Short-term inhalation of particulate transition metals has little effect on the electrocardiograms of dogs having preexisting cardiac abnormalities.

There is growing epidemiological evidence for statistical associations between increases in air pollution, especially particulate matter, and increases in cardiovascular morbidity and mortality. Laboratory studies have shown that transition metals contribute strongly to the effects of high lung doses of model particles on changes in the electrocardiograms of animals. The present study evaluated the effects of short-term inhalation exposure to respirable particles of specific oxide and sulfate forms of transition metals on heart rate and the electrocardiogram of old dogs having preexisting cardiac abnormalities. Conscious beagle dogs were exposed by oral inhalation for 3 h on each of 3 successive days to aerosols of manganese, nickel, vanadium, iron, and copper oxides, and nickel and vanadium sulfates as single compounds at concentrations of 0.05 mg/m(3). Electrocardiograms were recorded and evaluated for exposure-related changes in heart rate, heart rate variability, and abnormalities of waveforms. Although the electrocardiograms of this population of dogs having potential age and cardiovascular susceptibility factors reflected their underlying clinical abnormalities, no significant effect of exposure to the transition metal aerosols was observed.

Effect of inhaled residual oil fly ash on the electrocardiogram of dogs.

Epidemiology studies have found associations between increases in air pollutants and increases in morbidity and mortality from cardiovascular disease. The 1995 finding by Godleski et al. at Harvard that inhalation exposures of dogs to high concentrations of residual oil fly ash (ROFA) caused changes in the ST segment and T waves in the electrocardiogram (ECG) suggested a potential mechanism, and also suggested that inhaled metals might contribute to the effect. We conducted the present study to establish a baseline correspondence to the Godleski et al. findings in preparation for studies of the cardiac effects of specific particle-borne metals. The ROFA used in this study consisted of 45% carbon and 15.5% transition metals by mass. In vitro assays using cultured A549 cells and rat alveolar macrophages demonstrated that the ROFA was biologically active but was not highly cytotoxic. Four 10.5-yr-old beagles were exposed by oral inhalation to 3 mg/m3 of aerosolized ROFA for 3 h/day on 3 consecutive days. During the exposures, ECGs were continuously recorded from leads I, II, III, and V4. ECG data were also collected during three control exposures to clean air, during one of which changes were induced using drugs as a positive control. The ROFA exposures caused no consistent changes in the amplitude of the ST segment, the form or amplitude of the T wave, or arrhythmias. The data suggested a slight slowing of heart rate during exposure. Whether the difference between the present and previous findings resulted from differences in the composition of the two batches of ROFA or differences in methodology could not be determined by the study. This study did not address the cardiac effects of ROFA in subjects having preexisting cardiac susceptibility factors, nor was it a rigorous evaluation of effects on the frequency distribution of heart rate. Our results indicate that healthy dogs can inhale high concentrations of ROFA without changes in cardiac electrophysiology, which are detectable by clinical evaluations.

P-wave duration in a clinically normal hound population.

Electrocardiogram (ECG) analysis is a common noninvasive technique used for diagnosis of cardiac disease in the clinical and research branches of veterinary medicine. Accurate analysis of P-wave duration, amplitude, and morphology is crucial to identification of morphologic and functional changes of the atria. The published accepted maximal normal value for P-wave duration in the dog is < or = 40 milliseconds. We looked at P-wave duration in ECG obtained as part of routine quarantine health screening over a period of 1 year in 364 clinically normal hounds weighing 13 to 35 kg. The dogs were neither anesthetized nor sedated and were placed in standard position. P-wave duration was classically determined from the lead-II recording. Mean P-wave duration for all dogs (44.9 +/- 6.1 milliseconds) was greater than published accepted normal values for the dog. There was a significant difference in mean P-wave duration by body weight (P < 0.001); dogs weighing > or = 20 kg had longer mean P-wave durations than dogs weighing < 20 kg (45.3 and 41.6 milliseconds respectively). There were also significant differences in mean P-wave duration by sex (P < 0.01), with a greater mean duration for females (45.4 milliseconds) than for males (43.8 milliseconds). All other ECG parameters were within published accepted normal values. A P-wave of prolonged duration leads to a diagnosis of abnormalities in cardiac morphology and/or function. Published accepted normal values for P-wave duration, at least for a clinically normal hound population, appear to be shorter than the true normal values. An error in published accepted normal standards may lead to overdiagnosis of cardiac abnormalities, as well as to erroneous results in cardiovascular studies. Therefore we recommend that the standard for P-wave duration be increased above the currently accepted standard of < or = 40 milliseconds.

Cardiopulmonary disease in the geriatric dog and cat.

The incidence of cardiopulmonary disease increases with age. Degenerative valvular disease, chronic obstructive pulmonary disease, and arrhythmias are common in the geriatric dog. Chronic bronchial disease, pulmonary neoplasia, and arrhythmias occur in the geriatric cat. Systemic diseases in both species often show cardiopulmonary manifestations. Medical management to treat the underlying disease and to control clinical signs is complicated by altered absorption, metabolism, and elimination of drugs.

Clinical and pathologic findings in dogs with atherosclerosis: 21 cases (1970-1983).

Atherosclerosis was diagnosed on necropsy in 21 dogs in a 14-year period. Nine dogs died and 12 were euthanatized because of complications associated with the disease. The mean age was 8.5 +/- 0.5 years; 18 dogs were male. Three breeds (Miniature Schnauzer, Doberman Pinscher, and Labrador Retriever) had a higher prevalence of the disease than other breeds in the canine necropsy population of The Animal Medical Center. Most common clinical signs were lethargy, anorexia, weakness, dyspnea, collapse, and vomiting. Hypercholesterolemia, lipidemia, and hypothyroidism were common in affected dogs tested, and protein electrophoresis revealed high values for alpha 2 and beta fractions in all dogs tested. Electrocardiography indicated conduction abnormalities and myocardial infarction in 3 of 7 dogs. Necropsy revealed that affected arteries (including coronary, myocardial, renal, carotid, thyroidal, intestinal, pancreatic, splenic, gastric, prostatic, cerebral, and mesenteric) were yellow-white, thick and nodular, and had narrow lumens. Myocardial fibrosis and infarction also were observed in the myocardium. Histologically, affected arterial walls contained foamy cells or vacuoles, cystic spaces, mineralized material, debris with or without eroded intima, and degenerated muscle cells.

Ventricular preexcitation in seven dogs and nine cats.

Ventricular preexcitation was diagnosed in 6 dogs and 7 cats examined because of weakness, syncope, or congestive heart failure, and as an incidental finding in 1 dog and 2 cats. Reciprocating tachycardias were documented in 8 of the cases. Six of the cats had a pathologic diagnosis of primary cardiomyopathy. Two of the dogs had an associated congenital heart defect. Reciprocating tachycardias were controlled in 4 cases with digoxin, in 2 cases with propranolol, and in 1 case with quinidine. Conduction through the accessory pathway was altered by quinidine (2 cases), digoxin, and propranolol (1 case each), resulting in a lengthened P-R interval and more normal QRS complex configuration.

Mechanisms for atrial arrhythmias associated with cardiomyopathy: a study of feline hearts with primary myocardial disease.

The cellular electrophysiologic and structural characteristics of arrhythmic and non-arrhythmic atria isolated from feline hearts with spontaneously occurring cardiomyopathy were studied. The animals were divided into three groups according to the degree of left atrial enlargement: mild (group I), moderate (group II), and severe (group III). The right atria were of relatively normal size. Microelectrode recordings showed that inexcitable cells were present in both left and right atria of all groups but were most numerous in the left atria of group III animals. Most inexcitable cells had low resting membrane potentials. There was also a significant reduction in resting membrane potentials, maximum rate of phase 0 depolarization, and action potential amplitude of excitable cells in left atria of animals in groups II and III, whereas action potentials of excitable cells in the right atria were normal. Acetylcholine or norepinephrine often restored excitability to cells that originally did not generate action potentials. Norepinephrine also caused slow-response action potentials as well as abnormal automaticity and triggered activity due to delayed afterpotentials. The diseased atria showed marked structural abnormalities, which were most pronounced in group III cats, including large amounts of interstitial fibrosis, cellular hypertrophy and degeneration, and thickened basement membranes. Therefore electrophysiologic abnormalities and concurrent changes in cell structure may be involved in the genesis of atrial tachyarrhythmias caused by cardiomyopathy.

Effects of left atrial enlargement on atrial transmembrane potentials and structure in dogs with mitral valve fibrosis.

The effects of left atrial enlargement on atrial cell electrophysiology and structure were studied in dogs with mitral valve fibrosis. Thirteen dogs (Groups I) had left atrial enlargement and intermittent atrial arrhythmias; 10 dogs (Group II) had left atrial enlargement and chronic atrial fibrillation. The resting and action potentials of cells in isolated preparations from the enlarged left atrium were found not to differ from those in the nonenlarged right atrium or in the atrium of control dogs. The resting and action potentials of cells in Group II atria did not differ significantly from those in Group I atria. Some cells (15 percent of the total studied) in the atria of dogs in Groups I and II were inexcitable, but either superfusion with acetylcholine or norepinephrine restored excitability. The structural studies showed that the left atrium of the dogs in Groups I and II had a reduced number of muscle cell layers spanning the wall with an unusually large amount of connective tissue between greatly hypertrophied cells. Very few degenerating cells were seen. Dramatic abnormalities of cell electrophysiology may not be involved in the genesis of arrhythmias in the enlarged canine atrium, and the altered morphologic features of the atrium in these dogs may be important in the genesis of persistent atrial arrhythmias.

Safety assessment of a new anticancer compound, mitoxantrone, in beagle dogs: comparison with doxorubicin. I. Clinical observations.

Twenty-four adult beagle dogs were divided into four groups of three males and three females and received iv infusions of doxorubicin (36.05 mg/m2), mitoxantrone (2.58 or 5.15 mg/m2), or the vehicle (0.9% normal saline). All animals were given a single dose once every 3 weeks. The duration of the study was 30 weeks. Animals were observed for toxicologic and cardiotoxic signs. The methods used to evaluate the cardiotoxic potential of both mitoxantrone and doxorubicin were sequential endomyocardial biopsies, ECGs, blood pressure, and serum levels of the cardiospecific isoenzyme CPK-MB (MB band of CPK). Animals given mitoxantrone had signs of gastrointestinal toxicity and fluctuating decreases in wbc counts. Animals given doxorubicin had signs of gastrointestinal toxicity and cardiotoxicity, as well as alopecia, fluctuating decreases in wbc counts, and diffuse erythema. All three male animals given doxorubicin died during the study from apparent congestive heart failure. All dogs treated with doxorubicin had positive CPK isoenzyme elevation, ECG changes, or progressive cardiomyopathy prior to administration of the last dose. None of these signs was observed in dogs treated with mitoxantrone. One male dog given mitoxantrone died during the course of the study.