Measurement Of Myocardial Oxygen Consumption Research Articles

Abstract P512: Association Between Resting Rate Pressure Product and All-Cause Mortality Among United States Adults

Background: Rate pressure product (RPP) is a measure of myocardial oxygen consumption and often used to quantify cardiac exercise workload. We sought to determine whether resting RPP was associated with all-cause mortality in healthy U.S. adults. Methods: This was a nationally representative, retrospective cohort study of the 1999-2018 National Health and Nutrition Examination Survey (NHANES), linked to the National Death Index through 2019. We included adult, non-pregnant participants without cardiovascular disease, kidney dysfunction, hypertension, diabetes, or current chronotropic agent use. RPP was calculated as the product of mean systolic BP (of 3 sitting BPs) and resting heart rate, and classified into quintiles (Q1≤7300, Q2 [Ref]: 7300-8250, Q3: 8250-9200, Q4: 9200-10400, Q5: >10400). We used multivariable Cox regression to estimate risk of all-cause mortality, adjusting for demographics, CVD risk factors, and comorbidities, and accounting for the survey design. Results: Among 19,954 participants (mean age 40y; 9,653 [48%] female; 8,056 [66%] non-Hispanic White), 1,013 died over a median follow-up of 10.3 years (IQR, 5.6-15.5). Adults in Q3-Q5 had significantly increased unadjusted risk of all-cause mortality compared to Q2 (HR [95% CI], Q1: 0.89 [0.50,1.58], Q3: 1.69 [1.06,2.72], Q4: 1.97 [1.16,3.34], Q5: 2.69 [1.71,4.22]). Adjustment for covariates attenuated risks of mortality but remained 61% higher for Q5 (Q2 [Ref], Q1: 1.02 [0.77,1.36], Q3: 1.09 [0.85,1.40], Q4: 1.22 [0.93,1.59], Q5: 1.61 [1.25,2.07]). When stratifying by gender, men, but not women, demonstrated increased risk of mortality in Q4 and Q5 (Women, Q4: 0.84 [0.54,1.31], Q5: 1.33 [0.89,1.98]; Men, Q4: 1.53 [1.07,2.18], Q5: 1.79 [1.30,2.46]). Conclusion: Healthy adult participants with a resting RPP greater than 10,400 had 61% higher risk of all-cause mortality compared to a RPP less than or equal to 7,300. This effect seems to be more pronounced in men than women. Further longitudinal studies are needed to understand the independent, predictive value of RPP and factors (e.g. aerobic activity) driving RPP.

The blood pressure and heart rate during sauna bath correspond to cardiac responses during submaximal dynamic exercise

ObjectivesIn the present study, the reaction of blood pressure and heart rate are examined during and after a single acute sauna application. DesignIn 19 healthy adult volunteers (7 women, aged 46.4±10.2 years, BMI 24.4±2 kg /m2), blood pressure (BP) and heart rate (HR) were measured during a 25-minute sauna session (93°C, 13 % humidity) and during a subsequent 30-minute rest period. The parameters obtained were compared with the BP and HR responses during submaximal dynamic exercise testing. ResultsThe heat exposure resulted in a significant (p<0.01) and progressive increase in systolic and diastolic BP. After the sauna bath, BP decreased and showed significantly (p<0.001) lower values compared to baseline. HR also increased continuously during heat application (p<0.001), resulting in a significant increase (p<0.001) in systolic BP x HR as a measure of myocardial oxygen consumption. After the end of the sauna session, both the BP and the HR decreased steadily (p<0.001).When comparing BP and HR during the sauna session with the reaction during a dynamic exercise test, sauna bathing was equivalent to an exercise load of about 60-100 watts. ConclusionsContrary to popular belief, acute sauna use does not lead to a reduction, but to an increase in BP and HR with a consequent increase in myocardial oxygen consumption. The cardiac load during the sauna use corresponds to a moderate physical load of 60-100 watts.

Repeatable and reproducible measurements of myocardial oxidative metabolism, blood flow and external efficiency using 11C-acetate PET

BackgroundNon-invasive approaches to investigate myocardial efficiency can help track the progression of heart failure (HF). This study evaluates the repeatability and reproducibility of 11C-acetate positron emission tomography (PET) imaging of oxidative metabolism. Methods and resultsDynamic 11C-acetate PET scans were performed at baseline and followup (47 ± 22 days apart) in 20 patients with stable HF with reduced ejection fraction. Two observers blinded to patients’ clinical data used FlowQuant® to evaluate test–retest repeatability, as well as intra- and inter-observer reproducibility of 11C-acetate tracer uptake and clearance rates, for the measurement of myocardial oxygen consumption (MVO2), myocardial external efficiency (MEE), work metabolic index (WMI), and myocardial blood flow. Reproducibility and repeatability were evaluated using intra-class-correlation (ICC) and Bland–Altman coefficient-of-repeatability (CR). Test–retest correlations and repeatability were better for MEE and WMI compared to MVO2. All intra- and inter-observer correlations were excellent (ICC = 0.95-0.99) and the reproducibility values (CR = 3%-6%) were significantly lower than the test–retest repeatability values (22%-54%, P < 0.001). Repeatability was improved for all parameters using a newer PET–computed tomography (CT) scanner compared to older PET-only instrumentation. Conclusion11C-acetate PET measurements of WMI and MEE exhibited excellent test–retest repeatability and operator reproducibility. Newer PET–CT scanners may be preferred for longitudinal tracking of cardiac efficiency.

HIGHER MYOCARDIAL OXYGEN CONSUMPTION DURING SUBMAXIMAL EXERCISE IN SUBJECTS WITH ELEVATED PULSE WAVE VELOCITY

Objective: Blood pressure (BP) during standardized workload has prognostic value regarding future cardiovascular (cv) morbidity and mortality independent of BP at rest. Pulse wave velocity (PWV) as a marker of arterial stiffness has independent prognostic value for future cv events. This study was designed to compare BP response to exercise and myocardial oxygen consumption in subjects with elevated PWV with normal subjects. Design and method: In 103 subjects (72 males, aged 50.4 ± 13.3 years, BMI 25.3 ± 3.4 kg/m2) without antihypertensive medication, PWV was measured at rest and non-invasively by Mobil-O-Graph® (I.E.M. GmbH, GERMANY). During and after standardized exercise (50–100 watts, increments 10 watts/minute) BP was measured with the cuff method and the product of heart rate during exercise and systolic BP at 100 watts (BP100W, HR100W) was calculated as a usual measure of myocardial oxygen consumption. Results: Mean PWV at rest was 7,6 ± 1,7 m/sec and correlated significantly with systolic BP100W (176,6 ± 22,2 mmHg, p < 0.01, r = 0,51) and systolic BP 3 minutes after exercise (146,7 ± 19,7 mmHg, p < 0.01, r = 0,37). In subjects with elevated PWV, both mean HR100W and mean BP100W were higher (p < 0.01) when compared with the normal subjects. Subjects with a pathological PWV presented a 23% (p < 0.05) higher myocardial oxygen consumption than normals. Conclusions: There is a considerably stronger correlation between PWV at rest and systolic BP during submaximal exercise compared to BP measurements at rest. Subjects with elevated PWV as an early sign of hemodynamic alterations, have already a considerably higher HR and systolic BP (sBP) during submaximal exercise. Therefore, the product of both HR and sBP as a measure of myocardial oxygen consumption during submaximal exercise is considerably higher in those with the elevated PWV, thus resulting in a lower total physical capacity.

A comparative analysis of rate pressure product between prehypertensives and normotensives and its correlation with body mass index

Introduction: An escalating global epidemic of overweight and obesity had contributed to a significant increase in the prevalence of prehypertension wide across the nation. While the autonomic imbalance in pre-hypertensives has been extensively studied, the association of rate pressure product as a marker of myocardial oxygen consumption, with cardiovascular dysfunction in pre-hypertensives has received less attention. The present study aimed at comparing the rate pressure product between pre-hypertensives and normotensives and to measure its correlation with body mass index. Materials and methods: About 100 male study participants in the age group of 18-23 years were recruited for the present cross sectional study and were classified into pre-hypertensives and normotensives depending on their blood pressure measurements. Rate pressure product was measured as a product of systolic blood pressure and heart rate. The results were compared between pre-hypertensives and normotensives and also within the subgroups based on their body mass index. Results: The rate pressure product was significantly higher among pre-hypertensives compared to the normotensives, with a highest value among overweight pre-hypertensives (p < 0.0001). The rate pressure product also showed a significant positive correlation with body mass index only in pre-hypertensives. Conclusion: Thus rate pressure product, as a simple non-invasive measure of myocardial oxygen consumption, could be used for early detection of hemodynamic stress in young individuals with prehypertension and the cardiovascular risk with prehypertension may be linked to the rate pressure product and level of body mass index. Keywords: Body mass index, Normotensives, Pre-hypertensives, Rate Pressure Product

PP.38.17

Objective: Even in children high blood pressure (BP) can be observed more frequengtly. Previous studies in children determined BP only at rest, but as experienced from adult investigation BP-reaction due to exercise better predicts development of hypertension in later life. Therefore 6year old children were included in a study to assess BP at rest and both BP and heart rate (HR) reactions during and after standardized exercise. Design and method: In 180 children (aged 6.4 ± 0.5 years) BP and HR were measured indirectly with a sphygmomanometer in sitting position at rest and during standardized exercise on a bicycle ergometer (2 minutes 25 watts) and at rest thereafter. During ergometry BP was measured at the end of exercise and in the 5th minute of rest. HR was monitored continuously by ECG. Results: Average BP at rest was 100 ± 10.3/68.4 ± 8.1 mmHg. According to 115/75 mmHg as upper limit of normal pressure in this age group 34 children (16.8%) could be detected as hypertensives due to BP at rest. At a workload of 25 watts BP was 125 ± 13.4/74 ± 8.4 mmHg and HR was 155.4 ± 22.3 beats / minute. BP correlated with HR during exercise (p < 0.001). According to definition of upper BP limit during exercise in adults upper limit in children was defined as 140/85 mmHg (average + 1 sd). Taking this into account 31 children (17.2%) had abnormal BP increases during exercise. In 21 children both BP at rest and during exercise were above normal. HR at rest did not differ between children with normal and elevated BP. In contrast, HR during exercise was higher (p < 0.001) in children with elevated BP when compared with normotensives (165 ± 22 /minute versus 151 ± 21/minute). Consequently, product of HR x systolic BP, a measure of myocardial oxygen consumption (MOC), was 32% higher (p < 0.001) in hypertensives when compared with their normotensive counterparts. Conclusions: Even in young children a high percentage has elevated BP at rest and during exercise demonstrating impaired vasodilatation during exercise. Furthermore, elevated BP is associated with higher HR during exercise, which might be due to an increase in sympatho-adrenergic activity, which increases MOC during exercise.

South Asians Have Elevated Postexercise Blood Pressure and Myocardial Oxygen Consumption Compared to Europeans Despite Equivalent Resting Pressure

BackgroundStroke mortality rate is higher in South Asians than in Europeans, despite equivalent or lower resting blood pressure (BP). Elevated recovery BP after exercise predicts stroke, independently of resting values. We hypothesized that South Asians would have adverse postexercise hemodynamics and sought explanations for this.Methods and ResultsA population-based sample of 147 European and 145 South Asian middle-aged men and women performed the Dundee 3-minute step test. Cardiovascular risk factors were measured. BP, heart rate, and rate–pressure product, a measure of myocardial oxygen consumption, were compared. With 90% power and 5% significance, we could detect a difference of 0.38 of a standard deviation in any outcome measure. Resting systolic BP was similar in South Asians (144 mm Hg) and Europeans (142 mm Hg) (P=0.2), as was exercise BP (P=0.4). However, recovery systolic BP at 3 minutes after exercise was higher in South Asians by 4.3 mm Hg (95% confidence interval [CI], 0.2 to 8.3 mm Hg; P=0.04). This effect persisted when adjusted for exercise BP and work effort (5.4 mm Hg [95% CI, 2.2 to 8.7 mm Hg; P=0.001]). Adjustment for baroreflex insensitivity and greater aortic stiffness in South Asians contributes greatly to attenuating this ethnic difference (1.9 mm Hg [95% CI, −0.9 to 4.6 mm Hg; P=0.4]). Similarly, rate–pressure product recovery after exercise was impaired in South Asians by 735 mm Hg/min (95% CI, 137 to 1334 mm Hg/min; P=0.02); again, adjustment for baroreflex insensitivity and aortic stiffness attenuated this difference (261 mm Hg/min [95% CI, −39 to 561 mm Hg/min; P=0.3]).ConclusionPostexercise recovery of BP and rate–pressure product is impaired in South Asians compared to Europeans even though resting and exercise BP are similar. This is associated with the autonomic dysfunction and aortic stiffness in South Asians. (J Am Heart Assoc. 2012;1:e000281 doi: 10.1161/JAHA.111.000281.)

Aortic reservoir function, estimated myocardial demand and coronary perfusion pressure following steady‐state and interval exercise

Aortic reservoir function is a measure of the aorta's ability to distribute blood during diastole, attenuating the pulsatility of blood flow, and is important in balancing cardiac flow. Effects of acute high versus moderate exercise intensity on reservoir function and cardiac energetics is unknown. Eighteen athletes completed a interval (INT) and steady-state (SS) cycling bout at 60% of VO(2) peak. Reservoir function was calculated as the ratio of diastolic run-off to stroke volume and expressed as a percentage. Coronary perfusion pressure was derived from tissue Doppler imaging and echocardiography. Systolic tension-time integral (TTI) from the aortic pressure waveform served as a measure of myocardial oxygen consumption. All measures were made at rest, 30-min postexercise and 60-min postexercise. Average reservoir function before SS was 76%, which was reduced to 62% 30-min post-SS and 67% 60-min post-SS (P<0.05). Significantly greater reductions in reservoir function were seen following INT (from 71% pre-INT to 45% 30-min post-INT and 53% 60-min INT, P<0.05). Estimated coronary perfusion pressure was reduced 30min following INT but not SS; both bouts reduced coronary perfusion pressure at 60-min postexercise (P<0.05). TTI increased following both INT and SS at 30- and 60-min postexercise with greater increases following INT (P<0.05). Following exercise, reservoir function was associated with TTI (P<0.05), but not coronary perfusion pressure (P>0.05). We conclude that reservoir function is attenuated following acute SS and INT, but these reductions were greater post-INT, suggesting that exercise intensity affects reservoir function. Reduction of reservoir function following exercise is related to TTI, a reflection of myocardial oxygen consumption but apparently not associated with coronary perfusion pressure.

Blood Pressure And Heart Rate At Rest And During Exercise In 6-year-old Children

PURPOSE: Even in children an increase in cardiovascular risk profile and especially in high blood pressure (BP) can be observed in industrialized countries. Therefore 6-year-old children were included in a study to assess BP at rest and BP and heart rate (HR) reaction during exercise. METHODS: In 180 children (aged 6.4±0.5 years) BP and HR were measured indirectly with a mercury sphygmomanometer according to the Riva-Rocci-Korotkoff cuff method in a sitting position at rest and during standardized ergometric exercise on a bicycle ergometer (2 minutes 25 watts) and at rest after exercise testing. During the bicycle ergometry BP readings were taken the last 15 seconds of the 2nd minute and 5 minutes at rest after exercise. HR was monitored by ECG continuously during the test. RESULTS: Average BP at rest was 100±10.3/68.4±8.1 mmHg. According to 115/75 mmHg as upper limit of normal pressure in this age group 34 children (16.8%) could be detected as being hypertensive due to BP at rest. During exercise at a workload of 25 watts BP was 125±13.4/74±8.4 mmHg. Corresponding HR was 155.4±22.3 beats / minute. There was a significant positive correlation between BP and HR during exercise (p<0.001). According to definition of upper BP limit during exercise in adults upper limit in children was defined as 140/85 mmHg (average + 1 standard deviation). Taking this into account 31 children (17.2%) had abnormal BP increases during exercise. In 21 children both BP at rest and during exercise were above normal. HR at rest did not differ between children with normal and elevated BP. In contrast, HR during exercise was significantly higher (p<0.001) in children with elevated BP when compared with normotensive subjects(165±22 /minute versus 151±21/minute). Consequently, the product of HR x systolic BP, a measure of myocardial oxygen consumption, was 32% higher (p<0.001) in hypertensives when compared with their normotensive counterparts. CONCLUSIONS: Even in young children a high percentage has elevated BP at rest and during exercise demonstrating an impaired vasodilatation during exercise. Furthermore, elevated BP is associated with an increased heart rate during exercise, which might be due to increased sympahto-adrenergic activity, which elevates myocardial oxygen consumption during exercise.

Hibernating Myocardium

See related article, pages 103–112 Winter hibernation carries the promise of rejuvenation in the spring. In a similar fashion, myocardial “hibernation” describes a clinical phenomenon in which patients with ischemic left ventricular dysfunction demonstrate improved cardiac function following bypass surgery.1 The signature of myocardial hibernation is decreased blood flow with preserved glucose uptake, as demonstrated by positron emission tomography imaging, and identifies individuals with ischemic cardiomyopathy who may benefit from revascularization.2 In experimental models of hibernating myocardium, oxygen consumption is reduced in the absence of active ischemia.3,4 This implies that hibernation is a coordinated response to balance myocardial energy utilization with energy production capacity.5 However, within hibernating myocardium, several morphological and functional changes have been observed that can identify regions in which complete revascularization may not result in normalization of contraction.6–10 In fact, those myocardial regions with the greatest metabolic abnormalities in the hibernating tissue demonstrate the longest delay in recovery.11 In the current issue, Page et al12 demonstrate that the process of hibernation is associated with altered expression of mitochondrial proteins. Using 2D differential-in-gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry in a swine model of hibernation, they have found that key mitochondrial proteins associated with the electron transport chain are reduced. The functional importance of the decreased protein expression is documented by reduced activity measurements of the pyruvate dehydrogenase complex, cytochrome c oxidase, and citrate synthase. The parallel reductions in mitochondrial proteins and contractile function 5 months after placement of the coronary artery constrictor suggest that the “downregulation” of electron transport proteins is related to the reduced oxygen consumption. In fact, the reductions in ATPase correlate with the reduction in subendocardial blood flows in the hibernating myocardium. In addition, “upregulation” of several cytosolic proteins has been observed, including …

Cardiac Positron Emission Tomography

Positron emission tomography (PET) is a non-invasive radionuclide imaging technique that, when used with appropriate radiotracers and kinetic models, permits absolute quantitative measurements of myocardial perfusion, metabolism and receptor densityin vivo. Assessment of the coronary vasodilator reserve (ratio of hyperaemic to baseline myocardial blood flow) has provided insights into both the functional significance of coronary artery stenoses in patients with coronary artery disease and abnormalities of the coronary microcirculation in patients with different cardiomyopathies. The use of PET to identify myocardial viability (by preserved uptake of ¹⁸F-fluoro-deoxy-glucose) allows the localisation of hibernating myocardium and the quantification of infarct size in patients with coronary artery disease. Measurements of myocardial oxygen consumption using PET with oxygen-15 and ¹¹C-acetate have provided information on myocardial metabolism during ischaemia and myocardial stunning. Tracers and kinetic models have also been developed permitting investigation of the role of the cardiac autonomic nervous system in the pathophysiology of heart failure and arrhythmogenesis. The high spatial resolution of modern PET cameras and the validation of new tracers may provide further insights into cardiac pathophysiology, e.g. to assess the transmural distribution of myocardial blood flow and metabolism across the left ventricular wall.

Exaggerated chronotropic and energetic response to dobutamine after orthotopic cardiac transplantation

Background: After heart transplantation, the transplanted denervated heart displays both an exaggerated chronotropic and an exaggerated inotropic response to circulating catecholamines. This study assessed whether denervated transplanted hearts also display an exaggerated energetic response when challenged with dobutamine. Methods and Results: A total of 18 heart transplant recipients and 14 normal volunteers underwent measurements of myocardial oxygen consumption (MVO 2), external work (EW), and pressure-volume area (PVA), at rest and during infusion of dobutamine. At rest, calculated myocardial (PVA/MVO 2) and mechanical (EW/MVO 2) efficiencies were similar among transplant recipients and normal volunteers. During low-dose dobutamine infusion (8 μg/kg/min), transplant recipients exhibited a larger increase in heart rate (to 126 ± 14 vs 87 ± 26 beats/min, p < 0.001) and MVO 2 (to 269 ± 43 vs 233 ± 19 J/min/100g, p < 0.05) and a smaller increase in EW (64 ± 18 vs 72 ± 13 J/min/100g, p < 0.05) and PVA (70 ± 16 vs 81 ± 13 J/min/100g, p < 0.05) than did normal volunteers. As a result, both myocardial (26 ± 4 vs 35 ± 4%, p < 0.05) and mechanical (23 ± 4 vs 30 ± 4%, p < 0.001) efficiencies were lower during dobutamine infusion in transplant recipients than in normal volunteers. During the infusion of a higher dose of dobutamine (19 μg/kg/min), the chronotropic and inotropic responses of heart transplant recipients were even more exaggerated. The fall in myocardial efficiency induced by dobutamine correlated with the increase in heart rate ( r = −0.58) and could be reproduced in normal volunteers by coadministration of atropine. Conclusions: Transplant recipients exhibit a larger fall in contractile efficiency and a larger oxygen-wasting effect during dobutamine infusion than do normal volunteers. Because normal volunteers pre-medicated with atropine presented with a similar increase in heart rate and a similar fall in efficiency, the exaggerated energetic response of transplanted hearts to dobutamine likely resulted from the same mechanisms as their chronotropic supersensitivity, i.e., the loss of inhibitory parasympathetic innervation.

Increased aortic compliance maintains left ventricular performance at lower energetic cost.

The aim of this study was to investigate left ventricular contractility and energetic cost of cardiac ejection under conditions of acute increase in aortic compliance. In six anaesthetized pigs, ascending aortic compliance was increased by adding a volume chamber in parallel to the ascending aorta. Systemic vascular parameters, including characteristic impedance, peripheral resistance, total vascular compliance, and inertance, were estimated with a four-element windkessel model. Arterial elastance was derived from these parameters. Left ventricular systolic function was assessed by end-systolic pressure-volume relationship (end-systolic elastance), and stroke work. Pressure-volume area was used as a measure of myocardial oxygen consumption. Heart rate remained constant during the experimentation. Adding the aortic volume chamber significantly increased vascular compliance from 0. 95+/-0.08 to 1.17+/-0.06 ml/mmHg (P<0.01), while inductance, characteristic impedance, peripheral resistance, and arterial elastance remained statistically at basal values, respectively 0. 0020+/-0.0003 mmHg.s(2)/ml, 0.105+/-0.009 mmHg.s/ml, 1.27+/-0.12 mmHg.s/ml, and 2.43+/-0.21 mmHg/ml. During the same interval, stroke work and pressure-volume area decreased respectively from 2700+/-242 to 2256+/-75 mmHg.ml (P<0.01), and from 3806+/-427 to 3179+/-167 mmHg.ml (P<0.01). Stroke work and pressure-volume area decreased at matched end-diastolic volumes. In contrast, end-systolic elastance, ejection fraction, and stroke volume remained statistically unchanged, respectively at 2.29+/-0.14 mmHg/ml, 48.1+/-2.1 %, and 32. 4+/-1.7 ml. These data suggest that, when facing an increased aortic compliance, the left ventricle displays unchanged contractility, but the energetic cost of cardiac ejection is significantly decreased. These data may be of clinical importance when choosing an artificial prosthesis for ascending aortic replacement.

Simultaneous noninvasive determination of regional myocardial perfusion and oxygen content in rabbits: toward direct measurement of myocardial oxygen consumption at MR imaging.

To determine whether myocardial arterial perfusion and oxygen concentration can be quantified simultaneously from the same images by using spin labeling and the blood oxygenation level-dependent (BOLD) effect with fast spin-echo (SE) imaging. A T2-weighted fast SE pulse sequence was written to image isolated, arrested, blood-perfused rabbit hearts (n = 6) at 4.7 T. Perfusion images with intensity in units of milliliters per minute per gram that covered the entire left ventricle with 0.39 x 0.39 x 3.00-mm resolution were obtained in less than 15 minutes with a 32-fold reduction in imaging time from that of a previous study. Estimates of oxygen concentration were made from the same images acquired for calculation of perfusion images. Estimates of regional myocardial oxygen content could be made from the perfusion images; this demonstrated the feasibility of three-dimensional calculation of regional oxygen consumption, which requires concomitant measurement of both oxygen content and flow. Fast SE imaging was shown to be as sensitive to hemoglobin desaturation as standard SE imaging. Perfusion abnormalities and oxygen deficits were easily identified and verified qualitatively with gadopentetate dimeglumine on both perfusion and BOLD images obtained after coronary arterial ligation. T2-weighted fast SE imaging combined with perfusion-sensitive spin labeling can be used to measure myocardial arterial perfusion and oxygen concentration. This provides the groundwork for calculation of regional myocardial oxygen consumption.

In situ fiber-optic oxygen consumption measurements from a working mouse heart.

Luminescence-based imaging-fiber oxygen sensors (IFOSs) were utilized for the in situ measurement of oxygen consumption from intact perfused mouse hearts. IFOSs were fabricated using a technically expedient, photoinitiated polymerization reaction whereby an oxygen-sensitive polymer matrix was immobilized in a precise location on an imaging fiber's distal face. The oxygen-sensing layer used in this work comprised a transition metal complex, Ru(Ph2phen)3(2+), entrapped in a gaspermeable photopolymerizable siloxane membrane (PS802). The transduction mechanism was based upon the oxygen collisional quenching of the ruthenium complex luminescence; detection was performed utilizing an epi-fluorescence microscope/charge coupled device imaging system. IFOS measurements from working mouse hearts were validated through concurrent, blind, ex situ blood gas analyzer (BGA) measurements. The BGA and IFOS methodologies were utilized successfully to measure oxygen concentrations in aortic and pulmonary artery perfusates from the working mouse heart before and after isoproterenol administration. Coupled with coronary-flow measurements, these data were used to calculate myocardial oxygen consumption. Regression analysis of measurements of myocardial oxygen consumption showed that there was a strong correlation between the values generated by the BGA sampling and those obtained via in situ IFOS methods. To our knowledge, this research represents the first report of in situ fiber-optic sensor monitoring of oxygen content from the intact, beating mouse heart.

Enalaprilat Improves the Impaired Left Ventricular Pump Function during Exercise in Hypertensives with Coronary Microangiopathy and with Coronary Artery Disease

Background: The pump function during exercise can be disturbed not only in hypertensives with coronary artery disease (CAD), but also in those with a normal angiogram. Methods: In 10 hypertensive patients (group 1; aged 52±4 years, 1 men, 9 women) with ST segment depression during exercise and concomitant angina pectoris but normal coronary angiograms (microangiopathy) and without left ventricular hypertrophy (LVMI <110 g/m²), the left ventricular function at rest and during exercise was studied by cardiac catheterization and compared with 10 hypertensives with CAD (group 2; aged 57.6±4 years, 7 men, 3 women) and 10 hypertensives without ST segment depression (group 3; aged 51.8±5 years, 10 men) before and after intravenous administration of 1.25 mg enalaprilat. Results: The pulmonary capillary wedge pressure (PCWP) was normal at rest and pathologically increased at 60±13 W only in groups 1 and 2 (27.2±3 and 32.2±8 mm Hg, respectively), but not in group 3 (12.2±4 mm Hg; p<0.001). At the identical load level, the PCWP in patients with microangiopathy (group 1) was significantly (p<0.01) reduced after enalaprilat (–21.7%) and even normalized in 5 of 10 patients. This was accompanied by a significant (p>0.01) decrease in ST segment depression (–73.9%) and in the occurrence of angina pectoris, despite the fact that the rate–pressure product as a measure of myocardial oxygen consumption was significantly (p<0.05) increased. Also in patients with CAD enalaprilat had a significant effect on PCWP (p<0.01), ST segment depression (p<0.01), occurrence of angina pectoris (p<0.001), cardiac index (p<0.05), and stroke index (p<0.05) during exercise. In group 3 there were no significant changes in PCWP, cardiac index, and stroke index after enalaprilat either at rest or during exercise. Conclusion: The functional improvement under the action of enalaprilat suggests that the advantages of the drug may be mediated mainly through an increase in myocardial blood flow and that angiotensin II might be involved in the restricted increase in coronary blood flow during dynamic exercise in hypertensives with coronary microangiopathy.

Spin Label Oximetry to Assess Extracellular Oxygen During Myocardial Ischemia

We describe real-time measurement of myocardial oxygen consumption during ischemia in the intact heart. Measurement of extracellular oxygen concentration during myocardial ischemia by spin label oximetry has been limited by ischemia-induced reduction of the neutral, water-soluble nitroxide TEMPONE. We have overcome this problem by encapsulating the nitroxides. Isolated immature (7–10 d old) rabbit hearts ( n = 8) were perfused aerobically within the cavity of a loop gap resonator with bicarbonate buffer containing an oxygen-sensitive, lipid-soluble nitroxide ( 14N-TEMPO laurate in FC-43 perfluorocarbon micelles) and a much less oxygen-sensitive and positively charged nitroxide ( 15N-TEMPO choline in multilamellar vesicles) as an internal standard. The ratio of the ESR signal amplitudes of these nitroxides was used as a sensitive index of oxygen concentration. Sequestration of the nitroxides decreased their reduction rate by ascorbate in comparison with nonsequestered nitroxides. Hearts were subjected to 60 min of global no-flow ischemia at 20°C. Extracellular oxygen content (mean ± SD) during aerobic perfusion was 1195 ± 55 μmol/liter. The electron spin resonance signal from TEMPO laurate increased with the onset and progression of ischemia, consistent with a decrease in extracellular oxygen, while the signal for TEMPO choline was relatively unchanged. Extracellular oxygen content after 40 and 60 min of ischemia was reduced to 393 ± 27 μmol/liter ( p < .05) and 61 ± 5 μmol/liter ( p < .05), respectively. We conclude that spin-label oximetry can directly and precisely measure myocardial oxygen consumption at constant temperature during ischemia in the intact heart. Copyright © 1996 Elsevier Science Inc.

A novel inotropic vasodilator, OPC-18790, reduces myocardial oxygen consumption and improves mechanical efficiency with congestive heart failure

We analyzed the left ventricular (LV) pressure-volume relation and obtained direct measurements of myocardial oxygen consumption (MVo 2) before and after drug administration in 21 patients with New York Heart Association functional class II to III congestive heart failure to compare the mechanoenergetic effects of OPC-18790, a novel inotropic agent, and dobutamine. Pressure-volume data were obtained by the conductance method, and MVo 2 measurements were obtained with a double-thermistor coronary sinus catheter before and after administration of OPC-18790 and dobutamine. The LV end-diastolic volume index decreased significantly without an increase in the heart rate after administration of OPC-18790, unlike that after administration of dobutamine. Both drugs significantly increased the LV contractility index (E max) and caused similar improvements in ventricular-arterial coupling. OPC-18790 significantly reduced MVo 2, whereas dobutamine increased MVo 2. The ratio of the pressure-volume area to myocardial oxygen consumption (PVA/MVo 2) remained unchanged after administration of OPC-18790 and decreased after administration of dobutamine. The ratio of external work to the pressure-volume area (EW/PVA) was similarly increased by both drugs, resulting in an improvement in mechanical efficiency (EW/MVo 2) with OPC-18790 ( p < 0.05) and in a deterioration with dobutamine ( p < 0.05). OPC-18790 had an energetic advantage over dobutamine in spite of its positive inotropic effect. Our findings suggest that OPC-18790 may be useful for the treatment of patients with congestive heart failure.

Milrinone

To evaluate the hemodynamic effects of intravenous milrinone in neonates with low cardiac output after cardiac surgery. Prospective cohort study. Pediatric cardiac intensive care unit. Ten neonates with low cardiac output (cardiac index of < or = 3.0 L/min/m2) after corrective cardiac surgery were enrolled in the study. The neonates' ages ranged from 3 to 27 days (median 5) and their weights ranged from 2.0 to 4.8 kg (median 3.7). The diagnoses were: transposition of the great arteries (n = 6, including two with ventricular septal defect), tetralogy of Fallot (n = 2), truncus arteriosus (n = 1), and total anomalous pulmonary venous connection (n = 1). Milrinone was intravenously administered in three stages: a) baseline stage, in which patients had a stable hemodynamic status, ventilation and gas exchange, hemostasis, and body temperature; b) loading stage, in which a 50 microgram/kg intravenous loading dose of milrinone was administered over 15 mins; and c) infusion stage, in which milrinone was continuously infused at 0.50 microgram/kg/min for 30 mins. The mean heart rate increased after the loading stage (149 +/- 13 to 163 +/- 12 beats/min, p < .01) but slowed during the infusion stage (154 +/- 11 beats/min, p < .01 vs. loading stage). Both right and left atrial pressures were lowered in all ten neonates. Compared with baseline, mean arterial pressure decreased after the loading stage (66 +/- 12 to 57 +/- 10 mm Hg, p < .01) but did not decrease further at the infusion stage (59 +/- 12 mm Hg); changes in mean pulmonary arterial pressure were comparable. Cardiac index increased from a baseline mean of 2.1 +/- 0.5 to 3.0 +/- 0.8 L/min/m2 (p < .01) with the loading stage, and was maintained at 3.1 +/- 0.6 L/min/m2 during the infusion stage. Systemic vascular resistance index decreased below baseline values with loading, from 2136 +/- 432 to 1336 +/- 400 dyne.sec/cm5.m2 (p < .01), and pulmonary vascular resistance index also decreased with loading dose of milrinone, from 488 +/- 160 to 360 +/- 120 dyne.sec/cm5.m2 (p < .01). There was no change in the rate pressure index, an indirect measurement of myocardial oxygen consumption, throughout the study. Administration of milrinone in neonates with low cardiac output after cardiac surgery lowers filling pressures, systemic and pulmonary arterial pressures, and systemic and pulmonary vascular resistances, while improving cardiac index. Milrinone increases heart rate without altering myocardial oxygen consumption. While milrinone appears to be effective and safe during short-term use, the relative distribution of inotropic and vasodilatory properties of milrinone remains to be elucidated.

Antiarrhythmic effects of BN‐063, a newly synthesized adenosine A1 agonist, on myocardial ischaemia in rats

1. It has been shown that adenosine is able to reduce the severity of arrhythmias induced by myocardial ischaemia. In isolated preparations, the antiarrhythmic effect of adenosine on ventricular myocardium is known to antagonize the catecholamine-induced stimulation of intracellular cyclic AMP production, an effect mediated via adenosine A1 receptors. 2. The aim of this study was to evaluate the antiarrhythmic effect of BN-063 (1-cyclopropylisoguanosine), a newly synthesized selective adenosine A1 agonist, on ventricular arrhythmias in rats. 3. Arrhythmias were induced by left coronary artery ligation or by administration of isoprenaline (7 mg kg-1) subcutaneously. Pretreatment with BN-063 (0.25, 0.5 and 1.0 mg kg-1) 10 min prior to occlusion significantly delayed the onset of ventricular arrhythmias, reduced the total number of ventricular premature contraction (VPC) and ventricular tachycardia (VT), decreased the incidence of VT and ventricular fibrillation (VF) and mortality during the first 30 min following left coronary artery ligation. In contrast, pretreatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1 antagonist, was arrhythmogenic during the ischaemic period. The rate-pressure product, an index for indirect measurement of myocardial oxygen consumption, was also significantly reduced by BN-063 during ligation time. 4. The incidence of VT, VF and mortality was also significantly reduced when BN-063 was administered after left coronary artery ligation. 5. BN-063 converted the VF induced by isoprenaline to normal sinus rhythm and improved the survival rate. 6. It is concluded that, through activation of adenosine A1 receptors, BN-063 can suppress ventricular arrhythmias induced by myocardial ischaemia and catecholamines. The antiarrhythmic actions of BN-063 may be mediated by reducing heart rate and antagonizing the stimulatory effects of catecholamine in myocardial ischaemia.