METHODS AND RESULTS: Isolated rat hearts were aerobically perfused with blood for 20 minutes before being subjected to zero-flow normothermic global
ischemia for 35 minutes and reperfusion for 40 minutes. Hearts were perfused at a constant pressure for 60 mm Hg and were paced at 360 beats per minute. Left ventricular developed pressure and
ischemic contracture were assessed with an intraventricular balloon. Four groups (n=8 hearts per group) were studied: control hearts with 35 minutes of unprotected
ischemia, hearts preconditioned with one cycle of 3 minutes of
ischemia plus 3 minutes of reperfusion before 35 minutes of
ischemia, hearts subjected to
cardioplegia with St
Thomas' solution infused for 1 minute before 35 minutes of
ischemia, and hearts subjected to preconditioning plus
cardioplegia before 35 minutes of
ischemia. After 40 minutes of reperfusion, each intervention produced a similar improvement in postischemic left ventricular development pressure (expressed as a percentage of its preischemic value: preconditioning, 44 +/- 2%;
cardioplegia, 53 +/- 3%; preconditioning plus
cardioplegia, 54 +/- 4% and control, 26 +/- 6%, P<.05). However, preconditioning accelerated whereas
cardioplegia delayed
ischemic contracture; preconditioning plus
cardioplegia gave an intermediate result. Thus, times to 75%
contracture were as follows: control, 14.3 +/- 0.4 minutes; preconditioning, 6.2 +/- 0.3 minutes;
cardioplegia 23.9 +/- 0.8 minutes; and preconditioning plus
cardioplegia 15.4 +/- 2.4 minutes (P<.05 preconditioning and
cardioplegia versus control). In additional experiments, using blood- and
crystalloid-perfused hearts, we describe the relationship between the number of preconditioning cycles and
ischemic contracture.
CONCLUSIONS: Although preconditioning accelerates,
cardioplegia delays, and preconditioning plus
cardioplegia has little effect on
ischemic contracture, each affords similar protection of postischemic contractile function. These results question the utility of
ischemic contracture as a predictor of the protective efficacy of anti-ischemic interventions. They also suggest that preconditioning and
cardioplegia may act through very different mechanisms.