scholarly journals The effects of lidocaine on bupivacaine-induced cardiotoxicity in the isolated rat heart

2010 ◽  
pp. S65-S69
Author(s):  
I Křikava ◽  
J Jarkovský ◽  
P Štourač ◽  
M Nováková ◽  
P Ševčík

Bupivacaine is a widely used long-acting local anaesthetic. In clinical practice, a mixture of bupivacaine and lidocaine is often used in order to combine the faster onset of sensory blockade of lidocaine with more profound and longer duration of blockade by bupivacaine. The aim of this study was to compare the cardiotoxicity of large doses of bupivacaine and mixture of bupivacaine with lidocaine in the isolated rat heart and to estimate whether or not the addition of lidocaine in clinically relevant concentration increases bupivacaine-induced toxicity. Experiments were performed on 21 adult male rats divided into three groups: B (6 µg/ml bupivacaine), BL (6 µg/ml bupivacaine and 12 µg/ml lidocaine) and L (12 µg/ml lidocaine). The experiment consisted of three 30 min periods: stabilisation, perfusion and washout. The isolated hearts were perfused according to Langendorff with Krebs-Henseleit solution at constant pressure (80 mmHg) and 37 °C (CaCl2 1.25 mM) and the heart rate (based on RR interval assessment), PQ and QRS intervals were measured. The present study shows that the mixture of tested anaesthetics – bupivacaine and lidocaine – impairs the intraventricular conduction parameters (QRS interval prolongation) to a lesser extent than bupivacaine itself, and that this effect is marked mainly at the beginning of perfusion.

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
S Simovic ◽  
J Jeremic ◽  
G Davidovic ◽  
I Srejovic ◽  
S Mitrovic ◽  
...  

Abstract Introduction Amiodarone represents the most widely used antiarrhythmic drug, even though it has been shown that it has negative inotropic and lusitropic effect in healthy hears. On the other hand, dronedarone reduces the risk of recurrent atrial fibrillation, but with increased early mortality related to the worsening of heart failure. However, the mechanisms responsible for these fatal outcomes remain unclear and require further examinations.  Purpose To investigate acute, direct effects of Dronedarone and Amiodarone on cardiac contractility, coronary flow and oxidative stress parameters in isolated rat heart with hypertension. Methods  The present study was carried out on 18 isolated hearts of spontaneously hypertensive Wistar Kyoto male rats (6 weeks old, bodyweight 200 ± 10 g). After isolation, all hearts were retrogradely perfused according to Langendorff technique with a gradually increment of coronary perfusion pressure (CPP from 40 to 120 cm H2O) and randomly divided into 3 groups: Control (n = 6), Amiodarone (n = 6, isolated hearts perfused with Amiodarone in dose of 3 umol), Dronedarone (n = 6, isolated hearts perfused with Dronedarone in dose of 1.8 umol). During ex vivo protocol continuously were registered cardiac contractility parameters and coronary flow, while from collected coronary venous effluent markers of oxidative stress were measured. All hearts were then fixated and stained with Hematoxylin/eosin. Results  Dronedarone severely depressed the function of all cardiodynamic parameters of the heart compared with Amiodarone or Control while Amiodarone intensified the function of the isolated rat heart with hypertension compared to Control (dp/dt max mmHg/s at coronary perfusion pressure 120cmH2O Dronedarone vs. Amiodarone vs. Control 579.733 ± 202.27 vs. 3063.65 ± 467.93 vs. 2682.88 ± 368.75; p < 0.001. dp/dt min mmHg/s 120cmH2O -352.13 ± 204.65 vs. 1960 ± 242.21 vs. -1858.83 ± 118.23; p < 0.001. SLVP mmHg at CPP 120cmH20 27.8 ± 3.46 vs. 98.95 ± 11.78 vs. 71.45 ± 7.56; p < 0.001. DLVP mmHg at CPP 120cmH2O 6.32 ± 0.49 vs. 4.83 ± 0.54 vs. 0.85 ± 0.35; p < 0.001). Acute administration of Dronedarone decreased the level of NO2- and increased the level of H2O2 , while Amiodarone heightens O2- levels (O2- nmol/min g wt at coronary perfusion pressure 120cmH2O Dronedarone vs. Amiodarone vs. Control  28.62 ± 2.54 vs. 77.3 ± 8.86 vs. 31.72 ± 4.56; p < 0.001. H2O2 nmol/min g wt at CPP 120cmH2O 92.56 ± 11.65 vs. 48.63 ± 10.11 vs. 42.84 ± 84; p < 0.001. NO2- nmol/min g wt at CPP 120cmH2O 38.61 ± 4.94 vs.  82.28 ± 5.76 vs.  64.71 ± 3.51; p < 0.001). Pathohistological, structural changes were observed in both, experimental groups. Conclusions  Acute administration of Dronedarone depresses cardiac function in isolated, working rat heart with hypertension, with decreasing the NO2- levels, increasing the level of H2O2 and enhanced structural changes when compared to Amiodarone.


1980 ◽  
Vol 239 (3) ◽  
pp. H380-H390
Author(s):  
P. Carbonin ◽  
M. Di Gennaro ◽  
R. Valle ◽  
R. Beranbei ◽  
A. Habed

The electrogram (EG) of the isolated rat heart during ischemic or anoxic perfusion has been studied. Reduction of the coronary flow rate (CFR) induced an increase of voltage (V) both in unipolar epicardial EG and in transmural bipolar EG. The V increase did not occur during anoxic perfusin. The ischemic increase cannot be due to a disturbance in the His-Purkinje or intraventricular conduction because it was observed also in the circumscribed myocardial area, which was explored by means of the transmural bipolar EG. Likewise it cannot be due to an intramural block because it occurs before one observes an augmentation of epicardial activation time or a decrease of dV/dtmax. Therefore, the ischemic V increase should be due to a modification of transmembrane potential. The variation rate of V, of dP/dt, and of myocardial ATP behaved in a similar way during underperfusion. Varying intracellular Ca2+ by means of a Ca2+-free medium or verapamil reduces the ischemic V increase. The dynamics of the ischemic V increase may be represented in order of succession by: inhibition of oxidative metabolism, augmentation of intracellular Ca2+, increase of K+ conductance, and hyperpolarization of cardiac cells.


1982 ◽  
Vol 60 (12) ◽  
pp. 1526-1532
Author(s):  
Margaret P. Moffat ◽  
Morris Karmazyn ◽  
Naranjan S. Dhalla

The effect of hypoxic perfusion on isolated hearts from male and female rats fed either a control or 2% cholesterol supplemented diet was studied. Initiation of hypoxia produced a rapid decline in rate of hearts from either male or female animals irrespective of diet regimen. However, hearts from male rats fed a control diet exhibited a significantly higher (P < 0.01) resting rate during normoxic perfusion when compared with hearts from cholesterol-fed animals. Hypoxia also produced a rapid loss of myocardial contractile force and this effect was influenced by neither diet treatment nor animal gender. Similarly, there was little change in time to peak height of developed tension due to diet. Contracture development during hypoxic perfusion was significantly higher in hearts from female rats fed a cholesterol-supplemented diet compared with hearts from control diet fed female animals, whereas no changes were observed due to diet in hearts from male animals. Coronary resistance was increased as a result of hypoxic perfusion. In hearts from cholesterol-fed male rats this effect was substantially attenuated. Conversely, cholesterol supplementation resulted in a higher (P < 0.05) coronary resistance in hearts from female animals either during normoxic or the early period of hypoxic perfusion. Prostacyclin synthesis as measured by immunoreactive 6-keto-PGF1α efflux did not differ between hearts from either male or female rats during normoxic perfusion. Hypoxia significantly reduced 6-keto-PGF1α efflux from hearts of cholesterol-fed male rats whereas it produced no effect in any other treatment category. Our results demonstrate a substantial contribution of dietary cholesterol and animal gender in the response of the isolated rat heart to hypoxic perfusion.


1982 ◽  
Vol 60 (6) ◽  
pp. 819-824 ◽  
Author(s):  
Morris Karmazyn ◽  
Naranjan S. Dhalla

Previous reports have demonstrated an antagonistic influence of adenosine on the biological effects of prostaglandins (PGs). We examined such a possible relationship on the isolated rat heart perfused at constant pressure and maintained at a constant heart rate. PGE2 and PGF2α (2.8 × 10−11 to 2.8 × 10−7 M) exerted a positive inotropic influence on the heart with PGF2α demonstrating the greater maximum effect. PGI2 had a negative inotropic effect only at high concentrations (2.8 × 10−9 to 2.8 × 10−7 M). The coronary flow was decreased by both PGE2 and PGF2α. The concentrations of PGI2 employed had minimal vasoactive properties (20% increase in flow at 2.9 × 10−7 M). Adenosine at concentrations which increased coronary flow by 24 to 63% (0.1 to 10 μM) had no influence on either the alteration in contractile force produced by PGE2, PGF2α, or PGI2 or on the coronary effects of PGE2, or PGI2. Adenosine did however, attenuate the degree of coronary flow reduction produced by PGF2α administration. These results are suggestive of a selective inhibiting influence of adenosine on the coronary constricting effects of PGF2α in the isolated rat heart.


Author(s):  
Tetyana V Shimanskaya ◽  
Yulia V. Goshovska ◽  
Olena M. Semenykhina ◽  
Vadim F. Sagach

Circulation ◽  
1997 ◽  
Vol 95 (8) ◽  
pp. 2122-2129 ◽  
Author(s):  
Salvatore Pepe ◽  
Rui-Ping Xiao ◽  
Charlene Hohl ◽  
Ruth Altschuld ◽  
Edward G. Lakatta

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3148-3156 ◽  
Author(s):  
A. K. Snabaitis ◽  
M. J. Shattock ◽  
D. J. Chambers

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