Combination effects of gallic acid and cyclosporine A during ischemia/ reperfusion on rat electrocardiogram parameters and arrhythmia

Introduction: Myocardial ischemia leads to electrical disturbance in the heart because of reactive oxygen specious. This study aimed to investigate the effects of gallic acid and cyclosporine A (CsA) together on electrocardiogram parameters in myocardium following ischemia - reperfusion (I/R) in isolated hearts. Methods: In this research, 50 Wistar rats weighing 250-300g were randomly divided into the 5 following groups: control, sham and gallic acid (7.5, 15 and 30mg/kg) in combination with CsA (0.2μM). On the eleventh day, the hearts were removed and perfused with Krebs solution and ischemia was induced for 30min. Then, cyclosporine was administered for 10min at the 10 minutes before reperfusion and 10 minutes the beginning of reperfusion. By placing the electrode, the parameters of RR, PR, QT, TpeakTend, JT and QTcB interval, ST elevation, R, P, Q, S, T amplitude were recorded before ischemia and during reperfusion. Results: This study showed that RR, JT, interval, p duration, ST elevation and PVC numbers of control were increased during ischemia compared with sham and decreased using gallic acid (7.5, 15 and 30mg/kg) in combination with CsA. In addition, P, R, S, T amplitude during the ischemia were decreased in control compared with sham and increased with gallic acid (15mg/kg) in combination with CsA. Conclusion: In conclusion, the optimal combination of both drugs decreased arrhythmia occurrence while increased electrical velocity of conduction and wave amplitudes in isolated myocardium after ischemia reperfusion injury.

Structural and functional indicators of the heart of patients with ischemic heart disease and type 2 diabetes mellitus. Rhythmoinotropic response isolated myocardium at different levels of glycated hemoglobin

BACKGROUND: Adequate glycemic control can significantly reduce the risk of developing cardiovascular events. However, until now, glycaemic targets in aged patients remain a subject of discussion, especially in the conditions of the combined development of Type 2 Diabetes Mellitus (T2DM) and ischemic heart disease (IHD).AIMS: To examine the structural and functional heart parameters in patients with IHD associated with T2DM and the rhythmoinotropic responses of their isolated myocardium depending on glycated hemoglobin level.MATERIALS AND METHODS: The study included 44 patients with a diagnosis of "chronic IHD associated with T2DM", of which 2 groups were formed. Patients with glycated hemoglobin level (HbA1c) <8% were included in the 1st group, and patients with HbA1c ≥8% were included in the 2nd group. The structural and functional heart parameters obtained with ultrasonography, and the rhythmoinotropic responses of myocardium in patients ex vivo were analyzed using the right atrial appendage fragments obtained during elective coronary artery bypass graft. The inotropic response of muscle strips at a basic stimulation frequency of 0,5 Hz to testing influences was assessed. An extrasystolic test and post-rest test were performed.RESULTS: It was found that extrasystolic contractions of isolated myocardial strips in patients of the 2nd group appeared at shorter extrasystolic intervals, which indicates a greater excitability of the myocardium in patients of this group. Postextrasystolic muscle contractions in patients of the 2nd group had significant potentiation. The amplitude of the muscle strips contractions in patients of both groups was potentiative after short rest periods. However, with an increase in the rest duration, potentiation of contractions was observed only in the group with a higher HbA1c level. According to the ultrasonography data, it was found that the values of the endsystolic and diastolic volumes, the interventricular septum thickness and the left ventricular (LV) myocardium mass were significantly lower in the patients of the 1st group compared with the corresponding indicators in the patients of the 2nd group. The early LV filling velocity (peak E) was significantly lower in the patients of the 1st group, which indicates a slower LV relaxation. At the same time, the rapid LV filling velocity did not have a significant intergroup difference, but this indicator exceeded the reference values in both groups.CONCLUSIONS: With a moderately increased glycemic level (9,2 [8,0; 10,3]%), the structural and functional heart parameters are preserved both at the level of the isolated myocardial tissue and at the level of the whole heart.

Titin strain contributes to the Frank–Starling law of the heart by structural rearrangements of both thin- and thick-filament proteins

The Frank–Starling mechanism of the heart is due, in part, to modulation of myofilament Ca2+ sensitivity by sarcomere length (SL) [length-dependent activation (LDA)]. The molecular mechanism(s) that underlie LDA are unknown. Recent evidence has implicated the giant protein titin in this cellular process, possibly by positioning the myosin head closer to actin. To clarify the role of titin strain in LDA, we isolated myocardium from either WT or homozygous mutant (HM) rats that express a giant splice isoform of titin, and subjected the muscles to stretch from 2.0 to 2.4 μm of SL. Upon stretch, HM compared with WT muscles displayed reduced passive force, twitch force, and myofilament LDA. Time-resolved small-angle X-ray diffraction measurements of WT twitching muscles during diastole revealed stretch-induced increases in the intensity of myosin (M2 and M6) and troponin (Tn3) reflections, as well as a reduction in cross-bridge radial spacing. Independent fluorescent probe analyses in relaxed permeabilized myocytes corroborated these findings. X-ray electron density reconstruction revealed increased mass/ordering in both thick and thin filaments. The SL-dependent changes in structure observed in WT myocardium were absent in HM myocardium. Overall, our results reveal a correlation between titin strain and the Frank–Starling mechanism. The molecular basis underlying this phenomenon appears not to involve interfilament spacing or movement of myosin toward actin but, rather, sarcomere stretch-induced simultaneous structural rearrangements within both thin and thick filaments that correlate with titin strain and myofilament LDA.

Contractility and electroexcitability of isolated myocardium of right ventricular of rat heart depending on estrous cycle and pregnancy

It is known that women and rats have increased minute volume of blood flow (MV) during pregnancy. It is believed that this is due to an increase in heart rate. This remains unclear — whether pregnancy increases myocardial contractility (and consequently increases the stroke volume). There are no data on changes of myocardium electroexcitability during pregnancy. To clarify these issues, experiments were conducted on strips of right ventricular of 94 nonpregnant and 45 pregnant rats. The strips were perfused with Krebs solution at 37 °C, which is preenriched by pure oxygen, and after 30 minutes of adaptation evaluated force of contractions. They are caused by electrostimulation (5 ms, 1 Hz, 20 V) applied transmural. Then determined the excitation threshold, i.e, minimum voltage (V), wherein a single stimul (5 ms) induced contraction. It was found that the force of contraction (mN, mN/mg wet weight or mN/mg dry weight of strips ) and the excitation threshold do not depend on the phase of the estrous cycle, pregnancy, and the availability of its terms. This means that during pregnancy contractility of right ventricle of rats myocardial does not change, and even tends to decrease. Therefore, increasing of MV during pregnancy, most likely due to an increase in heart rate. It was also established that at the end of pregnancy water content increases (on 12 %) in the myocardium (perhaps by increasing the expression of aquaporins in cardiomyocytes) which is regarded as a reflection of adaptation. Refs 41. Figs 4.

Impact of hydroxyl radical-induced injury on calcium handling and myofilament sensitivity in isolated myocardium

Hydroxyl radicals (OH˙) are involved in the pathogenesis of reperfusion injury and are observed in acute heart failure, stroke, and myocardial infarction. Two different subcellular defects are involved in the pathogenesis of OH˙ injury, deranged calcium handling, and alterations of myofilament responsiveness, but their temporal impact on contractile function is not resolved. Initially, after brief OH˙ exposure, there is a corresponding marked increase in diastolic calcium and diastolic force. We followed these parameters until a new steady-state level was reached at ∼45 min post-OH˙ exposure. At this new baseline, diastolic calcium had returned to near-normal, pre-OH˙ levels, whereas diastolic force remained markedly elevated. An increased calcium sensitivity was observed at the new baseline after OH˙-induced injury compared with the pre-OH˙ state. The acute injury that occurs after OH˙ exposure is mainly due to calcium overload, while the later sustained myocardial dysfunction is mainly due to the altered/increased myofilament responsiveness.