Reduction of intrinsic contractile function of the left ventricle by taurine deficiency in cats.
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Biomedical subjects
Publications and source records attributed to P M Hogan.
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A 1-year-old male Cairn Terrier was evaluated for chronic coughing that was aggravated by eating or drinking. Radiography revealed an esophageal diverticulum, regional megaesophagus, and focal interstitial densities in the right caudal and middle lung lobes. Using fluoroscopy and contrast radiography, contrast material was seen to accumulate in the diverticulum and to reflux into the right middle, caudal, and accessory bronchi. Radiographic diagnosis was bronchoesophageal fistula. Via right eighth intercostal space thoracotomy, the abnormal connection between esophagus and caudal lobe of the right lung was identified, the lobe was resected, and the esophagus was closed. Histologic examination of the connecting tissue revealed a lining of stratified epithelium, with the superficial layer being predominantly ciliated columnar epithelium. Several findings led to the conclusion that the fistula was a congenital lesion, arising from aberrant formation of the respiratory tract from the embryologic digestive tract. Histologic examination revealed smooth muscle and lack of inflammation in tissue surrounding the fistula, which are criteria for identifying congenital bronchoesophageal fistula in human patients. The dog was young and did not have a history of esophageal foreign bodies. Postoperative complications were not encountered, and 9 months later, the dog was reported to be eating dry dog food without coughing. Congenital and acquired bronchoesophageal fistulas in dogs are reported infrequently. Furthermore, 2 of 12 previously reported bronchoesophageal fistulas in dogs, one of which was considered congenital, developed in Cairn Terriers.
Isovolumic left ventricular (LV) preparations were used to assess myocardial failure associated with dietary taurine deficiency in cats. Adult female cats (n = 12) were fed a purified diet devoid of taurine for 6-8 mo. Six of the cats received 1,000 mg of crystalline taurine orally once daily. The remaining six cats were not provided taurine replacement. Compared with control preparations, hearts isolated from taurine-deficient cats generated significantly lower values for developed LV systolic pressure (107 +/- 6 vs. 66 +/- 15 mmHg; P less than 0.05), maximal rate of LV pressure rise (+dP/dtmax; 1,103 +/- 38 vs. 718 +/- 172 mmHg/s; P less than 0.05), and fall (-dP/dtmax; 930 +/- 46 vs. 587 +/- 129 mmHg/s; P less than 0.05). LV function curves generated by hearts from taurine-deficient cats were shifted downward and to the right of control curves, demonstrating inotropic depression. In addition, end-diastolic pressure-volume (compliance) relationships in hearts from taurine-deficient cats were shifted downward and to the right of controls in the direction of increased chamber compliance or distensibility. Ten millimolar taurine significantly improved inotropic indexes only in hearts from taurine-deficient cats but failed to affect diastolic compliance. Myocardial contractile dysfunction and LV chamber dilatation in hearts from taurine-deficient cats verify a causal association between dietary deficiency of this amino acid and dilated cardiomyopathy in this species.
A 10-year-old Toy Poodle was admitted for evaluation of a chronic cough caused by a cranial mediastinal mass. The mass was diagnosed, by needle biopsy, as a thymoma. Detection of serum acetylcholine receptor antibodies suggested that the dog had subclinical myasthenia gravis. The dog underwent orthovoltage radiation treatment, which resulted in an approximate 60% reduction in tumor mass and freedom from clinical signs for 6 months. Concurrent use of prednisolone may have been associated with disappearance of the acetylcholine receptor antibodies.
From 1974 through 1984, the Orthopedic Foundation for Animals evaluated 143,218 radiographic submissions representing 151 breeds of dogs. All breeds from which there were 35 or more evaluations had some frequency of dysplasia. Seventy breeds, each with over 100 submissions, were tabulated and ranked according to frequency of hip dysplasia. Frequency of dysplasia varied from 0.6% in the Borzoi to 46.9% in the Saint Bernard. These data were compared with data obtained earlier (1966 to 1973) on evaluations in 38 breeds for changes in frequency. There was significant (P less than 0.05) reduction in frequency of dysplasia in 27 breeds, a significant (P less than 0.05) increase in frequency in only 1 breed (German Shorthaired Pointer), and no significant change in frequency in 10 breeds. The median significant decrease was 22.4%, and the range was from 3.1% in the Chesapeake Bay Retriever to 48.7% in the Keeshond. The reduction in frequency of hip dysplasia demonstrated the value of a control program. There were 5 breeds with a significant (P less than 0.05) decrease in frequency of dysplasia that had over 5,000 evaluations from 1974 to 1984. The decreases in frequency were independent of changes in American Kennel Club registrations for these breeds (a dramatic decline in registrations for the German Shepherd Dog and Old English Sheepdog, and a dramatic increase for the Rottweiler, Golden Retriever, and Labrador Retriever). Frequency regressed linearly in the German Shepherd Dog and Old English Sheepdog, but regressed nonlinearly in the other 3 breeds. The percentage reduction in frequency from the base frequency (1966 to 1973) for these breeds was 17.5% for the German Shepherd Dog, 23.1% for the Old English Sheepdog, 9.1% for the Rottweiler, 10.1% for the Golden Retriever, and 6.8% for the Labrador Retriever.
Studies were performed on canine cardiac Purkinje fibers to evaluate the effects of acidosis and bicarbonate (HCO3) on action potential repolarization. Extracellular pH (pHe) was reduced from 7.4 to 6.8 by increasing carbon dioxide (CO2) concentration from 4 to 15% in a HCO3-buffered solution or by NaOH titration in a Hepes-buffered solution. Both types of acidosis produced a slowing of the rate of terminal repolarization (i.e., period of repolarization starting at about -60 mV and ending at the maximum diastolic potential) with an attendant increase in action potential duration of 10--20 ms. This was accompanied by a reduction in the maximum diastolic potential of 2--8 mV. In contrast, if the same pH change was made by keeping CO2 concentration constant and lowering extracellular HCO3 from 23.7 to 6.0 mM, in addition to the slowing of terminal repolarization, the plateau was markedly prolonged resulting in an additional 50- to 80-ms increase in action potential duration. If pHe was held constant at 7.4 and HCO3 reduced from 23.7 mM to 0 (Hepes-buffered solution), the changes in repolarization were nearly identical to those seen in 6.0 mM HCO3 except that terminal repolarization was unchanged. This response was unaltered by doubling the concentration of Hepes. Reducing HCO3 to 12.0 mM produced changes in repolarization of about one-half the magnitude of those in 6.0 mM HCO3. These findings suggest that in Purkinje fibers, HCO3 either acts as a current that slows repolarization or modulates the ionic currents responsible for repolarization.
Microelectrode studies were undertaken to determine the cellular bases for hydrostatic pressure effects on impulse propagation and refractoriness in cardiac muscle. Canine Purkinje fibers, at 37 degrees C, were exposed to increases in hydrostatic pressure to 150 ATA. At 150 ATA membrane excitability was depressed and the maximum upstroke velocity (Vmax) of the action potential was reduced by 10%. Furthermore, the curve relating Vmax to takeoff potential (membrane responsiveness relation) shifted downward and to the right with the half inactivation voltage shifting in the hyperpolarizing direction by about 4 mV. Decreases in excitability and responsiveness occurred concomitantly with pressure-induced decreases in impulse conduction. Action potential duration (APD) increased significantly at 150 ATA. APD measured at -20 mV, -60 mV, and at maximum repolarization averaged 20.7, 15.5, and 13.5% longer than their respective 1-ATA values. The combined effects of increased APD and depressed responsiveness account for increased tissue refractoriness. The implications of the findings with regard to the arrhythmogenic nature of high hydrostatic pressure are discussed.
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The effects of hydrostatic pressure on cardiac conduction and excitability were studied in 39 rabbit right atrial preparations. Increases in pressure significantly increased atrial conduction time, i.e., 41% at 150 ATA. Excitability, determined from strength-duration (S-D) curves, was depressed by pressure. The slope constant of the S-D curve increased 64% at 150 ATA. Rheobase and the X-asymptote were not affected significantly. The depression of excitability partially accounted for the slowed conduction. Frequency stress and pressure had an additive effect to produce even greater decreases in excitability and increases in conduction time. Atrial refractoriness to premature stimuli also increased as a function of pressure. Nitrous oxide (2.5 ATA) partially reversed the effects of 150 ATA of pressure on conduction time and excitability. The results suggest that pressure acts by altering basic functional components of the myocardial cell membrane. Some of these changes, particularly when combined with frequency stress, i.e., rapid heart rate, may pose a serious threat to humans exposed to hyperbaric environments.
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To examine intrafamily spread of respiratory syncytial virus infections and their associated illnesses, 36 families with 188 members were studied during an outbreak of such infections. Nurses visited every three to four days to obtain specimens for viral isolation and interview household members. The virus infected 44.4 per cent of families, and 21.9 per cent of all members. All age groups had appreciable attack rates (with a range of 16.8 per cent in adults to 29.4 per cent in infants). In infected families, 45.9 per cent of members became infected, including 10 of 16 infants. Secondary attack rate for all ages was 27 per cent, and that for infants 45.4 per cent. An infant's older sibling appeared most likely to introduce the virus into the family. Associated acute respiratory illnesses occurred in 94.9 per cent of cases, and appeared more severe than those not associated with respiratory syncytial virus. When the virus was introduced into a family the high attack rate produced an illness of age-related severity.
Studies were performed on canine cardiac Purkinje fibers to evaluate the effects of manganese on membrane electrogenesis. The results indicate that manganese has a calciumlike effect on the excitatory sodium current and inhibitory effects on potassium conductance and slow inward current. The calciumlike effect of manganese on sodium current was reflected through a leftward (toward less negative potentials) and downward shift in the curve relating maximum upstroke velocity to membrane potential. The inhibitory action of manganese on potassium conductance was suggested by the following observations. (1) Manganese caused an initial increase in action potential duration largely due to a lengthening of the plateau and decreases in the rates of phase 3 and terminal repolarization. (2) Manganese increased the rate of diastolic depolarization. (3) Manganes blocked the initial fall in maximum diastolic potential accompanying rapid stimulation. (4) Manganese in high concentrations caused generalized depolarization which was reversed by rapid stimulation and by increased extracellular potassium concentrations. The action of manganese to block slow inward current was indicated by the eventual shortening of the plateau and by the elimination of responses initiated from low levels of membrane potential (less than minus 55 mv). In addition to these effects, manganese also reduced membrane excitability, eliminated arrhythmic beats occurring during low-frequency electrical stimulation, and caused membrane hyperpolarization which was blocked by tetrodotoxin.
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A technique for reconstruction of the thoracic esophagus was evaluated in 13 dogs. A 9 x 10 cm section of transversus abdominis muscle was harvested, fashioned into a tubular graft, and vascularized via the greater omentum. The vascularized tube was advanced into the caudal thorax through the diaphragm at a second surgery 20 to 44 days after harvesting the section of the transversus abdominis muscle. A 5 cm section of caudal thoracic esophagus was replaced with the vascular tubular graft. One dog died because of incarceration of the intestine within the tube and two dogs were euthanized because of infected tubes. One dog died due to an anesthetic complication, one dog had a diaphragmatic hernia and died, and one dog died from pyothorax. Leakage of luminal contents at the anastomoses did not occur in any dog. Seven dogs survived both surgeries but showed deglutitory difficulty 6 days postoperatively due to the grafted esophageal segments becoming severely strictured in each case. Angiography demonstrated vascularization of the full thickness of the graft in each of the seven dogs. An unacceptably high incidence of infection and stricture formation made this technique unsuitable for clinical use.