Q87689364
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Angina pectoris bez obstrukce koronárních tepen je častý nález u pacientů s bolestmi na hrudi, v jehož patofyziologii se uplatňují zejména dva mechanismy – strukturální nebo funkční poškození mikrocirkulace či funkční poškození epikardiálních tepen, případně jejich kombinace. Souhrnný článek se zabývá dia- gnostikou koronární mikrovaskulární dysfunkce se zaměřením na kontinuální termodiluci jako bezpečnou, jednoduchou, rychlou a na operatérovi nezávislou metodu. Popisuje teoretický základ i praktické aspekty s grafickými ukázkami měření.
Angina with non-obstructive coronary artery disease is a frequent finding in patients with chest pain. Its pathophysiology involves two main mechanisms: structural and functional dysfunction of microcircula- tion, functional dysfunction of epicardial arteries, and their combination. The review article focuses on the diagnostics of microvascular dysfunction, particularly continuous thermodilution, as a safe, easy, fast, and operator-independent method. It describes both theoretical background and practical aspects with graphical examples of measurements.
- Klíčová slova
- koronární průtok,
- MeSH
- angina pectoris * diagnóza klasifikace patofyziologie MeSH
- hemodynamické monitorování metody MeSH
- koronární cévy patologie MeSH
- lidé MeSH
- mikrocévy patologie MeSH
- mikrocirkulace MeSH
- perikard fyziologie MeSH
- termodiluce * metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
The aim of the present study was to perform kidney messenger ribonucleic acid (mRNA) analysis in normotensive, Hannover Sprague-Dawley (HanSD) rats and hypertensive, Ren-2 renin transgenic rats (TGR) after doxorubicin-induced heart failure (HF) with specific focus on genes that are implicated in the pathophysiology of HF-associated cardiorenal syndrome. We found that in both strains renin and angiotensin-converting enzyme mRNA expressions were upregulated indicating that the vasoconstrictor axis of the renin-angiotensin system was activated. We found that pre-proendothelin-1, endothelin-converting enzyme type 1 and endothelin type A receptor mRNA expressions were upregulated in HanSD rats, but not in TGR, suggesting the activation of endothelin system in HanSD rats, but not in TGR. We found that mRNA expression of cytochrome P-450 subfamily 2C23 was downregulated in TGR and not in HanSD rats, suggesting the deficiency in the intrarenal cytochrome P450-dependent pathway of arachidonic acid metabolism in TGR. These results should be the basis for future studies evaluating the pathophysiology of cardiorenal syndrome secondary to chemotherapy-induced HF in order to potentially develop new therapeutic approaches.
- MeSH
- doxorubicin škodlivé účinky MeSH
- hypertenze komplikace genetika patofyziologie MeSH
- krysa rodu rattus MeSH
- ledviny účinky léků patofyziologie MeSH
- messenger RNA genetika MeSH
- nemoci ledvin chemicky indukované genetika patofyziologie MeSH
- potkani Sprague-Dawley MeSH
- potkani transgenní MeSH
- protinádorová antibiotika škodlivé účinky MeSH
- regulace genové exprese účinky léků MeSH
- renin-angiotensin systém účinky léků MeSH
- renin genetika MeSH
- srdeční selhání chemicky indukované genetika patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Doxorubicin's (DOX) cardiotoxicity contributes to the development of chemotherapy-induced heart failure (HF) and new treatment strategies are in high demand. The aim of the present study was to characterize a DOX-induced model of HF in Ren-2 transgenic rats (TGR), those characterized by hypertension and hyperactivity of the renin-angiotensin-aldosterone system, and to compare the results with normotensive transgene-negative, Hannover Sprague-Dawley (HanSD) rats. DOX was administered for two weeks in a cumulative dose of 15 mg/kg. In HanSD rats DOX administration resulted in the development of an early phase of HF with the dominant symptom of bilateral cardiac atrophy demonstrable two weeks after the last DOX injection. In TGR, DOX caused substantial impairment of systolic function already at the end of the treatment, with further progression observed throughout the experiment. Additionally, two weeks after the termination of DOX treatment, TGR exhibited signs of HF characteristic for the transition stage between the compensated and decompensated phases of HF. In conclusion, we suggest that DOX-induced HF in TGR is a suitable model to study the pathophysiological aspects of chemotherapy-induced HF and to evaluate novel therapeutic strategies to combat this form of HF, which are urgently needed.
- MeSH
- doxorubicin toxicita MeSH
- kardiotoxicita MeSH
- krevní tlak * MeSH
- krysa rodu rattus MeSH
- potkani Sprague-Dawley MeSH
- protinádorové látky toxicita MeSH
- renin-angiotensin systém * MeSH
- renin genetika MeSH
- srdeční selhání etiologie metabolismus patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
We found recently that in Ren-2 transgenic hypertensive rats (TGR) addition of soluble epoxide hydrolase inhibitor (sEHi) to treatment with angiotensin-converting enzyme inhibitor (ACEi), surprisingly, increased the mortality due to heart failure (HF) induced by creation of the aorto-caval fistula (ACF). Since TGR exhibit sex-related differences in mortality, we examined here if such differentiation exists also in the response to the treatment with ACEi (trandolapril), alone or combined with sEHi [cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid, (c-AUCB)]. ACEi improved survival in males to 74 % (vs. 0 %) and in females to 65 % (vs. 32 %). ACEi and sEHi combined also improved the survival in male ACF TGR, however, it was significantly less (38 %) than after ACEi alone. In contrast, in females the combined treatment significantly improved the final survival rate (84 %). There were no significant sex-linked differences in survival rate in untreated or treated normotensive Hannover Sprague-Dawley rats. In conclusion, in HF patients with co-existing hypertension and RAS hyperactivity, the sex may co-determine the rate of HF progression, and can influence the effectiveness of the therapeutic measures applied. Therefore, in the relevant pre-clinical studies the sex-linked differences should be seriously considered. Our data indicate that TGR might be an optimal model for such studies.
- MeSH
- angiotensin konvertující enzym metabolismus MeSH
- cévní píštěle farmakoterapie genetika mortalita MeSH
- epoxid hydrolasy antagonisté a inhibitory metabolismus MeSH
- hypertenze farmakoterapie genetika mortalita MeSH
- inhibitory ACE aplikace a dávkování MeSH
- inhibitory enzymů aplikace a dávkování MeSH
- kombinovaná farmakoterapie MeSH
- krysa rodu rattus MeSH
- mortalita trendy MeSH
- náhodné rozdělení MeSH
- pohlavní dimorfismus * MeSH
- potkani Sprague-Dawley MeSH
- potkani transgenní MeSH
- renin * genetika MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
