Cardioprotection in pigs by exogenous norepinephrine but not by cerebral ischemia-induced release of endogenous norepinephrine

Background and Purpose-Endogenous norepinephrine release induced by cerebra l ischemia may lead to small areas of necrosis in normal hearts. Conversely , norepinephrine may be one of the mediators that limit myocardial infarct size by ischemic preconditioning, Because brief ischemia in kidneys or skel etal muscle limits infarct size produced by coronary artery occlusion, we i nvestigated whether cardiac norepinephrine release during transient cerebra l ischemia also elicits remote myocardial preconditioning. Methods-Forty-one crossbred pigs of either sex were assigned to 1 of 7 expe rimental groups, of which in 6 groups myocardial infarct size was determine d after a 60-minute coronary occlusion and 120 minutes of reperfusion. One group served as control (no pretreatment), while the other groups were pret reated with either cerebral ischemia or an intracoronary infusion of norepi nephrine. Results-In 10 anesthetized control pigs, infarct size was 84+/-3% (mean+/-S EM) of the area at risk after a 60-minute coronary occlusion and 120 minute s of reperfusion. Intracoronary infusion of 0.03 nmol/kg . min(-1) norepine phrine for 10 minutes before coronary occlusion did not affect infarct size (80+/-3%; n=6), whereas infusion of 0.12 nmol/kg . min(-1) limited infarct size (65+/-2%; n=7; P<0.05). Neither 10-minute (n=5) nor 30-minute (n=6) c erebral ischemia produced by elevation of intracranial pressure before coro nary occlusion affected infarct size (83+/-4% and 82+/-3%, respectively). M yocardial interstitial norepinephrine levels tripled during cerebral ischem ia and during low-dose norepinephrine but increased 10-fold during high-dos e norepinephrine. Norepinephrine levels increased progressively up to 500-f old in the area at risk during the 60-minute coronary occlusion, independen t of the pretreatment, while norepinephrine levels remained unchanged in ad jacent nonischemic myocardium and arterial plasma. Conclusions - Cerebral ischemia preceding a coronary occlusion did not modi fy infarct size, which is likely related to the modest increase in myocardi al norepinephrine levels during cerebral ischemia, The infarct size limitat ion by high-dose exogenous norepinephrine is not associated with blunting o f the ischemia-induced increase in myocardial interstitial norepinephrine l evels.