Does the degree of cyanosis affect myocardial adenosine triphosphate levels and function in children undergoing surgical procedures for congenital heart disease?

Najm, Hani K.; Wallen, W. Jack; Belanger, Michael; Williams, William G.; Coles, John G.; Arsdell, Glen S. Van; Black, Michael D.; Boutin, Christine; Wittnich, Carin

doi:10.1016/s0022-5223(00)70131-0

Cited by 42 publications

(43 citation statements)

References 22 publications

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“…For example, in the newborn myocardium, lower preischemic high-energy phosphate and glycogen reserves have been associated with lower ATP levels during ischemia, more rapid development of ischemic contracture, and increased postischemic ventricular dysfunction (10,13,26). In children undergoing congenital cardiac repair, slightly lower levels of preischemic ATP (ϳ4 mol/g dry weight) was also strongly associated with more rapid ATP depletion during ischemia, worse postoperative myocardial function, longer time spent in the intensive care unit (ICU), and longer hospital stays (27). Other investigators have suggested that accumulation of anaerobic end-products during ischemia and not reduced ATP levels is responsible for damage to the myocardium during ischemia and reperfusion (28).…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Newborn Myocardial Metabolism and Response to Ischemia

et al. 2011

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ABSTRACT:In children with congenital heart disease, female sex has been linked to greater in-hospital mortality associated with low cardiac output, yet the reasons for this are unclear. Therefore, we examined whether newborn sex differences in the heart's metabolic response to ischemia exist. Left ventricular (LV) in vivo and ischemic biopsies of newborn male and female piglets were compared. Tissue ATP, creatine phosphate (CP), glycogen, anaerobic end-products lactate and hydrogen ion (H ϩ ), and key regulatory enzymes were measured. Compared with males, newborn females displayed 14% lower ATP, 22% lower CP, and 32% lower glycogen reserves (p Ͻ 0.05) at baseline. During ischemia, newborn females accumulated 17% greater lactate and 40% greater H ϩ accumulation (p Ͻ 0.02), which was associated with earlier cessation of glycolysis and lower ischemic ATP levels (p Ͻ 0.02) compared with males. Newborn females demonstrated a greater ability to use their glycogen reserves, resulting in significantly lower (p Ͻ 0.003) glycogen levels throughout the ischemic period. Thus, newborn females are at a metabolic disadvantage because they exhibited lower energy levels and greater tissue lactic acidosis, both linked to an increase susceptibility to ischemic injury and impair myocardial function on reperfusion. (Pediatr Res 70: 148-152, 2011)

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Section: Discussionmentioning

confidence: 99%

Sex Differences in Newborn Myocardial Metabolism and Response to Ischemia

et al. 2011

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“…As the chronic hypoxia produces long-term changes in the myocardial metabolism and function, the sudden oxygen reintroduction further exacerbates these effects. The impaired contractility due to hypoxia-induced calcium overload and the loss of high energy phosphates are examples of the pathological events amplified by the reoxygenation [59,60]. In addition, the depletion of endogenous antioxidants that characterize chronic cyanosis cannot counteract the oxygen radical-mediated injury when oxygen is reintroduced [61].…”

Section: Reoxygenation and Reperfusion Injuriesmentioning

confidence: 99%

Hypoxia-Induced Molecular and Cellular Changes in the Congenitally Diseased Heart: Mechanisms and Strategies of Intervention

Iacobazzi¹,

Caputo²,

Ghorbel³

2017

Hypoxia and Human Diseases

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Tissue hypoxia plays a critical role in the pathobiology of congenital heart diseases, especially with regard to cyanotic patients. Here, we describe the cellular and molecular mechanisms induced by hypoxia in the diseased heart, with particular attention to the metabolic and functional changes that underlie the hypoxia-induced right ventricle remodelling. The role of reactive oxygen species in transcriptomic changes, DNA damage, contractile dysfunction and extracellular matrix remodelling will be addressed. Furthermore, the reoxygenation injury, which occurs when oxygen is reintroduced upon initiation of cardiopulmonary bypass, will be discussed. This allows a better understanding of the risks associated with the reoxygenation injury in children undergoing openheart surgery and helps to improve strategies of intervention for myocardial protection.

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“…Studies have identified that more rapid depletion of high-energy phosphates in the newborn heart is associated with a more rapid onset of ischemic contracture and increased postischemic ventricular dysfunction (15,24,33). In human infants undergoing cardiac surgery, a rather small difference in ischemic ATP levels (4 mol/g dry weight) was correlated with worse postischemic function, longer time spent in the ICU, and longer hospital stays (33). Other investigators have suggested that accumulation of anaerobic end products and not reduced ATP levels is responsible for damage to the myocardium during ischemia (17).…”

Section: Newborn Lv/rv Metabolic Differencesmentioning

confidence: 99%

“…Should these differences between the LV and RV hold in the clinical setting, this may offer a potential explanation for studies that have reported greater left ventricular postischemic dysfunction in normal newborn hearts and newborn hearts with right-sided pathology (1-3). In addition, caution should be exercised by both experimental and clinical investigators using RV biopsies to assess LV metabolism and function in the pediatric population (33,35), as they may be underestimating the potential risk factors associated with ischemia.…”

Section: Newborn Lv/rv Metabolic Differencesmentioning

confidence: 99%

Ventricle-Specific Metabolic Differences in the Newborn Piglet Myocardium In Vivo and During Arrested Global Ischemia

2008

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Ventricular dysfunction is reported greater in the left (LV) versus right ventricle (RV) in infants following surgically induced ischemia. Ventricle-specific differences in baseline metabolism may alter response to ischemia thus affecting postischemic functional recovery. This study identifies ventricle-specific metabolic differences in the newborn (piglet) heart at baseline (working) and during ischemia (arrested). Baseline LV citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase (HAD) activities were 15% and 18% lower (p Ͻ 0.02), whereas creatine kinase (CK) and phosphofructokinase (PFK) activities were 40% and 23% higher (p Ͻ 0.04) than the RV. Baseline LV glycogen reserves were also 55% higher (p ϭ 0.004). By 15 min of ischemia, LV ATP was 20% lower (p Ͻ 0.05), lactate was 51% higher (p ϭ 0.001), and hydrogen ions (H ϩ ) were 43% higher (p ϭ 0.03) compared with the RV. These differences persisted for the entire ischemic period (p Ͻ 0.02). After 45 min of ischemia, the LV used 58% less (p Ͻ 0.05) glycogen than the RV. These findings demonstrate that the enhanced glycolytic capacity of the newborn LV was accompanied by greater anaerobic end-product accumulation and lower energy levels during ischemia. This profile may offer one explanation for greater LV-dysfunction relative to the RV in children following ischemia. C linical studies continue to report persistent postoperative dysfunction in the left ventricle (LV) of children even after successful repair of pathology affecting the right ventricle (RV) (1,2). Experimental studies in the newborn heart suggest a lower tolerance of the LV to ischemia, as LV recovery of function following ischemia is far worse than that seen in the RV (3). Whether these findings are a result of ventricle-specific differences in postnatal myocardial metabolic maturation is currently unknown.During postnatal cardiac maturation, the LV undergoes rapid "physiologic" hypertrophy relative to the RV in response to postnatal changes in systemic and pulmonary circulation (4). Morphologic studies using newborn animals have reported a lower capillary density in the LV relative to the RV as noted by greater LV myocyte-to-capillary ratios and intercapillary distances (5). Lower tissue perfusion capacity in the face of increased postnatal ventricular workloads and rapid ventricular growth in the newborn LV may result in underperfusion. Whether this has detrimental effects on metabolic capacity and response to ischemia is unknown.During postnatal cardiac maturation, there is a shift in energy substrate reliance where the use of fatty acids dramatically increases and that of glucose decreases (6 -9). Central to this transition is an early decrease in the activity of key enzymes involved in the glycolytic pathway and an increase in the enzymes responsible for fatty acid and oxidative metabolism (8,9). Interestingly, studies have shown that adult hearts adapt to chronic increases in ventricular workloads by shifting energy substrate reliance away from fatty acid and oxidative pathways b...

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Does the degree of cyanosis affect myocardial adenosine triphosphate levels and function in children undergoing surgical procedures for congenital heart disease?

Abstract: The degree of cyanosis adversely affects myocardial adenosine triphosphate, function, and clinical outcome of children who undergo cardiac operation. Children with cyanosis should be identified as a higher risk group that could be targeted for supportive interventions.

Cited by 42 publications

References 22 publications

Sex Differences in Newborn Myocardial Metabolism and Response to Ischemia

Sex Differences in Newborn Myocardial Metabolism and Response to Ischemia

Hypoxia-Induced Molecular and Cellular Changes in the Congenitally Diseased Heart: Mechanisms and Strategies of Intervention

Ventricle-Specific Metabolic Differences in the Newborn Piglet Myocardium In Vivo and During Arrested Global Ischemia

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