Acute cardiac care & resuscitation
Targeting branched-chain amino acid (BCAA)/PPAR-γ axis with pioglitazone reverses insulin resistance and mitigates post-cardiac arrest injury
Authors' conclusion
Dysregulated BCAA metabolism triggers IR via PPAR-γ suppression after CA, exacerbating ischemic brain injury. Targeting the BCAA/PPAR-γ/IR axis with pioglitazone effectively reverses this pathology, providing a mechanistically grounded and highly translatable therapeutic strategy for post-resuscitation care.
Study context
- Population
- Cardiac arrest (CA) patients and controls; rat CA model; HT22 cellsretrospective cohort, CA patients 121 · prospective case-control, CA patients 25 · prospective case-control, controls 21
- Participants
- 25 vs 21
- Exposure
- 25 CA patients vs. 21 controls
- CA patientsn = 25
- Controlsn = 21
- Outcome
- Glucose variability
Methodological details25 CA patients vs. 21 controls, rat CA model, HT22 cell oxygen-glucose deprivation/reperfusion model
- 25 CA patients vs. 21 controls
- Rat CA model
- HT22 cell oxygen-glucose deprivation/reperfusion model
Main finding
As reported in the abstract
P < 0.0001
Observational data: associations, not effects.
Further findings
| Outcome | CA patients | Controls | Neurological Deficit Score | P value |
|---|---|---|---|---|
| Homeostasis model assessment of insulin resistanceElevated in CA patients | 4.98 | 2.62 | P = 0.001 | |
| Neurological Deficit Score with pioglitazone (rat) | 66.94 vs. 53.78 | P < 0.001 |
Systemic and cerebral insulin resistance (IR) in CA rat model · 72 h post-resuscitation
- Systemic and cerebral IR developed by 72 h post-resuscitation
- Systemic and cerebral insulin resistance developed by 72 h post-resuscitation in CA rat model; metabolic analysis uncovered localized BCAA accumulation in the post-CA hippocampus, driven by branched-chain ketoacid dehydrogenase kinase (BCKDK) upregulation
Post-CA survival with pioglitazone (rat)
- Improving post-CA survival
- by 40%
- P < 0.05
Original publication
Targeting BCAA/PPAR-γ axis with pioglitazone reverses insulin resistance and mitigates post-cardiac arrest injury. Resuscitation. Published 20 August 2026. doi:10.
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