Search

Pyruvate-fortified cardioplegia protects myocardium and hastens postsurgical recovery of patients undergoing cardiopulmonary bypass (CPB). Pyruvate reportedly suppresses degradation of the α-subunit of hypoxia-inducible factor-1 (HIF-1), an activator of the gene encoding the cardioprotective cytokine erythropoietin (EPO). This study tested the hypothesis that pyruvate-enriched cardioplegia evoked EPO expression and mobilized EPO signaling mechanisms in myocardium. Hearts of pigs maintained on CPB were arrested for 60 mm with 4:1 blood-crystalloid cardioplegia. The crystalloid component contained 188 mM glucose ± 24 mM pyruvate. After 30-mm cardiac reperfusion with cardioplegia-free blood, the pigs were weaned from CPB. Left ventricular myocardium was sampled 4 h after CPB for immunoblot assessment of HIF-1α, EPO and its receptor, the signaling kinases Akt and ERK, and endothelial nitric oxide synthase (eNOS), an effector of EPO signaling. Pyruvate-fortified cardioplegia stabilized arterial pressure post-CPB, induced myocardial EPO mRNA expression, and increased HIF-1α, EPO, and EPO-R protein contents by 60, 58, and 123%, respectively, vs. control cardioplegia (P < 0.05). Pyruvate cardioplegia also increased ERK phosphorylation by 61 and 118%, respectively, vs. control cardioplegia-treated and non-CPB sham myocardium (P < 0.01), but did not alter Akt phosphorylation. Nitric oxide synthase (NOS) activity and eNOS content fell 32% following control CPB vs. sham, but pyruvate cardioplegia prevented these declines, yielding 49 and 80% greater NOS activity and eNOS content vs. respective control values (P < 0.01). Pyruvate-fortified cardioplegia induced myocardial EPO expression and mobilized the EPOERK-eNOS mechanism. By stabilizing HIF-1α, pyruvate-fortified cardioplegia may evoke sustained activation of EPO's cardioprotective signaling cascade in myocardium. [ABSTRACT FROM AUTHOR]

Oxidative stress during cardiac arrest may inactivate myocardial enzymes and thereby exacerbate ischemic derangements of myocardial metabolism. This study examined the impact of cardiac arrest on left ventricular enzymes. Beagles were subjected to 5 mm of cardiac arrest and 5 mm of open-chest cardiac compressions (OCCC) before epicardial direct current countershocks were applied to restore sinus rhythm. Glutathione/glutathione disulfide redox state (GSH/GSSG) and a panel of enzyme activities were measured in snap-frozen left ventricle. To test whether oxidative stress during arrest inactivated the enzymes, metabolic (pyruvate) or pharmacological (N-acetyl-L-cysteine) antioxidants were infused intravenously for 30 mm before arrest. During cardiac arrest, activities of phosphofructokinase, citrate synthase, aconitase, malate dehydrogenase, creatine kinase, glucose-6-phosphate dehydrogenase, and glutathione reductase fell by 56, 81, 55, 34, 42, 55, and 45%, respectively, coincident with 50% decline in GSH/GSSG. OCCC effected full recovery of glutathione reductase and partial recovery of citrate synthase and aconitase, in parallel with GSH/GSSG. Phosphofructokinase, malate dehydrogenase, creatine kinase, and glucose-6- phosphate dehydrogenase recovered only after cardioversion. Antioxidant pretreatments augmented phosphofructokinase, aconitase, and malate dehydrogenase activities before arrest and enhanced these activities, as well as those of citrate synthase and glucose-6-phosphate dehydrogenase, during arrest. In conclusion, cardiac arrest reversibly inactivates several important myocardial metabolic enzymes. Antioxidant protection of these enzymes implicates oxidative stress as a principal mechanism of enzyme inactivation during arrest. [ABSTRACT FROM AUTHOR]

Presents a study which investigated the contractile and energetic effects of low versus high dobutamine doses in the hypoperfused right ventricular myocardium. Methods; Results; Discussion.

OBJECTIVE: To identify the best predictor among waist circumference, waist to hip ratio (WHR), weight and body mass index (BMI) of visceral obesity across 8.5-10.8y. We also examined whether changes in waist across the study period co-occur with changes in psychosocial distress or quality of life, and tested whether action levels of waist (level I < 80 cm, level 1-2:80-87.9 cm, level 2 ≥ 88 cm) differentiate between women with varying levels of psychosocial distress and quality of life. SUBJECTS AND MEASUREMENTS: Visceral adipose tissue (VAT) was determined by computerized-tomography at the L4-L5 disc space, and waist circumference, WHR, weight and BMI by anthropometric techniques in a populationbased sample of postmenopausal Healthy Women Study participants. Psychosocial distress and quality of life were assessed by standardized tests of personality and behavior. The n varied from 120-345, depending on the research question. RESULTS: Waist circumference was superior over the other anthropometric measures in predicting VAT accounting for 40.1-63.5% of the variance in VAT over the study period (P<0.001). Associations between symptoms of depression, anxiety or distress, Iow levels of social support or impaired quality of life with waist circumference were cross-sectional (P < 0.04), with lower levels of distress and less impaired daily functioning being characteristic to women at the action level I relative to levels 1 -2 or 2. Increasing anger over time was associated longitudinally with increasing waist circumference (P < 0.03). CONCLUSIONS: Identification of healthy women with large waist circumferences is important for prevention and intervention of poor quality of life and chronic disease. [ABSTRACT FROM AUTHOR]