Myocardial Oxidative Metabolism Research Articles

In vivo measurement of myocardial oxidative metabolism and blood flow does not show changes in cancer patients undergoing doxorubicin therapy.

The aim was to investigate in patients receiving doxorubicin whether any alteration in myocardial oxidative metabolism or blood flow as assessed by positron emission tomography (PET) could be observed either after the first dose of the drug, or during its chronic administration. Six female non-heart-failure cancer patients treated with doxorubicin were included in a longitudinal study. Resting radionuclide cineangiography and PET scanning with carbon-11 acetate were performed the day before the initiation of doxorubicin treatment at a dosage of 50 mg/m2 every 3 weeks, and 3 weeks after the cumulative administration of 300 mg/m2 (chronic toxicity). In addition, PET was performed 24 h after the first administration of doxorubicin (evaluation of acute toxicity). Myocardial oxidative metabolism and blood flow were assessed by PET (acute and chronic toxicity), and left ventricular ejection fraction was measured by radionuclide angiography (chronic toxicity). Using PET for both acute and chronic toxicity evaluations, no significant effect of doxorubicin was observed either on the flux through the tricarboxylic acid (TCA) cycle or on myocardial blood flow. However, systolic left ventricular function showed a small but significant impairment after the administration of 300 mg/m2 of doxorubicin. Other hypotheses should be explored to better explain the predominant mechanisms of the cardiotoxicity of anthracyclines in humans.

Myocardial hibernation: another view

In the following, three newer concepts are brought together: myocardial hibernation, heterogeneity in myocardial blood flow and oxidative metabolism, and effects of hibernating animal serum on non-hibernators. Myocardial hibernation is viewed as a protective mechanism that helps to maintain myocardial integrity and viability by down-regulating contractile function as an adaptation to reduced blood flow. Myocardial flow is considerably heterogeneous. Consequently, oxygen supply to the myocardium is also heterogeneous. Many lines of evidence show a close correlation between regional flow and regional metabolism. In low-flow/low-metabolism areas, myocardial function must be reduced, since the myocardium would otherwise undergo necrosis. Thus, others and we hypothesize that function must be down-regulated to induce hibernation in low-flow areas. Because no regional histologic differences exist (the mitochondria are uniformly distributed within the myocardium), the pattern of heterogeneity seems to shift over time. Hence, we hypothesize that such very regional hibernation presents an evolutionary, protective mechanism, permitting subsequent myocardial areas to rest within the ceaselessly working heart. We also hypothesize that this mechanism ensures the down-regulation of function following myocardial ischemia in order to induce myocardial hibernation on a broader level. Surprisingly, a substance (opioid in nature) contained in hibernator serum both induced hibernation-like state in non-hibernators and suppressed myocardial oxygen consumption. Thus, we lastly hypothesize that myocardial hibernation is a remnant of the early stages of evolution and is closer to physiologic hibernation than traditionally viewed.

Effect of plasma insulin level on myocardial blood flow and its mechanism of action

Considerable evidence suggests that coronary endothelium regulates myocardial blood flow and metabolism by elaborating vasoactive substances. The physiologic signals mediating this process are uncertain. To test the hypothesis that the process is influenced by physiologic variation in local insulin concentration, we examined the effect of direct intracoronary insulin infusion on myocardial blood flow and oxidative substrate metabolism in 10 patients with coronary heart disease. Ten men (aged 51 to 68 years) who were fasting received a 60-minute intracoronary infusion of insulin at a rate (10 mU/min) sufficient to raise coronary venous plasma insulin from 12 ± 4 to 133 ± 17 mU/ml without increasing the systemic insulin level. Local coronary hyperinsulinemia increased coronary sinus blood flow in every subject, from 50 ± 4 to 61 ± 6 ml/min (p <0.01). Insulin also increased myocardial uptake of glucose (from 6 ± 1 to 17 ± 6 mmol/min) and lactate (from 8 ± 2 to 12 ± 5 mmol/min), resulting in ∼30% increase in total oxidative substrate uptake, but without increasing myocardial oxygen consumption (7.0 ± 0.7 vs 7.1 ± 0.8 ml/min). Thus, physiologic elevation in the local plasma insulin concentration increases coronary blood flow in the absence of any increase in myocardial oxygen demand or consumption, suggesting a primary reduction in coronary tone, while simultaneously restraining the oxidation of imported substrates. These observations are consistent with insulin-mediated elaboration of vasoactive and/or paracrine factors within the coronary circulation.

Myocardial oxidative metabolism is promoted by repeat ischemia: Experimental validation with I-123 BMIPP

Myocardial oxidative metabolism is promoted by repeat ischemia: Experimental validation with I-123 BMIPP

Increased myocardial lactate oxidation in lambs with aortopulmonary shunts at rest and during exercise.

Free fatty acids are the major fuels for the myocardium, but during a higher load carbohydrates are preferred. Previously, we demonstrated that myocardial net lactate uptake was higher in lambs with aortopulmonary shunts than in control lambs. To determine whether this was caused by an increased lactate uptake and oxidation or by a decreased lactate release, we studied myocardial lactate and glucose metabolism with 13C-labeled substrates in 36 lambs in a fasting, conscious state. The lambs were assigned to two groups: a resting group consisting of 8 shunt and 9 control lambs, and an exercise group (50% of peak O2 consumption) consisting of 9 shunt and 10 control lambs. Myocardial lactate oxidation was higher in shunt than in control lambs (mean +/- SE, rest: 10.33 +/- 2.61 vs. 0. 17 +/- 0.82, exercise: 38.05 +/- 8.87 vs. 16.89 +/- 4.78 micromol. min-1. 100 g-1; P < 0.05). There was no difference in myocardial lactate release between shunt and control lambs. Oxidation of exogenous glucose, which was approximately zero at rest, increased during exercise in shunt and control lambs. The contribution of glucose and lactate to myocardial oxidative metabolism increased during exercise compared with at rest in both shunt and control lambs. We conclude that myocardial lactate oxidation is higher in shunt than in control lambs, both at rest and during exercise, and that the contribution of carbohydrates in myocardial oxidative metabolism in shunt lambs is higher than in control lambs. Thus it appears that this higher contribution of carbohydrates occurs not only in the case of pressure-overloaded hearts but also in myocardial hypertrophy due to volume overloading.

Extent of myocardial damage in regions with reverse redistribution at 3 h and at 24 h on 201Tl SPET: evaluation based on regional myocardial oxidative metabolism.

Reverse redistribution (RRD) of 201Tl is often observed in patients with recent myocardial infarction. However, the difference in the extent of myocardial damage between regions with 3-h RRD and those with 24-h RRD remains unknown. Accordingly, we investigated RRD from the standpoint of myocardial oxidative metabolism. Carbon-11 (11C) acetate dynamic myocardial PET scanning was performed at rest in 14 patients with recent myocardial infarction, and the clearance rate constant (Kmono) of 11C-acetate was calculated in 6-7 ROIs on the transaxial image in each patient using a monoexponential fit as an index of myocardial oxidative metabolism. Exercise 201Tl myocardial SPET was also performed. Ninety-two regions corresponding to the PET study were then classified based on the findings of transaxial 201Tl SPET imaging; that is, regions with reverse redistribution, regions with severely decreased 201Tl activity or no 201Tl activity on the 24-h delayed images, and regions with normal 201Tl activity throughout the study. Kmono in regions with reverse redistribution (0.051 +/- 0.009 min-1) was significantly lower than that in regions with normal 201Tl activity throughout the study (0.066 +/- 0.011 min-1) (P < 0.001) but significantly higher than that in regions with severely decreased or no 201Tl activity on the 24-h delayed images (0.037 +/- 0.003 min-1) (P < 0.001). Percent Kmono (i.e. Kmono in region with RRD/the mean of Kmono in all regions with a normal 201Tl SPET result) was significantly lower in the 3-h RRD regions (81.3 +/- 6.3%) than in the 24-h RRD regions (87.6 +/- 6.1%) (P < 0.05). Impairment of myocardial oxidative metabolism is observed in regions with RRD, suggesting that RRD corresponds to mild myocardial damage. Reverse redistribution on 24-h delayed images may indicate much milder myocardial damage compared with RRD on 3-h delayed images.

Prior preconditioning by ischemia or sevoflurane improves cardiac work per oxygen use in isolated guinea pig hearts after global ischemia.

Cardiac ischemic preconditioning is a phenomenon typically described as brief periods of ischemia that renders the myocardium resistant to subsequent longer term ischemia. This is often assessed by observations of reduced infarct size, attenuated mechanical dysfunction, or limited ultrastructural abnormality on reperfusion (1). The degree of mechanical and electrical cardioprotection provided by myocardial preconditioning and the mechanisms that potentially mediate its effects have been the focus of intense investigation. However, in only a few studies have there been attempts to understand how ischemic injury alters myocardial oxidative metabolism after reperfusion (2–5). The effect of preconditioning maneuvers on altering myocardial O2 utilization after ischemia and reperfusion is even less well examined. Myocardial O2 consumption is highly influenced by the contractile state of the myocardium and so it may be lower, as is mechanical function, after reperfusion. It is important to know if the available O2 is better or worse utilized to perform cardiac work after preconditioning, ischemia, and reperfusion.KeywordsIschemic PreconditionVolatile AnestheticGlobal IschemiaLeft Ventricular Develop PressureCardiac WorkThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Determination of deoxymyoglobin changes during graded myocardial ischemia: an in vivo 1H NMR spectroscopy study.

1H NMR spectroscopy was used to detect the proximal histidyl Ndelta proton signal of deoxymyoglobin from canine hearts in vivo during graded myocardial ischemia. The NMR signal intensity provided an indicator of intracellular oxygenation in myocardium. The relationship between the myocardial blood flow and the deoxymyoglobin concentration was successfully measured during resting, partial, and complete coronary artery occlusion conditions. The results demonstrate the feasibility to detect deoxymyoglobin using a 1H NMR spectroscopy technique in living hearts for the first time and the possibility to use this technique for investigating myocardial oxidative metabolism nondestructively and repetitively.

Cardiac Disease in Chronic Uremia: Pathophysiology

In chronic uremia, apart from frequent coronary lesions, further abnormalities of the heart recently reported include (1) left ventricular hypertrophy, not completely explained by hypertension, (2) interstitial myocardial fibrosis, for which parathyroid hormone is a permissive factor, (3) reduced myocardial perfusion reserve, secondary to functional and structural changes of intramyocardial arteries and to reduced capillary density, (4) abnormalities of myocardial metabolism, which act in concert with restriction of blood flow by microvascular abnormalities to reduce ischemic tolerance. Such metabolic abnormalities include diminished responsiveness to beta-adrenergic stimulation, abnormal control of intracellular calcium concentration, impaired maintenance of energy-rich nucleotide concentrations under conditions of ischemia, impaired insulin-mediated glucose uptake, and abnormalities of myocardial oxidative metabolism.

Superiority of C-11 acetate compared with F-18 fluorodeoxyglucose in predicting myocardial functional recovery by positron emission tomography in patients with acute myocardial infarction

In patients with chronic coronary artery disease, preservation of myocardial oxidative metabolism measured by positron emission tomography (PET) with 11C-acetate is a more accurate predictor of subsequent myocardial functional recovery than is maintenance of glucose metabolism estimated with 18F-fluorodeoxyglucose. However, whether measurements of myocardial oxidative metabolism are more accurate than measurements of glucose metabolism in predicting functional recovery in patients with recent myocardial infarction is unknown. Myocardial oxidative metabolism was measured within 10 days of infarction in 19 patients by analysis of the rate of myocardial clearance of 11C-acetate. Metabolism of glucose was assessed by analysis of the uptake of 18F-fluorodeoxyglucose. Criteria for prediction of the recovery of function based on measurements of oxidative metabolism and glucose metabolism were compared. Threshold criteria with 11C-acetate exhibited superior positive and negative predictive values (89% and 73%, respectively) compared with the criteria of 18F-fluorodeoxyglucose (65% and 57%, respectively) (p < 0.025). In addition, the magnitude of functional recovery after revascularization correlated with the severity of the metabolic abnormality present initially. In patients with recent myocardial infarction, the extent of functional recovery can be predicted accurately by measurement of regional oxidative metabolism by PET with 11C-acetate, and these measurements are superior to those of 18fluorodeoxyglucose.

Improvement of Myocardial Ischemic Dysfunction with Dichloroacetic Acid

We investigated metabolic factors related to the recovery of myocardial function during ischemia and after reperfusion using dichloroacetic acid (DCA) in canine models with repeated 10-min regional ischemia and reperfusion. Administration of 100 mg/kg DCA, which activates pyruvate dehydrogenase, improved regional wall motion significantly as compared with the nontreated controls (p < 0.05). The mechanism was studied by determining changes in myocardial levels of pH, glucose, lactate, and nonesterified fatty acids (NEFA). Glucose extraction was increased significantly during ischemia and reperfusion by the pretreatment of DCA (p < 0.01). the calculated contribution of glucose to myocardial oxidative metabolism during ischemia and reperfusion was greater than that of NEFA and lactate in case of DCA treatment. The uptake of [99mTc]pyrophosphate (PYP), which reflects myocardial injury, was also significantly suppressed by DCA (p < 0.01). pH was not affected by an infusion of DCA. These findings suggest that the activation of glucose metabolism by DCA, which is impaired and reduced during ischemia and reperfusion, may be responsible for the improved myocardial function after reperfusion.

Positron emission tomography with oxygen-15 of stunned myocardium caused by coronary artery vasospasm after recovery.

Stunned myocardium is often observed after unstable angina, myocardial infarction, thrombolysis, angioplasty, and bypass surgery but rarely after coronary vasospasm. A case of stunned myocardium caused by diffuse coronary artery vasospasm and mimicking myocardial infarction is reported. The patient had an emergency coronary angiography, which showed no pathological coronary disease, but the left ventricular ejection fraction showed severe left ventricular dysfunction. Repeat coronary angiography 24 days later after medical treatment (diltiazem and nitrates) showed complete recovery of wall function, and a diffuse vasospasm was induced in both coronary arteries (left anterior and right coronary arteries). Two days later the patient underwent a positron emission tomography study with water labelled with oxygen-15 to evaluate the viable myocardium and oxygen-15 to evaluate oxidative metabolism. The results showed normal myocardial blood flow and perfusable tissue density, confirming that the myocardium was viable, and normal myocardial oxidative metabolism, reflecting the recovery of the left ventricular function.

Relation between shock-related myocardial injury and defibrillation efficacy of monophasic and biphasic shocks in a canine model.

Certain biphasic waveforms with specific time ratios of positive and negative components require less energy for successful defibrillation of the fibrillating ventricles than monophasic waveforms. However, if more efficient waveforms were also to be associated with more injurious effects on myocardial function, they might not provide a true biological advantage. This study investigates the relation between defibrillation efficacy and potential toxicity of monophasic and asymmetric, single capacitor, biphasic waveforms with equal durations of positive and negative components. The myocardial lactate extraction rate (LER) was used to measure the injurious effects on myocardial oxidative metabolism of two synchronized 35-J shocks in sinus rhythm. LER, mean arterial pressure (MAP) and, in a subset of experiments, cardiac output (CO) and coronary blood flow (CBF) were measured at baseline, 30 seconds, 60 seconds, 90 seconds, 150 seconds, 300 seconds, and 600 seconds after the shocks. In 12 dogs, three different waveforms (M 10: monophasic 10 milliseconds; BI 10: biphasic 10 milliseconds; BI 20: biphasic 20 milliseconds) were tested as series of two consecutive shocks (60 seconds apart) resulting in a total of 36 sets of data. At baseline, LER was 25 +/- 11%. After monophasic shocks, LER decreased significantly more than after biphasic shocks (LER at 150 seconds: M 10: -6 +/- 31% versus BI 10: 21 +/- 15% versus BI 20: 21 +/- 16%; M 10 versus BI 10 and M 10 versus BI 20, P < .05) and showed also a slower recovery (LER at 300 seconds: M 10: 1 +/- 24% versus BI 10: 20 +/- 11% versus BI 20: 20 +/- 15%; M 10 versus BI 10 and M 10 versus BI 20, P < .05). The maximal decrease in LER was 41 +/- 27% for M 10 compared with 18 +/- 15% for BI 10 and 15 +/- 11% for BI 20 (both, M 10 versus BI 10 and M 10 versus BI 20, P < .05). There was a similar decrease in CO and MAP, with the lowest MAP after monophasic shocks. The maximal decrease in MAP was significantly greater after M 10 compared with BI 20 (-29 +/- 15 mm Hg versus -13 +/- 11 mm Hg, P < .05). The defibrillation threshold was 18.6 +/- 8 J for M 10 compared with 11.5 +/- 4.0 J for BI 10 (P < .05) and 15.0 +/- 6.1 J for BI 20, respectively (P = NS). Our results suggest that these specific biphasic waveforms are associated with less injurious effects on myocardial oxidative metabolism and hemodynamic performance. Given their higher defibrillation efficacy as well, biphasic waveforms may provide important long-term benefits in patients receiving frequent shocks from implantable cardioverter-defibrillators.

Prolonged neonatal myocardial preservation with a highly buffered low-calcium solution

Optimal methods of myocardial preservation remain controversial in the neonate. This study compared prolonged hypothermic storage of neonatal hearts with modified University of Wisconsin solution (group I) with a solution formulated to promote anaerobic glycolysis by providing proton buffering with histidine (100 mmol/L) and exogenous glucose and insulin (group II). Hearts from piglets aged 3 to 5 days were given a single dose of either solution ( n = 6 each), subjected to 20 hours of global ischemia at 4° C, and reperfused with an erythrocyte-enhanced perfusate in an isovolumic Langendorff preparation. After 1 hour of reperfusion, in comparison with hearts preserved with University of Wisconsin solution, those in group II demonstrated (mean ± standard error of the mean) greater left ventricular developed pressure (101 ± 7 versus 62 ± 9 mm Hg, p < 0.01) and the first derivative of left ventricular pressure (816 ± 23 versus 614 ± 69 mm Hg · sec -1, p < 0.05). Diastolic indices were reduced to a similar degree in the two groups. Myocardial oxygen consumption was significantly greater (38.8 ± 2.4 versus 11.8 ± 2.4 μl oxygen · min · g -1, p < 0.01) in group II hearts. Group I hearts vasoconstricted (6% increase in coronary vascular resistance) in response to an intracoronary infusion of acetylcholine (20 nmol·min -1); in contrast, acetylcholine produced coronary dilation in group II hearts (5% decrease in coronary resistance, p < 0.02) that was similar to that observed in nonischemic control hearts. These results demonstrate enhanced preservation of myocardial contractility, oxidative metabolism, and vascular function in neonatal hearts provided by a solution designed to buffer protons and promote anaerobic glycolysis during ischemia. (J THORAC CARDIOVASC SURG 1994;108:772-9)

Retrograde warm blood cardioplegia preserves hypertrophied myocardium: A clinical study

The ability of retrograde warn blood cardioplegia to preserve hypertrophied myocardium remains controversial. This two-part study was undertaken to address this question in patients subjected to aortic valve replacement for calcified aortic valve stenosis complicated with echocardiographically defined left ventricular hypertrophy. Part I was designed to assess the intraoperative patterns of myocardial oxidative metabolism in 20 patients in whom the severity of left ventricular hypertrophy was reflected by a mean (± standard error of the mean) myocardial mass index of 213 ± 15 g/m2. After antegrade arrest, warm blood cardioplegia was continuously given through the coronary sinus at a flow rate of 200 ± 5 mL/min. The use of a low-dilution cardioplegia delivery technique enabled us to keep hematocrit at 25.6% ± 0.9% and the care temperature was allowed to drift to 32.7 ± 0.2 °C. At the end of the arrest period, blood samples were simultaneously taken from inflow (coronary sinus catheter) and outflow (left coronary ostium) cardioplegia and assayed for blood gases, oxygen content and saturation and lactate. Part II was designed to compare the clinical outcomes of these 20 warm patients with those of 20 case-matched patients in whom a conventional hypothermic myocardial protection technique was used. The results of part I show that after an average arrest period of 72 ± 4 minutes, the residual oxygen demand was still high as reflected by a percent oxygen extraction of 34.8% ± 4.1%. This demand, however, was adequately met by the supply, as demonstrated by (1) the absence of transmyocardial acid production, (2) a negligible release (outflow minus inflow) of lactate (0.28 ± 0.1 mmol/L), and (3) a high residual oxygen saturation (65.7% ± 3.8%) in outflow cardioplegia. The results of part II show that the clinical outcomes of warm patients were overall good and not different from those of the cold group. We conclude that retrograde warm blood cardioplegia can adequately preserve hypertrophied myocardium by keeping its metabolism predominantly aerobic during aortic cross-clamping provided that measures are taken to optimize the determinants of the oxygen demand/supply ratio throughout. These measures include avoidance of left ventricular distention, immediate ablation of any recurring activity during arrest, maintenance of high retrograde flow rates, limitation of hemodilution, and uninterrupted mode of cardioplegia delivery.

Enhancement of regional myocardial efficiency and persistence of perfusion, oxidative, and functional reserve with paired pacing of stunned myocardium.

Stunned myocardium reflects postreperfusion dysfunction in myocardium that is destined to ultimately fully recover. Most investigators attribute postreperfusion stunning to a primary defect in excitation-contraction coupling or to an altered sensitivity of the myofilaments to calcium. The aim of the present study was to evaluate the interrelation between myocardial perfusion, oxidative metabolism, and function in an effort to better characterize the phenomenon of myocardial stunning, to define the regional efficiency of stunned myocardium, and to characterize its reserve capacity. Regional myocardial perfusion (measured with radiolabeled microspheres), myocardial oxygen consumption (MVO2) (quantified with positron emission tomography using 1-11C-acetate), and myocardial function (assessed with two-dimensional echocardiography) were evaluated in 12 anesthetized, closed-chest dogs subjected to 15 minutes of left anterior descending coronary artery occlusion followed by reperfusion. To evaluate flow, oxidative, and functional reserve after measurements were obtained 1 hour after reperfusion, dogs were subjected to paired pacing (an inotropic stimulus that does not alter systemic hemodynamics), and measurements were repeated. One hour after reperfusion, stunned myocardium was characterized by near-normal levels of myocardial perfusion (0.57 +/- 0.13 mL/g per minute, 81 +/- 13% of that in remote, normal regions) but severe dyskinesis (echo score, 2.6 +/- 0.7; percent wall thickening, 14 +/- 20%). Despite the low level of contractile function, MVO2 averaged 1.72 +/- 0.7 mumol/g per minute, 71 +/- 27% of that observed in remote myocardium. Regional myocardial efficiency (systolic wall thickening divided by MVO2) was markedly diminished. With paired pacing, myocardial perfusion increased proportional to that in remote myocardium, systolic function improved (echo score, 1.4 +/- 0.7; percent wall thickening, 30 +/- 15%), and regional MVO2 nearly doubled (to 3.41 +/- 1.82 mumol/g per minute, P < .05 for each paired measurement). Importantly, with paired pacing, regional myocardial efficiency nearly normalized in reperfused myocardium. Stunned myocardium is characterized by near-normal levels of perfusion and oxygen consumption despite marked dyskinesis. Myocardial efficiency is poor. With inotropic stimulation (in the present study, paired pacing), reperfused myocardium demonstrated considerable perfusion, oxidative, and functional reserve and a dramatic improvement in myocardial efficiency. These results may have implications for the treatment of postreperfusion pump failure.

Responses of blood flow, oxygen consumption, and contractile function to inotropic stimulation in stunned canine myocardium

To examine the effects of inotropic stimulation on regional myocardial blood flow (MBF), oxidative metabolism, and contractile function in stunned myocardium, nine closed-chest dogs were studied 2 hours postreperfusion after a 25 minute occlusion of the left anterior descending coronary artery (LAD). MBF was determined with microspheres, and regional myocardial oxygen consumption (MVO 2) was estimated from the rate constant k 1 of the rapid clearance phase of [1- 11C] acetate time activity curves, recorded with dynamic positron emission tomography. Myocardium at risk was determined from [ 13N] ammonia images obtained during occlusion. Wall motion, assessed by two-dimensional echocardiography, was impaired in postischemic myocardium in all dogs 2 hours after reperfusion. Dobutamine infusion increased the rate pressure product by 70% ± 31% and significantly improved contractile function in the postischemic region in all dogs. In remote myocardium, MVO 2 increased from 5.7 ± 1.2 to 8.6 ± 1.6 μmol/gm/min, and blood flow from 0.87 ± 0.16 to 1.52 ± 0.42 ml/gm/min in response to dobutamine. In reperfused myocardium, MVO 2 increased from 3.1 ± 0.7 to 7.4 ± 1.5 μmol/gm/min, and blood flow from 0.51 ± 0.12 to 1.2 ± 0.4 ml/gm/min. Oxygen extraction increased significantly in reperfused myocardium relative to remote myocardium consistent with a flow-limited response to dobutamine stimulation. The improvement in contractile function failed to correlate significantly with relative increases in MBF or MVO 2, suggesting that mechanical function is not as tightly coupled as MBF and MVO 2 in postischemic myocardium during inotropic stimulation.

An approach to ventricular efficiency by use of carbon 11-labeled acetate and positron emission tomography.

Positron emission tomography-derived 11C-labeled acetate kinetics have been shown to reflect myocardial oxidative metabolism. The objective of the study was to use this metabolic imaging technique in combination with an evaluation of left ventricular work as an index of ventricular mechanical efficiency. The effects of ventricular ejection fraction and loading on this index were studied quantitatively in a canine experimental model. There was a curvilinear relationship between efficiency and the end-diastolic volume per unit mass (r = 0.84), which appeared to integrate the main determinants of left ventricular mechanical performance successfully and allowed the detection of a decreased ventricular efficiency in acute experimental heart failure. This approach appears to have the potential to assess the energetic working point of the ventricle in clinical heart disease and follow the effects of therapy. The data demonstrate the feasibility of an estimate of ventricular efficiency that relies on noninvasive data-acquisition techniques.

Comparison of carbon-11-acetate with fluorine-18-fluorodeoxyglucose for delineating viable myocardium by positron emission tomography

Objectives. This study was designed to determine in patients with advanced coronary disease whether prediction of recovery of mechanical function after coronary revascularization could be accomplished more effectively by positron emission tomography (PET) with Carbon-11 (11C)-acetate than by PET with fluorine-18 (18F)-fluorodeoxyglucose.Background.Results of previous studies have demonstrated that preservation of myocardial oxidative metabolism (measured by PET with 11C-acetate) is necessary for recovery of systolic function after coronary revascularization.Methods. Myocardial oxidative metabolism was quantified before revascularization in 34 patients by the analysis of the rate of myocardial clearance of 11C-acetate. Metabolism of glucose was assessed by analysis of uptake of 18F-fluorodeoxyglucose. Receiver operating characteristic curves for predicting functional recovery were derived for the measurements of oxidative metabolism and glucose metabolism. In addition, criteria for prediction of recovery of function based on measurements of oxidative metabolism and glucose metabolism were developed and compared.Results. Analysis of receiver operating characteristic curves indicated that estimates of oxidative metabolism were more robust in predicting functional recovery than were estimates of glucose metabolism (p < 0.02). Moreover, thershold criteria with 11C-acetate exhibited superior positive and negative predictive values (67% and 89%, respectively) than did the criteria with 18F-fluorodeoxyglucose (52% and 81%, respectively), p < 0.01. In segments with initially severe dysfunction, estimates of oxidative metabolism tended to be more robust than estimates of glucose metabolism in predicting functional recovery. Moreover, in such segments, the threshold criteria with 11C-acetate to exhibit superior positive and negative predictive values (85% and 87%, respectively) than did the criteria with 18F-fluorodeoxyglucose (72% and 82%, respectively), although statistical significance was not achieved.Conclusions. In patients with advanced coronary artery disease, the extent to which functional recovery can be anticipated after coronary revascularization can be delineated accurately by quantification of regional oxidative metabolism by PET with 11C-acetate.

Assessment of the effects of dobutamine on myocardial blood flow and oxidative metabolism in normal human subjects using nitrogen-13 ammonia and carbon-11 acetate

The dual purposes of this study with positron emission tomography were to measure the effects of dobutamine on myocardial blood flow and oxidative metabolism, and to compare carbon-11 (C-11) acetate versus nitrogen-13 (N-13) ammonia in quantitating flow in normal subjects. Flow was quantitated with N-13 ammonia at rest and at peak dobutamine infusion (40 μg/kg/min) in 21 subjects. In 11 subjects, oxidative metabolism was also estimated at rest and peak dobutamine infusion using the clearance rate of C-11 acetate, k mono (min −1). A 2-compartment kinetic model was applied to the early phase of the C-11 acetate data to estimate flow. The rest and peak dobutamine rate-pressure products were 7,318 ± 1,102 and 19,937 ± 3,964 beats/min/mm Hg, respectively, and correlated well (r = 0.77) with rest and peak dobutamine flows of 0.77 ± 0.14 and 2.25 ml/min/g determined using N-13 ammonia as a flow tracer. Rest and dobutamine flows estimated with C-11 acetate were highly correlated with those determined with N-13 ammonia (r = 0.92). k mono increased from 0.05 ± 0.01 to 0.18 ± 0.02 min −1, and correlated highly with the increase in flows (r = 0.91) and rate-pressure products (r = 0.94). Thus, the increase in cardiac demand associated with dobutamine is highly correlated with an increase in supply and oxidative metabolism. C-11 acetate is a unique tracer that can be used to image both flow and metabolism simultaneously.