Catecholamines and preconditioning: studies of contraction and function in isolated rat hearts.
The aims of this study were to determine whether 1) like ischemic preconditioning, transient exposure to norepinephrine before ischemia exacerbates contracture during ischemia and 2) protection afforded by norepinephrine is stereospecific (receptor mediated). Isolated perfused rat hearts were randomized into five groups (n = 6/group): 1) ischemic preconditioning (3 min of ischemia + 3 min of reperfusion + 5 min of ischemia + 5 min of reperfusion), 2) untreated control, 3) vehicle control (ascorbic acid), 4) substitution of preconditioning ischemia by perfusion with d-norepinephrine, and 5) substitution of preconditioning ischemia by perfusion with l-norepinephrine. This was followed by 40 min of zero-flow ischemia and 50 min of reperfusion. Ischemic preconditioning and l-norepinephrine exacerbated contracture (time to 50% contracture = 9.2 +/- 1.1 and 9.0 +/- 1.1 vs. 13.3 +/- 0.3, 12.4 +/- 0.5, and 13.2 +/- 0.4 min for untreated control, vehicle control, and d-norepinephrine, respectively, P < 0.05). Postischemic left ventricular developed pressure was poor in untreated control (23.0 +/- 2.2%), vehicle control (26.9 +/- 2.3%), and d-norepinephrine (19.8 +/- 2.8%) groups but good in preconditioned (52.4 +/- 5.1%) and l-norepinephrine (52.5 +/- 1.1%) groups (P < 0. 05). Thus norepinephrine preconditioning, like ischemic preconditioning, causes a paradoxical exacerbation of contracture coupled with enhanced postischemic recovery; both effects are stereospecific.
Cardiovascular Research, The King's Center for Cardiovascular Biology and Medicine, The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, United Kingdom.
D J
DJ
Hearse
F J
FJ
Sutherland
D000818:Animals; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009200:Myocardial Contraction; D009638:Norepinephrine / Q000737:chemistry / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000737:chemistry / Q000494:pharmacology*; D016277:Ventricular Function, Left
D014662:Vasoconstrictor Agents; D009638:Norepinephrine