• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.437-449
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• 2001

Background : In the severe community-acquired pneumonia, it has been known that the immune status is occasionally suppressed. This study was performed to identify the immunologic markers related with the prognostic factors in severe community-acquired pneumonia. Methods : 23 patients with severe community-acquired pneumonia were involved in this study, and divided into survivor (16) and nonsurvivor (7) groups. In this study, the medical history, laboratory tests(complete blood counts, routine chemistry profile, immunoglobulins, complements, lymphocyte subsets, cytokines, sputum and blood culture, urine analysis), and chest radiographs were scrutinized. Results : 1) Both groups had lymphopenia(total lymphocyte count $995.6{\pm}505.7/mm^3$ in the survivor and $624.0{\pm}287.6/mm^3$ in the nonsurvivor group). 2) The T-lymphocyte count of the nonsurvivor group($295.9{\pm}203.0/mm^3$) was lower than the survivor group($723.6{\pm}406.5/mm^3$) (p<0.05). 3) The total serum protein(albumin) was $6.0{\pm}1.0(2.7{\pm}0.7)\;g/d{\ell}$ in the survivor and $5.2{\pm}1.5(2.3{\pm}0.8)g/d{\ell}$ in the nonsurvivor group. The BUN of the nonsurvivor group($41.7{\pm}30.0mg/d{\ell}$) was higher than that of the survivor group($18.9{\pm}9.8mg/d{\ell}$)(p<0.05). The creatinine concentration was higher in the nonsurvivor group($1.8{\pm}1.0mg/d{\ell}$) than that in the survivor group($1.0{\pm}0.3mg/d{\ell}$)(p<0.05). 4) The immunoglobulin G level was higher in the survivor group($1433.0{\pm}729.5mg/d{\ell}$) than in the nonsurvivor group($849.1{\pm}373.1mg/d{\ell}$) (p<0.05). 5) The complement $C_3$ level was $108.0{\pm}37.9mg/d{\ell}$ in the survivor group and $88.0{\pm}32.1mg/d{\ell}$ in the nonsurvivor group. 6) A cytokine study showed an insignificant difference in both groups. 7) Chronic liver disease, DM, and COPD were major underlying diseases in both groups. Conclusion : These results suggest that decreased a T-lymphocyte count and immunoglobulin G level, and an increased BUN and creatinine level may be associated with the poor prognosis of severe community-acquired pneumonia.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.478-486
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• 2000

Background : In acute lung injury, alveolar macrophages play a pivotal role in the inflammatory process during the initiation phase and in the reconstruction and fibrosis process during the later phase. Recently, it has been proven that alveolar macrophages are constituted by morphologically, biochemically and immunologically heterogenous cell subpopulations. The possibility of alterations to these characteristics of the alveolar macrophage population during lung disease has been raised. To investigate such a possibility a hyperoxic rat lung model was made to check the distributional and morphological changes of rat alveolar macrophage subpopulation in acute hyperoxic lung injury. Method : Alveolar macrophage were lavaged from normal and hyperoxic lung injury rats and separated by discontinuous gradients of percoll. After cell counts of each density fraction were accessed, the morphomeric analysis of alveolar macrophages was performed on cytocentrifuged preparations by transmission electron micrograph. Result : 1. The total alveolar macrophage cell count significantly increased up to 24 hours after hyperoxic challenge (normal control group $171.6{\pm}24.1{\times}10^5$, 12 hour group $194.8{\pm}17.9{\times}10^5$, 24 hour group $207.6{\pm}27.1{\times}10^5$, p<0.05). oHoHH However the 48 hour group ($200.0{\pm}77.8{\times}10^5$) did not show a significant difference. 2. Alveolar septal thickness significantly increased up to 24 hours after hyperoxic challenge(normal control group $0.7{\pm}0.2{\mu}m$, 12 hour group $1.5{\pm}0.4{\mu}m$, 24 hour group $2.3{\pm}0.4{\mu}m$, p<0.05). However the 48 hour group did not show further change ($2.5{\pm}0.4{\mu}m$). Number of interstitial macrophage markedly increased at 24 hour group. 3. Hypodense fraction(fraction 1 and fraction 2) of alveolar macrophage showed a significant increase following hyperoxic challenge ($\beta=0.379$.$\beta=0.694$. p<0.05) ; however, fraction 3 was rather decreased following the hyperoxic challenge($\beta=0.815$. p<0.05), and fraction 4 showed an irregular pattern. 4. Electron microscopic observation of alveolar macrophage from each fraction revealed considerable morphologic heterogeneity. Cells of the most dense subfraction(fraction 4) were small, round, and typically highly ruffled with small membrane pseudopods. Cells of the least dense fraction (fraction 1) were large and showed irregular eccentric nucleus and high number of heterogenous inclusions. Conclusion : In conclusion, these results suggest that specific hypodense alveolar macrophage subpopulation may play a an important role in an acute hyperoxic lung injury model But further study, including biochemical and immunological function of these subpopulations, is needed.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.449-458
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• 2003

Background : The poor prognostic factors of far-advanced pulmonary tuberculosis(FAPTB) are lymphocytopenia in the peripheral blood(PB)(< $1,000/mm^3$) and $T_4$-cell count ${\leq}500/mm^3$. However, the cause of PB lymphocytopenia in FAPTB is unclear. The aim of this study was to analyze the lymphocyte proportion and cytokines of the bone marrow(BM) in FAPTB patients with peripheral lymphocytopenia in order to clarify whether the limiting step of the lymphocytopenia occurs in production, differentiation, or circulation. Methods : This study included patients with FAPTB between August 1999 and August 2002 who visited Gachon Medical School Gil Medical Center. The exclusion criteria were old age(${\geq}65years$), cachexia or a low body weight, shock, hematologic diseases, or BM involvement of tuberculosis. The distributions of cells in PB and BM were analyzed and compared to the control group. The interleukin(IL)-2, IL-7, IL-10, TNF-${\alpha}$, Interferon-${\gamma}$, and TGF-${\beta}$ levels in the BM were measured by ELISA. Result : Thirteen patients(male : female=9:4) were included and the mean age was $42{\pm}12$years. The proportion and count of the lymphocytes in the PB were significantly lower in the FAPTB group ($7.4{\pm}3.0%$, $694{\pm}255/mm^3$ vs. $17.5{\pm}5.8%$, $1,377{\pm}436/mm^3$, each p=0.0001 and 0.002). The proportion of immature lymphocyte in the BM showed a decreasing trend in the FAPTB group($9{\pm}4%$ vs. $12{\pm}3%$, p=0.138). The IL-2($26.0{\pm}29.1$ vs. $112.2{\pm}42.4pg/mL$, p=0.001) and IL-10($3.4{\pm}4.7$ vs. $12.0{\pm}8.0pg/mL$, p=0.031) levels in the BM were significantly lower in the FAPTB group than those in control. The levels of the other cytokines in FAPTB group and control were similar. Conclusion : These results suggest that the cause of lymphocytopenia in PB is associated with a abnormality IL-2 and IL-10 production in the BM. More study will be needed to define the mechanism of a decreased reservoir in BM.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.71-79
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• 2003

Background : A bronchoalveolar lavage(BAL) is useful in diagnosing the etiology of bilateral pulmonary infiltrations, but may worsen the oxygenation and clinical status in severely hypoxemic patients. This study assessed the safety and efficacy of the continuous positive airway pressure(CPAP) using a conventional mechanical ventilator via a face mask as a tool for maintaining the oxygenation level during BAL. Methods : Seven consecutive patients with the bilateral pulmonary infiltrates and severe hypoxemia ($PaO_2/FIO_2$ ratio ${\leq}200$ on oxygen 10 L/min via mask with reservoir bag) were enrolled. The CPAP 5-6 $cmH_2O(F_IO_2\;1.0)$ was delivered through an inflatable face mask using a conventional mechanical ventilator. The CPAP began 10 min before starting the BAL and continued for 30 min after the procedure was completed. A bronchoscope was passed through a T-adapter and advanced through the mouth. BAL was performed using the conventional method. The vital signs, pulse oxymetry values, and arterial blood gases were monitored during the study. Results : (1) Median age was 56 years(male:female=4:3). (2) The baseline $PaO_2$ was $78{\pm}16mmHg$, which increased significantly to $269{\pm}116mmHg$(p=0.018) with CPAP. After the BAL, the $PaO_2$ did not decrease significantly but returned to the baseline level after the CPAP was discontinued. The $SpO_2$ showed a similar trend with the $PaO_2$ and did not decrease to below 90 % during the duration of the study. (3) The $PaCO_2$ increased and the pH decreased significantly after the BAL but returned to the baseline level within 30 min after the BAL. (5) No complications directly related to the BAL procedure were encountered. However, intubation was necessary in 3 patients(43 %) due to the progression of the underlying diseases. Conclusion : In severe hypoxemic patients, CPAP using a face mask and conventional mechanical ventilator during a BAL might allow minimal alterations in oxygenation and prevent subsequent respiratory failure.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1972.03a
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• pp.5-6
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• 1972

Noise and air pollution, which accompany the development of industry and the increase of population, contribute to the deterioration of urban environment. The air pollution level of Seoul has gradually increased and the city residents are suffering from a high pollution of noise. If no measures were taken against pollution, the amount of emission of pollutant into air would be 36.7 thousand tons per year per square kilometer in 1975, three times more than that of 1970, and it would be the same level as that of United States in 1968. The main sources of air pollution in Seoul are the exhaust has from vehicles and the combustion of bunker-C oil for heating purpose. Thus, it is urgent that an exhaust gas cleaner should be instaled to every car and the fuel substituted by less sulfur-contained-oil to prevent the pollution. Transportation noise (vehicular noise and train noise) is the main component of urban noise problem. The average noise level in downtown area is about 75㏈ with maximum of 85㏈ and the vehicular homing was checked 100㏈ up and down. Therefore, the reduction of the number of bus-stop the strict regulation of homing in downtown area and a better maintenance of car should be an effective measures against noise pollution in urban areas. Within the distance of 200 metres from railroad, the train noise exceeds the limit specified by the pollution control law in Korea. Especially, the level of noise and steam-whistle of train as measured by the ISO evaluation can adversely affect the community activities of residents. To prevent environmental destruction, many developed countries have taken more positive action against worsening pollution and such an action is now urgently required in this country.

• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.357-366
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• 1993

Background: Lung clearance of inhaled $^{99m}Tc$-DTPA reflects alveolar epithelial permeability and it had been reported as more sensitive than conventional pulmonary function tests in detecting lung epithelial damage. However, measuring lung clearance of inhaled $^{99m}Tc$-DTPA by gamma camera may not always reflect alveolar epithelial permeability exactly because it is influenced by mucociliary clearance depending on the site of particle deposition. Moreover, this method takes much time and patient's effort because he has to sit or lie still in front of the camera for a prolonged period. Most of the absorbed DTPA is excreted in urine within 24 hours and the amount of excreted DTPA in urine during the first few hours after inhalation is influenced by absorption rate which is correlated with the alveolar-epithelial permeability suggesting that the urinary excretion, especially in first few hours, may be an alternate index for lung clearance. The purpose of this study was to evaluate the usefulness of ratio of excreted $^{99m}Tc$-DTPA in 2 hour and 24 hour urine as an index of alveolar-epithelial damage. Methods: Pulmonary function tests including diffusing capacity and lung clearance of $^{99m}Tc$-DTPA measured by gama camera ($T_{1/2}$) and 2hr/24hr urine excretion ratio (Ratio) of inhaled $^{99m}Tc$-DTPA in 8 normal subjects and 14 patients with diffuse interstitial lung disease were compared. Results: 1) In the normal control, there was significant negative correlation between the $T_{1/2}$ and the Ratio (r=-0.77, p<0.05). In patients with diffuse interstitial lung disease, there also was significant negative correlation between $T_{1/2}$ and Ratio(r=-0.63, p<0.05). 2) In diffuse interstitial lung disease patients, the $T_{1/2}$ was $38.65{\pm}11.63$ min which was significantly lower than that of normal control, $55.53{\pm}11.15$ min and the Ratio was $52.15{\pm}10.07%$ also signifantly higher than that of the normal control, $40.43{\pm}5.53%$ (p<0.05). 3) There was no significant correlations between $T_{1/2}$ or Ratio and diffusing capactiy of lung in both patients and controls (p>0.05). Conclusion: These results suggests that 2hr/24hr urine excretion ratio of inhaled $^{99m}Tc$-DTPA is a useful simple bedside test in assessing alveolar epithelial permeability and that it may be used as an additive follow-up test in patients with diffuse interstitial lung disease complementing conventional pulmonary function tests.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.349-359
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• 1997

Background : The signal pathways and their precise roles for acute respiratory distress syndrome caused by endotoxin (ETX) has not been established. Since there has been several in vitro experiments suggesting that activation of protein kinase C (PKC) pathway may be responsible for endotoxin-induced inflammatory reaction, we performed in vivo experiments in the rats with the hypothesis that PKC-inhibition can effectively prevent endotoxin-induced acute lung injury. Methods : We studied the role of PKC in ETX-induced ALI using PKC inhibitor (staurosporine, STP) in the rat Specific pathogen free male Sprague-Dawley weighted from 165 to 270g were used for the study. Animals were divided into the normal control (NC)-, vehicle control (VC)-, ETX-, PMA (phorbolmyristateacetate)-, STP+PMA-, and STP+ETX-group. PMA (50mg/kg) or ETX (7mg/kg) was instilled through polyethylen catheter after aseptic tracheostomy with and without STP (0.2mg/kg)-pretreatment STP was injected via tail vein 30min before intratracheal injection (IT) of PMA or ETX. Bronchoalveolar lavage (BAL) was done 3-or 6-hrs after IT of PMA or ETX respectively, to measure protein concentration, total and differential cell counts. Results : The results were as follows. The protein concentrations in BALF in the PMA- and ETX-group were very higher than that of VC-group (p<0.001). When animals were pretreated with STP, the %reduction of the protein concentration in BALF was $64.8{\pm}8.5$ and $30.4{\pm}2.5%$ in the STP+PMA- and STP+ETX-group, respectively (p = 0.028). There was no difference in the total cell counts between the PMA-and VC-group (p = 0.26). However the ETX-group showed markedly increased total cell counts as compared to the VC- (p = 0.003) and PMA-group (p = 0.0027), respectively. The total cell counts in BALF were not changed after pretreatment with STP compared to the PMA- (p = 0.22) and ETX-group (p = 0.46). The percentage of PMN, but not alveolar macrophage, was significantly elevated in the PMA-, and ETX-group. Especially in the ETX-group, the percentage of PMN was 17 times higher than that of PMA (p < 0.001). The differential cell counts was not different between the PMA and STP+PMA On the contrary the STP+ETX-group showed decreased percentage of PMN (p = 0.016). There was no significant relationship between the protein concentration and the total or differential cell counts in each group. Conclusion : Pretreatment with PKC-inhibitor (staurosporine) partially but significantly inhibited ETX-induced ALI.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.823-834
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• 1998

Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.367-376
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• 1996

Background : The diagnosis of emphysema during life is based on a combination of clinical, functional, and radiographic findings, but this combination is relatively insensitive and nonspecific. The development of rapid, high-resolution third and fourth generation CT scanners has enabled us to resolve pulmonary parenchymal abnormalities with great precision. We compared the chest HRCT findings to the pulmonary function test and arterial blood gas analysis in pulmonary emphysema patients to test the ability of HRCT to quantify the degree of pulmonary emphysema. Methods : From october 1994 to october 1995, the study group consisted of 20 subjects in whom HRCT of the thorax and pulmonary function studies had been obtained at St. Mary's hospital. The analysis was from scans at preselected anatomic levels and incorporated both lungs. On each HRCT slice the lung parenchyma was assessed for two aspects of emphysema: severity and extent. The five levels were graded and scored separately for the left and right lung giving a total of 10 lung fields. A combination of severity and extent gave the degree of emphysema. We compared the HRCT quantitation of emphysema, pulmonary function tests, ABGA, CBC, and patients characteristics(age, sex, height, weight, smoking amounts etc.) in 20 patients. Results : 1) There was a significant inverse correlation between HRCT scores for emphysema and percentage predicted values of DLco(r = -0.68, p < 0.05), DLco/VA(r = -0.49, p < 0.05), FEV1(r = -0.53, p < 0.05), and FVC(r = -0.47, p < 0.05). 2) There was a significant correlation between the HRCT scores and percentage predicted values of TLC(r = 0.50, p < 0.05), RV(r = 0.64, p < 0.05). 3) There was a significant inverse correlation between the HRCT scores and PaO2(r = -0.48, p < 0.05) and significant correlation with D(A-a)O2(r = -0.48, p < 0.05) but no significant correlation between the HRCT scores and PaCO2. 4) There was no significant correlation between the HRCT scores and age, sex, height, weight, smoking amounts in patients, hemoglobin, hematocrit, and wbc counts. Conclusion : High-Resolution CT provides a useful method for early detection and quantitating emphysema in life and correlates significantly with pulmonary function tests and arterial blood gas analysis.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.153-168
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• 1998

Background: The existing data indicate that obstructive sleep apnea syndrome contributes to the development of cardiovascular dysfunction such as systemic hypertension and cardiac arrhythmias, and the cardiovascular dysfunction has a major effect on high long-term mortality rate in obstructive sleep apnea syndrome patients. To a large extent the various studies have helped to clarify the pathophysiology of obstructive sleep apnea, but many basic questions still remain unanswered. Methods: In this study, the influence of obstructive sleep apnea on systemic blood pressure, cardiac rhythm and urinary catecholamines concentration was evaluated. Over-night polysomnography, 24-hour ambulatory blood pressure and ECG monitoring, and measurement of urinary catecholamines, norepinephrine (UNE) and epinephrine (UEP), during waking and sleep were undertaken in obstructive sleep apnea syndrome patients group (OSAS, n=29) and control group (Control, n=25). Results: 1) In OSAS and Control, UNE and UEP concentrations during sleep were significantly lower than during waking (P<0.01). In UNE concentrations during sleep, OSAS showed higher levels compare to Control (P<0.05). 2) In OSAS, there was a increasing tendency of the number of non-dipper of nocturnal blood pressure compare to Control (P=0.089). 3) In both group (n=54), mean systolic blood pressure during waking and sleep showed significant correlation with polysomnographic data including apnea index (AI), apnea-hypopnea index (AHI), arterial oxygen saturation nadir ($SaO_2$ nadir) and degree of oxygen desaturation (DOD). And UNE concentrations during sleep were correlated with AI, AHI, $SaO_2$ nadir, DOD and mean diastolic blood pressure during sleep. 4) In OSAS with AI>20 (n==14), there was a significant difference of heart rates before, during and after apneic events (P<0.01), and these changes of heart rates were correlated with the duration of apnea (P<0.01). The difference of heart rates between apneic and postapneic period (${\Delta}HR$) was significantly correlated with the difference of arterial oxygen saturation between before and after apneic event (${\Delta}SaO_2$) (r=0.223, P<0.001). 5) There was no significant difference in the incidence of cardiac arrhythmias between OSAS and Control In Control, the incidence of ventricular ectopy during sleep was significantly lower than during waking. But in OSAS, there was no difference between during waking and sleep. Conclusion : These results suggested that recurrent hypoxia and arousals from sleep in patients with obstructive sleep apnea syndrome may increase sympathetic nervous system activity, and recurrent hypoxia and increased sympathetic nervous system activity could contribute to the development of cardiovascular dysfunction including the changes of systemic blood pressure and cardiac function.