Association between holiday and weekend admissions and mortality outcomes among patients with acute myocardial infarction receiving percutaneous coronary intervention in Taiwan.

There is a lack of studies that concurrently differentiate the effect of the holiday season from the weekend effect on mortality risk in patients with acute myocardial infarction (AMI). We evaluated the mortality risk among patients admitted with AMI who underwent percutaneous coronary intervention, using data from the Taiwan National Health Insurance Research Database. Adult AMI patients admitted during January and February between 2013 and 2020 were enrolled and classified into the holiday season (using the Chinese New Year holiday seasons as an indicator) (n = 1729), weekend (n = 4725), and weekday (n = 14,583) groups according to the first day of admission. A multivariable logistic regression model was used to assess the risk. With the weekday group or the weekend group as the reference, the holiday season group did not have increased risks of in-hospital mortality (adjusted odds ratio [aOR] 1.15; 95% confidence intervals [CI] 0.93-1.42 or aOR 1.23; 95% CI 0.96-1.56) and 7-day mortality (aOR 1.20; 95% CI 0.90-1.58 or aOR 1.24; 95% CI 0.90-1.70). Stratified and subgroup analyses showed similar trends. We conclude that holiday season-initiated admissions were not associated with higher mortality risks in AMI admission cases than weekday or weekend admissions.

Novel Application of Multiscale Cross-Approximate Entropy for Assessing Early Changes in the Complexity between Systolic Blood Pressure and ECG R-R Intervals in Diabetic Rats.

Cardiac autonomic neuropathy (CAN) is a common complication of diabetes mellitus, and can be assessed using heart rate variability (HRV) and the correlations between systolic blood pressure (SBP) and ECG R-R intervals (RRIs), namely baroreflex sensitivity (BRS). In this study, we propose a novel parameter for the nonlinear association between SBP and RRIs based on multiscale cross-approximate entropy (MS-CXApEn). Sixteen male adult Wistar Kyoto rats were equally divided into two groups: streptozotocin-induced diabetes and age-matched controls. RRIs and SBP were acquired in control rats and the diabetic rats at the onset of hyperglycemia and insulin-treated euglycemia to determine HRV by the ratio of low-frequency to high-frequency power (LF/HF) and Poincaré plot as SSR (SD1/SD2), BRS, and MS-CXApEn. SSR and BRS were not significantly different among the three groups. The LF/HF was significantly higher in the hyperglycemic diabetics than those in the controls and euglycemic diabetic rats. MS-CXApEn was higher in the diabetic hyperglycemic rats than the control rats from scales 2 to 10, and approached the values of controls in diabetic euglycemic rats at scales 9 and 10. Conclusions: We propose MS-CXApEn as a novel parameter to quantify the dynamic nonlinear interactions between SBP and RRIs that reveals more apparent changes in early diabetic rats. Furthermore, changes in this parameter were related to correction of hyperglycemia and could be useful for detecting and assessing CAN in early diabetes.

A Dietitian-Led Vegan Program May Improve GlycA, and Other Novel and Traditional Cardiometabolic Risk Factors in Patients With Dyslipidemia: A Pilot Study.

Background: Systematic inflammation and lipid profiles are two major therapeutic targets for cardiovascular diseases. The effect of a nutritionally balanced vegan diet on systematic inflammation and lipoprotein subclass awaits further examination. Objective: To investigate the change in novel and traditional cardiometabolic risk factors before and after a dietitian-led vegan program, and to test the bioavailability of vitamin B12 in Taiwanese purple laver as part of a vegan diet. Design: A one-arm pilot intervention study. Participants/Setting: Nine patients with dyslipidemia participated in this 12-week vegan program. Main Outcome Measures: Nuclear Magnetic Resonance (NMR) detected GlycA signals (systematic inflammation) and lipoprotein subclass (atherogenicity); trimethylamine N-oxide (TMAO); and other cardiometabolic risk factors. Statistical Analyses Performed: Wilcoxon signed-rank test. Results: In this 12-week vegan intervention emphasizing whole foods, systematic inflammation improved as indicated by a reduction in GlycA (median: -23 µmol/L, p = 0.01). LDL-c (low-density lipoprotein cholesterol) (median -24 mg/dl, p = 0.04) and LDL-p (low-density lipoprotein particles) (median -75 nmol/L, p = 0.02) both decreased significantly. VLDL (very-low-density lipoprotein) and chylomicron particles showed a decreasing trend (-23.6 nmol/L, p = 0.05). Without caloric restriction, body mass index (BMI) (-0.7 kg/m2, p = 0.03), waist circumferences (-2.0 cm, p < 0.001), HbA1c (-0.2%, p = 0.02), and (HOMA-IR) homeostatic model assessment for insulin resistance (-0.7, p = 0.04) have all improved. The change in the TMAO and vitamin B12 status as measured by holo-transcobalamin appeared to depend on baseline diets, TMAO, and vitamin B12 status. Conclusions: A dietitian-led vegan program may improve systematic inflammation and other novel and traditional cardiometabolic risk factors in high-risk individuals.

Peripartum cardiomyopathy and acute heart failure associated with prolonged tocolytic therapy in pregnancy: A case report.

RATIONALE: Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. Heart failure symptoms can mimic the physiological changes of normal pregnancy, and the diagnosis is based on echocardiography. PATIENT CONCERNS: A 38-year-old multiparous woman with a history of cervical incompetence underwent cervical cerclage and received tocolysis for 100 days. DIAGNOSES: She delivered vaginally at 37 weeks of gestation but developed postpartum decompensated acute heart failure with low left ventricular ejection fraction (LVEF: 34%) and was diagnosed with PPCM. INTERVENTIONS: She received standard therapy for acute heart failure. OUTCOMES: The patient's pulmonary edema cleared, and she was fully ambulatory 6 days after admission. A follow-up echocardiogram 3 months later demonstrated recovery of LVEF to 66%. LESSONS: Prolonged tocolysis may contribute to cardiomyopathy and should be used with caution. PPCM management requires standard treatments for acute heart failure with modifications for fetal safety.

Vegetarian diet and incidence of total, ischemic, and hemorrhagic stroke in 2 cohorts in Taiwan.

OBJECTIVE: To determine how a vegetarian diet affects stroke incidence in 2 prospective cohorts and to explore whether the association is modified by dietary vitamin B12 intake. METHODS: Participants without stroke in the Tzu Chi Health Study (cohort 1, n = 5,050, recruited in 2007-2009) and the Tzu Chi Vegetarian Study (cohort 2, n = 8,302, recruited in 2005) were followed until the end of 2014. Diet was assessed through food frequency questionnaires in both cohorts at baseline. Stroke events and baseline comorbidities were identified through the National Health Insurance Research Database. A subgroup of 1,528 participants in cohort 1 were assessed for serum homocysteine, vitamin B12, and folate. Associations between vegetarian diet and stroke incidences were estimated by Cox regression with age as time scale, adjusted for sex, education, smoking, alcohol, physical activities, body mass index (only in cohort 1), hypertension, diabetes, dyslipidemia, and ischemic heart diseases. RESULTS: Vegetarians had lower serum vitamin B12 and higher folate and homocysteine than nonvegetarians. In cohort 1, 54 events occurred in 30,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of ischemic stroke (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.08-0.88). In cohort 2, 121 events occurred in 76,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of overall stroke (HR, 0.52; 95% CI, 0.33-0.82), ischemic stroke (HR, 0.41; 95% CI, 0.19-0.88), and hemorrhagic stroke (HR, 034; 95% CI, 0.12-1.00). Our explorative analysis showed that vitamin B12 intake may modify the association between vegetarian diet and overall stroke (p interaction = 0.046). CONCLUSION: Taiwanese vegetarian diet is associated with a lower risk of ischemic and hemorrhagic strokes.

Intermittent Hypoxia Induces Autophagy to Protect Cardiomyocytes From Endoplasmic Reticulum Stress and Apoptosis.

Intermittent hypoxia (IH), characterized as cyclic episodes of short-period hypoxia followed by normoxia, occurs in many physiological and pathophysiological conditions such as pregnancy, athlete, obstructive sleep apnea, and asthma. Hypoxia can induce autophagy, which is activated in response to protein aggregates, in the proteotoxic forms of cardiac diseases. Previous studies suggested that autophagy can protect cells by avoiding accumulation of misfolded proteins, which can be generated in response to ischemia/reperfusion (I/R) injury. The objective of the present study was to determine whether IH-induced autophagy can attenuate endoplasmic reticulum (ER) stress and cell death. In this study, H9c2 cell line, rat primary cultured cardiomyocytes, and C57BL/6 male mice underwent IH with an oscillating O2 concentration between 4 and 20% every 30 min for 1-4 days in an incubator. The levels of LC3, an autophagy indicator protein and CHOP and GRP78 (ER stress-related proteins) were measured by Western blotting analyses. Our data demonstrated that the autophagy-related proteins were upregulated in days 1-3, while the ER stress-related proteins were downregulated on the second day after IH. Treatment with H2O2 (100 µM) for 24 h caused ER stress and increased the level of ER stress-related proteins, and these effects were abolished by pre-treatment with IH condition. In response to the autophagy inhibitor, the level of ER stress-related proteins was upregulated again. Taken together, our data suggested that IH could increase myocardial autophagy as an adaptive response to prevent the ER stress and apoptosis.

Intermittent Hypoxia Prevents Myocardial Mitochondrial Ca2+ Overload and Cell Death during Ischemia/Reperfusion: The Role of Reactive Oxygen Species.

It has been documented that reactive oxygen species (ROS) contribute to oxidative stress, leading to diseases such as ischemic heart disease. Recently, increasing evidence has indicated that short-term intermittent hypoxia (IH), similar to ischemia preconditioning, could yield cardioprotection. However, the underlying mechanism for the IH-induced cardioprotective effect remains unclear. The aim of this study was to determine whether IH exposure can enhance antioxidant capacity, which contributes to cardioprotection against oxidative stress and ischemia/reperfusion (I/R) injury in cardiomyocytes. Primary rat neonatal cardiomyocytes were cultured in IH condition with an oscillating O2 concentration between 20% and 5% every 30 min. An MTT assay was conducted to examine the cell viability. Annexin V-FITC and SYTOX green fluorescent intensity and caspase 3 activity were detected to analyze the cell death. Fluorescent images for DCFDA, Fura-2, Rhod-2, and TMRM were acquired to analyze the ROS, cytosol Ca2+, mitochondrial Ca2+, and mitochondrial membrane potential, respectively. RT-PCR, immunocytofluorescence staining, and antioxidant activity assay were conducted to detect the expression of antioxidant enzymes. Our results show that IH induced slight increases of O2-· and protected cardiomyocytes against H2O2- and I/R-induced cell death. Moreover, H2O2-induced Ca2+ imbalance and mitochondrial membrane depolarization were attenuated by IH, which also reduced the I/R-induced Ca2+ overload. Furthermore, treatment with IH increased the expression of Cu/Zn SOD and Mn SOD, the total antioxidant capacity, and the activity of catalase. Blockade of the IH-increased ROS production abolished the protective effects of IH on the Ca2+ homeostasis and antioxidant defense capacity. Taken together, our findings suggest that IH protected the cardiomyocytes against H2O2- and I/R-induced oxidative stress and cell death through maintaining Ca2+ homeostasis as well as the mitochondrial membrane potential, and upregulation of antioxidant enzymes.

Intermittent Hypoxia Inhibits Na+-H+ Exchange-Mediated Acid Extrusion Via Intracellular Na+ Accumulation in Cardiomyocytes.

BACKGROUND/AIMS: Intermittent hypoxia (IH) has been shown to exert preconditioning-like cardioprotective effects. It also has been reported that IH preserves intracellular pH (pHi) during ischemia and protects cardiomyocytes against ischemic reperfusion injury. However, the exact mechanism is still unclear. METHODS: In this study, we used proton indicator BCECF-AM to analyze the rate of pHi recovery from acidosis in the IH model of rat neonatal cardiomyocytes. Neonatal cardiomyocytes were first treated with repetitive hypoxia-normoxia cycles for 1-4 days. Cells were then acid loaded with NH4Cl, and the rate of pHi recovery from acidosis was measured. RESULTS: We found that the pHi recovery rate from acidosis was much slower in the IH group than in the room air (RA) group. When we treated cardiomyocytes with Na+-H+ exchange (NHE) inhibitors (Amiloride and HOE642) or Na+-free Tyrode solution during the recovery, there was no difference between RA and IH groups. We also found intracellular Na+ concentration ([Na+]i) significantly increased after IH exposure for 4 days. However, the phenomenon could be abolished by pretreatment with ROS inhibitors (SOD and phenanathroline), intracellular calcium chelator or Na+-Ca2+ exchange (NCX) inhibitor. Furthermore, the pHi recovery rate from acidosis became faster in the IH group than in the RA group when inhibition of NCX activity. CONCLUSIONS: These results suggest that IH would induce the elevation of ROS production. ROS then activates Ca2+-efflux mode of NCX and results in intracellular Na+ accumulation. The rise of [Na+]i further inhibits the activity of NHE-mediated acid extrusion and retards the rate of pHi recovery from acidosis during IH.

Symmetrical peripheral gangrene in sepsis after treatment with inotropes.

Symmetrical peripheral gangrene (SPG) is characterized by sudden onset of peripheral, frequently symmetrical, gangrene in the absence of major vascular occlusive disease. We report a case of four limb SPG caused by septic shock with disseminated intravascular coagulation (DIC) that had been treated with inotropes. This case shows that SPG may be present as a complication of sepsis due to systematic derangement that affects a wide range of organ systems, including coagulation and microcirculation. Early recognition and prompt management of sepsis and optimization of the process of weaning off the inotropes at the earliest opportunity are necessary to avoid SPG.

Sudden Cardiac Death Associated with Anomalous Origin of the Left Main Coronary Artery from the Right Sinus, with an Intramural Course.

Anomalous origin of the left main coronary artery from the right sinus of Valsalva is extremely rare and can lead to sudden cardiac death. We report a case in which an 18-year-old college student collapsed immediately after a long-distance run of 10 km. After cardiopulmonary resuscitation and electrical shock for ventricular fibrillation, she experienced a return of spontaneous circulation. Cardiac catheterization and cardiac computed tomographic angiography revealed an unusually long intramural course of the left main coronary artery from the right sinus of Valsalva. The young woman underwent a successful unroofing operation for coronary artery correction. She remained asymptomatic upon exercise during 2.5 years of follow-up.

N-terminal pro-B-type natriuretic peptide is inversely associated with metabolic syndrome in hypertensive patients.

BACKGROUND: It has been shown that metabolic syndrome is associated with lower levels of plasma N-terminal pro-B-type natriuretic peptide (Nt-proBNP) in the general population. However, there is no study about the association between Nt-proBNP and metabolic syndrome in hypertensive patients. AIM: : To elucidate the relationship between Nt-proBNP and components of metabolic syndrome in hypertensive patients. METHODS: Fasting blood samples were obtained from 74 hypertensive patients in our institution. Plasma levels of Nt-proBNP and other biochemical data were measured. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation. RESULTS: Forty-four hypertensive patients met the criteria for metabolic syndrome. We found that plasma Nt-proBNP levels were lower in hypertensive patients with metabolic syndrome attributable to inverse relationships between Nt-proBNP and albumin, triglyceride, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and pancreatic ß-cell function (HOMA-ß). We further performed a multivariable linear regression analysis. The result showed that HOMA-IR is the independent predictor of plasma Nt-proBNP levels in hypertensive patients. CONCLUSIONS: Plasma Nt-proBNP levels are inversely associated with metabolic syndrome in hypertensive patients. HOMA-IR is the independent predictor of Nt-proBNP in hypertensive patients.

Clinical Characteristics and In-Hospital Prognosis of Infective Endocarditis in Two Eastern Counties of Taiwan.

BACKGROUND: Infective endocarditis (IE) is a common and potentially serious disease. Although it is an illness that affects populations around the world, narrower descriptions of this disease as it impacts specific regions are uncommon. We analyzed the clinical characteristics of IE patients from two eastern counties in Taiwan and studied the relationship between the isolated pathogens and clinical outcomes in these patients. METHODS: This is a retrospective chart review study which enrolled patients who received services between January 2007 and December 2010. Subsequent to chart review, IE was confirmed in a total of 55 patients by the modified Duke criteria. RESULTS: Of these patients, 17 (31%) had previous traumatic open skin wounds. Pre-existing cardiac abnormalities were found in 47 (85%) patients, 28 of whom had valvular abnormalities. Staphylococcus aureus was isolated from the blood as the leading pathogen in 25 (45%) patients (including 23 methicillin-sensitive and 2 methicillin-resistant). Septic emboli and shock occurred in 27 (49%) of 55 patients; surgery was performed on 11 (20%) of those patients, and 4 (36%) of them died post-operatively. The total in-hospital mortality rate was 40% (n = 22). Staphylococcus aureus infection was associated with significantly higher complication and mortality rate than non-Staphylococcus aureus infection (59% vs. 41% and 64% vs. 36%, respectively; p < 0.05). In addition, patients with complications had a very high mortality rate (81.5%). CONCLUSIONS: We found that Staphylococcus aureus was the most common pathogen of IE in Eastern Taiwan, and was associated with higher rates of morbidities and mortality. KEY WORDS: Infective endocarditis; Septic shock; Staphylococcus aureus; Systemic embolization.

Inverse association of N-terminal pro-B-type natriuretic peptide with metabolic syndrome in patients with congestive heart failure.

BACKGROUND: Metabolic syndrome has been shown to be associated with lower levels of plasma N-terminal pro-B-type natriuretic peptide (Nt-proBNP) in the general population. We sought to elucidate the relationship between Nt-proBNP and components of metabolic syndrome in patients with congestive heart failure (CHF). METHODS: Fasting blood samples were obtained from 93 patients in our institution. Plasma levels of Nt-proBNP and other biochemical data were measured. The New York Heart Association (NYHA) classification system (I-IV) was used to define the functional capacity of CHF. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation. RESULTS: Forty-nine patients (52.7%) had CHF. There was a positive correlation between plasma Nt-proBNP levels and NYHA functional capacity in CHF patients. Plasma Nt-proBNP levels increased significantly with each increasing NYHA class of the disease. The prevalence of metabolic syndrome in CHF patients was higher than that in patients without CHF. Most importantly, we found that plasma Nt-proBNP levels were lower in CHF patients with metabolic syndrome attributable to inverse relationships between plasma Nt-proBNP and body mass index (ß = -0.297), plasma triglyceride (ß = -0.286) and homeostasis model assessment of insulin resistance (HOMA-IR; ß = -0.346). Fasting glucose to insulin ratio (FGIR, an insulin sensitivity index) was positively associated with plasma Nt-proBNP levels (ß = 0.491), and was the independent predictor of plasma Nt-proBNP levels in CHF patients. CONCLUSIONS: Plasma Nt-proBNP levels are inversely associated with metabolic syndrome in CHF patients. Reduced plasma Nt-proBNP levels in CHF patients may lead to impaired lipolysis and metabolic function, and may contribute to the development of metabolic syndrome in CHF patients.

Diffuse plexus-like coronary artery-left ventricular fistulae leading to coronary steal syndrome: a pattern of anomalous coronary microvascularization.

Coronary artery fistulae that drain into the left ventricle are extremely rare, and even fewer cases of fistulae involving all three of the coronary arteries have so far been reported. We herein report a 64-year-old woman with a unique pattern of coronary artery-left ventricular fistulae that involved all three of the coronary arteries. The multiple fistulae presented in a diffuse plexus-like arrangement. The fistulae resulted in a diastolic volume overload of the left ventricle (left-to-left shunt), as well as "coronary steal" with the shunting of blood away from the myocardium since the fistulae represented the path of least resistance.

Intrathoracic ancient neurilemoma mimicking mesenchymal thoracic tumor.

Ancient neurilemoma is a rare variant of neurilemoma and can grow into a large tumor, which results in several symptoms. It is often misdiagnosed to be malignant neoplasm because of its histological features of nuclear atypia. The authors reported an 87-year-old woman presenting with progressive dyspnea and chronic cough for more than 1 year. Computed tomography of the chest showed a huge heterogeneous, paravertebral mass with focal calcification, arising from intervertebral foramen. The tumor was successfully resected by thoracotomy and pathology disclosed ancient neurilemoma.

Pleural empyema secondary to rupture of amoebic liver abscess.

Amoebiasis is a worldwide parasitic infection although it is more prevalent in the subtropical and tropical countries. Extraintestinal amoebic infections currently have been reported in increased numbers of male homosexuals and immunocompromised patients. Here, we present an interesting case of a 27-year-old homosexual man with pleural empyema secondary to rupture of amoebic liver abscess. Using chest tube and percutaneous liver abscess drainage, the patient was treated with metronidazole followed by iodoquinol. His general condition improved dramatically. After one-year of follow-up, there was no evidence of relapse on plain chest radiography and abdominal CT scan.

Molecular determinants of the anticonvulsant felbamate binding site in the N-methyl-D-aspartate receptor.

The antiepileptic effect of felbamate (FBM) is ascribable to gating modification of NMDA receptors. Using site-directed mutagenesis and electrophysiological studies, we found that single-point mutations of four pairs of homologous residues in the external vestibule of the receptor pore, namely V644(NR1)-L643(NR2B) (the two inner pairs) and T648(NR1)-T647(NR2B) (the two outer pairs), significantly decrease FBM binding. Moreover, double mutations involving either the inner or the outer pair always show cooperative (nonadditive) effects on FBM binding, whereas double mutations involving both inner and outer pairs always show additive (noncooperative) effects. Most interestingly, triple mutations of any three of the four critical residues essentially abolish the effect of FBM. These findings indicate that T648(NR1)/T647(NR2B) and V644(NR1)/L643(NR2B) act cooperatively to contribute directly to the "outer binding region" and "inner binding region" in the FBM binding site, respectively. The outer and inner binding regions, however, seem to contribute independently to FBM binding. We conclude that residues L643 and T647 in NR2B as well as homologous residues V644 and T648 in NR1 are the major, and very likely the exclusive, molecular determinants constituting the FBM binding site in the NMDA receptor.

Effects of nitric oxide donor and nitric oxide synthase inhibitor on the resistance, exchange and capacitance functions of the canine intestinal vasculature.

In the present study, we determined the vascular functions using a canine model of isolated intestinal segment perfused with constant flow. The effects of an NO donor, S-nitroso-N-acetylpenicillamine (SNAP) and an NO synthase inhibitor, N(omega)-nitro-l-arginine methyl ester (l-NAME) on the vascular factors (resistance, exchange and capacitance) were evaluated. In condition of venous pressure at 0 mmHg, we determined and calculated arterial pressure (Pa) and capillary pressure (Pc). Vascular factors including total, pre- and post-capillary resistance (R(T), Ra and Rv), vascular compliance (VC) and capillary filtration coefficient (K(fc)) were obtained. SNAP at doses 10(-6) to 10(-4) mol/l produced vasodilatory effects. It dose-dependently reduced the Pa, Pc, R(T) and Ra, as well as the Ra/Rv ratio. The Rv was slightly decreased. This agent increased the vascular capacity, VC and K(fc). NO inhibition with l-NAME (10(-6) to 10(-4) mol/l) produced the opposite effects. The vasoconstrictory effects of l-NAME increased Pa, Pc, R(T) and Ra as well as the Ra/Rv ratio. It slightly raised the Rv. l-NAME reduced the vascular capacity, VC and K(fc). The effects of l-NAME were also dose-dependent. This study has provided a detailed data of the vasodilatory and vasoconstrictory effects NO donation and inhibition on vascular factors in the intestinal vasculature.

The activation gate and gating mechanism of the NMDA receptor.

The NMDA receptor opens in response to binding of NMDA and glycine. However, it remains unclear where and how gating of the NMDA receptor pore is accomplished. We show that different point mutations between S645 and I655 (thus including the highly conserved SYTANLAAF motif) of M3c in NR2B lead to constitutively open channels. The current through these constitutively open channels are readily blocked by external Mg2+ and MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate]. Also, the open-channel blocker MK-801 can no longer be trapped in these channels when NMDA and glycine are washed off. Moreover, M3c residues at or below A651(NR2B, A7 in SYTANLAAF) react with external methanethiosulfonate (MTS) reagents approximately 500 to 1000-fold faster in the presence than in the absence of agonists NMDA and glycine. In fact, the MTS modification rate shows exactly the same NMDA concentration dependence as channel activation. In contrast, those residues external to A651 are always modified with similar kinetics whether NMDA and glycine are present or not. Interestingly, MTS modification of A651C(NR2B) holds the channel constitutively open. Mutations of A651(NR2B) into arginine, tryptophan, or phenylalanine, and similar mutations of the corresponding A652 in NR1 also lead to constitutively open channels. Double-mutant cycle analysis further shows that the effects of A652(NR1) and A651(NR2B) mutations are evidently non-additive (i.e., cooperative) if mutated into residues with large side chains or with compensatory charges [e.g., A652E(NR1)+A651R(NR2B)]. The side chain of A7 thus plays a determinant role in the intersubunit distance at this level, which is directly responsible for the activation gate and activation-deactivation gating of the NMDA receptor.

Arterial haemodynamics on ventricular hypertrophy in rats with simulated aortic stiffness.

Aortic stiffness (AS) exerts significant impact on the cardiovascular risks. We developed a new model to produce AS. The purposes were to evaluate the haemodynamic consequence and to correlate the haemodynamic parameters with the extent of ventricular hypertrophy (VH). We applied silicon gel for embedding of the abdominal and/or thoracic aorta. After 1-4 weeks of AS, the left ventricular weight (LVW), LVW to body weight (BW) ratio (LVW/BW), and the morphological changes in cardiomyotes were quantified for VH. We determined the aortic pressure (AP), stroke volume, cardiac output, total peripheral resistance (TPR), characteristic impedance (Zc), pulse wave reflection (P(b)) and pulse wave velocity (PWV). Aortic embedding (AE) increased LVW, LVW/BW, systolic and pulse pressure (PP), Zc, P(b) and PWV accompanied by decreases in diastolic pressure and arterial compliance. The magnitude of these haemodynamic and cardiac changes were in an order of combined, thoracic and abdominal AE. Correlation analysis revealed that the VH was well correlated with pulsatile haemodynamics such as Zc, PP, P(b) and PWV, while less with steady components (Mean AP and TPR). Our results indicate that pulsatile haemodynamic parameters are significantly elevated after AS. The alterations in pulsatile haemodynamics are the major causes leading to VH.