Ghrelin reduced inflammation, oxidative stress, and cell death in rat hearts during cardiopulmonary bypass, improving cardiac function through an Akt-mediated signaling pathway.
Multiple injury markers reducedGhrelin simultaneously lowered TNF-α, IL-6, myeloperoxidase, oxidative stress, and apoptosis during cardiopulmonary bypass in rats
What the researchers found
Ghrelin provided comprehensive cardioprotection during cardiopulmonary bypass in rats:
• Reduced inflammatory markers: TNF-α, IL-6, and myocardial myeloperoxidase activity were all decreased
• Reduced apoptosis (programmed cell death) in heart muscle cells
• Decreased oxidative stress in cardiac tissue
• Lowered levels of myocardial injury markers
• Significantly improved cardiac function after CPB
• In cultured cardiomyocytes, ghrelin increased cell viability and decreased apoptosis during simulated CPB
• Blocking the ghrelin receptor (with [D-Lys3]-GHRP-6) or the PI3K/Akt pathway (with wortmannin) eliminated all protective effects, confirming the mechanism involves GHSR-1a receptor activation and downstream Akt signaling
Why it matters
Millions of patients undergo cardiopulmonary bypass annually for heart surgeries, and the procedure itself causes significant heart damage through inflammation and ischemia-reperfusion injury. There is an unmet clinical need for agents that protect the heart during CPB. This study suggests ghrelin could be such an agent, reducing multiple pathways of injury simultaneously through a well-defined mechanism.
How the study worked
Adult male Sprague-Dawley rats were subjected to cardiopulmonary bypass and randomized into four groups of 8: vehicle, ghrelin, ghrelin plus GHSR-1a inhibitor, and ghrelin plus PI3K inhibitor. Researchers measured inflammatory markers (TNF-α, IL-6, myeloperoxidase), oxidative stress, apoptosis, cardiac injury biomarkers, and cardiac function. Complementary in vitro experiments used cultured cardiomyocytes subjected to simulated CPB conditions to confirm findings and test mechanisms.
What this study cannot tell us
This was an animal study in rats, and CPB in rats differs from human cardiac surgery in duration, complexity, and scale. The study measured acute effects only — long-term cardioprotection was not assessed. Ghrelin dosing in rats may not translate directly to human dosing. The study used only male rats, limiting generalizability. No comparison was made with existing cardioprotective strategies used during human CPB.
How to read the evidence
This is a preclinical animal study with both in vivo (rat CPB model) and in vitro (cultured cardiomyocyte) components. The use of specific pathway inhibitors strengthens the mechanistic conclusions. However, no human data exists for ghrelin use during cardiac surgery, placing this at a preclinical evidence level.
When this study was published
Published in 2013, this study is about 13 years old. It contributed to the mechanistic understanding of ghrelin's cardioprotective properties. The concept of using ghrelin for cardiac protection during surgery has not yet advanced to human clinical trials.
The bigger picture
This study adds to the growing body of evidence that ghrelin has cardioprotective properties beyond its known roles in appetite and growth hormone release. Prior work showed ghrelin improves cardiac function in heart failure; this extends those findings to the surgical context of cardiopulmonary bypass. The identification of the GHSR-1a/Akt pathway as the mechanism provides a clear pharmacological target and explains how ghrelin protects the heart at the molecular level.
Questions still open
- Could ghrelin be administered to human patients during cardiac surgery to reduce bypass-related heart damage?
- How does ghrelin's cardioprotective effect compare to existing cardioplegia and myocardial protection strategies?
- Would the growth hormone-releasing effects of ghrelin cause problems if used perioperatively in cardiac surgery patients?
Common questions
Why does cardiopulmonary bypass damage the heart?
How does ghrelin protect the heart during bypass?
Read the original research
Cardioprotective effect of ghrelin in cardiopulmonary bypass involves a reduction in inflammatory response.
PloS one, 8(1), e55021
Citation
Cao, Yukun; Tang, Jun; Yang, Ting; Ma, Heng; Yi, Dinghua; Gu, Chunhu; Yu, Shiqiang. (2013). Cardioprotective effect of ghrelin in cardiopulmonary bypass involves a reduction in inflammatory response.. PloS one, 8(1), e55021. https://doi.org/10.1371/journal.pone.0055021