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Cerebral blood flow autoregulation protects brain tissue from blood pressure variations and maintains cerebral perfusion pressure by changes in vascular resistance. High salt (HS) diet impairs endothelium-dependent vasodilation in many vascular beds, including cerebral microcirculation, and may affect vascular resistance. The aim of present study was to determine if 7-day HS diet affected the reactivity of middle cerebral artery (MCA) to orthostatic challenge in healthy human individuals, and if autoregulatory mechanisms and sympathetic neural regulation were involved in this phenomenon. Twenty-seven persons participated in study (F:21, M:6, age range 19–24). Participants consumed 7-day low-salt (LS) diet (< 2.3 g kitchen salt/day) and afterwards 7-day HS diet (> 11.2 g kitchen salt/day). Blood and urine analysis and anthropometric measurements were performed after each diet. Arterial blood pressure, heart rate and heart rate variability, and cerebral and systemic hemodynamic parameters were recorded simultaneously with transcranial Doppler ultrasound and The Task Force® Monitor in response to orthostatic test. Participants remained normotensive during HS diet. Following both, the LS and HS dietary protocols, mean cerebral blood flow (CBF), as well as the velocity time integral and diastolic blood pressure decreased, and cerebral pulsatility index increased after rising up. Importantly, cerebrovascular resistance significantly increased in response to orthostasis only after HS diet. Urine concentration of noradrenaline and vanillylmandelic acid, baroreflex sensitivity (BRS), and sympathetic neural control was significantly decreased in HS diet. Results suggest that CBF in response to orthostatic test was preserved in HS condition due to altered vascular reactivity of MCA, with increased cerebrovascular resistance and blunted BRS and sympathetic activity.

IntroductionCoronary artery disease (CAD), the most common type of heart disease and the leading cause of death in developed countries, is clinically manifested with established endothelial dysfunction (ED), which presents one of the earliest symptoms underlying various cardiovascular diseases (CVDs). It has been extensively reported that flow-mediated dilation (FMD) of the brachial artery in response to post- occlusive reactive hyperemia, assessed with ultrasounds, is impaired in patients with CAD, reflecting both local and systemic ED. Increased oxidative stress levels has been identified as akey pathophysiological mechanism mediating the development of ED. Thus, this study aimed to assess the effect of supplementation of cardiovascular protective and antioxidant nutrients (e.g. polyunsaturated fatty acids (n-3 PUFA), selenium, vitamin E and lutein) in a form of functional food on brachial artery FMD in patients with chronic stable CAD.MethodsThirty patients with diagnosed chronic stable CAD (9 women and 21 men) were instructed to eat three hard boiled hen eggs per day during study protocol that lasted for 21 days (total of 63 eggs). Subjects were divided in experimental NUTRI4 group (15 subjects) which consumed n-3 polyunsaturated fatty acids (n-3 PUFAs), selenium, vitamin E and lutein enriched hen eggs (1050 mg of n-3 PUFA/day, 0.06 mg of selenium/day, 3.29 mg of vitamin E/day, and 1.85 mg of lutein/per day), and in control group (15 subjects) which consumed regular hen eggs produced on the same farm (249 mg of n-3 PUFA per day, 0.05 mg of selenium/day, 1.79 mg of vitamin E/day, and 0.33 mg of lutein/per day). Brachial artery FMD (following 5-minute vascular occlusion) and nitroglycerin (NTG) dilation (following 400 mcg of NTG sublingual administration) were assessed using ultrasound and appropriate vascular probe (GE Healthcare Vivid iQ R2). Obtained images were analyzed by Brachial Analyzer for Research v.6 software (Medical Imaging Applications, USA).ResultsBrachial artery FMD significantly increased in NUTRI4 group following respective dietary intervention (FMD % of dilation before 6.84 ±3.60 vs. after 9.14 ± 4.79, P=0.015), while it remained unchanged in controls (FMD % of dilation before 9.67 ± 3.60 vs. after 9.89 ± 3.26, P=0.850). Brachial artery NTG dilation did not significantly change in both NUTRI4 (NTG % of dilation before 13.70 ±7.19 vs. after 12.38 ± 6.12, P=0.502) and Control group (NTG % of dilation before 14.42 ± 6.40 vs. after 14.46 ± 5.95, P=0.985) following respective dietary protocol.ConclusionSupplementation of n-3 PUFA, selenium, vitamin E and lutein in a form of functional food improves brachial artery FMD (endothelium dependent vasodilation), but not NTG dilation (endothelium-independent) in chronic CAD patients, potentially by providing more favorable lipid and antioxidant milieu.

Activation of endothelial TGF-β signaling may be an important driver of atherogenesis and plays a key role in induction of vessel wall inflammation and development and progression of atherosclerosis. Previously, our studies on consumption of n-3 polyunsaturated fatty acids (n- 3 PUFAs) enriched eggs have shown a beneficial effect, by changing the free fatty acid profile to a more favorable lower n6/n3 ratio, lowering total cholesterol and LDL-cholesterol levels in cardiovascular patients with no adverse effects of daily eggs' consumption. The aim of this study was to determine effect of eggs enriched with n-3 PUFAs, vitamin E, selenium and lutein on the serum levels of pro-inflammatory cytokines. Randomized, double-blind, controlled, interventional study (Clinical Trials ID: NCT04564690) was conducted in patients with chronic coronary syndrome (diagnosed according to ESC guidelines for the diagnosis and management of chronic coronary syndromes, 2019) who consumed 3 hen eggs per day for 3 weeks. Control patients consumed ordinary: n3-PUFAs (438 mg/day), lutein (110 mg/day), selenium (0.181 mg/day) and vitamin E (595 mg mg/day) hen eggs and Nutri4 group patients consumed enriched hen eggs: n3-PUFAs (1026 mg/day), lutein (616 mg/day), selenium (0.191 mg/day) and vitamin E (1098 mg mg/day). All patients used statins and other standard drug therapy for CAD (ACE inhibitors, beta blockers, antiplatelet drugs), and some of them used ezetimibe depending on lipid profile. Written informed consent was obtained from each subject. The study protocol and procedures conformed with the standards set by the latest revision of the Declaration of Helsinki and were approved by the Ethical Committee of Osijek University Hospital. Serum levels of TGF-β, C3a, IFN-gamma, IL-6, IL-10, IL-17A(CTLA-8), IL-23, MCP-1 (CCL2) and TNF-alpha were measured with ThermoFisher Scientific ProcartaPlex antibody- based magnetic bead reagent kits and panels for multiplex protein quantitation using the Luminex 200 instrument platform. Quantitation was performed using ProcartaPlex Analysis Application and expressed as concentration in pg/ml, (sample N=9-10 per group). For group comparisons a OneWayANOVA test was used. Within-group comparisons were performed using paired t-test or Wilcoxon test, statistical significance was set as P

Introduction: Ventricular fibrillation (VF) and ventricular tachycardia (VT) are emergency conditions that can lead to sudden cardiac death (SCD), particularly in those with structural heart disease and reduced left ventricular function. This case report aims to showcase the recommended approach to diagnostic workup and initial treatment in a patient with heart failure and malignant arrhythmia Case report: We present a case report of a 78-year-old patient brought to the emergency department who, after receiving a SARS CoV-2 vaccine booster shot, had a cardiac arrest in the health center. It was confirmed the patient had VF and was defibrillated 3 times and successfully reanimated. He was hospitalized at the cardiology department. An emergency coronarography was performed and showed normal epicardial arteries. Laboratory results showed severe hypokalemia, but control tests showed normal potassium values, suggesting a laboratory error in the initial results and therefore excluded hypokalemia as a possible cause of VF. Echocardiography revealed dilated left ventricle, with hypocontractile wall motion. While hospitalized the patient had another cardiac arrest, this time the ECG showed VT. He was defibrillated and afterward had no recurring malignant arrhythmias. It was concluded that the malignant arrhythmia is a consequence of non-ischemic cardiomyopathy with a severely reduced ejection fraction of the left ventricle. An implantable cardioverter-defibrillator (CD) was implanted to the patient and his therapy was optimized Conclusion: SCD is a leading cause of death in developed countries, therefore its fast and effective treatment, as well as prevention, are the greatest priority. This case report highlights the significance of prompt resuscitation and defibrillation as an intervention for cardiac arrest, as well as the importance of an appropriate selection of patients as candidates for an ICD.

Consumption of n-3 polyunsaturated fatty acids (n- 3 PUFAs) pharmacological substitutes has strong potential to reduce cardiovascular risk and prevent adverse outcomes in existing cardiovascular diseases. The natural way of taking n-3 PUFAs is through food enriched with these nutrients - functional food. The aim of part of the research conducted at the Scientific Center of Excellence for Personalized Health Care is to produce hen eggs enriched with n-3 PUFAs and to examine the effect of consumption of such eggs on microvascular function in young, healthy subjects and patients with acute and chronic coronary heart disease. All protocols were approved by the relevant ethics committees and participants gave written informed consent. The results of these studies, which were conducted in protocols with 2 or 3 enriched or plain eggs a day for 3 weeks, showed that there was a significant benefit and enhancement of microvascular reactivity after eating enriched eggs in young healthy subjects and athletes, while no such effect was observed in cardiovascular patients. The effect was more pronounced at daily doses of n-3 PUFAs > 770mg / day. At the same time, no adverse effect of egg consumption on microvascular function, blood pressure, lipid profile or markers of inflammation and oxidative stress was observed in any group of subjects. On the contrary, some of the markers were improved in both healthy subjects and cardiovascular patients. In conclusion, consumption of n-3 PUFAs enriched eggs has a positive effect on vascular health. In principle, eggs should be a regular part of the daily diet.

Introduction: Hyperbaric oxygenation (HBO2) has the ability to alter protein expression, modulates signaling pathways, and influences vascular structure and function leading to changes in vasomotor responses. Adenosine receptors (AR) play an important role in the mechanism of action of oxygen as a vasoactive substance, the expression of which differs significantly between cell types. The aim of this study was to determine the expression of adenosine receptors' (A1R and A2aR) in cerebral blood vessels of Sprague-Dawley rats exposed to acute and intermittent HBO2. Methods: Male and female healthy Sprague-Dawley rats (N=18), 8-10 weeks old were divided into 3 groups: CTRL (control non-HBO2), A-HBO2 (exposed to single HBO2 at a pressure od 2 bars/ 2 hours) and 4D-HBO2 (animals exposed to HBO2 for 2 hours daily for 4 days, with sample isolation on 5th day). The rats were anesthetized with ketamine- chloride (3 ml/kg) and midazolam (0, 5 ml/kg) and decapitated. Afterwards, samples of surface brain blood vessels were used for qRT-PCR. Relative gene expression of A1R and A2aR genes was measured with HPRT1 as the housekeeping gene. Results: Acute exposure to HBO2 did not significantly alter A1R or A2aR gene expression. There was a significant increase in A1R i A2aR expression in the 4D-HBO2 group compared to CTRL. Discussion: High oxygen concentrations during HBO2 lead to changes in vascular reactivity mechanism. Adenosine A2aR are known to mediate a protective compensatory vasodilatory response to tissue hypoxia. Although A1R activation is known to cause vasoconstriction, some studies suggest that during hypoxia, A1R protects tissue from damage by reducing levels of ischemic mediator and by causing vasodilation. In addition, A1R can modulate A2aR expression. Also, A1R are known to be more sensitive to hypoxia. Conclusion: Intermittent exposure to hyperbaric oxygen acts as pseudohypoxia, resulting in a protective compensatory increase in adenosine A1R and A2aR gene expression.

INTRODUCTION: Previously, we showed that increased NaCl dietary intake impairs vascular function via increased oxidative stress. Carnosine (CAR ; β- alanyl-L-histidine) is a dipeptide that has anti- inflammatory, antioxidant activity and acts as a "scavenger" of ROS, reduces the levels of lipid peroxidation and low-density lipoprotein in the serum of aged rats. However, there are no studies that have examined the effect of carnosine supplementation on vascular function and oxidative stress levels following high salt intake. AIM: Present pilot study aimed to investigate the effect of carnosine supplementation on vascular function by examining acetylcholine-induced dilation of isolated aortic rings. MATERIALS AND METHODS: Healthy Sprague-Dawley rats (8-10 weeks old) were divided in four groups (3 rats per group) – CTRL (control group, 0.4% NaCl), HS (high salt diet, 4% NaCl in diet for 7 days), CTRL+CAR (oral carnosine supplementation, 150 mg/kg/day for 7 days) and HS+CAR group (HS and carnosine supplementation). Response to ACh and SNP (sodium nitro-prusside) was studied in isolated norepinephrine precontracted aortic rings (Isolated Organ Bath (Experimetria LTD)). All experimental procedures conformed to the European Guidelines for the Care and Use of Laboratory Animals (directive 86/609) and were approved by the local and national Ethical Committees (#2158- 61-46-22-14, EP355/2022). RESULTS: These preliminary results showed impaired ACh-induced relaxation of aortic rings in HS group compared to CTRL, and restored relaxation after carnosine supplementation. There are no differences in response to SNP among tested groups. CONCLUSION: Results suggest positive effect of carnosine on vascular function of rats on high salt diet. ACKNOWLEDGMENT: This study was supported by European Structural and Investment Funds through a grant to the Croatian National Science Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek # KK.01.1.1.01.0010. and by institutional grants from the Faculty of Medicine Osijek IP1-2022-MEFOS (PI Ines Drenjančević) and IP16-2022-MEFOS grant (PI Zrinka Mihaljević).

Introduction and Aim: This project tested the hypothesis that suppression of renin-angiotensin system (RAS) and sympathetic activity by 7 day high-salt (HS) diet lead to endothelial and leukocyte activation and further, impaired microvascular reactivity in humans, by increasing oxidative stress. Materials and Methods: Project lasted for 54 months (April 2017-October 2021). Overall 132 young healthy individuals were included in project studies. All subjects adhered to a 7-day low-salt diet (3.5g salt/day), followed by a 7-day HS diet (~14.7g salt/day) protocol. Functional assessment of microvascular endothelial function, adrenergic system activity, body composition and fluid status, RAS activity, catecholamines concentration, biomarkers of oxidative status, pro- and anti-inflammatory cytokines, frequencies of peripheral blood lymphocytes, and biomarkers of endothelial activation were measured before and after HS diet. To specifically test the role of oxidative stress and sympathetic system activity in changes of microvascular reactivity due to the HS diet one group of subjects was supplemented with oral antioxidants during the HS diet, while the other group was subjected to a mental stress test. Results and Conclusions: 7-day HS diet suppresses RAS and impairs microvascular endothelium- dependent vasodilation in healthy individuals ; these changes are independent of blood pressure, body composition or fluid retention, but are the consequences of the unique effect of HS on endothelial function. HS diet induces oxidative disbalance, with antioxidant supplementation during HS diet preserving both oxidative status and endothelial microvascular reactivity. HS diet also suppresses sympathetic activity which represents a physiological response, rather than direct pathophysiological mechanism by which HS diet affects microvascular endothelial function in healthy individuals. HS diet induces lymphocyte activation, resulting in enhanced production of pro-inflammatory, but also anti-inflammatory cytokines, while increased oxidative stress, due to HS loading, alters immune regulatory mechanisms. Taken together, oxidative disbalance has the pivotal role in HS diet-induced impairment of endothelial and microvascular function in healthy individuals.

*Corresponding authors: Aleksandar Kibel, MD, PhD. Email: alekibel@mefos.hr Zrinka Mihaljević, PhD. E-mail: zmihaljevic@mefos.hr Introduction: Hyperbaric oxygenation (HBO2) affects gene and protein expression, modulate signaling pathways and influence vascular structure and function .Adenosine receptors (AR) play an important role in the mechanism of action of oxygen as a signaling molecule and vasoactive substance, and their expression may be affected by HBO2. Objecitve: Present study aimed to determine the protein expression of adenosine A1 and A2a receptor in cerebral blood vessels of Sprague- Dawley rats after exposure to acute and intermittent HBO2. Methods: Male and femal healthy Sprague-Dawley rats aged 8-10 weeks were divided into 3 groups: CTRL (control non HBO2), A-HBO2 (animals exposed to single HBO2 for 2 hours) and 4D-HBO2 (animals exposed to HBO2 at a pressure od 2 bars for 2 hours daily for 4 days, with sample collection on the fifth day). Superficial brain blood vessels were collected to determine the protein expression of adenosine A1 and A2a receptors using the Western blot method. All experimental procedures conformed to the European Guidelines for the Care and Use of Laboratory Animals (directive 86/609) and were approved by the local and national Ethical Committee (#2158-61-07-21-88 ; EP-348/2021) Results: A1 receptor protein expression was significantly reduced in A-HBO2 rats compared to 4D-HBO2 (relative expression in relation to β- actin 0.5865 +/- 0.1259 vs 0.9316 +/- 0.1152, p=0.0191). A-HBO2 group had significantly reduced protein expression of A2a receptors compared to CTRL (0.2380 +/- 0.09028 vs 0.6833 +/- 0.1054, p

Introduction: Infective Endocarditis (IE) is an inflammation of the endocardium caused by microbial pathogens. It is a known infectious complication among intravenous drug addicts, with a high recurrence rate. The aim of this case report is to describe the characteristics and treatment approach of recurrent IE. Case report: We present a 38-year-old female patient with a long history of intravenous drug abuse, diagnosed with opioid addiction and chronic hepatitis B. In 2015 she was hospitalized due to sepsis and pneumonia and diagnosed with IE with vegetations on the tricuspid valve (TV). The patient underwent TV repair surgery. She was re-hospitalized in 2017 and an aortic valve endocarditis was diagnosed. It was managed with antibiotics, and the vegetation resolved. In 2018, the patient was again diagnosed with IE and vegetations of the TV. She underwent TV replacement with a bioprosthesis. Her clinical course was complicated by development of third-degree AV block, with a consequent placement of a permanent epicardial pacemaker. During her last hospitalization in 2019 due to the development of side effects of linezolid, an examination was performed by a cardiac surgeon who recommended further cardiac monitoring after which the patient stopped coming for recommended follow up visits. Conclusion: This case illustrates the challenges of recurrent IE treatment. IE is associated with intravenous drug use, which has a high recurrence rate due to drug use relapse and reinfections. Patients often require long-term hospitalization, intravenous antimicrobial therapy and if needed, cardiac surgery.

Patogeneza ateroskleroze i drugih kardiovaskularnih bolesti uključuje kroničnu upalu, visoki krvni tlak i povišene razine kolesterola u krvi. Upala povezana s aterosklerozom posredovana je složenim koktelom proupalnih citokina, kemokina, bioaktivnih lipida i adhezijskih molekula. Omega-6 (n-6) i omega-3 (n-3) polinezasićene masne kiseline (PUFA) su prekursori lipidnih medijatora, nazvanih eikozanoidi, koji igraju važnu ulogu u regulaciji upale. Eikozanoidi dobiveni iz n-6 PUFA (npr. arahidonske kiseline) imaju pro-upalno i imunoaktivno djelovanje, dok eikozanoidi dobiveni iz n-3 PUFA (npr. EPA i DHA) imaju protuupalna svojstva. Unos EPA i DHA (n-3 PUFA) hranom kroz konzumaciju masne ribe može smanjiti učestalost upalnih procesa kod mnogih kroničnih bolesti. Ova studija imala je za cilj odrediti serumske koncentracije proupalnih citokina IL-1α, IL-10, IL-6, MCP-1 i TNF-α u serumu kroničnih kardiovaskularnih bolesnika oba spola (nukupno = 19) prije i tri tjedana nakon konzumacije standardnih jaja (kontrolna skupina, n = 9) ili n- 3 PUFA obogaćenih kokošjih jaja (pokusna skupina, n = 10). Koncentracije spomenutih upalnih citokina određene su ProCarta Multiplex kitom na uređaju Luminex 200. Ispitanici su konzumirali tri kuhana jaja dnevno tijekom tri tjedna, ukupna količina n- 3 PUFA dnevno bila je 249 mg za kontrolnu skupinu, a za eksperimentalnu skupinu 1053 mg n-3 PUFA/dan. Rezultati su analizirani unutar grupe i između grupa korištenjem uparenog t-testa odnosno Wilcoxonovog testa i t-testa. Statistička značajnost postavljena je kao P

Objective: Hyperbaric oxygenation (HBO) affects vascular reactivitiy, which plays an important role in the pathophysiology of hypertension and other cardiovascular diseases. New data suggest important effects of HBO on oxidative stress and alteration of production of vasoactive metabolites in blood vessels ; however, the role of adenosine A1 and A2a receptors is still underinvestigated.This study aimed to determine the functional role of adenosine A1 and A2a receptors in changes of vascular reactivity in isolated middle cerebral arteries (MCA) of Spague- Dawley rats, after acute and intermittent HBO. Desing and Methods: Male and femal healthy Sprague-Dawley rats aged 8-10 weeks were divided into 3 groups: CTRL (control non HBO), A-HBO (single animals exposed to HBO for 2 hours) and 4D-HBO (animals exposed to HBO at a pressure od 2 bars for 2 hours daily for 4 days, with vascularexperiments conducted on the fith day). The rats were anesthetized with ketamine-chloride (3 ml/kg) and midazolam (0, 5 ml/kg) and decapitated. The MCA were isolated, cannulated and pressurized for 60’at 80 mmHg to assess basal diameter using pressure myograph Danish Myo Technology. A1 adenosin receptor selective agonist CCPA or A2a adenosin receptor agonist CGS in concentrations from 10-5 to 10-10 M were added to the vessel chamber, and blood vessel diameter was measured after incubation of the drug for 15 minutes. Statistical analyses were performed with Two-way ANOVA tests ; p