The effects of a self-care program on patients with heart failure.

BACKGROUND: A lack of adequate knowledge and misconceptions by heart failure (HF) patients can lead to the improper use of self-care skills, as well as a lack of confidence in those same self-care skills. The existing literature suggests that care providers using a video-tape or a teaching booklet to educate HF patients, combined with telephone or telemonitoring counseling can effectively promote self-care and reduce readmission rates, and in turn promote overall patient health. The aim of the present study was to investigate the effects of self-care programs in patients with HF. METHODS: A quasi-experimental design was used to investigate the effectiveness of a self-care program in HF patients. The patients were allocated into either the control group (usual care, n = 75) or the experimental group (self-care program, n = 56). The extent of patient knowledge about congestive HF (CHF) was tested at both the pre- and posteducation stages. We measured the self-care of HF index (SCHFI) and the New York Heart Association (NYHA) functional class a total of four times for each participant. Furthermore, hospital readmissions and mortality rates were also collected. RESULTS: The experimental group showed a significantly higher mean score in the knowledge of CHF during posteducation testing than the control group. The results of the self-care evaluation also revealed significant differences between the two groups by repeated general linear model measurement analysis. Self-care maintenance, self-care management, and self-care confidence significantly improved after the self-care program was completed. The NYHA functional class in the experimental group showed a significant improvement after hospital discharge when compared with those in the control group. However there was no significant difference in hospital readmission or mortality rate between the two groups. CONCLUSION: Our study reveals that self-care programs administered by HF patients can reinforce educational objectives and improve patient ability to effectively perform self-care.

Comparison of the effect of intensive versus conventional insulinotherapy in patients with cardiac surgery after cardiopulmonary bypass.

Hyperglycemia occurs commonly in clinically ill patients. Insulin therapy and glycemic control have been recommended for patients with septic shock. The present study investigated the effect of intensive (INIT) versus conventional insulinotherapy (COIT) in cardiac surgery patients who received cardiopulmonary bypass (CPB). In this quasi-experimental study, a total of 50 patients undergoing coronary artery bypass grafting (CABG) were recruited into the INIT and COIT groups. Study measures included serum glucose levels, cardiac output, cytokines, C-reactive protein (CRP), duration of mechanical ventilation and length of stay in the intensive care unit (ICU), and ICU mortality rate. In the INIT group, mean blood glucose level during the first two postoperative days was significantly lower than that in the COIT group. Cardiac output was significantly greater at the second postoperative days in the INIT patients than those in the COIT group. There were no differences in cytokines, CRP levels and the outcome data between two groups. Intensive insulinotherapy reduced the blood glucose and led to improve cardiac output after CABG in comparison with conventional insulinotherapy.

"Inflammatory response to colloids compared to crystalloid priming in cardiac surgery patients with cardiopulmonary bypass".

"Cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory response syndrome that may contribute to postoperative morbidity and mortality. We investigated the in-flammatory responses to colloids compared to crystalloid priming in cardiac surgery patients with cardiopulmonary bypass. Thirty patients undergoing coronary artery bypass grafting (CABG) preparing for CPB were randomized into Ringer's solution (RS), 10% hydroxyethyl starch (HES) or 25% human albumin (HA) group. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-1 ß (IL-1ß ), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured before CPB, at the end of CPB and 1, 6 and 12 h after CPB. Serum C-reactive protein (CRP) was determined pre-operatively and then daily for 2 days. Body-weight gain was significantly decreased on the day after surgery in the HES group than in the RS group. Volume priming in CPB for CABG patients using HA or HES preparation had less tendency for intense inflammatory response with lower levels of TNF-α, IL-1 ß , IL-6 and higher levels of IL-10 compared to patients treated with RS. HES prime had lower levels of circulating CRP than in patients treated with HA or Ringer prime on the second post-operative day. Our data indicate that volume priming using colloid during CPB in CABG patients might exert beneficial effects on inflammatory responses."

The protective role of nitric oxide and nitric oxide synthases in whole-body hyperthermia-induced hepatic injury in rats.

PURPOSE: The present study was designed to elucidate the role of endothelial nitric oxide (NO) synthase (eNOS), inducible NOS (iNOS)-derived NO and heat-shock protein (Hsp70) in a rat model of whole-body hyperthermia (WBH)-induced liver injury. MATERIALS AND METHODS: Real-time polymerase chain reaction, immunohistochemistry and western blot were used to observe the mRNA and protein expression of eNOS, iNOS and Hsp70. Rats were exposed to hyperthermia by immersion for 60 min at a conscious state in a water bath maintained at 41°C. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were used to assess liver injury 15 h after the hyperthermia challenge. Nitrosative and oxidative mediators, particularly NO and hydroxyl radical were measured. RESULTS: Plasma AST, ALT, hydroxyl radical, and NO were significantly increased after WBH. There were 4.14 ± 0.42, 2.82 ± 0.34 and 2.91 ± 0.16-fold increases in the mRNA expression of eNOS, iNOS and Hsp70. Immunohistochemistry and western blot showed up-regulation of eNOS, iNOS and Hsp70 protein. An eNOS inhibitor (N(ω)-nitro-L-arginine methyl ester (L-NAME)), or an iNOS inhibitor (aminoguanidine (AG)), significantly aggravated the liver injury. On the contrary, administration of NO precursor, L-arginine (L-ARG), attenuated the liver injury. Hsp70 inhibitor quercetin reduced Hsp70, while aggravating the WBH-induced hepatic changes. CONCLUSIONS: WBH induces increases in eNOS, iNOS and Hsp70 expression with increase in NO release. The deleterious effects of L-NAME and AG and the protective effects of L-ARG and Hsp70 inhibitor on the liver function and pathology suggest that NO and heat shock protein play a beneficial role in the WBH-induced hepatic injury.

Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate in isolated rat's lungs.

BACKGROUND: Phorbol myristate acetate (PMA) is a strong neutrophil activator and has been used to induce acute lung injury (ALI). Niacinamide (NAC) is a compound of B complex. It exerts protective effects on the ALI caused by various challenges. The purpose was to evaluate the protective effects of niacinamide (NAC) on the PMA-induced ALI and associated changes. METHODS: The rat's lungs were isolated in situ and perfused with constant flow. A total of 60 isolated lungs were randomized into 6 groups to received Vehicle (DMSO 100 µg/g), PMA 4 µg/g (lung weight), cotreated with NAC 0, 100, 200 and 400 mg/g (lung weight). There were 10 isolated lungs in each group. We measured the lung weight and parameters related to ALI. The pulmonary arterial pressure and capillary filtration coefficient (Kfc) were determined in isolated lungs. ATP (adenotriphosphate) and PARP [poly(adenosine diphophate-ribose) polymerase] contents in lung tissues were detected. Real-time PCR was employed to display the expression of inducible and endothelial NO synthases (iNOS and eNOS). The neutrophil-derived mediators in lung perfusate were determined. RESULTS: PMA caused increases in lung weight parameters. This agent produced pulmonary hypertension and increased microvascular permeability. It resulted in decrease in ATP and increase in PARP. The expression of iNOS and eNOS was upregulated following PMA. PMA increased the neutrophil-derived mediators. Pathological examination revealed lung edema and hemorrhage with inflammatory cell infiltration. Immunohistochemical stain disclosed the presence of iNOS-positive cells in macrophages and endothelial cells. These pathophysiological and biochemical changes were diminished by NAC treatment. The NAC effects were dose-dependent. CONCLUSIONS: Our results suggest that neutrophil activation and release of neutrophil-derived mediators by PMA cause ALI and associated changes. NO production through the iNOS-producing cells plays a detrimental role in the PMA-induced lung injury. ATP is beneficial, while PARP plays a deteriorative effect on the PMA-induced ALI. NAC exerts protective effects on the inflammatory cascade leading to pulmonary injury. This B complex compound may be applied for clinical usage and therapeutic regimen.

Effects of phorbol myristate acetate and sivelestat on the lung injury caused by fat embolism in isolated lungs.

BACKGROUND: Fat embolism syndrome (FES) associated with acute lung injury (ALI) is a clinical condition following long bone fracture. We have reported 14 victims due to ALI with FES. Our laboratory has developed an animal model that produced fat emboli (FE). The major purpose of this study was to test whether neutrophil activation with phorbol myristate acetate (PMA) and inhibition with sivelestat (SVT) exert protection on the lung. METHODS: The lungs of Sprague-Dawley rats were isolated and perfused. FE was produced by addition of corn oil micelles into the lung perfusate. PMA and SVT were given simultaneously with FE. Parameters such as lung weight/body weight ratio, LW gain, exhaled nitric oxide (NO), protein concentration in bronchoalveolar lavage relating to ALI were measured. The neutrophil elastase (NE), myeloperoxidase, malondialdehyde and phopholipase A2 activity were determined. We also measured the nitrate/nitrite, methyl guanidine (MG), and cytokines. Pulmonary arterial pressure and microvascular permeability were assessed. Lung pathology was examined and scored. The inducible and endothelial NO synthase (iNOS and eNOS) were detected. RESULTS: FE caused ALI and increased biochemical factors. The challenge also resulted in pulmonary hypertension and increased microvascular permeability. The NE appeared to be the first to reach its peak at 1 hr, followed by other factors. Coadministration with PMA exacerbated the FE-induced changes, while SVT attenuated the effects of FE. CONCLUSIONS: The FE-induced lung changes were enhanced by PMA, while SVT had the opposite effect. Sivelestat, a neutrophil inhibitor may be a therapeutic choice for patients with acute respiratory distress syndrome (ARDS) following fat embolism.

Hemodynamic mechanism of ventricular hypertrophy in hypertension.

Arterial hemodynamic assessments with technique of spectral analysis can obtain complete hemodynamic parameters including steady and pulsatile components. The steady parameters include arterial pressure (AP), heart rate, cardiac output, stroke volume and total peripheral resistance (TPR). Parameters of pulsatile hemodynamics are characteristic impedance (Zc), arterial compliance (Cm) and pulse wave reflection (Pb) etc. Studies of ventricular hypertrophy (VH) and arterial hemodynamics have disclosed several important findings. Hypertension in spontaneously hypertensive rat (SHR) and human subjects causes functional abnormalities in the resistance and Windkessel vessels. The extent of VH in SHR and hypertensive subjects was not correlated with AP and TPR, but positively correlated with pulsatile hemodynamic factors such as Zc and Pb. Many antihypertensive and vasodilators were capable of reducing the AP, but did not improve the VH. We have also investigated the effects of vasodilatory agents such as nifedipine (a calcium channel blocker), propranol (a non-selective ß-adrenergic blocker) and atenol (a selective ß-adrenergic inhibitor) on the arterial hemodynamics and VH. In addition, the effects of acute and chronic nitric oxide (NO) deprivation with Nω-nitro-L-arginine methyl ester (L-NAME) on the arterial hemodynamics and VH were evaluated. We compared the endothelium-dependent and -independent vasodilation to acetylcholine, sodium nitroprusside and S-nitroso-N-acetylpenicillanine and the endothelium-dependent or -independent vasoconstriction to norepinephrine and phenylephrine between SHR and normotensive Wistar Kyoto strain. In SHR with long-term administration of L-NAME, VH was associated with decreases in left ventricular cGMP and nitrate/nitrite accompanying increase in collagen content. Coadministration of NO precursor L-arginine improved the VH and fibrosis. In VH caused by long-term L-NAME, the LW/BW ratio, total number, numerical density and size of cardiomyocytes were correlated well with both steady and pulsatile hemodymanics. Aortic stiffness has significant impact on the cardiovascular risks. We simulated aortic stiffness by applying silicon gel embedding of the abdominal and/or thoracic aorta. Aortic stiffness did not affect the blood pressure and the steady hemodynamics. It caused VH associated with increases in the pulsatile hemodynamics. The extent of VH (LVW/BW, total number, numerical density, size of cardiomyocytes and collagen volume fraction) was correlated with the pulsatile hemodynamics (impedance, pulse wave velocity and wave reflection). The finding further supports the contention that blood pressure is not the determinant of VH. The ventricular afterload is the major cause of VH. The hemodynamic consequences of ovariectomy (Ovx), menopause and estrogen replacement were investigated. Ovx increased body weight, LVW/BW ratio, Zc and Pb, but decreased Cm. These changes were reversed by estrogen replacement. For steady hemodynamics, Ovx did not much alter the systolic, mean and diastolic pressure. The pulse pressure was slightly elevated. There was large increase in TPR. Again, these changes were reversed by estrogen supplement. The implication of these findings was that menopause tends to exert vasoconstrictory effects on the resistance and Windkessel vessels. On the contrary, estrogen possesses a vasodilatory influence on the systemic vessels.

Acute respiratory distress syndrome and lung injury: Pathogenetic mechanism and therapeutic implication.

To review possible mechanisms and therapeutics for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, sepsis, infections and others. Investigations have indicated the detrimental role of nitric oxide (NO) through the inducible NO synthase (iNOS). The possible therapeutic regimen includes extracorporeal membrane oxygenation, prone position, fluid and hemodynamic management and permissive hypercapnic acidosis etc. Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents, inhalation of NO, glucocorticoids, surfactant therapy and agents facilitating lung water resolution and ion transports. ß-adrenergic agonists are able to accelerate lung fluid and ion removal and to stimulate surfactant secretion. In conscious rats, regular exercise training alleviates the endotoxin-induced ALI. Propofol and N-acetylcysteine exert protective effect on the ALI induced by endotoxin. Insulin possesses anti-inflammatory effect. Pentobarbital is capable of reducing the endotoxin-induced ALI. In addition, nicotinamide or niacinamide abrogates the ALI caused by ischemia/reperfusion or endotoxemia. This review includes historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.

Acute lung injury and acute respiratory distress syndrome: experimental and clinical investigations.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can be associated with various disorders. Recent investigation has involved clinical studies in collaboration with clinical investigators and pathologists on the pathogenetic mechanisms of ALI or ARDS caused by various disorders. This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.

Involvement of nitric oxide in mesenteric vascular reactivity following intraperitoneal pancreatic juice in rats.

The purposes of this study were to examine the protein expressions of endothelial and inducible nitric oxide synthase (eNOS and iNOS) of the rat intestinal smooth muscle, and to elucidate the role of nitric oxide (NO) in the reactivity of the superior mesenteric artery (SMA) to vasoconstrictors following intraperitoneal (i.p.) injection of pancreatic juice. Immunohistochemistry was used to observe the protein expressions of eNOS and iNOS in the intestinal tissues 15 h after i.p. injection of pancreatic juice (1 ml/100 g body weight). To test the vascular reactiveness, SMA was isolated and perfused with Tyrode's solution at a constant flow rate of 5 ml/min. The changes in perfusion pressure as the measure of contractile responses to phenylephrine (PE) were monitored. I.P. injection of pancreatic juice induced increases of plasma levels of tumor necrosis factor α (TNFα) (P < 0.001; N = 7) and NO (P < 0.001; N = 7). Nω-nitro-L-arginine methyl ester (L-NAME) reduced the release of TNFα and NO. There were 8.3 ± 1.2-fold and 11.4 ± 2.8-fold increases in the protein expressions of eNOS and iNOS, respectively, in the intestinal tissue after pancreatic juice injection. PE (10⁻8 ~ 10⁻4 M) produced a dose-dependent vasoconstrictive effects on the SMA bed. Contractile responses to PE were attenuated in pancreatic juice-treated group. Addition of L-NAME (10⁻4 M) resulted in full recovery of the responses to phenylephrine in SMA bed, while aminoguanidine (AG, 10⁻4 M) caused only partial recovery. Our results indicate that i.p. injection of pancreatic juice results in a decrease in vascular reactivity of mesenteric vessels that is dependent on both eNOS and iNOS expressions in the intestinal vascular bed. Overproduction of NO elicits intestinal low vascular reactivity.

Oscillating gas bubbles as the origin of bowel sounds: a combined acoustic and imaging study.

Bowel sounds have been speculated to stem from the movement of gas or a mixture in the bowel lumen, with gas as the major component. The exact role and the mechanism through which gas participates have not been elucidated. Video images of actively moving bubbles under either real-time ultrasonography (RU, n = 4) or videofluoroscopy (VF, n = 4) with synchronous sound recording were studied and a total of 24 bubbling bowel sounds (BBS's) were obtained. The physical dimensions and acoustic parameters of bubbles were analyzed. Freely oscillating bubbles were demonstrated clearly in both groups. Bubble radii ranged from 1.5 to 7.2 mm and frequencies from 258.3 to 1,078 Hz. The bubble frequency correlated inversely with the radius (P < 0.01). The relevant acoustic features and parameters of bubble dynamics further supported the identification of gas bubbles. Although the acoustic features seemed to be of minor clinical significance, increased number of clustering or fixed, repetitive pattern of occurrences might suggest a poorer prognosis. In summary, oscillating gas bubbles are capable of producing BBS's and may play a central role in this newly recognized model of bowel sound genesis. The patterns of BBS's may be of prognostic value in clinical application, underlining the need for further study.

Enhancement effects of hypercapnia on the acute lung injury caused by acid aspiration.

Acid aspiration or intrapulmonary instillation of gastric particles causes lung inflammation leading to acute lung injury (ALI). Hypercapnia exerts different effects on ALI caused by various insults. The effects of hypercapnia on lung inflammation and injury due to acid aspiration are yet to be determined. The present study was designed to investigate the involvement of inducible nitric oxide synthase (iNOS) and other mediators in acid-aspiration-induced ALI. We also sought to evaluate the effects of hypercapnia on the lung and associated changes induced by acid aspiration. We used Spague-Dawley rats anesthetized with intraperitioneal pentobarbital (40 mg/kg). Gastric acid particles were prepared from the stomach contents of rats at necropsy. The rats were randomly assigned to receive intratracheal instillation of physiological saline solution (PSS) at pH 7.24 (Control group), PSS at pH 1.25 (Low pH, LPH group), gastric particles (GP group), and GP with low pH PSS (GPLPH group). There were 10 rats in each group. The animals were observed for 6 hrs. To evaluate the effects of hypercapnia, we carried out two series of experiments: one under normocapnia and the other under hypercapnia with alteration of CO2 fraction in inspired air. Arterial pressure (AP) was monitored from the femoral arterial catheter. Heart rate was obtained from AP traicing. We determined the blood gases and acid-base status. Lung weight to body weight (LW/BW) ratio, LW gain (LWG), protein concentration in bronchoalveolar lavage (PCBAL) and leakage of Evans blue dye tracer were measured. Plasma nitrate/nitrite, methyl guanidine (MG), myeloperoxidase (MPO), phospholipase A2 (PLA2), proinflammatory cytokines were assessed. Histopathological examination of the lung tissue was performed. We employed reverse-transcriptase polymerase chain reaction to detect the expression of iNOS mRNA. GP and GPLPH caused hypotension, decreases in PaO2, pH and SaO2, and an increase in PaCO2. The insults also elevated LW/BW, LWG, PCBAL and dye leakage, plasma nitrate/nitrite, MG, MPO, PLA2, tumor necrosis factor(alpha), interleukin-beta and interleukin-6. The lung pathology was characterized by alveolar edema and hemorrhage with inflammatory cells infiltration. Assessment of lung injury score revealed that GP and GPLPH caused ALI. Furthermore, hypercapnia significantly enhanced ALI and associated changes following LPH, GP and GPLPH. Intratracheal instillation of GP in normal or low pH PSS causes ALI accompanied with biochemical changes. The release of nitric oxide via iNOS isoform is detrimental to the lung. Hypercapnia tended to enhance ALI and associated changes induced by gastric acid instillation.

From neurogenic pulmonary edema to fat embolism syndrome: a brief review of experimental and clinical investigations of acute lung injury and acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is the most devastating form of acute lung injury (ALI) or pulmonary edema (PE). We presented the experimental studies and clinical investigations of two serious forms of ALI. Drastic and severe PE could be induced by intracranial hypertension or cerebral compression (CC). The CC-induced PE was attributed to overactivation of the medullary sympathetic mechanism. Sympathetic vasoconstriction of the systemic and pulmonary resistance and capacitance vessels caused shift of blood volume from the splanchnic vascular beds to the lung. The hemodynamic changes led to systemic and pulmonary hypertension. Consequently, left ventricular failure as evidenced by dramatic decline in aortic flow with a slow decrease in pulmonary flow resulted in pressure and volume loading in the pulmonary circulation. These changes finally produced severe alveolar flooding and sudden death. Vasodilators such as sodium nitroprusside or nitroglycerin were capable of reducing the CC-induced pulmonary pathology and hemodynamic alterations. Fat embolism syndrome (FES) is a serious clinical problem in patients suffering from long bone fractures. ARDS may develop and cause mortality. Our laboratory reported a total of 14 subjects associated with FES and died of ARDS. We also developed a simple technique to produce FES. Corn oil was mixed with distilled water to form fatty micelles. Intravenous administration of or introduction of fatty micelles in anesthetized rats or isolated perfused lungs caused severe alveolar damage. Our clinical observation and animal experimentation revealed that infusion of fatty acids caused physical phase, resulting in microvascular obstruction accompanied by pulmonary hypertension and increased capillary permeability. Thereafter, the lipases in the lung hydrolyzed the neutral fat and released free fatty acids and biochemical mediators which were toxic to the lung. Our data have suggested that nitric oxide (NO), inducible NO synthase (iNOS), phospholipase A2, free radical and inflammatory cytokines (tumor necrosis factor alpha, interleukin-1beta and interleukin-6) are involved in the biochemical phase of FES with ARDS. The alveolar macrophages are the major source of iNOS. Later study also found that neutrophil elastase and myeloperoxidase were elevated following fat embolism. N-acetylcysteine (an antioxidant), and NOS inhibitors such as Nomega nitro-L-arginine methyl ester (L-NAME), S-methylisothiourea (SMT) or L-N6 (1-iminoethyl)-lysine (L-Nil) were able to abrogate the FES or the fat embolism-induced changes.

Endothelin and gelatinases in renal changes following blockade of nitric oxide synthase in hypertensive rats.

We investigated the involvement of matrix metalloproteinases (MMPs), tissue inhibitor (TIMP) and endothelin-1 (ET-1) in the renal damage in spontaneously hypertensive rats (SHR) following nitric oxide (NO) deprivation. SHR received Nomega-nitro-L-arginine methyl ester (L-NAME) from 5 wk-old for a period of 30 days. An ETA antagonist, FR139317 was used. We gave SHR FR139317 alone and cotreatment with L-NAME. L-NAME caused systemic hypertension, decrease in plasma nitrate/nitrite, increases in blood urea nitrogen and creatinine, impairment of glomerular dynamics. NO deprivation reduced the renal tissue cGMP, but it increased the collagen volume fraction, number of sclerotic glomeruli, arteriolar injury score and glomerular injury score. In addition, L-NAME elevated the plasma ET-1 at day 5. Cotreatment with FR139317 alleviated the L-NAME-induced functional and structural changes of renal glomeruli. L-NAME administration for 5 to 10 days resulted in decreases in MMP2 and MMP9 with increasing TIMP2. After L-NAME for 15 days, opposite changes (increases in MMP2 and MMP9 with a decrease in TIMP2) were observed. FR139317 cotreatment ameliorated the L-NAME-induced changes in MMP2 and MMP9 throughout the 30-day observation period. The ETA antagonist cotreatment attenuated the L-NAME-induced increase in TIMP2 before day 15, but not after day 20. The results indicate that ET-1, MMPs and TIMP are involved at the early stage (before 10 days) of glomerular sclerosis and arteriosclerosis with functional impairment following NO deprivation. The changes in MMPs and TIMP at the late stage (after 20 days) may be a compensatory response to prevent further renal damage.

Oxidative and nitrosative mediators in hepatic injury caused by whole body hyperthermia in rats.

The involvement of oxidative and nitrosative mediators in liver injury caused by heat stress remains unclear. This study aimed to elucidate the role of endothelial nitric oxide synthase (eNOS), and inducible NOS (iNOS)-derived NO and nitrotyrosine in the whole-body hyperthermia (WBH)-induced liver injury. Rats were anesthetized with intraperitoneal pentobarbital, and were exposed to a heating lamp for 60 min to raise the core temperature to 42.5 degrees C. The rats were maintained at the hyperthermic state for an additional 50 min. Blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, creatine phosphokinase, amylase, lipase, nitrate/nitrite, methyl guanidine, and proinflammatory cytokines (tumor necrosis factoralpha, interleukin-1beta and interleukin-10) were measured before and 14 h after hyperthermia. Immunohistochemical staining was employed to detect the eNOS, iNOS and nitrotyrosine levels. Western blotting was used to examine the expression of heatshock protein 70 (HSP 70). Histopathological examination of the liver tissue was performed. WBH caused liver injury accompanied with significant increases in biochemical factors, nitrate/nitrite, methyl guanidine, and proinflammatory cytokines. In addition, WBH enhanced the eNOS, iNOS, nitrotyrosine and HSP 70 levels. WBH caused hepatic injury. The pathogenetic mechanism is likely mediated through the NOS-derived NO, free radical, proinflammatory cytokines and nitrotyrosine. The enhanced expression of HSP 70 may play a protective role.

Dynamic effects of respiration on aortic blood flow and its autonomic control in rats.

1. Respiratory related arterial pressure variability may reflect body fluid status and/or cardiac sympathetic function. The underlying mechanism is not clear. 2. In the present study, we used an electromagnetic blood flow meter to measure ascending aortic blood flow, from which stroke volume was integrated, to study respiration-stroke volume coupling and its underlying neural regulation. Experiments were performed on male Sprague-Dawley rats that were anaesthetized with pentobarbital sodium, paralysed with pancuronium and under mechanical ventilation. 3. Programmed irregular ventilation evoked significant variability in arterial pressure, aortic flow and stroke volume signals. Good coupling was noted between lung volume and aortic flow, as well as between lung volume and stroke volume; this coupling persisted under all experimental conditions. The aortic flow power and stroke volume variability and the transfer magnitude of the lung volume-aortic flow and lung volume-stroke volume couplings were suppressed by 1 mg/kg propranolol, but not by 0.3 mg/kg atropine or a combination of 0.3 mg/kg atropine and 2.5 mg/kg phentolamine. 4. These results suggest that respiratory related variability in aortic flow and stroke volume, which ultimately contributes to arterial pressure variability, is primarily under cardiac sympathetic control via beta-adrenoceptors in anaesthetized and mechanically ventilated rats.

Analysis of endothelial nitric oxide synthase gene polymorphisms with cardiovascular diseases in eastern Taiwan.

A few studies have been carried out to address the correlation between the endothelial nitric oxide synthase (eNOS) gene polymorphisms and cardiovascular diseases (CVD) within the Taiwanese population. However, no report has documented the situations in eastern Taiwan, which has different ethnic groups from those in western Taiwan. In this study, we explored the relationship between polymorphic eNOS alleles and CVD in eastern Taiwan. DNA extraction and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis were employed for the detection polymorphism in exon 7 of the eNOS gene. A total of 198 subjects was included. The subjects were 120 patients with CVD such as hypertension, coronary artery disease (CAD), and stroke. Normal subjects (78) served as control. Analysis of the gene polymorphism revealed that the frequency of the eNOS gene variant containing a 27-bp repeat in intron 4 is similar between control subjects (aa:ab:bb = 0%:21.8%:78.2%), and patients with CVD (aa:ab:bb = 3.3%:21.7%:75.0%). The frequency of the Glu298Asp (894G --> T) polymorphism in exon 7 of the eNOS gene was significantly different between control subjects (TT:GT:-GG = 7.7%:29.5%:62.8%) and patients with CVD (TT:GT:GG = 5.0%:74.2%:20.8%). These results suggest that the Glu298Asp polymorphism in exon 7 of the eNOS gene is likely to be a risk factor for CVD in the eastern Taiwanese population.

Protective effects of propofol on acute lung injury induced by oleic acid in conscious rats.

OBJECTIVES: Oleic acid has been used to induce acute lung injury (ALI) in animals. In patients with acute respiratory distress syndrome (ARDS), the blood level of oleic acid was increased. The mechanism and therapeutic regimen of ARDS and oleic acid-induced ALI remain undefined. In the present study, we investigated the oleic acid-induced changes in lung variables for the measure of ALI, inflammatory mediators, and neutrophil-derived substances. We evaluated the effects of pretreatment and posttreatment with propofol. DESIGN: Randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Fifty adult male Sprague-Dawley rats weighing 250-300 g. INTERVENTIONS: We employed a conscious and unrestrained rat model. Oleic acid at a dose of 100 mg/kg was administered intravenously. Propofol (30 mg/kg) was given by intravenous infusion (6 mg/kg/min for 5 mins) 30 mins before (pretreatment) and 30 mins after (posttreatment) oleic acid. MEASUREMENTS AND MAIN RESULTS: We monitored the arterial pressure, heart rate, and blood gas. The lung weight changes, exhaled nitric oxide, protein concentration in bronchoalveolar lavage, and Evans blue content in lung tissue were determined. The plasma nitrate/nitrite, methylguanidine, cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-10), neutrophil elastase, myeloperoxidase, malondialdehyde, and sodium- and potassium-activated adenosine triphosphatase (Na+-K+-ATPase) were detected. Histopathological examination of the lung was performed. Oleic acid caused systemic hypotension and severe ALI as evidenced by the increases in the extent of ALI, impairment of pulmonary functions (blood gas variables), and lung pathology. In addition, oleic acid significantly increased inflammatory mediators and neutrophil-derived factors but depressed Na+-K+-ATPase. The inducible nitric oxide synthase was up-regulated. Pre- or posttreatment with propofol was capable of reversing the oleic acid-induced changes and attenuating the extent of ALI. CONCLUSIONS: Oleic acid resulted in sepsis-like responses including ALI, inflammatory reaction, and increased neutrophil-derived factors. It depressed the Na+-K+-ATPase activity but up-regulated inducible nitric oxide synthase. Treatment with propofol abrogated or reversed the oleic acid-induced changes.

Pulmonary pathology in patients associated with scrub typhus.

AIMS: Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi. Severe cases resulting in mortality from this disease have rarely been reported. We present two scrub typhus cases (a man and a girl) who died of acute respiratory distress syndrome (ARDS). METHODS: Autopsies were performed. Histopathological and immunohistochemical stains were employed using specific antibody for O. tsutsugamushi and inducible nitric oxide synthase (iNOS). RESULTS: These subjects developed respiratory distress shortly after admission, and expired following respiratory failure. At autopsy, generalised lymphadenopathy was observed. The lung weight was about two-fold the normal value. Gross inspection revealed oedematous and haemorrhagic lungs. Microscopic examination revealed diffuse alveolar damage with hyaline membrane formation and interstitial pneumonitis with infiltration of inflammatory cells. Immunohistochemical stain showed O. tsutsugamushi antigen depositions in the endothelial cells. We also demonstrated iNOS in the alveolar macrophages and lung tissue debris in both cases. CONCLUSION: Scrub typhus is usually a mild infectious disease. Our cases present the most dramatic example of sudden death due to ARDS in a short period of time. The clinical investigation and analysis suggest direct endothelial cell invasion of the organism and marked iNOS expression may be involved in the pathogenesis of ARDS associated with scrub typhus.