There is ample evidence on the benefit of angiotensin receptor-neprilysin inhibitors (ARNIs) in heart failure, yet data regarding the potential protective action of ARNIs in hypertensive heart disease are sparse. The aim of this study was to show whether an ARNI exerts a protective effect in a model of Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension with a hypertensive heart and to compare this potential benefit with an angiotensin-converting enzyme inhibitor, captopril. Five groups of adult male Wistar rats were studied (14 per group) for four weeks: untreated controls; ARNI (68 mg/kg/day); L-NAME (40 mg/kg/day); L-NAME treated with ARNI; and L-NAME treated with captopril (100 mg/kg/day). L-NAME administration induced hypertension, accompanied by increased left ventricular (LV) weight and fibrotic rebuilding of the LV in terms of increased concentration and content of hydroxyproline in insoluble collagen and in total collagen and with a histological finding of fibrosis. These alterations were associated with a compromised systolic and diastolic LV function. Treatment with either an ARNI or captopril reduced systolic blood pressure (SBP), alleviated LV hypertrophy and fibrosis, and prevented the development of both systolic and diastolic LV dysfunction. Moreover, the serum levels of prolactin and prolactin receptor were reduced significantly by ARNI and slightly by captopril. In conclusion, in L-NAME-induced hypertension, the dual inhibition of neprilysin and AT1 receptors by ARNI reduced SBP and prevented the development of LV hypertrophy, fibrosis, and systolic and diastolic dysfunction. These data suggest that ARNI could provide protection against LV structural remodeling and functional disorders in hypertensive heart disease.
- Publikační typ
- časopisecké články MeSH
This study investigated whether sacubitril/valsartan or valsartan are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in two experimental models of pre-hypertension induced by continuous light (24 hours/day) exposure or by chronic lactacystin treatment, and how this potential protection interferes with the renin-angiotensin-aldosterone system (RAAS). Nine groups of three-month-old male Wistar rats were treated for six weeks as follows: untreated controls (C), sacubitril/valsartan (ARNI), valsartan (Val), continuous light (24), continuous light plus sacubitril/valsartan (24+ARNI) or valsartan (24+Val), lactacystin (Lact), lactacystin plus sacubitil/valsartan (Lact+ARNI) or plus valsartan (Lact+Val). Both the 24 and Lact groups developed a mild but significant systolic blood pressure (SBP) increase, LV hypertrophy and fibrosis, as well as LV systolic and diastolic dysfunction. Yet, no changes in serum renin-angiotensin were observed either in the 24 or Lact groups, though aldosterone was increased in the Lact group compared to the controls. In both models, sacubitril/valsartan and valsartan reduced elevated SBP, LV hypertrophy and fibrosis and attenuated LV systolic and diastolic dysfunction. Sacubitril/valsartan and valsartan increased the serum levels of angiotensin (Ang) II, Ang III, Ang IV, Ang 1-5, Ang 1-7 in the 24 and Lact groups and reduced aldosterone in the Lact group. We conclude that both continuous light exposure and lactacystin treatment induced normal-to-low serum renin-angiotensin models of pre-hypertension, whereas aldosterone was increased in lactacystin-induced pre-hypertension. The protection by ARNI or valsartan in the hypertensive heart in either model was related to the Ang II blockade and the protective Ang 1-7, while in lactacystin-induced pre-hypertension this protection seems to be additionally related to the reduced aldosterone level.
- MeSH
- acetylcystein analogy a deriváty MeSH
- aldosteron MeSH
- aminobutyráty * MeSH
- bifenylové sloučeniny farmakologie MeSH
- fibróza MeSH
- fixní kombinace léků MeSH
- hypertenze * farmakoterapie MeSH
- hypertrofie levé komory srdeční MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- prehypertenze * MeSH
- renin-angiotensin systém MeSH
- renin MeSH
- srdeční selhání * MeSH
- tepový objem MeSH
- tetrazoly farmakologie terapeutické užití MeSH
- valsartan farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Background: Anthracycline cardiotoxicity is a well-known complication of cancer treatment, and miRNAs have emerged as a key driver in the pathogenesis of cardiovascular diseases. This study aimed to investigate the expression of miRNAs in the myocardium in early and late stages of chronic anthracycline induced cardiotoxicity to determine whether this expression is associated with the severity of cardiac damage. Method: Cardiotoxicity was induced in rabbits via daunorubicin administration (daunorubicin, 3 mg/kg/week; for five and 10 weeks), while the control group received saline solution. Myocardial miRNA expression was first screened using TaqMan Advanced miRNA microfluidic card assays, after which 32 miRNAs were selected for targeted analysis using qRT-PCR. Results: The first subclinical signs of cardiotoxicity (significant increase in plasma cardiac troponin T) were observed after 5 weeks of daunorubicin treatment. At this time point, 10 miRNAs (including members of the miRNA-34 and 21 families) showed significant upregulation relative to the control group, with the most intense change observed for miRNA-1298-5p (29-fold change, p < 0.01). After 10 weeks of daunorubicin treatment, when a further rise in cTnT was accompanied by significant left ventricle systolic dysfunction, only miR-504-5p was significantly (p < 0.01) downregulated, whereas 10 miRNAs were significantly upregulated relative to the control group; at this time-point, the most intense change was observed for miR-34a-5p (76-fold change). Strong correlations were found between the expression of multiple miRNAs (including miR-34 and mir-21 family and miR-1298-5p) and quantitative indices of toxic damage in both the early and late phases of cardiotoxicity development. Furthermore, plasma levels of miR-34a-5p were strongly correlated with the myocardial expression of this miRNA. Conclusion: To the best of our knowledge, this is the first study that describes alterations in miRNA expression in the myocardium during the transition from subclinical, ANT-induced cardiotoxicity to an overt cardiotoxic phenotype; we also revealed how these changes in miRNA expression are strongly correlated with quantitative markers of cardiotoxicity.
- Publikační typ
- časopisecké články MeSH
Úvod: Ponechání pacienta na místě zásahu v přednemocniční neodkladné péči (PNP) je aktuální problematika. Na národní úrovní nejsou dostupná komparativní data ohledně ponechání pacienta na místě zásahu ani hodnocení bezpečnosti postupu. Cíl: Zjistit četnost ponechání pacienta na místě z rozhodnutí zdravotnických pracovníků a popsat charakteristiky těchto případů. Zhodnotit míru opakovaných výjezdů k pacientům ponechaným na místě zásahu. Metodika: Data byla sbírána z databáze výjezdové činnosti Zdravotnické záchranné služby Karlovarského kraje (ZZS KVK) za měsíc leden 2023. Celkem bylo identifikováno 335 pacientů ponechaných na místě z rozhodnutí výjezdové skupiny (z 3005 pacientů). Výsledky: Pacienti z primárních výjezdů jsou ponechávání na místě v 11,1 % (335/3005). Dominuje rozhodnutí zdravotnických záchranářů, kteří konzultují stav pacienta po telefonu s lékařem (90 % případů) nad ponecháním na místě výjezdovou skupinou rychlé lékařské pomoci. Mezi pacienty, kteří jsou ponecháváni na místě, převažují nespecifické zdravotní obtíže, ebrieta a psychiatrické stavy. Opakované výjezdy se uskutečnily k pacientům ponechaným na místě v 11,0 % (n = 37). Nejvíce opakovaných výjezdů se uskuteční do 24 hodin (51 % (n = 19)), respektive do 72 hodin (87 % (n = 32)). Vyšší četnost opakovaného výjezdu k těmto pacientům byla u starších pacientů. Exitus pacienta ponechaného na místě nebyl zaznamenán. Závěr: V Karlovarském kraji je ponecháváno na místě přes jedenáct procent pacientů z primárních výjezdů. Ponechání pacienta na místě zásahu lze považovat za bezpečnou součást poskytování PNP. Chybí doporučený postup na národní úrovni, který by zohledňoval stratifikaci rizik pro ponechávání pacientů na místě zásahů.
Introduction: Non-conveyance of patients following prehospital emergency care is a current issue. There are no available national comparative data on non-conveyance of the patient from scene or evaluation of the safety of the procedure. Aim: To evaluate the frequency of non-conveyance of the patient by the decision of healthcare workers and describe the characteristics of these cases. To find out the rate of repeated visits to patients left at the scene of intervention. Methods: The data was collected from the database of the Emergency medical services of Karlovy Vary region from 1st to 31st January 2023. A total of 335 patients were left on the place based on the decision of the ambulance crew (out of 3005 patients). Results: The non-conveyance rate of patients from primary calls was 11.1% (335/3005). The decision of paramedics, who consult the patient‘s condition over the phone with physician (90% of cases) dominates over leaving the patient on site by the ambulance crew with physician. The most common reasons for non-transport of the patient are non-specific health conditions, alcohol intoxication and psychiatric conditions. Repeated visits occurred to these patients in 11.0% (n = 37). Most of the repeated calls took place within 24 hours (51% (n = 19)) or within 72 hours (87% (n = 32)). A higher frequency of repeated visits to these patients was more common in older patients. No death of the patient left on the scene was recorded. Conclusion: In the Karlovy Vary region, over eleven percent of patients from primary visits during January 2023 were left on place. Non-conveyance of the patient can be considered safe part of providing prehospital emergency care. However, there is a lack of a national recommendations or guidelines that would consider the risks stratification for non-transport of the patient. Key words: emergency medical services – pre-hospital emergency care – paramedic – non-conveyance of the patient.
Doxorubicin (DOX) is a chemotherapeutic drug widely used for cancer treatment, but its use is limited by cardiotoxicity. Although free radicals from redox cycling and free cellular iron have been predominant as the suggested primary pathogenic mechanism, novel evidence has pointed to topoisomerase II inhibition and resultant genotoxic stress as the more fundamental mechanism. Recently, a growing list of microRNAs (miRNAs) has been implicated in DOX-induced cardiotoxicity (DIC). This review summarizes miRNAs reported in the recent literature in the context of DIC. A particular focus is given to miRNAs that regulate cellular responses downstream to DOX-induced DNA damage, especially p53 activation, pro-survival signaling pathway inhibition (e.g., AMPK, AKT, GATA-4, and sirtuin pathways), mitochondrial dysfunction, and ferroptosis. Since these pathways are potential targets for cardioprotection against DOX, an understanding of how miRNAs participate is necessary for developing future therapies.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Lactacystin is a specific proteasome inhibitor that blocks the hydrolysis of intracellular proteins by ubiquitin/proteasome system inhibition. The administration of lactacystin to rats induced hypertension and remodeling of the left ventricle and aorta. This study tested whether lactacystin induces structural and fibrotic rebuilding of the kidneys and whether melatonin and captopril can prevent these potential changes. Six weeks of lactacystin administration to rats increased their average systolic blood pressure (SBP). In the kidneys, lactacystin reduced glomerular density, increased the glomerular tuft area, and enhanced hydroxyproline concentrations. It also elevated the intraglomerular proportion including the amounts of collagen (Col) I and Col III. Lactacystin also raised the tubulointerstitial amounts of Col I and the sum of Col I and Col III with no effect on vascular/perivascular collagen. Six weeks of captopril treatment reduced SBP, while melatonin had no effect. Both melatonin and captopril increased glomerular density, reduced the glomerular tuft area, and lowered the hydroxyproline concentration in the kidneys. Both drugs reduced the proportion and total amounts of intraglomerular and tubulointerstitial Col I and Col III. We conclude that chronic lactacystin treatment stimulated structural and fibrotic remodeling of the kidneys, and melatonin and captopril partly prevented these alterations. Considering the effect of lactacystin on both the heart and kidneys, chronic treatment with this drug may be a prospective model of cardiorenal damage suitable for testing pharmacological drugs as protective agents.
- Publikační typ
- časopisecké články MeSH
This study investigated whether sacubitril/valsartan and ivabradine are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in a rat experimental model of spontaneous hypertension (spontaneously hypertensive rats, SHRs) and whether this potential protection is associated with RAAS alterations. Five groups of three-month-old male Wistar rats and SHRs were treated for six weeks as follows: untreated Wistar controls, Wistar plus sacubitril/valsartan, SHR, SHR plus sacubitril/valsartan, and SHR plus ivabradine. The SHRs developed a systolic blood pressure (SBP) increase, LV hypertrophy and fibrosis, and LV systolic and diastolic dysfunction. However, no changes in serum RAAS were observed in SHRs compared with the controls. Elevated SBP in SHRs was decreased by sacubitril/valsartan but not by ivabradine, and only sacubitril/valsartan attenuated LV hypertrophy. Both sacubitril/valsartan and ivabradine reduced LV collagen content and attenuated LV systolic and diastolic dysfunction. Sacubitril/valsartan increased the serum levels of angiotensin (Ang) II, Ang III, Ang IV, Ang 1-5, Ang 1-7, and aldosterone, while ivabradine did not affect the RAAS. We conclude that the SHR is a normal-to-low serum RAAS model of experimental hypertension. While the protection of the hypertensive heart in SHRs by sacubitril/valsartan may be related to an Ang II blockade and the protective Ang 1-7, the benefits of ivabradine were not associated with RAAS modulation.
- Publikační typ
- časopisecké články MeSH
AIMS: Acute heart failure represents a medical condition with very high mortality. Accurate risk stratification can help physicians to improve the health care about these patients. The aim of our study was to characterize real-life patients admitted for acute heart failure in a specific region with one tertiary medical centre and to describe risk factors of short-term and long-term mortality. METHODS AND RESULTS: We performed a retrospective analysis of patients admitted from January 2017 to December 2017 to Department of cardiology of the tertiary medical centre University Hospital in Hradec Kralove. We identified 385 patients admitted for acute heart failure to the standard care and intensive care unit. The median of age was 74 years (IQR 67.5-80) and 34% of patients were female. Hospital admission was due to de novo heart failure in 222 (57.7%) patients. The most common comorbidities were arterial hypertension (77.7%), dyslipidaemia (67.3%) and coronary artery disease (63.1%). Coronary artery disease (52.7% of cases) and valve disease (28.1% of cases) were the most common aetiologies of heart failure. The all-cause in-hospital mortality was 12.7%, 30-day mortality was 14.6% and 1 year mortality was 34%. Among risk factors of in-hospital mortality, the most significant factors were haemodialysis during the hospitalization [odds ratio (OR) 15.82, 95% confidence interval (CI) 2.96-84.57, P = 0.0008], chronic heart failure (OR 4.27, 95% CI 1.66-11.03, P = 0.001) and STEMI as a precipitating factor of heart failure (OR 4.19, 95% CI 1.23-14.25, P = 0.023). Haemodialysis during the hospitalization (OR 4.28, 95% CI 1.17-15.61, P = 0.025) and the comorbidity depression and anxiety (OR 3.49, 95% CI 1.45-8.39, P = 0.005) were the most significant risk factors of long-term mortality. CONCLUSIONS: Our study confirms very high mortality rates among patients with acute heart failure underlying poor prognosis of these patients. Comorbidities (peripheral artery disease, atrial fibrillation, chronic heart failure and depression and anxiety), precipitating factors of heart failure (myocardial infarction with ST segment elevation), complications occurring during the hospitalization (acute kidney injury, pulmonary ventilation for respiratory failure and haemodialysis) and the age of patients should be included in the risk stratification of in-hospital, 30 day and 1 year mortality.
- MeSH
- hospitalizace MeSH
- infarkt myokardu s elevacemi ST úseků * komplikace MeSH
- lidé MeSH
- nemoci koronárních tepen * komplikace MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- srdeční selhání * komplikace epidemiologie terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
