mechanism, diagnosis and treatment.

Renewed impact of lidocaine on refractory ventricular arrhythmias in the amiodarone era

BackgroundRecent guidelines for treating ventricular fibrillation (VF) and ventricular tachycardia (VT) stress class III antiarrhythmic drugs, but some malignant arrhythmias refractory to these agents still occur in clinical practice. The possibility of a new treatment strategy involving lidocaine and amiodarone combination therapy was evaluated. MethodsFrom September 2008 to September 2013, 62 patients were treated at our hospital with lidocaine. The medical records were retrospectively reviewed. Twenty inappropriate patients were excluded. The remaining 42 patients were analyzed. Patients were divided into two groups according to the effectiveness of lidocaine in terminating refractory ventricular arrhythmias: the effective group. ResultsLVEF was significantly higher in the lidocaine effective (E) group compared to the ineffective (I) group (44±16% vs. 32±10%, p=0.027). There were more patients already on amiodarone at the start of lidocaine therapy in the E group compared to the I group (11/26 vs. 1/16, p=0.012). Furthermore, patients receiving lidocaine without amiodarone were re-analyzed to estimate the actual effect of lidocaine. Of the 30 patients not receiving amiodarone, 15 were in the effective without amiodarone (E w/o A) group and 15 were in the ineffective without amiodarone (I w/o A) group. LVEF was significantly higher in the E w/o A group than in the I w/o A group (51±16% vs. 32±9%, p=0.001). ConclusionsThis retrospective study suggests that combination therapy with lidocaine and amiodarone can terminate most refractory ventricular arrhythmias. Even in patients with a sufficient LVEF not receiving amiodarone, it is possible that lidocaine can contribute to a favorable outcome.

Short-term effects of electrically induced tachycardia on antioxidant defenses in the normal and hypertrophied rat left ventricle

Increased oxidative stress resulting from enhanced production of reactive oxygen species and/or inadequate mechanisms of antioxidant defenses has been recognized as an important factor contributing to the initiation and progression of cardiac dysfunction under a wide variety of pathophysiological conditions. The main objective of this study was to examine the effect of electrically induced tachycardia on oxidative stress and the capacity of antioxidant defenses in the normal and hypertrophied left ventricle (LV) in the rat. Left ventricular hypertrophy (LVH) was produced by banding the descending abdominal aorta. The activities of antioxidant enzymes, concentrations of non-enzymatic antioxidants, and biomarkers of oxidative stress were measured in the LV of aortic-banded animals (LVH), untreated or banded rats subjected to short-term (45 min) atrial pacing [(CTR + S) and (LVH + S), respectively], and untreated (CTR) or sham-operated (SHAM) controls. The results indicate that the increase in heart rate in vivo as a result of atrial pacing to a maximum level, independent of sympathetic nerve activity, leads to a substantial increase in oxidative stress and a marked decline in the activities of antioxidant enzymes in both the normal and hypertrophied left ventricle of the rat. The accompanying increase in tissue content of alpha- and gamma-tocopherols seem to contribute to attenuation of the oxidant stress-related loss of thiol stores in the LV. Stable left ventricular hypertrophy induced by aortic banding for six weeks has a minor impact on the capacity of the endogenous antioxidant defense system in the LV, but significantly and negatively affects the ability of the heart LV to tolerate the stress of tachycardia.

Tedisamil (KC 8857) is a new specific bradycardic drug: Does it also influence myocardial contractility? Analysis by the conductance (volume) technique in coronary artery disease

To determine whether inotropism influences the bradycardic action of tedisamil, hemodynamic assessment was performed in 13 patients with ischemic coronary artery disease including analysis of end-systolic pressure-volume relationships after an infusion of tedisamil, 0.3 mg/kg, at rest, and during paced tachycardia stress. Slope E max fell by 14% at rest (13 patients) and by 10% during tachycardia ( 6 13 patients), whereas loops of end-systolic pressure-volume relationships moved rightward; all parameter changes indicated a lack of significant inotropism loss with tedisamil ( p > 0.05). Although the mean heart rate decreased from 77.5 to 64.7 beats/min and QT c duration increased by 14% ( p < 0.05), filling pressure and dp/dt min remained unchanged and vascular resistance increased by 30%. Parameters of left ventricular pump function (ejection fraction, stroke volume, left ventricular efficiency) decreased slightly (between 3% and 13%), whereas left ventricular volumes increased (end-diastolic volume by 6%, end-systolic volume by 23%). The respective parameter changes during tachycardia were comparable in tendency, and angina could no longer be induced during postdrug pacing stress. We concluded that the bradycardic effects of tedisamil are selectively generated without impairing either ventricular pump function or contractility in a clinically relevant fashion, whereas the postdrug anginal threshold appears elevated. Thus tedisamil can be used safely in ischemic coronary artery disease.

Effects of diltiazem during tachycardia-induced angina pectoris

To investigate the mechanism of relief of angina pectoris by diltiazem administration, 14 patients with effort angina were studied using a protocol to control heart rate. Coronary, systemic and left ventricular (LV) hemodynamic function was assessed at rest and during tachycardia stress (atrial pacing)-induced angina before and during diltiazem infusion. Angina occurred in all patients during tachycardia stress before diltiazem administration. During tachycardia stress at the heart rate that produced angina after diltiazem infusion, pressure-rate product, coronary sinus flow and resistance and ST-segment depression were all similar to findings before diltiazem. Although at the onset of angina, systolic pressure was usually slightly lower after diltiazem infusion (138 ± 11 vs 128 ± 11 mm Hg, p <0.05), the pacing rate at onset of angina was higher in only 3 patients and the pressure-rate product was higher in only 1 patient. After diftlazem, left ventricular end-diastolic pressure increased less frequently after interruption of pacing. The results suggest that diltiazem favorably afters the relation between myocardial oxygen demand and supply at rest, but during tachycardla, anginal threshold and coronary reserve do not change. Diftlazem's potent antianginal action, shown in previous investigations using exercise-induced angina, is not prominent when heart rate is controlled. The major benefit of diltiazem in patients with stress-induced angina is related to reduction of myocardial oxygen demand rather than improved myocardial oxygen delivery.

Adaptation to the stress of tachycardia in patients with coronary artery disease: insight into the mechanism of the warm-up phenomenon.

Adaptation to exercise or the "warm up phenomenon" has been observed in some patients with angina pectoris. To investigate adaptation, eleven patients with exertional angina pectoris and angiographic evidence of coronary artery disease underwent two identical bouts of sequential tachycardia stress separated by a brief recovery period. Manifestations of ischemia were less during the second stress, as evidenced by a reduction in the severity of angina pectoris, less ST segment depression, and improved lactate extraction. Peak coronary blood flow during the second stress (81 +/- 20 ml/min) was not significantly different from that during the first (95 +/- 32 ml/min). Regional myocardial oxygen consumption, however, was significantly (p = .03) lower during the second stress (8.8 +/- 2.4 ml O2/min) when compared with the first (11.4 +/- 3.0 ml O2/min). Thus, patients with coronary artery disease can develop anginal tolerance to the stress of tachycardia similar to that observed after repeated bouts of exercise. A relative reduction in myocardial oxygen consumption, rather than an increase in coronary blood flow, appears to account for this phenomenon.

Effects of timolol on platelets in coronary sinus blood and on myocardial ischemia during pacing-induced angina.

The effect of timolol on blood platelet function was studied in coronary sinus and caval vein blood at rest and during pacing-induced angina in 20 patients with coronary heart disease. During pacing-induced angina, lactate measurements confirmed that coronary sinus blood was sampled from ischemic regions in 13 men. The ischemia did not influence platelet function. In blood from non-ischemic myocardium, platelet activation was found during pacing: the ADP-induced aggregation, platelet retention and plasma beta-thromboglobulin levels increased moderately but significantly. Timolol administration prevented this platelet activation, possibly by inhibiting catecholamine release from the myocardium, and reduced the ischemic response during pacing as judged from lactate measurements and ST depressions. It is concluded that timolol reduced platelet activation induced in non-ischemic regions of the heart during tachycardia stress as well as myocardial ischemia.

Coronary circulatory dynamics before and after successful coronary angioplasty

The hypothesis that successful percutaneous transluminal coronary angioplasty restores normal coronary circulatory dynamics was tested. Regional coronary blood flow, myocardial oxygen consumption and lactate extraction were measured at rest and during sustained pacing tachycardia. Before angioplasty, tachycardia stress was associated with an attenuated blood flow and oxygen consumption response and the induction of anaerobic metabolism. After successful angioplasty, blood flow and myocardial oxygen consumption increased during tachycardia stress and aerobic metabolism was sustained. The influence of basal alpha-adrenergic tone in modifying the time course of blood flow response to abrupt pacing was also assessed. Patients with normal coronary arteries demonstrated delayed increase in blood flow after alpha-adrenergic blockade. Alpha-adrenergic blockade did not affect the time course of blood flow response in patients with coronary artery disease, suggesting that alpha-adrenergic tone was chronically withdrawn. In patients undergoing coronary angioplasty, flow response before angioplasty was delayed, consistent with withdrawal of basal alpha-adrenergic tone. After coronary angioplasty, a brisk flow response was observed, indicating that basal alpha-adrenergic tone had been restored. Thus, successful coronary angioplasty restores the normal responsiveness of the coronary circulation.

Influence of tachycardia stress and nitroglycerin on transcardiac thromboxane levels in coronary disease

Influence of tachycardia stress and nitroglycerin on transcardiac thromboxane levels in coronary disease

Effects of new calcium channel blocker of niludipine on the coronary hemodynamics, diastolic properties, and metabolic responses to tachycardia stress in patients with coronary disease.

A new calcium channel blocker, niludipine, was administered intravenously to nine patients with coronary artery disease in order to investigate its effects on left ventricular systolic and diastolic function, coronary sinus blood flow, and myocardial lactate metabolism. Coronary sinus pacing was performed in all patients and produced angina in six patients. Niludipine increased the resting heart rate from 75+/-3 beats/min (mean+/-SEM) to 82+/-3 (NS) and decreased the left ventricular systolic pressure from 155+/-4.7 mm Hg to 134+/-2.8 (p less than 0.05). Coronary sinus blood flow increased by 9%(NS). During pacing after niludipine, clinical improvement occurred in the six patients who had initially experienced angina. The extent of ischemic ST segment depression was decreased (-1.56+/-0.27 mm to -0.78+/-0.38, p less than 0.02) and myocardial lactate metabolism was improved. When pacing was terminated, niludipine suppressed the elevation of left ventricular end-diastolic pressure compared to pretreatment values (16.2+/-2.5 mm Hg vs 8.5+/-0.9, p less than 0.05) and decreased the left ventricular time constant T(26.4+/-3.6 msec to 20.2+/-2.4 p less than 0.05). The results suggest that niludipine appears to be beneficial in reducing systolic and diastolic work of the left ventricle during pacing induced angina without a significant change in total coronary sinus blood flow. Niludipine appears to have less of a hypotensive and reflex tachycardic effect than nifedipine.

Significance of platelet function and thromboxane B2 levels across the human myocardial vascular bed.

ABSTRACTThere is an intense interest in the role of platelets in the pathogenesis of myocardial ischemia. To determine platelet function in coronary circulation and the influence of various platelet‐active drugs, we have studied large number of patients with coronary disease (CD) defined as &gt;50 % luminal narrowing and subjects with normal coronary arteries (NCA). Blood samples were collected from aorta (Ao) and coronary sinus (CS) at rest, during and following atrial‐pacing induced tachycardia characterized by ECG changes and symptoms. Platelet aggregation (PAg) using epinephrine (E) and adenosine diphosphate (ADP) as stimulating agents and platelet counts were performed. In CD patients CS blood had lower (Pd&lt;0.01) PAg (E‐59 ± 8, ADP‐49 ± 7 %) than Ao blood (E‐74 ± 6, ADP‐68 ± 7 %). Platelet counts in CS blood (173,000 ± 16,000/mm3) were lower (P&lt;0.01) than in Ao blood (233,000 + 30,000/mm3). In NCA patients, the CS and Ao platelet counts and PAg were not significantly different. During tachycardia stress PAg and counts were unaltered in NCA patients. In contrast in CD patients PAg increased significantly (P&lt;0.05) in CS but not in Ao blood during stress and returned to baseline following tachycardia implying platelet activation during stress‐induced myocardial ischemia. Oral aspirin 650 mg abolished the differences in Ao and CS blood PAg (CS‐E 51 ± 8, ADP 54 ± 7%; Ao‐E 45 ± 8, ADP 55 ± 8 %), and in counts (CS‐221,000 ± 8,000/mm3; Ao‐230,000 ± 71,000/mm3) in CD patients. Aspirin also significantly decreased tachycardia‐related increase in PAg in CS blood. Administration of intravenous dipyridamole 25 mg in 8 other CD patients, resulted in increase in platelet counts in CS from 255,000 ± 29,000 to 286 ± 34,000/mm3 and in PAg from 30 ± 8 to 52 ± 9 %, while Ao blood counts and PAg were unchanged, so that the differences in Ao and CS platelet counts and aggregation were abolished. In other studies, we compared CD patients treated with and without propranolol. Propranolol‐treated patients had lower PAg in Ao as well as CS blood compared to non‐treated patients, but the gradients in PAg and counts between Ao and CS blood was still present. However, tachycardia‐related increase in CS PAg was markedly less in CS blood in propranolol‐treated patients compared to non‐treated patients.These data show that 1) gradient in platelet counts from Ao to CS exists related probably to platelet aggregate formation in atherosclerotic vessels, 2) activation of platelets leads to low PAg activity in CS blood, 3) tachycardia stress is associated with platelet activation at the level of myocardial vascular bed, 4) aspirin and dipyridamole modify these gradients, 5) aspirin blunts tachycardia‐related increase in CS PAg, 6) propranolol has potent PAg inhibitory effects and modifies platelet response to tachycardia stress.

Responses of Coronary Collateral Flow and Dependent Myocardial Mechanical Function to the Calcium Antagonist, Diltiazem

We sought to determine whether the calcium antagonist, diltiazem, increased regional myocardial collateral blood flow in a dog model in which the physiologic conditions thought to be associated with angina pectoris had been induced, and to determine if such changes would be reflected in alterations in function of the collateral-dependent myocardium. Regional myocardial function and blood flow were measured with instruments in dogs for weeks as the left circumflex artery was progressively stenosed to occlusion by an implanted ameroid constrictor. The extent of collateral development was determined in terms of the reduction in regional function induced by brief, total test occlusions. When collaterals had developed adequate for the metabolic requirements at rest, pacing tachycardia stress test produced ischemia-related hypofunction. Under these conditions, diltiazem, 20 mirogram/min/kg, increased blood flow via collateral channels from approximately 140 to 190 ml/min/100 g tissue (epicardium) and from 80 to 140 ml/min/100 g tissue (endocardium) in the colateral-dependent area without significant modification in hypofunction. Similar results were obtained in dogs with greater collateral flow reserve later in the collateral development process when the ameroid constrictor had completely occluded the vessel and stress testing did not produce hypofunction. Thus, diltiazem increased collateral flow to collateral-dependent myocardium under conditions simulating unstable angina pectoris.

Responses of Coronary Collateral Flow and Dependent Myocardial Mechanical Function to the Calcium Antagonist, Diltiazem

We sought to determine whether the calcium antagonist, diltiazem, increased regional myocardial collateral blood flow in a dog model in which the physiologic conditions thought to be associated with angina pectoris had been induced, and to determine if such changes would be reflected in alterations in function of the collateral-dependent myocardium. Regional myocardial function and blood flow were measured with instruments in dogs for weeks as the left circumflex artery was progressively stenosed to occlusion by an implanted ameroid constrictor. The extent of collateral development was determined in terms of the reduction in regional function induced by brief, total test occlusions. When collaterals had developed adequate for the metabolic requirements at rest, pacing tachycardia stress test produced ischemia-related hypofunction. Under these conditions, diltiazem, 20 mirogram/min/kg, increased blood flow via collateral channels from approximately 140 to 190 ml/min/100 g tissue (epicardium) and from 80 to 140 ml/min/100 g tissue (endocardium) in the colateral-dependent area without significant modification in hypofunction. Similar results were obtained in dogs with greater collateral flow reserve later in the collateral development process when the ameroid constrictor had completely occluded the vessel and stress testing did not produce hypofunction. Thus, diltiazem increased collateral flow to collateral-dependent myocardium under conditions simulating unstable angina pectoris.

Platelet function studies in coronary artery disease. VII. Effect of aspirin and tachycardia stress on aortic and coronary venous blood

The effects of orally administered aspirin (650 mg) on platelet aggregation patterns and counts in aortic and coronary venous blood were evaluated in patients with coronary artery disease. Studies were conducted at rest and during the stress of tachycardia. Before administration of aspirin, platelet aggregation and counts were lower (p < 0.01) in coronary venous blood than in aortic blood. The stress of tachycardia resulted in increased (p < 0.01) platelet aggregation only in coronary venous blood. After administration of aspirin, differences in platelet aggregation and counts between coronary venous and aortic blood at rest were eliminated, and the tachycardia-associated increase in coronary venous blood platelet aggregation was significantly reduced. These observations suggest that aspirin influences and abolishes the changes that occur in blood platelet function as platelets traverse the atherosclerotic myocardial vascular bed. The absence of an increase in platelet aggregation during the stress of tachycardia after administration of aspirin may have important pathophysiologic and therapeutic implications.

Reduction of exercise-induced regional myocardial dysfunction by propranolol. Studies in a canine model of chronic coronary artery stenosis.

Reduction of exercise-induced regional myocardial dysfunction by propranolol. Studies in a canine model of chronic coronary artery stenosis.

Platelet aggregation in aortic and coronary venous blood in patients with and without coronary disease. 3. Role of tachycardia stress and propranolol.

We studied 16 patients with coronary artery disease (CAD) to evaluate platelet aggregation in blood samples withdrawn simultaneously from the aorta and coronary sinus. At rest, mean platelet aggregation in coronary venous blood was significantly lower than that in aortic blood. Platelet counts in coronary venous blood were also lower than in the aortic blood in each of the six CAD patients in whom counts were done. Platelet aggregation was lower in seven patients who were taking propranolol than in the remaining nine who were not taking propranolol. During tachycardia stress, platelet aggregation increased in all patients, but the magnitude of increase was greater in patients not taking propranolol. In four other patients without CAD, platelet aggregation and counts were also studied in the same fashion and were similar in both the aortic and coronary venous blood. These data suggest that in certain CAD patients, platelet consumption or destruction within atherosclerotic vasculature may occur. Propranolol may reduce platelet aggregation at rest and modify excessive aggregation during tachycardia stress in certain CAD patients.

Coronary and myocardial metabolic effects of combined glyceryl trinitrate and propranolol administration. Observations in patients with and without coronary disease.

Coronary haemodynamic and metabolic effects of propranolol and glyceryl trinitrate were studied in 12 patients with coronary artery disease and 5 without coronary heart disease, at rest and during tachycardia stress. Propranolol-associated reductions in indices of myocardial oxygen demand, left ventricle work, tension time, and left ventricle oxygen utilisation (LVVO2) were reversed when heart rate was controlled by atrial pacing. Adding glyceryl trinitrate at rest also restored heart rate but decreased the left ventricular work index and tension time index as coronary resistance declined paradoxically. Tachycardia-related increases in tension time index and LVVO2 were unchanged after propranolol, and ischaemia (angina, ST depression, and reduced lactate extraction) was not altered in most of the patients. During tachycardia, the addition of glyceryl trinitrate decreased the tension time index and LVVO2; angina recurred in only 4 patients, and ST depression and lactate extraction improved. Similar haemodynamic changes occurred in the patients with normal coronary arteries. In contrast with propranolol administered alone, propranolol plus glyceryl trinitrate enhances tachycardia tolerance and prevents tachycardia-induced manifestations of ischaemia. This action is attributed to glyceryl trinitrate-associated improvement in the adequacy of myocardial perfusion.