Effect of trolox C on cardiac contracture induced by hydrogen peroxide

Abstract

Hydrogen peroxide (H 2 O 2 ) perfused into the aorta of the isolated rat heart induces a positive inotropic effect, with cardiac arrhythmia such as extrasystolic potentiation or cardiac contractures, depending on the dose. The last effect is similar to the "stone heart" observed in reperfusion injury and may be ascribed to lipoperoxidation (LPO) of the membrane lipids, to protein damage, to reduction of the ATP level, to enzymatic alterations and to cardioactive compounds liberated by LPO. These effects may result in calcium overload of the cardiac fibers and contracture ("stone heart"). Hearts from male Wistar rats (300-350 g) were perfused at 31 o C with Tyrode, 0.2 mM trolox C, 256 mM H 2 O 2 or trolox C + H 2 O 2 . Cardiac contractures (baseline elevation of the myograms obtained) were observed when hearts were perfused with H 2 O 2 (Tyrode: 5.9 ± 3.2; H 2 O 2 : 60.5 ± 13.9% of the initial value); perfusion with H 2 O 2 increased the LPO of rat heart homogenates measured by chemiluminescence (Tyrode: 3,199 ± 259; H 2 O 2 : 5,304 ± 133 cps mg protein -1 60 min -1 ), oxygen uptake (Tyrode: 0.44 ± 0.1; H 2 O 2 : 3.2 ± 0.8 nmol min -1 mg protein -1 ) and malonaldehyde (TBARS) formation (Tyrode: 0.12 ± 0; H 2 O 2 : 0.37 ± 0.1 nmol/ml). Previous perfusion with 0.2 mM trolox C reduced the LPO (chemiluminescence: 4,098 ± 531), oxygen uptake (0.51 ± 0) and TBARS (0.13 ± 0) but did not prevent the H 2 O 2 -induced contractures (33.3 ± 16%). ATP (Tyrode: 2.84 ± 0; H 2 O 2 : 0.57 ± 0) and glycogen levels (Tyrode: 0.46 ± 0; H 2 O 2 : 0.26 ± 0) were reduced by H 2 O 2 . Trolox did not prevent these effects (ATP: 0.84 ± 0 and glycogen: 0.27 ± 0). Trolox C is known to be more effective than α-tocopherol or γ-tocopherol in reducing LPO though it lacks the phytol portion of vitamin E to be fixed to the cell membranes. Trolox C, unlike vitamin A, did not prevent the glycogen reduction induced by H 2 O 2 . Trolox C induced a positive chronotropic effect that resulted in higher energy consumption. The reduction of energy level seemed to be more important than LPO in the mechanism of H 2 O 2 -induced contracture.

Radicais livres de oxigênio e exercício: mecanismos de formação e adaptação ao treinamento físico

“…In studies developed in our laboratory (18,19) using hearts isolated from rats in a coronary perfusion model (Langendorff), we demonstrated that both the vitamin A and the Trolox (vitamin E hydro soluble analogue) acted by reducing the lipoperoxidation levels and the H 2 O 2 -induced inotropic, chronotropic and lusitropic negative effects. This is due to the quencher capacity of the singlet oxygen of both vitamins.…”

Increased resistance to hydrogen peroxide‐induced cardiac contracture is associated with decreased myocardial oxidative stress in hypothyroid rats

“…The aorta was retroperfused with a Krebs-Henseleit solution as described elsewhere. 11 The solution was maintained at 318C, gassed with 95% O 2 and 5% CO 2 , and used for perfusion at a constant flow (10 mL/min). A water filled latex balloon connected to a pressure transducer (Isotec P23 XL -Hugo Sachs Elektroniks, March, Freiburg, Germany) was placed inside the left ventricle.…”

“…Indeed, several studies have shown that hypothyroid hearts are protected against ischemia-reperfusion, as they 10 Conversely, hydrogen peroxide (H 2 O 2 ), an important ROS, has been implicated in the mechanism of ischemic cardiac contracture, leading to ventricular dysfunction. 11 Thus, H 2 O 2 perfusion into the coronaries of isolated rat hearts has been proposed as a model to study cardiac contracture. 12 In this model, a dose dependent effect of H 2 O 2 on changes in positive inotropic effect, cardiac arrhythmias, such as post-extrasystolic potentiation, and cardiac contracture was also observed.…”

Sobretreinamento: teorias, diagnóstico e marcadores

“…This system consists of sexual hormones ceruloplasmin, coenzyme, uric acid, proteins of thermal shock, vitamin C, vitamin E among others (37) . In studies conducted in our laboratory (41)(42) using rats' isolated hearts, in a coronary perfusion model (Langendorff), it was demonstrated that both the vitamin A and Trolox (vitamin E hydro soluble analogue) acted reducing the lipoperoxidation indices and the inotropic, chronotopic and lusitropic negative effects induced by H 2 O 2 .…”