Mechanistic insights into cell-free hemoglobin-induced injury during septic shock

Autor: Harvey G. Klein, Juan J Lertora, Thomas F. Risoleo, Mark T. Gladwin, Elmira Alipour, Swati Basu, Willard N. Applefeld, Zoe G. Couse, Daniel B. Kim-Shapiro, Jing Feng, Steven B. Solomon, Robert L. Danner, Jesús Tejero, Charles Natanson, Jeffrey Wang, Vandana Sachdev, Junfeng Sun
Rok vydání: 2021
Předmět:
Zdroj: American journal of physiology. Heart and circulatory physiology. 320(6)
ISSN: 1522-1539
Popis: Cell-free hemoglobin (CFH) elevations are a known consequence of clinical sepsis. Using a two-by-two factorial design and extensive physiological and biochemical evidence, we found a direct mechanism of injury related to nitric oxide scavenging leading to pulmonary hypertension increasing right heart afterload, depressed cardiac function, worsening circulatory failure, and death, as well as an indirect mechanism related to iron toxicity. These discoveries alter conventional thinking about septic shock pathogenesis and provide novel therapeutic approaches.
Databáze: OpenAIRE