Americans shooting themselves in the foot: the epidemiology of podiatric self-inflicted gunshot wounds in the United States.

OBJECTIVE: To examine the epidemiology of Americans shooting themselves in the foot. DESIGN: Data from the Firearm Injury Surveillance Study (1993-2010) collected using the National Electronic Injury Surveillance System were examined. Non-fatal firearm-related injuries were recorded during patients' initial emergency department visits. SETTING: United States hospital emergency departments, 1993-2010. PARTICIPANTS: 69 111 individuals admitted to US emergency departments after non-fatal firearm-related incidents. MAIN OUTCOME MEASURE: Demographic and incident characteristics of patients presenting with self-inflicted gunshot wounds to the foot. RESULTS: Of the 69 111 reported firearm-related injuries, 667 (1.0%) were self-inflicted gunshot wounds to the foot. Of these, 597 of the patients (89.6%) were men and 51.7% (345) were aged between 15 and 34 years. Patients generally presented with puncture wounds (265 patients, 39.7%), foreign bodies (164 patients, 24.6%) and bruised egos. Those who shot themselves in the foot were significantly more likely than individuals with other firearm-related injuries to be male (odds ratio [OR], 1.28) and married (OR, 2.6). As the festive season approached, the number of incidents increased; November and December were peak months for shooting oneself in the foot. CONCLUSIONS: The nature of and the circumstances surrounding self-inflicted gunshot wounds to the foot were unique when compared with other firearm-related injuries. Through the large-scale examination of the characteristics of these incidents, trends in the nature of Americans shooting themselves in the foot have been elucidated. Young married men are at particular risk of shooting themselves in the foot. Particular caution must be taken during the festive season to avoid being caught under the missing toe.

Measurement and interpretation of electrocardiographic QT intervals in murine hearts.

Alterations in ECG QT intervals correlate with the risk of potentially fatal arrhythmias, for which transgenic murine hearts are becoming increasingly useful experimental models. However, QT intervals are poorly defined in murine ECGs. As a consequence, several different techniques have been used to measure murine QT intervals. The present work develops a consistent measure of the murine QT interval that correlates with changes in the duration of ventricular myocyte action potentials (APs). Volume-conducted ECGs were compared with simultaneously recorded APs, obtained using floating intracellular microelectrodes in Langendorff-perfused mouse hearts. QT intervals were measured from the onset of the QRS complex. The interval, Q-APR90, measured to the time at 90% AP recovery, was compared with two measures of the QT interval. QT1 was measured to the recovery of the ECG trace to the isoelectric baseline for entirely positive T-waves or to the trough of any negative T-wave undershoot. QT2-used extensively in previous studies-was measured to the return of any ECG trough to the isoelectric baseline. QT1, but not QT2, closely correlated with changes in Q-APR90. These findings were confirmed over a range of pacing rates, in low K(+) concentration solutions, and in Scn5a+/ΔKPQ hearts used to model human long QT syndrome. Application of this method in whole anesthetized mice similarly demonstrated a prolonged corrected QT (QTc) in Scn5a+/ΔKPQ hearts. We therefore describe a robust method for the determination of QT and QTc intervals that correlate with the duration of ventricular myocyte APs in murine hearts.

Conduction slowing contributes to spontaneous ventricular arrhythmias in intrinsically active murine RyR2-P2328S hearts.

INTRODUCTION: The familial condition catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by episodic bidirectional ventricular tachycardia (BVT), polymorphic ventricular tachycardia (PVT), and ventricular fibrillation following adrenergic challenge. It is associated with mutations involving the cardiac ryanodine receptor (RyR2). METHODS AND RESULTS: We explored for a slowing of myocardial conduction that could potentially result in a substrate for the spontaneous arrhythmogenesis that was observed following introduction of isoproterenol and caffeine in intrinsically beating murine RyR2-P2328S hearts. Such pharmacological challenge increased the number of arrhythmic episodes in electrocardiographic recordings from intact anesthetized mice, with the greatest effects in the homozygote RyR2(S/S). Arrhythmias took the form of bigeminy, BVT, monomorphic ventricular tachycardia, and PVT, as found in human CPVT. Ventricular epicardial conduction velocities (CVs) measured using multielectrode array recordings and maximum action potential upstroke rates, (dV/dt)(max), measured using intracellular microelectrodes were indistinguishable in untreated wild-type (WT) and RyR2(S/S). Pharmacological challenge of RyR2(S/S), but not WT hearts, then reduced CV and (dV/dt)(max) and also revealed a strongly arrhythmic phenotype. There was no evidence of gross structural or fibrotic changes in either RyR2(+/S) or RyR2(S/S) hearts on light microscopy. CONCLUSIONS: We associate altered ventricular myocardial CV potentially resulting in arrhythmogenic substrate with arrhythmic properties associated with genetic RyR2 alterations for the first time.

Determinants of myocardial conduction velocity: implications for arrhythmogenesis.

Slowed myocardial conduction velocity (θ) is associated with an increased risk of re-entrant excitation, predisposing to cardiac arrhythmia. θ is determined by the ion channel and physical properties of cardiac myocytes and by their interconnections. Thus, θ is closely related to the maximum rate of action potential (AP) depolarization [(dV/dt)max], as determined by the fast Na(+) current (I Na); the axial resistance (r a) to local circuit current flow between cells; their membrane capacitances (c m); and to the geometrical relationship between successive myocytes within cardiac tissue. These determinants are altered by a wide range of pathophysiological conditions. Firstly, I Na is reduced by the impaired Na(+) channel function that arises clinically during heart failure, ischemia, tachycardia, and following treatment with class I antiarrhythmic drugs. Such reductions also arise as a consequence of mutations in SCN5A such as those occurring in Lenègre disease, Brugada syndrome (BrS), sick sinus syndrome, and atrial fibrillation (AF). Secondly, r a, may be increased due to gap junction decoupling following ischemia, ventricular hypertrophy, and heart failure, or as a result of mutations in CJA5 found in idiopathic AF and atrial standstill. Finally, either r a or c m could potentially be altered by fibrotic change through the resultant decoupling of myocyte-myocyte connections and coupling of myocytes with fibroblasts. Such changes are observed in myocardial infarction and cardiomyopathy or following mutations in MHC403 and SCN5A resulting in hypertrophic cardiomyopathy (HCM) or Lenègre disease, respectively. This review defines and quantifies the determinants of θ and summarizes experimental evidence that links changes in these determinants with reduced myocardial θ and arrhythmogenesis. It thereby identifies the diverse pathophysiological conditions in which abnormal θ may contribute to arrhythmia.

Loss of Nav1.5 expression and function in murine atria containing the RyR2-P2328S gain-of-function mutation.

AIMS: Recent studies reported slowed conduction velocity (CV) in murine hearts homozygous for the gain-of-function RyR2-P2328S mutation (RyR2(S/S)) and associated this with an increased incidence of atrial and ventricular arrhythmias. The present experiments determined mechanisms contributing to the reduced atrial CV. METHODS AND RESULTS: The determinants of CV were investigated in murine RyR2(S/S) hearts and compared with those in wild-type (WT) and slow-conducting Scn5a(+/-) hearts. Picrosirius red staining demonstrated increased fibrosis only in Scn5a(+/-) hearts. Immunoblot assays showed similar expressions of Cx43 and Cx40 levels in the three genotypes. In contrast, Nav1.5 expression was reduced in both RyR2(S/S) and Scn5a(+/-) atria. These findings correlated with intracellular microelectrode and loose-patch-clamp studies. Microelectrode measurements showed reduced maximum rates of depolarization in Scn5a(+/-) and RyR2(S/S) atria compared with WT, despite similar diastolic membrane potentials. Loose-patch-clamp measurements demonstrated reduced peak Na(+) currents (INa) in the Scn5a(+/-) and RyR2(S/S) atria relative to WT, with similar normalized current-voltage relationships. In WT atria, reduction in INa could be produced by treatment with high extracellular Ca(2+), caffeine, or cyclopiazonic acid, each expected to produce an acute increase in [Ca(2+)]i. CONCLUSION: RyR2(S/S) atria show reduced levels of Nav1.5 expression and Na(+) channel function. Reduced Na(+) channel function was also observed in WT atria, following acute increases in [Ca(2+)]i. Taken together, the results suggest that raised [Ca(2+)]i produces both acute and chronic inhibition of Na(+) channel function. These findings may help explain the relationship between altered Ca(2+) homeostasis, CV, and the maintenance of common arrhythmias such as atrial fibrillation.