DSpace Collection:http://repository.usmf.md:80/handle/20.500.12710/7532024-03-28T23:33:26Z2024-03-28T23:33:26ZAngiotensin 1-7 blunts in vitro induced acute heart failureCobet, V.Tacu, L.Cobet, E.Rotaru, V.Ciobanu, L.Rotaru, A.http://repository.usmf.md:80/handle/20.500.12710/196992022-01-26T15:00:59Z2017-01-01T00:00:00ZTitle: Angiotensin 1-7 blunts in vitro induced acute heart failure
Authors: Cobet, V.; Tacu, L.; Cobet, E.; Rotaru, V.; Ciobanu, L.; Rotaru, A.
Abstract: Background: Angiotensin 1-7 (Ang 1-7) comprises consistent evidences regarding cardiovascular regulatory benefits due to Ang II receptor AT1 modulation via mass receptor.Aim: Evaluation of the Ang 1-7 cardiac effects in the in vitro induced acute heart failure.Material and methods: Acute heart failure (AHF) was induced using the model of isolated rat pumping heart perfused by Krebs solution without glucose during20 min according to Neely-Rovetto model (glucose is a single energetic substrate in this model) – control series. In another series heart has been perfused without glucose, but Ang 1-7 was added till final concentration of 10-7 M – medicated series. Left ventricle (LV) functional parameters were assayed during inotropic stimulation by norepinephrine (NE) and endothelin 1 (ET-1) in concentration of 10-6M, or ischemia-reperfusion impact (15 min of total ischemia followed by 20 min of reperfusion) reproduced in Langendorff isovolumic isolated heart. Results: Cardiac output (CO) significantly decreased after 20 min perfusion of isolate heart without glucose by 25,9% (29,4±1,3 vs 39,7±2,1 ml/min). Action of Ang 1-7led to a less decline of CO compared to control (34,8±1,6 vs 29,4±1,3 ml/min,p<0,05). NE stimulation induced an increase of control CO by 10,7% associated by LV end-diastolic pressure (LVEDP) elevation of 30,3% while in medicated series response was better: CO increased by 14,4% and LVEDP boosted only by 17,6%((19,3±1,6 (Ang 1-7) vs 27,4±1,7 (control) mm Hg, p<0,05). Stimulated by ET-1control isolated heart responded by a negative inotropic effect, and both systolicLV pressure and CO fallen respectively by 13,2% and 9,6%. Ang 1-7 insured a positive inotropic response during ET-1 action leading to CO and LV systolic pressure increase respectively by 10,5% and 11,7%. Ang 1-7 also improved the dynamics of LVEDP during ischemia-reperfusion. Thus, LVEDP was in medicated series significantly less than control index at finish of both ischemia (41,3±3,2 vs55,4±4,4 mm Hg) and reperfusion (17,2±1,4 vs 28,7±2,2 mm Hg) periods. Conclusion: Angiotensin 1-7 is a component of renin-angiotensin-aldosterone system which has a benefic action on acutely developing heart failure due to energy privation, manifested by improvement of the inotropic response of NE and reinstate positive inotropic of ET-1 action as well as significant diminution of LVEDP during ischemia-reperfusion syndrome.2017-01-01T00:00:00ZVanhoutte and Bowditch phenomena in heart failure: their relation toischemia-reperfusion impactTacu, L.Ivanov, M.Cobet, E.Rotaru, A.Ciobanu, L.Rotaru, V.Lutan, V.Feghiu, IUCobet, V.Popovici, M.http://repository.usmf.md:80/handle/20.500.12710/196982022-01-26T14:44:11Z2018-01-01T00:00:00ZTitle: Vanhoutte and Bowditch phenomena in heart failure: their relation toischemia-reperfusion impact
Authors: Tacu, L.; Ivanov, M.; Cobet, E.; Rotaru, A.; Ciobanu, L.; Rotaru, V.; Lutan, V.; Feghiu, IU; Cobet, V.; Popovici, M.
Abstract: Aim: Evaluation of both 15,16-epoxyeicosatrien (15,16-EET) induced coronaro dilation and Bowditch’s staircase in experimental heart failure (HF) as well as their influence on ischemic contracture and functional recovery of isolated heart during reperfusion.Material and methods:HF was reproduced by doxorubicin administration in rat (16mg/kg in 2 weeks). Vanhoutte’s phenomenon was estimated by coronary flow raising rate in isovolumic isolated heart perfused by Langendorff method during action of15,16-EET (10-4 M). Bowditch’s staircase was assayed by electrically induced heart rate (HR) rise till maximal level suitable to left ventricle (LV) systolic pressure elevation(LVSP). Ischemic contracture was appreciated by LV end-diastolic pressure (LVEDP)at the end of global 20 min ischemia period followed by 30 min period of reperfusion when LVSP dynamics has been recorded. Likewise, ischemia-reperfusion impact was attested in condition of 15,16-EET action during pre-ischemia (20 min) and reperfusion as well as after maximal HR reaching.Results:Coronarodilation effect of 15,16-EET has not been compromised in HF,because the coronary flow increased like in control comparatively to basal value(13,2±1,2% vs 13,9±1,1%). However, Bowditch’s staircase was earlier interrupted in comparison to control according to maximal HR matching to positive slope of LSD: 285±22,6 vs 372±29,4 1/min (p<0,05). Maximal ischemic LVEDP was significantly higher in HR: 47,6±3,3 vs 24,9±1,8 mmHg (p<0,001). On the other hand LVSP was at the end of reperfusion lower than control: 72,4±6,5 vs112,3±7,5 mmHg (p<0,01). Remarkably, 15,16-EET action before ischemia and during reperfusion notably improved dynamics of LVEDP and LVEDP in both control and HF (in the last even more evidently). Relative diminution of LVEDP measured14,3±1,4% in HF and 12,5±1,2% in control, and LVESP increment: 15,1±1,5%vs 13,7±1,3%. If the ischemia-reperfusion onset started after frequency pacingischemic contracture and functional LV recovery worsened similarly in both control and HF series: LVEDP increased by 19-20% while LVSP decreased by 17-18%.Conclusions:1. Derived (in cytochrome P450 biochemical way) from arachidonic acid 15,16-EET increases coronary flow in HF similarly to control and could be an important factor of coronary regulation by hyperpolarization mechanism in cases of endothelium dependent compromised coronary reactivity.2. 15,16-EET mitigates ischemia-reperfusion impact in HF while HR elevationworsens ischemic contracture and LV contraction recovery in reperfusion.2018-01-01T00:00:00ZRezerva coronariană în afecțiunea doxorubicinică a miocarduluiPopovici, MihailCobeţ, ValeriuCiobanu, LuciaPopovici, IonIvanov, VictoriaCiobanu, NicolaeMoraru, IonPanfile, ElenaTodiraş, MihailTacu, LiliaIvanov, Mihaelahttp://repository.usmf.md:80/handle/20.500.12710/196972022-07-11T11:45:20Z2016-01-01T00:00:00ZTitle: Rezerva coronariană în afecțiunea doxorubicinică a miocardului
Authors: Popovici, Mihail; Cobeţ, Valeriu; Ciobanu, Lucia; Popovici, Ion; Ivanov, Victoria; Ciobanu, Nicolae; Moraru, Ion; Panfile, Elena; Todiraş, Mihail; Tacu, Lilia; Ivanov, Mihaela
Abstract: Utilizând modelul de perfuzie a cordului izolat izovolumetric a fost evaluată în vitro reactivitatea coronariană în cardiomiopatia doxorubicinică, reprodusă la șobolani prin administrarea antraciclinei în doza cumulativă de 16 mg/kg. Valoarea rezervei funcționale coronariene este semnifi cativ redusă cu până la 43,2% în CMPDx la acțiunea endoteliu de-pendentă a factorilor vasotropi naturali: acetilcolina, adenozina și bradikinina. Totodată, coronarodilatarea mediată prin hiperpolarizare nu este periclitată, RFC iminentă acțiunii peroxidului de hidrogen și EET-11,12 fiind decelată la nivelul martor. Acest patern al reglării perfuziei coronariene poate fi un mecanism compensator în condițiile disfuncției endotleiale, întrucât acțiunea ET-1 pe fondalul blocării canalelor responsabile pentru hiperpolarizare, KCa, a condus la o reducere semnificativ mai concludentă a fluxului coronarian în CMPDx comparativ cu indicele martor.; Using the model of isovolumetric isolated heart has been assayed in vitro the coronary reactivity in doxorubicin induced cardiomyopathy (DxCMP), reproduced in rat by antracycline administration in cumulative dose of 16 mg/kg. The coronary functional reserve (CFR) value in DxCMP is significantly reduced by a range up to 43,2% in response to endothelium-dependent action of natural vasotropic agents such as acetylcholine, adenosine and bradykinin. However, the coronary dilation mediated by hyperpolarization is not jeopardized, and CFR inherent to hydrogen peroxide and 11.12 EET action was estimated equal to control level. This pattern of coronary perfusion regulation could be a compensatory mechanism in endothelial dysfunction because the endothelin-1 action preceded by KCa channels (responsible for hyperpolarization) blocking led to a significant more conspicuous diminution of coronary flow in DxCMP comparing to control index.; Используя модель перфузии изолированного сердца, была исследована коронарная реактивность при доксорубициновой кардио миопатии (ДКМП), воспроизведенной на крысах путём введения антрациклина в кумулятивной дозе, 16 мг/кг. Значение коронарного функционального резерва при ДКМ Показалось достоверно сниженной на величине до 43,2% при эндотелий зависимом воздействии натуральных факторов: ацетилхолина, аденозина и брадикинина. Тем не менее, коронарная дилатация о посредованной гиперполяризацией, на действие таких факторов, какперекисьводородаиэпоксиейкозатриены-11,12, была обнаружена нормальной. Этот механизмможетбытькомпенсаторнымвусловияэндотелиальнойдисфункции, посколькудействиеэндотелина-1 на фоне блокирования калиевых канальцев (KCa), ответственных за гиперполяризацию, привело к достоверно более выраженному снижению коронарного потока по сравнению с контрольным показателем.2016-01-01T00:00:00ZTaurine blunts doxorubicin cardiotoxicity: chronic and acute effectsCobet, V.Tacu, L.Hajawi, O.Rotaru, V.Frasineac, V.Braniste, A.http://repository.usmf.md:80/handle/20.500.12710/196962022-01-26T13:22:03Z2021-01-01T00:00:00ZTitle: Taurine blunts doxorubicin cardiotoxicity: chronic and acute effects
Authors: Cobet, V.; Tacu, L.; Hajawi, O.; Rotaru, V.; Frasineac, V.; Braniste, A.
Abstract: Aim. To study the functional statement of the isolated heart inherent to doxorubicin cardiotoxicity under the chronic and acute action of taurine.
Material and methods. Doxorubicin (Dx) cardiotoxicity manifested by heart failure development was reproduced classically by anthracycline
i/p administration in rats in cumulative dose of 16 mg/kg (4 mg/kg four times during 2 weeks) – Dx series. Series with chronic action of taurine (Tr) included rats receiving this aminoacid daily per os during Dx administration (100 mg/kg) – Dx + Tr series. Rats of both series were
sacrificed by euthanasia and the isolated heart was perfused by Krebs solution according to Langendorff (isovolumic heart) and Neely-Rovetto (working heart) methods in conditions of diverse hemodynamic and neuroendocrine efforts applying. Acute action of taurine was studied during its infusion in the perfusate of isolated hearts in final concentration of 40 µM. The hearts of intact rats constituted the control series.
Results. Chronic action of taurine has identified certain important functional benefits, the most important being underlined beneath. The
first, taurine reversed the negative inotropic effect of isolated heart on endothelin-1 (ET-1) action (10-7 M), detected in Dx series and manifested by both systolic pressure of left ventricle (LV) and cardiac output fall by about 9,1%. Taurine assured increase of these indices during
ET-1 stimulation. The second, Tr notably improved both isovolumic relaxation and contraction of myocardium exhibited by significant enhancement of Veragut index (118,6 ± 9,6 vs 94,8 ± 6,5 1/sec), +dP/dPmax (8389 ± 445 vs 7216 ± 363 mm Hg/sec) and -dP/dTmax (7526 ±
378 vs 5684 ± 322 mm Hg/sec) during efforts with volume and resistance. The third, Tr significantly decreased LV end diastolic pressure
(LVSDP) when coronary pressure of isovolumic heart elevated by 50% (from 80 up to 120 cm H20 column): 16,2 ± 1,2 vs 18,8 ± 1,4 mm Hg.
Acute Tr action manifested by: (i) significant LVSDP diminution during 30 min of ischemia (52,4 ± 3,1 vs 63,7 ± 4,4 mm Hg) and on 45th min
of reperfusion (18,3 ± 1,3 vs 22,8 ± 1,4 mm Hg), (ii) increased time of LV extrasystole appearance when the glucose content of Krebs solution was reduced by 50% (28,6 ± 2,8 vs 22,5 ± 2,4 min), and (iii) increased time of LV tachyarrhythmia appearance when the potassium content of Krebs solution raised up to 6,5 meq/L (9,2 ± 0,5 vs 6,9 ± 0,3 min).
Conclusion. Taurine, a natural calcium modulator of the heart, notably improves functional reserves of the myocardium exposed to cardiotoxic action of Dx, and could be seen as a relevant remedy of primary and secondary prophylaxis of Dx induced heart failure in oncologic
patients.2021-01-01T00:00:00Z