scholarly journals STUDY OF DOSE-DEPENDENT EFFECT OF 2-ETHYL-6-METHYL-3 HYDROXYPYRIDINE SUCCINATE ON THE CONTRACTILE FUNCTION OF ISOLATED RAT HEART

2017 ◽  
Vol 3 (1) ◽  
Author(s):  
O.G. Kesarev ◽  
◽  
L.M. Danilenko ◽  
M.V. Pokrovskii ◽  
A.S. Timokhina ◽  
...  
Keyword(s):  
Rat Heart ◽  
Contractile Function ◽  
Isolated Rat Heart ◽  
Dependent Effect ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Isolated Rat

scholarly journals The dose-dependent effect of chronic Verapamil treatment on cardiac function in isolated rat heart with Hypertension

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
S Simovic ◽  
J Jeremic ◽  
G Davidovic ◽  
I Srejovic ◽  
V Zivkovic ◽  
...  
Keyword(s):  
Heart Rate ◽  
Rat Heart ◽  
Coronary Flow ◽  
Chronic Treatment ◽  
Low Dose ◽  
Isolated Rat Heart ◽  
High Dose ◽  
Chronotropic Effects ◽  
Dose Dependent ◽  
Isolated Rat

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Verapamil, a calcium channel blocker, is used for treatment of hypertension, paroxysmal supraventricular tachycardia  and angina pectoris. It primarily blocks L-type calcium channels preventing excessive influx of calcium into cardiomyocytes, leading to negative inotropic effect, and smooth muscle cells resulting in reduced relaxation of vasculature. With calcium antagonism it also causes negative chronotropic effect. However, there is no data on it’s dose-dependent effects on cardiac dynamic parameters and heart rate on isolated rat heart with hypertension. Purpose To investigate chronic, dose-dependent effects of Verapamil on cardiodynamic parameters in isolated rat heart with hypertension. Methods The present 4-week study was carried out on 24 spontaneously hypertensive Wistar Kyoto male rats  (6 weeks old): Control (n = 6), rats treated with 0.5 mg/kg/day of Verapamil (n = 6), rats treated with 5 mg/kg/day of Verapamil (n = 6) and rats treated with 50 mg/kg/day of Verapamil (n = 6). Isolated rat hearts were perfused on Langendorff perfusion apparatus. Results Chronic, low-dose Verapamil treatment significantly depressed function of all cardiodynamic parameters of the hypertensive heart when compared to the rats treated with higher doses of Verapamil (p < 0.001), except on the coronary flow and heart rate when compared to the Control (p= 0.137; p = 1.000, respectively). There was no significant differences between Verapamil in middle dose (5 mg/kg/day) and the Control group in inotropic (p = 0.415) and lusitropic (p = 1.000) effects, while it significantly lowered values of coronary flow (p = 0.002). It achieved significantly lower inotropic, lusitropic and chronotropic effects (p < 0.001) than high Verapamil dose and significantly better inotropic (p = 0.017), lusitropic (p < 0.001), but not chronotropic effects than low-dose Verapamil treatment (p = 0.179). High-dose, chronic treatment with Verapamil significantly intensified function of  the isolated rat heart with hypertension when compared to Control and lower doses of Verapamil (p < 0.001), without significant effects on coronary flow (p = 0.363). Conclusions Chronic treatment with Verapamil in high dose achieved better inotropic, chronotropic and lusitropic effects than treatment in low and middle doses of Verapamil, without significant effects on coronary flow. There is dose-depended effect of chronic Verapamil treatment on cardiac function of isolated rat heart with hypertension.

Nitric oxide regulates oxygen uptake and hydrogen peroxide release by the isolated beating rat heart

1998 ◽  
Vol 274 (1) ◽  
pp. C112-C119 ◽  
Author(s):  
Juan J. Poderoso ◽  
Jorge G. Peralta ◽  
Constanza L. Lisdero ◽  
Maria Cecilia Carreras ◽  
Marcelo Radisic ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Rat Heart ◽  
Isolated Rat Heart ◽  
Superoxide Anion Production ◽  
Rat Heart Mitochondria ◽  
Hydrogen Peroxide Release ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Isolated Rat ◽  
Intact Heart

Isolated rat heart perfused with 1.5–7.5 μM NO solutions or bradykinin, which activates endothelial NO synthase, showed a dose-dependent decrease in myocardial O2uptake from 3.2 ± 0.3 to 1.6 ± 0.1 (7.5 μM NO, n = 18, P < 0.05) and to 1.2 ± 0.1 μM O2 ⋅ min−1 ⋅ g tissue−1 (10 μM bradykinin, n = 10, P < 0.05). Perfused NO concentrations correlated with an induced release of hydrogen peroxide (H2O2) in the effluent ( r = 0.99, P < 0.01). NO markedly decreased the O2 uptake of isolated rat heart mitochondria (50% inhibition at 0.4 μM NO, r = 0.99, P < 0.001). Cytochrome spectra in NO-treated submitochondrial particles showed a double inhibition of electron transfer at cytochrome oxidase and between cytochrome b and cytochrome c, which accounts for the effects in O2uptake and H2O2 release. Most NO was bound to myoglobin; this fact is consistent with NO steady-state concentrations of 0.1–0.3 μM, which affect mitochondria. In the intact heart, finely adjusted NO concentrations regulate mitochondrial O2uptake and superoxide anion production (reflected by H2O2), which in turn contributes to the physiological clearance of NO through peroxynitrite formation.

scholarly journals Effect of Chronic Continuous Normobaric Hypoxia on Functional State of Cardiac Mitochondria and Tolerance of Isolated Rat Heart to Ischemia and Reperfusion: Role of µ and δ2 Opioid Receptors

2019 ◽  
pp. 909-920 ◽  
Author(s):  
E.S. Prokudina ◽  
N.V. Naryzhnaya ◽  
A.V. Mukhomedzyanov ◽  
A.S. Gorbunov ◽  
Y. Zhang ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Opioid Receptors ◽  
Mitochondrial Function ◽  
Rat Heart ◽  
Contractile Function ◽  
Isolated Rat Heart ◽  
Retention Capacity ◽  
Calcium Retention ◽  
Calcium Retention Capacity ◽  
Isolated Rat

Chronic continuous normobaric hypoxia (CNH) increases cardiac tolerance to ischemia/reperfusion injury in vivo and this effect is mediated via µ and δ2 opioid receptors (ORs) activation. CNH has also been shown to be cardioprotective in isolated rat heart. In this study, we hypothesize that this cardioprotective effect of CNH is mediated by activation of µ and δ2 ORs and preservation of mitochondrial function. Hearts from rats adapted to CNH (12 % oxygen) for 3 weeks were extracted, perfused in the Langendorff mode and subjected to 45 min of global ischemia and 30 min of reperfusion. Intervention groups were pretreated for 10 min with antagonists for different OR types: naloxone (300 nmol/l), the selective δ OR antagonist TIPP(ψ) (30 nmol/l), the selective δ1 OR antagonist BNTX (1 nmol/l), the selective δ2 OR antagonist naltriben (1 nmol/l), the selective peptide μ OR antagonist CTAP (100 nmol/l) and the selective κ OR antagonist nor-binaltorphimine (3 nmol/l). Creatine kinase activity in coronary effluent and cardiac contractile function were monitored to assess cardiac injury and functional impairment. Additionally, cardiac tissue was collected to measure ATP and to isolate mitochondria to measure respiration rate and calcium retention capacity. Adaptation to CNH decreased myocardial creatine kinase release during reperfusion and improved the postischemic recovery of contractile function. Additionally, CNH improved mitochondrial state 3 and uncoupled respiration rates, ADP/O, mitochondrial transmembrane potential and calcium retention capacity and myocardial ATP level during reperfusion compared to the normoxic group. These protective effects were completely abolished by naloxone, TIPP(ψ), naltriben, CTAP but not BNTX or nor-binaltorphimine. These results suggest that cardioprotection associated with adaptation to CNH is mediated by µ and δ2 opioid receptors activation and preservation of mitochondrial function.

scholarly journals The Effects of Cisplatin and Its PT(II) Analogue on Oxidative Stress of Isolated Rat Heart/ Efekti Cisplatine I PT(II) Analoga Cisplatine Na Oksidacioni Stres Izolovanog Srca Pacova

2016 ◽  
Vol 17 (1) ◽  
pp. 15-20
Author(s):  
Isidora Stojic ◽  
Vladimir Zivkovic ◽  
Ivan Srejovic ◽  
Nevena Jeremic ◽  
Vladimir Jakovljevic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Heart ◽  
Chemical Reactivity ◽  
Antitumour Activity ◽  
Platinum Complexes ◽  
Thiobarbituric Acid ◽  
Isolated Rat Heart ◽  
Platinum Compounds ◽  
Dose Dependent ◽  
Isolated Rat

Abstract To date, numerous platinum (II) complexes have been successfully used in the treatment of different types of cancer. Therapeutic platinum complexes are different in terms of their structure, chemical reactivity, solubility, pharmacokinetics and toxicity. The aim of our research was the evaluation of cardiotoxicity of dichloro-(ethylendiamine) platinum (II) in a model of isolated rat heart using the Langedorff technique. Oxidative stress was assessed by determination of superoxide anion radical, hydrogen peroxide, Thiobarbituric Acid Reactive Substances and nitric oxide levels from coronary venous effluent. All reagents were perfused at increasing concentrations from 10-8 to 10-4 M for 30 minutes. In this paper, we report that substances administered at higher doses did not induce dose-dependent effects on oxidative stress markers. The results of this research may be of great interest for future studies in this area. There are many novel platinum compounds that had previously demonstrated antitumour activity, and these types of experiments in our study can assist in the examination of their cardiotoxicity. These results could be helpful for understanding dose-dependent side effects of existing and novel platinum compounds

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