Effect of glucagon on amitriptyline-induced cardiovascular toxicity in rats

BioMed Research International

Parodi

Jakovljević

et al. 2014

We estimated the influence of acute glucagon applications on 3H-histamine uptake by the isolated guinea-pig heart, during a single 3H-histamine passage through the coronary circulation, before and during anaphylaxis, and the influence of glucagon on level of histamine, NO, O2 −, and H2O2 in the venous effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not change 3H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, 3H-histamine Unet is increased and backflux is decreased when compared to the corresponding values in the absence of glucagon. During anaphylaxis, in the presence of glucagon, the values of 3H-histamine Umax and Unet are significantly higher and backflux is significantly lower in the presence of glucagon when compared to the corresponding values in the absence of glucagon. The level of endogenous histamine during anaphylaxis in the presence of glucagon (6.9–7.38 × 10−8 μM) is significantly lower than the histamine level in the absence of glucagon (10.35–10.45 × 10−8 μM). Glucagon pretreatment leads to a significant increase in NO release (5.69 nmol/mL) in comparison with the period before glucagon administration (2.49 nmol/mL). Then, in the presence of glucagon, O2 − level fails to increase during anaphylaxis. Also, our results show no significant differences in H2O2 levels before, during, and after anaphylaxis in the presence of glucagon, but these values are significantly lower than the corresponding values in the absence of glucagon. In conclusion, our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis.

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Glucagon Effects on³H-Histamine Uptake by the Isolated Guinea-Pig Heart during Anaphylaxis

BioMed Research International

Parodi

Jakovljević

et al. 2014

Drug and Chemical Toxicology

“…In our study, amitriptyline infusion did not cause any significant change in HR. We did not observe any significant changes in our previous studies (Kalkan et al, 2004;Kaplan et al, 2008). The reason for this is difficult to explain, but this could be due to the insensitivity of the Wistar rats to anticholinergic effects.…”

Section: Drug and Chemical Toxicology Downloaded From Informahealthcacontrasting

confidence: 64%

“…The use of vasopressor agents, such as norepinephrine, phenylephrine, or vasopressor doses of dopamine, may also be considered (Benowitz, 2004;Liebelt and Francis, 2002;Thanacoody and Thomas, 2005). Recent experimental studies have shown that many agents, such as L-NAME, a nitric-oxide synthase inhibitor, selective adenosine A 1 and A 2a receptor antagonists, and glucagon, are effective in reversing TCA-induced hypotension (Kalkan et al, 2004;Pentel et al, 1996;Tuncok et al, 2002;Kaplan et al, 2008). There are case reports suggesting the beneficial effects of vasopressin and glucagon in TCA overdose (Sensky and Olczak, 1999;Downes, 2003;Barry et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

An alternative antidote therapy in amitriptyline-induced rat toxicity model: theophylline

Oransay

Kalkan

Hocaoğlu

et al. 2010

We planned this study in order to investigate the effects of theophylline on cardiovascular parameters in an anaesthetized rat model of amitriptyline toxicity. In the preliminary study, we tested theophylline as 1 mg/kg of bolus, followed by a 0.5-mg/kg infusion. Toxicity was induced by the infusion of 0.94 mg/kg/min of amitriptyline up to the point of a 40-45% inhibition of mean arterial pressure (MAP). The rats were randomized to two groups: a group of 5% dextrose bolus followed by 5% dextrose infusion, and another group with theophylline bolus followed by infusion. Amitriptyline caused a significant decrease in MAP and prolongation in QRS; however, it did not alter heart rate (HR). When compared to the dextrose group, theophylline administration increased MAP, shortened prolonged QRS duration, and increased HR (P < 0.05, respectively). There was no statistically significant difference in the results of arterial blood-gas analyses among the groups (P > 0.05). Bolus doses followed by a continuous infusion of theophylline were found to be effective in reversing the hypotension and QRS prolongation seen in amitriptyline toxicity. One of the possible explanations of this beneficial effect is nonselective adenosine antagonism of theophylline. Further studies are needed to reveal the exact mechanism of the observed effect.

“…The glucagon is an endogenous polypeptide hormone that exerts both positive inotropic and the chronotropic effects on the myocardial tissue [23, 24]. The investigations of the glucagon influence on the transport of the radiolabeled histamine in the isolated guinea pig heart demonstrated the elevation of the histamine transport in the presence of glucagon [25, 26].…”

Section: Introductionmentioning

confidence: 99%

Glucagon Effects on Ischemic Vasodilatation in the Isolated Rat Heart

Pantović

Journal of Biomedicine and Biotechnology

et al. 2010

The myocardial reperfusion following ischemia leads to the ischemic vasodilation by affecting the release of various vasoactive substances, such as free radicals, NO, and histamine. In addition, some evidences suggest that glucagon itself may alter the release of those substances. In this study, we investigated the ischemic vasodilation of the isolated rat heart, as well as the concentrations of NO, TBARS, and histamine in the coronary venous effluent either in the presence or in the absence of glucagon. Our results showed that in the presence of glucagon, there was a faster restoration of coronary perfusion pressure during ischemic vasodilation compared to the absence of glucagon (124 ± 5.6 versus 81 ± 5.2 s) with no apparent changes in TBARS concentration. The glucagon's administration leads to the decreased release of histamine by approximately 35%. Biphasic release of NO in the presence of glucagon initially showed augmentation by 60%, followed by the significant attenuation of 45%.