Index Of Myocardial Oxygen Demand Research Articles

Hemodynamic and Pressor Responses to Combination of Yoga and Blood Flow Restriction.

A combination of yoga and blood flow restriction, each of which elicits marked pressor responses, may further increase blood pressure and myocardial oxygen demand. To determine the impact of a combination of yoga and blood flow restriction on hemodynamic responses, twenty young healthy participants performed 20 yoga poses with/without blood flow restriction bands placed on both legs. At baseline, there were no significant differences in any of the variables between the blood flow restriction and non-blood flow restriction conditions. Blood pressure and heart rate increased in response to the various yoga poses (p<0.01) but were not different between the blood flow restriction and non-blood flow restriction conditions. Rate-pressure products, an index of myocardial oxygen demand, increased significantly during yoga exercises with no significant differences between the two conditions. Rating of perceived exertion was not different between the conditions. Blood lactate concentration was significantly greater after performing yoga with blood flow restriction bands (p=0.007). Cardio-ankle vascular index, an index of arterial stiffness, decreased similarly after yoga exercise in both conditions while flow-mediated dilation remained unchanged. In conclusion, the use of lower body blood flow restriction bands in combination with yoga did not result in additive or synergistic hemodynamic and pressor responses.

Resting Coronary Blood Flow Velocity by Transthoracic Coronary Echocardiography is Higher in Patients with Cardiovascular Diseases Compared with the Healthy Adults

Transthoracic Coronary Echocardiography (TCE), defined as blood velocity detection mainly in the left anterior descending artery (LAD) by noninvasive Doppler echocardiography, has been employed to measure coronary blood flow velocity and coronary flow reserve in research labs and in clinical settings. Most prior studies focused on the coronary flow reserve data, and normal values for resting coronary artery flow velocity have rarely been reported. The purpose of this study was to examine resting coronary blood flow velocity in healthy subjects and patients with cardiovascular disease. We retrospectively collected resting coronary blood flow velocity data by TCE from 69 healthy subjects (42 M, 27 F, 60 ± 8 yrs) and 37 patients (27 M, 10 F, 63 ± 10 yrs) with various cardiovascular diseases (14 peripheral arterial disease, 5 Pre‐TAVR, 8 hypertrophy cardiomyopathy, 10 CABG). The patient group had higher systolic blood pressure (135 ± 18 vs. 120±14 mmHg, P value &lt;0.001), mean blood pressure (94 ± 11 vs. 89 ±10 mmHg, P value &lt;0.05), and Rate‐Pressure Product (RPP, an index of myocardial oxygen demand) (8617 ± 1702 vs. 7249 ± 1453. P value &lt; 0.001). Resting coronary blood flow velocities early (CBV1) and late (CBV2) in diastole were significantly higher in the patient group (CBV1: 27.6±8.6 vs. 19.0 ± 4.9 cm/s, P value &lt; 0.001; CBV2: 17.6 ± 5.5 vs. 13.4 ± 3.2 cm/s, P value &lt;0.001). After controlling for oxygen consumption (CBV/RPP), resting coronary blood flow velocity during the early diastolic period was still significantly higher in patients than in the healthy group (Adjusted CBV1: 3.3 ± 1.4 vs. 2.7 ± 0.8 au, P value &lt; 0.001). There was no significant difference in adjusted coronary blood flow velocity during the late diastolic period (Patient group vs. healthy group, 2.1 ± 0.8 vs.1.9 ± 0.5 au, P value = 0.105). Further studies are needed to explore the clinical implication and importance of higher resting coronary blood flow velocity data by TCE in patients.Support or Funding InformationSupported by National Institutes of Health Grants P01 HL134609 (Sinoway), and UL1 TR002014 (Sinoway).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Peripheral revascularization attenuates the exercise pressor reflex and increases coronary exercise hyperemia in peripheral arterial disease.

Peripheral arterial disease (PAD) is associated with augmented blood pressure (BP) and impaired coronary blood flow responses to exercise, which may increase cardiovascular risk. We investigated the effects of leg revascularization on the BP and coronary blood flow responses to exercise in PAD. Seventeen PAD patients (11 men, 66 ± 2 yr) performed single-leg plantar flexion exercise 24 h before and 1 mo following leg revascularization. BP and heart rate (HR) were measured continuously, and rate pressure product (systolic BP × HR) was calculated as an index of myocardial oxygen demand. Coronary blood velocity was obtained by transthoracic Doppler echocardiography in 8/17 subjects. The mean BP response to plantar flexion exercise was attenuated by leg revascularization (pre-revascularization: 15 ± 4 vs. post-revascularization: 7 ± 3 mmHg, P = 0.025). The HR response to plantar flexion was also attenuated following leg revascularization (pre-revascularization: 9 ± 1 vs. post-revascularization: 6 ± 1 beats/min, P = 0.006). The change in coronary blood velocity with exercise was greater at the post-revascularization visit: 4 ± 1 vs. pre-revascularization: -1 ± 2 cm/s ( P = 0.038), even though the change in rate pressure product was not greater following revascularization in these subjects (pre-revascularization: 2,796 ± 871 vs. post-revascularization: 1,766 ± 378 mmHg·beats/min, P = 0.082). These data suggest that leg revascularization alters reflex control of BP, HR, and coronary blood flow in response to exercise in patients with PAD. NEW & NOTEWORTHY We found that peripheral revascularization procedures lowered exercise blood pressure and improved coronary blood flow in patients with peripheral arterial disease.

The Exercise Pressor Reflex is attenuated and Coronary Exercise Hyperemia is improved by Peripheral Revascularization in Peripheral Arterial Disease

Patients with peripheral arterial disease (PAD) have a greater blood pressure (BP) response to exercise or augmented exercise pressor reflex. Our recent work showed that PAD patients also have impaired coronary blood flow responses to exercise which may increase cardiovascular risk. We investigated the effects of leg revascularization procedures on the BP and coronary blood flow responses to exercise in PAD. Seventeen PAD patients (11 men, 66 ± 2 yr) performed single‐leg plantar flexion exercise for up to 6 minutes twice: 24 hr before and one month following leg revascularization. BP and heart rate (HR) were measured continuously and rate pressure product (systolic BP × HR) was calculated as an index of myocardial oxygen demand. Coronary blood velocity was obtained by transthoracic Doppler echocardiography. The mean BP response to plantar flexion exercise was attenuated by leg revascularization (pre revascularization: 15 ± 4 vs. post revascularization: 7 ± 3 mmHg, P = 0.025). The HR response to plantar flexion was also attenuated following leg revascularization (pre revascularization: 9 ± 1 vs. post revascularization: 6 ± 1 beats/min, P = 0.006). The change in coronary blood velocity with exercise was significantly greater at the post revascularization visit: 4 ± 1 vs. pre revascularization: −1 ± 2 cm/s (P = 0.038). The rate pressure product response to exercise tended to be lower following revascularization but this did not reach statistical significance (pre revascularization: 2796 ± 871 vs. post revascularization: 1766 ± 378 mmHg*beats/minute, P = 0.082). These data suggest that leg revascularization improves reflex control of BP, HR, and coronary blood flow in response to exercise in patients with PAD.Support or Funding InformationP01 HL134609 (Sinoway)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Tumor Necrosis Factor-alpha Adversely Influences Myocardial Oxygen Demand and Exercise Tolerance in Postmenopausal Women

Oxidative stress-mediated arterial stiffening is related to the pathophysiological progression of vascular dysfunction with advancing age. However, the functional implications concerning the involvement of tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic responses at rest and during physical exertion are unclear. PURPOSE: The aims of this investigation were to examine the independent effects of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the influence of TNF-α on exercise tolerance. METHODS: Forty, postmenopausal (65 ± 3 years) women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake. Local pulse contour analyses were used to assess large artery compliance while rate-pressure product (RPP), a reliable index of myocardial oxygen demand, was measured at rest and during two submaximal workloads. RPP was calculated by dividing the product of heart rate and systolic blood pressure (via auscultation) by 100. Exercise tolerance corresponded with the cessation of the graded exercise test. P-values ≤ 0.05 were considered statistically significant for all analyses. RESULTS: Multiple linear regression revealed a positive association between TNF-α and RPP during submaximal exercise (partial r = 0.43; p = 0.015) adjusted for maximal heart rate, maximal oxygen uptake, large artery compliance, and percent body fat. Path analyses revealed a significant indirect effect of large artery compliance on exercise tolerance through TNF-α, β = 0.13, CI [0.03, 0.35] such that heightened levels of TNF-α translated to poorer exercise tolerance. CONCLUSIONS: These data indicate that TNF-α is independently associated with myocardial oxygen demand during submaximal exercise equating to 5 METs but not at rest and TNF-α mediates the indirect effects of large artery compliance on exercise tolerance. Future studies should explore differential responses to standardized exercise tasks among older adults and consider the influence of exercise training on myocardial oxygen demand and activity-related energy expenditure.

Lower rate-pressure product during submaximal walking: a link to fatigue improvement following a physical activity intervention among breast cancer survivors.

Research showing a link between exercise-induced changes in aerobic fitness and reduced fatigue after a cancer diagnosis has been inconsistent. We evaluated associations of fatigue and rate-pressure product (RPP), a reliable index of myocardial oxygen demand, at rest and during submaximal walking following a physical activity intervention among post-primary treatment breast cancer survivors (BCS). Secondary analyses of 152 BCS in a randomized controlled trial testing a physical activity intervention (INT) versus usual care (UC) were performed. The INT group completed counseling/group discussions along with supervised exercise sessions tapered to unsupervised exercise. Evaluations were made at baseline and immediately post-intervention (M3) on measures of physical activity (accelerometry), graded walk test, and average fatigue over the previous 7days. RPP was calculated by dividing the product of heart rate and systolic blood pressure by 100. Resting and submaximal RPPs were significantly improved in both groups at M3; however, the magnitude of change (∆) was greater in the INT group from stage 1 (∆RPP1; INT -13 ± 17 vs. UC -7 ± 18; p = 0.03) through stage 4 (∆RPP4; INT -21 ± 26 vs. UC -9 ± 24; p < 0.01) of the walk test. The INT group reported significantly reduced fatigue (INT -0.7 ± 2.0 vs. UC +0.1 ± 2.0; p = 0.02) which was positively associated with ∆RPP during stages 2-4 of the walk test but not ∆aerobic fitness. Lower RPP during submaximal walking was significantly associated with reduced fatigue in BCS. Exercise/physical activity training programs that lower the physiological strain during submaximal walking may produce the largest improvements in reported fatigue.

Association of aortic stiffness and wave reflections with coronary flow reserve in women without obstructive coronary artery disease: An ancillary study from the National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation (WISE)

Increased aortic stiffness and reduced coronary flow reserve (CFR) independently predict adverse outcomes. But information about relationships between arterial properties and CFR in subjects without obstructive coronary artery disease (CAD) is limited. CFR was measured (Doppler flow wire and intracoronary adenosine) in 50 women (age 53 ± 11 years) with symptoms and signs of myocardial ischemia without obstructive CAD. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was obtained via catheter pullback; radial artery pressure waves were measured by applanation tonometry and central aortic pressure synthesized. Overall, CFR (mean 2.61 ± 0.47) was significantly correlated with aPWV (r = -0.51), pulse wave amplification (r = 0.45), augmented pressure (r = -0.48), augmentation index (AIx, r = -0.44), aortic systolic pressure (r = -0.49), left ventricular wasted energy (LVEw, r = -0.47) (all P < .001), systolic pressure time index (r = -0.37, P < .008), and rate pressure product (r = -0.29, P < .04). In the multiple regression model including aPWV, CFR was still significantly correlated with aPWV (P < .008) and aortic systolic pressure (P < .01). No other measures contributed significant additional information. Women with CFR ≤2.5 versus those with CFR >2.5 had greater aPWV (894 ± 117 vs 747 ± 93 cm/s, P < .001), augmented pressure (14 ± 4.9 vs 11 ± 4.1 mmHg, P < .008), AIx (32 ± 6.6 vs 27 ± 6.6%, P < .003), LVEw (30 ± 12 vs 21 ± 10 dyne-s/cm(2) × 10(2), P < .02) and reduced pulse pressure amplification (1.20 ± .07 vs 1.26 ± .10, P < .008) and pressure wave travel time (133 ± 7.3 vs 138 ± 6.9 milliseconds, P < .04). Among symptomatic women without obstructive CAD, CFR was inversely related to aortic systolic pressure and indices of aortic stiffness. These changes in arterial properties increase left ventricular afterload requiring the ventricle to generate additional, but wasted, energy that increases indices of myocardial oxygen demand, reduces CFR and increases vulnerability to ischemia.

Effect of beta‐adrenergic blockade on coronary blood flow during isometric exercise in older adults (875.7)

The rise in heart rate (HR) and cardiac contractility during exercise is due to activation of myocardial β‐adrenergic receptors. In animals, β‐adrenergic receptors in the coronary vasculature also mediate a parallel increase in coronary blood flow. However, the role of β‐ adrenergic receptors in the human coronary circulation is unknown. We hypothesized that β‐adrenergic blockade with propranolol would attenuate reflex tachycardia and coronary hyperemia in response to isometric handgrip in healthy older adults. Six men (66 ± 2 yrs) performed isometric handgrip exercise at 40% of maximal voluntary contraction for 2 minutes after receiving intravenous propranolol or no treatment. HR and blood pressure were monitored continuously and rate‐pressure product (RPP) was calculated as an index of myocardial oxygen demand. Coronary blood flow velocity (CBV) was measured by transthoracic Doppler echocardiography and coronary vascular resistance (CVR) was calculated. The coronary supply to demand ratio was calculated as CVR/RPP. Propranolol decreased the HR (8 ± 3 vs. 4 ± 1) and RPP (2580 ± 612 vs. 1520 ± 163) responses to exercise but augmented the CVR/RPP response (‐0.24 ± .09 vs. ‐0.49 ± 0.15). Mean arterial pressure, CVR and CBV were unaltered. β‐adrenergic blockade not only decreased myocardial oxygen demand in response to exercise, it also improved oxygen supply.Grant Funding Source: Supported by NIH P01 HL096570 and UL1 TR000127

β-Adrenergic blockade enhances coronary vasoconstrictor response to forehead cooling

Forehead cooling activates the sympathetic nervous system and can trigger angina pectoris in susceptible individuals. However, the effect of forehead cooling on coronary blood flow velocity (CBV) is not well understood. In this human experiment, we tested the hypotheses that forehead cooling reduces CBV (i.e., coronary vasoconstriction) and that this vasoconstrictor effect would be enhanced under systemic β-adrenergic blockade. A total of 30 healthy subjects (age range, 23-79 years) underwent Doppler echocardiography evaluation of CBV in response to 60 s of forehead cooling (1°C ice bag on forehead). A subset of subjects (n = 10) also underwent the procedures after an intravenous infusion of propranolol. Rate pressure product (RPP) was used as an index of myocardial oxygen demand. Consistent with our first hypothesis, forehead cooling reduced CBV from 19.5 ± 0.7 to 17.5 ± 0.8 cm/s (P < 0.001), whereas mean arterial pressure increased by 11 ± 2 mmHg (P < 0.001). Consistent with our second hypothesis, forehead cooling reduced CBV under propranolol despite a significant rise in RPP. The current studies indicate that forehead cooling elicits a sympathetically mediated pressor response and a reduction in CBV, and this effect is augmented under β-blockade. The results are consistent with sympathetic activation of β-receptor coronary vasodilation in humans, as has been demonstrated in animals.

Effect of aging on cardiac function during cold stress in humans

To determine whether skin surface cooling increases left ventricular preload and contractility to a greater extent in older compared with young adults we studied 11 young (28 +/- 2 yr; means +/- SE) and 11 older (64 +/- 3 yr) adults during normothermia (35 degrees C water perfused through a tube-lined suit) and cooling (15 degrees C water perfused for 20 min) using standard and tissue Doppler echocardiography. Cooling significantly decreased skin surface temperature in young (Delta2.8 +/- 0.3 degrees C) and older (Delta3.0 +/- 0.3 degrees C) adults and increased rate-pressure product, an index of myocardial oxygen demand, in older (6,932 +/- 445 to 7,622 +/- 499 mmHg x beats/min for normothermia and cooling, respectively), but not young (7,085 +/- 438 to 7,297 +/- 438 mmHg x beats/min) adults. Increases in blood pressure (systolic and mean blood pressure) during cooling were greater (P < 0.05) in older than in young adults. Cooling increased preload in older (left ventricular end-diastolic volume from 106 +/- 7 to 126 +/- 9 ml and left ventricular internal diameter in diastole from 4.69 +/- 0.12 to 4.95 +/- 0.14 cm; both P < 0.01), but not young adults (left ventricular end-diastolic volume from 107 +/- 7 to 111 +/- 7 ml and left ventricular internal diameter in diastole from 4.70 +/- 0.10 to 4.78 +/- 0.10 cm). Indices of left ventricular contractility (ejection fraction, myocardial acceleration during isovolumic contraction, and peak systolic mitral annulus velocity) were unchanged during cooling in both young and older adults. Collectively, these data indicate that cooling increases left ventricular preload, without affecting left ventricular contractility in older but not young adults. Greater increases in preload and afterload during cooling in older adults contribute to greater increases in indices of myocardial oxygen demand and may help explain the increased risk of cardiovascular events in cold weather.

Effects of Leg Blood Flow Restriction during Walking on Cardiovascular Function

Exercise with limb blood flow restriction (BFR) is a very popular exercise modality in Japan and is spreading widely to the rest of the world. The underlying principle of this training modality is that under the conditions of restricted blood flow, even low-intensity exercise can provide significant muscle strength and hypertrophy. One concern, however, is that BFR during exercise may place unnecessary burden on those with compromised cardiac function. We determined the impact of leg BFR during walking on cardiovascular function in 17 young (26 ± 1 yr) healthy volunteers. Each subject underwent five bouts of 2-min treadmill walking at 2 miles·h(-1) with 1-min interval either with or without tourniquet cuffs inflated on both thighs. Heart rate increased more during the BFR session, whereas stroke volume decreased greater during the BFR session. Blood pressure increased significantly and substantially during the BFR session. Consequently, an increase in double product, an index of myocardial oxygen demand, was more than threefold higher in the BFR condition. Systemic arterial compliance evaluated by stroke volume/pulse pressure ratio significantly increased during the control session by 14% but reduced during the BFR condition by 19%. Popliteal artery flow-mediated vasodilation decreased significantly after the exercise with BFR but not after the control session. Even at low intensity, the aerobic exercise with BFR requires a greater cardiac work and decreases endothelial function. Limb BFR during exercise may need to be more cautiously prescribed to those with compromised cardiac conditions.

Successful Retrial of ECT Two Months After ECT-Induced Takotsubo Cardiomyopathy

heart failure; however, recovery of cardiac function is often complete within the first week following the insult. Cardiac enzymes may be mildly elevated, but on cardiac catheterization there is usually no evidence of coronary artery disease, or only "mild luminal irregularities" may be noted (7). Contraction band necrosis may be seen on biopsy in the more serious cases. The cause of takotsubo cardiomyopathy is unknown, but several mechanisms have been suggested, including ischemia from coronary artery spasm, microvascular spasm, and direct myocyte injury (5).

Cocaine and Ethanol: Combined Effects on Coronary Artery Blood Flow and Myocardial Function in Dogs

In combination, cocaine and ethanol are more cardiotoxic than is either substance alone. These substances together constitute a drug abuse combination that commonly results in fatality. Previously the authors have demonstrated that cardiotoxicity of cocaine and ethanol is in part due to synergistic myocardial-depressant effects. However, it remains unclear whether this myocardial depression is associated with concomitant adverse effects on coronary blood flow in relation to these substances. The aim of this study was to investigate combined effects of cocaine and ethanol on myocardial blood flow, in relation to indices of myocardial function. Anesthetized dogs were instrumented for hemodynamic monitoring with Doppler flow probes placed on the circumflex and left anterior descending (LAD) coronary arteries. Dogs were randomized to three groups (each n = 6): ethanol (E, 1.5 g/kg followed by placebo), cocaine (C, placebo followed by cocaine, 7.5 mg/kg IV), or cocaine plus ethanol (C + E). All measurements were made at control, after placebo or ethanol, and then at fixed time intervals after cocaine or placebo bolus over 3 hours. In both the C + E and the C groups, circumflex blood flow (CBF) decreased by 71% (95% confidence interval [CI] = 56% to 85%) and 57% (95% CI = 43% to 72%, both p < 0.04 vs. baseline) immediately after cocaine bolus. This was associated with transient depression of cardiac output, myocardial contractile function, and rate-pressure product (RPP), all indices of myocardial oxygen demand. A subsequent rebound increase of coronary sinus blood flow (CSBF) of 56% (95% CI = 26% to 137%, p < 0.03) compared to baseline occurred only in the C group and was associated with increases of myocardial contractile function and RPP. In the C + E group, 2 hours after drug administration, there was a decrease in CSBF of 49% (95% CI = 32% to 67%; p < 0.01) compared to baseline, which was associated with concomitant numerical decreases of the indices of myocardial oxygen demand and accumulation of cocaethylene. Acute decreases in myocardial flow secondary to cocaine, and cocaine and ethanol in combination, were similar and temporally associated with cocaine's direct myocardial-depressant effects. Rebound increases in myocardial function and blood flow due to cocaine were attenuated by ethanol. Delayed myocardial depression and decreases in myocardial blood flow were observed only with coadministration of cocaine and ethanol.

Concentrated Ambient Particles Alter Myocardial Blood Flow during Acute Ischemia in Conscious Canines

BackgroundExperimental and observational studies have demonstrated that short-term exposure to ambient particulate matter (PM) exacerbates myocardial ischemia.ObjectivesWe conducted this study to investigate the effects of concentrated ambient particles (CAPs) on myocardial blood flow during myocardial ischemia in chronically instrumented conscious canines.MethodsEleven canines were instrumented with a balloon occluder around the left anterior descending coronary artery and catheters for determination of myocardial blood flow using fluorescent microspheres. Telemetric electrocardiographic and blood pressure monitoring was available for four of these animals. After recovery, we exposed animals by inhalation to 5 hr of either filtered air or CAPs (mean concentration ± SD, 349.0 ± 282.6 μg/m3) in a crossover protocol. We determined myocardial blood flow during a 5-min coronary artery occlusion immediately after each exposure. Data were analyzed using mixed models for repeated measures. The primary analysis was based on four canines that completed the protocol.ResultsCAPs exposure decreased total myocardial blood flow during coronary artery occlusion by 0.12 mL/min/g (p < 0.001) and was accompanied by a 13% (p < 0.001) increase in coronary vascular resistance. Rate–pressure product, an index of myocardial oxygen demand, did not differ by exposure (p = 0.90). CAPs effects on myocardial blood flow were significantly more pronounced in myocardium within or near the ischemic zone versus more remote myocardium (p interaction < 0.001).ConclusionsThese results suggest that PM exacerbates myocardial ischemia by increased coronary vascular resistance and decreased myocardial perfusion. Further studies are needed to elucidate the mechanism of these effects.

Myocardial oxidative metabolic supply-demand relationships in patients with nonischemic dilated cardiomyopathy

Nonischemic dilated cardiomyopathy (NIDCM) is associated with left ventricular remodeling, hypertrophy, and mitochondrial metabolic abnormalities in vitro. We evaluated the hypothesis that energy supply, as judged by the rate of myocardial oxidative metabolism, is inadequate to meet oxygen demand in patients with NIDCM compared with normal subjects. We used positron emission tomography to determine the myocardial carbon 11 acetate decay rate (kmono) as an index of energy supply, and we compared kmono with the rate-pressure product (RPP) as an index of metabolic demand in 7 patients with NIDCM and 7 normal subjects. The mean kmono value (SEM) was 0.060 +/- 0.006 min(-1) in NIDCM patients versus 0.054 +/- 0.002 in normal subjects (P = not significant). The RPP was 9949 +/- 931 beats/min.mm Hg in NIDCM patients and 6521 +/- 476 in normal subjects (P = .007). The relationship of kmono to this index of demand (kmono/RPP) was 6.2 x 10(-6) in NIDCM patients but was 8.5 x 10(-6) in normal subjects (P = .003). Thus RPP, as an index of myocardial oxygen demand, was poorly matched by the rate of oxidative metabolism in those patients with NIDCM. The kmono was closely related to RPP in normal subjects (r = 0.83, P = .02) but not in NIDCM patients. Furthermore, there was no significant relationship between kmono and wall stress as another index of oxygen demand. These results are consistent with a mitochondrial metabolic abnormality in heart failure. This metabolic mismatch detected by positron emission tomography may contribute to the pathophysiology of congestive heart failure and left ventricular remodeling.

Effect of stimulants on 24-h ambulatory blood pressure in children with ADHD: a double-blind, randomized, cross-over trial

Millions of children with attention deficit hyperactivity disorder (ADHD) are treated with stimulant medications. To evaluate cardiovascular risk, 24-h ambulatory blood pressure monitoring (ABPM) was performed on and off medication. Thirteen subjects underwent APBM both on stimulant therapy and placebo using a placebo-controlled, double-blind, randomized, cross-over design. After a 3-day run-in followed by a 24-h monitoring period, subjects crossed over to the alternate therapy for repeated ABPM. Subjects demonstrated elevations in most hemodynamic parameters derived from ABPM during the active treatment period. Total diastolic blood pressure (69.7 mmHg vs 65.8 mmHg, p =0.02) and waking diastolic blood pressure (75.5 mmHg vs 72.3 mmHg, p =0.03) were significantly higher during active treatment. Total heart rate was also significantly higher during active treatment (85.5 beats/min vs 79.9 beats/min, p =0.004). The rate-pressure product (the product of systolic blood pressure x heart rate), an index of myocardial oxygen demand, was higher during active treatment (9,958 vs 9,076, p =0.008). This study provides evidence for a possible negative cardiovascular effect of stimulant medications in children with ADHD. This potential cardiovascular risk should be balanced against the beneficial behavioral effects of this class of medication.

Comparison of the effects of dexmedetomidine and esmolol on myocardial oxygen consumption in dogs

The beta-adrenergic blocker esmolol and the alpha 2-adrenergic agonist dexmedetomidine have the potential to decrease perioperative myocardial ischaemia. The pathophysiological mechanisms involved in these anti-ischaemic properties have not been thoroughly studied. We compared the effects of esmolol and dexmedetomidine on two indices of overall myocardial oxygen demand and on directly measured myocardial oxygen consumption of the left anterior coronary artery territory. Eleven mongrel dogs were instrumented to measure aortic and left ventricular pressure, aortic and left anterior coronary artery flow and myocardial wall thickening. Variables related to myocardial oxygen metabolism were also determined. Measurements were performed during four sequential experimental conditions in each dog (Control 1: esmolol; Control 2: dexmedetomidine). Esmolol and dexmedetomidine decreased haemodynamic indices of myocardial oxygen demand to a similar extent: esmolol decreased the rate-pressure product by 16+/-3% and the pressure-work index (PWI) by 16+/-3%, dexmedetomidine decreased the rate-pressure product by 26+/-3% and the PWI by 16+/-7%. However, these similar decreases resulted from different haemodynamic effects of the two study drugs. Dexmedetomidine had a more pronounced bradycardic effect than esmolol (P = 0.01) and increased systolic aortic pressure (SAP) by 15+/-4% while esmolol decreased SAP by 8+/-2% (P < 0.01). dP/dt(max) and regional myocardial area decrease were lower after esmolol than after dexmedetomidine. Neither drug had an effect on myocardial oxygen consumption. Esmolol and dexmedetomidine decreased two haemodynamic indices of overall myocardial oxygen demand to a similar extent but neither drug decreased directly measured myocardial oxygen consumption in the territory of the left anterior descending artery.

The effect of diabetes on heart rate and other determinants of myocardial oxygen demand in acute coronary syndromes.

To compare major determinants of myocardial oxygen demand (heart rate, blood pressure and rate pressure product) in patients with and without diabetes admitted with acute coronary syndromes. A cross-sectional study of the relation between diabetes and haemodynamic indices of myocardial oxygen demand in 2542 patients with acute coronary syndromes, of whom 1041 (41.0%) had acute myocardial infarction and 1501 (59.0%) unstable angina. Of the 2542 patients, 701 (27.6%) had diabetes. Major haemodynamic determinants of myocardial oxygen demand were higher in patients with than without diabetes: heart rate 80.0 +/- 20.4 vs. 75.2 +/- 19.2 beats/minute (P < 0.0001); systolic blood pressure 147.3 +/- 30.3 vs. 143.2 +/- 28.5 mmHg (P = 0.002); rate-pressure product 11533 +/- 4198 vs. 10541 +/- 3689 beats/minute x mmHg (P < 0.0001). Multiple regression analysis confirmed diabetes as a significant determinant of presenting heart rate [multiplicative coefficient (MC) 1.05; 95% confidence interval (CI) 1.03-1.07; P < 0.0001], rate pressure product (MC 1.09; CI 1.05-1.12; P < 0.0001) and systolic blood pressure, which was estimated to be 3.9 mmHg higher than in patients without diabetes (P=0.003). These effects of diabetes were independent of a range of baseline variables including acute left ventricular failure and mode of presentation (unstable angina or myocardial infarction). In acute coronary syndromes, heart rate and other determinants of myocardial oxygen demand are higher in patients with than without diabetes, providing a potential contributory mechanism of exaggerated regional ischaemia in this high-risk group.

Impact of coronary artery disease on left ventricular systolic function and geometry in hypertensive patients with left ventricular hypertrophy (the LIFE study)

Hypertensive patients with left ventricular (LV) hypertrophy have a higher incidence of cardiovascular events than those without it. We hypothesized that a close relation exists between clinical evidence of coronary artery disease (CAD) and alterations in LV structure and function that contribute to their higher risk. Echocardiograms were recorded in 963 hypertensive patients (mean age 66 ± 7 years, 41% women) with electrocardiographic LV hypertrophy, and divided into 149 with and 814 without clinical (prior myocardial infarction or angina pectoris) or electrocardiographic (Minnesota codes 1.1, 1.2) evidence of CAD. Patients with CAD had larger LV internal dimensions (5.5 ± 0.6 vs 5.2 ± 0.5 cm), increased LV mass (136 ± 31 vs 122 ± 24 g/m2, and 62.4 ± 19.4 vs 55.5 ± 12.1 g/m2.7), lower ejection fraction (58 ± 10% vs 62 ± 8%), higher circumferential end-systolic wall stress (cESS) (198 ± 59 vs 181 ± 47 kdynes/cm2, all p <0.001), and higher total peripheral resistances (2,088 ± 628 vs 1,963 ± 553 dynes · s · m2/cm3, p = 0.02). Although eccentric LV hypertrophy predominated, the CAD group had a greater prevalence of this geometric pattern than the non-CAD group (56% vs 47%, p <0.02). An index of myocardial oxygen demand per beat—the LV mass · cESS · ejection time—was 20% higher in patients with CAD. In conclusion, clinical evidence of CAD in hypertensive patients with electrocardiographic evidence of LV hypertrophy identifies subjects with structural and functional abnormalities at high risk for cardiovascular events. LV mass · cESS · ejection time, a noninvasive index that parallels myocardial oxygen demand per beat, is especially high in hypertensive patients with CAD.

DOUBLE PRODUCT BREAK POINT AND ISCHEMIA THRESHOLD DURING EXERCISE TESTING: ARE THEY RELATED?

1207 We have previously shown that the double product break point (DPBP) is highly correlated with the lactate and ventilatory thresholds in patients with known coronary artery disease (CAD) and that 3 months of exercise training improves the DPBP in these patients. Since the double product is an indirect index of myocardial oxygen demand, the DPBP would be expected to be related to the onset of myocardial ischemia. The purpose of our investigation was to determine if the DPBP was related to the onset or threshold for myocardial ischemia (IT) during exercise testing in patients with known obstructive CAD. Eleven patients with angiographically defined CAD and a prior positive exercise test were recruited for this investigation. Each patient was exercise tested to symptom-limited maximal level on an individualized RAMP treadmill protocol. A 12-lead ECG, blood pressure, symptoms, and expired gases (oxygen consumption [VO2]) were measured each minute during exercise. The double product was obtained every 15 seconds from the brachial artery using a Kyokko Bussan automated system. After completion of the exercise test, all 12 lead ECG tracings from each test were sent to three blinded clinicians for determination of the IT (i.e. ≥ 1mm horizontal or down-slopping ST segment depression in at least 2 leads). The same three observers received blinded plots of the DP vs. VO2 to determine the DPBP for each test. Each observer reported the time and VO2 at the IT and DPBP. The average of the 3 reported values were used for statistical analyses. Paired t tests indicated that the mean (± SEM) time and VO2 between the DPBP and IT were significantly different (312 ± 32 vs. 492 ± 58 seconds & 1300 ± 88 vs. 1637 ± 122 ml/min, respectively). However, regression analysis of DPBP vs. IT revealed a significant (p<.01) correlation (r=.71) and a relatively small standard error of the estimate (SEE=301 ml/min). The DBPB appears to precede the IT by a VO2 of approximately 300 ml/min and occurs at 67.3 ± 7.2 % of the VO2 peak. Prescribing exercise at the DPBP would result in an exercise intensity that would be unlikely to elicit myocardial ischemia, yet would provide an adequate training stimulus for CAD patients.