Nitric oxide-generating beta-adrenergic blocker nipradilol preserves postischemic cardiac function.
BACKGROUND
Preconditioning protects the heart from ischemic injury, but some of its effects are reversed by beta-adrenergic blockade. We hypothesize that because nitric oxide is known to precondition the heart, the nitric oxide-generating beta-blocker nipradilol may simultaneously precondition and provide clinically relevant beta-blockade.


METHODS
Isolated, crystalloid-perfused rabbit hearts underwent 1 hour of left anterior descending coronary artery ischemia followed by 1 hour of reperfusion. Before ischemia, six hearts received nipradilol, six received the nitric oxide donor L-arginine, four hearts received the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester before L-arginine, nine underwent ischemic preconditioning, and six received beta-blockade by esmolol before ischemic preconditioning. Seven hearts received no pretreatment (control). Action potential duration and ventricular pressure were measured. Infarct size was determined at the end of reperfusion.


RESULTS
Both L-arginine and ischemic preconditioning prolonged action potential duration significantly at 60 minutes of reperfusion. Compared with control, infarct size was reduced by ischemic preconditioning (26%+/-4% versus 49%+/-3%, IPC versus control; p<0.01), L-arginine (24%+/-2%; p<0.01 versus control), and nipradilol (24%+/-2%; p<0.01 versus control). Only nipradilol preserved peak developed pressure during reperfusion.


CONCLUSIONS
Despite its properties as a beta-adrenergic blocking agent, nipradilol was able to precondition the heart, probably as a result of its ability to produce nitric oxide.
Horimoto
H
H
Division of Cardiothoracic Surgery, University Hospital at Stony Brook, State University of New York, 11794-8191, USA.
Saltman
A E
AE
Gaudette
G R
GR
Krukenkamp
I B
IB
D000200:Action Potentials; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D017725:Ventricular Pressure / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D011412:Propanolamines; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; C036089:nipradilol; C036604:esmolol; D019331:NG-Nitroarginine Methyl Ester