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Volume 15 Supplement 3

Sepsis 2011

  • Poster presentation
  • Open Access

Cardiovascular effects of β-blockade in a sheep model of severe sepsis

  • 1, 2, 3,
  • 1,
  • 1,
  • 3 and
  • 1
Critical Care201115 (Suppl 3) :P36

https://doi.org/10.1186/cc10405

  • Published:

Keywords

  • Atenolol
  • Renal Blood Flow
  • Sympathetic Nerve Activity
  • Sheep Model
  • Cardiac Sympathetic Nerve

Introduction

In sepsis, sympathetic nerve activity is differentially increased in individual organs. The increased cardiac sympathetic nerve activity is partly responsible for the increase in heart rate (HR) and cardiac output (CO) opposing the development of hypotension [1]. Recently, in a rat septic model, β-blockade appeared safe and decreased the inflammatory response and mortality [2]. Accordingly, we sought to investigate the cardiovascular effects of selective β1-receptor blockade in a sheep model of sepsis.

Methods

Eight merino ewes were studied in a university-affiliated research institute in Melbourne. The study design was a prospective interventional crossover animal study. The animals had renal and cardiac flow probes implanted to continuously measure CO and renal blood flow (RBF). Every animal was randomly allocated to receive sepsis and atenolol (atenolol group, AG) or sepsis alone (control group, CG) and then crossed over. After 24 hours of baseline period, sepsis was induced through a bolus of live Escherichia coli by a continuous infusion for a total 24 hours of sepsis. After the first 8 hours of sepsis (development sepsis period, DS), a bolus of atenolol (10 mg bolus) was given followed by a continuous infusion of 0.125 mg/kg/hours for 16 hours. Two-way repeated-measure ANOVA was performed to compare the average of periods and group interaction. P < 0.05 was considered significant (not significant (NS), P > 0.05).

Results

Animals in the AG and CG had similar baseline values and developed a similar hyperdynamic state in the DS (Figure 1 and Table 1). Atenolol reduced CO and HR without changes in stroke volume. Hypotension was slightly greater in the AG than in the CG (MAP: 81.5 vs. 86.1 mmHg) with a greater decrease in total peripheral conductance (16.8 vs. 22.1 l/minute/mmHg). Changes in lactate level were similar. Similar increases in RBF and in renal vascular conductance (RVC) were observed in the AG and CG and after an initial increase in diuresis in the DS, oliguria similarly subsequently developed in both groups. Creatinine clearance decreased in a similar way in the AG and CG from 59.2 (± 2.8) to 32 (± 5.7) ml/minute and from 65.2 (± 9.9) to 36 (± 7) ml/minute, respectively (P = 0.381). One animal in the AG and two in the CG died in the 24 hours after the end of sepsis.
Figure 1
Figure 1

Hemodynamic variables during baseline and sepsis in the atenolol (AG, white circles, dotted line) and control (CG, black triangles, continuous line) groups.

Table 1

Hemodynamic and renal findings during baseline, development (DS) and intervention sepsis periods in the CG and AG groups

 

Group

Baseline period

Development sepsis period (DS)

Sepsis intervention period

P value

CO

CG

3.68 (0.29)

3.68 (0.29)

4.12 (0.29)

<0.001

 

AG

3.21 (0.22)

3.21 (0.22)

5.63 (0.53)

 

HR

CG

66.0 (6.5)

66.0 (6.5)

108.8 (8.6)

<0.001

 

AG

59.7 (6.4)

59.7 (6.4)

111.6 (8.4)

 

MAP

CG

93.7 (5.1)

102.5 (3.6)

86.1 (4.1)

0.035

 

AG

96.3 (5.0)

102.5 (3.8)

81.5 (4.3)

 

RBF

CG

217.3 (14.8)

217.3 (14.8)

324.8 (19.7)

0.194

 

AG

214.7 (19.9)

214.7 (19.9)

292.3 (27.4)

 

UO

CG

31.1 (7.1)

84.1 (20.4)

22.1 (4.8)

0.097

 

AG

34.8 (7.0)

52.3 (17.4)

16.8 (11.0)

 

TPC

CG

38.2 (3.4)

38.9 (3.4)

63.9 (6.8)

0.084

 

AG

34.3 (3.1)

37.3 (3.2)

51.4 (6.8)

<0.001

SV

CG

51.4 (3.7)

39.1 (3.6)

35.5 (8.2)

0.147

 

AG

51.2 (4.6)

36.7 (3.5)

39.6 (3.6)

 

RVC

CG

2.39 (0.18)

3.26 (0.26)

3.74 (0.41)

0.55

 

AG

2.23 (0.16)

2.88 (0.26)

3.53 (0.44)

 

Values are the mean (± standard error). P value: two-way repeated-measures ANOVA interaction between treatment group and time (see text for definitions).

Conclusion

β-blockade in hyperdynamic sepsis appears safe. It results in only limited decreases in mean arterial pressure, and does not increase lactate levels or worsen renal function.

Authors’ Affiliations

(1)
Howard Florey Institute, University of Melbourne, Parkville, Australia
(2)
Department of Anaesthesia and Intensive Care, Cernusco sul Naviglio, AO Melegnano, PO Uboldo, Italy
(3)
Department of Intensive Care and Department of Medicine, Austin Health, Melbourne, VIC, Australia

References

  1. Ramchandra R, Wan L, Hood SG, Frithiof R, Bellomo R, May CN: Septic shock induces distinct changes in sympathetic nerve activity to the heart and kidney in conscious sheep. Am J Physiol Regul Integr Comp Physiol 2009, 297: R1247-R1253. 10.1152/ajpregu.00437.2009View ArticlePubMedGoogle Scholar
  2. Ackland GL, Yao ST, Rudiger A, et al.: Cardioprotection, attenuated systemic inflammation, and survival benefit of β1-adrenoceptor blockade in severe sepsis in rats. Crit Care Med 2010, 38: 388-394. 10.1097/CCM.0b013e3181c03dfaView ArticlePubMedGoogle Scholar

Copyright

© Calzavacca et al. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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