Alternative TitleInvestigation of basic and clinical implications of plasma atrial natriuretic peptide measurement in cats
Note (General)[Introduction] Cardiac biomarkers are proteins or hormones that are produced in the heart and secreted or released into the blood. Several hormones and peptides, including atrial natriuretic peptide (ANP) and cardiac troponin, are used in veterinary practice as cardiac biomarkers. ANP is mainly synthesized and stored in the atrial myocardium as a prohormone and cleaved into two segments in response to wall stretching. N-terminal proANP and biologically active C-terminal ANP are released into the blood from the left atrium. Previous studies have demonstrated that elevated left atrial pressure is significantly associated with an increase in plasma ANP in dogs and cats. In addition, increases in circulating ANP levels reflect the severity of chronic heart failure. Hypertrophic cardiomyopathy (HCM) is most commonly seen in cats. Although an echocardiographic examination is the gold standard for diagnosing cardiomyopathy, the main limitation of this method is that it requires dedicated equipment and a high level of skill. Therefore, establishment of a simple method for diagnosing feline cardiomyopathy is required. However, basic information about potential feline ANP assays is lacking, and only a few studies have evaluated the clinical implications of plasma ANP measurement in cats. This study established an ANP assay system in cats and defined the diagnostic accuracy of using plasma levels of ANP to identify cardiomyopathy severity in cats. [Chapter 1] To investigate whether the human α-ANP kit can be applied to measure feline ANP, dilution detection and storage stability were evaluated using feline plasma. Plasma levels of ANP were determined using a chemiluminescence enzyme immunoassay. A plasma sample from a cat with heart failure was serially diluted, and parallelism was confirmed with a human ANP standard. Next, to evaluate the storage stability of ANP, changes in ANP levels in the sample stored at room temperature was evaluated. Serum levels of ANP markedly decreased from baseline over time, whereas the levels in plasma containing aprotinin did not decrease until 12 h. Finally, the relationship between the storage temperature of the sample and the ANP measurement was evaluated. Plasma levels in samples stored at -70°C were similar to those at baseline for 14 days. Similarly, ANP levels were maintained for 7 days in samples stored at -20°C. By contrast, plasma levels stored at 4°C decreased to 93.3% of baseline after 1 day, and decreased significantly to 57.6% and 18.0% after 7 and 14 days of storage, respectively. These results suggest that aprotinin should be routinely added to blood samples and that plasma samples should be immediately frozen. [Chapter 2] To investigate the influence of hemodynamics on plasma levels of ANP in cats, we nalyzed the relationship between blood pressure and ANP levels in the blood of healthy anesthetized cats. Plasma levels of ANP decreased rapidly and significantly during anesthesia. In addition, the levels were significantly correlated with systolic arterial pressure (r = 0.59) and mean arterial pressure (r = 0.56). These results suggest that excitement or systemic blood pressure may affect plasma levels of ANP in cats. [Chapter 3] This study included 78 clinically healthy cats and 83 cats with cardiomyopathy. We investigated the cutoff values of plasma ANP as an indicator of the cardiomyopathy severity. Diseased cats were divided into asymptomatic cats without left atrial dilation, asymptomatic cats with left atrial dilation, and cats experiencing heart failure. The plasma levels of ANP in clinically healthy cats was 43.3 (interquartile range 33.0-56.3) pg/mL. The values were significantly higher in cardiomyopathic cats with left atrial dilation and heart failure. A level of ≥77.5 pg/mL indicated cardiomyopathy without left atrial dilation with a sensitivity of 66.3% and a specificity of 84.6%. The use of plasma levels of ANP > 110.9 pg/mL to identify cats with left atrial dilation had a sensitivity of 73.6% and specificity of 93.5%. To identify cats with heart failure, a cutoff value of 118.6 pg/mL resulted in good sensitivity (85.2%) and specificity (85.1%). The areas under the ROC curve were 0.80, 0.86, and 0.87, respectively. These results suggest that plasma levels of ANP reflect left atrial dilation associated with cardiomyopathy, and are a useful predictor of left atrial dilation induced by cardiomyopathy. [Conclusions] These results indicate that a mouse anti-human ANP monoclonal antibody has an affinity towards feline ANP. In addition, the results indicate the importance of routinely using aprotinin during blood collection to measure feline ANP, and suggest that feline plasma samples should be frozen immediately at -20°C or less and assayed within 7 days. Systemic blood pressure also affected plasma levels of ANP in cats; therefore, blood should be collected at rest to obtain accurate ANP measurements. Finally, ANP levels increased concomitantly with increased cardiomyopathy severity. An ANP level > 77.5 pg/mL was predictive of cardiomyopathy, and levels > 110.9 pg/mL were predictive of cardiomyopathy with left atrial dilation. Although an ANP measurement alone cannot be used to diagnose any cardiac disease, such data may provide supportive information for assessing the severity of cardiomyopathy.
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Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2019-01-04T08:16:43+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション