Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock.

Dhainaut, Jean-François; Huyghebaert, M F; Monsallier, J F; Lefèvre, Guillaume; Dall’Ava-Santucci, Josette; Brunet, F.; Villemant, D.; Carli, A; Raichvarg, D

doi:10.1161/01.cir.75.3.533

Cited by 340 publications

(146 citation statements)

References 34 publications

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“…The only exception, however, is lactate, the uptake of which is 15 times higher than in control lambs. This is the result not only of an increased myocardial blood flow but also of an additionally increased lactate An increased myocardial lactate utilization has been previously demonstrated at rest (35,36), during exercise (4, 10-12, 17, 35, 37-39), or during septic shock (40). However, a common feature in all of these studies is an increased arterial lactate concentration.…”

Section: Discussionmentioning

confidence: 78%

Myocardial Carbohydrate, Ketone, and Fatty Acid Uptake in Conscious Lambs with Aortopulmonary Shunts1

et al. 1992

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ABSTRACT. A left to right shunt increases myocardial work and is often accompanied by increased catecholamine levels. Because both increased myocardial work and increased catecholamine levels may induce increased fatty acid utilization, which could increase resting myocardial oxygen consumption and therefore unfavorably affect coronary reserve, we studied myocardial uptake of glucose, pyruvate, lactate, &OH-butyrate, acetoacetate, FFA, and triglycerides in 12 7-wk-old lambs with aortopulmonary left to right shunts (58 f 2% of left ventricular output, mean f SEM) and in 10 control lambs 2 wk after surgery. Despite the shunt, systemic blood flow in the shunt lambs was maintained at the same level as in the control lambs. This was accomplished by an increased heart rate and stroke volume. Furthermore, the shunt was accompanied by an increased myocardial oxygen consumption in the shunt lambs (834 f 70 versus 528 f 43 pmol 02-mine' -100 g-I; p c 0.05). There were no significant differences in arterial substrate concentrations between the two groups. The same was true for arteriovenous differences across the myocardium, with the exception of lactate, which was substantially higher in shunt than in control lambs (72 f 25 versus 18 f 23 pmol/L; p < 0.05). As a consequence, myocardial lactate uptake in the shunt lambs was increased 15-fold (18 2 6 versus 1 f 2 pmol. min-I. 100 g-I; p c 0.02), whereas uptake of the other substrates merely paralleled the increased myocardial blood flow. Our data demonstrate that myocardial substrate uptake is not substantially different between shunt and control lambs, with the exception of lactate, of which the extraction is 10-fold higher than in control lambs. We speculate that the increased myocardial lactate utilization may reflect an increase of lactate and pyruvate dehydrogenase activities. A left to right shunt through a ventricular septa1 defect or ductus arteriosus imposes an increased work load on the heart because of its effect on left ventricular wall stress, external work, contractility, and heart rate (1-3). This effect is accompanied by an increased myocardial oxygen consumption (3), which reflects increased oxidation of substrates to meet the increased ATP demand (4). Often, an increased work load leads not only to increased substrate uptake, but also to a change in the pattern of myocardial substrate utilization (5), as has been shown in hearts with increased afterload (6), contractility (7), and thyroxineinduced volume load (8, 9) and during exercise (5,(10)(11)(12). Furthermore, catecholamines are often increased in the presence of a substantial left to right shunt (13), and they are also known to affect myocardial metabolism (14,15). Through their effect on myocardial performance, catecholamines stimulate glucose and fatty acid utilization by the myocardium, and, through activation of lipoprotein lipase, they enhance fatty acid utilization (5, [14][15][16].These considerations suggest that a left to right shunt could lead to a change in myocardial substrate metabolism....

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Section: Discussionmentioning

confidence: 78%

Myocardial Carbohydrate, Ketone, and Fatty Acid Uptake in Conscious Lambs with Aortopulmonary Shunts1

et al. 1992

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“…In a recent human autopsy study of patients who had succumbed to severe sepsis, buildup of lipids was found inside cardiomyocytes (51). During sepsis, human cardiomyocytes have also displayed diminished uptake of ketone bodies, free fatty acids, and glucose (23). In parallel, septic mice presented with increased intracardiomyocyte deposits of glycogen (52).…”

Section: Metabolic Changesmentioning

confidence: 98%

“…This hypothesis was soon abandoned after direct measurements of coronary blood flow were obtained, showing no reduced, but rather increased, coronary blood flow (22,23). In later studies, however, increased levels of plasma troponin were observed and correlated with the severity of myocardial depression during sepsis and septic shock (24).…”

Section: Decreased Coronary Blood Flowmentioning

confidence: 99%

Molecular Events in the Cardiomyopathy of Sepsis

Flierl

Rittirsch

Huber‐Lang

et al. 2008

Mol Med

109

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Septic cardiomyopathy is a well-described complication of severe sepsis and septic shock. However, the interplay of its underlying mechanisms remains enigmatic. Consequently, we constantly add to our pathophysiological understanding of septic cardiomyopathy. Various cardiosuppressive mediators have been discovered, as have multiple molecular mechanisms (alterations of myocardial calcium homeostasis, mitochondrial dysfunction, and myocardial apoptosis) that may be involved in myocardial dysfunction during sepsis. Finally, the detrimental roles of nitric oxide and peroxynitrite have been unraveled. Here, we describe our present understanding of systemic, supracellular, and cellular molecular mechanisms involved in sepsis-induced myocardial suppression. SYSTEMIC, SUPRACELLULAR MECHANISMS Decreased Coronary Blood FlowOne of the first suggestions was that reduced coronary perfusion in the septic heart might be responsible for a setting of global cardiac ischemia. This hypothesis was soon abandoned after direct measurements of coronary blood flow were obtained, showing no reduced, but rather increased, coronary blood flow (22,23). In later studies, however, increased levels of plasma troponin were observed and correlated with the severity of myocardial depression during sepsis and septic shock (24). Myocardial necrosis could not be observed in patients who died from septic shock (3,25), however, raising the question whether increases in troponin were due to cytokine-induced, transient increases in cardiomyocyte membrane permeability to troponin. To date, this remains to be determined. Alterations of MicrovasculatureThere is now increasing evidence that sepsis and septic shock leads to changes of the myocardial microvasculature. In a canine model of endotoxemia, maldistribution of heterogeneous coronary blood flow has been reported (26). These findings might be caused by endothelial swelling and nonocclusive intravascular fibrin deposits in the microvasculature (27). In parallel, activated cardiomyocytes from septic mice promoted transendothelial migration and activation of circulating neutrophils into the interstitium (28) where these cells may augment the sepsis-induced intracardial inflammation, and contribute to an increased vascular leakage, which has been described to also impair cardiac function and compliance secondary to myocardial edema (29,30). Yet, studies have failed to confirm cellular hypoxia in a murine sepsis model (31). Cardiosuppressing Circulating Proinflammatory MediatorsAnother hypothesis suggested circulating myocardium-depressing factors as the cause of septic cardiomyopathy (32). Parrillo et al. (33) confirmed the existence of a cardiodepressant substance by incubating isolated rat cardiomyocytes with serum obtained from septic shock patients, leading to decreased amplitude and velocity of cardiomyocyte shortening. Levels of cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and the complement anaphylatoxin, C5a, are known to be elevated in the circulation during sepsis an...

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“…Myocardial depression and elevated serum levels of cardiac troponin are common in sepsis, and associated with poor outcome 6, 7. These findings are difficult to reconcile with the normal or even elevated myocardial blood flow found in sepsis 8, 9. Brain function is often affected very early in sepsis, so‐called septic encephalopathy, and survivors often show ischemic lesions on magnetic resonance imaging (MRI), suffering severe permanent neurological sequelae 10.…”

mentioning

confidence: 99%

Microcirculatory dysfunction and tissue oxygenation in critical illness

Østergaard

Granfeldt

Secher

et al. 2015

Acta Anaesthesiol Scand

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Severe sepsis is defined by organ failure, often of the kidneys, heart, and brain. It has been proposed that inadequate delivery of oxygen, or insufficient extraction of oxygen in tissue, may explain organ failure. Despite adequate maintenance of systemic oxygen delivery in septic patients, their morbidity and mortality remain high.The assumption that tissue oxygenation can be preserved by maintaining its blood supply follows from physiological models that only apply to tissue with uniformly perfused capillaries. In sepsis, the microcirculation is profoundly disturbed, and the blood supply of individual organs may therefore no longer reflect their access to oxygen.We review how capillary flow patterns affect oxygen extraction efficacy in tissue, and how the regulation of tissue blood flow must be adjusted to meet the metabolic needs of the tissue as capillary flows become disturbed as observed in critical illness. Using the brain, heart, and kidney as examples, we discuss whether disturbed capillary flow patterns might explain the apparent mismatch between organ blood flow and organ function in sepsis. Finally, we discuss diagnostic means of detecting capillary flow disturbance in animal models and in critically ill patients, and address therapeutic strategies that might improve tissue oxygenation by modifying capillary flow patterns.

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Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock.

Cited by 340 publications

References 34 publications

Myocardial Carbohydrate, Ketone, and Fatty Acid Uptake in Conscious Lambs with Aortopulmonary Shunts1

Myocardial Carbohydrate, Ketone, and Fatty Acid Uptake in Conscious Lambs with Aortopulmonary Shunts1

Molecular Events in the Cardiomyopathy of Sepsis

Microcirculatory dysfunction and tissue oxygenation in critical illness

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