Impact of preanaesthetic electrocardiogram on decision making and modification of anaesthetic protocols in dogs.

BACKGROUND: This retrospective observational study explored the impact of preanaesthetic electrocardiogram (ECG) assessment on preoperative echocardiography requests and modifications to a standardised anaesthetic protocol in healthy dogs. METHODS: A total of 228 healthy dogs with no previously diagnosed heart disease that underwent general anaesthesia at Complutense Veterinary Teaching Hospital from December 2017 to June 2018 were included. Preanaesthetic ECGs were assessed for abnormalities, and the findings were documented. The number of dogs requiring echocardiography, based on ECG findings, and the echocardiography results were recorded. All anaesthesia-related decisions were documented. RESULTS: Overall, 72 dogs (31.6%) exhibited ECG abnormalities. Echocardiography was requested for five dogs (2.2%). The anaesthetic protocol was changed in 11 dogs (15.3% of those with ECG abnormalities). P wave disturbances, ventricular premature complexes and impulse conduction issues were abnormalities that prompted echocardiography. Bradycardia and electrical impulse conduction abnormalities influenced protocol modifications. LIMITATIONS: The limited sample size meant that it was not possible to investigate potential correlations between demographics and ECG alterations. CONCLUSIONS: Preanaesthetic ECG screening was useful for promoting echocardiography and influencing anaesthesia plans in a subset of dogs. Despite this, further assessment of the impact of routine use of non-targeted preoperative ECG on anaesthesia-related outcomes is warranted.

Association between Thoracic Radiographic Changes and Indicators of Pulmonary Hypertension in Dogs with Heartworm Disease.

Pulmonary hypertension (PH) is a consequence of pulmonary endarteritis during infection with Dirofilaria immitis in dogs. Echocardiography is the technique of choice but is not always accessible to all clinicians. This study aimed to evaluate the association of the radiological findings in dogs with heartworm disease and the presence or absence of echocardiographically characterised PH. The study included 62 heartworm-infected dogs that underwent thoracic radiographs and echocardiography. The studied dogs showed moderate to severe PH when the Right Pulmonary Artery Distensibility (RPAD) Index was <29.5%. The RPAD Index was used for comparison with thoracic radiographs. The Vertebral Heart Size (VHS), right cranial pulmonary artery passing through the fourth rib in the laterolateral projection (CrPA/R4) ratio, and right caudal pulmonary artery to the ninth rib in the dorsoventral projection (CdPA/R9) ratio showed significant differences between dogs with/without PH (p < 0.001). Sensitivity (sen) and specificity (sp) cut-off values were obtained: VHS ≥ 9.53 (sen 93.75%, sp 63.33%); CrPA/R4 ≥ 1.08 (sen 87.5%, sp 70%); and CdPA/R9 ≥ 1.10 (sen 96.88%, sp 76.66%). The CrPA/R4 and CdPA/R9 ratios showed potential as a preliminary screening tool for PH in heartworm-infected dogs, suggesting that they may reliably indicate the presence of PH and guide the decision for further diagnostic testing.

Machine Learning Techniques for Canine Myxomatous Mitral Valve Disease Classification: Integrating Anamnesis, Quality of Life Survey, and Physical Examination.

Myxomatous mitral valve disease (MMVD) is a prevalent canine cardiac disease typically diagnosed and classified using echocardiography. However, accessibility to this technique can be limited in first-opinion clinics. This study aimed to determine if machine learning techniques can classify MMVD according to the ACVIM classification (B1, B2, C, and D) through a structured anamnesis, quality of life survey, and physical examination. This report encompassed 23 veterinary hospitals and assessed 1011 dogs for MMVD using the FETCH-Q quality of life survey, clinical history, physical examination, and basic echocardiography. Employing a classification tree and a random forest analysis, the complex model accurately identified 96.9% of control group dogs, 49.8% of B1, 62.2% of B2, 77.2% of C, and 7.7% of D cases. To enhance clinical utility, a simplified model grouping B1 and B2 and C and D into categories B and CD improved accuracy rates to 90.8% for stage B, 73.4% for stages CD, and 93.8% for the control group. In conclusion, the current machine-learning technique was able to stage healthy dogs and dogs with MMVD classified into stages B and CD in the majority of dogs using quality of life surveys, medical history, and physical examinations. However, the technique faces difficulties differentiating between stages B1 and B2 and determining between advanced stages of the disease.

Usefulness of Tissue Doppler Imaging for the Evaluation of Pulmonary Hypertension in Canine Heartworm Disease.

BACKGROUND: Dirofilaria immitis is a nematode that produces proliferative pulmonary endarteritis in dogs due to direct contact of the adult parasites with the intima layer of the pulmonary arteries, leading to irreversible severe structural damage and sustained pulmonary hypertension (PH), which can produce severe cardiorespiratory disorders. The purpose of this study was to assess the diagnostic value of the echocardiography tissue Doppler imaging (TDI) in determining the presence of PH in dogs with heartworm disease. METHODS: There were 116 heartworm-infected dogs with PH and 33 healthy dogs included in the study. Based on the right pulmonary artery distensibility index (RPADi) < 29.5%, PH was present in 47.4% of infected dogs. Additionally, the animals were evaluated using other standard alternative echocardiographic measures to estimate PH. Moreover, a total of eight echocardiographic measurements were analysed using the TDI to determine its usefulness in diagnosing PH (E', A', S, E':A', global TDI, HRI-IVCT, HRI-IVRT, R-TEI). RESULTS: The TDI measurements showed significant differences between dogs with and without PH, demonstrating a positive correlation with respect to the RPADi. In addition, cut-off values for the detection of PH with excellent sensitivity and specificity were found for E':A', global TDI, HRI-IVCT, HRI-IVRT and R-TEI. CONCLUSIONS: The TDI mode may be useful as an adjunct diagnostic method for the determination of PH in dogs with Dirofilaria immitis.

Evaluation of heart fatty acid-binding protein as a biomarker for canine leishmaniosis.

BACKGROUND: Myocarditis frequently occurs in canine leishmaniosis (CanL). Heart fatty acid-binding protein (HFABP) is a biomarker of myocardial damage. METHODS: This study aimed to compare HFABP concentration (HFABPc) in healthy dogs and dogs at different stages of CanL and evaluate the correlation of this biomarker with several clinicopathological and echocardiographic variables. Thirty-one dogs diagnosed with CanL and 10 healthy dogs were included. RESULTS: HFABPc was not statistically different (p > 0.05) between groups of dogs at different LeishVet stages of CanL or between groups with high versus low to intermediate serology titres. In 70% of CanL dogs, HFABPc was within the 95% confidence interval limits of the mean of healthy dogs. A moderate negative correlation with globulin (r = -0.519; p = 0.03) and haematocrit (HCT) (r = -0.538; p = 0.02) was observed. No other significant correlation (p > 0.05) was observed with any other variable. LIMITATIONS: Many statistical tests were performed, and therefore, type I error cannot be ruled out. CONCLUSION: HFABPc is not consistently elevated in dogs with CanL and is not associated with the severity of the disease, or most echocardiographic or clinicopathological variables studied. The correlation with globulin and HCT was not strong and not considered clinically significant. HFABPc lacks sufficient predictive capacity in dogs with CanL, discouraging further research or clinical use of this biomarker in this disease.

Echocardiographic Assessment of the Pulmonary Vein to Pulmonary Artery Ratio in Canine Heartworm Disease.

Background:Dirofilaria immitis produces proliferative pulmonary endarteritis and pulmonary thromboembolism in infected dogs. The pulmonary vascular lesions lead to irreversible and persistent structural damage and, as a consequence, sustained precapillary pulmonary hypertension (PH). The purpose of this study was to assess the diagnostic value of the pulmonary vein to pulmonary artery ratio (PV:PA ratio) to determine moderate or severe PH (>50 mmHg) in dogs with heartworm disease. METHODS: A total of 151 naturally heartworm-infected and 66 healthy dogs were included in the study. The presence/absence of PH was based on the right pulmonary artery distensibility index (RPAD index < 29.5%), and the PV:PA ratio was echocardiographically measured by the time-motion mode (M mode) and two-dimensional mode (2D mode). Other echocardiographic parameters were also assessed (pulmonary trunk to aorta ratio, tricuspid regurgitation pressure gradient, and AT:ET ratio). RESULTS: The results of the PV:PA ratio showed a highly positive correlation between the M and 2D modes (r = 0.928). The PV:PA ratio obtained by the M mode was identified as the strongest predictor for RPAD index (R2 0.628, p < 0.0001) with a good diagnostic accuracy (AUC = 0.99). The results of PV/PA by the 2D mode showed a similar prediction for the RPAD index (R2 0.606, p < 0.0001) with a good diagnostic accuracy (AUC = 0.98). Both of the 2D and M modes' PV:PA ratios decreased significantly with the presence of PH. A cut-off value of ≤0.845 showed high sensitivity and specificity for the M mode (97% and 94%, respectively) and the 2D mode (96% and 93%, respectively). CONCLUSIONS: The PV:PA ratio may be useful as a complementary diagnostic method for the estimation of moderate or severe PH in dogs with heartworm.

Right Ventricle Strain Assessed by 2-Dimensional Speckle Tracking Echocardiography (2D-STE) to Evaluate Pulmonary Hypertension in Dogs with Dirofilaria immitis.

Echocardiographic assessment of the right ventricle is helpful for analysing the pathophysiology of heartworm disease and detecting pulmonary hypertension (PH) in dogs. In veterinary cardiology, the study of myocardial deformation using two-dimensional speckle tracking (2D-STE) echocardiography has become increasingly acknowledged as useful for quantifying right ventricular function. The aim of this study was to evaluate the usefulness of myocardial deformation strain of the right ventricular free wall (FWS), global deformation strain of the right ventricle, including the interventricular septum (GS), and tissue motion annular displacement of the tricuspid valve (TMAD) in a cohort of dogs with heartworm (Dirofilaria immitis) disease and to determine cut-off values for detecting the presence of PH. Out of the 93 dogs tested, 71% were diagnosed with heartworm infection. PH was identified in 41% of the infected dogs following the American College of Veterinary Internal Medicine (ACVIM) guidelines, based on the peak tricuspid regurgitation velocity to calculate the tricuspid regurgitation pressure gradient (TRPG), while other routine measurements were used, including the right pulmonary artery distensibility index (RPADi). The 2D-STE mode measurements were determined using Right Ventricular Automated Function Imaging (RV AFI®) software. The statistical analysis showed significant differences in the studied parameters among dogs with and without PH. Additionally, sensitivity (sen) and specificity (sp) cut-off values were obtained (GS ≥ -21.25%, sen 96%, sp 86.4%; FWS ≥ -21.95%, sen 92.56%, sp 95.5%; TMAD ≤ 0.85 cm, sen 70.4%, sp 83.3%). These results demonstrated that GS, FWS, and TMAD could be used as supplementary and alternative variables to conventional echocardiographic measurements when detecting PH in dogs with heartworm disease.

Impact of Obesity on Lung Function in Cats with Bronchoconstriction.

Obesity is a nutritional disorder commonly diagnosed in adult cats that has been associated with an increased risk of different chronic diseases including respiratory diseases. The main objective of this study is to define if there is a relation between lung function measured by barometric whole-body plethysmography and obesity in cats with bronchoconstriction. Fifty-three cats were included in the study. All animals presented a bronchoconstriction status diagnosed with an Enhanced Pause (Penh) value higher than the reference range. Based on a standardized 9-point body condition scale, 36 cats were normal-weight cats (with BCS < 6), and 17 cats were considered overweight or obese cats (with BCS ≥ 6). Overweight cats were mainly male cats and older, and presented lower tidal volume values, lower minute volume values, and lower peak inspiratory and expiratory flows than normal-weight cats. According to the results of the present study, overweight cats showed a more compromised lung function parameters related to restrictive pattern compared with normal-weight cats. However, overweight cats did not show a higher bronchoconstriction level compared with normal-weight cats.

Supplementation with a Cocoa-Carob Blend, Alone or in Combination with Metformin, Attenuates Diabetic Cardiomyopathy, Cardiac Oxidative Stress and Inflammation in Zucker Diabetic Rats.

Diabetic cardiomyopathy (DCM) is one of the main causes of mortality among diabetic patients, with oxidative stress and inflammation major contributors to its development. Dietary flavonoids show strong antioxidant and anti-inflammatory activities, although their potential additive outcomes in combination with antidiabetic drugs have been scarcely explored. The present study investigates the cardioprotective effects of a cocoa-carob blend (CCB) diet, rich in flavonoids, alone or in combination with metformin, in the development of DCM. Zucker diabetic fatty rats (ZDF) were fed with a CCB rich-diet or a control diet, with or without metformin for 12 weeks. Glucose homeostasis, cardiac structure and function, and oxidative and inflammatory biomarkers were analysed. CCB improved glucose homeostasis, and mitigated cardiac dysfunction, hypertrophy, and fibrosis in ZDF rats. Mechanistically, CCB counteracted oxidative stress in diabetic hearts by down-regulating NADPH oxidases, reducing reactive oxygen species (ROS) generation and modulating the sirtuin-1 (SIRT1)/ nuclear factor E2-related factor 2 (Nrf2) signalling pathway, overall improving antioxidant defence. Moreover, CCB suppressed inflammatory and fibrotic reactions by inhibiting nuclear factor kappa B (NFκB) and pro-inflammatory and pro-fibrotic cytokines. Noteworthy, several of these effects were further improved in combination with metformin. Our results demonstrate that CCB strongly prevents the cardiac remodelling and dysfunction observed in diabetic animals, highlighting its potential, alone or in adjuvant therapy, for treating DCM.

Gut Microbiota Profile Identifies Transition From Compensated Cardiac Hypertrophy to Heart Failure in Hypertensive Rats.

Microcirculatory alterations displayed by patients with heart failure (HF) induce structural and functional intestinal changes that may affect normal gut microbial community. At the same time, gut microbiota can influence pathological mechanisms implicated in HF progression. However, it is unknown whether gut microbiota dysbiosis can precede the development of cardiac alterations in HF or it is only a mere consequence. Our aim was to investigate the potential relationship between gut microbiota composition and HF development by comparing spontaneously hypertensive heart failure and spontaneously hypertensive rat models. Gut microbiota from spontaneously hypertensive heart failure, spontaneously hypertensive rat, and normotensive Wistar Kyoto rats at 9 and 19 months of age was analyzed by sequencing the 16S ribosomal RNA gene, and KEGG metabolic pathways associated to 16S profiles were predicted. Beta diversity, Firmicutes/Bacteroidetes ratio, taxonomic abundances, and potential metabolic functions of gut microbiota were significantly different in spontaneously hypertensive heart failure with respect to spontaneously hypertensive rat before (9 months) and after (19 months) cardiac differences were presented. Nine-month-old spontaneously hypertensive heart failure showed a significant increase in the genera Paraprevotella, Oscillospira, Prevotella 9, Faecalitalea, Faecalibacterium, Ruminiclostridium 6, Phascolarctobacterium, Butyrivibrio, Parasutterella, and Parabacteroides compared with both Wistar Kyoto and spontaneously hypertensive rat, while Ruminiclostridium 9, Oscillibacter, Ruminiclostridium, Mucispirillum, Intestinimonas, and Akkermansia were diminished. Of them, Akkermansia, Prevotella 9, Paraprevotella, and Phascolarctobaterium were associated to changes in cardiac structure and function. Our results demonstrate an association between specific changes in gut microbiota and the development of HF in a hypertensive model of HF and further support the intervention to restore gut microbiota as an innovative therapeutic strategy for preventing HF.

Anesthetic management of a dog with severe subaortic stenosis and mitral valve disease complicated with atrial fibrillation undergoing ovariohysterectomy.

The anesthetic management in patients with subaortic stenosis and mitral valve disease should involve intensive monitoring and the anesthesiologist's main concern is to ensure oxygen delivery and tissue perfusion. Since anesthetic procedures in such patients are rare, there is no previous report about the anesthetic management. A 5.5-year old, 32-kg Boxer, suffering a severe heart disease due to a final stage subaortic stenosis and mitral insufficiency, was anesthetized for an ovariohysterectomy to remove an ovarian tumor that was producing high-volume ascites. Methadone (0.3 mg kg-1) was administered intramuscularly (IM) for pre-anesthetic medication, etomidate (1.3 mg kg-1) and midazolam (0.2 mg kg-1) were used for the induction of anesthesia and after endotracheal intubation, anesthesia was maintained with sevoflurane vaporized in oxygen and air. Fentanyl (5-10 µg kg-1 h-1) and paracetamol (15 mg kg-1) were administered to improve analgesia. Previous persistent atrial fibrillation was refractory to medication (digoxin, diltiazem, and pimobendan) and continued during the anesthetic procedure. Dobutamine (1.5-5 µg kg-1 minute-1) helped to maintain mean arterial blood pressure above 60 mmHg. Epidural morphine (0.1 mg kg-1) and incisional bupivacaine (2 mg kg-1) were administered at the end of surgery to provide postoperative analgesia. Anesthesia was otherwise uneventful, and recovery was considered excellent.

Acute phase proteins and markers of oxidative stress to assess the severity of the pulmonary hypertension in heartworm-infected dogs.

BACKGROUND: Canine heartworm infection is characterized by pulmonary endarteritis and pulmonary hypertension (PH). The aim of the present study was to evaluate the relationship between PH with the concentrations of different positive (C-reactive protein [CRP] and haptoglobin [Hp]) and negative (albumin and paraoxonase-1 [PON-1]) acute phase proteins (APP), as well as the oxidative stress, by measuring glutathione peroxidase (GPx) and total antioxidant capacity (TAC) in 27 heartworm-infected dogs on Day 0 (diagnosis) and Day 120 (1 month after the last adulticide injection). Presence/absence of PH was determined by the Right Pulmonary Artery Distensibility (RPAD) Index. RESULTS: On Day 0, 62.9% of the dogs showed PH. Concentrations of CRP and Hp were higher in dogs with PH, especially in dogs with moderate-severe PH (P < 0.005 and P < 0.05, respectively). Albumin and PON-1 concentrations were higher in dogs without PH (P < 0.05 for albumin). On Day 120, 59.2% of the dogs presented with PH; CRP decreased while Hp increased (P < 0.005 and P < 0.05, respectively). Also, albumin and PON-1 rose, especially in absence of PH. There were not significant changes in the serum values of GPx and TAC. CONCLUSIONS: CRP and Hp have a potential prognostic role in dogs with dirofilariasis because increases in positive APP correlated with presence and severity of PH. CRP decreased, but Hp persisted at an elevated level in dogs with PH 1 month after the end of the adulticide treatment. CRP and Hp could work as early biomarkers of PH and be useful to stage the disease and to monitor the evolution of the patient and indirectly evaluate the persistence of arterial damage after the parasites have been eliminated. Albumin and PON-1 also showed potential value as markers of PH, although further research is necessary to determine its utility.

Diagnostic accuracy of electrocardiographic P wave related parameters in the assessment of left atrial size in dogs with degenerative mitral valve disease.

The purpose of this research was to compare the accuracy of newly described P wave-related parameters (P wave area, Macruz index and mean electrical axis) with classical P wave-related parameters (voltage and duration of P wave) for the assessment of left atrial (LA) size in dogs with degenerative mitral valve disease. One hundred forty-six dogs (37 healthy control dogs and 109 dogs with degenerative mitral valve disease) were prospectively studied. Two-dimensional echocardiography examinations and a 6-lead ECG were performed prospectively in all dogs. Echocardiography parameters, including determination of the ratios LA diameter/aortic root diameter and LA area/aortic root area, were compared to P wave-related parameters: P wave area, Macruz index, mean electrical axis voltage and duration of P wave. The results showed that P wave-related parameters (classical and newly described) had low sensitivity (range=52.3 to 77%; median=60%) and low to moderate specificity (range=47.2 to 82.5%; median 56.3%) for the prediction of left atrial enlargement. The areas under the curve of P wave-related parameters were moderate to low due to poor sensitivity. In conclusion, newly P wave-related parameters do not increase the diagnostic capacity of ECG as a predictor of left atrial enlargement in dogs with degenerative mitral valve disease.

Central corneal thickness and intraocular pressure in captive black-footed penguins (Spheniscus dermersus).

OBJECTIVE: To determine the central corneal thickness (CCT) by ultrasonic pachymetry and the effect of these values on the measurements of intraocular pressures (IOP) with rebound tonometry (TonoVet(®) ) in a captive flock of black-footed penguins (Spheniscus dermersus). Variations in CCT by age and weight, and variations in IOP by age were compared. ANIMAL STUDIED: Both eyes of 18 clinically normal black-footed penguins (Spheniscus dermersus) were used. PROCEDURE: The IOP was measured by the TonoVet(®) in both eyes of all the penguins. CTT measurements were performed 5 min later in all eyes using an ultrasound pachymeter. RESULTS: The mean IOP values ± SD were 31.77 ± 3.3 mm Hg (range of mean value: 24-38). The mean CCT values were 384.08 ± 30.9 µm (range of mean value: 319-454). There was no correlation between IOP and CCT values (P = 0.125). There was no difference in CCT measurements by age (P = 0.122) or weight (P = 0.779). A correlation was observed (P = 0.032) between IOP values and age. The coefficient of correlation was negative (ρ = -0.207). CONCLUSIONS: Ultrasound pachymetry has shown to be a reliable and easy technique to measure CCT in penguins. No correlation was observed between IOP and CCT values in this study. IOP showed a significant but weak decrease as age increased in the black-footed penguin.

Pulmonary function in obese vs non-obese cats.

Obesity is a risk factor in the development of several respiratory diseases. Lung volumes tend to be decreased, especially expiratory reserve volume, increasing expiratory flow limitation during tidal breathing. Barometric whole-body plethysmography is a non-invasive pulmonary function test that allows a dynamic study of breathing patterns. The objective of this study was to compare pulmonary function variables between obese and non-obese cats through the use of barometric whole-body plethysmography. Nine normal-weight and six obese cats were placed in the plethysmograph chamber, and different respiratory variables were measured. There was a significant decrease in tidal volume per kilogram (P = 0.003), minute volume per kilogram (P = 0.001) and peak inspiratory and expiratory flows per kilogram (P = 0.001) in obese cats compared with non-obese cats. Obesity failed to demonstrate a significant increase in bronchoconstriction index variable enhanced pause (Penh), as previously reported in humans and dogs. The results show that feline obesity impairs pulmonary function in cats, although a significant increase in bronchoconstriction indexes was not observed. Non-invasive barometric whole-body plethysmography can help characterise mechanical dysfunction of the airways in obese cats.

Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms.

BACKGROUND: Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart. METHODS: Goto-Kakizaki (GK) rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin) or vehicle (n=10, each). After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays. RESULTS: Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36), alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells. CONCLUSIONS: Sitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36) promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actions.

Eplerenone attenuated cardiac steatosis, apoptosis and diastolic dysfunction in experimental type-II diabetes.

BACKGROUND: Cardiac steatosis and apoptosis are key processes in diabetic cardiomyopathy, but the underlying mechanisms have not been elucidated, leading to a lack of effective therapy. The mineralocorticoid receptor blocker, eplerenone, has demonstrated anti-fibrotic actions in the diabetic heart. However, its effects on the fatty-acid accumulation and apoptotic responses have not been revealed. METHODS: Non-hypertensive Zucker Diabetic Fatty (ZDF) rats received eplerenone (25 mg/kg) or vehicle. Zucker Lean (ZL) rats were used as control (n = 10, each group). After 16 weeks, cardiac structure and function was examined, and plasma and hearts were isolated for biochemical and histological approaches. Cultured cardiomyocytes were used for in vitro assays to determine the direct effects of eplerenone on high fatty acid and high glucose exposed cells. RESULTS: In contrast to ZL, ZDF rats exhibited hyperglycemia, hyperlipidemia, insulin-resistance, cardiac steatosis and diastolic dysfunction. The ZDF myocardium also showed increased mitochondrial oxidation and apoptosis. Importantly, eplerenone mitigated these events without altering hyperglycemia. In cultured cardiomyocytes, high-concentrations of palmitate stimulated the fatty-acid uptake (in detriment of glucose assimilation), accumulation of lipid metabolites, mitochondrial dysfunction, and apoptosis. Interestingly, fatty-acid uptake, ceramides formation and apoptosis were also significantly ameliorated by eplerenone. CONCLUSIONS: By blocking mineralocorticoid receptors, eplerenone may attenuate cardiac steatosis and apoptosis, and subsequent remodelling and diastolic dysfunction in obese/type-II diabetic rats.

Eplerenone enhances cardioprotective effects of standard heart failure therapy through matricellular proteins in hypertensive heart failure.

AIMS: The addition of an aldosterone receptor antagonist on top of current optimal therapy (based on angiotensin II inhibition) has demonstrated an important clinical benefit in heart failure patients with systolic dysfunction. Whether this finding also applies to heart failure patients with preserved systolic function is unknown. Therefore, we have studied the effect of adding eplerenone to standard pharmacological heart failure therapy (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and diuretic and ß-blocker) in the progression of heart failure in spontaneously hypertensive heart failure (SHHF) rats. METHODS AND RESULTS: Two-month-old SHHF rats were randomized to receive no treatment (SHHF group), a standard heart failure therapy (quinapril-torasemide-carvedilol; ST-SHHF group), or the combination of eplerenone and standard heart failure therapy (Eple+ST-SHHF group) for 20 months. Untreated SHHF was characterized by progressive left ventricular hypertrophy, fibrosis, and myocardial contractile and relaxation abnormalities, leading to pulmonary congestion. Despite similar blood pressure control, the addition of eplerenone to standard heart failure therapy further prevented left ventricular hypertrophy, contractile and relaxation alterations, and pulmonary congestion than standard heart failure therapy alone. ST-SHHF and Eple + ST-SHHF rats showed similar inhibition of structural extracellular matrix proteins collagen I, collagen III and fibronectin and metalloproteinase (MMP)-2, MMP-7, MMP-12, and MMP-13. However, only the coadministration of eplerenone with standard heart failure therapy normalized the expression of matricellular proteins thrombospondin 1, tenascin C, periostin, and secreted protein acidic rich in cysteine/osteonectin to values comparable to normotensive rats. CONCLUSION: In a hypertensive heart failure rat model, the addition of eplerenone to conventional heart failure therapy further improves cardiac structural and functional parameters, delaying the progression of heart failure. These beneficial effects of eplerenone were associated with normalization of matricellular protein expression.

Rosuvastatin added to standard heart failure therapy improves cardiac remodelling in heart failure rats with preserved ejection fraction.

AIMS: Although statins may provide potential therapeutic pathways for patients with heart failure with preserved ejection fraction (HFpEF), no studies have evaluated statins in combination with standard HF therapy, which would reflect clinical practice more closely. To address this question, we evaluated whether rosuvastatin added to a standard HF therapy provides additional improvement in cardiac structure and function in rats with hypertensive heart failure (SHHF). METHODS AND RESULTS: Two-month-old SHHF rats were randomly assigned to four groups: (i) non-treated SHHF rats; (ii) rosuvastatin-treated SHHF rats; (iii) SHHF rats treated with quinapril plus torasemide plus carvedilol (considered as standard HF therapy); and (iv) SHHF rats treated with the combination of standard HF therapy and rosuvastatin. The administration of a standard anti-hypertensive HF therapy to SHHF rats for 17 months attenuated left ventricular (LV) chamber dilatation, cardiac hypertrophy, fibrosis, and inflammation compared with non-treated SHHF rats. Rosuvastatin alone prevented LV dilatation and cardiac inflammation similar to standard HF therapy-treated SHHF, despite being unable to normalize blood pressure (BP) or influence cardiac hypertrophy. However, and importantly, the addition of rosuvastatin to the standard HF therapy further prevented LV dilatation, preserved cardiac function, and normalized inflammation. CONCLUSION: These data show that the use of rosuvastatin plus a standard HF therapy results in a significant additional improvement in HF and cardiac remodelling in a rat model of HFpEF. These beneficial effects were independent of BP and plasma lipid changes, and seem to be due, at least in part, to decreased myocardial inflammation.