Myocardial protective effect of octylguanidine against the damage induced by ischemia reperfusion in rat heart

Abstract

This study shows that the hydrophobic cation octylguanidine protects against myocardial damage induced by ischemia-reperfusion. The protective effect of the amine was analyzed after 5 min of coronary occlusion followed by 5 min reperfusion in rat hearts. ECG tracings from rats treated with an i.v., injection of 5 mg/kg of octylguanidine showed a total absence of post-reperfusion arrhythmias, conversely to what was observed in untreated rats. The histological images showed that myocardium fibers from treated rats were in good shape and retained their striae, also there was absence of edema. Furthermore, the accumulation of 201Tl in hearts from these rats indicated that the tissue did not suffer disruption or impairment in membrane functions. The above correlated with the fact that mitochondria isolated from the ventricular free wall from treated rats preserved their ability to synthesize ATP. We propose that the protective effect of octylguanidine might be due to its documented inhibitory action on the opening of mitochondrial non-specific pores, a mechanism which is associated in heart injury as induced by reperfusion.

In hyperthyroid rats octylguanidine protects the heart from reperfusion damage

“…To this regard, we demonstrated previously that OG protects mitochondria from permeability transition as induced by carboxyatractyloside, through blocking ANT [26]. We also showed that OG maintains the myocardium in a good shape, protecting it against the damage induced by ischemia/reperfusion [27]. The results in this work indicate that OG inhibited reperfusion arrhythmias and reduced the incidence of ventricular tachycardia in hearts isolated from hyperthyroid rats.…”

“…The mass and purity of the reagent was assessed by Dr. Roberto Arreguín from the Instituto de Química, UNAM, by using two methods, mass spectrometry and high performance liquid chromatography, indicating that the purity attained was 90% and 98%, respectively, with a molecular weight of 171 Da, which agrees closely with its molecular composition. In agreement with previous work [27], the amine was administered at a dose of 5 mg/kg body weight, injected through the femoral vein 10 min before starting the ischemic period.…”

“…The ischemic period lasted 5 min. This time was selected in agreement with previous reports [15,27,38]. Nevertheless, to get a better insight about the myocardial damage, experiments with 20 min of reperfusion were also performed.…”

“…overload [26]. Besides, the ability of OG to avoid heart damage promoted by ischemia/reperfusion [27] was also documented. The mechanism by which OG blocks the pore and, in consequence, protects from reperfusion damage, could be explained as follows: the positive charge of the guanide group might interact with negative charges of amino acid residues of the translocase; certainly, the carrier possesses 15 glutamate and 6 aspartate residues [28], these residues may form a negative pocket for the guanidinium group, whereas the alkyl chain penetrates into the hydrophobic milieu of the inner membrane, fixing the carrier in the closed conformation.…”

Pharmacological Strategies to Contend Against Myocardial Reperfusion Damage: Diverse Chemicals for Multiple Targets

“…4), have been used as protectors against reperfusion injury [55,56]. Other examples are sanglifehrin A [57] and, more recently, NIM811 [58] and octylguanidine [59].…”