Time Course of Hemodynamic Responses to Different Doses of Lipopolysaccharide in Unanesthetized Male Rats.

Fernanda Brognara,Jaci Airton Castania,Helio Cesar Salgado,Alexandre Kanashiro,Daniel Penteado Martins Dias

doi:10.3389/fphys.2019.00771

Abstract

Lipopolysaccharide (LPS) administration is a well-known method to induce systemic inflammation widely used for investigating new therapeutic strategies for sepsis treatment, which is characterized by clinical manifestations such as tachycardia and hypotension. However, there are different doses of LPS used in several studies, and the hemodynamic responses were not always well characterized. Thus, the present study aimed to evaluate the arterial pressure, heart rate, heart rate variability, and baroreflex function from rats, over time, to different doses of LPS. Femoral artery and vein catheters were inserted into anesthetized Wistar-Hannover male rats for arterial pressure recording and LPS administration, respectively. On the next day, the arterial pressure was recorded before and after (90, 180, and 360 min) LPS injection (0.06, 20, 30, and 40 mg/kg). All doses of LPS tested increased the heart rate and decreased baroreflex sensitivity over time. In addition, while LPS administration of 20, 30, and 40 mg/kg increased the mean arterial pressure over time, 0.06 mg/kg decreased the mean arterial pressure at 360 min, as compared to baseline values. Furthermore, high doses of LPS decreased the power of the HF band of the cardiac interval spectrum over time, and the higher dose increased the power of the LF band. Our data indicate that high doses of LPS promote hypertensive response over time, while a low dose decreases arterial pressure. Moreover, the changes in heart rate variability and baroreflex function elicited by LPS may be not associated with arterial pressure response produced by the endotoxemia.

Highlights

Models of endotoxemia have been used to explore the host innate immunity involved in the inflammatory response and searching therapeutic approaches for the treatment of inflammatory diseases (Borovikova et al, 2000; Bassi et al, 2015; Halbach et al, 2017)
No changes in mean arterial pressure were observed over time in the saline group (Figure 1A and Table 1)
We described the changes in arterial pressure and heart rate as well as the heart rate variability, over time, elicited by different doses of LPS administration

Summary

Introduction

Models of endotoxemia have been used to explore the host innate immunity involved in the inflammatory response and searching therapeutic approaches for the treatment of inflammatory diseases (Borovikova et al, 2000; Bassi et al, 2015; Halbach et al, 2017). LPS is a component of the outer membrane of Gram-negative bacteria, which is a potent activator of the innate immunity, after being recognized by toll-like receptor 4 (Raetz and Whitfield, 2002; Beutler and Rietschel, 2003). This receptor is responsible for the activation of the nuclear factor-κB pathway that leads the synthesis and release of some pro-inflammatory mediators such as cytokines by macrophages (Beutler and Rietschel, 2003; Café-Mendes et al, 2017). The present study aimed to evaluate the arterial pressure, heart rate, and the heart rate variability responses from unanesthetized rats, over time, to different doses of LPS

Methods

Results

Conclusion