Cardiotoxicity Potential of Loxosceles intermedia Venom in Cavia porcelus

Loxosceles Sphingomyelinase Induces Complement-Dependent Dermonecrosis, Neutrophil Infiltration, and Endogenous Gelatinase Expression

Secondary Hemophagocytic Lymphohistiocytosis (HLH) From a Brown Recluse Spider Bite

Sphingomyelinases D (SMases D) from Loxosceles spider venom are the principal toxins responsible for the manifestation of dermonecrosis, intravascular hemolysis, and acute renal failure, which can result in death. These enzymes catalyze the hydrolysis of sphingomyelin, resulting in the formation of ceramide 1-phosphate and choline or the hydrolysis of lysophosphatidyl choline, generating the lipid mediator lysophosphatidic acid. This report represents the first crystal structure of a member of the sphingomyelinase D family from Loxosceles laeta (SMase I), which has been determined at 1.75-angstrom resolution using the "quick cryo-soaking" technique and phases obtained from a single iodine derivative and data collected from a conventional rotating anode x-ray source. SMase I folds as an (alpha/beta)8 barrel, the interfacial and catalytic sites encompass hydrophobic loops and a negatively charged surface. Substrate binding and/or the transition state are stabilized by a Mg2+ ion, which is coordinated by Glu32, Asp34, Asp91, and solvent molecules. In the proposed acid base catalytic mechanism, His12 and His47 play key roles and are supported by a network of hydrogen bonds between Asp34, Asp52, Trp230, Asp233, and Asn252.

An 80-year-old man with syncope was admitted for evaluation. His clinical examination revealed nothing remarkable. He had no history of heart disease, his blood pressure and electrolyte levels were normal, and he was taking no medications known to cause bradyarrhythmia. Overnight telemetry revealed the electrocardiogram displayed below (Fig. 1).The rhythm strip suggests which diagnosis?D) Junctional escape and intermittent capture beatsThe telemetry strip displayed junctional rhythm, sinus capture after every second junctional rhythm, and right bundle branch block (RBBB) of the sinus-captured beat (Fig. 2). This rare phenomenon, wherein a sinus-captured beat occurs after 2 junctional escape beats, is termed escape-reentry-capture trigeminy.1In isorhythmic atrioventricular (AV) dissociation (Answer A), the atria and ventricles beat at the same rate but are dissociated from each other; here, however, the junctional beat with retrograde conduction to the atria rules out dissociation between competing rhythms. The lack of clear P waves preceding the QRS complexes and the absence of progressive PR prolongation makes Mobitz type I AV block (Answer B) unlikely. Premature ventricular contractions in trigeminy (Answer C) are unlikely because the wide complexes with RBBB morphology are preceded by a P wave, and the QRS pattern simulates a “typical” RBBB. The 2 junctional beats followed by P-wave capture makes premature atrial complexes in trigeminy (Answer E) unlikely.Escape-reentry-capture occurs in the presence of sinus nodal dysfunction (sick sinus syndrome) when the sinus impulse rate is slower than the junctional escape rate. The inverted P wave in Figure 2 (arrows) suggests that the first junctional beat was conducted retrograde to the atria, that the next junctional beat was not, and that the subsequent sinus beat was conducted with an RBBB. This aberrancy may be explained by the “long-short” sequence that prolongs the effective refractory period of the right bundle. Consequently, the sinus rate was apparently slow enough to be captured in a trigeminal pattern. Note also that the junctional rhythm did not affect the sinus rate. The patient was given a permanent pacemaker. This case illustrates the escape-reentry-capture phenomenon in a trigeminal pattern caused by sinus nodal dysfunction.Conflict of Interest Disclosure: NoneFunding/Support: None

Pearls About Loxoscelism

In four patients with WPW syndrome atrial and ventricular premature beats were induced and the changes in form of the ventricular and atrial complexes were studied. Results indicate that, depending upon the timing of the premature atrial beat and the state of refractoriness of the His and Kent bundles, excitation of the ventricles occurs predominantly through the atrioventricular nodal system, predominantly through the Kent bundle or exclusively through one or both conduction systems. With short delays conduction through the Kent bundle may be blocked and only normal excitation of the ventricles occurs. In one patient with a history of attacks of tachycardia these normal QRS complexes were followed by retrograde activation of the atria by the Kent bundle, and attacks of supraventricular tachycardia of shorter or larger duration occurred. They stopped spontaneously, sometimes by delay or block, either of retrograde Kent conduction or of antegrade A-V nodal conduction, making it possible for the sinus node to capture the ventricles. They also could be terminated by induced atrial premature beats. In two patients tachycardias could be induced by appropriately timed ventricular premature beats during regular driving of the right ventricle. In one of these patients a circus movement, involving the Kent bundle, is probably present. By appropriate stimulation of the atria or ventricles during an attack of supraventricular tachycardia in this patient, one cycle length could be shortened without changing those of the following beats. These results suggest that a circus movement involving the atria, the normal atrioventricular conduction system and the Kent bundle is present. In the other patient, not fulfilling the WPW criteria, ventricular or atrial premature beats did not interfere with the basic rhythm of the tachycardia. Two hypotheses for this tachycardia are given: nodal tachycardia caused by rapid firing of the A-V node or a nodal tachycardia caused by a reciprocal mechanism in the A-V junction. The attacks could be blocked too by appropriately timed atrial and ventricular premature beats. No ventricular type of tachycardia could be demonstrated.

Two Successive Necrotic Lesions Secondary to Presumed Loxosceles Envenomation

Background Symptomatic bradycardia usually has a single mechanism and treatment modality. Identifying the culprit mechanism can be challenging, especially when faced with concurrent pathologies. We present a case of severe symptomatic bradycardia where appropriate management of one mechanism unmasked a second mechanism, with a need for pacemaker placement. Case Presentation A 56-year-old patient presented with beta blocker overdose and severe bradycardia. The initial ECG showed sinus bradycardia with a sinus cycle length of 2060ms and 2:1 AV conduction, with each conducted P wave preceded by a long-coupled junctional escape beat. Atropine resulted in shortening of the junctional escape interval but had no effect on the sinus rate. There was now 1:1 AV conduction, with each P wave being preceded by a faster junctional escape beat. Glucagon resulted in acceleration of the sinus rate to a cycle length of ~820ms (73 bpm) with return of 1:1 AV conduction, a PR interval of 200ms, and no junctional beats. Conducted beats showed a right bundle branch block and left axis deviation. The dependence of AV conduction on a preceding QRS complex within a certain window of time highly suggested infranodal conduction disease manifesting as phase 4 AV block. While normal sinus rates and 1:1 AV conduction were restored with glucagon, the presence of infranodal disease warranted dual chamber pacemaker implantation. In follow-up, with atrial pacing support, there was < 1% ventricular pacing. Discussion Two causes of bradycardia were simultaneously present - sinus bradycardia due to beta blocker overdose, and 2nd degree AV block due to His-Purkinje disease. Phase 4 AV block is a mechanism of paroxysmal AV block (PAVB) in patients with diseased His-Purkinje system. Spontaneous depolarization occurs in diseased fibers during prolonged periods of ventricular pause, such as with slowing of the sinus rate. The sodium channels are blocked during phase 4 of the action potential and therefore the conduction system is incapable of depolarizing due to low resting membrane potentials. In this case, AV 1:1 conduction can only be restored with a premature ventricular contraction. This is an overall under-recognized entity and should be managed with pacemaker implantation.

Hives and Fever in a 13-year-old Boy.

The aim is to assess the relationship between systolic, diastolic, and pulse blood pressure (SBP, DBP, PBP) during ventricular extrasystoles (VE) and the individual characteristics of ectopic beats.Methods. The primary method of investigation was BP measurement for each heartbeat. Inclusion criteria were the presence of ≥10000 monomorphic VE per day. A total of 53 patients were included, either without structural heart changes or with minimal structural alterations. The mean of systolic, diastolic, and pulse BP (SBP, DBP, and PBP) during VE (SBP VE, DBP VE, PBP VE) and during post-extrasystolic sinus contraction (post VE SBP, post VE DBP, post VE PBP) were calculated for each patient as fractions of 1.0.Results. The QRS complex width in VE originating from the right ventricular outflow tract is greater than from the left ventricular outflow tract; fragmentation of the QRS complex is more commonly observed in these VE. Significant correlations were observed between SBP VE and mean coupling interval (CI), PBP VE and CI, and SBP VE and PBP VE, though not between DBP VE and CI. DBP VE was significantly associated with VE count and daily VE percentage, while PBP VE was associated with left ventricular ejection fraction. It has been shown that post-VE SBP and post VE DBP are lower, while post VE PBP is higher compared to the corresponding parameters of sinus beats preceding the VE. Significant relationships were found between post VE SBP and post VE PBP, the duration of the post-extrasystolic pause, and the presence of paired VE; between post VE DBP and post VE PBP, DBP VE, CI VE, the presence of non-sustained ventricular tachycardia, and daily VE percentage; between post VE PBP and DBP VE, the presence of non-sustained ventricular tachycardia, daily VE percentage, and post-extrasystolic pause duration. Post VE PBP was equally determined by values of post VE SBP and DBP.Conclusion. With the shortening of the VE coupling interval, its SBP decreases, while DBP increases slightly, which may determine its hemodynamic significance. In post-extrasystolic sinus beats, both SBP and DBP decrease.

Dual intraventricular response after cardiac resynchronization

Bites of Loxosceles spiders can lead to a set of clinical manifestations called loxoscelism, and are considered a public health problem in many regions. The signs and symptoms of loxoscelism are divided into cutaneous and systemic forms. The former is more frequent and includes signs of envenoming at the bite site or neighboring regions. Systemic loxoscelism, although much less frequent, is associated with complications, and can even lead to death. It may include intravascular hemolysis, acute renal failure, and thrombocytopenia. Loxosceles venoms are enriched with phospholipases D (PLDs), which are a family of isoforms found at intra-species and inter-species levels. Under experimental conditions, these enzymes reproduce the main clinical signs of loxoscelism, including an exacerbated inflammatory response at the bite site and dermonecrosis, as well as thrombocytopenia, intravascular hemolysis, and acute renal failure. The role of PLDs in cutaneous loxoscelism was described over forty years ago, when studies identified and purified toxins featured as sphingomyelinase D. More recently, the production of recombinant PLDs and discoveries about their structure and mechanism has enabled a deeper characterization of these enzymes. In this review, we describe these biochemical and functional features of Loxosceles PLDs that determine their involvement in systemic loxoscelism.

Systemic loxoscelism is a rare complication after Loxosceles reclusa (brown recluse spider) envenomation. Loxosceles venom contains pro-inflammatory proteins, which have been shown to be elevated in patients with hemophagocytic lymph histiocytosis. We present a case of a 10-year-old male that developed presumed systemic loxoscelism, secondary hemophagocytic lymphohistiocytosis with hepatic dysfunction and renal failure. He was treated with dexamethasone and made a full recovery.

Cardiac Arrhythmias in COVID-19 Infection.

Objectives Describe the development of warm autoimmune hemolytic anemia warm (AIHA) secondary to a brown recluse spider (Loxosceles reclusa) bite is known as systemic loxoscelism; and review epidemiology, clinical manifestations, diagnostic work-up, pathophysiology, and treatment options associated with warm AIHA secondary to systemic loxoscelism. Methods Cases series of two cases of warm AIHA due to systemic loxoscelism and a review of the current literature: epidemiology, clinical manifestations, diagnostic work-up, pathophysiology, and treatment options associated with warm AIHA secondary to systemic loxoscelism. Results Presented here are two cases of warm AIHA due to systemic loxoscelism. Each patient was generally healthy appearing and presented with symptomatic anemia in the setting of brown recluse spider bites. Both patients were eventually found to have warm AIHA. Upon recognition of the diagnosis, the patients were started on corticosteroids and aggressive intravenous fluid hydration. In addition, they received transfusions of packed red blood cells. Their clinical courses improved, and they recovered to eventually be discharged home. Conclusion Envenomation by a brown recluse spider, Loxosceles reclusa, can result in systemic loxoscelism which can cause warm AIHA. The diagnosis of warm AIHA is confirmed by the direct antiglobulin/Coomb's test. Warm AIHA can be a life-threatening disease process. Hemodynamic support with intravenous fluids and RBC transfusion is the initial step in the management of these patients. Corticosteroids are the mainstay of current management. Second line treatments include rituximab. Rarely patients require splenectomy for refractory disease. Corticosteroids should be tapered over a three-month period.