Abstract 282: Mitochondrial Complex I Induced Myocardial Stunning Following Cardiopulmonary Resuscitation
Bibliographic record
Abstract
Background: Cardiogenic shock following cardiopulmonary resuscitation (CPR) for sudden cardiac arrest is common, occurring even in the absence of acute coronary artery occlusion, and contributes to high rates of post-CPR mortality. The pathophysiology of this shock is unclear and effective therapies for improving clinical outcomes are lacking. Methods and Results: Using a murine model of asystolic cardiac arrest, we investigated the pathophysiology of post-CPR cardiogenic shock and discovered that duration of cardiac arrest (4, 8, 12 or 16-minute) prior to CPR determined post-resuscitation success rates, degree of neurological injury, and severity of myocardial dysfunction. Post-CPR cardiac dysfunction was not associated with myocardial necrosis, apoptosis, inflammation, or mitochondrial permeability transition pore opening and recovered within several days, indicative of myocardial stunning. Post-CPR myocardial stunning was associated with increases in ventricular and mitochondrial reactive oxygen species (ROS, P <0.001 vs Sham, respectively). Seahorse micropolarimetry of isolated post-CPR cardiac mitochondria revealed decreased rates of maximal oxygen consumption rates (OCR) for both Complex I and Complex II vs controls ( P <0.01 vs Sham, respectively), indicating inhibition of mitochondrial oxidative phosphorylation. Paradoxically, in the presence of ADP stimulated coupled respiration, post-CRP mitochondria demonstrated increased OCR ( P <0.05 vs Sham) and increased rates of proton leak ( P <0.05 vs Sham), suggesting Complex I as the site of ROS generation. These findings were not observed at complex II. S1QEL, a complex I-specific superoxide inhibitor, administered during CPR, decreased myocardial ROS generation while improving post-CPR myocardial function ( P <0.01 vs CPR control), neurological injury ( P <0.01 vs CPR control), and survival ( P <0.01 vs CPR control). Conclusions: Our results demonstrate that cardiogenic shock following resuscitation from cardiac arrest is consistent with myocardial stunning mediated by mitochondrial complex I injury and ROS generation. Targeting this mechanism represents a novel and practical therapy for improving sudden cardiac arrest resuscitation outcomes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".