Experimental parameters and infarct size in closed chest pig LAD ischemia reperfusion models; lessons learned.
BACKGROUND
Preclinical models that resemble the clinical setting as closely as possible are essential in translating promising therapies for the treatment of acute myocardial infarction. Closed chest pig left anterior descending coronary artery (LAD) ischemia reperfusion (I/R) models are valuable and clinically relevant. Knowledge on the influence of experimental design on infarct size (IS) in these models is a prerequisite for suitable models. To this end, we investigated the impact of several experimental features (occlusion and follow-up time and influence of area at risk (AAR)) on IS.


METHODS
A total of fifty-one female Landrace pigs were subjected to closed chest LAD balloon occlusion and evaluated in three substudies with varying protocols. To assess the relationship between time of occlusion and the IS, 18 pigs were subjected to 60-, 75- and 90 min of occlusion and terminated after 24 h of follow-up. Influence of prolonged follow-up on IS was studied in 18 pigs after 75 min of occlusion that were terminated at 1, 3 and 7 days. The relation between AAR and IS was studied in 28 pigs after 60 min of occlusion and 24 h of follow-up. The relation between VF, number of shocks and IS was studied in the same 28 pigs after 60 min of occlusion.


RESULTS
Increasing occlusion time resulted in an increased IS as a ratio of the AAR (IS/AAR). This ranged from 53 ± 23% after 60 min of occlusion to 88 ± 2.2% after 90 min (P = 0.01). Increasing follow-up, from 1 to 3 or 7 days after 75 min of occlusion did not effect IS/AAR. Increasing AAR led to a larger IS/AAR (r2 = 0.34, P = 0.002), earlier VF (r2 = 0.32, P = 0.027) and a higher number of shocks (r2 = 0.29, P = 0.004) in pigs subjected to 60 min of occlusion.


CONCLUSIONS
These experiments describe the association of occlusion time, follow-up duration, AAR and VF with IS in closed chest pig LAD I/R models. These results have important implications for future I/R studies in pigs and can serve as a guideline for the selection of appropriate parameters and the optimal experimental design.
['Silvis|Max J M|MJM|', 'van Hout|Gerardus P J|GPJ|', 'Fiolet|Aernoud T L|ATL|', 'Dekker|Mirthe|M|', 'Bosch|Lena|L|', 'van Nieuwburg|Martijn M J|MMJ|', 'Visser|Joyce|J|', 'Jansen|Marlijn S|MS|', 'Timmers|Leo|L|', 'de Kleijn|Dominique P V|DPV|0000-0003-2714-2140']
D000818:Animals D021721:Balloon Occlusion D004195:Disease Models, Animal D004554:Electric Countershock D005260:Female D009203:Myocardial Infarction D015425:Myocardial Reperfusion D015428:Myocardial Reperfusion Injury D009206:Myocardium D034421:Sus scrofa D013997:Time Factors D014693:Ventricular Fibrillation
LAD Myocardial infarction Ischemia/reperfusion injury Pig model