Abstract
IntroductionActivation of the sympathetic nervous system has beneficial cardiovascular effects in sepsis, but there is also evidence that sympatholytics have beneficial actions in sepsis. We therefore determined the effect of selective β1-adrenoceptor blockade on cardiac and renal function and cytokine release in ovine hyperdynamic sepsis.MethodsHyperdynamic sepsis was induced by infusion of live E. coli for 24 hours in nine conscious sheep instrumented with flow probes on the pulmonary and left renal artery. Cardiovascular and renal function and levels of plasma cytokines were determined in a control group and during selective β1-adrenoceptor blockade with atenolol (10 mg intravenous bolus then 0.125 mg/kg/h) from 8 to 24 hours of sepsis.ResultsHyperdynamic sepsis was characterized by hypotension with increases in cardiac output (CO), heart rate (HR) and renal blood flow (RBF), and acute kidney injury. Atenolol caused sustained reductions in HR (P <0.001) and CO (P <0.001). Despite the lower CO the sepsis-induced fall in mean arterial pressure (MAP) was similar in both groups. The sepsis-induced increase in RBF, decrease in renal function and increase in arterial lactate were unaffected by atenolol. Sepsis increased plasma levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-10. Atenolol caused a further increase in IL-10, but did not affect levels of TNF-α or IL-6.ConclusionsIn sepsis, selective β1-adrenoceptor blockade reduced CO, but not MAP. During sepsis, atenolol did not alter the development of acute kidney injury or the levels of pro-inflammatory cytokines, but enhanced the release of IL-10. Atenolol appears safe in sepsis, has no deleterious cardiovascular or renal effects, and has an anti-inflammatory effect.
Highlights
Activation of the sympathetic nervous system has beneficial cardiovascular effects in sepsis, but there is evidence that sympatholytics have beneficial actions in sepsis
The hypotension resulted from peripheral vasodilatation, as shown by the progressive increase in total peripheral conductance (TPC) (Figure 2)
Atenolol reduced cardiac output (CO) within 1 hour and heart rate (HR) remained reduced there was a slow increase in CO due to a progressive increase in stroke volume (SV) during the septic period (Figure 1, Table 1)
Summary
Activation of the sympathetic nervous system has beneficial cardiovascular effects in sepsis, but there is evidence that sympatholytics have beneficial actions in sepsis. Inotropic treatment with the β-1 adrenoceptor agonist dobutamine has been used to increase cardiac output in sepsis, a recent study found dobutamine treatment was associated with increased mortality [5] and Despite the overall beneficial effects of catecholamines in sepsis, there are indications that a protracted and excessive increase in sympathetic nerve activity during critical illness may become maladaptive and exert adverse effects. There is evidence in septic shock that inhibiting sympathetic outflow, or blocking the action of catecholamines, may improve survival. Selective β1blockade starting two days before treatment with lipopolysaccharide (LPS) or cecal ligation puncture significantly improved survival, this effect was substantially reduced if β-blockers were not given until 6 h after induction of endotoxemia [12]. Metoprolol reduced plasma levels of interleukin 6 (IL-6) hepatic expression of pro-inflammatory cytokines and cardiac expression of IL-18
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