Journal
CRITICAL CARE MEDICINE
Volume 37, Issue 4, Pages 1397-1402Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0b013e31819cecd6
Keywords
sepsis; cytochrome oxidase; caffeine; mitochondria; enzyme inhibition; isolated heart; cardiac dysfunction
Categories
Funding
- NIH/NIGMS [5K08GM074117-04]
- Maria Fared Children's Hospital Foundation [5R01GM059930-08]
- University of Pennsylvania
Ask authors/readers for more resources
Objective: Impaired mitochondrial function is a potential cause of sepsis-associated myocardial depression. Cytochrome oxidase (CcOX), the terminal oxidase of the electron transport chain, Is Inhibited in the septic heart. Caffeine increases CcOX activity by increasing cyclic adenosine monophosphate and protein kinase A activity. We hypothesized that caffeine will restore myocardial CcOX activity increase cardiac function, and improve survival during sepsis. Design: Prospective randomized controlled study. Setting: University hospital-based laboratory. Subjects. One hundred twenty Sprague-Dawley male rats. Interventions., Sprague-Dawley male rats underwent cecal ligation and puncture (CLP) or sham operation. At 24 and 48 hours, rats underwent intraperitoneal injection of either caffeine (7.5 mg/kg, the equivalent of 1-1.5 cups of coffee) or equal volume of saline. Measurements and Main Results. One hour following the 48-hour injection, steady-state CcOX kinetic activity was measured in isolated mitochondria and normalized to citrate synthase activity. Cardiac function was assessed using an isolated rat heart preparation and survival was tracked to 96 hours. CLP significantly decreased myocardial CcOX activity, oxygen consumption, left ventricular pressure, and pressure developed during isovolumic contraction (+dP/dt) and relaxation (-dP/dt). Caffeine restored CcOX activity and increased left ventricular pressure and +/-dP/dt toward sham values following CLP. Survival significantly improved following CLP in caffeine-injected animals compared with saline injection. Conclusion: Caffeine may be a novel therapy to treat sepsis-associated myocardial depression. (Crit Care Med 2009; 37: 1397-1402)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available