Blood Vessel Topography of the Feet in Selected Species of Birds of Prey and Owls.

Birds of prey and owls are susceptible to diseases of and traumatic injuries to their feet, which regularly require surgical intervention. A precise knowledge of the blood vessel topography is essential for a targeted therapy. Therefore, the metatarsal and digital vasculature was examined in eight species of birds of prey and owls. The study included contrast micro-computed tomography scans and anatomical dissections after intravascular injection of colored latex. In all examined species, the dorsal metatarsal arteries provided the main supply to the foot and their branching pattern and number differed between species. They continued distally as digital arteries. All examined species showed a basic pattern of four collaterally located digital blood vessels per toe: a prominent artery and small vein on one side and a small artery and prominent vein on the other side. Digital veins united to form common digital veins, most of which joined into a superficial, medially located metatarsal vein. This vein provided the main drainage of the foot. The detailed visualization of the topography of pedal blood vessels will help veterinary surgeons during surgical procedures. In addition, differences in the plantar arterial arch between hawks and falcons were discussed regarding their possible influence on the prevalence of pododermatitis (bumblefoot).

Ectoparasites of European hedgehogs (Erinaceus europaeus) in Germany and their health impact.

BACKGROUND: The European hedgehog (Erinaceus europaeus) is known for high levels of ectoparasitism that not only represents a health risk for the animals themselves, but also for pet animals and humans as hedgehogs are frequently taken into human care. In the present study, patterns of ectoparasite infestation were assessed in hedgehogs taken into care at northern German animal rehabilitation centres. METHODS: Ectoparasites (ticks, fleas and mites) of 498 hedgehogs were collected over a period of 3 years from July 2018 to May 2021. Species were identified based on morphological characteristics and also via amplification and sequencing of the partial cytochrome c oxidase subunit 2 (COX-2) gene for fleas of the family Ceratophyllidae. Seasonal changes in infestation patterns as well as correlations with animal age, body weight and health status were assessed using generalised linear models. RESULTS: Infestation with ticks, fleas and mites occurred throughout the year. Overall, 86.5% (431/498) of the examined hedgehogs were infested with ticks, 91.4% (455/498) with fleas and 17.7% (88/498) with mites. Ixodes ricinus and Ixodes hexagonus/Ixodes canisuga were the most common tick species detected, with the additional occurrence of one Ixodes frontalis. Significant seasonal changes were observed for I. ricinus, but not for I. hexagonus/I. canisuga. Additionally, I. ricinus nymph prevalence declined significantly as of 2020, probably as a consequence of the climate change-related drought as of 2018. In hedgehogs with flea infestations, Archaeopsylla erinacei, Ceratophyllus sciurorum, Nosopsyllus fasciatus and Ctenocephalides felis were identified. In all cases of mite infestation, Caparinia tripilis was detected, in addition to specimens of the family Macronyssidae and free-living mites of the family Acaridae. Statistical analyses showed correlations regarding the factors month, year, body weight and age, but no correlation was evident regarding the health status of the animals. CONCLUSIONS: With a detected infestation rate of 98.6%, almost all of the examined hedgehogs were infested with at least one ectoparasite species. The seasonal activity patterns of the different ectoparasite species together with the complex annual cycle of hedgehogs lead to different seasonal patterns in ectoparasite prevalence and infestation intensities. Due to the risk of transmission of zoonotic pathogens as well as the possible negative impact on the host itself, hedgehogs should be treated against ectoparasites when taken into care facilities.

Surgical removal of an atypical histiocytic cell proliferation in a bearded dragon (Pogona vitticeps).

A 4-year-old female bearded dragon (Pogona vitticeps) was referred to the Clinic for Small Mammals, Reptiles and Birds of the University of Veterinary Medicine, Hannover, Germany for diagnostics and treatment of a growing mass in the right cervical region. The owner reported that the mass had grown over the past 4 weeks with only little alteration in the lizard´s behavior when the animal started rubbing its neck against the cage equipment. Physical examination as well as ultrasonographic and computed tomographic diagnostics revealed a highly vascularized mass, which allowed for the hypothesis of an aneurysm or a neoplasia. Complete surgical resection of the mass could be performed uneventfully. The bearded dragon recovered well from anesthesia and the surgical procedure. The microbiological sample of the excised mass revealed Group F-67 Salmonella. Histopathological examination of the excised mass revealed a histiocytic cell proliferation with centrally located blood filled cavities, hemorrhages and granulation tissue resembling features of a pseudoaneurysm. This report describes the diagnosis of an atypical growing mass in a bearded dragon and its successful removal.

Surgical Stabilisation of a Coxofemoral Luxation in a Northern Goshawk (Accipter gentilis) with Transarticular Pinning.

A 3-year-old male northern goshawk (Accipiter gentilis) used in falconry for hunting was diagnosed with a craniodorsal coxofemoral luxation of the left leg after an unsuccessful hunting flight. Closed reduction in the dislocation was unsuccessful and the hip joint reluxed again with slight abduction of the limb. An open surgical reduction with a transarticular stabilization using a normogradely inserted Kirschner wire was performed. The implant was removed surgically after five weeks. After about seven weeks, the owner saw no abnormalities in the loading of the limbs, and the goshawk was successfully used for hunting after nine months in the next hunting season.

Treatment options, complications and long-term outcomes for limb fractures in pet rabbits.

BACKGROUND: Limb fractures represent the most common orthopaedic disease in pet rabbits. However, only a few studies have evaluated therapeutic details of limb fractures. There are no data available for long-term outcomes of limb fracture treatment. METHODS: The medical records of six institutions were reviewed retrospectively to identify cases of traumatic limb bone fractures in pet rabbits between 1999 and 2020. The medical records (n = 387) were analysed for details of fracture prevalence, aetiology, therapy protocols, treatment complications, outcome and long-term effects. In addition to the retrospective data evaluation, 13 rabbits were re-evaluated in person in recent clinical analyses, including orthopaedic examination, radiography and computed-tomographic imaging. Details of long-term effects of fracture treatment were requested over the telephone for a further 232 animals using a standardised questionnaire. RESULTS: Long bone fractures accounted for the majority of all fractures (296/387; 76.5%). Hindlimb fractures (301/387; 77.7%) were more common than forelimb fractures (86/387; 22.2%), and tibial fractures and combined fractures of the tibia and fibula (119/387; 30.8%) were observed most frequently. Most fracture treatments were based on osteosynthesis procedures (243/328; 74.1%). Treatment complications occurred in 130 out of 328 (39.6%) cases. A high bodyweight (p = 0.047) and an older age (p = 0.01) were found to be significant risk factors for the emergence of therapy complications. Overall, 75.4% of animals (175/232) had a satisfactory long-term outcome. Limb posture anomalies were evaluated in 61 cases (26.3%). LIMITATIONS: The multi-centre approach led to the inclusion of various institutions, veterinarians, treatment protocols and rabbit populations that might have influenced the results. The medical records were reviewed retrospectively, so there were some data that were lacking or could not be collected in a standardised manner. Furthermore, rabbit owners' evaluation of long-term outcomes might be prone to error, despite the use of a standardised interview questionnaire. CONCLUSION: Limb fractures are a common orthopaedic issue in pet rabbits. The patient's bodyweight and age are significant risk factors for the emergence of complications during the fracture treatment process. Long-term orthopaedic effects, such as abnormal limb posture and permanent lameness of the affected limb, were observed regularly.

[Limb fractures in pet rabbits (Oryctolagus cuniculus f. domestica) - A case series of orthopedic long-term effects in fracture patients]. / Gliedmaßenfrakturen beim Kaninchen (Oryctolagus cuniculus f. domestica).

OBJECTIVE: Limb fractures account for a large proportion of all orthopedic diseases in pet rabbits and are a common reason for presentation. The fracture etiologies and characteristics vary considerably in comparison to trauma of the extremities in cats and dogs. For this reason, conservative and surgical treatment options need to be adapted. To our knowledge, long-term effects of limb fracture therapies in pet rabbits have not been described scientifically. MATERIALS AND METHODS: This article features a case series of 13 pet rabbits with limb fractures. Their medical records were analyzed retrospectively and all patients were presented for a follow-up examination including clinical and orthopedic examination. RESULTS: Orthopedic anomalies (abducted limb postures) were identified in four patients. Arthrotic ossification was found in twelve of thirteen animals - in six cases to a high extent. Measurement of the fractured bones revealed a shortening in ten of thirteen cases. CONCLUSION AND CLINICAL RELEVANCE: Orthopedic long-term complications following fracture treatments were commonly detected in the patient population of this study. Permanent issues may result in anomalies of limb posture or postural control which are not noticed by the rabbit owners in every case. Ultimately, the patients should be examined routinely after the conclusion of fracture therapy in order to detect and adequately treat possible orthopedic complications.

Tolerability of Atovaquone-Proguanil Application in Common Buzzard Nestlings.

Differences in drug tolerability among vertebrate groups and species can create substantial challenges for wildlife and ex situ conservation programmes. Knowledge of tolerance in the use of new drugs is, therefore, important to avoid severe toxicity in species, which are both commonly admitted in veterinary clinics and are of conservation concern. Antimalarial drugs have been developed for use in human medicine, but treatment with different agents has also long been used in avian medicine, as haemosporidian infections play a major role in many avian species. This study investigates the effects of the application of atovaquone-proguanil (Malarone®, GlaxoSmithKline) in common buzzards (Buteo buteo). The potential effects of treatment on body condition, growth rate, and chemical blood parameters of nestlings were assessed. All individuals survived the treatment, and no effects on body condition, growth rate, and chemical blood parameters were observed. Our results suggest the tolerability of Malarone® in common buzzards at a single dose of on average 11 mg/kg body weight. For its safe use, we recommend further studies to determine pharmacokinetics in different avian species as well as to assess the effects of repeated treatment.

Performing a Three-Dimensional Finite Element Analysis to Simulate and Quantify the Contact Pressure in the Canine Elbow Joint: A Pilot Study.

OBJECTIVE: The aim of this study was to measure surface pressures and force distribution on radius and ulna in healthy and dysplastic elbow joints in different positions using the finite element analysis (FEA). STUDY DESIGN: FEA was performed on computed tomographic data of healthy and fragmented coronoid process diseased elbow joints of Labrador Retrievers. It considered the articular cartilage, collateral ligaments, triceps and biceps muscle. The analysis of each joint was performed in four positions (standing position: 145 degrees and three positions of the stance phase of gait: beginning: 115 degrees, middle: 110 degrees, end: 145 degrees joint angle) in consideration of different ground reaction forces (standing: 88.3 N; stance phase of gait: 182.5 N). RESULTS: Mean values of total force of 317.5 N (standing), 590.7 N (beginning), 330.9 N (middle) and 730.9 N (end) were measured. The percentual force distribution resulted in a total of 49.56 ± 26.58% on the ulna with a very inhomogeneous distribution. A significant difference was detected between the positions 'standing' and 'end' (p = 0.0497) regardless of the joint condition. In some FEA results, visual assessment of the surface pressures indicated an increase in pressure in the region of the medial compartment without a uniform pattern. An increase in pressure resulted in an area increase in the pressure marks on the joint surface and measurable pressure was increased at a larger joint angle. CLINICAL SIGNIFICANCE: FEA can provide information about the transmission of force in the joint. Prior to the use of FEA in scientific clinical research for the simulation of force, further model improvements are necessary.

Ex Vivo Evaluation of the Cranial Tibial Artery and Its Compression through Fragment Rotation during Tibia Plateau Levelling Osteotomy: An Angiographic Three-Dimensional Reconstruction.

OBJECTIVE: To illustrate the arterial vascularity of the proximal tibia three-dimensionally and to evaluate the impact of fragment rotation on the cranial tibial artery by tibia plateau levelling osteotomy (TPLO). METHODS: Radiographic angiography and computed tomography (CT) were performed on 12 pelvic limbs from six large-breed canine cadavers before and after TPLO. Three-dimensional (3D) models of the stifle, including osseous and vascular structures, were obtained, and the integrity of the cranial tibial artery was assessed. Post-TPLO CT images were used to analyze compression of the cranial tibial artery by the rotated fragment. RESULTS: The uncompressed cranial tibial artery caliber, measured proximally and distally to the osteotomy, was 9.52 mm2 (6.07-18.90 mm2). In all adequately rotated fragments, the mean caliber of the artery on the level of the osteotomy was 1.57 mm2 (0.89-2.93 mm2) after TPLO. This represented a significant decrease of approximately 81%. Only slight cross-sectional area decrease (8.8%) was seen in one limb, which was revealed to have insufficient fragment rotation (2.83 mm). Another limb only showed signs of stretching of the artery (31.51%), which was under-rotated and medially displaced. Pre-TPLO 3D reconstructions were mainly consistent with previous anatomic studies except for the distance between tibial cortex and cranial tibial artery, which appeared closer. CONCLUSION: Sufficient fragment rotation leads to compression of the cranial tibial artery. Intraoperative hemorrhage can be caused by laceration of the main cranial tibial artery or by multiple small branches reaching craniolaterally.

[Studies on the use of iodine-containing contrast agent diatrizoate in rabbits (Oryctolagus cuniculus)]. / Untersuchungen zum Einsatz des jodhaltigen Kontrastmittels Amidotrizoesäure beim Kaninchen (Oryctolagus cuniculus).

OBJECTIVE: The use of the iodine-containing contrast agent diatrizoate was investigated in healthy rabbits and in rabbits with gastric dilatation and intestinal obstruction. For this purpose, transit times through the gastrointestinal tract and clinical use were investigated during a one year period. In addition, a possible influence on thyroid hormone levels was evaluated. MATERIAL AND METHODS: Transit times of contrast agent through the different intestinal sections were examined radiographically in 14 healthy rabbits. For this purpose, 7 ml/kg of a 300 mg iodine/ml and 600 mg diatrizoate/ml containing solution were administered. Radiographs were obtained at different time intervals. Three different doses (D1 2 ml/kg, D2 7 ml/kg, D3 10 ml/kg) were administered, and blood samples were collected at two time points (60 min, 24 h) to analyze thyroid hormone levels (TT4, fT4, TSH). In addition, 70 rabbits that had received the contrast agent diatrizoate because of gastric dilatation and suspected intestinal obstruction were retrospectively evaluated during a period of one year. Focus was placed on arrival of the contrast agent in the cecum, laboratory changes, and mortalities. RESULTS: In all healthy rabbits, contrast medium was detectable in the cecum after a mean of 45-60 min. In the animals suffering from gastrointestinal obstruction, this was delayed to a mean of 121.2 min. These animals showed hypothermia in 92.4 % and hyperglycemia in 45.9 %. 56.1 % exhibited an increase in urea and 33.9 % an increase in creatinine. In 71.4 % of cases, medical treatment was possible, however 12 % of these individuals succumbed to the disease. 28.6 % of the cases were managed surgically which was associated with a mortality of 50 %. TT4, fT4, and TSH levels displayed significant alterations among the three contrast agent doses (p < 0.05). These changes were found to be transient when follow-up was performed two weeks later. CONCLUSION AND CLINICAL RELEVANCE: When ileus is suspected in rabbits, diatrizoate may be helpful in evaluating the progression of the disease in addition to the use of native radiographs. Sufficient hydration and monitoring of renal function are advisable. Transient changes in thyroid hormones were evident but lacked clinical relevance.

Influence of anesthesia with isoflurane on myocardial velocities of racing pigeons (Columba livia f. domestica).

OBJECTIVE: Tissue Doppler imaging (TDI) is a new technique to measure the myocardial velocities of the avian heart. Using this technique, the present study investigated the influence of isoflurane anesthesia on the systolic and diastolic longitudinal myocardial velocities in racing pigeons. MATERIAL AND METHODS: Racing pigeons (n = 40) were anesthetized with isoflurane with a semi-open anesthesia system with an anesthetic mask and spontaneous breath. The echocardiographic examination was performed during the stage of surgical anesthesia with the failure of the toe pinch and wing twitch reflexes and with deep regular breaths. Echocardiographic measurements were taken in conscious and anesthetized pigeons in the right parasternal longitudinal horizontal heart view. RESULTS: The results demonstrated a significant decrease in heart rate, systolic and diastolic A' wave myocardial velocities. The diastolic E' wave velocities were less influenced by anesthesia and significantly decreased only for some heart wall segments. The systolic myocardial velocities were significantly negatively correlated with the heart rate. Using the TDI curve, the isovolumic contraction (IVC) and relaxation time (IVR) and the time of atrioventricular delay during anesthesia could be determined. There is a significant increase in IVR and atrioventricular delay during anesthesia CONCLUSION AND CLINICAL RELEVANCEN: A higher heart rate in anesthesia should be interpreted as a compensation for reduced heart performance. The results of the present study indicate the necessity for establishing normal heart values in conscious and anesthetized pigeons.

Analysis of the B-Type Natriuretic Peptide and the Aminoterminal-Pro-B-Type Natriuretic Peptide in Different Parrot, Raptor and Owl Species.

The B-type natriuretic peptide (BNP), a member of the natriuretic peptide family and a cardiac hormone, is produced mainly in the ventricular myocytes and released into the circulation due to mechanical stimuli during an increasing cardiac wall stretch. BNP has a significant role in the regulation of the cardiovascular system and body fluid. The concentration of this hormone and of the biologically inactive amino-terminal-prohormone in the blood plasma is a helpful diagnostic tool for detecting cardiovascular diseases in human medicine and can be used as a prognostic marker for the risk of mortality, whilst such a tool does not exist for avian medicine. To date, the amino acid sequence of BNP is not known for many of the species commonly presented in avian consultation. In this study, the amino acid sequence of BNP and the prepropeptide was described for 12 parrot species as well as 3 raptor and 3 owl species by polymerase chain reaction (PCR) after RNA isolation from the heart. The results showed a high similarity between the amino acid sequences in the mature peptide region of the BNP. The prepropeptide showed several differences between the examined species, some of them shared by closely related species.

Experimental evidence for proarrhythmic effects of nonsteroidal anti-inflammatory drugs in a sensitive whole-heart model.

BACKGROUND: Previous studies have raised serious concerns on cardiovascular safety of widely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, the aim of this study was to characterize the electrophysiological effects of certain NSAIDs in an established whole heart model of proarrhythmia. METHODS AND RESULTS: Thirty-eight hearts of New Zealand White rabbits were harvested and retrogradely perfused employing a Langendorff setup, and electrophysiology studies were performed to investigate action potential duration at 90% of repolarization (APD90 ), QT intervals, and effective refractory period (ERP). After generating baseline data, hearts were perfused with ibuprofen (Group 1, n = 12; 10 and 30 µM), indomethacin (Group 2, n = 13; 10 and 20 µM) and diclofenac (Group 3, n = 13; 10 and 20 µM), respectively, and the pacing protocols were repeated for each concentration. In all groups, perfusion with the NSAIDs resulted in a significant and reproducible shortening of APD90 and QT interval. In all groups, the arrhythmia susceptibility was significantly raised as occurrence of monomorphic ventricular tachycardia under programmed ventricular stimulation was significantly increased under perfusion with ibuprofen, indomethacin and diclofenac in all concentrations. CONCLUSION: The perfusion with ibuprofen, indomethacin and diclofenac in commonly used doses raised the arrhythmia susceptibility in an established rabbit whole-heart model while APD shortening and shortened ERP seem to be crucial for arrhythmogenesis.

[Extraction of diseased mandibular incisors in the guinea pig (Cavia porcellus) via ventral mandibular trepanation]. / Extraktion erkrankter Unterkieferinzisivi beim Meerschweinchen (Cavia porcellus) via ventraler Mandibulatrepanation.

OBJECTIVE: This retrospective study describes the use of ventral mandibular trepanation for extraction of diseased mandibular incisors in guinea pigs and evaluates the clinical outcome. MATERIAL AND METHODS: In 40 guinea pigs with abnormal feed intake, at least one mandibular incisor was extracted via ventral mandibular trepanation. The diagnosis of primary mandibular incisor disease was based on the findings of the clinical general examination and intraoral and radiographic examination under general anesthesia. Following the procedure radiographs were taken and the patients were monitored and cared for as inpatients until discharge. Regular re-examinations were undertaken in order to assess and treat the surgical sites. RESULTS: A total of 42 altered mandibular incisors were extracted via ventral mandibular trepanation. Macrodonts (25/42) and periapical and alveolar changes (8/42) were the main reasons for extraction. Tooth residuals of unknown etiology (4/42) as well as such resulting from failed conventional extraction attempt using luxators (3/42) and traumatically loosened incisors (2/42) were also extracted. Tooth-associated jaw abscesses were found in 40 % of the guinea pigs. In addition, 40 % of the animals presented secondary elongation of the molars requiring occlusal equilibration. In all patients, it was possible to completely remove the altered incisors or residuals. On average, independent feed intake was observed 2 days after surgery and the animals were discharged. Complete healing of the surgical site was observed on average after 39 days (minimum 9 days, maximum 98 days). A total of 22 animals were evaluated 6 months following surgery and showed no further tooth-associated complaints. CONCLUSION AND CLINICAL RELEVANCE: Ventral mandibular trepanation allows diseased mandibular incisors in guinea pigs to be removed entirely within one surgery and thus represents a curative procedure. Unlike the conventional extraction with luxators, it does not bear the risk of tooth fractures resulting in tooth fragments remaining in the alveolus.

The prevalence of Leucocytozoon spp. in nestlings of three wild raptor species including implications on haematological and blood chemistry values.

Leucocytozoonosis is a vector-borne infection of birds, caused by members of the haemosporidian genus Leucocytozoon. The clinical presentation may range from asymptomatic to severe disease. Consequences of Leucocytozoon infection on blood profiles remain to be described, especially for different host species in the wild. In the current study, the prevalence of Leucocytozoon infection was determined in wild nestlings of three European raptor species, the common buzzard (Buteo buteo, n = 464), red kite (Milvus milvus, n = 46) and northern goshawk (Accipiter gentilis, n = 18). Among 528 nestlings, 51.9% (n = 274) were infected with Leucocytozoon spp., whereby the highest prevalence was found in common buzzards (54.9%), followed by red kites (32.6%) and northern goshawks (22.2%). For a subset of 87 individuals (50 common buzzards, 29 red kites, 8 northern goshawks), a detailed analysis of differential leukocyte counts and several blood chemistry parameters in response to infection was conducted: AP (alkaline phosphatase), AST (aspartate aminotransferase), GLDH (glutamate dehydrogenase), LDH (lactate dehydrogenase), GGT (gamma glutamyl transferase), CK (creatine kinase), BuChE (butyrylcholinesterase), BA (bile acids), ALB (albumin) and TP (total protein). Even though in the physiological range, infected nestlings displayed significantly increased levels of heterophils, aspartate aminotransferase, lactate dehydrogenase, bile acids and butyrylcholinesterase, but decreased lymphocyte and monocyte values compared to uninfected ones. Furthermore, significant species differences with regard to blood parameters, but no sex differences were found. Overall, obtained results show a high prevalence, but a low pathogenicity of Leucocytozoon spp. in wild raptor chicks, presumably resulting from coevolutionary adaptation, but show signatures of infection in the haematological and blood chemistry profiles.

Monitoring of Organochlorine Pesticide and Polychlorinated Biphenyl Residues in Common Swifts (Apus apus) in the Region of Hannover, Lower Saxony, Germany.

The use of pesticides is associated with the decline of several avian species. In this study, we monitored the organochlorine contaminants in common swifts (Apus apus) in the years 2016 to 2018. These long-distance migrants breed in Europe and winter in Africa. Their only feeding source is aerial plankton. Pooled organ samples of 42 adult and 40 juvenile swifts were tested with the multi-residue method by gas chromatography-mass spectrometry (GC-TOF/MS). Predominantly, 4,4'-DDE, dieldrin, hexachlorobenzene (HCB), lindane and polychlorinated biphenyls (PCBs) were found in most of these common swifts. Only 4,4'-DDE (adult: 83 ± 70 µg/kg, juvenile: 17 ± 39 µg/kg) and dieldrin (adult: 2 ± 3 µg/kg, juvenile: 0.3 ± 1 µg/kg) concentrations were significantly different between adult and juvenile birds. All detected concentrations in our study were far lower than the previously recorded pesticide concentrations of common swifts in Italy and those which are known to cause toxicity and death in birds.

Proarrhythmic potential of metoclopramide in a sensitive whole-heart model.

BACKGROUND: Metoclopramide (MCP) is a dopamine D2 -receptor antagonist, mainly used to treat post-operative or chemotherapy-induced nausea. While it is very effective in the cure of gastric symptoms, MCP can cause severe neurologic side effects. Furthermore, there is growing evidence for severe arrhythmic side effects resulting from inhibitory effects on cardiac sodium and potassium channels. METHODS AND RESULTS: Thirteen hearts of New Zealand white rabbits were retrogradely perfused, and electrophysiology studies were performed to obtain action potential duration (APD90 ) and effective refractory period (ERP). After generating baseline data, the hearts were perfused with increasing concentrations of metoclopramide (MCP 10 µM, MCP 50 µM, MCP 100 µM) and the standardized protocol was repeated for each concentration. Perfusion with MCP resulted in a significant prolongation of APD90 and QT interval. In parallel, the incidence of ventricular tachycardias was significantly increased by high doses of MCP. CONCLUSION: This is the first experimental study that investigated the effect of increasing doses of metoclopramide on a sensitive whole-heart model of proarrhythmia. MCP led to a significant increase in action potential duration and QT interval; meanwhile, the number of ventricular tachycardias was significantly increased.

Diastolic and Systolic Longitudinal Myocardial Velocities of Healthy Racing Pigeons (Columba livia f. domestica) Measured by Tissue Doppler Imaging.

Tissue Doppler imaging (TDI) is a noninvasive sonographic method of acquiring and quantifying myocardial velocities. This technique is used in human and small animal medicine to diagnose cardiac diseases. Using this technique, we evaluated the longitudinal myocardial peak velocities of the interventricular septum, and the left and right ventricular free walls in the systole and diastole in 40 racing pigeons. The TDI examinations confirmed the movement of the heart base toward the apex in the systole and away from the apex in the diastole. Inhomogeneous distribution of the myocardial velocities with a statistically significant velocity gradient from the basal to the apical myocardial segments was found. The left and right free walls have significantly higher myocardial velocities than the myocardium of the septum. The myocardial velocities during active ventricular filling were significantly higher in the right ventricular free wall than in the left one. The validation of the method resulted in coefficients of variation between 3% and 33% for the systolic and 3% and 75% for the diastolic individual myocardial velocities. Weekly repeated measurements resulted in variation coefficients between 3% and 45% for systolic and diastolic myocardial velocities, respectively.

Divergent Electrophysiological Effects of Loperamide and Naloxone in a Sensitive Whole-Heart Model.

Several case reports suggest QT prolongation leading to ventricular arrhythmias with fatal outcome after intoxication with the µ-opioid receptor agonist and anti-diarrheal agent loperamide. The number of cases of loperamide misuse are growing due to its potential stimulating effects. Loperamide intoxications can be treated by naloxone. However, previous reports described a further QT prolongation associated with naloxone administration. Therefore, the aim of this study was to investigate the effects of loperamide and naloxone on the cardiac electrophysiology in a sensitive whole-heart model. Twenty-six hearts of New Zealand White rabbits were retrogradely perfused in a modified Langendorff apparatus. Monophasic action potentials were recorded by endo- and epicardially positioned catheters. Hearts were stimulated at different cycle lengths, thereby obtaining action potential duration at 90% of repolarization (APD90) and QT intervals. Programmed ventricular stimulation was used to assess ventricular vulnerability. Fourteen hearts were perfused with ascending concentrations of loperamide (0.2 µM, 0.35 µM, and 0.5 µM) after obtaining baseline data. Another 12 hearts were treated with naloxone (0.1 µM, 0.5 µM, 2 µM). Loperamide led to a significant increase in QT interval, APD90, and ventricular tachycardia (VT) episodes. In contrast, naloxone led to a decrease in QT interval and APD90. Accordingly, the number of VT episodes was unaltered. To the best of our knowledge, this is the first experimental study that investigated the effects of loperamide and naloxone in a whole-heart model. Loperamide led to a significant increase in action potential duration and QT interval. Simultaneously, the number of ventricular tachycardias was significantly increased. In contrast, naloxone led to a shortening of the action potential duration without altering arrhythmia susceptibility.

SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition.

T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.