Reviving vacuum-dried encapsulated ram spermatozoa via ICSI after 2 years of storage.

Introduction: Freeze-drying techniques give alternative preservation mammalian spermatozoa without liquid nitrogen. However, most of the work has been conducted in the laboratory mouse, while little information has been gathered on large animals that could also benefit from this kind of storage. Methods: This work adapted a technique known as vacuum-drying encapsulation (VDE), originally developed for nucleic acid conservation in anhydrous state, to ram spermatozoa, and compared it to canonical lyophilization (FD), testing long-term storage at room temperature (RT) and 4°C. Results and discussion: The results demonstrated better structural stability, namely lipid composition and DNA integrity, in VDE spermatozoa than FD ones, with outcomes at RT storage comparable to 4°C. Likewise, in VDE the embryonic development was higher than in FD samples (12.8% vs. 8.7%, p < 0.001, respectively). Our findings indicated that in large mammals, it is important to consider dehydration-related changes in sperm polyunsaturated fatty acids coupled with DNA alterations, given their crucial role in embryonic development.

Echocardiographic measurements and cardiac anatomy in healthy Western hognose snakes (Heterodon nasicus).

This study aims to describe the most important cardiac structures in the Heterodon nasicus through echocardiography and anatomical dissection. Echocardiographic and echo-Doppler measurements were performed on twenty healthy adult Heterodon nasicus (10.10). The values of the ventricular length, aortic diameter, pulmonary trunk diameter, the mean thickness of the interventricular septum, and thicknesses of the wall of the cavum pulmonale (Cav. P) and cavum arteriosum (Cav. A), were measured. The aortic flow and pulmonary trunk flow were recorded. Two dead specimens (1.1) were dissected. The male's pulmonary trunk diameter was bigger compared to the female's in both the long and short axis. The reproductive ecology of Heterodon nasicus has yet to be fully elucidated upon, however, male territorialism and dispersal from the hibernacula, and multiple male courtships toward a single female were described, hence, the more active reproductive activity of the male and the consequent sexual selection toward a higher aerobic performance can be hypothesised. A moderate interventricular right to left shunt was noticed in the Cav. V of all the specimens, which is considered normal and should not confuse the clinician. Congenital defects, cardiomyopathies, valvulopathies, and pericardial diseases are known to occur in ophidians and other reptiles. Reliable data and profound knowledge of the anatomy and physiology of the ophidian heart are fundamental for the in vivo diagnosis of cardiac diseases in snakes.

Inflammatory, Mechanical and Infectious Complications Associated with Peripheral Intravenous Catheters in Dogs and Cats: A Risk Factor Analysis.

The placement of peripheral intravenous catheters (PIVC) is potentially associated with complications that negatively impact healthcare. Our study investigated factors associated with the occurrence of PIVC-related complications in dogs and cats at a Veterinary Teaching Hospital. The second aim was to determine the prevalence of PIVC bacterial colonization. A total of 76 dogs and 40 cats with PIVCs were evaluated for the occurrence of phlebitis and mechanical complications. The devices were removed when they ceased to be functional or when complications occurred, and the content was submitted for bacterial cultures and antimicrobial susceptibility tests. Both multivariable linear regression models and ROC analysis were employed. Complications were recorded in 46.6% of cases, and 20.7% of catheters yielded a positive culture. Among the isolates, 45% were classified as multi-resistant. In dogs, a ≥36-h indwelling time was associated with an increased risk of complications. Male cats seem more prone to developing complications, while the insertion of PIVCs under sedation may represent a protective factor in this species. In conclusion, PIVC-associated complications were frequently observed, and the high rate of positive culture for PIVCs, together with the presence of multi-resistant isolates, is a cause of concern in a hospital setting.

The Fatty Acid-Based Erythrocyte Membrane Lipidome in Dogs with Chronic Enteropathy.

Canine chronic enteropathies (CEs) are inflammatory processes resulting from complex interplay between the mucosal immune system, intestinal microbiome, and dietary components in susceptible dogs. Fatty acids (FAs) play important roles in the regulation of physiologic and metabolic pathways and their role in inflammation seems to be dual, as they exhibit pro-inflammatory and anti-inflammatory functions. Analysis of red blood cell (RBC) membrane fatty acid profile represents a tool for assessing the quantity and quality of structural and functional molecular components. This study was aimed at comparing the FA membrane profile, determined by Gas Chromatography and relevant lipid parameter of 48 CE dogs compared with 68 healthy dogs. In CE patients, the levels of stearic (p < 0.0001), dihomo-gamma-linolenic, eicosapentaenoic (p = 0.02), and docosahexaenoic (p = 0.02) acids were significantly higher, and those of palmitic (p < 0.0001) and linoleic (p = 0.0006) acids were significantly lower. Non-responder dogs presented higher percentages of vaccenic acid (p = 0.007), compared to those of dogs that responded to diagnostic trials. These results suggest that lipidomic status may reflect the "gut health", and the non-invasive analysis of RBC membrane might have the potential to become a candidate biomarker in the evaluation of dogs affected by CE.

Detection of Serum Allergen-Specific IgE in Atopic Dogs Tested in Northern Italy: Preliminary Study.

Canine atopic dermatitis (CAD) is a pruritic allergic skin disease associated with IgE-mediated hypersensitivity. IgE is detected using Serum Allergen-Specific IgE test (SAT) in order to identify allergens. The present study aims to identify the environmental allergens in atopic dogs living in Northern Italy using SAT. The screening SAT (sSAT), using a monoclonal antibody cocktail-based ELISA to identify indoor and outdoor allergens, was performed. In all positive samples, an anti-IgE monoclonal antibody ELISA test was performed to extend panel of allergens. Out of 117 selected dogs, 69 were included in the study; 71% were positive and 29% were negative to sSAT. Among the 49 positive sSAT, 53% were positive for both indoor and outdoor, 38.8% only for indoor, and 8.2% only for outdoor allergens. This is the first study on the frequency of allergens involved in CAD in Italy using SAT. IgE hypersensitivity in atopic dogs of Northern Italy is usually associated with indoor allergens, primarily house dust mites. Among the outdoor allergens, an important role was played by Rumex acetosa. Polysensitization also commonly occurs. Therefore, since the numerous factors affect the IgE positivity in CAD, specific panels for geographical areas should be considered and re-evaluated at time intervals.

Evaluation of eutectic lidocaine/prilocaine cream for jugular blood sampling in cats.

OBJECTIVES: The study aimed to evaluate the efficacy of a eutectic lidocaine/prilocaine cream (EMLA cream; Astra Pharmaceuticals) in reducing pain and reaction to venepuncture during jugular blood sampling in cats after a 30-min topical application time. METHODS: The study was a prospective, blind, controlled clinical trial. Eighteen healthy client-owned cats were randomly allocated to two study groups. All cats were clipped on the left jugular groove region and then, depending on the study group, either the placebo (liquid paraffin) or EMLA cream was applied to the region. The area was then kept protected for the next 30 mins. Except for the operator who administered the product, all operators were blinded to the study groups. Blood sampling was performed by an experienced operator and a stress score was assigned to each cat according to the reactions observed during the venepuncture. Also, the procedure was classified as being 'easy' or 'difficult' by the same operator. RESULTS: A significantly reduced stress score was observed in cats that received the EMLA cream compared with those belonging to the placebo group (P = 0.048); withdrawal movements were observed in 1/9 cats treated with the EMLA cream vs 7/9 cats of the placebo group (P = 0.015). The jugular venepuncture was defined as easy in 1/9 cats that received the placebo and in 8/9 cats in the EMLA group (P = 0.015). CONCLUSIONS AND RELEVANCE: The present study provides evidence for the efficacy of the EMLA cream after a 30-min application time for jugular venepuncture in cats, together with significantly reduced stress for patients. Therefore, this study supports the routine use of EMLA cream as good practice to enhance the welfare of cats and to simplify venepuncture procedures.

Frequency of Blood Types A, B and AB in a Population of Non-Pedigree Domestic Cats from Central Italy.

Blood transfusion reactions and neonatal isoerythrolysis are common events in the feline population due to the presence of natural alloantibodies in the AB blood group system. It is known that the frequency of feline blood types varies according to the geographic region and breed. Therefore, the aims of this study were to investigate the frequency of AB blood groups in non-pedigree domestic cats in Central Italy and estimate the risk of a life-threatening transfusion reaction and neonatal isoerythrolysis, caused by mismatched transfusion or incompatible random mating, respectively. The AB blood group was determined on non-pedigree domestic feline patients and potential blood donors submitted at the Veterinary Teaching Hospitals of the Universities of Teramo (Abruzzo Region, Teramo, Italy) and Perugia (Umbria Region, Teramo, Italy), and visited at veterinary practitioners in Rome (Lazio Region, Teramo, Italy) using commercial immunochromatographic cartridges and commercial agglutination cards. There were four hundred and eighty-three cats included in the study. The frequencies of the blood types were: 89.9% type A, 7.0% type B, and 3.1% type AB. The probability of an acute hemolytic transfusion reaction or a neonatal isoerythrolysis was 6.5%. Although the frequency of type B in non-pedigree domestic cats living in Central Italy was relatively low, to reduce the risk of fatal transfusion reactions, blood group typing is recommended before each transfusion.

Early Renal Involvement in Cats with Natural Feline Morbillivirus Infection.

Feline morbillivirus (FeMV) is a newly discovered paramyxovirus infecting domestic cats and its role in the pathogenesis of feline chronic kidney disease (CKD) has been suggested, however not confirmed. The primary aim of the study was to evaluate the renal damage associated with FeMV infection in cats. In this retrospective study, clinical and clinicopathological data were compared among 14 FeMV naturally infected, 21 CKD and 22 healthy cats. FeMV positive cats had serum chemistry analytes and main urine chemistry results similar to the healthy subjects. FeMV positive cats had significantly decreased urine specific gravity (median 1054, range 1022-1065) and urine creatinine (median 227.23 mg/dL, range 83.02-489.75) when compared with healthy cats (median 1067, range 1040-1080, P < 0.001; median 406.50 mg/dL, range 195.32-575.58; P < 0.001, respectively). Urine protein:creatinine ratio (UPC) results of FeMV and CKD were not different (median 0.20, range 0.08-1.03; median 0.23, range 0.10-0.80, respectively), however UPC results were significantly increased in both groups, if compared with healthy cats (median 0.1, range 0.04-0.250, P < 0.01). Based on clinical data, serum creatinine concentration, urine specific gravity and UPC results, CKD was suspected by clinicians in 3/14 FeMV cats. Urine protein sodium-dodecyl-sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in 10/13 (77%) FeMV cats indicated a tubular pattern, with a decrease of uromodulin and an increase in the number and intensity of low molecular weight proteins. FeMV infection can be associated with different grades of renal dysfunction ranging from mild tubular proteinuria with less concentrated urine to azotemia in cats younger than those typically affected by CKD.

Evaluation of Bronchoscopy and Bronchoalveolar Lavage Findings in Cats With Aelurostrongylus abstrusus in Comparison to Cats With Feline Bronchial Disease.

The cat lungworm Aelurostrongylus abstrusus is a cause of lower respiratory tract disease worldwide. Bronchoscopy and bronchoalveolar lavage (BAL) are important tools for diagnosing respiratory diseases in cats. Therefore, the aim of the study was to investigate the usefulness of bronchoscopy and BAL in the diagnosis of A. abstrusus. Findings from bronchoscopic examination and BAL of 24 naturally infected cats were evaluated and compared with those of 12 cats with idiopathic Feline Bronchial Diseases (FBDs). Data were analyzed using Mann-Whitney or Fisher's exact tests. No significant bronchoscopic differences were detected between cats with aelurostrongylosis and FBDs in bronchial mucus, nodular lesions, and airway collapse. On the other hand, airway hyperemia, epithelial irregularities, and bronchial stenosis were observed more frequently in cats affected by FBDs than aelurostrongylosis, while bronchiectasis was found only in cats infected by A. abstrusus. Neutrophilic, eosinophilic, lymphocytic, and mixed inflammation were recorded in both groups. Bacteria or bacterial DNA was identified regardless of the presence or absence of A. abstrusus with no significant differences between groups. Larvae of A. abstrusus were cytologically detected in 5 of the 24 cats (20.8%) with aelurostrongylosis. These results indicate that, although some findings on bronchoscopic examination (i.e., bronchiectasis) can be described more frequently in cats infected by A. abstrusus, bronchial alterations and cytological findings in aelurostrongylosis are not specific unless larvae are observed and overlap with those of other feline airway diseases.

Comparison of clinical and imaging findings in cats with single and mixed lungworm infection.

OBJECTIVES: This study has compared clinical and imaging features in 52 cats naturally infected by respiratory nematodes Aelurostrongylus abstrusus, Troglostrongylus brevior and Capillaria aerophila, and in both monospecific and mixed infections. METHODS: Medical records of cats with a lungworm disease were retrospectively reviewed. Cats with clinical examination findings, haematobiochemical analysis and thoracic radiography were included in the study and clinical and radiographic scores were assigned. For eight cats CT of the thorax was also available and analysed. A statistical analysis was performed to investigate the potential correlation between clinical and radiographic score, and to evaluate the effect of age, sex and infection on clinical and radiographic severity. RESULTS: Monospecific infections by A abstrusus (32/52), T brevior (6/52) and C aerophila (5/52) and coinfections by T brevior/ A abstrusus (7/52), T brevior/ C aerophila (1/52) and A abstrusus/ C aerophila (1/52) were diagnosed. Cats with mixed infections showed higher clinical scores compared with cats with monospecific parasitoses ( P <0.05), while no differences were observed for radiographic scores. No correlation between clinical and radiographic scores was found (rs = 0.50), and these scores were not affected by patient age or sex. CT, performed on cats infected with A abstrusus, T brevior or A abstrusus/T brevior, provided additional information in cats with mild radiographic signs. CONCLUSIONS AND RELEVANCE: This study indicates that clinical parameters may be more severe in mixed infections than in monospecific parasitoses. A significant correlation between clinical and radiographic score was not detected, while several subclinically infected cats showed radiographic changes. In cats with mild-to-moderate lung patterns, the ventrodorsal/dorsoventral projection showed lesions that are not visible in the lateral projections, especially in the caudal lobes.

Serological and molecular investigation of 2117-like vesiviruses in cats.

Vesivirus 2117 was first discovered as a contaminant in Chinese hamster ovary (CHO) cell cultures used for human drug production. Similar vesiviruses (VeVs) have been detected recently in dogs. In order to address the hypothesis that cats may also be exposed to 2117-like VeVs, in this study, we screened 236 feline sera using an enzyme-linked immunosorbent assay (ELISA) based on a recombinant VP1 protein from the canine VeV Bari/212/07/ITA. IgG antibodies against the 2117-like VeV were detected in 37.3% of the sera tested. Also, by screening cat faecal specimens, the RNA of a 2117-like VeV was detected in a clinically healthy cat.

Single and mixed feline lungworm infections: clinical, radiographic and therapeutic features of 26 cases (2013-2015).

Objectives The aim of this study was to retrospectively describe clinical, radiographic and therapeutic features of feline lungworm infection. Methods Medical records of cats with lungworm diagnosis, thoracic radiography and without concurrent diseases between 2013 and 2015 were reviewed. Collection of data included physical examination, haematology, serum biochemistry, therapy with a variety of anthelmintics and outcomes. Results Thirty-seven records were recovered and 26 were included in the study. Single infections by Aelurostrongylus abstrusus (n = 15), Troglostrongylus brevior (n = 3) and Capillaria aerophila (n = 1) and coinfections by T brevior/ A abstrusus (n = 6) and T brevior/ C aerophila (n = 1) were diagnosed. The most common respiratory signs were coughing (n = 12), increased vesicular sounds (n = 10), dyspnoea (n = 9), such as laboured breathing, orthopnoea or open-mouth breathing, and tachypnoea (n = 6). Two cats were subclinically infected. The most common laboratory abnormality was anaemia (n = 7). Radiographic patterns recorded were interstitial (n = 24), bronchial (n = 21), alveolar (n = 10) and vascular (n = 2). Twenty-five cats had a complete recovery within 2-6 weeks of therapy. One kitten died 7 days after the diagnosis. Conclusions and relevance Lungworms should always be included in the differential diagnosis in cats living in endemic areas and presenting with respiratory signs and radiographic abnormalities. A copromicroscopic examination should be considered as the first diagnostic step for all cats at risk of lungworm infections. In most cases, timely therapy with a variety of anthelmintics guarantees recovery.

Sensitivity, specificity, and interobserver variability of survey thoracic radiography for the detection of heart base masses in dogs.

OBJECTIVE To determine the sensitivity, specificity, and interobserver variability of survey thoracic radiography (STR) for the detection of heart base masses (HBMs) in dogs. DESIGN Retrospective case-control study. ANIMALS 30 dogs with an HBM and 120 breed-matched control dogs (60 healthy dogs and 60 dogs with heart disease and no HBM). PROCEDURES In a blinded manner, 2 observers (designated as A and B) evaluated STR views from each dog for a mass-like opacity cranial to the heart, tracheal deviation, cardiomegaly, findings suggestive of pericardial effusion or right-sided congestive heart failure, and soft tissue opacities suggestive of pulmonary metastases. Investigators subsequently provided a final interpretation of each dog's HBM status (definitely affected, equivocal, or definitely not affected). RESULTS Considering equivocal interpretation as negative or positive for an HBM, the sensitivity of STR for diagnosis of an HBM was 40.0% (95% confidence interval [CI], 22.5% to 57.5%) and 56.7% (95% CI, 38.9% to 74.4%), respectively, for observer A and 63% (95% CI, 46.1% to 80.6%) and 80.0% (95% CI, 65.7% to 94.3%), respectively, for observer B. The corresponding specificity was 96.7% (95% CI, 93.5% to 99.9%) and 92.5% (95% CI, 87.8% to 97.2%), respectively, for observer A and 99.2% (95% CI, 97.5% to 100%) and 92.5% (95% CI, 87.8% to 97.2%), respectively, for observer B. The presence of a mass-like opacity cranial to the heart or tracheal deviation, or both, was significantly associated with a true diagnosis of HBM. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that STR is a highly specific but not a highly sensitive predictor of HBM in dogs.

Invasive pleural malignant mesothelioma with rib destruction and concurrent osteosarcoma in a dog.

A 7-year-old Dachshund was clinically examined because of a 10-day history of lameness in the left hind limb. On the basis of radiological and cytological findings, an osteosarcoma of the left acetabular region was suspected. The dog underwent a hemipelvectomy and osteosarcoma was diagnosed by subsequent histopathological examination. An immovable subcutaneous mass was noted on the left chest wall during the physical examination and non-septic neutrophilic inflammation was diagnosed by cytology. Forty days later, the dog showed signs of respiratory distress with an in-diameter increase of the subcutaneous mass up to 4 cm. Thoracic radiography and ultrasonography revealed pleural effusion and a lytic process in the fourth left rib. Furthermore, ultrasound examination revealed a mixed echogenic mobile structure with a diameter of around 2 cm floating within the pleural fluid of the left hemithorax close to the pericardium. The dog underwent surgery for an en bloc resection of the subcutaneous mass together with the fourth rib and the parietal pleura. Moreover, the left altered lung lobe, corresponding to the mobile structure detected by ultrasound, was removed. Based on cytological, histopathological, and immunohistochemical examinations, an invasive epithelioid pleural malignant mesothelioma was diagnosed.

Irreversible pulmonary hypertension associated with Troglostrongylus brevior infection in a kitten.

A four month-old kitten was referred at the Veterinary Teaching Hospital of Teramo, Italy. Physical examination, echocardiography, thoracic radiography, copromicroscopy and biomolecular assays led to a diagnosis of severe parasitic bronchopneumonia by Troglostrongylus brevior complicated by pulmonary hypertension. A single administration of a spot on solution containing imidacloprid 10%/moxidectin 1% was effective in stopping larval shedding but clinical, radiographic and echocardiographic signs of bronchopneumonia and pulmonary hypertension still persisted after further follow-ups.While cases of pulmonary hypertension are known in infections by Aelurostrongylus abstrusus, this is the first report of irreversible pulmonary hypertension in a kitten with troglostrongylosis.

First report of feline morbillivirus in Europe.

Feline morbillivirus was detected in urine samples of a 15 year old cat suffering from severe nephropathy. Viral RNA was not detected in blood and faecal samples and also the most common pathogens associated to cat kidney failure were not found. This report describes the first evidence of feline morbillivirus in Europe.

Proteomics-driven analysis of ovine whey colostrum.

The aim of this study was to shed light in to the complexity of the ovine colostrum proteome, with a specific focus on the low abundance proteins. The ovine colostrum is characterized by a few dominating proteins, as the immunoglobulins, but it also contains less represented protein species, equally important for the correct development of neonates. Ovine colostrum, collected immediately after lambing, was separated by 1D SDS-PAGE. Proteins bands were digested with trypsin and the resulting peptides were analyzed by LC-MS/MS. On the basis of the Swiss-Prot database, a total of 343 unique proteins were identified. To our knowledge, this study represents the most comprehensive analysis of ovine colostrum proteome.

Red blood cell distribution width in dogs with chronic degenerative valvular disease.

OBJECTIVE: To evaluate RBC distribution width (RDW) in dogs with chronic degenerative valvular disease (CDVD) with compensated or decompensated heart failure. DESIGN: Retrospective case-control study. ANIMALS: 27 healthy dogs and 135 dogs with CDVD (87 dogs with compensated heart failure and 48 dogs with decompensated heart failure). PROCEDURES: The RDW and various CBC and serum biochemical variables were compared among groups. Correlations between RDW and various echocardiographic variables were evaluated. RESULTS: Mean ± SD RDW in dogs with CDVD (13.1% ± 1.0%) was not significantly different from that of healthy dogs (12.8% ± 0.8%). The RDW of dogs with CDVD and compensated heart failure (13.0% ± 1.0%) was not significantly different from that of dogs with CDVD and decompensated heart failure (13.2% ± 1.1%). The RDW had a significant, weak, negative correlation with Hct (correlation coefficient, -0.250), hemoglobin concentration (correlation coefficient, -0.219), and mean corpuscular volume (correlation coefficient, -0.211). The RDW had a significant, weak, positive correlation with 1 echocardiographic index of CDVD severity (ie, the left atrium-to-aorta ratio [correlation coefficient, 0.183]). CONCLUSIONS AND CLINICAL RELEVANCE: In this study population, RDW did not seem to be associated with the presence of heart failure or CDVD.

Evaluation of the cardiac toxicity of N-methyl-glucamine antimoniate in dogs with naturally occurring leishmaniasis.

The aim of this study was to evaluate the cardiotoxic effects of pentavalent antimonial compounds in dogs with leishmaniasis. Twenty-eight dogs with clinical disease due to natural infection with Leishmania infantum were treated with 75 mg/kg meglumine antimoniate SC every 12h for 60 days. Serum cardiac troponin I (cTnI) concentrations were determined and routine and 24h ambulatory electrocardiographic monitoring was performed before the onset (T0) and at the end of treatment (T60). No abnormalities were found in routine and 24h electrocardiographic tracings before and after treatment. No statistical difference was found between serum cTnI concentrations or corrected QT intervals at T0 and T60. There was no evidence of laboratory or electrocardiographic features of cardiac toxicity in dogs with leishmaniasis treated with a therapeutic dose of meglumine antimoniate for 60 days.

Complementary therapeutic effects of dual delivery of insulin-like growth factor-1 and vascular endothelial growth factor by gelatin microspheres in experimental heart failure.

AIMS: Strategies to prevent adverse left ventricular (LV) remodelling after myocardial infarction have included several traditional approaches and novel cell-based or gene therapies. Delivery of growth factors in post-infarction heart failure has emerged as a valuable alternative strategy. Our aim was to investigate the effects of sequential release of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) from biodegradable gelatin microspheres in experimental heart failure. METHODS AND RESULTS: Gelatin hydrogel microspheres were known to guarantee a sustained release of encapsulated growth factors, characterized by an initial burst followed by a slower release. Rats with moderate myocardial infarction were randomized to receive empty microspheres (MI), microspheres loaded with IGF-1 or VEGF, or a combination thereof (DUAL). Myocardial injections of microspheres were performed at the time of surgery, and treatment lasted 4 weeks. Echocardiography, LV catheterization, morphometric histology and immunohistochemistry, and molecular assessment of downstream mediators [e.g. Akt, endothelial nitric oxide synthase (eNOS), and sarco/endoplasmic reticulum calcium ATPase-2 (SERCA-2)] were assessed at the end of the treatment period. Infarct sizes were 33 ± 2, 28 ± 4, 24 ± 3, and 16 ± 3% in the MI, IGF-1, VEGF, and DUAL groups, respectively. IGF-1 attenuated LV remodelling, improved LV systolic and diastolic function, increased myocyte size, and reduced apoptotic deaths, capillary loss, and indexes of inflammation. VEGF-treated animals displayed a marked myocardial neoangiogenesis that led to the formation of mature vessels if combined with IGF-1 delivery. Downstream effects of IGF-1 were principally mediated by the Akt-mTOR (mammalian target of rapamycin)-dependent pathway, and both growth factors, particularly VEGF, induced a robust and sustained increase of eNOS. CONCLUSION: IGF-1 and VEGF exerted complementary therapeutic effects in post-infarction heart failure. Biodegradable gelatin microspheres provide sustained and controlled growth factor release locally, exposing myocardial tissue without the side effects of systemic administration.