Chih-Hsuan Yen

A single minute lesion around the ventral respiratory group in medulla produces fatal apnea in cats

In 35 adult cats anesthetized with intraperitoneal chloralose and urethane, the ventrolateral medulla was explored by microinjection of kainic acid (KA, 24 mM, 200 nl) with metal electrode-tubing or glass micropipette to determine regions which elicit persistent apnea. Persistent apnea is defined as: (1) In spontaneously breathing cats, termination of respiration over 3 min with a decrease of the mean systemic arterial pressure (MSAP) to 25 mm Hg. (2) In animals under artificial ventilation and paralyzed by gallamine, cessation of bilateral phrenic nerve (PNA) activities over 25 min. The apnea producing area was located dorsal to the rostral pole of the lateral reticular nucleus, ventromedial to the ambiguous nucleus and immediately caudal to the retrofacial nucleus. Functionally, this region includes the rostral part of the ventral respiratory group (rVRG) encompassing the pre-BOtzinger area. We define this region as the VRG apnea producing area (VRG-Apa). Fatal apneusis was observed under following conditions: (1) Persistent apnea was produced after a single KA microinjection in one side of the VRG-Apa (5 animals). Microinjection of sodium glutamate (0.25 M, 70-200 nl) in the same area produced only brief apnea, while microinjection of kynurenic acid (0.1 M, 200 nl) showed little effect on the respiration but slightly increased the SAP. (2) Positioning an electrode nearby but not in the VRG-Apa with or without KA injection did not produce apnea. But when a second electrode insertion to the opposite VRG-Apa immediately produced persistent apnea even without KA injection (6 animals). (3) Midsagittal division of the medulla 0-5 mm rostral to the obex produced persistent silence of PNA on both sides in artificial ventilated animals (7 animals), while similar division 0-5 mm caudal to the obex (4 animals) produced a brief but reversible quiescence of PNA. In conclusion, findings of the present study support the existence of a restricted region of VRG-Apa. VRG-Apa on both sides are closely connected, and integrity of both VRG-Apa is essential for normal respiration.

Differential actions of the medial region of caudal medulla on autonomic nerve activities

1. The inhibitory effects produced by activation of the medial region of caudal medulla on activities of the left and right cardiac sympathetic, vagus and greater splanchnic nerves were studied in chloralose‐urethane anaesthetized cats.

The relationship among atrium electromechanical interval, insulin resistance, and metabolic syndrome.

BACKGROUND Metabolic syndrome (MS) is an important risk factor of atrial fibrillation. However, an understanding of the adverse effects of MS on left atrial (LA) functional assessment in terms of electromechanical interval, a convenient parameter that can reflect the process of LA remodelling, has been lacking. The goal of this study was to investigate the association between electromechanical interval and MS. METHODS In all, 337 patients (91 with MS) with mean age of 51.9 ± 9.0 years were enrolled. Metabolic syndrome was defined by National Cholesterol Education Program-Adult Treatment Panel III score. Insulin resistance was assessed by the homeostasis model assessment-insulin resistance method. The electromechanical interval, defined as the time from initiation of P wave deflection to peak of mitral inflow Doppler A wave (PA-PDI), was measured. RESULTS Patients with MS had significantly longer PA-PDI intervals compared with those of patients without MS (131.0 ± 12.4 milliseconds vs. 123.2 ± 14.0 milliseconds, P < 0.001). Longer PA-PDI intervals were observed in subjects with higher metabolic scores (P < 0.05). In patients with small LA size, PA-PDI intervals, but not LA dimensions, were significantly different between groups with and without MS (P < 0.05). Additionally, PA-PDI interval was positively correlated with insulin resistance (r = 0.267, P < 0.001). CONCLUSIONS PA-PDI intervals were longer in patients with MS compared with those of patients without MS and tracked with insulin resistance. PA-PDI may be a useful clinical parameter to represent the degree of atrial remodelling in subjects with metabolic derangements.

The association between atrium electromechanical interval and pericardial fat.

Objectives Pericardial fat (PCF) may induce local inflammation and subsequent structural remodeling of the left atrium (LA). However, the adverse effects of PCF on LA are difficult to be evaluated and quantified. The atrial electromechanical interval determined by transthoracic echocardiogram was shown to be a convenient parameter which can reflect the process of LA remodeling. The goal of the present study was to investigate the association between the electromechanical interval and PCF. Methods and Results A total of 337 patients with mean age of 51.9±9.0 years were enrolled. The electromechanical interval (PA-PDI) defined as the time interval from the initiation of the P wave deflection to the peak of the mitral inflow A wave on the pulse wave Doppler imaging was measured for every patient. The amount of PCF was determined by multi-detector computed tomography. The PA-PDI interval was significantly correlated with the amount of PCF (r = 0.641, p value <0.001). Graded prolongation of PA-PDI interval was observed across 3 groups of patients divided according to the tertile values of PCF. The AUC for the PA-PDI interval in predicting an increased amount of PCF (third tertile) was 0.796. At a cutoff value of 130 ms identified by the ROC curve, the sensitivity and specificity of PA-PDI interval in identifying patients with a highest tertile of PCF were 63.4% and 85.3%, respectively. Conclusions The PA-PDI intervals were longer in patients with an increased amount of PCF. It may be a useful parameter to represent the degree of PCF-related atrial remodeling.

Cardiac mechanics and ventricular twist by three-dimensional strain analysis in relation to B-type natriuretic peptide as a clinical prognosticator for heart failure patients.

Background Three dimensional (3D) echocardiography-derived measurements of myocardial deformation and twist have recently advanced as novel clinical tools. However, with the exception of left ventricular ejection fraction and mass quantifications in hypertension and heart failure populations, the prognostic value of such imaging techniques remains largely unexplored. Methods We studied 200 subjects (mean age: 60.2±16 years, 54% female, female n = 107) with known hypertension (n = 51), diastolic heart failure (n = 61), or systolic heart failure (n = 30), recruited from heart failure outpatient clinics. Fifty-eight healthy volunteers were used as a control group. All participants underwent 3D-based myocardial deformation and twist analysis (Artida, Toshiba Medical Systems, Tokyo, Japan). We further investigated associations between these measures and brain natriuretic peptide levels and clinical outcomes. Results The global 3D strain measurements of the healthy, hypertension, diastolic heart failure, and systolic heart failure groups were 28.03%, 24.43%, 19.70%, and 11.95%, respectively (all p<0.001). Global twist measurements were estimated to be 9.49°, 9.77°, 8.32°, and 4.56°, respectively. We observed significant differences regarding 3D-derived longitudinal, radial, and global 3D strains between the different disease categories (p<0.05), even when age, gender, BMI and heart rate were matched. In addition, 3D-derived longitudinal, circumferential, and 3D strains were all highly correlated with brain natriuretic peptide levels (p<0.001). At a mean 567.7 days follow-up (25th–75th IQR: 197–909 days), poorer 3D-derived longitudinal, radial, and global 3D strain measurements remained independently associated with a higher risk of cardiovascular related death or hospitalization due to heart failure, after adjusting for age, gender, and left ventricular ejection fraction (all p<0.05). Conclusions 3D-based strain analysis may be a feasible and useful diagnostic tool for discriminating the extent of myocardial dysfunction. Furthermore, it is able to provide a prognostic value beyond traditional echocardiographic parameters in terms of ejection fraction.

Effects of carbenoxolone on flow-mediated vasodilatation in healthy adults

Gap junctions play a key role in maintaining the functional integrity of the vascular wall. Using carbenoxolone (CBX) as a gap junction blocker, we aimed to assess the contribution of gap junctions in the vascular wall to flow-mediated vasodilatation (FMD) in healthy adults. Percentage FMD (%FMD) and circulating vasoactive molecules/activity, including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), aldosterone, cortisol, plasma renin activity (PRA), and endothelin (ET-1), were measured in 25 healthy volunteers (mean age: 30.1 ± 5.4 yr; 14 males) before and after oral administration of CBX (100 mg). %FMD decreased after ingestion of CBX (9.71 ± 3.1 vs. 3.40 ± 2.0%; P < 0.0001). The levels of ANP, BNP, cortisol, and ET-1 remained stationary, while both PRA and aldosterone decreased (P < 0.005) after CBX ingestion. Blood pressure and heart rate were minimally changed by CBX. Inhibition of gap junctional communication by CBX impairs FMD in healthy persons, suggesting that physiologically, vascular gap junctions participate in the maintenance of FMD. CBX does not induce the release of vasoconstricting molecules or enhance vasoconstriction, suggesting that inhibition of gap junctional communication by CBX underlies the impairment of FMD. Therefore, administering CBX in FMD examination can be a way to follow the effect of gap junctions on endothelial function, but further work remains to verify the specificity of CBX effect.

A meta-analysis comparing SPECT with PET for the assessment of myocardial viability in patients with coronary artery disease.

ObjectiveThe aim of this meta-analysis was to examine the diagnostic accuracy of single-photon emission computed tomography (SPECT) for the assessment of myocardial viability in patients with coronary artery disease as compared with PET. Materials and methodsThe literature was searched using the following keywords: single-photon emission computed tomography, positron emission tomography, perfusion, viability, myocardial infarction. Studies involving patients with coronary artery disease, left ventricular dysfunction, or a history of myocardial infarction and that compared SPECT and PET for the assessment of myocardial viability were included in the analysis. ResultsEight studies including 310 patients were included in the meta-analysis. The total number of myocardial segments analyzed was 3580. The sensitivity and specificity of SPECT for the eight studies ranged from 59 to 95% and from 79 to 100%, respectively. The pooled sensitivity of SPECT was 82% [95% confidence interval (CI): 81–84%]. The pooled specificity of SPECT was 88% (95% CI: 86–90%). For all studies, the pooled diagnostic odds ratio was 62.60 (95% CI: 19.29–203.15) and the area under the receiver-operating characteristic curve was 0.945, indicating that SPECT could accurately assess myocardial viability. ConclusionThe meta-analysis indicated that SPECT can accurately assess myocardial viability, as compared with PET, and supports the use of SPECT for the assessment of myocardial viability in patients with coronary artery disease.

PATTERN AND IMPACT OF ALTERED REGIONAL MYOCARDIAL EXCURSION ON GLOBAL VENTRICULAR PERFORMANCE AFTER FIRST-TIME ACUTE ANTERIOR WALL MYOCARDIAL INFARCTION BY REAL-TIME THREE-DIMENSIONAL ECHOCARDIOGRAPHY

SUMMARY Background The regional wall motion score index obtained by two-dimensional echocardiography in myocardial infarction (MI) has a significant impact on left ventricular (LV) global contractility and is of extraordinary prognostic value, whereas data regarding real-time three-dimensional echocardiography (RT-3DE) are lacking. We sought to clarify the relationship between RT-3DE and LV contractility in patients after MI. Methods RT-3DE was performed in 50 patients with anterior wall acute myocardial infarction and 30 normal controls. Global (16 segments) and regional ring-based LV systolic excursions were analyzed offline using the commercially available software Q-Lab version 5.0. The correlations between the LV global and regional systolic excursions and the global LV contractile performance were examined in the MI patients, and further compared with the control group. Results The global and regional (basal and middle ring-based) LV systolic excursions were lower in the MI patients (age, 61.8 ± 13.1 years) than in the normal controls (age, 40.0 ± 15.4 years). Global excursion showed inverse linear relationships with LV end-systolic volume ( r =-0.26, p r =-0.22, p p = 0.08) and stroke volume ( p = 0.49). Conclusion Regional wall motion abnormalities quantified by RT-3DE are clinically convenient and feasible in both MI patients and the normal population. This rapid and objective quantification may also help discriminate abnormal from normal regional and global functions after infarction and, therefore, has the potential to be an attractive solution for clinical diagnosis.

The Relationship among Carotid Artery Remodeling, Cardiac Geometry, and Serum N-Terminal Pro-B-Type Natriuretic Peptide Level in Asymptomatic Asians: Sex- Differences and Longitudinal GEE Study

Background Carotid artery remodeling is known to be associated with a variety of cardiovascular diseases. However, there is limited information regarding gender differences in carotid remodeling. We sought to investigate the associations among blood pressure (BP), carotid artery remodeling and cardiac geometries, and further explore gender differences. Materials and Methods In a large cohort of asymptomatic adults undergoing routine health screening with repeated observations, we related measures of carotid artery diameter (CCAD) to various BP components, cardiac geometries and blood N-terminal pro-brain natriuretic peptide (NT-proBNP) level, both from baseline cross-sectional and longitudinal dataset using generalized estimating equations (GEE). Results A total of 2,914 person-visits (baseline: n=998, mean age: 47 ± 8.9 years, 34% female) were studied (median: 6 ± 1.73 years follow up). We observed that CCAD was larger in men (p<0.01) and positively related to baseline age or all blood pressure components (including systolic BP [SBP], diastolic BP [DBP] and pulse pressure [PP], all p<0.01) even after accounting for clinical covariates, which did not change significantly at follow up (repeat-visit longitudinal GEE models). At baseline, per each increased unit of CCAD was associated with elevated LV mass index (β-coef: 6.72, with odds ratio [OR]: 1.47, 95% CI: 1.06 to 2.07 for ventricular hypertrophy; AUROC: 0.65, CCAD cut-off: 7.25mm) and NT-proBNP (β-coef: 5.35, OR: 4.22, 95% CI: 1.42 to 12.6 for >=300pg/mL; AUROC: 0.79, CCAD cut-off: 7.95mm, all p<0.05), which remained significant in multi-variate and longitudinal models. There was a prominent sex interaction (p for interaction with age and systolic BP: 0.004 and 0.028 respectively), where the longitudinal associations of age and systolic BP with increasing CCAD as more pronounced in women than men. Conclusion These data demonstrated that carotid artery remodeling may parallel subclinical biomarker of cardiac dysfunction, and further showed greater effects of aging and higher blood pressure on such remodeling process in women than men. Further study is warranted to understand how this predisposition of elderly hypertensive women to vascular remodeling may play a role in clinical settings.

Severe Pulmonary Embolism in a Young Man Post Knee Arthroscopic Anterior Cruciate Ligament Repair: A Case Report and Literature Review

Thromboprophylaxis of post knee arthroscopy is a matter of debate. Herein, we report the case of a young man who developed a sub-massive pulmonary embolism following knee arthroscopic anterior cruciate ligament repair, with an initial presentation of syncope. Right sided electrocardiography revealed ST-segment elevation and mild elevation of troponin I. Emergent cardiac catheterization reveal a myocardial bridge at the left anterior descending artery, however no occlusion or thrombus was found. Echocardiography showed a D shaped left ventricle in the apical four chamber view. Computed tomography pulmonary angiography confirmed a pulmonary embolism at bilateral distal pulmonary arteries with involvement of the distal branches. We further discuss the need of thromboprophylaxis after knee arthroscopy. (J Intern Med Taiwan 2012; 23: 106-113)