Table 1.

Limitations in pig models for cardioplegic arrest.

Limitation	References
Animal number
limited number of animals	[21,27,28,29,31,35,36,49,57,58,59,60,61,62,63,64]
Time limits
short cross clamping time	[23,24,49,58]
short reperfusion/recovery time	[23,25,27,28,31,32,33,38,60,61,62,64,65,66]
short observation period/no long-term follow up	[26,32,59,63,65]
Randomization & blinding
no randomization	[60,63]
surgeon/observer not blinded	[37,60,63]
Comparability with clinical settings
use of young, healthy animals without clinically relevant pathology	[21,23,24,25,29,31,32,33,44,57,61,64]
results not fully comparable with humans	[26,29,44,49,58,67,68]
the use of neonatal piglets not allowed (animal protection requirements)	[49,58]
standardization of interventions/no individual treatment	[21,23,24,25,26,31,32,46,49,64]
model restricted to mild ischemia	[35,48,66]
reperfusion phase departed from clinical normality	[66]
Study endpoints
effect on study endpoint not fully reached	[36,69]
endpoint not suited	[56,62]
lack of measurement of end-point related parameters	[26,50,68]
use of surrogate markers for endpoint measurement	[26]
Missing data and measurements
missing control	[32,50]
the number of tested factors in one study limited	[24,57,65]
missing measurement/correlation with cardiac function	[56,61,69]
myocardial temperature not monitored	[55]
missing dose-response relationship for tested supplement	[50]
missing pressure-volume measurements	[21]
missing histological examination	[62]
wrong time point of blood/biopsy withdrawal	[44,60]