Chronic heart failure is associated with reduced myocardial β-adrenergic receptor expression and mitochondrial function. Since these data coincide with increased plasma catecholamine levels, we investigated the relation between myocardial β-receptor expression and mitochondrial respiratory activity under conditions of physiological catecholamine concentrations. This post hoc analysis used material of a prospective randomized, controlled study on 12 sexually mature (age 20–24 weeks) Early Life Stress or control pigs (weaning at day 21 and 28–35 after birth, respectively) of either sex. Measurements in anesthetized, mechanically ventilated, and instrumented animals comprised serum catecholamine (liquid-chromatography/tandem-mass-spectrometry) and 8-isoprostane levels, whole blood superoxide anion concentrations (electron spin resonance), oxidative DNA strand breaks (tail moment in the “comet assay”), post mortem cardiac tissue mitochondrial respiration, and immunohistochemistry (β₂-adrenoreceptor, mitochondrial respiration complex, and nitrotyrosine expression). Catecholamine concentrations were inversely related to myocardial mitochondrial respiratory activity and β₂-adrenoceptor expression, whereas there was no relation to mitochondrial respiratory complex expression. Except for a significant, direct, non-linear relation between DNA damage and noradrenaline levels, catecholamine concentrations were unrelated to markers of oxidative stress. The present study suggests that physiological variations of the plasma catecholamine concentrations, e.g., due to physical and/or psychological stress, may affect cardiac β₂-adrenoceptor expression and mitochondrial respiration.

Early life stress (ELS) significantly increases the risk of chronic cardiovascular diseases and may cause neuroinflammation. This post hoc study, based on the material available from a previous study showing elevated “serum brain injury markers” in male control animals, examines the effect of sex and/or ELS on the cerebral and cardiac expression of the H₂S and oxytocin systems. Following approval by the Regional Council of Tübingen, a randomized controlled study was conducted on 12 sexually mature, uncastrated German Large White swine of both sexes. The control animals were separated from their mothers at 28–35 days, while the ELS group was separated at day 21. At 20–24 weeks, animals underwent anesthesia, ventilation, and surgical instrumentation. An immunohistochemical analysis of oxytocin, its receptor, and the H₂S-producing enzymes cystathionine-β-synthase and cystathionine-γ-lyase was performed on hypothalamic, prefrontal cortex, and myocardial tissue samples. Data are expressed as the % of positive tissue staining, and differences between groups were tested using a two-way ANOVA. The results showed no significant differences in the oxytocin and H₂S systems between groups; however, sex influenced the oxytocin system, and ELS affected the oxytocin and H₂S systems in a sex-specific manner. No immunohistochemical correlate to the elevated “serum brain injury markers” in male controls was identified.

Background: Equivocal data exist on whether noradrenaline during resuscitation from circulatory shock affects tissue mitochondrial respiration. Therefore, we examined the relation between myocardial mitochondrial respiration and plasma noradrenaline concentrations during continuous i.v. noradrenaline. Methods: After anesthesia and (neuro)surgical instrumentation, pigs underwent two hours of subdural blood injection and subsequent systemic blood removal, followed by fluid resuscitation, re-transfusion of shed blood, and noradrenaline to maintain cerebral perfusion pressure at pre-shock levels. Before, immediately after the challenge, and after 48 h of resuscitation, we measured whole blood superoxide anion levels (electron spin resonance) and DNA strand breaks ("tail moment" in the comet assay), and plasma noradrenaline (HPLC/tandem mass-spectrometry), NOx (chemoluminescence), isoprostane and troponin (ELISA) concentrations. Immediate post mortem myocardial samples were analyzed for mitochondrial respiration (high-resolution respirometry for Complex I/II activity, oxidative phosphorylation, and maximal uncoupled electron transfer capacity) as well as β ₁ -/β ₂ -adrenergic receptor and mitochondrial complex I/II expression, and nitrotyrosine formation (immunohistochemistry). Results: At 48 h of resuscitation, plasma noradrenaline concentrations were 200-fold those at baseline, while NOx levels had doubled. Myocardial mitochondrial respiration was unrelated to noradrenaline, NOx, or nitrotyrosine, but directly related to both the β ₁ - and β ₂ -adrenoceptor expression (oxidative phosphorylation: r = 0.466, p = 0.059 and r = 0.750, p = 0.0005, respectively; maximal uncoupled electron transfer capacity: r = 0.514, p = 0.035 and r = 0.772, p = 0.0003, respectively). Oxidative phosphorylation was inversely related to the plasma troponin-I levels (r = -0.479, p = 0.060). While plasma NOx levels correlated with plasma noradrenaline levels (r = 0.519, p = 0.033), whole blood superoxide anion levels and cardiac nitrotyrosine formation did not. Conclusions: In a long-term, resuscitated porcine model of acute subdural hematoma and hemorrhage, plasma NOx levels correlated with noradrenaline plasma levels, whereas mitochondrial respiration and other markers of radical formation or oxidative/nitrosative stress were unrelated to noradrenaline concentrations. β-adrenergic receptor expression was also unrelated to noradrenaline, while mitochondrial respiration was directly related to both the β ₁ - and β ₂ -adrenoceptor expression. Our results suggest that the impaired mitochondrial respiration reported during septic shock for skeletal muscle may be absent in the heart during continuous i.v. noradrenaline for resuscitation from trauma-and-hemorrhage. Nevertheless, cardiac tissue injury is associated with reduced mitochondrial respiration.