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

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.

Keywords: arterial pressure; baroreflex sensitivity; heart rate; heart rate variability; lipopolysaccharide; unanesthetized rats.

Figure 1

Time course of mean arterial pressure (MAP) and heart rate (HR) response to different doses of lipopolysaccharide in unanesthetized rats. Saline: panels (A,F); 0.06 mg/kg of LPS: panels (B,G); 20 mg/kg of LPS: panels (C,H); 30 mg/kg of LPS: panels (D,I); 40 mg/kg of LPS: panels (E,J). Data are expressed as mean ± standard error of the mean. ^*p < 0.05 vs. baseline counterpart; ^†p < 0.05 vs. 90 min counterpart; ^#p < 0.05 vs. 180 min counterpart.

Figure 2

Effects of different doses of lipopolysaccharide in the heart rate variability from unanesthetized rats. The heart rate variability parameters are the following: LF band (LF), HF band (HF), LF/HF ratio, and LF from the systolic arterial pressure (LF-SAP). Saline: panels (A,F,K,P); 0.06 mg/kg of LPS: panels (B,G,L,Q); 20 mg/kg of LPS: panels (C,H,M,R); 30 mg/kg of LPS: panels (D,I,N,S); 40 mg/kg of LPS: panels (E,J,O,T). Data are expressed as mean ± standard error of the mean. ^*p < 0.05 vs. baseline counterpart; ^#p < 0.05 vs. 90 min counterpart. LF, low frequency; HF, high frequency.

Figure 3

Effects of different doses of lipopolysaccharide in the baroreflex sensitivity in unanesthetized rats. Baroreflex sensitivity analysis by cross-spectral (panels (A–E)) and the sequence method (panels (F–J)), after saline or LPS administration. Saline: panels (A,F); 0.06 mg/kg of LPS: panels (B,G); 20 mg/kg of LPS: panels (C,H); 30 mg/kg of LPS: panels (D,I); 40 mg/kg of LPS: panels (E,J). Data are expressed as mean ± standard error of the mean. ^*p < 0.05 vs. baseline counterpart; ^#p < 0.05 vs. 90 min counterpart.