Phenylephrine induces delayed cardioprotection against necrosis without amelioration of stunning.
BACKGROUND
Alpha-adrenergic stimulation induces protection in reperfused ischemic (I/R) myocardium 24 hours later. We tested the hypothesis that phenylephrine improves dysfunction after global I/R by limiting cell death not stunning.


METHODS
Rabbits were pretreated with either phenylephrine or vehicle. Twenty-four hours later, isolated hearts underwent either 45 (infarction protocol) or 20 minutes (stunning protocol) of global ischemia before 2 hours of reperfusion (n = 6 per group). Cell death was determined by triphenyl tetrazolium chloride staining (infarction) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) (apoptosis).


RESULTS
Compared with vehicle, phenylephrine pretreatment improved post-I/R-developed pressures in hearts after infarction (53.2 +/- 4.0 vs 35.8 +/- 4.1 mm Hg, p = 0.01) but not stunning protocol (64.3 +/- 8.9 vs 57.7 +/- 6.2 mm Hg, p = NS). The improved developed pressure was due to better diastolic recovery. Systolic pressures were similar between groups. Phenylephrine markedly decreased infarction (9.0 +/- 1.9% vs 40.8 +/- 1.8% for vehicle, p < 0.001) and TUNEL-positive staining. Stunned hearts of either group had less than 3% infarction and no apoptosis.


CONCLUSIONS
Phenylephrine pretreatment 24 hours before global I/R improves function by limiting infarction but not stunning.
Baghelai
K
K
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA. kbaghela@hsc.vcu.edu
Graham
L J
LJ
Wechsler
A S
AS
Jakoi
E R
ER
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D017682:Myocardial Stunning / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D010656:Phenylephrine / Q000494:pharmacology*; D011817:Rabbits
D002316:Cardiotonic Agents; D010656:Phenylephrine