Loading…
Insulin Postconditioning Reduces Infarct Size in the Porcine Heart in a Dose-Dependent Manner
Aim: Insulin and glucose may have opposite effects when used to reduce ischemia–reperfusion injury. When insulin is administered alone, feeding state determines tolerance and further induces metabolic and hormonal changes. Higher insulin doses are needed for similar activation of cardioprotective Ak...
Saved in:
| Published in: | Journal of cardiovascular pharmacology and therapeutics 2017-03, Vol.22 (2), p.179-188 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Request full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Aim:
Insulin and glucose may have opposite effects when used to reduce ischemia–reperfusion injury. When insulin is administered alone, feeding state determines tolerance and further induces metabolic and hormonal changes. Higher insulin doses are needed for similar activation of cardioprotective Akt signaling in the fed compared to the fasted pig heart. Thus, the aim of the study was to investigate the effects of 2 prespecified insulin doses on infarct size, apoptosis, metabolism, and cardiac function in a clinically relevant, randomized large animal model using conventional percutaneous catheter intervention techniques and including different fasting states.
Methods and Results:
Twenty-seven female pigs were subjected to 40-minute ischemia and 120-minute reperfusion. Pharmacological postconditioning with intracoronary infusions administered over 3 × 30 seconds was performed at immediate reperfusion. Animals were randomly assigned to 3 groups—preexperimental fasting and intracoronary saline (controls), preexperimental fasting and 0.1U of insulin (fasted Ins0.1U
), and preexperimental feeding and 1.0U of insulin (fed Ins1.0U
). A significant reduction in infarct size was demonstrated in the fed Ins1.0U group (P = .047) but not in the fasted Ins0.1U group (P = .531) compared to controls (infarct size normalized to area at risk ± standard deviation: controls 70.2% ± 12.9%, fasted Ins0.1U 65.0% ± 9.4%, and fed Ins1.0U 54.4% ± 7.3%). Infarct limitation was associated with more uncleaved caspase-3 in the area of risk and the infarcted area, lower circulating free fatty acids, and less increase in heart rate during reperfusion. Fed animals had higher levels of glucose, carnitine, potassium, and normetanephrine and higher heart rate at baseline compared to controls.
Conclusion:
Insulin postconditioning reduced infarct size in the in vivo pig heart, but the beneficial effects were restricted to the highest dose, which is limited by side effects and can only be given to nonfasted animals. The finding challenges successful general use of insulin in the treatment of reperfusion injury in clinical acute myocardial infarction. |
|---|---|
| ISSN: | 1074-2484 1940-4034 |
| DOI: | 10.1177/1074248416657611 |