Beta1-Adrenergic receptor antagonism abrogates cardioprotective effects of intermittent hypoxia.
Adaptation to hypoxia lessens myocardial ischemic injury. This study tested whether hypoxia-induced beta-adrenergic activity mobilizes mechanisms that protect myocardium during subsequent ischemia and reperfusion. Dogs were intermittent hypoxia conditioned (IHC) by a 20 days program of 5-8 daily, 5-10 min cycles of normobaric hypoxia (FIO2 = 9.5-10%), or sham conditioned with normoxic air, and metoprolol (beta1-adrenoceptor antagonist) was administered throughout the IHC program. Twenty-four hours after the last IHC session, the left anterior descending coronary artery (LAD) was occluded for 60 min, and then reperfused for 5 h. Area at risk (AAR) and infarct size (IS) were measured. IHC lowered IS/AAR from 38+/-6% in sham-conditioned dogs to 1.1+/-0.3%, and eliminated ventricular tachycardia (VT) and fibrillation (VF) that occurred in 14 of 17 non-conditioned dogs. Metoprolol blunted IHC-evoked cardioprotection (IS/AAR=27+/-3%), and VT and/or VF occurred in 5 of 6 dogs. Metoprolol did not exacerbate ischemic injury in sham-conditioned dogs (IS/AAR=38+/-2%). Neither IHC nor metoprolol affected hematocrit or LAD collateral blood flow. A single IHC session failed to protect ischemic myocardium (IS/AAR = 36+/-8%), and protection was incomplete after 10 days of IHC (IS/AAR = 13+/-5%), suggesting that de novo protein synthesis was required for protection. Thus, episodic beta1-adrenergic activation during IHC evokes progressive development of powerful resistance to myocardial ischemia.
Mallet
Robert T
RT
Department of Integrative Physiology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, USA. malletr@hsc.unt.edu
Ryou
Myoung-Gwi
MG
Williams
Arthur G
AG
Howard
Linda
L
Downey
H Fred
HF
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D003097:Collateral Circulation; D003326:Coronary Circulation; D004285:Dogs; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D000860:Hypoxia / Q000503:physiopathology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000209:etiology; D010100:Oxygen / Q000097:blood
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D006454:Hemoglobins; D010100:Oxygen