TRANSIENT BETA-ADRENERGIC STIMULATION CAN PRECONDITION THE RAT-HEART AGAINST POSTISCHEMIC CONTRACTILE DYSFUNCTION

Objective: The aim was to assess the abilities of exogenous noradrenal ine, isoprenaline, and phenylephrine to precondition the isolated rat heart against ischaemic and reperfusion injury. Methods: The isovolume tric Langendorff rat heart model was used to determine postischaemic r ecovery of left ventricular function. The hearts were subjected to 30 min of normothermic global ischaemia followed by 30 min reperfusion. T reated hearts were perfused with noradrenaline (10(-7) M), isoprenalin e (10(-8) M), or phenylephrine (10(-6) M, 10(-5) M, and 10(-4) M) for 5 min followed by 5 min washout before the 30 min ischaemic period. Re sults: Control hearts recovered 47.6(SEM 4.3)% of baseline heart rate X developed pressure after 30 min reperfusion, whereas noradrenaline a nd isoprenaline treated hearts recovered 75.1(4.6) and 76.4(4.6)%, res pectively (p < 0.001 v control). Left ventricular end diastolic pressu res at the end of reperfusion were 48.8(4.0), 20.0(2.4), and 21.6(2.7) mm Hg for control, noradrenaline treated (p < 0.001 v control), and i soprenaline treated (p < 0.001 v control) hearts respectively. beta Bl ockade with propranolol during noradrenaline treatment blocked the pl otective effects. No concentration of phenylephrine used was able to e nhance postischaemic heart rate X developed pressure significantly, or result in improved (lower) postischaemic left ventricular end diastol ic pressure. During treatment with noradrenaline and phenylephrine (10 (-5) M), lactate release was 13.0(1.0) and 11.0(0.9) mu mol.5 min(-1), respectively (p = NS); these values were significantly (p < 0.001) gr eater than baseline value of 3.7(0.5) mu mol.5 min(-1). Immediately be fore the 30 min ischaemic period, control and phenylephrine treated gr oups had glycogen levels of 132(14) and 128(5) nmol.mg(-1) protein, re spectively (p = NS), whereas the glycogen content of the noradrenaline treated group was only 96(5) nmol.mg(-1) protein (p < 0.05 v control and phenylephrine treated). Conclusions: Transient beta adrenergic but not alpha(1) adrenergic stimulation can precondition the isolated per fused rat heart. The mechanism of protection may, at least in part, be due to transient demand ischaemia. Partial depletion of glycogen foll owing treatment may play a role in the observed protective effects.