Sudden Death In Dogs Research Articles

Morte súbita causada por embolismo tumoral em um cão

ABSTRACT: Tumor embolization is a well-described cause of unexpected death in human oncologic patients; however, it is poorly explored in veterinary medicine. We report a case of pulmonary tumor embolization in a dog with sudden death. During necropsy, a neoplastic mass was observed replacing the left adrenal gland and forming an intravascular thrombus within the central adrenal vein. A large embolus occluded the left pulmonary artery. The adrenal mass was histologically confirmed as a pheochromocytoma, and the embolus was constituted of neoplastic cells. Multiple smaller neoplastic emboli were observed within the pulmonary artery branches. Tumor embolization should be considered as a possible cause of sudden death in dogs, particularly in oncologic patients.

Association of sotalol versus atenolol therapy with survival in dogs with severe subaortic stenosis

Introduction/objectivesDogs with severe subaortic stenosis (SAS) are at risk of dying suddenly from fatal arrhythmias. Survival is not improved when treated with pure beta-adrenergic receptor (β)-blockers; however, the effect of other antiarrhythmic drugs on survival is unknown. Sotalol is both a β-blocker and a class III antiarrhythmic drug; the combination of these differing mechanisms may provide benefit to dogs with severe SAS. The primary objective of this study was to compare survival in dogs with severe SAS that were treated with either sotalol or atenolol. The secondary objective was to evaluate the effect of pressure gradient (PG), age, breed, and aortic regurgitation on survival. AnimalsForty-three client-owned dogs. Materials and methodsRetrospective cohort study. Medical records of dogs diagnosed with severe SAS (PG ≥ 80 mmHg) between 2003 and 2020 were reviewed. ResultsNo statistical difference was identified in survival time between dogs treated with sotalol (n=14) and those treated with atenolol (n=29) when evaluating all-cause mortality (p=0.172) or cardiac-related mortality (p=0.157). Of the dogs that died suddenly, survival time was significantly shorter in dogs treated with sotalol compared to those treated with atenolol (p=0.046). Multivariable analysis showed that PG (p=0.002) and treatment with sotalol (p=0.050) negatively influenced survival in the dogs that died suddenly. ConclusionsSotalol did not have a significant effect on survival overall but may increase the risk of sudden death in dogs with severe SAS compared to atenolol.

De-risking Clinical Trials: The BIAL Phase I Trial in Foresight.

De-risking Clinical Trials: The BIAL Phase I Trial in Foresight.

Probable Sudden Unexpected Death in Dogs With Epilepsy (pSUDED).

Sudden unexpected death in human epileptic patients (SUDEP) is defined as death related to recurrent unprovoked seizures, death occurring unexpectedly, and suddenly in a patient with reasonable state of health, without an obvious medical cause of death, trauma, asphyxia, or intractable status epilepticus, and in post mortem examination no obvious reason for death can be found. “Probable SUDEP” (pSUDEP) is defined as SUDEP not confirmed pathologically. The adapted abbreviation for dogs is used in the following: “pSUDED” (probable sudden unexpected death in dogs with epilepsy). The aim of the present monocentric retrospective study using an online questionnaire was to evaluate the occurrence of pSUDED. Data of canine patients presented with seizures between 01/1998 and 05/2018 were retrospectively analyzed and classified according to their etiology (n = 1,503). Owners were contacted by telephone to participate in answering a validated questionnaire. A total of 509 owners were reached, and 373 owners completed the questionnaire. In addition to signalement (e.g., breed), special attention was paid to the frequency and presentation of seizures and seizures in the context of death. Fifty-one percent (191/373) of the dogs were dead at the endpoint of the study. A large proportion of the dogs was euthanized (149/191) because of seizure severity or health problems unrelated to seizures. Idiopathic epilepsy (IE) was diagnosed in 19/34 dogs which died unexpectedly. Of these seven animals had to be excluded for further investigation of pSUDED because of status epilepticus or aspiration pneumonia as a result of the seizures. In 12 dogs with IE the last seizure event occurred between 6 h and ~3 months before death. pSUDED was suspected in these dogs and an occurrence rate of 4.5–10% was calculated. pSUDED appears in a similar occurrence rate as human SUDEP and should be considered as a possible complication in epileptic dogs. The results of this study suggest that dogs with IE but especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. Owners of dogs with seizures should be educated about the risk of sudden death in dogs with epilepsy.

Preparation and immunological characterization of an inactivated canineClostridium perfringenstype A vaccine

Clostridium perfringens is the main cause of sudden death in dogs and currently there is no vaccine to prevent it. In this study, a canine C. perfringens type A strain was used to prepare a vaccine. C. perfringens was inactivated by formaldehyde and adjuvants were added. The safety and immunological characteristics of the inactivated C. perfringens vaccine were evaluated in mice and dogs. The results showed that the C. perfringens vaccine was safe and had immunoprotective activity. The serum antibody titre of immunized mice reached up to 6·25×104 . Both single immunization of 4ml and dual immunizations of 2ml each provided good immune protection, with five of five immunized dogs surviving. This study also studied a detoxified crude α-toxin extract vaccine. The results showed that a single immunization with 0·5ml of the detoxified crude α-toxin extract vaccine provided immune protection, with five of five immunized dogs surviving. The inactivated C. perfringens type A vaccine can be used to prevent canine C. perfringens infections. SIGNIFICANCE AND IMPACT OF THE STUDY: Clostridium perfringens is the main cause of sudden death in dogs and currently there is no vaccine to prevent it. In this study, an inactivated canine C. perfringens vaccine and a detoxified crude α-toxin vaccine were prepared. The safety and protective effects of these vaccines were evaluated using mouse and dog models. The vaccines were shown to be safe and to provide immune protection effects that can be used to prevent canine C. perfringens infection.

Time-domain signal-averaged electrocardiogram in healthy German Shepherd and Boxer dogs

Signal-averaged electrocardiogram (SAECG) identifies ventricular late potentials (LP), low-amplitude electrical signals that are markers of slow cardiac conduction in fibrous myocardium, consisting in a predictive factor for sudden death in dogs at risk of sustained ventricular tachycardia. The aim of this study was to establish reference values of SAECG for German Shepherd and Boxer dogs. SAECG was performed in 19 German Shepherd and 28 Boxer client-owned dogs, and parameters analyzed were QRSd (duration of filtered QRS), LAS<40μV (duration of low-amplitude signals in terminal portion of filtered QRS) and RMS40 (root square of mean voltage over the last 40 milliseconds of filtered QRS), with two different filters (25-250 Hz and 40-250 Hz). Statistical analyses was achieved by T Student test (p<0.05) to identify differences between the two groups and between the values obtained with the two filters. No statistical difference was found in SAECG variables between the two breeds with the two different filters (p>0.05). Achieving normal values of SAECG in German Shepherd and Boxer dogs is important to further research late potentials in animals of these breeds with hereditary ventricular tachycardia or arrhythmogenic cardiomyopathy and identification of individuals at high risk of cardiac-related sudden death.

COMPUTED TOMOGRAPHIC AND RADIOGRAPHIC CHARACTERISTICS OF AORTIC LESIONS IN 42 DOGS WITH SPIROCERCOSIS

Spirocerca lupi is a common cause of vomiting, regurgitation, and sudden death in dogs that live in tropical or subtropical regions. Sudden death due to aortic rupture may occur with no preceding clinical signs. The purpose of this prospective study was to compare radiographic and computed tomographic (CT) characteristics of aortic lesions in a cohort of 42 dogs with endoscopically confirmed spirocercosis. Dorsoventral and right lateral recumbent thoracic radiographic findings were compared with pre- and postcontrast thoracic CT findings. Aortic mineralization was detected using CT in 18/42 dogs (43%). Three dogs had faint diffuse aortic wall mineralization. Using CT as the reference standard, radiographs had a sensitivity and specificity of 6% and 96%, respectively, for detecting aortic mineralization. A total of 20 aortic aneurysms were detected using CT in 15/42 dogs (36%). Using CT as the reference standard, radiographs had a sensitivity and specificity of 86% and 56%, respectively, for detecting aortic aneurysms. Respiratory motion, aortic displacement by esophageal masses and Spirocerca nodules adjacent to the aorta mimicked aneurysm formation on radiographs. Aortic thrombi were seen in two dogs in postcontrast CT images. Findings from this study indicated that aortic mineralization and aneurysm formation are common in dogs with spirocercosis. Findings also supported the use of pre- and postcontrast CT as effective methods for detecting and characterizing these lesions.

Comparative medical features of canine and human bartonellosis

E. B. Breitschwerdt and R. G. MaggiIntracellular Pathogens Research Laboratory, Center for Comparative Medicine and TranslationalResearch, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USAINTRODUCTIONBartonella species are increasingly recognised asimportant bacterial pathogens in veterinary andhuman medicine. These organisms can be trans-mitted by an arthropod vector or alternatively byanimal scratches or bites. Among the 22 species orsubspecies known today, seven species, includingthree subspecies of Bartonella henselae, and fourgenotypes of Bartonella vinsonii subsp. berkhoffii,have been detected in or isolated from pet dogs,thereby highlighting the zoonotic potential ofthese bacteria [1–4].Bartonella vinsonii subsp. berkhoffiiSince the isolation of B. vinsonii subsp. berkhoffiifrom the blood of a dog with intermittent epi-staxis and endocarditis in 1993, this organism hasbecome an important pathogen in dogs and is anemerging pathogen in people [1,2]. Current evi-dence indicates that canids, including coyotes,dogs and grey foxes, potentially serve as reservoirhosts. In dogs, B. vinsonii subsp. berkhoffii has beenidentified as an important cause of endocarditisand has been associated with cardiac arrhyth-mias, myocarditis, granulomatous rhinitis, ante-rior uveitis and chorioretinitis. More recently, thisspecies has been detected in a dog with systemicgranulomatous disease involving the spleen,heart, lymph nodes, liver, kidney, lung, medias-tinum and salivary glands, and also in the bloodand lymph nodes of dogs with lymphoma, and inthe saliva of healthy dogs [3–5]. In addition,co-infection with two of the four previouslydescribed B. vinsonii subspecies berkhoffii geno-types was identified in the same dog.Bartonella henselaeBased upon molecular evidence, B. henselae hasbeen implicated in several pathological conditionsin dogs, including peliosis hepatis, granuloma-tous hepatitis, generalised pyogranulomatouslymphadenitis, and endocarditis. It is unclear asto how dogs become infected and whether dogsserve as accidental hosts or as chronically bacte-raemic reservoirs for B. henselae. More recently,Bartonella spp. were detected in the blood andlymph nodes of healthy golden retrievers and ingolden retrievers with lymphoma [3,4]. Molecularprevalence of Bartonella spp. infection was 18% inboth study populations.Other Bartonella speciesSimilar to people, dogs can develop endocarditisand presumably other serious disease manifesta-tions when infected with both reservoir andnon-reservoir Bartonella species. Non-reservoirBartonella species, including Bartonella clarridgeiae,BartonellawashoensisandBartonellaelizabethae,havebeen associated with endocarditis, hepatic diseaseand sudden death in dogs. More recently, Barto-nella quintana DNA has been detected in two dogswith endocarditis, and in the blood and lymphnodes of dogs with lymphoma, and in the blood,lymph nodes and saliva of healthy dogs [4,5].BARTONELLA PRE-ENRICHMENTCULTUREWhen testing cat blood samples, B. henselae andB. clarridgeae can be isolated effectively using agar

Correspondence

Correspondence

Miocardite chagásica em caninos no Estado do Rio Grande do Sul

Neste trabalho, são relatados dois casos de morte súbita por doença de Chagas aguda em caninos da zona rural de Porto Alegre, Rio Grande do Sul, Brasil. Os cães, um macho Pit Bull com nove meses (canino 1) e uma fêmea Labrador Retriever com dois anos (canino 2), morreram em janeiro de 2005 e maio de 2008, respectivamente. As necropsias revelaram aumento cardíaco em ambos os casos. O coração do canino 2 apresentou formato globoso com múltiplas áreas pálidas na musculatura cardíaca, mais evidentes no ventrículo direito e câmaras cardíacas dilatadas, principalmente as da direita. Ao exame histológico, ambos os casos apresentaram alterações semelhantes caracterizadas por infiltrado inflamatório difuso não-purulento acentuado, predominantemente linfocitário intersticial. Nas fibras miocárdicas, havia grande número de pseudocistos, repletos de formas amastigotas do Trypanosoma cruzi. Ao teste sorológico TESA-blot, amostra do canino 2 foi positiva para anticorpos IgM e IgG anti-T.cruzi, achado característico da fase aguda da miocardite chagásica. Os resultados indicam que a doença de Chagas deve ser investigada em casos de morte súbita em cães na região Sul do Brasil e que a espécie pode servir como reservatório e sentinela da doença em humanos.

A growth hormone secretagogue prevents ischemic-induced mortality independently of the growth hormone pathway in dogs with chronic dilated cardiomyopathy.

To determine the functional role of growth hormone (GH) secretagogue in myocardium with ischemia, left ventricular (LV) pressure gauge, wall thickness crystals, coronary occluder, pacers, and catheters were implanted in 26 dogs. Beginning 1 week after ventricular pacing (240 beats/min) was initiated, dogs were treated (s.c.) with GH releasing peptide-6 (GHRP-6, n = 8, 0.2 mg/kg/day), GH (n = 7, 0.06 mg/kg/day), or vehicle (n = 11). Two weeks of pacing was associated with similar decreases in LV pressure, rate of change of LV pressure, systolic wall thickening (WT), and an increase in left atrial pressure in all groups. Coronary artery occlusion (CAO) resulted in a similar loss of WT in ischemic regions, which did not recover during reperfusion period in all groups. WT in nonischemic regions, however, was enhanced in the GHRP-6 group compared with the GH and vehicle groups, e.g., increase of WT after 1 h of reperfusion was greater (p <0.05) in the GHRP-6 (+53 +/- 8%) than in the GH (+14 +/- 12%) or (+14 +/- 6%). There were no differences in myocardial blood flow, hemodynamics, or arrhythmic beats among all groups during CAO and reperfusion periods. Strikingly, no dogs in the GHRP-6 group died during CAO, whereas the survival rates for GH and vehicle groups were 57 and 55%, respectively. Our data demonstrate, for the first time, that chronic therapy with a GH secretagogue prevents sudden death in dogs with dilated cardiomyopathy subjected to acute ischemia. This seems to be related to an enhanced nonischemic compensatory mechanism mediated by the GH secretagogue receptors rather than via the GH/insulin growth factor-1 pathway.

Re: 'Mitral valve prolapse in the dog: a model of mitral valve prolapse in man' (Cardiovasc Res 2000;47:234–243)

We thank Dr. Cheng for his kind words about our review. In his letter, Dr. Cheng discusses the causes for sudden cardiac death associated with mitral valve prolapse (MVP), focussing on possible mechanisms for fatal ventricular arrhythmias, and invites us to come with comments. As pointed out in our review, the incidence of sudden death in dogs with MVP is low. In our experience, both mild, clinically silent cases and more severe cases with marked regurgitation are affected, analogous …

Bartonella vinsonii subsp. berkhoffii and related members of the alpha subdivision of the Proteobacteria in dogs with cardiac arrhythmias, endocarditis, or myocarditis.

Cardiac arrhythmias, endocarditis, or myocarditis was identified in 12 dogs, of which 11 were seroreactive to Bartonella vinsonii subspecies berkhoffii antigens. Historical abnormalities were highly variable but frequently included substantial weight loss, syncope, collapse, or sudden death. Fever was an infrequently detected abnormality. Cardiac disease was diagnosed following an illness of short duration in most dogs, but a protracted illness of at least 6 months' duration was reported for four dogs. Valvular endocarditis was diagnosed echocardiographically or histologically in eight dogs, two of which also had moderate to severe multifocal myocarditis. Four dogs lacking definitive evidence of endocarditis were included because of seroreactivity to B. vinsonii antigens and uncharacterized heart murmurs and/or arrhythmias. Alpha proteobacteria were not isolated from the blood by either conventional or lysis centrifugation blood culture techniques. Using PCR amplification and DNA sequencing of a portion of the 16S rRNA gene, B. vinsonii was identified in the blood or heart valves of three dogs. DNA sequence alignment of PCR amplicons derived from blood or tissue samples from seven dogs clustered among members of the alpha subdivision of the Proteobacteria and suggested the possibility of involvement of one or more alpha proteobacteria; however, because of the limited quantity of sequence, the genus could not be identified. Serologic or molecular evidence of coinfection with tick-transmitted pathogens, including Ehrlichia canis, Babesia canis, Babesia gibsonii, or spotted fever group rickettsiae, was obtained for seven dogs. We conclude that B. vinsonii subsp. berkhoffii and closely related species of alpha proteobacteria are an important, previously unrecognized cause of arrhythmias, endocarditis, myocarditis, syncope, and sudden death in dogs.

QT prolongation and torsades de pointes induced by an antifungal agent, D0870, in conscious dogs

D0870 (( R)-2-(2,4-difluoro-phenyl)-1-[3-[( E)-4-(2,2,3,3-tetrafluoropropoxy)-styryl]-1 H-1,2,4-triazol-1-yl]-3-(1 H-1,2,4-triazole-1-yl) propan-2-ol), a novel bis-triazole antifungal agent, induced sudden deaths at a high dose of 5 mg/kg/day in a 6-month toxicity study in dogs. In the present study, we intended to elucidate the cause of the sudden death in dogs. When used in a single dose, D0870 induced prolongation of QTc intervals in proportion to its plasma concentration, and the threshold plasma concentration of the drug causing 10% QTc prolongation was estimated to be 3.8 μg/ml. Then, we conducted a study to induce sudden death in dogs using loading (50 mg/kg) and maintenance (5 mg/kg/day) doses with long-term ambulatory electrocardiographic monitoring. Marked QTc prolongation (52–96%), ventricular premature contractions, and T-wave alternans were observed in all 10 animals treated with the drug, and seven out 10 animals died of ventricular fibrillation (VF) associated with torsades de pointes (TdP) when the dogs were treated with D0870 for 14 or 16 days. The TdPs were elicited in both tachycardia and bradycardia, and some of them in the former proceeded to VF. Consequently, we clarified that D0870-induced sudden death is primarily attributable to the development of TdP preceding VF and may be enhanced by sympathetic nervous tone produced by emotional or physical stress.

Age dependence of the development of ventricular arrhythmias in a canine model of sudden cardiac death.

The age-dependence of the development of ventricular arrhythmias was studied in German shepherd dogs with inherited ventricular arrhythmias and sudden death. A colony of German shepherd dogs has been established that exhibit inherited ventricular arrhythmias and sudden death. The incidence of arrhythmias increases with age. Because ventricular tachycardia is associated with bradycardia, it was hypothesized that the increased incidence of arrhythmias was related to age-dependent slowing of heart rate. Arrhythmia counts and RR intervals were measured from serial ambulatory ECG recordings obtained in 71 dogs (1-48 weeks). In addition, 19 dogs were challenged with phenylephrine (10 micrograms/kg i.v.) at 15, 28, and 45 weeks of age, 10 dogs were challenged with epinephrine (1 microgram/kg i.v.) at 3, 5, 7, 9, 11, 18, and 28 weeks of age, and 10 dogs were challenged at 28 weeks with epinephrine (2.5 micrograms/kg i.v.), before and after propranolol (0.5 mg/kg i.v.). The incidence and severity of ventricular arrhythmias increased between 7 and 28 weeks of age and decreased between 28 and 44 weeks of age. The age-dependent increase in the incidence of ventricular tachycardia was associated with age-dependent reductions in sinus rate. Baroreflex-mediated slowing of the heart rate unmasked arrhythmias in young animals that did not spontaneously display arrthythmias and exacerbated existing arrhythmias in older animals. However, the magnitude of baroreflex-induced bradycardia was similar from 7-18 weeks of age, yet the incidence of arrhythmias increased progressively. Moreover, the waning of ventricular arrhythmias in older animals was not associated with more rapid sinus rates. The risk for sudden death in dogs with inherited ventricular arrhythmias increases with age in part because of age-dependent slowing of heart rate and in part because of other heart-rate-independent factors. The correspondence between the development of ventricular tachycardia and sinus pauses is consistent with the hypothesis that ventricular arrhythmias are initiated by early afterdepolarization-induced triggered activity.

Transmembrane Potential Characteristics and Muscarinic and Beta‐Adrenergic Responsiveness in Purkinje Fibers From a Canine Model of Lethal Ventricular Arrhythmias

Autonomic Modulation of Lethal Arrhythmias. Susceptibility to sudden death in dogs with healed myocardial infarction can be defined by the response to transient ischemia during treadmill exercise and can often be predicted by the baroreceptor slope, which is determined from least squares regression of the RR interval, or heart rate, response to increasing systolic pressure during a phenylephrine infusion. We used standard microelectrode techniques to study isolated Purkinje fiber bundles as well as subendocardial Purkinje fibers overlying the infarcted myocardium of dogs classified by treadmill testing as resistant or susceptible to sudden death. We determined the response to isoproterenol (Iso) alone and in the presence of acetylcholine (ACh). Control action potential (AP) characteristics for both groups were similar except for the following: in normal Purkinje fibers, susceptible dogs had a significantly lower AP overshoot and Vmax than resistant dogs. In addition, fibers from the in arct zones of susceptible dogs had lower maximal diastolic potentials than those from the normal Purkinje fibers of susceptible dogs. Iso significantly shortened AP duration in normal and infarct zone fibers of both groups. ACh alone had no effect on AP duration. In the infarct zone, ACh 10−7M did not antagonize Iso‐induced shortening of AP duration in susceptible or resistant dogs; but ACh 10−5M completely blocked Iso effects in resistant dogs. In normal Purkinje fibers, ACh antagonism of Iso effects was seen in susceptible and resistant animals. Iso and ACh had no significant effect on other transmembrane potential characteristics. The differences between resistant and susceptible dogs in control transmembrane characteristics and accentuated antagonism may contribute to the substrate that increases the likelihood of sudden death in this model.

Relative importance of hypertension after coronary occlusion in chronic hypertensive dogs with LVH.

We have shown that there was a 50% increase in infarct size and a threefold increase in the incidence of sudden death following coronary occlusion in dogs with hypertension and left ventricular hypertrophy (LVH). To further investigate this problem, we separated the effects of hypertension from those of LVH by decreasing arterial pressure either by renal anastomosis or intravenous administration of nitroprusside in dogs with chronic renal hypertension and LVH. In 123 conscious dogs, the circumflex coronary artery was acutely occluded. Hemodynamics were monitored, myocardial perfusion was measured with labeled microspheres, the risk area was defined by postmortem angiography, and infarct size was determined pathologically 48 h after occlusion. The incidence of sudden death following acute coronary occlusion decreased dramatically in dogs with LVH if the arterial pressure was decreased with either nitroprusside or renal anastomosis. In addition, if arterial pressure was decreased with nitroprusside or renal anastomosis, infarct size in dogs with LVH was not augmented. In conclusion, normotension induced by renal anastomosis or nitroprusside returned infarct size and the incidence of sudden death in dogs with chronic hypertension and LVH toward control values. Thus it is likely that hypertension, as opposed to LVH, is the critical factor responsible for the increase in infarct size and the high incidence of sudden death observed in dogs with hypertension and LVH following sudden coronary occlusion.