Cardiac L-type calcium channel and its alterations in cardiac hypertrophy and heart failure

There are two type of cardiac calcium channel current, both are inward current: (1) L-type Ca²⁺channel current (I_ca-L), plays a major role in determining myocyte action potential plateau characteristics as well as initiating the myocyte excitation-contraction coupling; (2) T-type Ca²⁺ channel current (I_ca-T), probably plays an important role in pacemaker activity. The alterations of L-type calcium channel abundance and function in cardiac hypertrophy and heart failure are determined by the the species difference, especially by the stage of the disease process and the degree of the disease. Both abundance and function of L-type calcium channel decrease in severe hypertrophy and heart failure.     

Cytokine production in mice with experimental cardiomyopathy treated with anti-L3T4 monoclonal antibody at different stages

AIM: To clarify the mechanism of treating autoimmune cardiomyopathy at different stages with anti-L3T4 monoclonal antibody. METHODS: Mice immunized with human mitochondria ADP/ATP peptides were used as the cardiomyopathy (DCM) group, and the sham-immunized mice were regarded as the controls. Mice receiving early treatment were immunized with the same peptides, followed by the injection of 400 μg of anti-L3T4 on day 0, 1 and 2 post-immunization. Mice in the late treatment group were immunized as of the early treatment group but anti-L3T4 was administered 3 months post-immunization. The cytokine expression was measured with three-color flow cytometry to quantitate the splenic Th1/Th2 cell subsets in the different groups of mice. In addition, serum and myocardial cytokines were measured by enzyme-linked immunosorbent assay and real-time PCR. RESULTS: Th1 and Th2 subsets in the early treatment group were similar to those in control group, but were drastically lower than those in DCM group. Mice in the late treatment group showed an increased level of Th1-related cytokines, while the Th2 level was between the DCM and early treatment group. IFN-γ and IL-6 levels in early treatment group were similar to those in control group. In the early treatment group, IL-4 level was higher than that in control and lower than that in DCM group, whereas IL-2 and TNF-α contents were lower than those in control and DCM group. In the late treatment group, IFN-γ and IL-2 levels were higher than those in DCM group and lower than those in the early treatment group, while IL-6 and IL-4 levels were lower than those in DCM group. CONCLUSION: These results suggest that the cytokine production in cardiomyopathic mice may be repressed by treatment with anti-L3T4 at different stages. Early treatment with anti-L3T4 has better inhibitory function than treatment in late stage of autoimmune cardiomyopathy.     

24‐Hour Kinetics of Cardiac Troponin‐T Using a “High‐Sensitivity” Assay in Thoroughbred Chuckwagon Racing Geldings after Race and Associated Clinical Sampling Guidelines

Background

A “high‐sensitivity” cardiac troponin‐T (hscTnT) assay recently has been validated for use in horses and is a specific biomarker of myocardial damage. Postexercise release kinetics of cTnT utilizing the hscTnT assay have yet to be established in horses.

Objectives

To determine: (1) cTnT release kinetics in racing Thoroughbreds after a high‐intensity 5/8th mile Chuckwagon race; (2) the effects of age on pre‐ and postrace cTnT concentrations; and (3) sampling guidelines for clinicians evaluating horses presenting after exercise.

Animals

Samples were obtained from 38 Thoroughbred geldings aged 5–16 years before racing and immediately, 2, 3, 4, 6, 12, and 24 hour postrace.

Methods

Prospective, observational study with convenience sampling. A fifth‐generation hscTnT assay was used for plasma sample analysis, and concentrations were compared at all time‐points. Correlations were determined between cTnT concentrations and age. Biochemistry analysis was performed to assess rhabdomyolysis, renal failure, and exercise‐induced dehydration.

Results

All horses with measureable cTnT concentrations had significant postexercise increases in cTnT with a median peak (8.0 ng/L) at 3‐hour postrace. All horses had peak postexercise cTnT concentrations 2‐ to 6‐hour postrace ≤ the 99th percentile upper reference limit of 23.2 ng/L, after which all cTnT concentrations decreased until returning to baseline by 12–24 hours. There was no correlation over time between cTnT concentrations and age.

Conclusions and Clinical Importance

In racing Thoroughbreds completing short‐duration, high‐intensity Chuckwagon races, cTnT concentrations are expected to be increased 2‐ to 6‐hour postrace and to decrease by 12–24 hours while remaining ≤23.2 ng/L throughout. This study contributes to establishing guidelines for clinical use of the hscTnT assay in exercising horses.     

Prospective clinical evaluation of serum cardiac troponin T in dogs admitted to a veterinary teaching hospital

The purpose of this study was to measure serum cardiac troponin T (cTnT) with a commercially available human enzyme-linked immunoassay (ELISA) test in various groups of dogs, including those undergoing doxorubicin chemotherapy. Serum samples were obtained from 6 groups of dogs: (1) normal adult dogs (n = 15); (2) dogs with asymptomatic dilated cardiomyopathy (n = 5); (3) dogs with congestive heart failure (n = 10); (4) dogs with untreated neoplasia (n = 20); (5) dogs with skeletal muscle trauma (n = 10); and (6) dogs with neoplasia receiving doxorubicin chemotherapy (n = 4). One serum sample was obtained from each of the normal dogs, those with asymptomatic cardiomyopathy, those with congestive heart failure, and those with untreated neoplasia. Serum samples were obtained serially from the dogs that were undergoing doxorubicin chemotherapy; samples were collected before doxorubicin (30 mg/m2) administration and then 1, 5, 7, and 14 days after administration throughout 6 cycles for a cumulative total dose of 180 mg/m2. All normal dogs, dogs with untreated neoplasia, and dogs with asymptomatic dilated cardiomyopathy had cTnT concentrations below the lower limits of detection for the assay used (<0.05 ng/mL). Detectable concentrations of cTnT were found in 3 dogs with congestive heart failure and in 2 dogs with skeletal muscle trauma. Detectable concentrations also were found in both dogs that had received 180 mg/m2 of doxorubicin. We conclude that dogs with congestive heart failure and those with skeletal muscle trauma and dogs with neoplasia receiving high-dose doxorubicin chemotherapy may have increased serum cTnT concentration, which may be suggestive of myocardial damage.     

Cellular mechanisms of losartan on reversing left ventricular hypertrophy in spontaneously hypertensive rats

AIM:To investigate the role of proliferation and apoptosis in hypertensive left ventricular hypertrophy (LVH) and the effect of AT₁ blockade with losartan. METHODS:Left ventricles (LV) from 12, 24-week-old SHR (SHR₁₂, SHR₂₄), 24-week-old SHR treated with losartan (15 mg·kg^-1·d^-1, SHR-L₂₄) during 12 weeks, and age-matched WKY rats (WKY₁₂, WKY₂₄) were studied. Expression of PCNA was examined by immunohistochemistry. Apoptotic cells in LV sections were assessed by TUNEL method. Levels of fas mRNA were quantitated by RT-PCR. RESULTS: Compared with age-matched WKY, SHR₁₂ and SHR₂₄ showed increased LV hypertrophied index (HI), increased apoptotic index (AI) of myocytes (P＜0.01), but decreased AI of fibroblasts (P＜0.05). Moreover, SHR₁₂ exhibited increased PCNA labeling of myocytes (P＜0.05) with similar positive rates of fibroblasts.It was also showed that losartan reversed HI, significantly reduced the AI of myocytes and significantly increased the AI of fibroblasts. RT-PCR disclosed that levels of fas mRNA positively correlated with the frequency of apoptosis in LV of either SHR or WKY (r=0.52, P＜0.05). CONCLUSION:The cellular changes of LVH in adult SHR manifest as the imbalance between proliferation and apoptosis of myocytes, and insufficient apoptosis of fibroblasts. The mechanisms of losartan on reversing LVH may be mediated through adjusting the abnormal amount of cells and the expression of fas gene.     

Echocardiographic Findings in 11 Cats with Acromegaly

Background

Information regarding cardiac changes in domestic cats with acromegaly is limited.

Hypothesis/Objectives

The objective of this study was to describe the echocardiographic findings in cats with acromegaly.

Animals

Eighteen cats diagnosed with acromegaly at Colorado State University between 2008 and 2012. Of these 18 cats, 11 had echocardiography performed.

Methods

A retrospective review of medical records was made to identify cats with acromegaly that also had echocardiography performed.

Results

Of the 11 cats identified, 7 had left ventricular concentric hypertrophy, 6 had left atrial enlargement, and 7 had evidence of abnormal diastolic function. All 11 cats had evidence of structural or functional cardiac disease.

Conclusions and Clinical Importance

Cardiovascular abnormalities frequently are present in cats with acromegaly, and a complete cardiac evaluation should be considered in these patients.     

Pericardial effusion in cats: a retrospective study of clinical findings and outcome in 146 cats

BACKGROUND: Pericardial effusion (PE) in dogs most often is associated with neoplasia or idiopathic pericarditis, and frequently causes cardiac tamponade. Studies of PE in the cat are limited. HYPOTHESIS: Congestive heart failure (CHF) is the most common cause of PE in the cat. ANIMALS: All cats diagnosed with PE on echocardiographic examination at the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania (MJR-VHUP) from 2000 to 2005. METHODS: The clinical and pathologic findings in 146 cats with PE were reviewed. Records were examined retrospectively to identify additional underlying conditions. Follow-up status and cause of death were determined by review of the medical records or phone interviews with the owners. RESULTS: The most common cause of PE in this study was CHF (75%). Biochemical abnormalities were uncommon, but aspartate aminotransferase (AST) activity frequently was increased (85%). Follow-up information was available on 108 cats (74%). Median survival time (MST) was 144 days for cats that were not euthanized within 24 hours (n = 85). The MST of cats with heart failure was 41 days, whereas the MST of cats without heart failure was 361 days, when those euthanized within 24 hours were excluded. CONCLUSIONS: Survival time of cats with heart failure in this study was significantly shorter than previously reported, and significantly shorter than in cats without heart failure as a cause of PE.     

Relationship of Body Size to Metabolic Markers and Left Ventricular Hypertrophy in Cats

Background

Cats with hypertrophic cardiomyopathy (HCM) are larger and have higher insulin‐like growth factor‐1 (IGF‐1) concentrations than cats without HCM.

Hypothesis/Objectives

The aim of this study was to assess echocardiographic findings in a colony of adult cats to determine the relationship between early growth and left ventricular hypertrophy (LVH).

Animals

Twenty‐eight neutered adult cats (20 males, 8 females) from a colony ≥3 years of age for which growth curves were available.

Methods

Case–control study. Physical examination and echocardiography were performed, and body weight, body condition score (BCS), and head length and width were measured. Circulating glucose, insulin, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), and IGF‐1 concentrations were measured and growth data were collected. Stepwise multivariate analyses were performed.

Results

Mean age was 5.2 ± 1.1 years. Current BCSs ranged from 4 to 9 (median, 6) and mean body weight was 4.88 ± 1.29 kg. Variation in body weight was apparent by 6 (mean = 3.26 ± 0.80 kg) and 12 months of age (mean = 4.02 ± 1.02 kg). Cardiac abnormalities included a cardiac murmur (n = 7; 24%), gallop (n = 3; 10%), and arrhythmia (n = 1; 4%). Fourteen of 28 cats (50%) had echocardiographic evidence of LVH. Head width (P = .017), body weight (P < .001), NT‐proBNP (P = .023), and IGF‐1 (P = .013–.022) were significantly associated with selected measures of LVH.

Conclusions and Clinical Importance

Potential associations between body size, IGF‐1, LVH, and HCM warrant future prospective studies.     

Determination of the prevalence of whole blood taurine in Irish wolfhound dogs with and without echocardiographic evidence of dilated cardiomyopathy

ObjectivesTaurine plays an important role in maintaining myocardial function. Irish wolfhound dogs (IW) are at risk for dilated cardiomyopathy (DCM), but a relationship between whole blood taurine (WBT) deficiency and DCM has not been established. Our aim was to determine prevalence of WBT deficiency in IW with and without DCM and assess its association with diet.Animals115 privately owned IW.MethodsWhole blood taurine was measured in IW that received cardiovascular examination. Dietary history was recorded; crude protein and energy intake were estimated.ResultsForty-nine (42.6%) had DCM; 66 (57.4%) had no DCM. Dogs with DCM were older ([median; inter-quartile range or IQR] 5.3; 4.3, 6.2 years) than dogs without heart disease (3; 2, 4 years; P < 0.001). There was no significant relationship between WBT concentration and age (P = 0.64). Whole blood taurine was severely reduced (<130 nmol/mL) in 8 dogs (4 with and 4 without DCM) and moderately reduced (130–179.9 nmol/mL) in 32 dogs (12 with DCM and 20 without DCM). Follow up of dogs without DCM revealed that a higher proportion of dogs with any degree of WBT deficiency developed DCM later compared to dogs with normal WBT (P < 0.001).ConclusionsWhole blood taurine deficiency occurred in IW with and without DCM. Based on taurine measurement on a single occasion, there was no clear relationship between low WBT and presence of DCM in this population. Regardless of WBT, DCM affected predominantly older dogs, suggesting a relatively late onset disease in the IW.