TABLE 3.
Experimental models used to define the role of HDL metabolism on cardioprotection
| Animal model | Ischaemia/reperfusion protocol | Treatment | Key findings | Reference |
|---|---|---|---|---|
| Mice | ||||
| C57BL/6 mice on normal and HFD | 30 min ischaemia/1 hr reperfusion | rHDL (25‐mg ApoA1/ml) delivered during reperfusion | Reduction in infarct size in mice on normal and HFD | Heywood et al., 2017 |
| C57Bl6/N mice | 30 min ischaemia/24 hr reperfusion | HDL administered intravenously for 21 days prior to ischaemia | Reduction in infarct size | Theilmeier et al., 2006 |
| C57BL/6 mice | 35 min ischaemia/45 min reperfusion | rHDL (100, 200, and 400 μg·ml−1) perfused for 7 min at onset of reperfusion | Dose‐dependent reduction in infarct size | Frias et al., 2013 |
| C57BL/6 mice | 45 min ischaemia/24 hr reperfusion | rHDL enriched with S1P infused 1 min before reperfusion | Reduction in infarct size | Brulhart‐Meynet et al., 2015 |
| ApoA1−/− C57BL/6 mice | 30 min ischaemia/3 hr reperfusion | — | Increase in infarct size in ApoA1−/− mice | Dadabayev et al., 2014 |
| Rats | ||||
| Healthy male Sprague–Dawley rats | 15 min ischaemia/20 min reperfusion | Physiological concentrations of HDL infused during I/R | Reduction in the incidence of arrhythmias | Mochizuki et al., 1991 |
| Healthy male Sprague–Dawley rats | 20 min ischaemia/30 min reperfusion | HDL (0.5 and 1.0 mg·ml−1) perfused 10 min prior to ischaemia | Improved post‐ischaemic left ventricular functional recovery at reperfusion | Calabresi et al., 2003 |
| Healthy male Sprague–Dawley rats | 20 min ischaemia/30 min reperfusion | Synthetic HDL (0.5, 1.0, and 2.0 mg·ml−1) perfused 10 min prior to ischaemia | Dose‐dependent improved left ventricular functional recovery | Rossoni et al., 2004 |
| Healthy male Sprague–Dawley rats | 20 min ischaemia/30 min reperfusion | Synthetic HDL (1.0 mg·ml−1) perfused 10 min prior to ischaemia | Improvement in post‐ischaemic left ventricular developed pressure recovery and attenuation of coronary perfusion pressure elevation | Gomaraschi et al., 2008 |
| Healthy male Wistar rats | Rat coronary artery ligation | rHDL was infused 10 min before permanent ligation | Reduction of fibrosis in ligated hearts | Kiya et al., 2009 |
| Healthy male Sprague–Dawley rats | 30 min ischaemia/3 hr reperfusion | Synthetic HDL infused 10 min before reperfusion | Reduction in creatine kinase, TNF‐α, and IL‐6 in cardiac tissue | Gu et al., 2007 |
| Healthy male Wistar rats | 5 min ischaemia/3 min reperfusion | rHDL was infused 10 min before occlusion | Suppression of reperfusion‐induced arrhythmias | Imaizumi et al., 2008 |
| Healthy male Wistar rats | 35 min ischaemia/90 min reperfusion | HDL from healthy and MI patients infused during first 7 min of reperfusion | HDL isolated from MI patients failed to reduce the infarct size | Soares et al., 2019 |
| Rabbits | ||||
| Healthy Male New Zealand White rabbits | 30 min ischaemia/1 hr reperfusion ApoA1‐Milano | Hearts were treated during the 10‐min pretreatment and the 60 min of reperfusion with ApoA1‐Milano | Reduction of tissue lipid hydroperoxides in hearts subjected to global ischaemia | Marchesi et al., 2008 |
| Healthy Male New Zealand White rabbits | 30 min ischaemia/4 hr reperfusion | 100 mg·kg−1 synthetic ApoA1‐Milano (ETC‐216) 1 day before and at the time of the surgical procedure | Reduction in infarct size |
Marchesi et al., 2004 Marchesi et al., 2008 |
| Pigs | ||||
| Young healthy pigs | 60‐min closed‐chest coronary balloon occlusion followed by reperfusion for 3 days when cardiac magnetic resonance was performed | Isolation of HDL particles from hypercholesterolaemic and non‐hypercholesterolaemic pigs. 4 days and 1 day before the induction of ischaemia, two intravenous infusions of 15 mg·kg−1 HDL particles were performed | HDL particles from hypercholesterolaemic pigs are not cardioprotective | Vilahur, Gutiérrez, et al., 2015 |