Reduced Plasma NT-proBNP Levels Months after Myocardial Infarction Postconditioned with Lactate-Enriched Blood.

BACKGROUND: We recently reported a new approach, namely postconditioning with lactate-enriched blood (PCLeB), for cardioprotection in patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: We examined the effects of PCLeB on plasma NT-proBNP levels months after myocardial infarction (MI). METHODS: The study included consecutive patients (n = 31) undergoing percutaneous coronary intervention (PCI) for anterior STEMI within 12 h of symptom onset in our hospital between March 2014 and August 2018. We retrospectively compared plasma NT-proBNP levels several months after MI in these patients with those in historical control patients (n = 32). The control patients included consecutive patients who underwent successful PCI without PCLeB for anterior STEMI within 12 h of symptom onset in our hospital between March 2009 and February 2014. We compared the highest plasma NT-proBNP values 6-10 months after MI in the postconditioned patients with the lowest plasma NT-proBNP values 6-10 months after MI in the control patients. In the PCLeB protocol, the duration of each brief reperfusion was increased stepwise from 10 to 60 s. Lactated Ringer's solution (30 mL) was injected directly in the culprit coronary artery at the end of each brief reperfusion. Each ischemic episode lasted 60 s. RESULTS: Plasma NT-proBNP levels in the postconditioned patients months after MI (211 ± 207 pg/mL) were significantly lower than those in the control patients (516 ± 598 pg/mL; p < 0.0001). CONCLUSION: PCLeB was associated with reduced plasma NT-proBNP levels months after MI.

A second-look endoscopy may not reduce the bleeding after endoscopic submucosal dissection for gastric epithelial neoplasm.

BACKGROUND: Gastric endoscopic submucosal dissection (ESD) has gradually come to be recommended as the optimal treatment for early gastric cancer; however, one of the primary issues is postoperative bleeding. Although second-look endoscopy is conventionally performed to reduce the risk of postoperative bleeding, its benefit has not yet been clearly elucidated. The objective of this study was to elucidate the benefit of second-look endoscopy. METHODS: A total of 459 lesions in patients were underwent gastric ESD from May 2004 to April 2013 at our hospital were included in the analysis. The patients were divided into those who had bleeding within 24 hours after ESD (immediate bleeding) and those in whom bleeding occurred 24 hours or more after the procedure (delayed bleeding); the underlying disease, age, lesion site, diameter of the resected specimen, and lesion diameter were analyzed to identify the risk factors for postoperative bleeding after ESD. RESULTS: Post-ESD immediate or delayed bleeding occurred in 23 of the 459 cases (5.0%). Second-look endoscopy was performed in 210 of 447 cases (47.0%) excluding 12 cases with immediate bleeding; in the remaining 237 of the 447 cases (53.0%), it was not performed. Post-ESD delayed bleeding occurred in 6 of the 210 cases (2.9%) and 5 of the 237 cases (2.1%), with no statistically significant difference between the two groups. Overall, the following factors were identified as the risk factors for postoperative bleeding: young age (P = 0.005), lesions in the L segment (P = 0.042), and large size of the resected specimen (P = 0.005). The risk factors identified in the immediate bleeding group were lesions in the L segment (P = 0.032), large size of the resected specimen (P < 0.001), and large tumor size (P = 0.011), and those in the delayed bleeding group were young age (P = 0.013) and concomitant renal disease (P = 0.011). CONCLUSIONS: The results of this study suggest that second-look endoscopy after gastric ESD may not be useful for preventing postoperative bleeding.

The Null technique as a novel, potential first-line method of device delivery for complicated lesions during percutaneous coronary intervention.

Aim: During percutaneous coronary intervention (PCI), complicated lesions in the target coronary artery often hinder device delivery. Fluid lubricants have commonly been used to reduce friction between adjacent solid materials in manufacturing, thus achieving smoother action. This ex vivo experimental study examined whether a contrast medium could function as a fluid lubricant during PCI. Methods and results: We used two different coronary artery lesion models with distinct complexities made from silicon. Each model was fit into the ex vivo PCI-simulation system. This ex vivo laboratory equipment consisted of ordinary PCI instruments and an aorta model from the Valsalva sinus to the descending aorta. A Wolverine™ cutting balloon catheter was advanced through each lesion model via a guide catheter set into the system. The maximum force required to push the catheter through the lesion models was measured while the vessel system was filled with either normal saline or contrast medium. The maximum force required was significantly lower with the contrast medium (1.38 ± 0.21 N in the normal-saline condition vs. 0.92 ± 0.05 N in the contrast-medium condition in the lesion model A, p < 0.001; 1.30 ± 0.07 N in the normal-saline condition vs. 1.14 ± 0.04 N in the contrast-medium condition in the lesion model B, p < 0.001). Conclusions: The contrast medium for vessel system filling reduced the force required to push the devices through the lesion models. This contrast medium represents a potential candidate for a liquid lubricant to facilitate device delivery for complicated coronary lesions.

The usefulness of measuring liver stiffness by transient elastography for assessing hepatic fibrosis in patients with various chronic liver diseases.

BACKGROUND/AIMS: The degree of hepatic fibrosis is an important factor for prognosis and management of patients with chronic liver disease; however, liver biopsy is an invasive method of measuring fibrosis. Here, we investigated the diagnostic utility of liver stiffness, as measured by transient elastography in assessing hepatic fibrosis of viral chronic liver disease and nonalcoholic fatty liver disease (NAFLD). METHODOLOGY: Four hundred and nine eligible patients underwent transient elastography to measure liver stiffness. Liver biopsy for histopathological assessment of fibrosis (F0-F4) was performed in 71 of these patients. Serum levels of hyaluronic acid were determined in 110 patients. We assessed liver stiffness in several chronic liver diseases and compared correlations among liver stiffness, hepatic fibrosis stage and serum hyaluronic acid levels. RESULTS: A steady stepwise increase in liver stiffness was observed with progressing severity of hepatic fibrosis (p<0.0001) in 71 patients who underwent liver biopsy. In 32 chronic viral hepatitis patients, measuring liver stiffness was useful for differentiating between F1, or F2, or F3 and F4, while in 32 NAFLD liver stiffness can differentiate between F0 and F1, F2, or F3, F1 and F3 or F4 and F2 and F4. There was no significant correlation between liver fibrotic stages and serum hyaluronic levels. CONCLUSIONS: The present data advocates measuring liver stiffness for assessing hepatic fibrosis is more sensitive in NAFLD than viral chronic diseases, and liver stiffness is useful compared to serum hyaluronic acid level in estimating hepatic fibrosis.

[Prophylaxis and treatment of NSAID-related peptic ulceration: present status and prospects].

Non-steroidal anti-inflammatory drugs (NSAIDs) including low dose aspirin have been widely prescribed to elderly patients for treatment of OA and RA as well as for primary and secondary prevention of atherosclerotic thrombotic events. Nonetheless, NSAIDs' effectiveness in the treatment and prophylaxis of such diseases may be limited by the risk of upper gastrointestinal (GI) complications such as ulceration, hemorrhage and perforation. NSAID administration is associated with several-fold increase in the upper GI bleeding in the Japanese general population. Such GI risk is known to increase in patients with a prior history of peptic ulcer disease, advanced age, and concomitant use of corticosteroids, clopidogrel, or anticoagulants with NSAIDs or aspirin. Mechanisms of NSAID-induced GI injury are believed to be through local effects within the GI mucosa that cause topical injury and through systemic inhibition of cyclo-oxygenase (CO) resulting in depletion of mucosal protective prostaglandins. Herein, we focus on the strategy to manage NSAID- or aspirin-induced peptic ulcerations and their complications, based on the scientific evidence.

Effect of vitamin K2 on the development of hepatocellular carcinoma in type C cirrhosis.

BACKGROUND/AIMS: Hepatocellular carcinoma occurs frequently in cirrhosis related to hepatitis C virus (type C cirrhosis), and preventative treatment with interferon is costly and likely to cause adverse reactions. Menatetrenone, a vitamin K2 preparation, has recently been reported to inhibit the posttreatment relapse of hepatocellular carcinoma. We therefore examined whether menatetrenone could prevent the development of hepatocellular carcinoma in patients with type C cirrhosis. METHODOLOGY: This prospective, randomized trial recruited patients with type C cirrhosis, platelet count of 10 x 10(4) microl or less, and no history of hepatocellular carcinoma. Patients were assigned to a menatetrenone group (n = 22, 4 5mg of menatetrenone daily, orally) or a control group (n = 18). Follow-up with image diagnosis was performed every 3-6 months. RESULTS: No adverse events of menatetrenone treatment were observed. Hepatocellular carcinoma occurred in 2 of 22 patients in the menatetrenone group (9.1%) and 5 of 18 patients in the control group (27.8%); however, this difference did not reach statistical significance. CONCLUSIONS: The present findings suggest that menatetrenone has some inhibitory effect on development of hepatocellular carcinoma in patients with type C cirrhosis. Consequently, to further validate its benefits, we believe that menatetrenone should be actively administered to patients with intractable (interferon-resistant) cirrhosis.

[A case of acute pancreatitis with systemic lupus erythematosus].

A 16-year-old girl had been given a diagnosis of systemic lupus erythematosus (SLE) at age 4, and a diagnosis of nephrotic syndrome caused by lupus nephritis at age 9. Medical treatment began with steroids from age 4. She developed acute pancreatitis in May 2007. Abdominal computed tomography showed cystic lesions in the abdominal cavity, and surgical drainage was performed for intracystic bleeding, infection and alimentary canal perforation.

Left Ventricular Diastolic Dysfunction Is Associated With the Prevalence of Paroxysmal Atrial Fibrillation Determined on the Latest Echocardiographic Criteria.

Background: The relationship between left ventricular diastolic dysfunction (LVDD) and paroxysmal atrial fibrillation (PAF) remains unclear because of a lack of standard measures to evaluate LVDD. Accordingly, we examined the association between the prevalence of PAF and each LVDD grade determined according to the latest American Society of Echocardiography guidelines. Methods and Results: In all, 2,063 patients without persistent AF who underwent echocardiography at Saitama Municipal Hospital from July 2016 to June 2017 were included in the study. Patients were divided into LVDD 6 categories: No-LVDD (n=1,107), Borderline (n=392), Grade 1 (n=204), Indeterminate (n=62), Grade 2 (n=254), and Grade 3 (n=44). PAF was documented in 111 (10.0%), 81 (20.7%), 28 (13.7%), 6 (9.7%), 52 (20.5%), and 24 (54.5%) patients in the No-LVDD, Borderline, Grade 1, Indeterminate, Grade 2, and Grade 3 categories, respectively. PAF prevalence was higher in patients with Grade 3 LVDD across the whole study population. Subgroup analyses showed that the prevalence of PAF increased with increased LVDD grade in patients with reduced left ventricular ejection fraction. This relationship was significant in multivariate analysis including various patient characteristics. Conclusions: LVDD severity determined on the basis of the latest echocardiographic criteria was associated with the prevalence of PAF. The present findings shed light on the development of new therapeutic markers for PAF.

Soluble elastin decreases in the progress of atheroma formation in human aorta.

BACKGROUND: The serum levels of soluble elastin increase in patients with aortic dissection, but its distribution and characteristics are unclear. METHODS AND RESULTS: The 173 aortic specimens were categorized into 4 groups under microscopy (non-atherosclerotic aorta, n=13; fiber-rich plaque, n=77; lipid-rich plaque, n=66; ruptured plaque, n=17). Soluble elastin was abundant within the intima of both the non-atherosclerotic aorta and fiber-rich plaque, rather than in the media, and was decreased within the intima of lipid-rich and ruptured plaques. Soluble elastin levels decreased with progress of atherosclerosis (6.0 +/-0.3 microg/mg protein in non-atherosclerotic aorta; 5.8 +/-0.2 microg/mg protein in fiber-rich plaque; 4.9 +/-0.2 microg/mg protein in lipid-rich plaque; 2.8 +/-0.4 microg/mg protein in ruptured plaque, P<0.05). As well, both matrix metalloprotease-9 activity and elastin mRNA expression showed inverse distribution against soluble elastin (r=0.437, P<0.0001; r=0.186, P<0.05, respectively). Multivariable analysis revealed a decrease in the level of soluble elastin in ruptured plaque (2.8 +/-0.4 microg/mg protein in ruptured plaque, n=18; 5.5 +/-0.2 microg/mg protein in non-ruptured plaque, n=155, P<0.01). Furthermore, western blot showed soluble elastin consists of heterogeneous molecular pattern proteins. CONCLUSIONS: Both the synthesis and degradation of elastin may be enhanced in active atherosclerotic lesions.

Postconditioning with Lactate-enriched Blood for Cardioprotection in ST-segment Elevation Myocardial Infarction.

The beneficial effects of reperfusion therapy for ST-segment elevation myocardial infarction (STEMI) is attenuated by reperfusion injury. No approach has been proven successful in preventing this injury in the clinical setting to date. Meanwhile, a novel approach for cardioprotection in patients with STEMI, i.e., postconditioning with lactate-enriched blood (PCLeB), has recently been reported. PCLeB is a modification of the original protocol of postconditioning, aimed at increasing the delay in the recovery from tissue acidosis produced during ischemia. This was sought to achieve controlled reperfusion with tissue oxygenation and minimal lactate washout. In this modified postconditioning protocol, the duration of each brief reperfusion is gradually increased in a stepwise manner from 10 to 60 s. Each brief ischemic period lasts for 60 s. At the end of each brief reperfusion, injection of lactated Ringer's solution (20-30 mL) is performed directly into the culprit coronary artery immediately before the balloon inflation and the balloon is quickly inflated at the lesion site, so that the lactate is trapped inside the ischemic myocardium during each brief repetitive ischemic period. After seven cycles of balloon inflation and deflation, full reperfusion is performed. Stenting is performed thereafter, and the percutaneous coronary intervention is completed. Excellent in-hospital and 6 month outcomes in a limited number of patients with STEMI treated using PCLeB have already been reported. This method article provides a detailed description of each step of the PCLeB procedures.

Muscle squeezing immediately after coronary reperfusion therapy using postconditioning with lactate-enriched blood.

BACKGROUND: We recently reported a new approach for cardioprotection, postconditioning with lactate-enriched blood (PCLeB), and a patient with ST-segment elevation myocardial infarction (STEMI), in whom muscle squeezing of the culprit coronary artery was observed immediately after reperfusion with PCLeB. In this study, we examined the prevalence of muscle squeezing immediately after reperfusion in patients with anterior STEMI treated using PCLeB. METHODS AND RESULTS: PCLeB is a modified postconditioning protocol that comprises intermittent reperfusion and timely coronary injections of lactated Ringer's solution. We treated 30 consecutive patients with anterior STEMI using PCLeB. Among the 30 patients, 4 patients exhibited muscle squeezing of the left anterior descending artery (LAD) immediately after reperfusion. We performed follow-up coronary angiography in 23 patients and found another patient who exhibited muscle squeezing of the LAD. Thus, of 30 patients, 5 were confirmed to have myocardial bridging and 4 exhibited muscle squeezing immediately after reperfusion with PCLeB. No patient died or experienced re-hospitalization for heart failure or recurrent ischemic events at 6 months except for one patient with malignancy. CONCLUSION: Muscle squeezing immediately after reperfusion therapy is not a rare phenomenon in patients with anterior STEMI treated using PCLeB.

Effect of a single 20-mg tablet of Atorvastatin on brachial artery blood flow in normolipidemic male smokers versus nonsmokers.

This study evaluated the acute effect of statin administration in smokers. We conducted a prospective study to determine the acute effect (24 hours) of single-dose atorvastatin (20 mg) on brachial artery endothelial function using vascular ultrasonography (flow-mediated vasodilation [FMD]) and blood flow in normolipidemic smokers (10 men, 42 +/- 9 years of age) and healthy nonsmokers (10 men, 39 +/- 7 years of age). Atorvastatin increased brachial artery percent FMD in smokers from 4.1 +/- 1.4% to 5.7 +/- 1.7% (p <0.0005), whereas we found no significant change after atorvastatin in nonsmokers (from 5.8 +/- 1.2% to 5.9 +/- 1.2%, p = NS). The velocity time integral also showed a significant increase as percent FMD in smokers 24 hours after taking atorvastatin (from 19 +/- 11 to 25 +/- 12 cm, p <0.05), whereas no significant change occurred in nonsmokers (from 18 +/- 9 to 19 +/- 10 cm, p = NS). Baseline brachial artery diameter significantly dilated in smokers after taking atorvastatin compared with before taking atorvastatin (from 4.23 +/- 0.5 to 4.35 +/- 0.4 mm, p <0.05), but did not change in nonsmokers (from 4.26 +/- 0.6 to 4.31 +/- 0.6 mm, p = NS). In conclusion, single-dose atorvastatin restores endothelial function and increases brachial artery blood flow in normolipidemic men smokers within 24 hours. These findings suggest early benefits of statin therapy on endothelial function in smokers.

Systemic peripheral vascular resistance as a determinant of functional cardiac reserve in response to exercise in patients with heart disease.

Resting cardiac function is a poor indicator of functional cardiac reserve that is invoked during exercise. The objective of this study was to investigate the relationship between functional cardiac reserve and systemic vascular resistance (SVR) using an ambulatory radionuclide monitoring system (the Vest system) in patients with heart disease. The study population consisted of 29 patients (all male [mean +/- SD age, 63 +/- 10 years]), 23 with coronary artery disease, 3 with dilated cardiomyopathy, and 3 with hypertensive heart disease. All patients underwent cardiopulmonary stress testing using a ramped treadmill protocol and the Vest system. The anaerobic threshold (AT) was autodetermined using the V-slope method. Systemic vascular resistance was calculated using the mean blood pressure and cardiac output as determined using the Vest system parameters. All patients exercised beyond the AT until exhaustion. Resting left ventricular ejection fraction, peak ejection ratio, and peak filling ratio increased with the AT (P < .01 for all). Resting SVR decreased with the AT (P < .01). The percentage changes from rest to the AT in SVR correlated with those from rest to the AT in ejection fraction, peak ejection ratio, and peak filling ratio (r = -0.735, r = -0.510, and r = -0.697, respectively; P < .01). These findings indicate that SVR as recorded using the Vest system is a good determinant of functional cardiac reserve in patients with heart disease. Therefore, cardiopulmonary function testing combined with the Vest system is a good modality for the evaluation of functional cardiac reserve.

Impact of postconditioning with lactate-enriched blood on in-hospital outcomes of patients with ST-segment elevation myocardial infarction.

BACKGROUND: Reperfusion injury offsets the beneficial effects of reperfusion therapy for ST-segment elevation myocardial infarction (STEMI). In our previous reports, postconditioning with lactate-enriched blood (PCLeB) induced excellent microcirculation recovery and less inflammation in STEMI patients. This study aimed to determine the in-hospital outcomes of STEMI patients treated using PCLeB. METHODS: Fifty-five consecutive STEMI patients were treated using PCLeB (Age 66.6±13.8years, 76.4% men) within 12h of symptom onset. In our modified postconditioning protocol, the duration of each brief reperfusion was prolonged from 10s to 60s in a stepwise manner. Lactated Ringer's solution (20-30mL) was injected directly into the culprit coronary artery at the end of each brief reperfusion and the balloon was quickly inflated at the lesion site, whereby lactate could be trapped inside the ischemic myocardium. Each brief ischemic period lasted 60s. After 7cycles of balloon inflation and deflation, full reperfusion was performed. Thereafter, stenting was performed and percutaneous coronary intervention (PCI) was completed. RESULTS: The mean corrected thrombolysis in myocardial infarction frame count was 20.1±10.1 after PCI completion. The mean peak serum creatine kinase and creatine kinase-MB levels were 2751±2227IU/L and 276±181IU/L respectively. None of the study patients died during their hospital stay or required continuation of oral diuretic or inotropic therapy for heart failure on discharge. CONCLUSIONS: PCLeB led to zero in-hospital mortality and no overt heart failure on discharge in 55 consecutive STEMI patients undergoing reperfusion therapy.

Provocation of microvessel spasm by low-dose acetylcholine in patients with suspected coronary artery disease--two case reports.

Endothelial dysfunction plays an important role in the pathogenesis of cardiac syndrome X, and intracoronary low-dose acetylcholine infusion is a widely used diagnostic modality for studying the coronary artery endothelial function. The authors herein report 2 cases of cardiac syndrome X with coronary artery endothelial dysfunction and microvessel spasm. The findings of non-invasive testing were positive for ischemia. Coronary angiograms appeared entirely normal in both cases. However, the intracoronary infusion of low-dose (1.5-15 microg/minute) acetylcholine demonstrated an impairment of the coronary blood flow response and consequently provoked an ST-segment elevation in an electrocardiogram. The coronary angiograms showed no spasm in the epicardial arteries. These patients are thus suggested to have cardiac syndrome X with microvessel spasms associated with coronary artery endothelial dysfunction.

Effects of chronic sleep deprivation on autonomic activity by examining heart rate variability, plasma catecholamine, and intracellular magnesium levels.

Chronic sleep deprivation is associated with cardiovascular events. In addition, autonomic activity determined from the levels of the heart rate variability (HRV), plasma catecholamine, and intracellular magnesium (Mg) are important in the pathophysiology of cardiovascular events. This study therefore aimed to determine the effects of chronic sleep deprivation on autonomic activity by examining the HRV, plasma catecholamine, and intracellular magnesium levels. Thirty (30) healthy male college students ranging in age from 20 to 24 years of age (average 22 +/- 1 years; mean +/- SD) with no coronary risk factors such as hypertension, diabetes mellitus, hyperlipidemia or a family history of premature coronary artery disease (CAD) were included in the study. Over a 4-week period, the volunteers' plasma levels of epinephrine, norepinephrine, and erythrocyte-Mg were measured. The study was made during the 4 weeks before and immediately after college finals exams. HRV, obtained from 24-hour ambulatory ECG monitoring, included time and frequency domain indices. The HRV indices and erythrocyte-Mg decreased while norepinephrine increased during chronic sleep deprivation. It is concluded that chronic sleep deprivation causes an autonomic imbalance and decreases intracellular Mg, which could be associated with chronic sleep deprivation-induced cardiovascular events.

Assessment of autonomic activity during daily life of patients with head-up tilt-induced prolonged asystole.

Autonomic activity is important in the pathophysiology of neurally mediated syncope (NMS) patients diagnosed by the head-up tilt (HUT) test, and prolonged systole induced by HUT is associated with a malignant vasovagal syndrome. This study investigated whether or not daily autonomic activity evaluated by heart rate variability (HRV) assessed through 24-hour ambulatory ECG monitoring was augumented in HUT-induced asystole (AS; > 30 s) and whether or not HRV differed between NMS patients with and without AS. Ambulatory ECG monitoring was performed in 176 patients with suspected NMS and in 62 age-matched healthy control subjects (C group, age: 36 +/- 13 yr), with HRV time and frequency domain indices measured within 48 hours of HUT. Six patients displayed prolonged AS (PAS group, age: 33 +/- 12 yr), and 109 patients had positive HUT (P group, age: 29 +/- 17 yr), while 61 patients had negative HUT (N group, age: 40 +/- 18 yr). Several HRV indices in the P group were higher than those in the N and C groups. However, HRV indices did not differ between the P group and the PAS group. It is concluded that impairment of autonomic activity specifically related to orthostatic stress could be important in the pathophysiology of HUT-induced prolonged asystole, while impairment of autonomic activity in daily life is not as important in NMS patients with HUT-induced prolonged asystole.

Day-to-day variability of the long-term fractal component of heart rate variability (beta) and the effect of an antianginal agent in patients with silent myocardial ischemia.

The deterioration of the long-term fractal component of heart rate variability (beta) is reported in patients with organic heart disease. To examine the day-to-day variability of beta and to study the effects of nipradilol (NIP), an antianginal agent, on beta in patients with coronary artery disease (CAD), we performed 24-hour ambulatory ECG (AECG) in 24 patients with silent myocardial ischemia (SMI) and obtained the conventional frequency domain heart rate variability (HRV) indices and beta using the MemCalc system. Patients were divided into two groups: group I consisted of 10 patients (64 +/- 5 years of age) for the assessment of the day-to-day variability of beta; group II comprised 14 patients (60 +/- 6 years of age) for evaluation of the effect of NIP (3 mg b.i.d). In group I, AECG was repeated twice a week, while AECG was recorded before NIP treatment (placebo) and on the last day of the 4-week NIP treatment in group II. In group I, there was significant correlation between the values of beta on day 1 and day 2 (r = 0.79, p < 0.05), the difference being 0.09 +/- 0.15 (coefficient of variance: 6.8%). Bland and Altman's analysis indicated that the results were easily reproducible, making this approach feasible for clinical use. In group II, NIP significantly decreased the values of beta by 10.6% (from -1.23 +/- 0.09 to -1.18 +/- 0.07; p < 0.05). NIP also significantly increased the conventional HRV indices. The degree of decrement of beta by NIP was larger than that of the day-to-day variability. In conclusion, a day-to-day variability exists in beta in patients with SMI, but its value is relatively small. A daily dose of 6 mg NIP ameliorates beta and overcomes this variability.

Effect of chronic stress and sleep deprivation on both flow-mediated dilation in the brachial artery and the intracellular magnesium level in humans.

BACKGROUND: Chronic mental and physical stress has been suggested to be a trigger for cardiovascular events. In addition, a reduction in levels of intracellular magnesium has been reported to cause vasoconstriction while enhancing platelet-dependent thrombosis. HYPOTHESIS: The purpose of this study was to investigate whether chronic stress affects endothelial function and intracellular magnesium levels in humans. METHODS: Flow-mediated dilation (endothelium-dependent vasodilation) and sublingual nitroglycerin-induced dilation (0.3 mg, endothelium-independent vasodilation) were measured in the brachial artery in 30 healthy male college students, aged 22 +/- 1 years, using high-resolution ultrasound both before and immediately after a 4-week final term examination period. Erythrocyte magnesium concentration was measured simultaneously. All students had chronic sleep deprivation for 4 weeks, during which sleep lasted < 80% of that on ordinary days; in addition, the students were under great stress to pass the examination. This condition was considered to be chronic stress. RESULTS: Chronic stress decreased flow-mediated dilation and erythrocyte magnesium concentration (from 7.4 +/- 3.0 to 3.7 +/- 2.3%, p < 0.05; from 5.7 +/- 0.4 to 5.5 +/- 0.4 mg/ml, p < 0.05, respectively). The change in flow-mediated dilation correlated significantly with that of the erythrocyte magnesium concentration (r = 0.43, p < 0.05), but not with nitroglycerin-induced dilation. CONCLUSIONS: Chronic stress was found to attenuate endothelial function, which may also be associated with a reduction in the intracellular magnesium level in humans.