Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning

ZQ Zhao, JS Corvera, ME Halkos… - American Journal …, 2003 - journals.physiology.org
ZQ Zhao, JS Corvera, ME Halkos, F Kerendi, NP Wang, RA Guyton, J Vinten-Johansen
American Journal of Physiology-Heart and Circulatory Physiology, 2003journals.physiology.org
MATERIALS AND METHODS Surgical preparation. The experimental animals were handled
in compliance with the Guiding Principles in the Use and Care of Animals published by the
National Institutes of Health (NIH Publication No. 85-23, Revised 1996). The Institutional
Animal Care and Use Committee of Emory University approved the study protocol.
Heartworm-free adult dogs of either sex weighing 25–35 kg were initially premedicated with
an intramuscular injection of morphine sulfate (4 mg/kg) followed by continuous inhalation of …
MATERIALS AND METHODS
Surgical preparation. The experimental animals were handled in compliance with the Guiding Principles in the Use and Care of Animals published by the National Institutes of Health (NIH Publication No. 85-23, Revised 1996). The Institutional Animal Care and Use Committee of Emory University approved the study protocol. Heartworm-free adult dogs of either sex weighing 25–35 kg were initially premedicated with an intramuscular injection of morphine sulfate (4 mg/kg) followed by continuous inhalation of isoflurane (0.5–2%) after endotracheal intubation. Dogs were ventilated with a volume-cycled respirator using oxygen-enriched room air. The left femoral artery was cannulated with a polyethylene catheter for blood sampling. The chest was opened by a left lateral thoracotomy, and the heart was suspended in a pericardial cradle. Millar cathetertipped pressure transducers were inserted into the aorta via the internal mammary artery and into the left ventricle through an apical incision, respectively. A pair of 5-MHz ultrasonic crystals was implanted in the anterior midmyocardium and connected to a sonomicrometer (model 120, Triton Technology; San Diego, CA) to measure regional contractile function. A Doppler flow probe was placed on the proximal LAD coronary artery and connected to a pulsed Doppler flowmeter (Triton Technology) for the measurement of instantaneous CBF. A catheter was inserted into the left atrium for injection of colored microspheres to measure regional myocardial blood flow. A 2-0 silk suture was passed below the first diagonal branch of the LAD distal to the flow probe to occlude the LAD. All dogs were then systemically heparinized with 300 U/kg heparin sodium before the start of the experiment.
Experimental protocol. All animals were randomly assigned to one of three groups (Fig. 1): 1) control (n 10), the LAD was reversibly occluded for 60 min followed by 3 h of reperfusion; 2) preconditioning (n 9), the LAD was occluded for 5 min followed by 10 min of reperfusion before the 60 min of prolonged occlusion; 3) postconditioning (n 10), after 60 min of LAD occlusion, reperfusion was initiated for 30 s followed by 30 s of reocclusion, repeated for three cycles (3 min total intervention). Reperfusion was continued for a total of 3 h in all experiments.
American Physiological Society