Acute cardiac care & resuscitation
Targeting branched-chain amino acid (BCAA)/PPAR-γ axis with pioglitazone reverses insulin resistance and mitigates post-cardiac arrest injury
- A retrospective cohort (121 cardiac arrest (CA) patients) and a prospective case-control study (25 CA patients vs. 21 controls)
- rat CA model
- HT22 cell oxygen-glucose deprivation/reperfusion model
+2 more
- rat CA model
- HT22 cell oxygen-glucose deprivation/reperfusion model
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
Main finding
As reported in the abstract
Glucose variability
P < 0.0001
Observational data: associations, not effects.
Further findings
| Outcome | CA patients | controls | Neurological Deficit Score | P value |
|---|---|---|---|---|
| Homeostasis model assessment of insulin resistance · elevated 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:10.1016/j.resuscitation.2026.111272
Summarised from the published abstract; every number is checked against it