Cardiovascular drugs attenuated myocardial resistance against ischaemia-induced and reperfusion-induced injury in a rat model of repetitive occlusion

Abstract

ObjectiveWe investigated the impact of cardioprotective drugs on ST-elevation, arrhythmias and infarct size in a rat model of repetitive coronary artery occlusion.MethodsSeventy Sprague-Dawley rats were randomised to two control and five treatment groups. Placebo was either implantation of a pneumatic occluder onto the left anterior descending coronary artery (LAD) without starting repetitive occlusion (SHAM) or subsequent RO of the LAD over 10 days without medication (ROP). Treatment groups underwent RO and additionally received nitroglycerin (NTG), metoprolol, verapamil (VER), ranolazine (RAN) or candesartan (CAN). Two weeks after the intervention, rats underwent a single, sustained LAD occlusion followed by reperfusion. To evaluate differences in cardiac resistance against myocardial ischaemia and reperfusion injury, cardiac surrogate parameters including maximal ST-elevation, arrhythmias and infarct size were assessed.ResultsCompared with sham, RO alone and RO plus nitroglycerin were associated with significantly lower maximal ST-elevation and percentage of infarcted myocardium (SHAM 0.12 mV, ROP 0.06 mV (p=0.004), NTG 0.05 mV (p=0.005); SHAM 16.2%, ROP 6.6% (p=0.008), NTG 5.9% (p=0.006). Compared with RO alone, RO plus RAN was accompanied by increased ST-elevation (0.13 mV, p=0.018) and RO plusVER or CAN by more infarcted myocardium (14.2%, p=0.004% and 15.5%, p=0.003, respectively). Rats treated with VER, RAN or CAN tended to severe arrhythmias more frequently than those of the control groups.ConclusionsRO led to an increased myocardial resistance against ischaemia and reperfusion injury. Concomitant administration of nitroglycerin did not affect the efficacy of RO. Cardiovascular channel or receptor blockers reduced the efficacy of RO.

ArrhythmoGenoPharmacoTherapy

“…Thus, the preservation of cell membrane integrity includes maintenance of Ca 2+ homeostasis, various types of ion exchange receptormediated mechanisms, osmotic control, and the preservation of the rich-energy phosphates. Therefore, interventions, e.g., Ca 2+ channel antagonists (Tosaki et al, 1987a;Otani et al, 2013;Becerra et al, 2016), beta-adrenergic receptor blockers (Tosaki et al, 1987b;Winchester and Pepine, 2014;Gatzke et al, 2018), and several other newly discovered molecular structures and interventions (Wilder et al, 2016;Bukhari et al, 2018;Gatzke et al, 2018), which directly or indirectly contribute to the preservation of the aforementioned processes can diminish the incidence of reperfusion-induced arrhythmias, heart failure, and sudden cardiac death. In addition, during the past three decades several new mechanisms have been proved and implicated based on molecular biological studies, as endogenous mediators, into the pathways of ischemia/reperfusion-induced injury and arrhythmogenesis, including gaseous molecules; nitric monoxide, carbon dioxide, and hydrogen sulfide.…”

A comparative study between angiotensin receptor neprilysin inhibitor (thiorphan/irbesartan) with each of nitrate and carvedilol in a rat model of myocardial ischemic reperfusion injury

“…Furthermore, Wang and his colleagues [44] reported that the administration of NTG decreased ET-1 and CK-MB levels with the resulting prevention of myocardial pathological damage in a rat model of IR injury. Moreover, NTG could activate Na + /K + ATPase pump in the heart and thereby limits Na + and Ca 2+ overload and arrhythmias and decreases the ST segment elevation [45,46].…”

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

“…Furthermore, myocardial stunning (dysfunction) may help to regulate the massive amount of ROS production in myocytes following an I/R injury ( Najafi et al 2018 ). CAT along with the SOD and GPx, play a significant role in the protection against LPO ( Gatzke et al, 2018 , Han et al, 2019 ). According to a recent study, erythrocyte reduction of CAT and SOD in acute myocardial infarction patients is caused by inactivation/alteration of these antioxidant enzymes through cross linking or exhaustion of these antioxidant enzymes through LPO ( Qu et al, 2019 , Li et al, 2021 ).…”

“…During the reperfusion phase of I/R damage, autophagy, apoptosis, and necrosis all cause cell death ( Liu et al 2019 ). Recent years have seen significant enhancements in the protective strategies to suppress all features of post ischemic injury in cardiovascular diseases ( Gatzke et al, 2018 , Liu et al, 2019 ). Due to the scarcity of therapy options, a safer and more effective technique for developing cardiovascular drugs is urgently needed ( Badalzadeh et al, 2014 , Geldi et al, 2018 ).…”