Coronary Sinus Oxygen Content Research Articles

Invited Commentary

Invited Commentary

Effect of Heart tablets on cardiac hemodynamics and myocardial oxygen consumption in anesthetized dogs

To observe the pharmacological effects of Heart tablets on cardiac function and its mechanism, the effects on cardiac hemodynamics and myocardial oxygen consumption in anesthetized dogs were observed. Observe the effect of Heart tablets on coronary blood flow, cardiac output, myocardial oxygen consumption and other indicators in normal anesthetized dogs. The Heart tablets can increase femoral arterial blood pressure, while no effect is found on the heart rate, standard II ECG PR interval, QRS interval, QT interval, T wave and other parameters. The tablets can expand coronary artery and peripheral vessel, increase coronary blood flow, lower coronary resistance and increase cardiac blood supply capacity, improve left ventricular function, ameliorate cardiovascular adaptability, increase dp/dt(max), enhance myocardial activity and have a positive regulatory role in heart. At the meantime raise the cardiac output and stroke volume were raised, so that blood pressure can be increased, while the total peripheral resistance was decreased. The coronary vein sinus oxygen content were significantly increased and myocardial oxygen consumption index and myocardial oxygen utilization were reduced. The tablets can adjust and improve the cardiovascular system.

Comparison of adenosine, isoflurane, and desflurane on myocardial tissue oxygen pressure during coronary artery constriction in dogs

Objective: To compare adenosine-, isoflurane-, or desflurane-induced hypotension with and without left anterior descending (LAD) coronary artery constriction for the effects on myocardial tissue oxygen pressure (PmO 2) in dogs. Design: Prospective, randomized, nonblinded. Setting: University teaching hospital. Participants: Male nonpurpose-bred dogs (n = 18). Interventions: Dogs were anesthetized with 1.5% isoflurane (n = 12) or 8% desflurane (n = 6). A flow probe and balloon occluder were placed on the LAD artery. A probe that measured myocardial oxygen pressure was inserted into the middle myocardium in the LAD region. Myocardial oxygen consumption (MVO 2) was calculated as LAD flow x arterial minus coronary sinus oxygen content. Measures and Main Results: Measures were made during hypotension produced by adenosine infusion, 2.8% isoflurane, or 14% desflurane with and without LAD constriction to decrease blood flow 30%. Without LAD artery constriction, adenosine infusion increased LAD flow 90% and MVO 2 70%, 2.8% isoflurane produced no change in MVO 2, and 14% desflurane decreased MVO 2 25%, but no treatment changed PmO 2. LAD artery constriction decreased PmO 2 50% by itself. Adenosine infusion during LAD constriction decreased tissue oxygen pressure an additional 60%, 2.8% isoflurane produced no change, and 14% desflurane increased PmO 2 100%. Conclusion: There was an inverse relationship between the effect of adenosine, 2.8% isoflurane, and 14% desflurane on MVO 2 and PmO 2 during ischemia. This is consistent with reports that increasing oxygen demand worsens myocardial ischemia.

Sodium nitroprusside–induced, but not desflurane–induced, hypotension decreases myocardial tissue oxygenation in dogs anesthetized with 8% desflurane

Objective: To compare sodium nitroprusside (SNP)–induced hypotension with desflurane-induced hypotension for the effects on myocardial blood flow and tissue oxygenation in dogs. Design: Prospective, randomized, crossover, nonblinded. Setting: University teaching hospital. Participants: Male nonpurpose-bred hounds (n = 8). Interventions: Dogs were anesthetized with 8% desflurane. Catheters were inserted into the femoral artery and coronary sinus. A flow probe was placed in the left anterior descending (LAD) branch of the coronary artery. A sensor that measured myocardial oxygen pressure (PmO2) was inserted into the myocardium of the left ventricle. Myocardial oxygen consumption (MV̇O2) was calculated as LAD flow × arterial − coronary sinus oxygen content. Measurements and Main Results: Measurements were made at baseline blood pressure levels of 99 mmHg (measure 1), during hypotension to 62 to 66 mmHg using intravenous SNP or 14% desflurane (measure 2), and during SNP or 14% desflurane with blood pressure support using phenylephrine (measure 3). Each dog randomly received both hypotensive treatments, separated by 1 hour. Baseline measures were PmO2 = 46 ± 9 mmHg, LAD flow = 43 ± 11 mL/min, and MV̇O2 = 2.47 ± 0.73 mL O2/min. During hypotension induced with SNP, PmO2 decreased 30% (p < 0.05), LAD flow increased 40% (p < 0.05), and MV̇O2 did not change. During hypotension induced with 14% desflurane, PmO2 did not change, and LAD flow and MV̇O2 decreased 25% and 40% (p < 0.05). Blood pressure support with phenylephrine increased LAD flow and MV̇O2 but did not change PmO2 during SNP or 14% desflurane treatment. Conclusion: SNP-induced hypotension produced myocardial vasodilation, but tissue oxygenation was impaired. PmO2 was maintained during desflurane-induced hypotension. Copyright 2002, Elsevier Science (USA). All rights reserved.

Discussion

Discussion

Endogenous plasma endothelin concentrations and coronary circulation in patients with mild dilated cardiomyopathy

OBJECTIVETo determine whether increased plasma concentrations of endothelin-1 (ET-1) and big endothelin (BET) play a role in the regulation of coronary circulation in patients with idiopathic dilated cardiomyopathy (IDCM).SETTINGTertiary referral...

Nitroglycerin-induced hypoxemia does not produce myocardial ischemia

Objective: Nitroglycerin has been the drug of choice for relieving myocardial ischemia for more than a hundred years. Several studies have indicated that a significant reduction in arterial oxygen tension (PaO 2) occurs after the administration of sublingual nitroglycerin to patients with coronary artery disease breathing room air. Because available oxygen in arterial blood is reduced, it would be reasonable to assume that oxygen delivery to the myocardium would also be impaired. The purpose of this study was to investigate whether nitroglycerin-induced arterial desaturation results in compromised oxidative metabolism of myocardium assessed by coronary sinus lactate concentration and oxygen content in patients with coronary artery disease undergoing coronary artery bypass surgery. Participants: Ten randomly selected patients undergoing coronary bypass surgery. Setting: All studies were performed at Siyami Ersek Cardiovascular and Thoracic Surgery Center. Methods: A catheter was inserted into the radial artery to measure blood gases and arterial lactate concentration. After sternotomy, and aortic and venous cannula placement, a coronary sinus catheter was introduced into the coronary sinus to measure oxygen content and lactate concentration. Control coronary sinus and arterial blood samples were obtained before nitroglycerin infusion. Nitroglycerin was then given in a dose of 2 μg/kg/min for a period of 5 minutes. At the end of 5 minutes, second samples were obtained from the coronary sinus and arterial catheters. Main Results: It was found that arterial and coronary sinus oxygen tension decreased significantly. Arterial lactate concentration did not change, coronary sinus lactate concentration decreased. Despite a substantial fall in arterial oxygen tension after administration of nitroglycerin, a significant reduction in coronary sinus lactate concentration occurred. Conclusion: Nitroglycerin-induced hypoxia does not compromise oxidative metabolism of myocardium as can be assessed by a concomitant decrease in coronary sinus lactate concentration.

Coronary sinus oxygen content and lactate extraction during hyperventilation in patients with coronary artery disease

Coronary sinus oxygen content and lactate extraction during hyperventilation in patients with coronary artery disease

The Circulatory Effects of Epinephrine Infusion in the Anesthetized Piglet

There are few published data regarding the circulatory effects of systemic epinephrine infusions in newborn subjects. We therefore instrumented six piglets aged 5 to 10 d while they were under pentobarbitone anesthesia for determination of cardiac output, left anterior descending coronary artery flow, systemic and pulmonary pressures, and mixed venous, arterial and coronary sinus gases. Systemic, coronary, and pulmonary vascular resistances, coronary oxygen consumption, and myocardial oxygen extraction ratio were calculated. Epinephrine was infused at doses from 0.2 to 3.2 micrograms/kg/min doubling at 15-min intervals, and measurements were taken after stability had been obtained. Cardiac output increased at the lowest dose investigated, i.e. 0.2 micrograms/kg/min, and progressively increased as the dose was advanced up to 1.6 micrograms/kg/min, decreasing significantly at 3.2 micrograms/kg/min. Blood pressure increased progressively, being significantly above baseline at 0.8, 1.6, and 3.2 micrograms/kg/min and having increased by approximately 81% at the highest dose investigated. Pulmonary arterial pressures were also increased at 1.6 and 3.2 micrograms/kg/min, but only by 35% at the highest dose of 3.2 micrograms/kg/min. Systemic and pulmonary vascular resistances both decreased at the three lower doses investigated and then began to increase progressively; however, the systemic vascular resistance increased to a significantly greater degree than pulmonary vascular resistance. Coronary oxygen consumption increased progressively as the epinephrine dose was increased; however, coronary blood flow and coronary oxygen delivery increased more than oxygen consumption, leading to a progressive reduction in myocardial oxygen extraction ratio and a progressive increase in coronary sinus oxygen content. Whole-body oxygen consumption was increased, but to a lesser extent than systemic oxygen transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of R-PIA, a selective A1 adenosine agonist, on haemodynamics and ischaemic arrhythmias in pigs

Adenosine has previously been shown to protect against ischaemia induced ventricular arrhythmias. The aim of this study was to determine whether stimulation of A1 adenosine receptors with a selective agonist also protects against arrhythmias, and to attempt to elucidate the underlying mechanisms. Large White/Welsh Landrace cross breed domestic pigs (25-40 kg) subjected to left anterior descending coronary artery occlusion were used. R-PIA [R(-)N6-(2-phenylisopropyl) adenosine; 5 micrograms.kg-1] was given prior to coronary artery occlusion and the effects on haemodynamic variables and early ischaemic arrhythmias in the absence and presence of right atrial pacing were studied. The three experimental groups were: solvent controls, n = 10; R-PIA without pacing, n = 10; R-PIA with atrial pacing, n = 10. Ex vivo assessment of platelet aggregation was also performed to determine any inhibitory effects of R-PIA on platelets. Administration of R-PIA without atrial pacing reduced the total number of ventricular ectopic beats induced by coronary occlusion, from 326(SEM 71) in controls to 121(30) (p < 0.05) and the incidence of ventricular fibrillation from 70% to 20% (p < 0.05). At the dose used, R-PIA reduced heart rate from 102(7) to 74(3) beats.min-1, with a consequent reduction in mean arterial blood pressure from 95(4) to 81(3) mm Hg. Atrial pacing following drug administration, at a rate of 109(5) beats.min-1, restored blood pressure and abolished the antiarrhythmic effects of R-PIA. Drug intervention had no effect on either ex-vivo platelet aggregation or coronary sinus oxygen content, suggesting a lack of activity at A2 adenosine receptors. An A1 adenosine receptor agonist exerts a marked protection against ischaemia induced ventricular arrhythmias and fibrillation in pigs. The reversal of this effect by restoring heart rate suggests that the drug induced bradycardia may be important in the antiarrhythmic action of R-PIA, possibly via an anti-ischaemic effect.

Lack of relation of coronary sinus oxygen content to extent of coronary artery disease or left ventricular dysfunction

A recent study suggests that the prognosis of patients with congestive heart failure is related to the oxygen content of coronary sinus blood: the lower the oxygen content at rest, the worse the outlook. 1 Although it is hypothesized that the oxygen content of coronary sinus blood decreases as coronary artery disease worsens, no previous study has assessed the relation, if any, between the oxygen content of coronary sinus blood at rest and the extent of (1) atherosclerotic coronary artery disease, or (2) left ventricular systolic dysfunction. This study was performed for this purpose.

Assessment of myocardial oxygen consumption (Vo2) and systolic pressure-volume area (PVA) in human hearts.

Several studies have recently reported that the relationship between myocardial oxygen consumption per beat (Vo2) and left ventricular (LV) systolic pressure-volume area (PVA), which represents total mechanical energy generated by contraction, is linear and independent of loading conditions in excised, supported, and intact hearts. We assessed the Vo2-PVA relationship in nine patients with heart disease. LV volume and pressure were measured simultaneously by conductance catheter and tip-micromanometer. Vo2 was calculated from the difference between arterial and coronary sinus oxygen content, and coronary sinus blood flow measured by the thermodilution method. We obtained the linear relationship between Vo2 and PVA by dextran infusions (median r = 0.917). The slope of the Vo2-PVA relationship was (1.82 +/- 0.66) x 10(-5) mlO2 mmHg-1 ml-1 and the contractile efficiency, the reciprocal of the slope of the Vo2-PVA relationship, was 40 +/- 13%. The Vo2 intercept, which reflects Vo2 for non-mechanical work, was 0.0284 +/- 0.0286 ml O2 beat-1. These results suggest that PVA is a good predictor of myocardial oxygen consumption and a powerful tool to evaluate the coupling of LV mechanical performance to energy use in human hearts.

Decreased coronary sinus oxygen content: A predictor of adverse prognosis in patients with severe congestive heart failure

Patients with congestive heart failure have abnormal coronary hemodynamics, characterized by decreased coronary sinus oxygen content, increased coronary sinus blood flow and increased myocardial oxygen consumption. To evaluate their prognostic importance, the clinical characteristics and systemic and coronary hemodynamics were related to survival in 91 patients with severe congestive heart failure and decreased ejection fraction (25.5 ± 10% [mean ± SD]). In 69 patients congestive heart failure was due to or secondary to coronary artery disease (group 1) and in 22 it was due to idiopathic dilated cardiomyopathy (group 2). Five patients were in functional class II, 48 in class III and 38 in class IV. The median survival time was 20.7 months.As assessed with the Cox proportional hazards model, coronary sinus oxygen content was most strongly associated with a poor prognosis. On the basis of a comparison between the lowest (coronary sinus oxygen content ≤4.44 vol%) and highest quintile (coronary sinus oxygen content >4.44 vol%), a low coronary sinus oxygen content was associated with a 2.34-fold increased risk of dying (95% confidence interval, 1.31 to 4.08). A low systolic blood pressure and a high diastolic pulmonary artery pressure were also significantly associated with increased mortality. Patients in the subgroup with a low coronary sinus oxygen content had values for functional class, ejection fraction and systemic hemodynamics similar to those of patients in the subgroup with high coronary sinus oxygen content.It is concluded that a low coronary sinus oxygen content indicative of noncompensated metabolic demand suggests a poor prognosis in patients with severe congestive heart failure.

Myocardial effects of adenosine‐ and sodium nitroprusside‐induced hypotension: a comparative study in patients anaesthetized for abdominal aortic aneurysm surgery

The effects of adenosine and sodium-nitroprusside (SNP) on central and myocardial haemodynamics and metabolism were evaluated during fentanyl anaesthesia (100 micrograms.kg-1) in six patients with peripheral vascular disease. The investigation was performed during stable anaesthesia, before scheduled abdominal aortic graft surgery. Adenosine and SNP were infused intravenously in random order over 20 min, leaving a 30-min control period in between. The vasodilators were titrated in order to reduce mean arterial pressure by approximately 25%. Adenosine (90 +/- 20 micrograms.kg-1.min-1) reduced mean arterial pressure from 10.9 +/- 0.3 to 8.4 +/- 0.4 kPa (82 +/- 3 to 63 +/- 3 mmHg), and SNP (0.7 +/- 0.1 micrograms.kg-1.min-1) from 11.0 +/- 0.2 to 8.4 +/- 0.3 kPa (83 +/- 3 mmHg to 63 +/- 3 mmHg), during the hypotension period. Cardiac index remained unaffected during induced hypotension with both vasodilators, while heart rate increased during SNP infusion (8 +/- 3%) and remained unaffected with adenosine. Left ventricular stroke work index and myocardial oxygen consumption decreased during SNP infusion (33 +/- 3% and 17 +/- 5%, respectively), while these parameters were unchanged with adenosine. Adenosine hypotension increased coronary sinus flow 1-2 fold (128 +/- 26%), together with increased coronary sinus oxygen content (96 +/- 11%). In contrast, coronary sinus flow decreased during SNP hypotension (-15 +/- 4%) with unaffected coronary sinus oxygen content. It is concluded that adenosine, in contrast to SNP, is associated with a hyperkinetic myocardial circulation.

Heart and brain nucleotide pools during hemorrhage and resuscitation

Sequential 31P nuclear magnetic resonance (NMR) spectra were measured in adult dogs to determine the relationship between cardiac function and myocardial intracellular pH (pHi) and phosphorylated energy metabolites during 2 h of hemorrhagic shock. Simultaneous measurements of coronary blood flow (radioactive microspheres), arterial and coronary sinus pH, blood gases, and oxygen content were performed. In addition, changes in brain NMR spectra were correlated with changes in cerebral blood flow during shock. Two hurs of hypovolemic shock resulted in significant decreases in phosphocreatine (PCr), PCr-to-ATP ratio, and pHi, whereas Pi rose significantly relative to baseline values. Return of shed blood and crystalloid fluid resuscitation improved cerebral and coronary perfusion and returned cardiac contractile function to near baseline values. We conclude that severe and sustained hemorrhagic shock produced significant alterations in brain and heart phosphorylated metabolites as well as significant intracellular acidosis; however, these changes in energy metabolites were reversible with adequate fluid resuscitation from shock.

Rest and exercise cardiovascular effects of terazosin in congestive heart failure

This study investigated the acute effects of the α 1 antagonist terazosin on myocardial circulatory responses at rest and during exercise. Ten patients with congestive heart failure (class III and IV) underwent hemodynamic evaluation before and after a 5-mg oral dose of terazosin. At rest and during exercise, terazosin significantly decreased pulmonary capillary wedge pressure, systemic vascular resistance and mean arterial pressure while cardiac index increased. Stroke volume index increased (p < 0.01) during exercise while left ventricular stroke work index remained unchanged in both experimental conditions. Terazosin administration significantly decreased both rest and exercise myocardial oxygen consumption while exercise coronary sinus oxygen content increased and arterial-coronary sinus oxygen difference diminished (p < 0.05). Parallel with these changes, a blockade decreased the ratio of coronary blood flow to total cardiac output. Coronary vascular resistance remained unaltered with a blockade both at rest and during exercise. Coronary blood flow tended to diminish with decreased myocardial oxygen demand. Alpha 1 blockade induces systemic vasodilation and improves myocardial circulatory parameters with-out inducing coronary dilation or altering metabolic autoregulation.

Effect of direct mechanical ventricular assistance on myocardial hemodynamics during ventricular fibrillation.

Direct mechanical ventricular assistance (DMVA) is a method of biventricular circulatory support that employs a pneumatic device to apply both systolic and diastolic forces directly to the ventricular myocardium. This study investigated the effects of DMVA on myocardial hemodynamics when applied after a prolonged cardiopulmonary arrest. Seven swine weighting 28.3 +/- 2.5 kg were instrumented for regional myocardial blood flow (MBF) measurements using tracer microspheres. Ventricular fibrillation was then induced. After 10 min of ventricular fibrillation, CPR was initiated for 3 min. DMVA was then applied through median sternotomy. Defibrillation was attempted after 3.5 min of DMVA. If unsuccessful, DMVA was instituted for another 17.5 min and a subsequent defibrillation attempt was made. Arterial oxygen content (CaO2), coronary sinus oxygen content (CcSO2), myocardial oxygen delivery/consumption (mDO2/mVO2), extraction ratio (ER), and endocardial/epicardial blood flow ratio (EN/EP) were determined during CPR, during the initial application of DMVA (DMVA1), and after the subsequent 17.5 min of DMVA in those animals not initially defibrillated (DMVA2). Three of the seven animals were successfully defibrillated during DMVA1. After the additional 17.5 min of DMVA, only one other animal was defibrillated. There was a significant improvement in CaO2, CcSO2, MBF, mDO2, mVO2, ER, and EN/EP after DMVA1 compared to CPR. Only mVO2 and ER improved significantly after DMVA2. These findings support the concept that physical diastolic augmentation may improve myocardial hemodynamics when DMVA is applied during cardiac arrest.

The effect of UK14,304-18 (an alpha-2 adrenergic agonist) on myocardial blood flow during cardiopulmonary resuscitation

Several recent studies have suggested that adrenergic drugs with peripheral postsynaptic alpha-2 agonist properties increase aortic diastolic pressure (ADP), and thus in the setting of CPR, may improve myocardial blood flow (MBF). This preliminary study investigated the effect of UK14,304-18, a postsynaptic alpha-2 adrenergic agonist on ADP, MBF, myocardial oxygen delivery/utilization (MDO 2/MVO 2), endocardial/epicardial blood flow ratio (EN/EP), coronary sinus oxygen content (C csO 2) and extraction ratio (ER) during CPR. Five swine were instrumented for MBF measurements using tracer microspheres. Catheters were also placed to measure arterial oxygen content (C aO 2) and C csO 2. ADP, MBF, MDO 2/MVO 2, EN/EP, ER, C aO 2 and C csO 2 were measured during normal sinus rhythm (NSR), and during CPR following a 10-min cardiorespiratory arrest. Following this, each animal received 2.0 mg/kg of UK14,304-18 through a right atrial line. ADP, MBF, MDO 2/MVO 2, EN/EP, ER, C aO 2 and C csO 2 were again determined. Defibrillation was then attempted. To determine whether UK14,304-18 improved ADP, MBF and MDO 2 over MVO 2, compared to CPR alone, results were compared using a paired Student t-test. Statistical significance was considered at the P ⩽ 0.05 level. No significant improvement in ADP, MBF, MDO 2 or ER was noted following the administration of UK14,304-18. The lack of improvement in ADP and MBF may be secondary to a centrally acting postsynaptic alpha-2 agonist effect because of disruption of the blood brain barrier following a prolonged cardiac arrest or because of pharmacologically or structurally distinct populations of peripheral postsynaptic alpha-2 adrenoreceptors that develop in this setting. This study suggests that UK14,304-18 does not improve myocardial hemodynamics at these doses during CPR following a 10-min arrest.

The effect of norepinephrine versus epinephrine on myocardial hemodynamics during CPR

Alpha-adrenergic agonists improve myocardial blood flow during CPR by increasing aortic diastolic pressure. Adrenergic agonists with beta-2 properties may enhance peripheral vasodilation and may prove less beneficial during CPR. The purpose of this study was to compare epinephrine (E), an alpha-1,2; beta-1,2 agonist, versus norepinephrine, an alpha-1,2; beta-1 agonist, on myocardial hemodynamics during CPR. Twenty swine were instrumented for pressure, arterial and coronary sinus oxygen content (CAO2 and CCSO2, respectively), and myocardial blood flow measurements using tracer microspheres. CAO2, CCSO2, myocardial blood flow, myocardial oxygen delivery (MDO2) and myocardial oxygen consumption (MVO2), extraction ratio, and aortic diastolic pressure were determined during normal sinus rhythm and during CPR following a ten-minute arrest. After three minutes of CPR, the animals were allocated to receive either norepinephrine 0.08 mg/kg (n = 5), norepinephrine 0.12 mg/kg (n = 5), norepinephrine 0.16 mg/kg (n = 5), or epinephrine 0.20 mg/kg (n = 5). One minute after drug administration, all hemodynamic parameters were again determined. Three and one half minutes after drug administration defibrillation was attempted. A Newman-Keuls multiple comparison procedure was used to compare differences following drug administration. During CPR, aortic diastolic pressure averaged less than 13 mm Hg, and myocardial blood flow averaged less than 6 mL/min/100 g. All doses of norepinephrine and epinephrine improved all hemodynamic parameters over those seen during CPR. The two highest doses of norepinephrine significantly improved extraction ratio compared with norepinephrine 0.08 mg/kg (P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of enalapril on myocardial noradrenaline overflow during exercise in patients with chronic heart failure.

The effects of the angiotensin converting enzyme inhibitor enalapril on myocardial sympathetic tone, as represented by noradrenaline overflow, were studied in 14 men with congestive heart failure (mean ejection fraction 20%) in a double blind crossover comparison with placebo. Arterial and coronary sinus catecholamine concentrations and oxygen content, and coronary sinus blood flow, were measured at rest and during peak symptom limited upright exercise on a bicycle ergometer. There were no significant changes four hours after the first dose of enalapril, but after six weeks of treatment (10-20 mg/day) enalapril reduced myocardial overflow of noradrenaline at peak exercise. The external workload (exercise duration) increased from baseline values after both placebo and enalapril, and there was no difference between placebo and enalapril at six weeks. Heart work, however, was lower after enalapril: stroke work index was reduced at rest and the double product was lower at peak exercise. The reduction in maximal myocardial oxygen consumption after enalapril did not reach statistical significance. Coronary sinus adrenaline concentrations after enalapril and after placebo were not significantly different. The long term reduction of myocardial sympathetic activity on exercise may represent a significant benefit from angiotensin converting enzyme inhibition in heart failure and may reflect a reduced cardiac workload.