Unique Properties of Cardiac Action Potentials Recorded with Voltage-Sensitive Dyes

Unique Properties of Optical Action Potentials. Introduction: Optical mapping with voltage-sensitive dyes has made it possible to record cardiac action potentials with high spatial resolution that is unattainable by conventional techniques. Optically recorded signals possess distinct properties that differ importantly from electrograms recorded with extracellular electrodes or action potentials recorded with microelectrode techniques. Despite the growing application of optical mapping to cardiac electrophysiology, relatively little quantitative information is available regarding the characteristics of optical action potentials recorded from cardiac tissue. Methods and Results: A high-resolution optical mapping system and microelectrode techniques were used to determine the characteristics of guinea pig ventricular action potentials recorded with the voltage-sensitive dye di-4-ANEPPS. The effects of optical magnification, tissue-light interaction, sampling rate, voltage resolution, spatial resolution, and cardiac motion on action potential signal characteristics were determined. The optical action potential signal represents the relative change in transmembrance potential arising from a volume of cells, where the area of a recording site is determined by optical magnification and detector area, and the depth of recording is determined by system optics and the visible light transmission characteristics of cardiac muscle. Using photographic lenses, the depth of tissue contributing to the signal is < 250 μm. The action potential plateau and final repolarization can be accurately reconstructed from data digitized at modest sampling rates (450 to 750 Hz), since the frequency content of optical action potentials is band-limited to approximately 150 Hz. However, faster sampling rates are needed to depict the subtle details of the action potential upstroke. In addition to temporal resolution, it is essential to achieve sufficient dynamic range and voltage resolution to accurately represent the time course of membrane potential change. Voltage resolution is inversely related to the square of spatial resolution, hence, there exists an inherent trade-off between increased spatial resolution and diminished voltage resolution. Cardiac motion, which can otherwise limit spatial resolution as well as signal fidelity, can be effectively reduced using mechanical stabilization of the heart without distorting action potential characteristics. Conclusions: Optical mapping with voltage-sensitive dyes provides high-fidelity multisite action potential recording with flexible spatial resolution. When recording cardiac action potentials with voltage-sensitive dyes, the Interdependence of temporal, spatial, and voltage resolutions must be carefully considered.     

Tissue Magnesium Levels and the Arrhythmic Substrate in Humans

Magnesium and Arrhythmias. Introduction: Magnesium deficiency has been implicated in the pathogenesis of sudden death, but the investigation of arrhythmic mechanisms has been hindered by difficulties in measuring cellular tissue magnesium stores.
Methods and Results: To see if magnesium deficiency is associated with a propensity toward triggered arrhythmias, we measured tissue magnesium levels and QT interval dispersion (as an index of repolarization dispersion) in 40 patients with arrhythmic complaints. Magnesium was measured in sublingual epithelium using X-ray dispersive analysis. QT interval dispersion was assessed on 12-lead surface F-XCs in all patients, and programmed stimulation was performed in 28. The sublingual epithelial magnesium level ([Mg]_i), but the not the serum level, correlated Inversely with QT interval dispersion in 40 patients (r = 0.58, P < 0.0.5); in 12 patients undergoing repeat testing on therapy, the change in magnesium also correlated inversely with the change in QT dispersion (r = 0.61, P < 0.05). Patients with left ventricular ejection fractions > 40% had significantly higher tissue magnesium and lower QT dispersion (34.5 ± 0.5 mEq/L, 81 ± 8 msec) than those with left ventricular ejection fractious < 40% (32.7 ± 0.5 mEq/L, P < 0.01, and 114 ± 9 msec, P < 0.05). There was no difference in either [Mg]_i, or QT dispersion in the 16 patients with inducible monomorphic ventricular tachycardia versus the 12 noninducible patients.
Conclusion: Reduced tissue magnesium stores may represent a significant risk factor for arrhythmias associated with abnormal repolarization, particularly in patients with poor left ventricular systolic function, but may not represent a risk for excitable gap arrhythmias associated with a fixed anatomic substrate (e.g., monomorphic ventricular tachycardia).     

Predictors of fibrosis in Asian patients with non-alcoholic steatohepatitis

Background and Aim: Non‐alcoholic steatohepatitis (NASH) is increasingly recognized as an important cause of chronic liver disease. However, data on Asians with NASH is lacking in the literature. The aim of the present study was to describe the clinical, biochemical and histological characteristics of NASH in Asians and to determine the predictors for septal fibrosis. Method: Sixty consecutive patients aged over 18 years with elevated serum alanine transferase, sonographic evidence of steatosis, and consent for liver biopsy were included. Patients with chronic hepatitis B or C, alcoholic, autoimmune, genetic, or drug‐induced liver disease were excluded. Clinical, biochemical and histological variables were tested for association with septal liver fibrosis (F2/3). Results: Median age of the cohort was 45.5 years (range 21–75 years) and 63% were male. Ninety percent of patients were obese (body mass index [BMI]≥ 25), 70% had hypertriglyceridemia, 68% had hypercholesterolemia, 58% had metabolic syndrome, 53% had hypertension, 47% had diabetes mellitus (DM), and 18% had obstructive sleep apnea. Sixty‐eight percent had gamma‐glutamyl transferase (GGT) ≥ 2 × upper limit of normal (ULN), 55% had alanine aminotransferase (ALT) ≥ 2 × ULN, and 23% had aspartate aminotransferase (AST) ≥ 2 × ULN. Of the 40 non‐diabetic patients undergoing oral glucose tolerance testing, 45% had normal tests, 30% had impaired glucose tolerance, 23% DM, and 2% impaired fasting glucose. Eighteen patients (30%) had septal fibrosis (F2/3), but none had cirrhosis. Necroinflammatory grade ≥ 2 (odds ratio [OR] 13), AST ≥ 2 × ULN (OR 5.3) and DM (OR 5) were significantly and independently correlated with septal fibrosis. Conclusion: Septal fibrosis is common in Asians with NASH. Necroinflammatory grade ≥ 2, AST ≥ 2 × ULN and DM are independent predictors for septal fibrosis.     

Reentrant Circuits and the Effects of Heptanol in a Rabbit Model of Infarction with a Uniform Anisotropic Epicardial Border Zone

Reentry in Rabbit Ventricles. Introduction: The purpose was to study reentry in a rabbit model of infarction.
Methods and Results: A model of an infarct epicardial border zone was produced in Langendorff perfused rabbit hearts by freezing the inner two thirds of the left ventricular wall, allowing only a thin epicardial muscle layer to survive. Reentrant circuits causing stable ventricular tachycardia occurred in the surviving rim of epicardial muscle as shown by mapping impulse propagation with a 196–electrode array. The circuits were functional, and reentry did not occur around an anatomical obstacle. Slow conduction in the circuits was caused by the anisotropic properties of the epicardial muscle. Activation in the circuits was slow transverse to the long axis of the fiber bundles and rapid parallel to the long axis. Other features of the circuits, including orientation of the central functional line of block parallel to the fiber long axis, and an oval shape are also characteristic of anisotropic reentry. Since the slow conduction causing reentry is a result of poor transverse intercellular coupling, we determined whether the "uncoupler" heptanol would cause block in the circuits and terminate tachycardia. Heptanol in concentrations up to 1.2 mM slowed conduction in the transverse and longitudinal directions in the circuits and sometimes extended the central line of functional block. It did not, however, stop reentry because the reentrant impulse was still able to conduct around the ends of the block line.
Conclusion: Drugs that decrease intercellular coupling may not be effective antiarrhythmic agents when uniform anisotropy causes functional reentry.     

Hemolytic-uremic Syndrome Associated with Emphysematous Cholecystitis

A 34-year old man presented with jaundice, nausea and vomiting. He had previously been in good health but was a chronic drug abuser and regularly consumed large amounts of wine. Emphysematous cholecystitis was diagnosed by abdominal radiography. Examination of the peripheral blood smear, blood count and serum chemistries revealed a microangiopathic hemolytic anemia, thrombocytopenia and renal insufficiency.
He was treated with antibiotics and intravenous fluids and had clinical, hematologic and biochemical improvement over the course of the next four weeks. At surgery, a chronically inflamed gallbladder, containing multiple stones, was resected. There was no evidence of vasculitis.
Although emphysematous cholecystitis associated with hemolytic-uremic syndrome is most unusual, other diseases of infectious etiology have been reported in association with the hemolytic-uremic syndrome. The possible etiologic role of endotoxin is discussed, as are the importance of recognizing the hemolytic-uremic syndrome in patients with underlying or concurrent bacterial infections and the problem of management in such a case.     

Electrophysiological Evaluation of Moricizine in Patients with Sustained Ventricular Tachyarrhythmias: Low Efficacy and High Incidence of Proarrhythmia

In patients with history of sustained ventricuiar tachyarrhythmias, the efficacy and safety of moricizine have not been systematically evaluated by electrophysiological studies. We performed electrophysiological testing in these patients in the drug-free state and then after moricizine loading, and evaluated the safety profile of moricizine during in-hospital loading and follow-up. The study population comprised of 31 patients with clinically sustained ventricular tachyarrhythmia. The underlying heart disease was coronary in 25 patients, cardiomyopathy in 5 patients, and none in 1 patient. The left ventricular (LV) ejection fraction ranged from 15%-69% (mean 39 ± 15%). During the baseline drug-free electrophysiological testing, sustained ventricular tachycardia was inducibie in 27 patients, ventricuiar fibrillation in 1 patient, and reproducible, nonsustained ventricular tachycardia (15–25 sec) in 3 patients. All 31 patients received moricizine to the maximum tolerated dose (851 ± 185 mg) over a period of 2–7 days. Six patients developed ventricular proarrhythmia within the first 4 days. Proarrhythmia required multiple cardioversions in three patients, was not associated with QT prolongation, and spontaneously resolved 6–24 hours after withdrawal of moricizine. Of the remaining 25 patients, 24 underwent electrophysiological testing on moricizine and 4 patients (16%) were rendered noninducible. The VT cycle length in the other 20 patients slowed from 243 ± 30 msec to 299 ± 60 msec (P < 0.09). Four noninducibie patients, two patients with inducible but slowed VTand one patient who had refused further testing were discharged on moricizine. Among these seven patients, recurrent arrhythmic events occurred in two patients, ventricular proarrhythmia in one patient, complete AV block in one patient, and severe disabling headache in one patient. Only two patients have continued to take moricizine without side effects or recurrent arrhythmic events during a follow-up of 4 months and 9 months, respectively. Moricizine is only rarely effective for long-term treatment of patients with spontaneous sustained ventricular tachyarrhythmias, It renders ventricular tachyarrhythmias noninducible in a small minority (16%) and is associated with a high incidence (23%) of ventricular proarrhythmias.     

Pulp response to traumatic crown fractures

Amongst all dental traumas in the permanent dentition, crown fractures account for the largest majority. This review paper will discuss the different levels of fracture, from the most superficial ones only affecting the enamel to the deepest ones with pulp exposure, including crown–root fractures. It will focus on the pulp by evaluating the pulp response to trauma and to the subsequent treatment. An attempt to correlate epidemiological, experimental, histopathological, and clinical studies will be made, so that the clinician can better understand the underlying processes which evolve towards pulp healing or pulp necrosis, thus success or failure. If handled properly, prognosis of the pulp following a traumatic crown fracture is good. In the permanent dentition, success rate ranges between 72% and 100%, the highest success rate corresponding to superficial fractures and the lowest success rate to fractures with pulp exposure.     

Strategic Messaging to Promote Policies that Advance Racial Equity: What Do We Know,and What Do We Need to Learn?

Policy Points

• Many studies have explored the impact of message strategies to build support for policies that advance racial equity, but few studies examine the effects of richer stories of lived experience and detailed accounts of the ways racism is embedded in policy design and implementation.
• Longer messages framed to emphasize social and structural causes of racial inequity hold significant potential to enhance support for policies to advance racial equity.
• There is an urgent need to develop, test, and disseminate communication interventions that center perspectives from historically marginalized people and promote policy advocacy, community mobilization, and collective action to advance racial equity.