We studied the influence of experimentally induced DM1, in combination with different dietary n6:n3 polyunsaturated fatty acid (PUFA) ratios on different types of nerve fibers in rat myocardium, in order to reveal whether protective/unfavorable effects of different PUFAs on myocardial function in diabetic patients could be a (partial) repercussion of their effect on the changes in cardiac innervation. The control group (c) and diabetic group (stz) were fed with an n6/n3 ratio of ≈7; the diet of the stz+n6 group had an n6/n3 ratio ≈60, while the diet for the stz+DHA group contained 2.5% of fish oil (containing 16% eicosapentaenoic acid—EPA and 19% docosahexaenoic acid—DHA), n6/n3 ratio of ≈1. DM1 was induced by i.p. injection of streptozotocin (55 mg/kg) and rats were euthanized 30 days after induction. Immunohistochemistry was used for the detection and quantification of different types of neuronal fibers in the cardiac septum. We found changes in cardiac innervations characteristics for the initial phase of experimental DM1, which manifested as an increase in total number and area density of all neuronal fibers, measured by Pgp9.5 immunoreactivity. By detailed analysis, we found that this increase consisted mostly of heavy myelinated NF200 immunoreactive fibers and TH immunoreactive sympathetic fibers, while the density of ChAT immunoreactive parasympathetic fibers decreased. In the deep (middle) part of the myocardium, where rare fibers (of all studied types) were found, significant differences were not found. Surprisingly, we found a more consistent protective effect of n6 PUFAs, in comparison to n3 PUFAs supplementation. These results may provide a better understanding of the potential impacts of different PUFA ratios in the diet of diabetic patients on cardiac innervation and genesis and outcome of diabetic autonomic cardiomyopathy.
BackgroundMitochondrial dysfunction is one of key factors causing heart failure. We performed a comprehensive analysis of expression of mitochondrial quality control (MQC) genes in heart failure.MethodsMyocardial samples were obtained from patients with ischemic and dilated cardiomyopathy in a terminal stage of heart failure and donors without heart disease. Using quantitative real‐time PCR, we analysed a total of 45 MQC genes belonging to mitochondrial biogenesis, fusion‐fission balance, mitochondrial unfolded protein response (UPRmt), translocase of the inner membrane (TIM) and mitophagy. Protein expression was analysed by ELISA and immunohistochemistry.ResultsThe following genes were downregulated in ischemic and dilated cardiomyopathy: COX1, NRF1, TFAM, SIRT1, MTOR, MFF, DNM1L, DDIT3, UBL5, HSPA9, HSPE1, YME1L, LONP1, SPG7, HTRA2, OMA1, TIMM23, TIMM17A, TIMM17B, TIMM44, PAM16, TIMM22, TIMM9, TIMM10, PINK1, PARK2, ROTH1, PARL, FUNDC1, BNIP3, BNIP3L, TPCN2, LAMP2, MAP1LC3A and BECN1. Moreover, MT‐ATP8, MFN2, EIF2AK4 and ULK1 were downregulated in heart failure from dilated, but not ischemic cardiomyopathy. VDAC1 and JUN were only genes that exhibited significantly different expression between ischemic and dilated cardiomyopathy. Expression of PPARGC1, OPA1, JUN, CEBPB, EIF2A, HSPD1, TIMM50 and TPCN1 was not significantly different between control and any form of heart failure. TOMM20 and COX proteins were downregulated in ICM and DCM.ConclusionsHeart failure in patients with ischemic and dilated cardiomyopathy is associated with downregulation of large number of UPRmt, mitophagy, TIM and fusion‐fission balance genes. This indicates multiple defects in MQC and represents one of potential mechanisms underlying mitochondrial dysfunction in patients with heart failure.
Background Diabetic patients tend to have increased platelet reactivity after coronary artery bypass grafting (CABG). The aim of this study was to determine the association between hemoglobin A1c (HbA1c) values and platelet reactivity and to evaluate the consequent impact on clinical outcomes in patients undergoing CABG. Methods This prospective observational trial consecutively enrolled 225 diabetic patients undergoing CABG, between February 2014 and October 2018. HbA1c levels and platelet function (multiple electrode aggregometry [MEA]) were analyzed the day before surgery and on postoperative day 4 (POD 4). Patients were divided into two groups according to the HbA1c value: HBA1c < 7% and HbA1c ≥ 7%. Results Significantly higher postoperative ASPI (platelet function test based on arachidonic acid) and ADP (platelet function test based on adenosine diphosphate) test values were observed at POD 4 compared with preoperative values (ASPI test: p < 0.001; ADP test: p < 0.001). The prevalence of preoperative aspirin resistance (AR) was 46.4% relative to 57.2% after surgery showing consistent increase in postoperative AR by approximately 10%. In addition, the prevalence of AR in the HbA1c < 7% group was higher by 10% compared with the HbA1c ≥ 7% group, both before and after surgery. We did not demonstrate differences in clinical outcomes between the HbA1c groups. Conclusion Perioperative assessment of platelet reactivity in diabetic patients detects those with AR who may be at increased risk of adverse ischemic events. A personalized approach guided by MEA and administration of early and more potent antiaggregation therapy after CABG can be beneficial in this group of patients.
Introduction: Aortic valve pathology carries a high mortality burden. Its incidence is growing in proportion to the continuous ageing of the population. Surgery remains the gold standard in the treatment of severe aortic valve disease. Methods: We performed a retrospective analysis of the University Hospital Center Zagreb's cardiac surgical database from 2009 to 2020, focusing on surgical aortic valve replacement (SAVR). We dichotomized patients with respect to the date of their surgical procedures into two eras. Group 1 included patients operated from 2009-2014, whereas Group 2 included patients operated on from 2015-2020. Results: A total of 1012 SAVRs were identified during the study period. The procedural volume over the two identical 6-year time periods increased in the latter era from 413 to 598. When comparing groups 1 and 2, we have observed in increase in the number of patients with diabetes (19% vs. 26%, P=0.015) and coronary artery disease (14% vs. 18%, P=0.099). The composite risk assessment score increased significantly from 3.0±2.4 to 3.2±2.7, P=0.023. Despite an increase in the comorbidity burden of the targeted patient population, the periprocedural mortality remained the same (2.1% vs 2.5%, P=0.835). The per-patient averaged volume of transfused packed red blood cells decreased from 839±954 to 614±821 ml, P<0.001. An increase in the proportion of tissue valve implantations in comparison to mechanical prostheses was also noted in the present era (58% vs 68%, P=0.001) Conclusion: Despite an increasingly more complex patient population referred for SAVR in the contemporary era, the results have remained excellent. The introduction of transcatheter methods should measure up to the surgical standard.
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