Naloxone blocks transferred preconditioning in isolated rabbit hearts

Area of Science:

• Cardiovascular Physiology
• Ischemic Preconditioning
• Pharmacology

Background:

• Ischemic preconditioning (PC) confers cardioprotective benefits.
• These benefits can be transferred via coronary effluent, suggesting circulating factors.
• The exact nature and mechanism of these transferable factors remain unclear.

Purpose of the Study:

• To concentrate and recover cardioprotective factors from coronary effluent using reverse phase chromatography.
• To investigate the role of opioid receptor activation in the cardioprotection mediated by these transferred factors.

Main Methods:

• Isolated rabbit hearts were perfused with buffer.
• Coronary effluent from ischemic preconditioned (PC) or normoxic hearts was concentrated.
• Hearts were subjected to global ischemia, and infarct size (area of necrosis) was measured.
• The effect of opioid antagonist naloxone on protection was assessed.

Main Results:

• Concentrate from PC hearts significantly reduced infarct size compared to controls.
• Concentrate from normoxic hearts had no protective effect.
• Naloxone abolished the cardioprotective effect of PC concentrate, but not conventional PC.
• Opioid receptor blockade abrogated the transferred cardioprotection.

Conclusions:

• Cardioprotective factors present in coronary effluent can be concentrated and transferred.
• The protective mechanism of these transferred factors critically involves opioid receptor activation.
• This suggests a novel therapeutic strategy targeting opioid receptors for cardiac protection.