The effects of esmolol on the control of coronary blood flow and myocardial oxygen supply-demand balance in sepsis

dc.creatorDigilio, Michaelaen_US
dc.creatorWarne, Cooperen_US
dc.creatorHeard, Michaelen_US
dc.creatorTucker, Selinaen_US
dc.creatorEssajee, Salen_US
dc.creatorBradford, Ni' Ja D.en_US
dc.creatorHodge, Lisaen_US
dc.creatorTune, Johnathanen_US
dc.creatorDick, Gregoryen_US
dc.description.abstractPurpose: Sepsis is an acute organ dysfunction secondary to infection that results in tachycardia, tachypnea, fever, decreased blood pressure, and lactic acidosis. This results in an overall myocardial oxygen supply-demand imbalance leading to cardiac dysfunction and ultimately death. The current treatment for sepsis is antibiotic therapy, vasopressors, and fluid therapy. However, this regimen does not address the tachycardia that leads to cardiovascular decompensation. Beta-blocker therapy addresses this myocardial oxygen supply-demand imbalance and is expected to promote survival in sepsis. We hypothesize that treatment with beta-blocker therapy during acute sepsis will address the myocardial oxygen supply-demand imbalance to maintain coronary perfusion pressure, improve myocardial oxygen delivery, and promote survival. Methods: Female and male Yorkshire pigs were used as the animal model for this project. Pigs were anesthetized, intubated, and a rectal thermometer and oximeter were placed. Catheters placed in ear vein, great cardiac vein, femoral artery, and bilateral femoral veins. Pressure transducer placed in the femoral artery. A transonic flow transducer placed around the left anterior descending artery. After instrumentation, baseline values were collected. Then, infusion with Escherichia coli lipopolysaccharide (LPS) at 10 µg/kg over the course of 2 hours was used to induce sepsis. LPS was infused via the femoral vein at a rate of 0.5mL/min. After 2 hours, intervention began depending on the treatment group. Intervention lasted 4 hours. Experiment groups included Sham (without LPS, fluids, norepinephrine (NE), or esmolol), Control (with LPS, no fluids, NE, or esmolol), Standard (with LPS, fluids, and NE), and Experimental (with LPS, fluids, NE and esmolol). Doses: LPS 10 µg/kg, esmolol escalating from 100mg/hr, and NE escalating from 0.4 µg/kg/min. Goals during the intervention included keeping the mean arterial pressure (MAP) above 65mmHg and heart rate below 100. Results: All control pigs died during the 4-hour follow-up. 1 out of 3 standard treatment pigs survived. All esmolol-treated pigs survived. The esmolol group had better MAP, coronary blood flow, myocardial oxygen delivery, and oxygen extraction than the standard treatment group. Conclusion: Esmolol improves survival, coronary perfusion pressure, and myocardial oxygen delivery. This data provides support for our hypothesis and the clinical use of esmolol in sepsis.en_US
dc.titleThe effects of esmolol on the control of coronary blood flow and myocardial oxygen supply-demand balance in sepsisen_US