N-terminal atrial natriuretic peptide immunoreactivity in plasma of cats with hypertrophic cardiomyopathy

Atrial natriuretic peptide (ANP) is an important regulator of fluid homeostasis and vascular tone. We sought to compare N-terminal ANP immunoreactivity (ANP-IR) in plasma from cats with and without hypertrophic cardiomyopathy (HCM). Secondarily, we evaluated relationships between ANP-IR and echocardiographical variables in cats with HCM and healthy cats. Venous blood samples were obtained from 17 cats with HCM and from 19 healthy cats. Plasma ANP-IR concentration was determined by an enzyme-linked immunoassay. Two cats with HCM had clinical evidence of congestive heart failure; the remainder had subclinical disease. Plasma ANP-IR concentration was higher in cats with HCM (3,808 +/- 1,406 fmol/L, mean +/- SD) than in control cats (3,079 +/- 1,233 fmol/L), but this difference was not statistically significant (P = .11; 95% confidence interval [CI] = -166 to 1,622). There was a significant, but modest correlation between plasma ANP-IR concentration and left ventricular posterior wall thickness (r = 0.42; P = .01). Additionally, plasma ANP-IR concentration was weakly correlated with left atrial size (r = 0.35; P = .03). A linear regression model was developed to further explore these relationships. Atrial size and wall thickness were included in the model; the 2 explanatory variables had an interactive effect on plasma ANP-IR concentration (R2 = 0.27; P = .02). There was no appreciable correlation between plasma ANP-IR concentration and any other echocardiographical variable. In a population that included cats with subclinical disease, those with HCM did not have significantly higher plasma ANP-IR concentration than did healthy cats. An exploratory multivariable regression analysis suggested a linear relationship between ANP-IR concentration and atrial size, wall thickness, and their interaction.     

Genomic sequence and cardiac expression of atrial natriuretic peptide in cats

OBJECTIVE: To determine the nucleotide and amino acid sequence of atrial natriuretic peptide (ANP) in cats and its typical regions of cardiac expression. ANIMALS: 5 healthy adult mixed-breed cats. PROCEDURE: Total RNA was extracted from samples obtained from the left and right atrium, left and right ventricle, and interventricular septum of each cat. The RNA was used to produce cDNA for sequencing and northern blot analysis. Genomic DNA was extracted from feline blood samples. Polymerase chain reaction primers designed from consensus sequences of other species were used to clone and sequence the feline ANP gene. RESULTS: The feline ANP gene consists of 1,072 nucleotides. It consists of 3 exons (123, 327, and 12 nucleotides) separated by 2 introns (101 and 509 nucleotides). It has several typical features of eukaryotic genes and a putative steroid-response element located within the second intron. Preprohormone ANP consists of 153 amino acids. The amino acid sequence of the active form of feline ANP (ANP-30) is identical to that of equine, bovine, and ovine ANP-30 and differs from that of human, canine, and porcine ANP-28 only by 2 carboxy-terminal arginine residues. The ANP mRNA was detected only in the left and right atria. CONCLUSIONS AND CLINICAL RELEVANCE: The genetic and protein structure and principal regions of cardiac expression of feline ANP are similar to those of other species. Results of this study should be helpful in future studies on the natriuretic response in cats to diseases that affect cardiovascular function.     

Peri-operative changes in echocardiographic measurements and plasma atrial and brain natriuretic peptide concentrations in 3 dogs with patent ductus arteriosus

Peri-operative changes in echocardiographic measurements and plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were investigated for 1 month in 3 dogs with patent ductus arteriosus (PDA). Post-operative left ventricular end-diastolic dimention and fractional shortening decreased in all cases. Pre-operatively increased plasma ANP concentrations reduced dramatically after the operation. Peri-operative changes in plasma BNP levels had slightly S-shaped curves in all cases. These observations suggest that post-operative responsiveness of ANP and cardiac function are rapid in comparison with cardiac morphological changes, and BNP has a different pathophysiological significance from ANP in dogs with PDA.     

Usefulness of cardiac hormones for evaluating valvular disease in cynomolgus monkeys (Macaca fascicularis)

Nonhuman primates are commonly used as experimental animals due to their biological resemblance to humans. In patients with cardiac disease, the levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) tend to increase in response to cardiac damage, and they are thus used as indicators for the diagnosis of human heart failure. However, no reference values for ANP and BNP have been reported for heart disease in nonhuman primates. In this study, we recorded the age, sex, and body weight of 202 cynomolgus monkeys, and performed evaluations to assess the ANP and BNP levels, electrocardiography and echocardiography, and accordingly divided the monkeys into two groups: healthy monkeys and those with spontaneous cardiac disease. Statistical analysis was performed to determine the relationship of ANP and BNP with the factors of age, sex, and body weight. No significant relationship was found between the levels of ANP and BNP and the factors of age, sex, and body weight. However, both the ANP and BNP levels were significantly different between the healthy monkeys and monkeys with valvular disease. Similar to humans, the ANP and BNP levels tended to increase with the progression of cardiac disease in monkeys. Based on these results, we concluded that ANP and BNP are indicators of cardiac disease in nonhuman primates, and that this nonhuman primate cardiac disease model is applicable for cardiology research in humans.     

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

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.     

Evaluation of plasma C-terminal atrial natriuretic peptide in healthy cats and cats with heart disease

BACKGROUND: The clinical implications of evaluating C-terminal atrial natriuretic peptide (ANP) concentration in cats are still controversial. HYPOTHESIS: The objective of this study was to investigate the relationship between plasma C-terminal ANP concentration and left atrial pressure (LAP) in healthy cats with volume overload (study 1), and to compare plasma C-terminal ANP in normal cats and cats with cardiomyopathy (study 2). ANIMALS: Five healthy adult cats were used in study 1, and clinically healthy cats (n=8) and cats with cardiomyopathy (n=14) were used in study 2. METHODS: In study 1, cats were anesthetized and given acetated Ringer's solution (100 mL/kg/h for 60 minute) via the cephalic vein. Hemodynamic measurements and blood samples, collected from the jugular vein, were performed at 10-min intervals. In study 2, blood samples from normal cats and cats with cardiomyopathy were collected from the cephalic vein. The plasma C-terminal ANP concentration was determined by radioimmunoassay for human alpha-ANP. RESULTS: In study 1, volume overload significantly increased the C-terminal ANP concentration and LAP from baseline. The C-terminal ANP concentration was strongly correlated with the mean LAP. In study 2, age, E wave velocity, and the ratios of the left atrium to aorta were significantly higher in the cats with cardiomyopathy compared with the normal cats. The C-terminal ANP concentration was significantly higher in the cats with cardiomyopathy compared with the normal cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest that the measurement of plasma C-terminal ANP in cats may provide additional information for the diagnosis of heart disease.     

Preliminary immunohistochemical study of natriuretic peptide receptor localization in canine and feline heart

We examined the immunohistochemical distributions of natriuretic peptide receptor (NPR)-A, -B and -C that bind with natriuretic peptide hormones A, B and C in four healthy crossbreed young canine and feline cardiac tissues using specific antibodies against human antigens. Cross-immunoreactivities between antigens and antibodies were confirmed using western blot analysis. NPR-A and -C were expressed more strongly in dogs than cats. In both species, these expressions were stronger in the atria than the ventricles, with stronger expression in the left ventricles than the right. NPR-B was largely very weekly or undetected. In canine and feline cardiac tissues, the expressional distribution of NPR-A, -B, and -C closely matched with that of atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide as the ligands for corresponding receptors.     

Prospective screening for occult cardiomyopathy in dogs by measurement of plasma atrial natriuretic peptide, B-type natriuretic peptide, and cardiac troponin-I concentrations

OBJECTIVE: To evaluate the use of measuring plasma concentrations of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and cardiac troponin-I (cTnI) to detect dogs with occult dilated cardiomyopathy (DCM). ANIMALS: 118 client-owned dogs. PROCEDURES: Dogs were prospectively examined by use of ECG; echocardiography; and evaluation of concentrations of ANP, BNP, and cTnI. Occult DCM was diagnosed by evaluation of echocardiographic left ventricular dimensions and detection of ventricular arrhythmias on ECG. Sensitivity and specificity of assays for measurement of plasma concentrations of ANP, BNP, and cTnI to detect dogs with occult DCM were determined. RESULTS: Occult DCM was diagnosed in 21 dogs. A concentration of > 6.21 pg/mL for BNP had a sensitivity of 95.2% and specificity of 61.9% for identifying dogs with occult DCM. In contrast, concentrations of ANP and cTnI had relatively low predictive values. CONCLUSIONS AND CLINICAL RELEVANCE: Blood-based screening for occult DCM in dogs can be accomplished by use of a BNP assay. Additional studies should be performed to optimize this method of screening dogs to detect occult DCM.     

Assessment of left ventricular longitudinal function in cats with subclinical hypertrophic cardiomyopathy using tissue Doppler imaging and speckle tracking echocardiography

Hypertrophic cardiomyopathy (HCM) in cats is characterized by concentric left ventricular (LV) hypertrophy and both diastolic and systolic dysfunction. Although impaired cardiac function detected by tissue Doppler imaging (TDI) in cats with HCM was previously reported, reference ranges of TDI in normal cats and cats with HCM have been reported as widely variable. Two-dimensional speckle tracking echocardiography (STE) was useful for assessment of cardiac function in human patients with HCM, but clinical utility was not known in cats. The aim of this study was to assess global and segmental LV myocardial function using STE in cats with HCM whose TDI variables were within the reference range. A total of 35 cats of different breeds were enrolled in this study. The HCM group (n=22) was cats diagnosed as HCM without left atrial enlargement and with normal TDI measurements. HCM cats were further divided into a segmental hypertrophy (S-HCM) group and a diffuse hypertrophy (D-HCM) group. The control group consisted of 13 clinically healthy cats. No cats in any group showed any clinical symptoms. Conventional echocardiography, TDI, and global and segmental STE indices were evaluated and compared between groups. Only the longitudinal strain rate during early diastole was significantly decreased in both HCM groups, even in all segments including those without hypertrophy in S-HCM group. This study suggests that STE parameters are the more sensitive variables compared with conventional TDI parameters to detect early myocardial diastolic dysfunction in cats with HCM.     

Diagnostic accuracy of plasma atrial natriuretic peptide concentrations in cats with and without cardiomyopathies

Objectives

Plasma atrial natriuretic peptide (ANP) levels have been reported to be elevated in cats with cardiomyopathy. We investigated the diagnostic accuracy of plasma ANP concentration as an indicator of the severity of cardiomyopathies.

Plasma atrial and brain natriuretic peptide levels in dogs with congestive heart failure.

Plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured in 6 dogs with experimental mitral regurgitation (MR) and 19 canine patients with asymptomatic and symptomatic congestive heart failure (CHF). In dogs with experimental MR, ANP and BNP concentrations were significantly correlated with pulmonary capillary wedge pressure (PCWP) (ANP; r=0.852, P=0.0004, BNP; r=0.832, P=0.0008). ANP level was shown to have a predominant effect on PCWP in comparison with BNP using multiple regression analysis. In canine patients with asymptomatic and symptomatic CHF, ANP and BNP concentrations were significantly different among the heart failure classes according to the New York Heart Association functional classification (ANP; P=0.0165, BNP; P=0.0005). In addition, ANP and BNP levels in dogs with decompensated heart failure (n=10) significantly increased in comparison with those in dogs with compensated heart failure (n=9). There was however no correlation between ANP and BNP levels in each heart failure class. In conclusion, plasma ANP and BNP levels may become predictors of PCWP and the severity of heart failure in dogs with MR, although further investigations on ANP and BNP levels in more clinical cases are required.     

Comparison of myocardial contrast enhancement via cardiac magnetic resonance imaging in healthy cats and cats with hypertrophic cardiomyopathy

OBJECTIVE: To quantify myocardial contrast enhancement (MCE) of the left ventricle (LV) by use of cardiac magnetic resonance imaging (CMRI) in healthy cats and cats with hypertrophic cardiomyopathy (HCM) and to compare MCE between the 2 groups. ANIMALS: 10 healthy cats and 26 Maine Coon cats with moderate to severe HCM but without clinical evidence of congestive heart failure. PROCEDURE: Anesthetized cats underwent gradient echo CMRI examination. Short-axis images of the LV were acquired before and 7 minutes after IV administration of gadolinium dimeglumine. Regions of interest were manually traced in the quadrants of 5 mid-LV slices acquired at end systole, and the MCE percentage was calculated from summed weight-averaged data from all slices. Doppler tissue imaging echocardiography was performed to measure the early diastolic myocardial velocity (Em) as an index of diastolic function. Three-way repeated-measures ANOVA was used to determine differences in MCE between cats with HCM and healthy cats. Simple linear regression was used to assess whether MCE was correlated with LV mass, LV mass index (LVMI), or Em. A Student t test was used to compare the SDs of the postcontrast myocardial signal intensity between the 2 groups. RESULTS: There was no difference in MCE between cats with HCM and healthy cats. There was no correlation of MCE with LV mass, LVMI, or Em. There was no difference in heterogeneity of signal intensities of LV myocardium between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Contrast-enhancement CMRI was not useful in detecting diffuse myocardial fibrosis in cats with HCM.     

Tissue Doppler imaging and gradient echo cardiac magnetic resonance imaging in normal cats and cats with hypertrophic cardiomyopathy

Cats with hypertrophic cardiomyopathy (HCM) often develop diastolic dysfunction, which can lead to development of left congestive heart failure. Tissue Doppler imaging (TDI) echocardiography has emerged as a useful, noninvasive method for assessing diastolic function in cats. Cardiac magnetic resonance imaging (cMRI) has been performed in cats and accurately quantifies left ventricular (LV) mass in normal cats. However, assessment of cardiac function in cats by cMRI has not been performed. Six normal Domestic Shorthair cats and 7 Maine Coon cats with moderate to severe HCM were sedated, and TDI of the lateral mitral annulus was performed. Peak early diastolic velocity (Em) was measured from 5 nonconsecutive beats. Cats were anesthetized with propofol and electrocardiogram-gated gradient echo cMRI was performed during apnea after hyperventilation. Short-axis images of the LV extending from the mitral annulus to the apex were obtained throughout the cardiac cycle. LV mass at end systole and LV volumes throughout the cardiac cycle were quantified according to Simpson's rule. To assess the possible influence of propofol on diastolic function, TDI was performed on the 7 cats with HCM while sedated and then while anesthetized with propofol. Em was significantly lower in cats with HCM than normal cats (6.7 +/- 1.3 cm/s versus 11.6 +/- 1.9 cm/s, P < .001, respectively). There was no difference in the cMRI indices of diastolic function in normal and HCM cats. Propofol did not reduce diastolic function (Em) in cats with HCM but mildly reduced systolic myocardial velocity (S) in Maine Coon cats with HCM that were anesthetized with propofol (P = .87 and P = .03, respectively).     

Measurements of plasma endothelin immunoreactivity in healthy cats and cats with cardiomyopathy

Plasma concentrations of endothelin-1 (ET-1), the most potent endogenous pressor substance discovered to date, are abnormally high in humans with congestive heart failure (CHF), and they correlate with the degree of functional impairment. We sought first to validate a human sandwich ELISA kit that targets that portion of the amino acid sequence that is identical in cats. The assay demonstrated linearity (R2 = .9968) and parallelism (P = .5339), recovery of spiked human ET-1 in cat plasma averaged 98.7%, and intraassay precision had a coefficient of variation <10%. We subsequently determined ET-1 immunoreactivity in healthy cats and in cats with myocardial disease with and without CHF, systemic thromboembolism (STE), or both. Plasma ET-1 immunoreactivity was measured in 12 healthy cats and in 28 cats with primary myocardial disease, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive or unclassified cardiomyopathy (RCM and UCM), respectively. Plasma ET mean (95% CI) concentrations were 0.777 (0.6536-0.924) fmol/mL in the control cats, 1.427 (0.922-2.209) fmol/mL in 12 cats with cardiomyopathy (HCM = 11, RCM/UCM = 1) but without CHF or evidence of STE, and 2.360 (1.666-3.343) fmol/mL in 16 cats with cardiomyopathy (HCM = 8, RCM/UCM = 7, DCM = 1) and CHF (n = 15) or STE (n = 4). Plasma immunoreactivity of ET-1 was significantly higher in cats with myocardial disease without CHF/STE versus normal cats (P < .05) and in cats with myocardial disease with CHF/STE versus normal cats (P < .001).     

Increased mean arterial pressure and aldosterone-to-renin ratio in Persian cats with polycystic kidney disease

Polycystic kidney disease (PKD) in Persian cats has been increasingly reported and compared to human autosomal dominant polycystic kidney disease (ADPKD) in the last decade. In cats, however, few studies have dealt with the occurrence and hormonal determinants of hypertension, one of the most common extrarenal manifestations of ADPKD in humans. The purpose of this study was to compare Persian cats >4 years old with PKD to unaffected control cats with regard to blood pressure (BP), plasma renin activity (PRA), serum aldosterone concentration, plasma atrial natriuretic peptide (ANP) concentration, and aldosterone-to-renin ratio (ARR). Three gender- and age-matched groups were studied, each consisting of 7 cats: (1) a control group without cysts, (2) a group with mild PKD, and (3) a group with severe PKD (multiple cysts and renal enlargement). Mild renal insufficiency was found in only 1 of 14 cats with PKD. Cats with PKD had a higher mean arterial pressure (P = .04) and more often had a high ARR (P = .047) than did control cats. Tendencies toward higher diastolic and systolic arterial pressures (DAPs and SAPs, respectively) and lower PRAs were observed in cats with PKD compared to controls (.05 < P < or = .1). No significant differences were found between the groups in serum aldosterone and plasma ANP concentrations. None of the cats had echocardiographic evidence of cardiac hypertrophy. In conclusion, cats with PKD had a minor increase in mean arterial pressure compared to control cats, and half of the cats had a high ARR.     

The diagnostic significance of the plasma N-terminal pro-B-type natriuretic Peptide concentration in asymptomatic cats with cardiac enlargement

We evaluated the diagnostic significance of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration in asymptomatic cats with cardiac enlargement. The plasma NT-proBNP concentration was measured in 21 clinically healthy control cats, and 67 asymptomatic cats with cardiac enlargement defined as end-diastolic interventricular septum thickness (IVSd) and/or diastolic left ventricular posterior wall thickness (LVPWd) >0.6 cm, vertebla heart scale (VHS) >7.8, and/or left atria/aorta ratio (LA/Ao) >1.5. The plasma NT-proBNP concentration in the asymptomatic cats with cardiac enlargement (median: 662.0, range: 24.0-2,449.0 pmol/l) was significantly higher than that in the controls (24.0, 24.0-95.0 pmol/l, P<0.001). The plasma NT-proBNP concentration was significantly correlated with the VHS, LA/Ao, IVSd and LVPWd (r=0.578, P<0.001; r=0.462, P<0.001; r=0.563, P<0.001; and r=0.764, P<0.001, respectively). Receiver operating characteristic analysis showed a cut-off value of 95.0 pmol/l for the detection of asymptomatic cats with cardiac enlargement, sensitivity and specificity of 88.1 and 100%, respectively, and an area under the curve of 0.971. These results suggest that the determination of the plasma NT-proBNP concentration can be a useful screening test for asymptomatic cats with cardiac enlargement.     

The effect of atenolol on NT-proBNP and troponin in asymptomatic cats with severe left ventricular hypertrophy because of hypertrophic cardiomyopathy: a pilot study

Background: Atenolol often is used empirically in cats with hypertrophic cardiomyopathy (HCM) before the onset of heart failure, although evidence of efficacy is lacking. Cardiac biomarkers play a critical role in the early detection of subclinical cardiac disease, in the prediction of long‐term prognosis, and in monitoring the response to therapy in humans. Hypothesis: Circulating concentrations of the biomarkers N‐terminal pro‐B type natriuretic peptide (NT‐proBNP) and cardiac troponin I (cTnI) will decrease after chronic administration of atenolol PO to cats with severe HCM but no signs of heart failure. Animals: Six Maine Coon or Maine Coon cross cats with severe HCM. Methods: Cats were treated with atenolol (12.5 mg PO q12 h) for 30 days. No cat had left ventricular dynamic outflow tract obstruction caused by systolic anterior motion of the mitral valve. The concentrations of NT‐proBNP and cTnI were assayed before and on the last day of drug administration. Results: There was no statistically significant change in NT‐proBNP (median before, 394 pmol/L; range, 71–1,500 pmol/L; median after, 439 pmol/L; range, 24–1,500 pmol/L; P = .63) or in cTnI (median before, 0.24 ng/mL; range, 0.10–0.97 ng/mL; median after, 0.28 ng/mL; range, 0.09–1.0 ng/mL; P = .69) after administration of atenolol. Conclusions: Atenolol administration did not decrease NT‐proBNP or cTnI concentrations in cats with severe left ventricular hypertrophy caused by hypertrophic cardiomyopathy. These results suggest that atenolol did not decrease myocardial ischemia and myocyte death in these cats. A larger clinical trial is warranted to verify these findings.     

Utility of measuring plasma N-terminal pro-brain natriuretic peptide in detecting hypertrophic cardiomyopathy and differentiating grades of severity in cats

Background: Cats with hypertrophic cardiomyopathy (HCM) often have no clinical signs or subtle signs. Measurement of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) has been demonstrated in people to be highly specific for heart disease and also correlates with severity of HCM. NT‐proBNP may also be valuable in detecting and grading HCM in cats, but results to date have been equivocal. Objectives: The aims of this study were to evaluate NT‐proBNP as a screening test for diagnosis of HCM in cats and determine an appropriate cut‐off value and to determine if NT‐proBNP concentrations correlated with severity of HCM in cats. Methods: Plasma NT‐proBNP concentrations were measured in 201 cats using an ELISA designed for use in cats. Cats were classified using echocardiography as clinically healthy controls (n=99) or cats with equivocal (n=9), mild (n=15), moderate (n=17), or severe (n=61) HCM. Results: NT‐proBNP concentrations (median; 25th–75th interquartile percentiles) in mildly (216.1; 87.6–392.5 pmol/L), moderately (282.7; 131.9–466.6 pmol/L), and severely (839.5; 655.3–1046.4 pmol/L) affected cats were significantly higher than those in healthy controls (18.9; 3.4–62.4 pmol/L). Concentrations in severely affected cats were significantly higher than in cats from other HCM groups. There was no significant difference between mild and moderate HCM. Cut‐off values >49 pmol/L had a sensitivity of 97.8% and specificity of 66.7%; >100 pmol/L had a sensitivity of 92.4% and specificity of 93.9%; and >150 pmol/L had a sensitivity of 88% and a specificity of 100%. Conclusions: NT‐proBNP with a cut‐off value of >100 pmol/L was useful in detecting even mild HCM. Cats with increased NT‐proBNP concentrations should be examined by echocardiography.     

Localization profiles of natriuretic peptides in hearts of pre-hibernating and hibernating Anatolian ground squirrels (Spermophilus xanthoprymnus)

The Anatolian ground squirrel (Spermophilus xanthoprymnus) is a typical example of true mammalian hibernators. In order to adapt to extreme external and internal environments during hibernation, they lower their body temperatures, heart rates and oxygen consumption; however, pathological events such as ischemia and ventricular fibrillation do not occur in their cardiovascular systems. During the hibernation, maintenance of cardiac function is very important for survival of ground squirrels. Natriuretic peptides (NPs) are key factors in the regulation of cardiovascular hemostasis. Since NPs’ role on the protection of heart during hibernation are less clear, the aim of this study was to investigate dynamic changes in NPs content in the cardiac chambers and to reveal the possible role of NPs on establishing cardiac function in ground squirrel during hibernation using immunohistochemistry. The immunohistochemical results indicate that cardiac NP expressions in atrial and ventricular cardiomyocytes were different from each other and were sex-independent. ANP and BNP were expressed in a chamber-dependent manner in female and male squirrel hearts. Furthermore, cardiac NPs expression levels in hibernation period were lower than those at the pre-hibernation period. During prehibernation period, ANP, BNP and CNP were expressed in the white and beige adipocytes of epicardial adipose tissue (EAT); while during hibernation period, the brown adipocytes of EAT were positive for BNP and CNP. These data suggest that the hibernation-dependent reduction in levels of NPs, particularly ANP, in cardiac chambers and EAT may be associated with low heart rate and oxygen consumption during hibernation. However, further studies are needed to better delineate the roles of NPs during the hibernation.

     

Circulating natriuretic peptides in cats with heart disease

BACKGROUND: Circulating natriuretic peptide concentrations are increased in cats with myocardial dysfunction. HYPOTHESIS: Serum N-terminal fragment of proatrial natriuretic peptide (NT-proANP) and NT-probrain natriuretic peptide (proBNP) concentrations may predict the presence of heart disease (HD) and congestive heart failure (CHF). A positive relationship is also predicted among natriuretic peptide (NP) concentrations, a noninvasive estimate of left ventricular filling pressure (E/E(a)), and an echocardiographic measure of left atrial (LA) size (LA/aortic diameter [Ao]). METHODS: Serum NP concentrations were measured in 28 healthy control and 50 study cats using sandwich enzyme immunoassays. The study group comprised cats, with HD but no CHF (HD - CHF, n = 17) and cats with CHF (HD + CHF, n = 33). The relationship among NP concentrations, LA size, and E/E(a) was examined. The ability of NP to distinguish control from study cats, and HD - CHF from HD + CHF cats, was explored using receiver operator curve analysis. RESULTS: NP concentrations were significantly lower in control than in study cats (P= .0001). The NT-proBNP concentrations were positively correlated with LA/Ao ratio (rho= 0.34; P= .02) and with E/E(a) ratio (rho= 0.68; P < .05). An NT-proBNP concentration of 49 fmol/mL gave a sensitivity and specificity of 100 and 89.3%, respectively, for correctly distinguishing 96.2% of control from study cats. Pairwise comparisons of the areas under the curve identified a statistically significant difference (P= .011) between NT-proANP and NT-proBNP to distinguish control from study cats. NT-proANP and NT-proBNP concentrations were significantly higher in HD + CHF cats than in HD - CHF cats (P= .0023 and .0001, respectively). CONCLUSIONS: Serum concentrations of NT-proANP and particularly NT-proBNP were different in healthy control cats, asymptomatic cats with HD, and cats with CHF, suggesting that measurement of NP concentrations may prove clinically useful as an initial screening test for cats with suspected cardiac disease.