Heart rate dynamics in iNOS knockout mice

Mani, AR; Ollosson, Richard; Mani, Yasaman; Ippolito, Silvia; Moore, Kevin

doi:10.1016/j.lfs.2006.05.014

Cited by 21 publications

(13 citation statements)

References 42 publications

(57 reference statements)

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“…Decreased HRV during experimental endotoxemia has been previously reported in both animal models (8,21) and humans (2,7), consistent with findings in neonates and adults with sepsis (6,10,13,22,25). The mechanism of this effect is not well understood but could be through direct or indirect effects of LPS on pacemaker cell electrophysiology or on autonomic nervous system activity.…”

Section: Discussionsupporting

confidence: 85%

“…In acute illness, elevated plasma IL-6 has also been linked to depressed HRV in adults with sepsis (32). In experimental sepsis in both animal models and healthy human volunteers, administration of lipopolysaccharide (LPS, endotoxin from gram-negative bacteria) decreases HRV (2,7,8,21). While these data point to an association between the systemic inflammatory response and changes in HRV, causal links between the two have not been established.…”

mentioning

confidence: 99%

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Endotoxin depresses heart rate variability in mice: cytokine and steroid effects

Fairchild¹,

Saucerman

Raynor³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

107

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Heart rate variability (HRV) falls in humans with sepsis, but the mechanism is not well understood. We utilized a mouse model of endotoxemia to test the hypothesis that cytokines play a role in abnormal HRV during sepsis. Adult male C57BL/6 mice underwent surgical implantation of probes to continuously monitor electrocardiogram and temperature or blood pressure via radiotelemetry. Administration of high-dose LPS (Escherichia coli LPS, 10 mg/kg, n = 10) caused a biphasic response characterized by an early decrease in temperature and heart rate at 1 h in some mice, followed by a prolonged period of depressed HRV in all mice. Further studies showed that LPS doses as low as 0.01 mg/kg evoked a significant decrease in HRV. With high-dose LPS, the initial drops in temperature and HR were temporally correlated with peak expression of TNFalpha 1 h post-LPS, whereas maximal depression in HRV coincided with peak levels of multiple other cytokines 3-9 h post-LPS. Neither hypotension nor hypothermia explained the HRV response. Pretreatment with dexamethasone prior to LPS significantly blunted expression of 7 of the 10 cytokines studied and shortened the duration of depressed HRV by about half. Interestingly, dexamethasone treatment alone caused a dramatic increase in both low- and high-frequency HRV. Administration of recombinant TNFalpha caused a biphasic response in HR and HRV similar to that caused by LPS. Understanding the role of cytokines in abnormal HRV during sepsis could lead to improved strategies for detecting life-threatening nosocomial infections in intensive care unit patients.

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Section: Discussionsupporting

confidence: 85%

mentioning

confidence: 99%

Endotoxin depresses heart rate variability in mice: cytokine and steroid effects

Fairchild¹,

Saucerman

Raynor³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

107

View full text Add to dashboard Cite

show abstract

“…There were no significant differences in SDNN among the experimental groups. The SDNN of the isolated hearts of the control group was lower than the SDNN of the control group recorded from conscious healthy rats (5.96 ± 0.63 msec, P<0.05), which is probably due to the effect of denervation of the heart and lack of autonomic control of cardiac pacemaker (Mani et al 2006b).…”

Section: Resultscontrasting

confidence: 56%

Increased sample asymmetry and memory of cardiac time-series following endotoxin administration in cirrhotic rats

et al. 2016

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Sepsis, and other causes of acute systemic inflammation, can reduce heart rate variability (HRV) and increase cardiac cycle regularity in mammals. Thus, HRV monitoring has been used for early detection of sepsis in adults and neonates. Liver cirrhosis is associated with reduced basal HRV and the development of tolerance to the cardiac chronotropic effects of bacterial endotoxin. This may pose limitations on the use of heart rate monitoring in early detection of sepsis in this patient population. In a study to develop a physiomarker for the detection of sepsis in cirrhosis, we observed that endotoxin administration in adult cirrhotic rats leads to the development of transient heart rate decelerations, a phenomenon which has been reported in neonates with sepsis, and quantified using sample asymmetry analysis. In the present study, cirrhosis was induced by surgical ligation of the bile duct in rats. Cirrhotic rats were given intraperitoneal injections of either saline or endotoxin (1 mg kg). Changes in sample asymmetry and memory length of cardiac time-series were studied in conscious rats using implanted telemetric probes. Cirrhotic (but not control) rats exhibited increased sample asymmetry following endotoxin injection, which was consistent with the development of transient heart rate deceleration. Endotoxin administration in cirrhotic rats was associated with prolongation of memory length for observing decelerating perturbations in the cardiac rhythm. These findings may have application in the development of an HRV monitoring system for early detection of sepsis in cirrhosis.

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“…We believe that the origin of that increased level of NO is from iNOS source, and it contributes to the inflammatory response as literature has demonstrated during acute phase of T. cruzi infection. Corroborating this, data from the literature showed that in iNOS knockout mice present higher heart rate compared to control (Mani et al, 2006). Also in nNOS knockout mice it is observed an increase in heart rate due to inhibition of adrenergic-adenylate cyclase signaling within sino atrial node myocytes (Choate et al, 2008).…”

Section: Discussionmentioning

confidence: 77%

Moderate Treadmill Exercise Training Improves Cardiovascular and Nitrergic Response and Resistance to Trypanosoma cruzi Infection in Mice

et al. 2017

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There is evidence suggesting that exercise training (ET) acts as a factor toward resistance to Trypanosoma cruzi infection. However, the effects of mean arterial pressure (MAP), heart rate (HR), and nitric oxide (NO) during the acute phase of infection has not been elucidated yet. Swiss mice were randomly assigned into four groups: sedentary control (SC, n = 30), trained control (TC, n = 30), sedentary infected (SI, n = 30), and trained infected (TI, n = 30). ET was performed on the treadmill for 9 weeks. After training, the mice were infected with 5 × 103 trypomastigotes of T. cruzi (Y strain) or PBS. We observed resting bradycardia and improved performance in trained animals compared with sedentary ones. On the 20th day post-infection (DPI), we found a decrease in HR in SI animals compared to TI animals (699.73 ± 42.37 vs. 742.11 ± 25.35 bpm, respectively, P < 0.05). We also observed increased production of NO in cardiac tissue on the 20th DPI in the SI group, normalized in TI group (20.73 ± 2.74 vs. 6.51 ± 1.19 μM, respectively). Plasma pro-inflammatory cytokines (IL-12, TNF-α, IFN-γ,) and MCP-1 were increased in SI animals, but decreased in TI animals. The increase in parasitemia on the 15th and 17th DPI in the SI group was attenuated in the TI group. Our results suggest that previous ET plays a preventive role in resistance to T. cruzi infection, modulating cardiovascular aspects, inflammatory reaction, and NO levels of infected mice.

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Heart rate dynamics in iNOS knockout mice

Cited by 21 publications

References 42 publications

Endotoxin depresses heart rate variability in mice: cytokine and steroid effects

Endotoxin depresses heart rate variability in mice: cytokine and steroid effects

Increased sample asymmetry and memory of cardiac time-series following endotoxin administration in cirrhotic rats

Moderate Treadmill Exercise Training Improves Cardiovascular and Nitrergic Response and Resistance to Trypanosoma cruzi Infection in Mice

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