scholarly journals Activity Exerted by Fluoro-2,4-Dioxaspiro[Bicyclo[3.3.1]Indene Derivative Against Ischemia/Reperfusion Injury

2020 ◽  
Vol 9 (4) ◽  
pp. 1474-1484
Keyword(s):  
Heart Failure ◽  
Biological Activity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Thromboxane A2 ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Infarct Area ◽  
Cox 2

Several drugs for the treatment of heart failure; however, some of these drugs can produce some secondary effects such as arrhythmias and hypercalcemia and others. The aim of this investigation was to evaluate the biological activity of a Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative against both infarct area and left ventricular pressure. The effect exerted of a Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative against both infarct area and left ventricular pressure was evaluated in an ischemia/reperfusion model using indomethacin and ramatroban as a control. Furthermore, a theoretical study was carried out to determine the interaction of Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative with COX-1, COX-2, and thromboxane A2 using the 5u6x, 3ntg, and 6iiu proteins as controls. The results showed that Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative decrease the infarct and left ventricular pressure; however, this effect was inhibited in the presence of ramatroban. In addition, other data indicated that Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative could interact with both COX-2 and thromboxane A2 protein surface. All these data indicate that the biological activity of Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative against infarct area and left ventricular pressure was via both COX-2 and thromboxane A2 inhibition. Therefore, this compound could be s candidate for the treatment of heart failure.

scholarly journals New Amino-steroid-anthracenone with Biological Activity Against Ischemia-reperfusion Injury in a Wistar Rat Model

2018 ◽  
Vol 8 (1) ◽  
pp. 10-20 ◽  
Author(s):  
Figueroa-Valverde Lauro ◽  
Rosas-Nexticapa Marcela ◽  
Mateu-Armand Virginia ◽  
Herrera-Meza Socorro ◽  
Díaz-Cedillo Francisco ◽  
...  
Keyword(s):  
Biological Activity ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Receptor Activation ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Infarct Area ◽  
Camp Levels

Objective: The main objective of this study was to evaluate the biological activity of an ASA (Amino-Steroid-Anthracenone derivative) against heart failure caused by the ischemia- reperfusion injury (translated as infarct area). Methods: Biological activity exerted by ASA (0.001-100 nM) on infarct area was determined using an ischemia-reperfusion injury model. In addition, to characterize the molecular mechanism involved in the effect exerted by ASA on left ventricular pressure, some drugs such as estrone (0.001-100 nM), tamoxifen (1 nM), butoxamine (1 nM) and ZM-241385 (1 nM) were used. Results: The experimental data showed that ASA decreased the infarction area significantly (p = 0.05) compared to estrone. Other results indicated that ASA decreased left ventricular pressure and this effect was inhibited by ZM-241385. In addition, ASA increased cAMP levels in a time-dependent manner compared to control conditions. Conclusion: The results showed that ASA decreases ischemia-reperfusion injury (translated as infarct area) via A2 adenosine receptor activation and these phenomena involve changes in cAMP levels.

scholarly journals Synthesis and Biological Activity of a Bis-steroid-methanocyclobutanaphthalene- dione Derivative against Ischemia/Reperfusion Injury via Calcium Channel Activation

2020 ◽  
Vol 19 (4) ◽  
pp. 393-412
Author(s):  
Figueroa-Valverde Lauro ◽  
Diaz-Cedillo Francisco ◽  
Rosas-Nexticapa Marcela ◽  
Mateu-Armand Virginia ◽  
Garcimarero-Espino E. Alejandra ◽  
...  
Keyword(s):  
Biological Activity ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Bay K 8644 ◽  
Ventricular Pressure ◽  
Dione Derivative

Background: There is some experimental data on the effect exerted by some steroid derivatives against ischemia/reperfusion injury; however, the molecular mechanism is very confusing, perhaps this phenomenon could be due to the protocols used and/or differences in the chemical structure of each one of the steroid derivatives. Objective: The aim of this study was to synthesize a new bis-steroid-methanocyclobutanaphthalene- dione derivative using some tools chemical. Methodology: The biological activity exerted by the bis-steroid-methanocyclobutanaphthalene- dione derivative against ischemia/reperfusion injury was evaluated in an isolated heart model using noradrenaline, milrinone, dobutamine, levosimendan, and Bay-K- 8644 as controls. In addition, other alternative experiments were carried out to evaluate the biological activity induced by the bis-steroid-methanocyclobuta-naphthalene-dione derivative against left ventricular pressure in the absence or presence of nifedipine. Results: The results showed that 1) the bis-steroid-methanocyclobuta-naphthalene-dione derivative significantly decreases the ischemia-reperfusion injury translated as a decrease in the the infarct area in a similar manner to levosimendan drug; 2) both bis-steroidmethanocyclobuta- naphthalene-dione and Bay-K-8644 increase the left ventricular pressure and 3) the biological activity exerted by bis-steroid-methanocyclobuta-naphthalenedione derivative against left ventricular pressure is inhibited by nifedipine. Conclusion: In conclusion, the bis-steroid-methanocyclobuta-naphthalene-dione derivative decreases the area of infarction and increases left ventricle pressure via calcium channels activation; this phenomenon could constitute a new therapy for ischemia/reperfusion injury.

Synthesis and Biological Activity of the Pyridine-Hexacyclic-Steroid Derivative on a Heart Failure Model

2021 ◽  
Vol 21 ◽  
Author(s):  
Figueroa-Valverde Lauro ◽  
López-Ramos Maria ◽  
Díaz-Cedillo Francisco ◽  
Rosas-Nexticapa Marcela ◽  
Mateu-Armad Maria Virginia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Biological Activity ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Pyridine Derivative ◽  
Dependent Manner ◽  
Inotropic Activity ◽  
Heart Failure Model ◽  
Chemical Strategies

Background: Several drugs with inotropic activity have been synthesized; however, there is very little information on biological activity exerted by steroid derivatives in the cardiovascular system. Objective: The aim of this research was to prepare a steroid-pyridine derivative to evaluate the effect it exerts on left ventricular pressure and characterize its molecular interaction. Methods: The first stage was carried out through the synthesis of a steroid-pyridine derivative using some chemical strategies. The second stage involved the evaluation of the biological activity of the steroid-pyridine derivative on left ventricular pressure using a model of heart failure in the absence or presence of the drugs, such as flutamide, tamoxifen, prazosin, metoprolol, indomethacin, and nifedipine. Results: The results showed that steroid-pyridine derivative increased left ventricular pressure in a dose-dependent manner (0.001-100 nM); however, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These results indicate that positive inotropic activity produced by the steroid-pyridine derivative was via calcium channel activation. Furthermore, the biological activity exerted by the steroid-pyridine derivative on the left ventricle produces changes in cAMP concentration. Conclusion: It is noteworthy that positive inotropic activity produced by this steroid-pyridine derivative involves a different molecular mechanism compared to other positive inotropic drugs. Therefore, this steroid could be a good candidate for the treatment of heart failure.

scholarly journals Synthesis of new azaindeno-acetonitrile derivative with inotropic activity against heart failure model

2019 ◽  
Vol 9 (6) ◽  
pp. 4598-4604
Keyword(s):  
Heart Failure ◽  
Biological Activity ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Failure Model ◽  
Inotropic Activity ◽  
Inotropic Drugs ◽  
Heart Failure Model ◽  
Steroid Derivative

Several steroid derivatives have prepared as inotropic drugs; however, there are few reports on azaindeno-steroid derivatives with inotropic activity. The objective of this investigation was to prepare some azaindeno-acetonitrile derivatives (compounds 3 to 7) to evaluate their biological activity on left ventricular pressure. The first step was achieved by preparation of azaindeno-steroid derivatives using reactions of etherification and addition. The second stage involves the evaluation of biological activity from azaindeno-steroid derivatives on left ventricular pressure in a heart failure model using either estrone or an enone-steroid derivative (compound 2) as controls. The results showed that only compound 6 increases left ventricular pressure compared with estrone, compounds 2-5 and 6. In conclusion, the positive inotropic effect exerted by compound 6 depends on the functional groups involved in its chemical structure.

scholarly journals Biological Activity Exerted by Crocodylus moreletii Oil Against Heart Failure using an Ischemia/Reperfusion Model

2020 ◽  
Vol 9 (3) ◽  
pp. 1284-1293
Keyword(s):  
Heart Failure ◽  
Fatty Acids ◽  
Biological Activity ◽  
Sodium Oleate ◽  
Perfusion Pressure ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Biological Evaluation ◽  
Infarct Area ◽  
Crocodylus Moreletii

Several bioactive substances have been isolated from some crocodiles for therapeutic purposes; however, there is scarce information on the biological activity of Crocodylus moreletii against heart failure. The aim of this investigation was to evaluate the biological activity of Crocodylus moreletii oil against either heart failure and perfusion pressure. Fatty acids involved in the Crocodylus moreletii oil was determinate by gas chromatography analysis. In addition, the effect exerted by Crocodylus moreletii oil against heart failure (translated as infarct area) was evaluated using either sodium oleate or methyl linolelaidate as controls in an ischemia-reperfusion injury model. In addition, the biological activity of either Crocodylus moreletii (Duméril & Bibron, 1851) oil or sodium oleate or methyl linolelaidate on perfusion pressure was evaluated using an isolated rat heart model. The results showed a high concentration of linolelaidate (23.3%) and oleate (20.3%) fatty acids in the sample from Crocodylus moreletii. Also, the results of biological evaluation shown that both Crocodylus moreletii oil and sodium oleate decreased the infarct area through increase either perfusion pressure and resistance coronary compared with methyl linolelaidate. In conclusion, the results suggest that both Crocodylus moreletii oil and sodium oleate can exert changes on perfusion pressure and coronary resistance translated as a decrease of infarct area and consequently bring a cardioprotective effect.

scholarly journals The crosstalk of HDAC3, microRNA-18a and ADRB3 in the progression of heart failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jingtao Na ◽  
Haifeng Jin ◽  
Xin Wang ◽  
Kan Huang ◽  
Shuang Sun ◽  
...  
Keyword(s):  
Heart Failure ◽  
Expression Patterns ◽  
Systolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Luciferase Reporter ◽  
Left Ventricular Ejection ◽  
Tunel Staining ◽  
Ventricular Ejection Fraction

Abstract Background Heart failure (HF) is a clinical syndrome characterized by left ventricular dysfunction or elevated intracardiac pressures. Research supports that microRNAs (miRs) participate in HF by regulating  targeted genes. Hence, the current study set out to study the role of HDAC3-medaited miR-18a in HF by targeting ADRB3. Methods Firstly, HF mouse models were established by ligation of the left coronary artery at the lower edge of the left atrial appendage, and HF cell models were generated in the cardiomyocytes, followed by ectopic expression and silencing experiments. Numerous parameters including left ventricular posterior wall dimension (LVPWD), interventricular septal dimension (IVSD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LEVDP), heart rate (HR), left ventricular pressure rise rate (+ dp/dt) and left ventricular pressure drop rate (-dp/dt) were measured in the mice. In addition, apoptosis in the mice was detected by means of TUNEL staining, while RT-qPCR and Western blot analysis were performed to detect miR-18a, HDAC3, ADRB3, cMyb, MMP-9, Collagen 1 and TGF-β1 expression patterns. Dual luciferase reporter assay validated the targeting relationship between ADRB3 and miR-18a. Cardiomyocyte apoptosis was determined by means of flow cytometry. Results HDAC3 and ADRB3 were up-regulated and miR-18a was down-regulated in HF mice and cardiomyocytes. In addition, HDAC3 could reduce the miR-18a expression, and ADRB3 was negatively-targeted by miR-18a. After down-regulation of HDAC3 or ADRB3 or over-expression of miR-18a, IVSD, LVEDD, LVESD and LEVDP were found to be decreased but LVPWD, LVEF, LVFS, LVSP, + dp/dt, and −dp/dt were all increased in the HF mice, whereas fibrosis, hypertrophy and apoptosis of HF cardiomyocytes were declined. Conclusion Collectively, our findings indicate that HDAC3 silencing confers protection against HF by inhibiting miR-18a-targeted ADRB3.

scholarly journals Time delay to peak left ventricular pressure rise identifies the substrate for dyssynchronous heart failure and detects disease modification with resynchronization- an observational clinical study

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
H Odland ◽  
T Holm ◽  
S Ross ◽  
LO Gammelsrud ◽  
R Cornelussen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Nyha Class ◽  
Pressure Rise ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Cardiac Resynchronization ◽  
Disease Modification ◽  
Volumetric Response

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian South East Health Authorities Introduction Identification of disease modification prior to implantation of Cardiac Resynchronization Therapy may help select the right patients, increase responder-rates and promote the utilization of CRT. We tested the hypothesis that shortening of time-to-peak left ventricular pressure rise (Td) with CRT is useful to predict long-term volumetric response (End-systolic volume (ESV) decrease >15%) to CRT. Methods Forty-five heart failure patients admitted for CRT implantation with a class I/IIa indication according to current ESC/AHA guidelines were included in the study. Td was measured from onset QRS at baseline and from onset of pacing with CRT. Results Baseline characteristics were mean age 63 ± 10 years , 71% males, NYHA class 2.5, 87% LBBB, QRS duration 173 ± 15ms, EF biplane 31 ± 1%, ESV 144 ± 12mL and end-diastolic volume 2044 ± 14mL. At 6-months follow-up six patients increased ESV by 5 ± 8%, while 37 responders (85%) had a mean ESV decrease of 40 ± 2%.  Responders presented with a higher Td at baseline compared to non-responders (163 ± 4ms vs 119 ± 9ms, p < 0.01). Td decreased to 156 ± 4ms (p = 0.02) with CRT in responders, while in non-responders Td increased to 147 ± 10ms (p < 0.01) with CRT. A decrease in Td of less than +3.5ms from baseline accurately identified responders to therapy (AUC 0.98, p < 0.01, sensitivity 97%, specificity 100%). AUC was 0.92 for baseline Td and a cut-off at 120ms yielded a sensitivity of 100% and specificity of 80% to identify volumetric responders. A linear relationship between the change in Td from baseline and ESV decrease on long term was found (β=-61, R = 0.58, P < 0.01). Conclusions Td at baseline and the shortening of Td with CRT accurately identifies responders to CRT, with incremental value on top of current guidelines, in a population with already high response rates. Td carries the potential to become the marker for prediction of long-term volumetric response in CRT candidates. Abstract Figure.

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