Hemin, inducer of heme-oxygenase 1, improves functional recovery from myocardial stunning in conscious dogs.
OBJECTIVE
To examine the effects of pretreatment with hemin, an inducer of the potential antioxidative enzyme heme-oxygenase 1 (HO-1) or heat-shock protein 32, on myocardial stunning.


METHODS
Randomized animal study.


METHODS
Animal laboratory of a university hospital.


METHODS
Chronically instrumented mongrel dogs (n = 44).


METHODS
Dogs underwent chronic instrumentation for measurement of hemodynamics and myocardial wall thickening fraction (WTF). Experiments with 12 dogs were performed on separate days in a crossover fashion: (1) 10 minutes of left anterior descending (LAD) coronary artery occlusion after application of hemin (9 mg/kg/d) for 1 week and (2) 10 minutes of LAD coronary artery occlusion without hemin pretreatment. In control experiments (n = 32), the reversible induction of HO-1, using gel electrophoresis and Western blotting, was determined.


RESULTS
WTF was measured as a baseline value before hemin administration and at predetermined time points until complete recovery from stunning. LAD artery occlusion caused a significant reduction in the WTF in the LAD-perfused area with and without hemin, without significant hemodynamic changes. At all time points, after 1 minute of reperfusion, the WTF as percentage of baseline values was significantly higher after hemin pretreatment (p < 0.05). Baseline WTF values were reached after 24 hours with and after >48 hours without hemin pretreatment (p < 0.05).


CONCLUSIONS
Hemin pretreatment attenuates myocardial stunning in conscious dogs.
Weber
T P
TP
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, and Institut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität, Münster, Germany. weber@anit.uni-muenster.de
Meissner
A
A
Boknik
P
P
Hartlage
M G
MG
Möllhoff
T
T
Van Aken
H
H
Rolf
N
N
D000818:Animals; D001783:Blood Flow Velocity; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000201:enzymology; D004285:Dogs; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D011292:Premedication; D018617:Ultrasonography, Doppler, Pulsed; D017725:Ventricular Pressure
D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1