Vagal cardiac control in rats with LPS-induced lung injury.

Heart rate variability (HRV) as an index of cardiac autonomic control in acute lung injury (ALI) has been evaluated in anaesthetized rats intratracheally instilled with bacterial lipopolysaccharide (LPS) and ventilated with breathing frequency of 60/min, 40% oxygen, inspiratory time 40%, tidal volume of 6 mL/kg. ECG was recorded before and 30, 60, 120, 180 and 240 min after LPS or saline (control) administration. HRV was quantified by time and frequency-domain analysis (mean RR interval, SDRR, RMSSD and spectral power in high frequency (HF) band. Lactate in plasma, and oxidative stress, IL-1ß, IL-5, IL-12p70 and IL-13 and galectin-3 in heart tissue raised in LPS-injured rats. Overall HRV magnitude (SDRR) and marker of vagal heart rate control (RMSSD), as well as frequency domain parameter, spectral power HF was increased 120 and 180 min since ALI onset. In conclusion, LPS-induced ALI is accompanied by altered vagal cardiac control mediated by autonomic nervous system, likely based on the close relationship between immune response and vagally mediated autonomic nervous activity.

Vagal-immune interactions involved in cholinergic anti-inflammatory pathway.

Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve and inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They brought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-alpha and other proinflammatory cytokines production and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey´s inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of vagally-mediated anti-inflammatory pathway in the treatment strategies.

Heart rate variability and inflammatory response in rats with lipopolysaccharide-induced endotoxemia.

The aim of the study was to evaluate short-term heart rate variability (HRV) as an index of cardiac autonomic control in rats with lipopolysaccharide (LPS)-induced endotoxemia. Animals were injected intraperitoneally with LPS (100 microg/kg b.w.) and control group with an equivalent volume of saline. ECG recordings were done before (base) and 60, 120, 180, 240 and 300 min after LPS or saline administration. HRV magnitude was quantified by time and frequency-domain analysis (mean RR interval, SDRR, RMSSD, spectral powers in low (LF) and high frequency (HF) bands. Heart tissue homogenates and plasma were analyzed to determine interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and oxidative stress level (TBARS). Administration of lipopolysaccharide was followed by continuous rise in colonic body temperature compared to saline-treated controls. Endotoxemia in rats was accompanied by significant decrease in HRV spectral activity in high-frequency range at maximal body temperature (logHFpower: 1.2+/-0.5 vs. 1.9+/-0.6 ms(2), P<0.01). Increased IL-6 was found in heart tissue homogenates of LPS rats (8.0+/-0.6 vs. 26.4+/-4.8 pg/ml, (P<0.05). In conclusions, reduced HRV in HF band may indicate a decreased parasympathetic activity in LPS-induced endotoxemia as basic characteristics of altered cardiac control during response to endotoxemia.

Changes in lung surfactant proteins in rats with lipopolysaccharide-induced fever.

The study was designed to prove the hypothesis that lipopolysaccharide (LPS)-induced fever elicits the changes in surfactant specific proteins, potentially related to thermal tachypnea. In adult rats fever was induced by intraperitoneal administration of LPS at a dose 100 microg/kg of body weight; control group received saline. Respiratory parameters, arterial blood gases and pH and colonic body temperature (BT) were recorded. Five hours later, surfactant proteins (SP) A, B, C and D were evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue (LT). LPS evoked monophasic thermic response (at 300 min 38.7+/-0.2 vs. 36.4+/-0.3 °C, P 0.05) and an increase in minute ventilation due to changes in breathing rate and tidal volume. LPS-instilled animals had higher levels of SP-A and SP-D in LT (P 0.05 and 0.01), and higher SP-D in BALF (P 0.01) than controls. SP-B increased in LT and SP-C in BALF of animals with LPS (both P 0.05 vs. controls). The changes in all surfactant specific proteins are present in LPS-induced fever. Alterations of proteins related to local immune mechanisms (SP-A, SP-D) are probably a part of general inflammatory response to pyrogen. Changes in proteins related to surface activity (SP-B and SP-C) might reflect the effort of the body to stabilize the lungs in thermal challenge.

Effects of hypovolemia on hypercapnic ventilatory response in experimental hyperthermia.

The present study was undertaken to evaluate the effects of hypercapnia on the cardiorespiratory control in normovolemic and hypovolemic rabbits during exogenous hyperthermia. Hypovolemia was induced by administration of furosemide, the body temperature (Tb) was gradually elevated to 42 degrees C by body surface heating. Subsequently, Tb was lowered back to the initial values by gradual cooling. Recordings were done at normothermia (TN=38 degrees C), during heating at 40 degrees C (TH1) and 42 degrees C (TH2), and in the course of Tb reverting toward the baseline values back at 40 degrees C (TC1), and finally after full return to the initial temperature value (TC2). The hypercapnic ventilatory response (HCVR) was estimated as the slope of minute volume (VE) on end-tidal CO2 (ETCO2) curves. We found that heating caused an increase in the VE slope in the normovolemic (NV), but not in hypovolemic (HV), rabbits. Between-group comparison revealed a significant increase in HCVR at TH2 and TC1 in NV vs. HV rabbits. Hypercapnia in hyperthermia (at TC2) was accompanied by a significant decrease in heart rate only in the hypovolemic group. Recovery of Tb was unaccompanied by appreciable changes in HCVR in either NV or HV groups. In the course of cooling, a decrease in heart rate during hypercapnic challenge was present in both group, in HV the drop was less prominent. We conclude that hypercapnia during heat stress in both normovolemic and hypovolemic rabbits is associated with altered cardiorespiratory responses. HCVR during exogenous hyperthermia is augmented in normovolemic, but not in hypovolemic, rabbits.

Effects of acute normovolemic haemodilution on cardiorespiratory changes in hyperthermia and its physical treatment.

As only one experimental study examining the effects of haemodilution on circulatory responses to hyperthermia has so far been published and there is no information on respiratory responses to hyperthermia during haemodilution or anaemia, this paper studied the effects of acute normovolemic haemodilution on cardiorespiratory changes during 42 degrees C hyperthermia and its recovery by body surface cooling in 16 anaesthetized adult rabbits. The animals were divided into two groups: haemodiluted group (Hct = 18.6 +/- 0.4%) and control group (Hct = 41.1 +/- 0.9%). In the haemodiluted group, acute normovolemic haemodilution was induced by 60% replacement of total blood volume with dextran. Haemodilution produced significant increases in minute volume (V(E), p < 0.02), heart rate (HR, p < 0.02) and central venous pressure (CVP, p < 0.02), but there was no significant change in mean arterial pressure (MAP). Hyperthermia caused significant increases in V(E) and HR in both the groups; however, V(E) and HR values were significantly higher in the haemodiluted group compared to the controls. CVP decreased (p < 0.05) during 42 degrees C hyperthermia only in the controls in the panting phase. MAP did not significantly change during over-heating in controls, but it significantly (p < 0.02) rose in the haemodiluted group. In the recovery phase, cooling led to significant decreases in HR and MAP in both the groups and to further increases in V(E) (p < 0.05) in controls, whereas V(E) decreased in the haemodiluted animals. There were found no significant cardiorespiratory differences between the two groups during cooling. Hyperthermia was accompanied by the higher values of minute volume and heart rate in the haemodiluted animals, indicating a greater activation of the respiratory and cardiovascular systems, which could result in diminished functional cardiorespiratory reserve and a higher risk of respiratory and circulatory failures in haemodiluted/anaemic animals during hyperthermia. In the phase of recovery of the body temperature there were no significant cardiorespiratory differences found between the two groups.

[Chemical regulation of respiration and its evaluation]. / Chemická regulácia dýchania a jej hodnotenie.

Chemical control of breathing, via variations in blood chemistry, affect activity of respiratory center and adjust ventilation proportionate to actual metabolic demands. Two control mechanisms ensure chemical control of breathing. Peripheral chemoreceptors are located in the carotid and aortic bodies. They are complex sensors are respond to both: hydrogen ion concentration and to the partial pressure of oxygen in arterial blood. Central chemoreceptors are located near ventrolateral surface of medulla oblongata and sense H+ ion concentration in their local environment. Measuring the chemoreflexes can provide very important information describing the behavior of the regulatory system not only in the normal but also in the pathological conditions due to respiratory instability.

Do the oscillations of cardiovascular parameters persist during voluntary apnea in humans?

The aim of this study was to ascertain the persistence of heart rate and blood pressure oscillations at the onset of voluntary apnea in humans and to assess the dependence of the fluctuations parameters on the chemoreceptor activity. In 24 young subjects (10 males, 14 females, mean age 20.4 years) heart rate (represented by its reciprocal value--RR-intervals), systolic blood pressure (SBP) and diastolic blood pressure (DBP) during controlled breathing (CB) of atmospheric air and oxygen followed by apnea were recorded continuously. The cosine functions were then fitted by nonlinear regression analysis to the heart rate, SBP and DBP oscillations during CB and at the onset of apnea. The parameters of oscillations were different during atmospheric air breathing compared to oxygen breathing. During oxygen breathing there was an increase of the RR-interval oscillations--relative bradycardia and enhanced magnitude of respiratory sinus arythmia. During apnea, the base level of the blood pressure oscillations was higher after breathing of atmospheric air compared to oxygen breathing. At least one cosine-like wave oscillation was present at the onset of apnea in the heart rate, SBP and DBP and the second wave was present in all assessed parameters in at least 70% of recordings. The oscillations in RR-intervals are, to some extent, independent of blood pressure oscillations. No significant gender differences were found either in the duration of breath holding or in the RR and SBP oscillations parameters.

Heart rate recovery after exercise: relations to heart rate variability and complexity.

Physical exercise is associated with parasympathetic withdrawal and increased sympathetic activity resulting in heart rate increase. The rate of post-exercise cardiodeceleration is used as an index of cardiac vagal reactivation. Analysis of heart rate variability (HRV) and complexity can provide useful information about autonomic control of the cardiovascular system. The aim of the present study was to ascertain the association between heart rate decrease after exercise and HRV parameters. Heart rate was monitored in 17 healthy male subjects (mean age: 20 years) during the pre-exercise phase (25 min supine, 5 min standing), during exercise (8 min of the step test with an ascending frequency corresponding to 70% of individual maximal power output) and during the recovery phase (30 min supine). HRV analysis in the time and frequency domains and evaluation of a newly developed complexity measure - sample entropy - were performed on selected segments of heart rate time series. During recovery, heart rate decreased gradually but did not attain pre-exercise values within 30 min after exercise. On the other hand, HRV gradually increased, but did not regain rest values during the study period. Heart rate complexity was slightly reduced after exercise and attained rest values after 30-min recovery. The rate of cardiodeceleration did not correlate with pre-exercise HRV parameters, but positively correlated with HRV measures and sample entropy obtained from the early phases of recovery. In conclusion, the cardiodeceleration rate is independent of HRV measures during the rest period but it is related to early post-exercise recovery HRV measures, confirming a parasympathetic contribution to this phase.

Heart rate recovery after exercise: relations to heart rate variability and complexity

Physical exercise is associated with parasympathetic withdrawal and increased sympathetic activity resulting in heart rate increase. The rate of post-exercise cardiodeceleration is used as an index of cardiac vagal reactivation. Analysis of heart rate variability (HRV) and complexity can provide useful information about autonomic control of the cardiovascular system. The aim of the present study was to ascertain the association between heart rate decrease after exercise and HRV parameters. Heart rate was monitored in 17 healthy male subjects (mean age: 20 years) during the pre-exercise phase (25 min supine, 5 min standing), during exercise (8 min of the step test with an ascending frequency corresponding to 70 percent of individual maximal power output) and during the recovery phase (30 min supine). HRV analysis in the time and frequency domains and evaluation of a newly developed complexity measure - sample entropy - were performed on selected segments of heart rate time series. During recovery, heart rate decreased gradually but did not attain pre-exercise values within 30 min after exercise. On the other hand, HRV gradually increased, but did not regain rest values during the study period. Heart rate complexity was slightly reduced after exercise and attained rest values after 30-min recovery. The rate of cardiodeceleration did not correlate with pre-exercise HRV parameters, but positively correlated with HRV measures and sample entropy obtained from the early phases of recovery. In conclusion, the cardiodeceleration rate is independent of HRV measures during the rest period but it is related to early post-exercise recovery HRV measures, confirming a parasympathetic contribution to this phase

'Respiratory' oscillations of cardiovascular parameters during voluntary apnea.

The aim of this study was to ascertain the persistence of heart rate and blood pressure oscillations at the onset of voluntary apnea in humans. In 24 young subjects (10 males, 14 females, mean age 20.4 years) RR intervals, systolic blood pressure (SBP) and diastolic blood pressure (DBP) during controlled breathing (CB) of atmospheric air followed by voluntary apnea on FRC level were recorded continuously. The cosine functions were then fitted by nonlinear regression analysis to heart rate, SBP and DBP oscillations during CB and at the onset of apnea. During apnea, the changes of base of RR intervals indicate primary tachycardic reaction followed by a decrease in heart rate. The base of the blood pressure oscillations was higher (hypertensive reaction) in apnea. At least one cosine-like wave oscillation was present at the onset of apnea in heart rate, SBP and DBP and the second wave was present in all assessed parameters at least in 70% of recordings. There were no significant gender differences neither in the duration of breath holding nor in the RR and SBP oscillations parameters.