Klapcinska, B., S. Jagsz, E. Sadowska-Krepa, J. Gorski, K. Kempa and J. Langfort (2008). "Effects of castration and testosterone replacement on the antioxidant defense system in rat left ventricle". J. Physiol. Sci. 58(3): 173-177.
There is strong evidence that oxidative stress plays a key role in the pathophysiol. of several cardiovascular diseases. On the other hand, the presence of specific receptors for androgens and estrogens in the myocardium implies that sex hormones play a physiol. role in cardiac function, myocardial injury, and the regulation of the redox state in the heart. The present study was designed to det. whether castration and androgen replacement result in changes in the capacity of the antioxidant defense system in the left ventricle (LV) of adult male rats. To assess this, the activities of antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPX], catalase [CAT], and glutathione reductase [GR]), concns. of nonenzymic antioxidants (reduced glutathione [GSH] and alpha - and gamma -tocopherols), and oxidative stress biomarkers (tissue sulfhydryl groups, protein nitrotyrosine levels, and lipid peroxidn.) were measured in castrated animals (CAS), castrates replaced with testosterone (CAS + T), and sham-operated controls (Sham). Testosterone was not detectable in serum from gonadectomized rats. The results indicate that castration significantly and neg. affected the antioxidant status of rat LV, as evidenced by a significant decline in activities of all antioxidant enzymes, by a tendency toward lower levels of GSH and protein thiol groups, and by enhanced lipid peroxidn. and higher nitrotyrosine concns. in left ventricular tissue. Increases in LV tissue concns. of alpha - and gamma -tocopherols seem to be a compensatory response to enhanced oxidative stress induced by gonadectomy. The reestablishment of physiol. serum testosterone level by androgen replacement resulted in a tendency toward a further decrease in the antioxidant defense status in the LV tissue. [on SciFinder (R)]
MacDonald Kristin, A., D. Kittleson Mark, H. Kass Philip and M. Meurs Kathryn (2007). "Tissue Doppler imaging in Maine Coon cats with a mutation of myosin binding protein C with or without hypertrophy". J Vet Intern Med FIELD Full Journal Title:Journal of veterinary internal medicine / American College of Veterinary Internal Medicine 21(2): 232-7.
BACKGROUND: The cardiac myosin binding protein C gene is mutated in Maine Coon (MC) cats with familial hypertrophic cardiomyopathy. HYPOTHESES: Early diastolic mitral annular velocity is incrementally reduced from normal cats to MC cats with only an abnormal genotype to MC cats with abnormal genotype and hypertrophy. ANIMALS: Group 1 consisted of 6 normal domestic shorthair cats, group 2 of 6 MC cats with abnormal genotype but no hypertrophy, and group 3 of 15 MC cats with hypertrophy and abnormal genotype. METHODS: The genotype and echocardiographic phenotype of cats were determined, and the cats were divided into the 3 groups. Tissue Doppler imaging (TDI) of the lateral mitral annulus from the left apical 4-chamber view was performed. Five nonconsecutive measurements of early diastolic mitral annular velocity (EM) or summated early and late diastolic velocity (EAsum) and heart rate were averaged. RESULTS: There was an ordered reduction in Em-EAsum as group number increased (group 1, range 9.7-14.7 cm/s; group 2, range 7.5-13.2 cm/s; group 3, range 4.5-14.1 cm/s; P = .001). Using the lower prediction limit for normal Em-EAsum, the proportion of cats with normal Em-EAsum decreased as the group number increased (P = .001). However, Em-EAsum was reduced in only 3 of 6 cats in group 2. CONCLUSION: The incremental reduction of Em-EAsum as group severity increased indicates that diastolic dysfunction is an early abnormality that occurs before hypertrophy development. TDI measurement of Em or EAsum of the lateral mitral annulus is an insensitive screening test for identification of phenotypically normal, genotypically affected cats. [on SciFinder (R)]
Chetboul, V., S. Blot, C. Sampedrano Carolina, J.-L. Thibaud, N. Granger, R. Tissier, P. Bruneval, F. Gaschen, V. Gouni, P. Nicolle Audrey and J.-L. Pouchelon (2006). "Tissue Doppler imaging for detection of radial and longitudinal myocardial dysfunction in a family of cats affected by dystrophin-deficient hypertrophic muscular dystrophy". J Vet Intern Med FIELD Full Journal Title:Journal of veterinary internal medicine / American College of Veterinary Internal Medicine 20(3): 640-7.
Diagnosis of feline hypertrophic cardiomyopathy currently is based on the presence of myocardial hypertrophy detected using conventional echocardiography. The accuracy of tissue Doppler imaging (TDI) for earlier detection of the disease has never been described. The objective of this sudy was to quantify left ventricular free wall (LVFW) velocities in cats with hypertrophic muscular dystrophy (HFMD) during preclinical cardiomyopathy using TDI. The study animals included 22 healthy controls and 7 cats belonging to a family of cats with HFMD (2 affected adult males, 2 heterozygous adult females, one 2.5-month-old affected male kitten, and 2 phenotypically normal female kittens from the same litter). All cats were examined via conventional echocardiography and 2-dimensional color TDI. No LVFW hypertrophy was detected in the 2 carriers or in the affected kitten when using conventional echocardiography and histologic examination, respectively. The LVFW also was normal for 1 affected male and at the upper limit of normal for the 2nd male. Conversely, LVFW dysfunction was detected in all affected and carrier cats with HFMD when using TDI. TDI consistently detects LVFW dysfunction in cats with HFMD despite the absence of myocardial hypertrophy. Therefore, TDI appears more sensitive than conventional echocardiography in detecting regional myocardial abnormalities. [on SciFinder (R)]
Hyun, C. and I.-C. Park (2006). "Congenital heart diseases in small animals: Part II. Potential genetic aetiologies based on human genetic studies". Vet. J. FIELD Full Journal Title:Veterinary Journal 171(2): 256-262.
A review. Comparative genetics provides veterinary researchers and clinicians with invaluable information for the understanding the possible genetic etiologies and the disease process in congenital heart defects (CHDs) of dogs and cats. Although, the demand on this type of research has increased in the veterinary field, to date no fundamental genetic studies have been reported in the veterinary literature. In this second part of a two-part review, the general features and pathogenesis of major CHDs in humans and small animals are discussed. In addn., the known genetic etiologies in human CHDs have been considered in parallel to CHDs in small animals. [on SciFinder (R)]
MacDonald Kristin, A., D. Kittleson Mark, F. Larson Richard, P. Kass, T. Klose and R. Wisner Erik (2006). "The effect of ramipril on left ventricular mass, myocardial fibrosis, diastolic function, and plasma neurohormones in Maine Coon cats with familial hypertrophic cardiomyopathy without heart failure". J Vet Intern Med FIELD Full Journal Title:Journal of veterinary internal medicine / American College of Veterinary Internal Medicine 20(5): 1093-105.
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common heart disease of cats, resulting in left ventricular (LV) hypertrophy, myocardial fibrosis, and diastolic dysfunction. HYPOTHESIS: Ramipril will reduce LV mass, improve diastolic function, and reduce myocardial fibrosis in cats with HCM without congestive heart failure (CHF). ANIMALS: This prospective, blinded, placebo-controlled study included 26 Maine Coon and Maine Coon cross-bred cats with familial HCM but without CHF. METHODS: Cats were matched for LV mass index (LVMI) and were randomized to receive ramipril (0.5 mg/kg) or placebo q24h for 1 year, with investigators blinded. Plasma brain natriuretic peptide (BNP) concentration, plasma aldosterone concentration, Doppler tissue imaging (DTI), and systolic blood pressure were measured at baseline and every 3 months for 1 year. Cardiac magnetic resonance imaging (cMRI) was performed to quantify LV mass and myocardial fibrosis by delayed enhancement (DE) cMRI at baseline and 6 and 12 months. Plasma angiotensin-converting enzyme (ACE) activity was measured on 16 cats 1 hour after PO administration. RESULTS: Plasma ACE activity was adequately suppressed (97%) in cats treated with ramipril. LV mass, LVMI, DTI, DE, blood pressure, plasma BNP, and plasma aldosterone were not different in cats treated with ramipril compared with placebo (P = .85, P = .94, P = .91, P = .89, P = .28, P = .18, and P = .25, respectively). CONCLUSION: Treatment of Maine Coon cats with HCM without CHF with ramipril did not change LV mass, improve diastolic function, alter DE, or alter plasma BNP or aldosterone concentrations in a relevant manner. [on SciFinder (R)]
Cesta, M. F., C. J. Baty, B. W. Keene, I. W. Smoak and D. E. Malarkey (2005). Pathology of end-stage remodeling in a family of cats with hypertrophic cardiomyopathy. United States, Laboratory of Experimental Pathology, National Institute of Environmental Sciences, Research Triangle Park, NC 27709, USA: 458-67.
End-stage hypertrophic cardiomyopathy (ES-HCM), affecting 5-10% of human hypertrophic cardiomyopathy (HCM) patients, is characterized by relative thinning of the ventricular walls and septum with dilation of the ventricular lumen, decreased fractional shortening, and progression to heart failure. C. J. Baty and others recently documented similar progressive changes to ES-HCM in a family of four cats through serial echocardiograms. At the time of heart failure, these cats exhibited changes similar to those exhibited by human ES-HCM patients. Our objectives were to describe the pathologic alterations associated with ES-HCM and investigate the pathogenesis in three of the four cats. Grossly, there was left atrial dilation with relative thinning of the interventricular septum (IVS) and left ventricular free wall (LVFW). The left atrium contained large thrombi in two of the three cats, and all three cats died following thromboembolization of the aortic bifurcation. Histologically, all three cats had subendocardial and myocardial fibrosis, predominantly of the IVS and LVFW, and one cat had acute, multifocal, myocardial infarcts with mononuclear inflammatory cell infiltrates. The pathogenesis of ES-HCM is uncertain, but theories implicate occlusion of the coronary blood flow by thickening of the coronary vessels, coronary vascular thromboembolism or coronary vessel spasm, apoptosis of myocytes, and myocardial hypertrophy beyond the ability of the vasculature to supply blood. Apoptosis assays did not reveal any apoptotic myocytes. Considering the hypercoagulative state of these cats, coronary vascular thromboembolism could be a major contributing factor. We cannot exclude apoptosis or coronary vessel spasm on the basis of the data presented. [on SciFinder (R)]
Meurs, K. M., X. Sanchez, R. M. David, N. E. Bowles, J. A. Towbin, P. J. Reiser, J. A. Kittleson, M. J. Munro, K. Dryburgh, K. A. MacDonald and M. D. Kittleson (2005). "A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy". Hum. Mol. Genet. FIELD Full Journal Title:Human Molecular Genetics 14(23): 3587-3593.
Hypertrophic cardiomyopathy (HCM) is one of the most common causes of sudden cardiac death in young adults and is a familial disease in at least 60% of cases. Causative mutations have been identified in several sarcomeric genes, including the myosin binding protein C (MYBPC3) gene. Although numerous causative mutations have been identified, the pathogenetic process is still poorly understood. A large animal model of familial HCM in the cat has been identified and may be used for addnl. study. As the first spontaneous large animal model of this familial disease, feline familial HCM provides a valuable model for investigators to evaluate pathophysiol. processes and therapeutic (pharmacol. or genetic) manipulations. The MYBPC3 gene was chosen as a candidate gene in this model after identifying a redn. in the protein in myocardium from affected cats in comparison to control cats (P<0.001). DNA sequencing was performed and sequence alterations were evaluated for evidence that they changed the amino acid produced, that the amino acid was conserved and that the protein structure was altered. We identified a single base pair change (G to C) in the feline MYBPC3 gene in affected cats that computationally alters the protein conformation of this gene and results in sarcomeric disorganization. We have identified a causative mutation in the feline MYBPC3 gene that results in the development of familial HCM. This is the first report of a spontaneous mutation causing HCM in a non-human species. It should provide a valuable model for evaluating pathophysiol. processes and therapeutic manipulations. [on SciFinder (R)]
Baty Catherine, J. (2004). "Feline hypertrophic cardiomyopathy: an update". Vet Clin North Am Small Anim Pract FIELD Full Journal Title:The Veterinary clinics of North America. Small animal practice 34(5): 1227-34.
HCM continues to be a challenging disease for veterinarians. Acute cases with ATE or CHF are difficult to manage, and we still lack the tools to advise owners well with regard to their pet's prognosis. Nevertheless, it appears that the historical view of HCM as a serious disease with a poor prognosis is now being adjusted to accommodate the apparently large numbers of asymptomatic cats with much longer survival times. Although there is evidence of a genetic cause of the disease in at least several families of cats, no disease-associated mutation has been found to be causative of feline HCM. Prophylactic treatment of asymptomatic or mildly affected cats continues to be empiric, but a randomized, double-blind, placebo-controlled, multicenter study on chronic therapy of symptomatic HCM cats should provide new guidance for practitioners managing these cases. Copyright 2004 Elsevier Inc. [on SciFinder (R)]
Takemura, N., K. Nakagawa, N. Machida, M. Washizu, H. Amasaki and H. Hirose (2003). Acquired mitral stenosis in a cat with hypertrophic cardiomyopathy. Japan, Department of Veterinary Internal Medicine, Nippon Veterinary and Animal Science University, Musashino City, Tokyo, Japan: 1265-7.
A seven-year-old castrated male domestic shorthair cat was diagnosed with hypertrophic cardiomyopathy (HCM) and suspected mitral stenosis (MS) based on electrocardiography, thoracic radiographs and echocardiographic findings. Post-mortem examination of the heart revealed morphological features consistent with HCM. In addition, there was marked fibrous deposition on the surfaces of the chordae tendineae extending to both mitral valve leaflets, which caused total chordal fusion into pillars of fibrous tissue and fusion of the commissures. The present case indicates that acquired MS can occur in association with HCM in the cat. [on SciFinder (R)]
Nakagawa, K., N. Takemura, N. Machida, M. Kawamura, H. Amasaki and H. Hirose (2002). Hypertrophic cardiomyopathy in a mixed breed cat family. Japan, Kawamura Animal Hospital, 1-45-3 Nishigaoka, Kita-Ku, Tokyo 115-0056, Japan: 619-21.
A spayed female mixed cat (case 1) and its female offspring, the result of a pairing between case 1 and its male sibling, were diagnosed with hypertrophic cardiomyopathy (HCM). A pedigree survey revealed that the prevalence of HCM was at least 12.5% in the family, which was considered to be significantly higher than that in a hospital-based population (approximately 1.6%). Thus, this finding seems to support the suspected occurrence of familial HCM in this group of related cats. [on SciFinder (R)]
Kittleson, M. D., K. M. Meurs, M. J. Munro, J. A. Kittleson, S. K. Liu, P. D. Pion and J. A. Towbin (1999). "Familial hypertrophic cardiomyopathy in maine coon cats: an animal model of human disease". Circulation FIELD Full Journal Title:Circulation 99(24): 3172-80.
BACKGROUND: A naturally occurring animal model of familial hypertrophic cardiomyopathy (FHCM) is lacking. We identified a family of Maine coon cats with HCM and developed a colony to determine mode of inheritance, phenotypic expression, and natural history of the disease. METHODS AND RESULTS: A proband was identified, and related cats were bred to produce a colony. Affected and unaffected cats were bred to determine the mode of inheritance. Echocardiography was used to identify affected offspring and determine phenotypic expression. Echocardiograms were repeated serially to determine the natural history of the disease. Of 22 offspring from breeding affected to unaffected cats, 12 (55%) were affected. When affected cats were bred to affected cats, 4 (45%) of the 9 were affected, 2 (22%) unaffected, and 3 (33%) stillborn. Findings were consistent with an autosomal dominant mode of inheritance with 100% penetrance, with the stillborns representing lethal homozygotes that died in utero. Affected cats usually did not have phenotypic evidence of HCM before 6 months of age, developed HCM during adolescence, and developed severe HCM during young adulthood. Papillary muscle hypertrophy that produced midcavitary obstruction and systolic anterior motion of the mitral valve was the most consistent manifestation of HCM. Cats died suddenly (n=5) or of heart failure (n=3). Histopathology of the myocardium revealed myocardial fiber disarray, intramural coronary arteriosclerosis, and interstitial fibrosis. CONCLUSIONS: HCM in this family of Maine coon cats closely resembles the human form of FHCM and should prove a valuable tool for studying the gross, cellular, and molecular pathophysiology of the disease. [on SciFinder (R)]
Bailey, B. A., K. Dipla, S. Li and S. R. Houser (1997). "Cellular basis of contractile derangements of hypertrophied feline ventricular myocytes". J. Mol. Cell. Cardiol. FIELD Full Journal Title:Journal of Molecular and Cellular Cardiology 29(7): 1823-1835.
The objective of this study was to further explore the cellular basis of the reduced rate and magnitude of contraction of feline left ventricular myocytes with severe hypertrophy induced by slow progressive pressure overload. A 3.0 mm internal diam. band was placed around the ascending aorta of 12 young (8-10 wk old) cats, and sham operations were performed in 13 others. This caused no major pressure overload initially, but 15 wk later there was a significant pressure gradient across the band (56 mmHg) and the heart wt. to body wt. ratio had increased from 4.2-7 mg/kg. Contraction rates and magnitudes of myocytes isolated from the hearts with hypertrophy (LVH) were significantly slower and smaller, resp., than those from control (C) animals. Indo-1 fluorescence transients in LVH myocytes were significantly smaller in magnitude and longer in duration than in C, suggesting that contractile defects result from Ca2+ derangements. Elevation of bath Ca2+ increased the peak Indo-1 fluorescence and the rate and magnitude of contraction in all myocytes. At the bath Ca2+ which had maximal inotropic effects there were no differences in the peak Indo-1 fluorescence in LVH and C myocytes, but contraction magnitude remained significantly smaller in LVH. This suggests that there are Ca2+-independent contractile derangements in LVH. In support of this hypothesis, the relation between contraction magnitude and the peak Indo-1 fluorescence (index of myofibrillar Ca2+ sensitivity) was significantly shifted in LVH myocytes, suggesting that myofibrillar Ca2+ sensitivity was reduced. There was also a significant shift of the terminal portions of hysteresis loops of cell length v Indo-1 fluorescence ratio, providing addnl. support for this idea. Expts. with isoproterenol suggest that it can reduce myofibrillar Ca2+ sensitivity in C, but not LVH myocytes. The idea that increased internal resistance to shortening (internal load) is responsible for the contractile defects of LVH myocytes was examd. by defining the relation between the rate of relengthening and the magnitude of shortening. There was no significant difference in this relation between C and LVH myocytes. In addn., colchicine (which depolymerizes microtubular tubulin) had no significant effect on contraction magnitude in either C or LVH myocytes. These results suggest that the contractile properties of feline LVH myocytes result from changes in cellular Ca2+ regulation and myofibrillar Ca2+ sensitivity, but not from changes in the internal loading. [on SciFinder (R)]
Baty, C. J. (1996). Molecular basis of feline familial hypertrophic cardiomyopathy: examination of cardiac troponin-T and b-myosin heavy chain genes (sarcomeric): 99 pp.
Marian, A. J., Q. T. Yu, D. L. Mann, F. L. Graham and R. Roberts (1995). "Expression of a mutation causing hypertrophic cardiomyopathy disrupts disrupts sarcomere assembly in adult feline cardiac myocytes". Circ. Res. FIELD Full Journal Title:Circulation Research 77(1): 98-106.
Mutations in the b-myosin heavy chain (bMyHC) induce hypertrophic cardiomyopathy (HCM), cardiac hypertrophy, and sarcomere disarray, with the latter being the characteristic hallmark. Thus, the authors sought to det. whether expression of mutant bMyHC in adult feline cardiac myocytes, a species known to develop HCM with a phenotype identical to that in humans, induces sarcomere disarray. A full-length bMyHC cDNA was cloned from a human heart cDNA library, and an HCM-causing mutation (Arg403Gln) was induced in the bMyHC cDNA by site-directed mutagenesis using polymerase chain reaction (PCR). The normal and mutant bMyHC cDNAs were cloned into pDE1spIB shuttle vector, downstream from a cytomegalovirus (CMV) promoter. Replication-deficient recombinant adenoviral constructs (Ad5/CMV/bMyHC-N and Ad5/CMV/bMyHC-403) were generated through homologous recombination of pDE1spIB/CMV/bMyHC-N or Ad5/CMV/bMyHC-403 and pBHG10 after cotransfection in 293 host cells. Infection of COS-1 cells with the bMyHC construct resulted in the expression of a full-length myosin protein. Efficiency of infection of isolated adult cardiac myocytes was >95%. Expression of the bMyHC constructs into mRNA at 48 h after infection of feline cardiac myocytes was confirmed by reverse transcription-PCR. The net total protein and b-myosin synthesis were detd. bg using the amt. of incorporation of [3H]phenylalanine into total protein and b-myosin, resp. Although the total amt. of protein synthesis was equal among exptl. groups, the net myosin synthesis at 48 h was greater in cardiac myocytes infected with normal or mutant bMyHC constructs than control myocytes or those infected with vector alone. Electron microscopic examn. showed only minor changes in the structure of sarcomeres in all exptl. groups at 48 h after infection. However, disruption of the sarcomeric structures at 120 h after infection with the mutant bMyHC construct was obsd. in ~50% of the myocytes examd., whereas the structure of the sarcomeres remained largely intact in myocytes infected with normal bMyHC construct, adenoviral vector alone, or control cardiocytes. Similar results were confirmed by immunofluorescence using MF-20 antibody to myosin. Thus, disruption of sarcomere assembly and myofibrillar organization due to mutant bMyHC protein is the primary defect in HCM. [on SciFinder (R)]
Karimova, R. F. and Z. N. Solomatina (1973). "Effect of hyperglycemia, hypoglycemia, and castration on the toxicity of convallatoxin and strophanthin". Mater. Nauchn. Konf., Alma-At. Gos. Med. Inst., 43rd FIELD Full Journal Title: : 431-2.
Cats were more sensitive to the toxic effects of convallatoxin (I) [508-75-8] and strophanthin [560-53-2] when they were castrated at an early age, but less sensitive when castrated as adults. Cats with exptl. hypoglycemia were less sensitive to the drugs than were controls, while cats with hyperglycemia were more sensitive. [on SciFinder (R)]
