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.

Oxidative stress during cardiac arrest may inactivate myocardial enzymes and thereby exacerbate ischemic derangements of myocardial metabolism. This study examined the impact of cardiac arrest on left ventricular enzymes. Beagles were subjected to 5 min of cardiac arrest and 5 min of open-chest cardiac compressions (OCCC) before epicardial direct current countershocks were applied to restore sinus rhythm. Glutathione/glutathione disulfide redox state (GSH/GSSG) and a panel of enzyme activities were measured in snap-frozen left ventricle. To test whether oxidative stress during arrest inactivated the enzymes, metabolic (pyruvate) or pharmacological (N-acetyl-l-cysteine) antioxidants were infused intravenously for 30 min before arrest. During cardiac arrest, activities of phosphofructokinase, citrate synthase, aconitase, malate dehydrogenase, creatine kinase, glucose-6-phosphate dehydrogenase, and glutathione reductase fell by 56, 81, 55, 34, 42, 55, and 45%, respectively, coincident with 50% decline in GSH/GSSG. OCCC effected full recovery of glutathione reductase and partial recovery of citrate synthase and aconitase, in parallel with GSH/GSSG. Phosphofructokinase, malate dehydrogenase, creatine kinase, and glucose-6-phosphate dehydrogenase recovered only after cardioversion. Antioxidant pretreatments augmented phosphofructokinase, aconitase, and malate dehydrogenase activities before arrest and enhanced these activities, as well as those of citrate synthase and glucose-6-phosphate dehydrogenase, during arrest. In conclusion, cardiac arrest reversibly inactivates several important myocardial metabolic enzymes. Antioxidant protection of these enzymes implicates oxidative stress as a principal mechanism of enzyme inactivation during arrest.

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1974. Comparative effects of prostaglandins A-and B. on vascular airway resistances and adrenergic neurotransmission. Can. J. Physiol. Pharmacol. 52,690-705.Prostaglandin Ba (PGBY) may be formed from PGAY in vivo. The following study compares the effects of equivalent concentrations of PGAL and PGB, on systemic pressure, heart rate, airway resistance, cutaneous vascular resistance, and responses to sympathetic nerve stimulation and to ilorepinephrine and tyramine in the acutely denervated canine hind paw perfused with autologous blood at constant flow. Yntra-arterial (La.) PGBs (1 and 10 @g/min) produced concentration-dependent vasoconstriction. Fifteen minutes after PGB.! adnliilistration the pressor responses of the paw to sympathetic nerve stimulation were enhanced, whereas the pressor responses to norepinephrine and tyramine were unchanged. In contrast, low concentrations of PGA, produced systemic and transient cutaneous dilation whereas the higher concentration (10 pglrnin i.a.) produced systemic dilation and constriction of the acutely denervated paw. The pressor responses of the perfused paw to sympathetic nerve stimulation were enhanced with the higher infusion rate of PGAZ. However, the pressor responses to norepiiaephrine and tyramine were unchanged during PGA-. In addition, PGB-, but not PGA2. increased airway resistance. These results suggest that: (1) PGBe and PGAY have different effects on systemic pressure and airway resistance but have similar effects on the c~atanesus vascular bed; (2) both FGB-and PGA-selectively enhance neurotransmitter release from the catecholamine pool susceptible to activation by the nerve action potential; and ( 3 ) PGB2 is more potent in its abiIity to enhance neurotransmitter release than P6;A2. The vasoconstrictisn and facilitation of sympathetic neurotransmission by PGA-may be related to formation of PGBl within the paw. GREENBERG, S., HOWARD, L. et WILSON, W. W. 1974. Comparative effects of prostaglandins Ar and B2 on vascular airway resistances aiad adrenergic neurotransmission. Can. J. Physiol. Pharmacol. 52,699-705.La prsstaglnndine B1 (PGB-) peut. ire ~' i v o , 8tre form6e ii partir de la PGA2. Ge travail est une Ctude comparative des effets de la PGA, et de la PGB2 sur la pression artkrielle. la frtquence cardiaque et la resistance des voies respiratsires. Sur la patte arrikre dknervte de chien, perfuste ii d6bit constant avec du sang autologue, nous avons kgalement cornpart I'action de ces prostnglandines sur la resistance vasculaire cutanie ainsi que sur les effets de la nsrtpinCphrine, de la tyramine et de la stimulation adrtnergique. L'administration intra-arttrielle (i.a.) de PGB? (1 et 10 @g/min) produit une vasoconstrictioil dose-dependante. Quinze minutes aprks I'administration de PGB-, la rkponse pressive de B a patte i la stimulation adrknergique est augmentke tandis que les rtponses pressives 5 la nsripintphrine et la tyramine sont inchangees. La PGAa (1 ,ug/min i.a.) produit une vasodilatation systtmique et cutanie transitoire tandis qu'a dose plus 6...

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