Myocardial lactate metabolism: evidence of lactate release during net chemical extraction in man.

Gertz, Edward W.; Wisneski, Judith A.; Neese, Richard A.; Bristow, James; Searle, G. L.; Hanlon, Joseph T.

doi:10.1161/01.cir.63.6.1273

Cited by 195 publications

(117 citation statements)

References 24 publications

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“…The mean subendocardial blood flow during the most severe underperfusion level was 0.34±0.14 (ml/min)/g (p<0.001). During that time, subepicardial blood flow did not change significantly from the control measurements ( Subendocardial Blood Flow ((ml/min)/g) FIGURE 2. Scatterplot of regional contractile function, expressed as a percent of control value, as a function of subendocardial blood flow (ml/min/g, measured by microspheres) in the anterior wall.…”

Section: Hemodynamicsmentioning

confidence: 87%

Myocardial lactate release during ischemia in swine. Relation to regional blood flow.

et al. 1990

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To determine the relation between regional myocardial blood flow, contractile function, and myocardial lactate release during mild-to-moderate regional myocardial ischemia, nine openchest swine were instrumented for measurement of regional myocardial blood flow (microsphere method), contractile function (sonomicrometry), and hemodynamics. In all nine animals, subendocardial blood flow was 0.99± 0.21 (ml/min)/g during control and 0.34±0.14 (ml/min)/g during the most severe grade of underperfusion (p<0.001) in the left anterior descending coronary arterial distribution. Regional myocardial lactate release was 0.15±0.09 and 1.19+0.75 ,mol/ml, respectively (p<0.003). A highly significant inverse correlation was observed between subendocardial blood flow and myocardial lactate release during the graded reductions in blood flow (r= -0.71, p<0.001). Results from sonomicrometry showed a significant reduction in contractile ventricular function in the anterior wall during the graded reductions in blood flow. The regional arterial-venous glucose difference increased significantly with underperfusion in the left anterior descending coronary arterial distribution, from 0.14±+0.15 to 0.56+±0.37 ,umol/ml (p<0.003). The contribution of exogenous glucose to lactate release also increased significantly; 0.04±+0.03 ,umol/ml of the lactate came from exogenous glucose during control compared with 0.64+±0.59 ,umol/ml during the most severe underperfusion (p<0.02). A significant positive correlation exists between lactate release and lactate from exogenous glucose during graded underperfusion (r=0.96, p<0.001). In summary, these data demonstrate a close inverse relation between regional myocardial lactate release and regional subendocardial blood flow during graded ischemia. (Circulation 1990;81:1948-1958 M cyocardial lactate production has been used as a marker of ischemia in patients and in experimental animal studies.1 Lactate represents the end product of anaerobic or nonoxidative glycolysis. However, lactate is also an important substrate for the myocardium; lactate is converted to pyruvate, which undergoes oxidative decarboxylation to acetyl coenzyme A and subsequently enters the citric acid cycle. Using isotopically labeled lactate, we23 have shown that the myocardium releases or produces lactate when there is net chemical extraction in normal subjects and in patients with ischemic heart disease. This finding implies that both metabolic pathways, that is, nonox-

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Section: Hemodynamicsmentioning

confidence: 87%

Myocardial lactate release during ischemia in swine. Relation to regional blood flow.

et al. 1990

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“…Subendocardial hypoperfusion, with redistribution of flow to the epicardial vessels, has been demonstrated in canine septic shock.36 Global net lactate extraction can obscure regional lactate production in patients with coronary artery disease. 37 The measurements reported here of coronary blood flow, lactate metabolism, and oxygen extraction reflect the global myocardial circulation. The status of the coronary microcirculation and of regional flow distribution in human septic shock will require further investigation of localized areas of myocardium.…”

Section: Discussionmentioning

confidence: 99%

The coronary circulation in human septic shock.

Cunnion

Schaer²,

Parker³

et al. 1986

Circulation

418

134

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Reversible myocardial depression, manifested by ventricular dilatation and decreased ejection fraction, is common in human septic shock. A proposed mechanism, based on animal studies, is myocardial ischemia resulting from inadequate coronary blood flow. Coronary flow observations have not been reported for human septic shock. To determine whether myocardial depression in human septic shock is associated with reduced coronary flow, thermodilution coronary sinus catheters were placed in seven patients with septic shock for measurements of coronary flow and myocardial metabolism. Four of the seven patients developed myocardial depression. These patients had coronary flow similar to or higher than that of control subjects and similar to that of the other three patients, who did not develop myocardial depression. None of the patients had net myocardial lactate production. In general, compared with values in control subjects, the oxygen content difference (arterial minus coronary sinus) was narrowed, and the fractional extraction of arterial oxygen was diminished. This pattern of disordered coronary autoregulation is analogous to the pattern of arteriovenous shunting in other organs in patients with septic shock. The preservation of coronary flow, the net myocardial lactate extraction, and the increased availability of oxygen to the myocardium argue against global ischemia as the cause of myocardial depression in human septic shock. Circulation 73, No. 4, 637-644, 1986. MYOCARDIAL DEPRESSION within the first several days of human septic shock is characterized by dilatation of the left ventricle, a decrease in left ventricular ejection fraction, and maintenance of normal or increased cardiac index. 1 2 In survivors, these profound changes in ventricular function are transient and the ejection fraction generally returns to normal in 7 to 10 days.' The pathogenesis of myocardial depression in septic shock is unclear, but in canine preparations of endotoxic shock myocardial depression has been attributed to myocardial hypoperfusion caused by reduced coronary blood flow.3-7Human coronary blood flow has been studied extensively in normal subjects and in patients with coronary artery disease, by means of nitrous oxide washout, inert gas washout, and thermodilution techniques. The determinants of myocardial lactate metabolism and myocardial oxygen consumption have been characterized. Measurements dial lactate metabolism, and myocardial oxygen consumption have been reported in cardiogenict but not in septic shock in human beings. The current study was undertaken to determine whether myocardial depression in human septic shock is associated with changes in coronary blood flow and whether such changes could explain the depressed cardiac function. MethodsPatients. From October 1982 to February 1984, seven patients with septic shock were studied in the Medical Intensive Care Unit of the National Institutes of Health. The diagnosis of septic shock was based on hypotension (mean arterial pressure less than 60 mm Hg), t...

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“…The model was based on direct ART/ CS plasma measurements of 11 C-lactate and its metabolites in myocardium, which showed that once it is taken up by myocardium, 11 C-lactate is either oxidized or returned back to the vasculature (backdiffusion), with negligible conversion into 11 Cpyruvate and 11 C-alanine. Thus, the model configuration is based on the assumption that no tracer is retained by the myocardium (19).…”

Section: Pet Measurements Of Exogenous Lactate Metabolismmentioning

confidence: 99%

L-3-11C-Lactate as a PET Tracer of Myocardial Lactate Metabolism: A Feasibility Study

Herrero¹,

Dence²,

Coggan³

et al. 2007

Journal of Nuclear Medicine

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Lactate is a key myocardial energy source. Lactate metabolism is altered in a variety of conditions, such as exercise and diabetes mellitus. However, to our knowledge, noninvasive quantitative measurements of myocardial lactate metabolism have never been performed because of the lack of an adequate radiotracer. In this study we tested L-3-11 C-lactate ( 11 C-lactate) as such a tracer. Methods: Twenty-three dogs were studied under a wide range of metabolic interventions. 11 C-Lactate and 13 C-lactate were injected as boluses and PET data were acquired for 1 h. Concomitant arterial and coronary sinus (ART/CS) blood samples were collected to identify 13 C-lactate metabolites and to measure fractional myocardial extraction/production of 11 C metabolite fractions ( 11 C acidic: 11 CO 2 and 11 C-lactate; 11 C basic: 11 C-labeled amino acids; and 11 C neutral: 11 C-glucose). Lactate metabolism was quantified using 2 PET approaches: monoexponential clearance analysis (oxidation only) and kinetic modeling of PET 11 C-myocardial curves. Results: Arterial 11 C acidic, neutral, and basic metabolites were identified as primarily 11 C-labeled lactate 1 pyruvate, glucose, and alanine, respectively. Despite a significant contribution of 11 C-glucose (23%-45%) and 11 C-alanine (,11%) to total arterial 11 C activity, both were minimally extracted (1)/produced(2) by the heart (1.7% 6 1.0% and 20.12% 6 0.84%, respectively). Whereas extraction of 11 C-lactate correlated nonlinearly with that of unlabeled lactate extraction (r 5 0.86, P , 0.0001), 11 CO 2 production correlated linearly with extraction of unlabeled lactate (r 5 0.89, P , 0.0001, slope 5 1.20 6 0.13). In studies with physiologic free fatty acids (FFA) (415 6 216 nmol/mL), 11 C-lactate was highly extracted (32% 6 12%) and oxidized (26% 6 14%), and PET monoexponential clearance and kinetic modeling analyses resulted in accurate estimates of lactate oxidation and metabolism. In contrast, supraphysiologic levels of plasma FFA (4,111 6 1,709 nmol/mL) led to poor PET estimates of lactate metabolism due to negligible lactate oxidation (1% 6 2%) and complete backdiffusion of unmetabolized 11 C-lactate into the vasculature (28% 6 22%). Conclusion: Under conditions of net lactate extraction, L-3-11 Clactate faithfully traces myocardial metabolism of exogenous lactate. Furthermore, in physiologic substrate environments, noninvasive measurements of lactate metabolism are feasible with PET using myocardial clearance analysis (oxidation) or compartmental modeling. Thus, L-3-11 C-lactate should prove quite useful in widening our understanding of the role that lactate oxidation plays in the heart and other tissues and organs.

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Myocardial lactate metabolism: evidence of lactate release during net chemical extraction in man.

Cited by 195 publications

References 24 publications

Myocardial lactate release during ischemia in swine. Relation to regional blood flow.

Myocardial lactate release during ischemia in swine. Relation to regional blood flow.

The coronary circulation in human septic shock.

L-3-11C-Lactate as a PET Tracer of Myocardial Lactate Metabolism: A Feasibility Study

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