An explanation of the preconditioning phenomenon must account for the biolo
gy of the phenomenon. Here we provide a more thorough characterization of i
schaemic preconditioning (IPC), examining temporal characteristics and the
importance of the size of area at risk. IPC was induced by two 10-min LAD o
cclusions separated by 30 min reperfusion in pentobarbital anaesthetized op
en-chest pigs. The last brief occlusion was followed by either 30 min, 2 h
or 4h of reperfusion, The degree of protection was evaluated by measuring i
nfarct size after either 45 or 60 min LAD occlusion followed by 2 h of repe
rfusion. To examine the importance of the size of area at risk, the occlusi
on site on LAD was varied between pigs, IPC followed by 30 min and 2 h of r
eperfusion reduced infarct size from 58+/-2% of area at risk to 15+/-4% (P<
0.05) and 15+/-6% (P<0.05), respectively, by 45 min of LAD occlusion, After
4 h of reperfusion the infarct size-limiting effect of IPC was still promi
nent when a test ischaemic period of 45 min was used (47 +/- 5% vs 13 +/- 1
%: P<0.05). IPC was paralleled by an increased incidence of ventricular fib
rillation during the early phase of the prolonged LAD occlusion after 30 mi
n, 2 h and 4 h of reperfusion. Although no correlation was found between in
farct size (as a percentage of area at risk) and area at risk (as a percent
age of Ventricular weight) in control pigs, a positive correlation was foun
d between these variables in preconditioned pigs. We conclude that the infa
rct size-limiting effect of IPC lasts at least 4 h and that it is parallele
d by profibrillatory effects in open-chest pigs. Furthermore, the infarct s
ize-limiting effect of IPC depends on the size of area at risk, being most
pronounced when area at risk is small. (C) 1999 Academic Press.