Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
-
There is evidence to suggest that the hypothermia observed in the most severe cases of systemic inflammation or sepsis is a regulated response with potential adaptive value, but the mechanisms involved are poorly understood. Here, we investigated the interplay between brain oxygenation (assessed by tissue P o2 ) and the development of hypothermia in unanesthetized rats challenged with a hypotension-inducing dose of bacterial LPS (1 mg/kg i.v.). At an ambient temperature of 22°C, oxygen consumption (V̇O 2 ) began to fall only a few minutes after the LPS injection, and this suppression in metabolic rate preceded the decrease in core temperature. ⋯ On the other hand, the decrease in V̇O 2 usually preceded the rise in P o2 , and an inverse correlation between V̇O 2 and brain P o2 was consistently observed. These findings do not support the existence of a closed-loop feedback relationship between brain oxygenation and hypothermia in systemic inflammation. The data are consistent with a feedforward mechanism in which hypothermia is triggered (possibly by cryogenic inflammatory mediators) in anticipation of changes in brain oxygenation to prevent the development of tissue hypoxia.
-
Background: The high mortality rates of patients who are resuscitated from cardiac arrest (CA) are attributed to post cardiac arrest syndrome (PCAS). This study evaluated the effect of hyperoxygenation and targeted temperature management (TTM) on PCAS in rats with different causes of CA. Methods and Results: One hundred sixty-eight Sprague-Dawley rats were equally divided into asphyxial and dysrhythmic groups. ⋯ Compared with NO-NT (57.7% ± 14.9% and 40.3% ± 7.8%), the collagen volume fraction and the proportion of fluoro-jade B-positive area in HO-HT (14.0% ± 5.7% and 28.0% ± 13.3%) were significantly reduced. Conclusion: The beneficial effects of hyperoxygenation and TTM are dependent on the cause of arrest: hyperoxygenation benefits asphyxial, whereas TTM benefits dysrhythmic CA. The combination of hyperoxygenation and TTM could effectively improve the functional outcome of PCAS regardless of the cause of CA.
-
β 3 -adrenergic receptor (β 3 -AR) has been proposed as a new therapy for several myocardial diseases. However, the effect of β 3 -AR activation on sepsis-induced myocardial apoptosis is unclear. Here, we investigated the effect of β 3 -AR activation on the cardiomyocyte apoptosis and cardiac dysfunction in cecal ligation and puncture (CLP)-operated rats and lipopolysaccharide (LPS)-treated cardiomyocytes. ⋯ Furthermore, administration of β 3 -AR antagonist, SR59230A (5 mg/kg), significantly decreased the maximum rate of left ventricular pressure rise (+dP/dt) in CLP-induced septic rats. SR59230A not only increased myocardial apoptosis, reduced p-Akt Ser473 and Bcl-2 contents, but also increased mitochondrial Bax, cytoplasm cytochrome c, cleaved caspase-9, and cleaved caspase-3 levels of the myocardium in septic rats. These results suggest that endogenous β 3 -AR activation alleviates sepsis-induced cardiomyocyte apoptosis via PI3K/Akt signaling pathway and maintains intrinsic myocardial systolic function in sepsis.