Effects of epinephrine and norepinephrine on hemodynamics, oxidative metabolism, and organ energetics in endotoxemic rats

Lévy, Bruno; Mansart, Arnaud; Bollaert, Pierre‐Édouard; Franck, P.; Mallié, Jean-Pierre

doi:10.1007/s00134-002-1611-0

Cited by 69 publications

(52 citation statements)

References 34 publications

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“…It is obviously different from a previously used hypokinetic model (12), which led to major decreases in aortic and regional blood flow, pronounced lactic acidosis, and major gut mucosa injury.…”

Section: Characterization Of Endotoxic Modelcontrasting

confidence: 75%

Comparative effects of vasopressin, norepinephrine, and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Lévy

Vallée²,

Lauzier³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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. Comparative effects of vasopressin, norepinephrine, and L-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock. Am J Physiol Heart Circ Physiol 287: H209 -H215, 2004. First published February 26, 2004 10.1152/ajpheart.00946.2003, a standard of care, AVP, an alternative candidate, and L-canavanine (LC), a selective inhibitor of inducible nitric oxide synthase, were compared for efficacy and innocuousness on global and regional hemodynamics, plasmatic and tissue lactate-to-pyruvate ratio (L/P), tissue high-energy phosphates, renal function, and tissue capillary permeability in a rat model of endotoxic normokinetic shock. Mean arterial pressure (MAP) decreased (ϳ35%) but aortic blood flow increased during endotoxin infusion (P Ͻ 0.05 vs. control). Additionally, there was a decrease in mesenteric (MBF) and renal (RBF) blood flows along with regional-to-systemic ratio (P Ͻ 0.05 vs. control). All tested drugs restored MAP to basal levels but slightly decreased abdominal aortic flow; however, RBF and MBF remained unchanged. Endotoxin significantly decreased diuresis and inulin clearance (ϳ3-to 4-fold), whereas AVP or LC attenuated this drop (P Ͻ 0.05 vs. control). In contrast, NE did not improve endotoxininduced renal dysfunction. Endotoxin induced gut and lung hyperpermeability (P Ͻ 0.05 vs. control). Endotoxin-induced gut hyperpermeability was inhibited by AVP, LC, and NE. Endotoxin-induced lung hyperpermeability was further worsened by NE (ϳ2-fold increase) but not AVP infusion (P Ͻ 0.05 vs. endotoxin). LC significantly improved endotoxin-induced pulmonary hyperpermeability. Endotoxin increased renal lactate and decreased renal ATP. NE did not change renal lactate or renal ATP. AVP and LC decreased renal lactate and normalized renal ATP. Finally, endotoxin was associated with increased lactate levels and L/P (ϳ2-and 1.5-fold increases vs. control, respectively), whereas AVP and LC, but not NE, normalized both parameters after endotoxin challenge. These results suggest that, in a short-term endotoxic shock model, AVP improves systemic hemodynamics without side effects and has particular beneficial effects on renal function. septic shock; vascular permeability; renal function THE HUMAN RESPONSE to septic challenge usually includes increased cardiac output, decreased peripheral resistance, low arterial pressure, and increased vascular permeability. AVP, also known as "the" antidiuretic hormone (ADH), is an emerging alternative candidate for management of redistributive shock (7). Indeed, AVP exhibits strong vasoconstrictor effects through stimulation of the V1 receptor leading to arterial pressure improvement (28). Moreover, low concentrations of exogenous AVP mediate vasodilatation in coronary, cerebral, and pulmonary arterial circulation (20). The recognized effects of AVP on renal function are complex and include association of an antidiuretic effect through stimulation of V2 receptors, an increase of diuresis/natriuresis through V1 receptors by efferent arteriolar vasoconstric...

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Section: Characterization Of Endotoxic Modelcontrasting

confidence: 75%

Comparative effects of vasopressin, norepinephrine, and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Lévy

Vallée²,

Lauzier³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…We found 56 experiments performed in small animals [20, 24, 26, 27, 39, 42, 43, 44, 55, 57, 58, 59, 62, 63, 64, 67, 68, 72, 77, 79, 81, 82, 87, 88, 89, 90, 93, 94, 96, 97, 99, 100, 103, 104, 105, 110, 116, 120, 121, 122, 129, 132, 133, 134, 137, 138, 139, 141, 142, 143, 147, 148, 149, 150, 151] and 81 performed in large animals [21, 22, 23, 25, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 56, 60, 61, 65, 66, 69, 70, 71, 73, 74, ...…”

Section: Resultsmentioning

confidence: 99%

“…We found 137 animal studies [20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113...…”

Section: Resultsmentioning

confidence: 99%

“…Of 78 articles using flow probes [21, 22, 23, 24, 25, 26, 27, 28, 31, 32, 35, 41, 42, 45, 49, 50, 51, 52, 53, 54, 56, 58, 60, 62, 63, 65, 66, 69, 71, 72, 73, 74, 75, 78, 80, 81, 83, 85, 86, 89, 90, 91, 92, 95, 99, 100, 102, 106, 108, 109, 110, 111, 112, 113, 114, 115, 117, 118, 119, 121, 124, 126, 127, 128, 131, 135, 140, 141, 142, 143, 144, 145, 146, 152, 153, 154, 155], 36 (46.2%) showed a decreased RVR, 11 (14.1%) an unchanged RVR, and 31 (39.7%) a decreased RVR. Of 59 studies using other methods [20, 29, 30, 33, 34, 36, 37, 38, 39, 40, 43, 44, 4...…”

Section: Resultsmentioning

confidence: 99%

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Renal Vascular Resistance in Sepsis

et al. 2006

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Aims: To assess changes in renal vascular resistance (RVR) in human and experimental sepsis and to identify determinants of RVR. Methods: We performed a systematic interrogation of two electronic reference libraries using specific search terms. Subjects were animals and patients involved in experimental and human studies of sepsis and septic acute renal failure, in which the RVR was assessed. We obtained all human and experimental articles reporting RVR during sepsis. We assessed the role of various factors that might influence the RVR during sepsis using statistical methods. Results: We found no human studies, in which the renal blood flow (and, therefore, the RVR) was measured with suitably accurate direct methods. Of the 137 animal studies identified, 52 reported a decreased RVR, 16 studies reported no change in RVR, and 69 studies reported an increased RVR. Consciousness of animals, duration of measurement, method of induction of sepsis, and fluid administration had no effect on the RVR. On the other hand, on univariate analysis, size of the animals (p<0.001), technique of measurement (p = 0.017), recovery after surgery (p = 0.004), and cardiac output (p <0.001) influenced the RVR. Multivariate analysis, however, showed that only cardiac output (p = 0.028) and size of the animals (p = 0.031) remained independent determinants of the RVR. Conclusions: Changes in RVR during sepsis in humans are unknown. In experimental sepsis, several factors not directly related to sepsis per se appear to influence the RVR. A high cardiac output and the use of large animals predict a decreased RVR, while a decreased cardiac output and the use of small animals predict an increased RVR.

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“…Sepsis leads to reduced substrate oxidation and increased cardiac inflammation. Most (35)(36)(37)(38)(39)(40)(41)(42)(43) but not all (44 -46) studies also report reduced cardiac ATP production in sepsis. The differences between the two groups of studies may be attributed to the different sepsis induction methods and time courses that were followed in each case.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of c-Jun-N-terminal Kinase Increases Cardiac Peroxisome Proliferator-activated Receptor α Expression and Fatty Acid Oxidation and Prevents Lipopolysaccharide-induced Heart Dysfunction

Drosatos

Drosatos-Tampakaki

Khan

et al. 2011

Journal of Biological Chemistry

106

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Septic shock results from bacterial infection and is associated with multi-organ failure, high mortality, and cardiac dysfunction. Sepsis causes both myocardial inflammation and energy depletion. We hypothesized that reduced cardiac energy production is a primary cause of ventricular dysfunction in sepsis. The JNK pathway is activated in sepsis and has also been implicated in impaired fatty acid oxidation in several tissues. Therefore, we tested whether JNK activation inhibits cardiac fatty acid oxidation and whether blocking JNK would restore fatty acid oxidation during LPS treatment. LPS treatment of C57BL/6 mice and adenovirus-mediated activation of the JNK pathway in cardiomyocytes inhibited peroxisome proliferator-activated receptor ␣ expression and fatty acid oxidation. Surprisingly, none of the adaptive responses that have been described in other types of heart failure, such as increased glucose utilization, reduced ␣MHC:␤MHC ratio or induction of certain microRNAs, occurred in LPS-treated mice. Treatment of C57BL/6 mice with a general JNK inhibitor (SP600125) increased fatty acid oxidation in mice and a cardiomyocyte-derived cell line. JNK inhibition also prevented LPS-mediated reduction in fatty acid oxidation and cardiac dysfunction. Inflammation was not alleviated in LPS-treated mice that received the JNK inhibitor. We conclude that activation of JNK signaling reduces fatty acid oxidation and prevents the peroxisome proliferator-activated receptor ␣ downregulation that occurs with LPS.Septic shock is the most severe complication of sepsis and is associated with reduced cardiac contractility (1, 2). Hearts rely mostly (70%) on fatty acid (FA) 3 oxidation for energy homeostasis (3), and in sepsis, cardiac FA oxidation is markedly reduced. Unlike heart failure (4), this reduction of FA oxidation in sepsis is not compensated by a simultaneous increase in glucose oxidation (5-7). Thus, sepsis leads to cardiac energy deficiency.LPS is a bacterial cell wall component that induces many of the pathophysiological consequences of sepsis, including cardiac dysfunction. LPS associates with plasma LPS-binding protein and targets cluster of differentiation (CD)14 and toll-like receptor 4 (8). This binding leads to production of inflammatory cytokines, such as TNF␣, IL-1, and IL-6, which might directly alter heart function (9 -12). LPS also alters cardiac energy utilization by reducing the expression of peroxisome proliferator-activated receptor (PPAR)␣ and its downstream genes required for FA oxidation (13,14). It is unknown whether the LPS-induced reduction in cardiac energy production is mediated by inflammation.LPS activates the JNK signaling pathway (15,16). JNK is a stress-activated protein kinase (17) that phosphorylates c-Jun, which then forms homo-or heterodimers with c-Fos or activating transcription factor, forming the activating protein 1 complex (18). LPS activates JNK in the heart, but it is not clear whether this pathway leads to impaired cardiac FA oxidation. Inhibition of JNK improves FA oxidation in...

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Effects of epinephrine and norepinephrine on hemodynamics, oxidative metabolism, and organ energetics in endotoxemic rats

Abstract: Our data demonstrate in a rat model of endotoxemia that epinephrine-induced hyperlactatemia is not related to cellular hypoxia.

Cited by 69 publications

References 34 publications

Comparative effects of vasopressin, norepinephrine, and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Comparative effects of vasopressin, norepinephrine, and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Renal Vascular Resistance in Sepsis

Inhibition of c-Jun-N-terminal Kinase Increases Cardiac Peroxisome Proliferator-activated Receptor α Expression and Fatty Acid Oxidation and Prevents Lipopolysaccharide-induced Heart Dysfunction

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