Baroreflex control of heart rate during heating in subjects with low orthostatic tolerance

BACKGROUND: Heat stress induces a reduction of orthostatic tolerance. The cardiovascular responses, including the cardiac baroreflex response to heat stress, were examined to test the hypothesis that subjects with orthostatically low tolerance demonstrate an impaired baroreflex control of heart rate (HR) during heat stress. METHODS: There were 44 healthy young volunteers who underwent whole body heat stress produced by a hot-water-perfused suit during supine rest for 45 min and 75 degrees head-up tilt (HUT) for 6 min. Esophageal temperature, HR, arterial pressure, and skin blood flow in the forearm and palm were measured continuously throughout the experiment. The sensitivity of the arterial baroreflex control of HR was calculated from the spontaneous changes in beat-to-beat arterial pressure and HR. RESULTS: The HUT was uneventful for 22 volunteers (higher tolerance group), but 22 volunteers (lower tolerance group) reached presyncope after 195 +/- 19 s. Esophageal temperature, HR, arterial pressure, and skin blood flow changed similarly in the two groups during heating. In the preheating condition, the sensitivity of the baroreflex control of HR did not differ significantly between the two groups. Heating did not alter the sensitivity of baroreflex control of HR in the higher tolerance group, but decreased it significantly in the lower tolerance group. Heating increased the number of heartbeats used for analysis of the baroreflex sensitivity in the higher tolerance group, but did not change it in the lower tolerance group. CONCLUSIONS: These results suggest that the impairment of vagal baroreflex control of HR during heat exposure aggravates the orthostatic intolerance in heat-stressed humans.     

The effect of β-blocker on hamster model BIO 53.58 with dilated cardiomyopathy determined using<Superscript>123</Superscript>I-MIBG myocardial scintigraphy

OBJECTIVE: 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is currently used to evaluate cardiac sympathetic nerve function, but MIBG also has the capacity to evaluate dilated cardiomyopathy (DCM) severity and therapeutic effectiveness. In this study, we administered beta-blockers to a DCM hamster model and evaluated the effect of therapy using MIBG. We also pathologically compared the effects of myocardial fibrosis suppression. METHODS: BIO 53.58 hamsters were divided into the following five groups based on beta-blocker administration: vehicle (COT), 2 mg/kg/day carvedilol (CLT), 20 mg/kg/day (CHT) carvedilol, 4 mg/kg/day (MLT) metoprolol, 40 mg/kg/day (MHT) metoprolol. F1B hamsters were administered a vehicle (COF). Plasma catecholamine, noradrenaline (p-NADR), adrenaline (p-ADR), and dopamine (p-DOPA) were assayed, and MIBG was performed. The count ratio of the heart to the mediastinum (H/M) and left ventricle myocardial washout ratio (WR) were calculated. We then performed an autopsy and calculated the percent change in fibrotic area from myocardial sections. RESULTS: H/M of the initial image in the COT group was significantly lower at 2.4 +/- 0.2 than the 2.9 +/- 0.7 in the COF group (p < 0.05). The CLT and CHT groups had higher H/M values compared to the COT group (3.1 +/- 0.6, 3.0 +/- 0.6 versus 2.4 +/- 0.2: p < 0.05). Significant correlations were evident between the H/M of the delayed image and p-NADR and p-DOPA (p < 0.05, p < 0.01, respectively) as well as between WR and p-NADR and p-DOPA (p < 0.05). Percent change in fibrotic area was significantly lower in the beta-blocker groups than in the COT group (p < 0.05). Significant negative correlations were seen between the H/M of the delayed image and the percent change in fibrosis area. CONCLUSIONS: The delayed image H/M and WR acutely reflected cardiac disorder and sympathetic nerve function disorder in BIO 53.58 hamsters. In the carvedilol-administered groups, there was improvement compared to the initial H/M image, indicating the efficacy of the beta-blocker in DCM.     

Graphical analysis of<Superscript>99m</Superscript>Tc thyroid scintigraphy

A new non-invasive simple method for quantitative evaluation of thyroid was presented using graphical analysis of the transfer process of technetium-99m pertechnetate (99mTc) from the blood to thyroid. Thirty subjects were studied. After a bolus injection of 111 MBq of 99mTc, the data were recorded on a 128 x 128 matrix as 60 frames of 1.5-second duration. ROIs were placed over the aortic arch and bilateral thyroid lobes. The activity of the aorta was monitored instead of the arterial activity. Graphical analysis by plotting B(t)/A(t) versus integral(0)t A(tau)d tau/A(t) gave a straight line within the first 30 seconds in all subjects. The slope of the line was the unidirectional influx rate of 99mTc (k(u)). Thyroid perfusion index (TPI) was calculated to standardize where the ratio of ROI(thyroid) size to ROI(aorta) size was set as 10. K(u) and TPI showed good correlation with 99mTc thyroid uptake. Hyperthyroid patients showed high values of k(u) and TPI. Considering that these indices were determined at the first pass of 99mTc, this method may be helpful especially in the evaluation of thyroid perfusion.     

Increased myocardial uptake of iodine-123 metaiodobenzylguanidine on delayed images, compared with early images, in patients with multiple system atrophy

We present 2 interesting cases of multiple system atrophy in which increased myocardial iodine-123 metaiodobenzylguanidine uptake was observed on delayed images (3 hours after injection) compared with early images (15 minutes after injection). These findings have not been previously described. The duration of symptoms was less than 1 year in both these patients. The mechanism responsible for these findings is not clearly understood, but could be related to the pathophysiological changes in the early stage of multiple systemic atrophy.     

A case of severe bradycardia and AV block during administration of propofol

A 69-yr-old man underwent emergency laparotomy. He was in endotoxic shock. Preoperative evaluation including a full blood count, chest X-ray and ECG were normal. Body temperature was 37.4 degrees C. Preoperative arterial pressure was 140/80 mmHg and heart rate 65 bpm. Anesthesia was induced with ketamine 100 mg, propofol 20 mg, fentanyl 50 micrograms and vecuronium 4 mg and maintained with propofol 4 mg.kg-1.hr-1 and fentanyl. Soon after opening the abdominal peritoneum, severe bradycardia (< 20 bpm) occurred, but it was effectively treated by ephedrine 16 mg. After that, surgery was performed uneventfully. In the intensive care unit (ICU), the patient developed four episodes of severe atrioventricular (AV) block after stimulation of the trachea by suction drainage under sedation with propofol, although there was no AV block during sedation with ketamine and propofol. After stopping propofol, the AV block was no longer observed. He was discharged from the ICU on the 12th postoperative day. Postoperative Holter ECG and echocardiography showed no abnormalities. It is likely that stimulation of the trachea triggered vagovagal reflex and propofol prolonged AV conduction, causing the AV block.     

Mechanism of QT interval prolongation induced by sevoflurane in guinea-pig ventricular myocyte

BACKGROUND: Sevoflurane causes QT interval prolongation clinically, but its precise mechanism has not been clarified. We examined the mechanism of QT interval prolongation induced by sevoflurane by means of electrophysiological technique in guinea-pig ventricular myocyte. METHODS: Electrocardiogram was recorded in guinea-pig and effect of sevoflurane (1, 2, 4%) was examined. Action potential (AP), delayed rectified potassium current (IKr), and L-type calcium channel current (ICa) were monitored as whole-cell current and by voltage clamp techniques in guinea-pig single ventricular myocytes. Sevoflurane was applied by bubbling into the bathing solution. RESULTS: Sevoflurane (1, 2, 4%) increased QTc value. Sevoflurane prolonged the duration of AP at 2%, but shortened it at 6%. IKr was reduced to 35% of control in the presence of 2% sevoflurane, but a higher concentration (6%) did not show further inhibition. ICa was reduced only to 87% of control in the presence of 2% sevoflurane and the reduction was dose-dependent (4, 6%). CONCLUSIONS: Sevoflurane 2% inhibited IKr, but it showed only slight inhibition on ICa. Because the duration of AP is regulated by ICa (plateau phase) and IKr (repolarization), greater inhibition of IKr than ICa could result in prolongation of AP. It is suggested that this mechanism may play a role in QT interval prolongation under sevoflurane anesthesia.     

Nonoperative assessment of nodal status for locally advanced cervical squamous cell carcinoma treated by radiotherapy with regard to patterns of treatment failure

PURPOSE: Lymph node metastasis is a major prognostic factor in the treatment of cervical cancer, but its nonsurgical assessment is not necessarily accurate, particularly in small nodes. We evaluated whether node-negative status could be accurately assessed using a low cutoff measure. METHODS AND MATERIALS: The subjects were 84 patients with Stage IIB-IVA cervical squamous cell carcinoma treated by definitive radiotherapy. Nodal status was assessed by CT as negative (<5 mm), possibly positive (5-10 mm), or probably positive (>10 mm). Cause-specific survival and the disease-free rate, including the pelvic recurrence-free and distant metastasis-free rates, were estimated. RESULTS: The cause-specific survival, disease-free rate, and pelvic recurrence-free rate at 5 years were significantly higher for the 32 patients with node-negative disease (83.5%, 86.1%, and 86.1%) and the 17 patients with possibly node-positive disease (59.2%, 93.8%, and 93.8%) than for the 35 patients with probably node-positive disease (32.6%, 22.0%, and 46.8%), respectively. No significant difference was found between negative and possibly node-positive status. In contrast, the distant metastasis-free rate differed significantly among node-negative (96.4%), possibly node-positive (59.3%), and probably node-positive (35.1%) status. CONCLUSION: Node-negative status assessed using a strict cutoff measure may be useful as a strong predictor of cervical cancer being confined to the pelvis.     

Assessment of urinary cotinine as a marker of nicotine absorption from tobacco leaves: a study on tobacco farmers in Malaysia

To assess dermal absorption of nicotine from tobacco leaves in relation to Green Tobacco Sickness (GTS), urinary cotinine concentrations were measured in 80 male tobacco-growing farmers and in 40 healthy males (controls) who did not handle wet tobacco leaves in Kelantan, Malaysia. Among non-smokers, urinary cotinine levels in farmers were significantly higher than those of controls; farmers with urinary cotinine of 50 ng/ml/m2 or above showed eye symptoms more frequently than those below this level (p<0.05). Farmers who did not wear protective equipment had subjective symptoms more frequently than those who used the equipment (p<0.05); some of these symptoms were seen more frequently in organophosphate (Tamaron) users than in non-users. As tobacco farmers evidence a risk of nicotine poisoning from tobacco leaves, assessment including GTS together with effects of pesticides will be necessary.     

Suppression of dextran sodium sulfate-induced colitis in mice by zerumbone, a subtropical ginger sesquiterpene, and nimesulide: separately and in combination

Ulcerative colitis (UC) and Crohn's disease are inflammatory disorders of unknown cause and difficult to treat, though some synthetic chemicals, including ligands for peroxisome proliferator-activated receptors (PPARs), are anticipated to be useful drugs. In contrast, few food phytochemicals have been reported to suppress colitis in animal models. The present study was undertaken to explore the suppressive efficacy of zerumbone (ZER), a sesquiterpenoid present in the rhizome of Zingiber zerumbet Smith that is used as a condiment in Southeast Asian countries and known to be a potent suppressant of cyclooxygenase (COX)-2 and inducible nitric oxide synthase expression in cell culture systems. Acute colitis was induced by exposing female ICR mice to 5% DSS in drinking water for 1 week. One week prior to DSS administration, the experimental mice were fed ZER alone, nimesulide (NIM, a selective COX-2 inhibitor) alone, or both in combination (1000 ppm each) for a total of 2 weeks. Inflammatory biomarkers, i.e. interleukin (IL)-1alpha and IL-1beta, tumor necrosis factor (TNF)-alpha, and prostaglandin (PG)E(2) and PGF(2alpha) in colonic mucosa were quantified by an enzyme-linked immunosorbent assay in conjunction with histological alterations. Oral feeding of ZER significantly lowered the levels of IL-1beta [inhibitory rate (IR)=34%], TNF-alpha (IR=29%), and PGE(2) (IR=73%) and suppressed DSS-induced colitis, whereas NIM suppressed the histological changes induced by DSS without affecting inflammatory biomarkers. However, their treatment in combination was most effective for suppressing these biomarkers. Our results suggest that ZER is a novel food factor for mitigating experimental UC and that use of a combination of agents, with different modes of actions, may be an effective anti-inflammatory strategy.