Targeting hydrogen sulfide and nitric oxide to repair cardiovascular injury after trauma

靶向硫化氢和一氧化氮以修复创伤后心血管损伤

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Abstract

The systemic cardiovascular effects of major trauma, especially neurotrauma, contribute to death and permanent disability in trauma patients and treatments are needed to improve outcomes. In some trauma patients, dysfunction of the autonomic nervous system produces a state of adrenergic overstimulation, causing either a sustained elevation in catecholamines (sympathetic storm) or oscillating bursts of paroxysmal sympathetic hyperactivity. Trauma can also activate innate immune responses that release cytokines and damage-associated molecular patterns into the circulation. This combination of altered autonomic nervous system function and widespread systemic inflammation produces secondary cardiovascular injury, including hypertension, damage to cardiac tissue, vascular endothelial dysfunction, coagulopathy and multiorgan failure. The gasotransmitters nitric oxide (NO) and hydrogen sulfide (H(2)S) are small gaseous molecules with potent effects on vascular tone regulation. Exogenous NO (inhaled) has potential therapeutic benefit in cardio-cerebrovascular diseases, but limited data suggests potential efficacy in traumatic brain injury (TBI). H(2)S is a modulator of NO signaling and autonomic nervous system function that has also been used as a drug for cardio-cerebrovascular diseases. The inhaled gases NO and H(2)S are potential treatments to restore cardio-cerebrovascular function in the post-trauma period.

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