Effect of preischemic beta-adrenoceptor stimulation on postischemic contractile dysfunction.
OBJECTIVE
Short periods of preischemic beta-adrenoceptor stimulation protect hearts against postischemic left ventricular dysfunction. It was the aim of this study to decide whether this procedure mimics ischemic preconditioning by the generation of preischemic hemodynamic and energetic stress or whether it represents an endogenous phenomenon and to investigate the influence of age and hypertension.


METHODS
Isolated rat hearts were investigated ex vivo by Langendorff perfusion and exposed to an established ischemia/reperfusion protocol (45 min no-flow ischemia and 90 min reperfusion). Left ventricular developed pressure (LVDP), rate pressure product, and +/-dP/dt were analyzed.


RESULTS
Isoprenaline concentration dependently increased LVDP up to 40+/-15 mm Hg (approximately EC(50) of 9.9+/-0.5 nM). Isoprenaline given prior to ischemia attenuated the subsequent postischemic ventricular dysfunction (approximately EC(50) of 1.4+/-0.2 pM). However, concentrations high enough to improve LVDP in normoxic hearts did not improve postischemic recovery albeit a significant reduction of hypercontraction-induced cell damage. The effect on functional recovery was attenuated by atenolol, H89, and wortmannin suggesting that beta-adrenoceptor stimulation, protein kinase A, and PI 3-kinase activation are involved. The effect was conserved in hearts from 13 month old rats but lost in age-matched spontaneously hypertensive rats.


CONCLUSIONS
The study identifies preischemic beta-adrenoceptor stimulation as a pharmacological preconditioning protocol that does not simply mimic classical ischemic preconditioning by induction of hemodynamic or energetic stress prior to a prolonged ischemic period. The observed loss of effectiveness in hypertensives may contribute to the reduced ischemic tolerance of hypertensives.
Maier
Thorsten
T
Physiologisches Institut, Justus-Liebig-University Giessen, Germany.
Schreckenberg
Rolf
R
Schlüter
Klaus-Dieter
KD
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000375:Aging / Q000378:metabolism; D000818:Animals; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol