Pathophysiology of chronic cyanosis in a canine model

Fm, Lupinetti; Th, Wareing; Cb, Huddleston; Jc, Collins; Rj, Boucek; Hw, Bender; Jw, Hammon

doi:10.1016/s0022-5223(19)38633-7

Cited by 36 publications

(6 citation statements)

References 34 publications

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“…This unintended injury could explain why cyanotic infants are more sensitive to surgical ischemia, and often experience myocardial dysfunction despite performing an apparently technically successful operation with good myocardial protection. 2,3,13,14,[19][20][21]23 Since the cyanotic (hypoxic) neonatal myocardium is susceptible to a reoxygenation injury during the abrupt reintroduction of molecular oxygen, and this damage is produced to oxygen free radicals, it may be possible to minimize the reoxygenation injury by either gradually restoring oxygen levels, or leukodepleting the blood, as white blood cells are a primary source of oxygen free radicals. [24][25][26][27][28] We tested both of these hypotheses in our acute hypoxic piglet model.…”

Section: Experimental Studiesmentioning

confidence: 99%

Hypoxia, reoxygenation and the role of systemic leukodepletion in pediatric heart surgery

Allen

Ilbawi

2001

Perfusion

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As cardiopulmonary bypass (CPB) in infants and neonates is becoming more frequent, the technical performance of these operations for congenital heart disease has made significant progress. However, little research has been carried out into the conduct of CBP in producing myocardial and pulmonary dysfunction. Postoperative organ dysfunction is a problem, particularly for cyanotic infants. This paper examines the experimental and clinical experience of injury brought about by abrupt reoxygenation of the hypoxic, or cyanotic, heart. The modalities of gradual reoxygenation and leukodepletion in limiting this injury are examined, leading to the conclusion that injury can be reduced and possibly ameliorated by changes in intraoperative management during CBP in children with cyanotic disease.

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Section: Experimental Studiesmentioning

confidence: 99%

Hypoxia, reoxygenation and the role of systemic leukodepletion in pediatric heart surgery

Allen

Ilbawi

2001

Perfusion

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“…Most previous experimental investigations used adult animal models and were characterized by short durations or variable levels of hypoxia. [1][2][3][4][5][6][7][8][9] This study was intended to investigate the primary metabolic effects of chronic hypoxia on otherwise normally developed neonatal myocardium. To accomplish this, a new animal model of induced chronic hypoxia in the newborn piglet without surgical alterations was developed.…”

mentioning

confidence: 99%

Chronic hypoxia induces adaptive metabolic changes in neonatal myocardium

Plunkett¹,

Hendry²,

Anstadt³

et al. 1996

The Journal of Thoracic and Cardiovascular Surgery

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The effect of chronic hypoxia on neonatal myocardial metabolism remains undefined. With a new neonatal piglet model, we determined changes in myocardial metabolism during global ischemia after chronic hypoxia. Five-day-old piglets (N = 30) were randomly assigned to two groups and exposed to an atmosphere of 8% oxygen or to room air for 28 days before they were killed. Left ventricular myocardium was then analyzed at control and at 15-minute intervals during 60 minutes of global normothermic ischemia to determine high-energy phosphate levels, glycogen stores, and lactate accumulation. Time to peak ischemic myocardial contracture was measured with intramyocardial needle-tipped Millar catheters as a marker of the onset of irreversible ischemic injury. Results showed an initially greater level of myocardial adenosine triphosphate in the hypoxic group (27 +/- 1.2 vs 19 +/- 1.8 micromol/gm dry wt, p = 0.001) and a delay in adenosine triphosphate depletion during 60 minutes of global ischemia compared with the control group. Initial energy charge ratios (1/2 adenosine diphosphate + adenosine triphosphate/adenosine monophosphate + adenosine diphosphate + adenosine triphosphate) were also greater in the hypoxic group (0.96 +/- 0.01 vs 0.81 +/- 0.04, p = 0.01) and remained so throughout global ischemia. Initial glycogen stores were greater in the hypoxic group (273 +/- 13.3 vs 215 +/- 14.7 micromol/gm dry weight, p = 0.02) when compared with the control group. Lactate levels in the hypoxic group were initially higher (19.1 +/- 6.4 vs 8.9 +/- 3.1 micromol/gm dry weight, p = 0.001) compared with control levels and remained elevated throughout 60 minutes of ischemia. Time to peak ischemic contracture was prolonged in the hypoxic group (69.5 +/- 1.8 vs 48.9 +/- 1.4 minutes, p = 0.001) compared with the controls group. These data show that chronic hypoxia results in significant myocardial metabolic adaptive changes, which in turn result in an improved tolerance to severe normothermic ischemia. These beneficial effects are associated with elevated baseline glycogen storage levels and an accelerated rate of anaerobic glycolysis during ischemia.

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“…61 decreases mitochondrial enzyme activity and increases lactate production in cardiomyocytes, leading to inefficient myocardial mechanics. 64,65 In addition, polycythemia, which is often seen in patients with congenital heart disease with chronic cyanosis, can predispose patients to thrombosis secondary to sludging. This can affect coronary blood flow and contribute to ventricular dysfunction.…”

Section: Cyanosismentioning

confidence: 99%

Evaluation and Management of Chronic Heart Failure in Children and Adolescents With Congenital Heart Disease: A Scientific Statement From the American Heart Association

Amdani,

Conway,

George

et al. 2024

Circulation

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With continued medical and surgical advancements, most children and adolescents with congenital heart disease are expected to survive to adulthood. Chronic heart failure is increasingly being recognized as a major contributor to ongoing morbidity and mortality in this population as it ages, and treatment strategies to prevent and treat heart failure in the pediatric population are needed. In addition to primary myocardial dysfunction, anatomical and pathophysiological abnormalities specific to various congenital heart disease lesions contribute to the development of heart failure and affect potential strategies commonly used to treat adult patients with heart failure. This scientific statement highlights the significant knowledge gaps in understanding the epidemiology, pathophysiology, staging, and outcomes of chronic heart failure in children and adolescents with congenital heart disease not amenable to catheter-based or surgical interventions. Efforts to harmonize the definitions, staging, follow-up, and approach to heart failure in children with congenital heart disease are critical to enable the conduct of rigorous scientific studies to advance our understanding of the actual burden of heart failure in this population and to allow the development of evidence-based heart failure therapies that can improve outcomes for this high-risk cohort.

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Pathophysiology of chronic cyanosis in a canine model

Cited by 36 publications

References 34 publications

Hypoxia, reoxygenation and the role of systemic leukodepletion in pediatric heart surgery

Hypoxia, reoxygenation and the role of systemic leukodepletion in pediatric heart surgery

Chronic hypoxia induces adaptive metabolic changes in neonatal myocardium

Evaluation and Management of Chronic Heart Failure in Children and Adolescents With Congenital Heart Disease: A Scientific Statement From the American Heart Association

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