β-Adrenergic receptor blockade mimics ischemic preconditioning in protecting against myocardial sympathetic activity during global ischemia

Abstract

Study objectives: Cardiac preconditioning is associated with improved cardiac function after global ischemia. During global cardiac ischemia, developed pressure and heart rate typically decrease. We have previously suggested that ischemic preconditioning results from norepinephrine release from adrenergic nerve termini in the heart. The study objectives are to assess cardiac function and energy expenditure after cyclic ischemia and β-adrenergic blockade. Methods: Isolated rat hearts (n=12) were subject to 4 cycles of ischemia (5 minutes) followed by reperfusion (5 minutes). Developed pressure and heart rate were assessed using high-resolution time-series analysis, and adenosine triphosphate (ATP) expenditure was calculated. Results: Immediately after the onset of transient ischemia, there was a brief period when developed pressure (Δ +13±3 mm Hg; P<.05 versus baseline) and heart rate (Δ +51±0.12 beats/min) increased. This inotropic and chronotropic reflex occurred within 10 seconds of ischemia. Subsequent cycles of transient ischemia and reperfusion differentially reduced the inotropic (Δ −30±15%; P<.05 fourth versus first cycle) and chronotropic (Δ −53±23%; P<.05 versus baseline) aspects of the reflex, with eventual diminution of both reflexes after 4 cycles. Attenuation of the compensatory reflex resulted in decreased contractile work and energy expenditure during repeated episodes of global ischemia, with a net ATP savings of 4.3 μmol/g wet weight. The inotropic and chronotropic responses during all cycles of ischemia were attenuated by 10 μM propranolol. Conclusion: This study reports a novel, locally mediated adrenergic sympathetic response that results in a desperate energy expenditure during global cardiac ischemia. Ischemic preconditioning curtails this reflex after the onset of global ischemia, and the preconditioning effect may be replicated using β-blockade. Blocking this adrenergic response may prevent energy expenditure on potentially futile cardiac contractile work during prolonged global ischemia and prove beneficial in protecting cardiac function during acute ischemic states, such as coronary syndromes, arrest, shock, and trauma. Study objectives: Cardiac preconditioning is associated with improved cardiac function after global ischemia. During global cardiac ischemia, developed pressure and heart rate typically decrease. We have previously suggested that ischemic preconditioning results from norepinephrine release from adrenergic nerve termini in the heart. The study objectives are to assess cardiac function and energy expenditure after cyclic ischemia and β-adrenergic blockade. Methods: Isolated rat hearts (n=12) were subject to 4 cycles of ischemia (5 minutes) followed by reperfusion (5 minutes). Developed pressure and heart rate were assessed using high-resolution time-series analysis, and adenosine triphosphate (ATP) expenditure was calculated. Results: Immediately after the onset of transient ischemia, there was a brief period when developed pressure (Δ +13±3 mm Hg; P<.05 versus baseline) and heart rate (Δ +51±0.12 beats/min) increased. This inotropic and chronotropic reflex occurred within 10 seconds of ischemia. Subsequent cycles of transient ischemia and reperfusion differentially reduced the inotropic (Δ −30±15%; P<.05 fourth versus first cycle) and chronotropic (Δ −53±23%; P<.05 versus baseline) aspects of the reflex, with eventual diminution of both reflexes after 4 cycles. Attenuation of the compensatory reflex resulted in decreased contractile work and energy expenditure during repeated episodes of global ischemia, with a net ATP savings of 4.3 μmol/g wet weight. The inotropic and chronotropic responses during all cycles of ischemia were attenuated by 10 μM propranolol. Conclusion: This study reports a novel, locally mediated adrenergic sympathetic response that results in a desperate energy expenditure during global cardiac ischemia. Ischemic preconditioning curtails this reflex after the onset of global ischemia, and the preconditioning effect may be replicated using β-blockade. Blocking this adrenergic response may prevent energy expenditure on potentially futile cardiac contractile work during prolonged global ischemia and prove beneficial in protecting cardiac function during acute ischemic states, such as coronary syndromes, arrest, shock, and trauma.