Characteristics of electrocardiographic changes with some representative antiarrhythmic drugs in adult rats.

The characteristics of ECG changes with representative antiarrhythmic drugs; procainamide (PA) (class Ia), lidocaine (LC) (class Ib), propranolol (PN) (class II), and verapamil (VP) (class IV) were investigated in adult rats. Action potential (AP) was also recorded from myocardial cells during electrical stimuli with frequencies of 1-5 Hz. All the four drugs produced ECG abnormalities which contained AV and SA blocks at middle and high dose levels. Three drugs except VP induced a prolongation of QRS complex and notched QRS at low or middle dose level. As compared such effects with those in dogs and humans, some differences were noted as follows: (1) a dose-dependent prolongation of QT interval by LC and PN, and (2) a shortening of RR interval by VP at the dose of 0.6 mg/kg or less. LC and PN elongated the QT interval in the unipolar precordial chest lead ECGs at right anterior chest positions. These two drugs did not affect the duration of AP (APD90), whereas maximum upstroke velocity (Vmax) decreased. These results suggest that the prolongation of QT interval with LC and PN was due to a delay in local ventricular conduction time, especially on the right ventricle. The shortening of RR interval by VP was clearly blocked by the pretreatment with PN, indicating that this shortening reflected the sympathetic nervous reflex presumably due to the peripheral vasodilation effect of VP.     

Correlation of QT dispersion with indices used to evaluate the severity of familial ventricular arrhythmias in Boxers

OBJECTIVE: To measure QT interval duration and QT dispersion in Boxers and to determine whether QT variables correlate with indices of disease severity in Boxers with familial ventricular arrhythmias, including the number of ventricular premature complexes per day, arrhythmia grade, and fractional shortening. ANIMALS: 25 Boxers were evaluated by ECG and echocardiography. PROCEDURE: The QT interval duration was measured from 12-lead ECG and corrected for heart rate (QTc), using Fridericia's formula. The QT and QTc were calculated for each lead, from which QT and QTc dispersion were determined. Echocardiography and 24-hour ambulatory ECG were performed to evaluate for familial ventricular arrhythmias. Total number of ventricular premature complexes, arrhythmia grade, and fractional shortening were determined and used as indices of disease severity. RESULTS: There was no correlation between any QT variable and total number of ventricular premature complexes, arrhythmia grade, or fractional shortening. No difference between QT dispersion and QTc dispersion was identified, and correction for heart rate did not affect the results. CONCLUSIONS AND CLINICAL RELEVANCE: QT interval duration and dispersion did not correlate with indices of disease severity for familial ventricular arrhythmias. Heart rate correction of the QT interval did not appear to be necessary for QT dispersion calculation in this group of dogs. QT dispersion does not appear to be a useful noninvasive diagnostic tool in the evaluation of familial ventricular arrhythmias of Boxers. Identification of affected individuals at risk for sudden death remains a challenge in the management of this disease.     

Hemodynamic and electrophysiologic effects of ontazolast in dogs

OBJECTIVE: To determine whether QT interval is prolonged or sudden death is caused by ventricular fibrillation resulting from torsades de pointes and to identify hemodynamic effects of ontazolast. ANIMALS: 28 Beagles. PROCEDURE: Physiologic variables were measured for 2 hours in conscious dogs given ontazolast (0, 1, or 3 mg/kg of body weight, IV) and for 1 hour in anesthetized dogs given cumulative doses of ontazolast (0, 1, 3, 6, or 8 mg/kg, IV). RESULTS: Ontazolast prolonged QT interval and QT interval corrected for heart rate (QTc) at doses of 6 mg/kg in anesthetized dogs. At 8 mg/kg, both variables remained prolonged but tended to decrease. In conscious dogs, ontazolast increased QT interval and QTc 15 minutes after administration, but both variables returned to reference ranges by 60 minutes. In conscious dogs, ontazolast increased maximum rate of increase of left ventricular pressure and maximal velocity of fiber shortening, indicators of inotropy, and increased tau, indicating a decreased rate of relaxation. One conscious dog receiving 3 mg/kg developed nonfatal torsades de pointes, but another conscious dog developed ventricular fibrillation. Two anesthetized dogs receiving 6 mg/kg developed early afterdepolarizations, and all dogs developed secondary components in theirT waves. CONCLUSION AND CLINICAL RELEVANCE: Ontazolast possesses potent class-III antiarrhythmic properties and induces prolongation of QTc in a dose-dependent fashion. Because there was a clear dose-dependent prolongation of QT interval in all instances, ontazolast may serve as a positive-control compound for studying other compounds that are believed to prolong the QT interval.     

Effects of moxifloxacin on QT interval in conscious dogs

Moxifloxacin has been shown to induce QT prolongation in both clinical and preclinical models. However, the ability to observe this effect at clinically relevant concentration in normal conscious dogs has not been reported. The purpose of this study was to investigate the effects of moxifloxacin on the QT interval in conscious, healthy dogs. Four male mongrel dogs were chronically instrumented for the measurement of arterial blood pressure, left ventricular blood pressure, cardiac output, electrocardiograms (ECGs), and body temperature. Animals were administered a 1-h i.v. infusion of moxifloxacin once per day via a catheter in the cephalic vein. Each dog received all doses (0, 1, 10, 25 and 50 mg/kg) in an escalating fashion. Moxifloxacin caused a statistically significant increase in arterial blood pressure at 50 mg/kg. A dose-response effect on QT and QTc prolongation was observed. A statistically significant prolongation in the QT interval was observed at 10, 25 and 50 mg/kg and a prolongation of QTc was observed at 25 and 50 mg/kg. These effects occurred at clinically relevant plasma concentrations. This study demonstrate that a study design with four dogs was sensitive enough to measure moxifloxacin-induced QT prolongation at clinically relevant plasma concentrations.     

Diagnosis and treatment of cardiac arrhythmias

Cardiac arrhythmias are probably more common in horses than in any other domestic animal species. The most frequent clinical complaint associated with cardiac arrhythmias is exercise intolerance. Physical examination is characterized by auscultation abnormalities such as fast or slow heart rate, irregular rhythm, extra sounds, long pauses, or abnormal heart sounds. The electrocardiogram is used to make a definitive diagnosis of the dysrhythmia. Other laboratory and cardiac function tests are employed to determine the etiology and to assess the significance of the arrhythmia. Antiarrhythmic therapy is given when clinical signs specifically related to the arrhythmia are present, when hemodynamic parameters are compromised by the arrhythmia, or when the ECG reveals abnormalities that put the patient at risk for development of more severe arrhythmias. The cardiovascular drugs most frequently used are digoxin and quinidine. Digoxin is most commonly used for supraventricular arrhythmias, especially arrhythmias characterized by fast heart rates. Quinidine is very effective for short-term treatment of ventricular and supraventricular arrhythmias but must be used with caution because of the potential for toxic side effects. The cardiac arrhythmias due to vagal tone (sinus arrhythmia, sinus block, sinus arrest, sinus bradycardia, wandering pacemaker, first-degree AV block, and second-degree AV block) that are found in resting horses are generally considered to be normal and generally do not require therapy.     

Comparison of the effects of thiopentone and propofol on the electrocardiogram of dogs

Sixty-four dogs were randomly assigned to receive either thiopentone or propofol and their electrocardiograms were recorded immediately before and shortly after they were anaesthetised. Thiopentone caused a marked increase in QT and JT intervals, a flattening of the T-wave and an increase in precordial QT dispersion. Propofol induced a less marked increase in QT and JT intervals, corrected for heart rate. Both agents induced an increase in heart rate and a decrease in heart rate variability, consistent with reduced vagal tone. Shortly after anaesthesia was induced, thiopentone affected ventricular repolarisation to a far greater extent than propofol, changes which suggest that it may be more likely to induce re-entrant ventricular arrhythmogenesis and could be associated with an increase in sympathetic tone. Propofol may therefore be more suitable than thiopentone for dogs with a susceptibility to ventricular arrhythmias or a long QT interval.     

Geriatric pharmacology.

When faced with the geriatric dog or cat, the practitioner should consider the following: 1. Avoid using any drugs at all unless there are definite therapeutic indications. If the patient has some degree of renal insufficiency, try to select drugs that are hepatically metabolized and excreted in bile rather than eliminated by the kidneys (eg, doxycycline, tolfenamic acid). If hepatic insufficiency is present, select drugs that do not undergo metabolism before renal excretion (eg, penicillins, cephalosporins). 2. If therapeutic drug monitoring is available, tailor the drug dosage regimen to that specific patient (eg, phenobarbital, digoxin, amino-glycosides). 3. If therapeutic drug monitoring is unavailable, determine if there are clinically proven adjusted dosage regimens for specific drugs. The package insert on human pharmaceutics often gives guidelines for adjusting dosages in geriatric patients. 4. If the drug has not been sufficiently studied to have dosage adjustment recommendations, determine if there is sufficient information about its kinetics to estimate the proper drug dose in a geriatric patient. Some general guidelines for commonly used drugs in geriatric veterinary patients are provided in Table 1. In general, if the Vd changes in your patient, change the dose. If the elimination half-life changes, change the dosing interval. 5. Carefully monitor treated patients for signs of efficacy and toxicity.     

Effects of trimethoprim–sulfadiazine and detomidine on the function of equine Kv11.1 channels in a two‐electrode voltage‐clamp (TEVC) oocyte model

The long QT syndrome (LQTS) is a channelopathy that can lead to severe arrhythmia and sudden cardiac death. Pharmacologically induced LQTS is caused by interaction between drugs and potassium channels, especially the K_v11.1 channel. Due to such interactions, numerous drugs have been withdrawn from the market or are administered with precautions in human medicine. However, some compounds, such as trimethoprim–sulfonamide combinations are still widely used in veterinarian medicine. Therefore, we investigate the effect of trimethoprim–sulfadiazine (TMS), trimethoprim, sulfadiazine, and detomidine on equine‐specific K_v11.1 channels. K_v11.1 channels cloned from equine hearts were heterologously expressed in Xenopus laevis oocytes, and whole cell currents were measured by two‐electrode voltage‐clamp before and after drug application. TMS blocked equine K_v11.1 current with an IC₅₀ of 3.74 mm (95% CI: 2.95–4.73 mm ) and affected the kinetics of activation and inactivation. Similar was found for trimethoprim but not for sulfadiazine, suggesting the effect is due to trimethoprim. Detomidine did not affect equine K_v11.1 current. Thus, equine K_v11.1 channels are also susceptible to pharmacological block, indicating that some drugs may have the potential to affect repolarization in horse. However, in vivo studies are needed to assess the potential risk of these drugs to induce equine LQTS.     

Long QT syndrome in dogs with tick toxicity (Ixodes holocyclus)

OBJECTIVE: To evaluate cardiac electrical function in dogs with tick toxicity. DESIGN: A prospective clinical investigation of 39 client-owned dogs treated for naturally occurring tick toxicity. PROCEDURE: An ECG was performed on each dog on several occasions; at admission to hospital with tick toxicity, 24 h later, at discharge from hospital when clinically normal and approximately 12 months later. RESULTS: The mean QT interval corrected for heart rate (QTc) was prolonged at admission, 24 h and at discharge compared to the QTc measured 12 months later. T wave morphology was altered in dogs at admission. All other parameters were within normal limits. CONCLUSIONS: The prolonged QTc interval and altered T wave morphology of dogs with tick toxicity reflects delayed cardiac repolarisation and is comparable with long QT syndrome (LQTS) in people who are predisposed to polymorphic ventricular tachycardia and sudden death. Resolution of ECG changes lagged behind clinical recovery.     

Normal electrocardiographic QT interval in race-fit Standardbred horses at rest and its rate dependence during exercise

ObjectivesCardiac repolarization, measured as QT and T_peak to T_end (T_pT_e) intervals on the ECG, is important, as irregularities caused by diseases, ventricular hypertrophy, drugs and genetic defects can trigger arrhythmias which predispose human patients to syncope and sudden cardiac death. In horses, repolarization is not well described and therefore QT analysis cannot yet be used diagnostically. Therefore, we sought to describe reference values for the normal QT and T_pT_e intervals in Standardbreds and to determine the best method for heart rate (HR) correction.Animals30 Standardbreds.MethodsQT and T_pT_e intervals were measured during rest and exercise and plotted against HR converted to R_peak to R_peak interval (RR). Data were fitted with relevant regression models. Intra- and inter-observer agreement was assessed using Bland–Altman analyses.ResultsData were best described by a piecewise linear model (r² > 0.97). Average prediction error of this model was smaller than for both Bazett and Fridericia corrections. Coefficient of repeatability of intra- and inter-observer variability was 8.76 ms and 5.64 ms respectively and coefficient of variation was 1.77% and 2.76% respectively. T_pT_e increased with RR in stallions.ConclusionsThe QT interval in Standardbred horses shortens with decreasing RR interval (increasing HR) as in humans, but in a markedly different order as it clearly follows a piecewise linear model. The equine QT interval can be measured easily and there is small intra- and inter-observer variability. This model of the equine QT interval provides clinicians with a method that could support a diagnosis of repolarization disturbances in horses.     

Third degree atrioventricular block following non-penetrating chest trauma in a dog

A two-year-old mixed breed dog was referred to the University of Florida Veterinary Medical Teaching Hospital for the management of post traumatic ventricular arrhythmias. Electrocardiography revealed third degree atrioventricular (AV) block. An echocardiogram demonstrated an echogenic, pedunculated mass arising from the caudoventral aspect of the atrial septum. The mass was believed to represent a haematoma or a thrombus associated with trauma to this region of the atrial septum. The patient was managed conservatively; third degree AV block was still pre- sent five days after trauma. The owner of the dog refused specific therapy of the arrhythmia. The patient was discharged and, unfortunately, lost to follow-up. Third degree AV block has not previously been reported following accidental, blunt thoracic trauma in the dog.     

QT instability,an indicator of augmented arrhythmogenesis,increases with the progression of myxomatous mitral valve disease in dogs

Objectives

To investigate QT instability in dogs with myxomatous mitral valve disease (MMVD) and to determine if this is associated with arrhythmogenesis.

Antimicrobial drug use in veterinary medicine

Recognizing the importance of antimicrobial resistance and the need for veterinarians to aid in efforts for maintaining the usefulness of antimicrobial drugs in animals and humans, the Board of Regents of the American College of Veterinary Internal Medicine charged a special committee with responsibility for drafting this position statement regarding antimicrobial drug use in veterinary medicine. The Committee believes that veterinarians are obligated to balance the well-being of animals under their care with the protection of other animals and public health. Therefore, if an animal's medical condition can be reasonably expected to improve as a result of treatment with antimicrobial drugs, and the animal is under a veterinarian's care with an appropriate veterinarian-client-patient relationship, veterinarians have an obligation to offer antimicrobial treatment as a therapeutic option. Veterinarians also have an obligation to actively promote disease prevention efforts, to treat as conservatively as possible, and to explain the potential consequences associated with antimicrobial treatment to animal owners and managers, including the possibility of promoting selection of resistant bacteria. However, the consequences of losing usefulness of an antimicrobial drug that is used as a last resort in humans or animals with resistant bacterial infections might be unacceptable from a public or population health perspective. Veterinarians could therefore face the difficult choice of treating animals with a drug that is less likely to be successful, possibly resulting in prolonged or exacerbated morbidity, to protect the good of society. The Committee recommends that voluntary actions be taken by the veterinary profession to promote conservative use of antimicrobial drugs to minimize the potential adverse effects on animal or human health. The veterinary profession must work to educate all veterinarians about issues related to conservative antimicrobial drug use and antimicrobial resistance so that each individual is better able to balance ethical obligations regarding the perceived benefit to their patients versus the perceived risk to public health. Specific means by which the veterinary profession can promote stewardship of this valuable resource are presented and discussed in this document.     

D0870, an antifungal agent, induces reverse use-dependent QT prolongation in dogs

We previously reported that D0870 induced QT prolongation and sudden death due to torsades de pointes (TdP) in dogs and that catecholamines played an important part in the development of the sudden death. In the present study, we analyzed in detail the ambulatory electrocardiographic recordings obtained from the just-mentioned study to elucidate the mechanism of the onset of TdPs and conducted an in vitro study using isolated canine Purkinje fibers to assess the effect of D0870 on repolarization. The hearts with TdPs observed before the sudden death showed a higher sinus rate for 5 and 10 sec before the onset, a shorter coupling interval, and a higher ventricular tachycardia rate compared with those having the non-sustained TdPs. These findings suggest that D0870-induced fatal TdPs may be provoked by a triggered activity developed from delayed after depolarizations. In contrast, as the pause-dependent, non-sustained TdPs in bradycardia showed a typical "short-long-short" sequence, they may be developed from early afterdepolarization . Moreover, the results of the in vitro study supported our contention that D0870 induced QT prolongation in a reverse use-dependent manner in vivo and suggested that it may inhibit not only rapidly activating delayed rectifier potassium current (Ik(r)) but also L-type Ca current (I(ca-L)).     

Generalised peripheral oedema associated with amlodipine therapy in two dogs

This report details two cases of adverse drug reactions to amlodipine. The first case presented with diffuse peripheral oedema and a history of amlodipine therapy. Haematology, clinical chemistry, endocrine testing, thoracic, abdominal and cardiac imaging revealed no cause for oedema. Amlodipine therapy was discontinued and oedema diminished markedly within 72 hours. The second case presented for bilateral retinal detachments secondary to systemic hypertension. Haematology, clinical chemistry, thoracic and abdominal imaging were unremarkable and amlodipine therapy was begun. Within 72 hours, diffuse peripheral oedema developed that was unresponsive to therapy and the dog was euthanised. Veterinarians should be aware of the potential serious adverse events associated with commonly used drugs; severe, diffuse oedema is a possible adverse drug event in dogs treated with amlodipine .     

Evaluation of QT interval prolongation in dogs with heart failure

Comparison of the QT interval and corrected QT interval values that were calculated by the methods of Bazett (QTc1) and Fridericia (QTc2) were made between dogs with or without cardiac diseases to determine the influence of the QT interval on canine heart failure. Upon comparison of the measured values on ECG between the cardiac disease and non-cardiac disease groups, it was observed that the heart rate(HR) was significantly higher in the cardiac disease group than in the non-cardiac disease group, although the QT interval was similar in the two groups. The QTc1 and QTc2 were significantly longer in the cardiac disease group than in the non-cardiac disease group. With the progression of the New York Heart Association Class, the HR tended to increase. The QTc1 and QTc2 became significantly prolonged with the progression of heart failure. Nevertheless, because Bazett's correction formula is known to overcorrect when the HR is high, it was considered that the QTc1 was actually overcorrected by high HR with the progression of heart failure. The QTc2, on the other hand, was only slightly influenced by HR, suggesting that the prolongation was due to the progression of heart failure. These results suggest that the prolongation of QTc2 in cardiac disease reflects the substantial prolongation of the QT interval without the influence of HR. It is suggested that the QTc2 could be a useful parameter for assessing the degree of heart failure in dogs with cardiac disease.     

Ventricular Tachyarrhythmias in 106 Cats: Associated Structural Cardiac Disorders

Background: Ventricular tachyarrhythmias occur in association with cardiac and extracardiac disorders in many species of animals, but information identifying concurrent disorders in cats with such arrhythmias is scarce. Methods: We investigated coexisting diseases by retrospectively evaluating medical records of cats with ventricular tachyarrhythmias seen during a 51‐month period at 1 institution. For comparative purposes, we evaluated records of dogs with similar arrhythmias during the same time period. All cats and dogs had premature ventricular complexes, accelerated idioventricular rhythm, ventricular tachycardia, or some combination of these arrhythmias, and all had undergone echocardiography during the same visit that led to the diagnosis of ventricular tachyarrhythmia. Results and Conclusions: Most (102/106; 96%) cats had at least 1 echocardiographically apparent abnormality concurrent with ventricular tachyarrhythmias. Ventricular tachyarrhythmias in cats were most commonly associated with myocardial disease (eg, left ventricular concentric hypertrophy [n = 66], restrictive or unclassified cardiomyopathy [n = 17], and dilated cardiomyopathy [n = 6]). When comparing dogs and cats that had ventricular tachyarrhythmias and were diagnosed on the same clinical service of the same institution, an echocardiographically apparent cardiac lesion was seen more often in cats (102/106, 96%) than in dogs (95/138, 69%) (P < .001).     

Positive Coombs' test results in two dogs treated with amiodarone

Effects of amiodarone, an antiarrhythmic drug that is effective in suppressing severe ventricular arrhythmias that are refractory to other antiarrhythmic drugs, were evaluated in 2 dogs with cardiac disease. One dog was a Doberman Pinscher with cardiomyopathy that developed severe thrombocytopenia after receiving amiodarone for 7 months. The second was a Giant Schnauzer with acquired mitral valve degeneration that developed regenerative anemia after receiving amiodarone for 5 months. Results of direct Coombs' tests were positive in both dogs. Adverse effects of amiodarone are numerous; in dogs, the most common adverse effects are anorexia and hepatotoxicosis. Frequent CBC and serum biochemical analyses should be performed when amiodarone is administered with the intent of continuing the drug indefinitely.     

Pain management in ruminants.

Based on the available literature, the most important tool available in modern veterinary medicine is preemptive analgesia. Veterinarians must capture "opportunities" to prevent the onset of pain, prevent noxious stimuli or their perception, and limit the pain-stress-distress cascade that results in altered behavior and deviation from physiologic norms. Rational treatment of pain requires an appreciation of its consequences, a fundamental understanding of the mechanisms that are responsible for its production,and a practical appreciation of the analgesic drugs that are available. The goal of pain treatment should be to restore normal (physiologic) pain responses and to eliminate pathologic pain processes. In this context, pain therapy should be directed at the multiple mechanisms (multimodal therapy)responsible for its production, and analgesic therapies should be instituted before (preemptive therapy) pain is initiated (eg, surgery) whenever possible.     

Selection of antibiotics for meticillin‐resistant Staphylococcus pseudintermedius: time to revisit some old drugs?

The aim of this review is to consider systemic therapy options for meticillin-resistant Staphylococcus pseudintermedius (MRSP). Infections caused by MRSP in small animals--particularly dogs--have been frustrating veterinarians in recent years. After a susceptibility test is performed, veterinarians are left to select from drugs that have not been frequently encountered on a susceptibility report. Some of these are old drugs that have not been used regularly by veterinary dermatologists. As MRSP is, by definition, resistant to all β-lactam antibiotics, including cephalosporins, penicillins and amoxicillin-clavulanate combinations, the β-lactam drugs are not an option for systemic treatment. As most MRSPs are multidrug resistant, familiar drugs, such as trimethoprim-sulfonamides, fluoroquinolones, macrolides and lincosamides (clindamycin), are also not usually an option for treatment. Therefore, veterinarians are left with drugs such as rifampicin, chloramphenicol, tetracyclines, aminoglycosides and vancomycin to choose from on the basis of an in vitro susceptibility test. Some of these drugs were originally approved over 50 years ago and may not be familiar to some veterinarians. Each of these drugs possesses unique properties and has particular advantages and disadvantages. Veterinarians should be particularly aware of the adverse effects, limitations and precautions when using these drugs. New drugs also have been developed for meticillin-resistant Staphylococcus aureus in humans. These include linezolid, ceftaroline, daptomycin and tigecycline. Although these drugs are very infrequently--if ever--considered for veterinary use, the properties of these drugs should also be known to veterinary dermatologists.