β-Adrenoreceptor Agonist Isoproterenol Alters Oxidative Status, Inflammatory Signaling, Injury Markers and Apoptotic Cell Death in Myocardium of Rats

Abstract

Sustained high levels of circulating catecholamines are reported to induce cardiotoxicity. Isoproterenol (ISP), a synthetic catecholamine has been widely employed to induce myocardial injury, though the role of inflammation and apoptosis is not well established. This study was designed to investigate the underlying mechanism of oxidative damage, inflammatory signaling, cell death in ISP induced myocardial infarction in rats. Wistar albino rats were divided in two groups: group I (sham control) and group II (ischemic control). ISP (85 mg/kg, s.c.) was administered at an interval of 24 h to group II for two consecutive days. On day third, after 48 h of the first injection of ISP, blood was collected from retro orbital plexus of rat eyes to estimate the biochemical parameters. Glutathione (GSH) and superoxide dismutase (SOD) were measured for antioxidant status. Similarly, malondialdehyde (MDA) was measured as an index of lipid peroxidation. Cardiac markers (SGOT, CK-MB, TropI and LDH) and pro-inflammatory cytokines (IL-6, CRP and TNF-α) were also estimated in ISP-induced rats. At the end of experiments animals were sacrificed for histopathological studies. GSH and SOD showed significant decrease after ISP challenge as compared to sham (control) group (p < 0.01) while MDA level, increased significantly (p < 0.01). ISP, also increased the level of cardiac markers and markers of inflammation significantly (p < 0.01), which was further verified by histopathological studies of the heart tissues. The study confirmed that ISP causes detrimental changes in the myocardium by altering cardiac and inflammatory markers, which leads to severe necrosis. The deleterious effects produced by ISP substantiate its suitability as a novel animal model for evaluation of cardioprotective agents/drugs.

Selective ablation of ligament of Marshall inhibits ventricular arrhythmias during acute myocardial infarction: Possible mechanisms

“…Inhibitor for superoxide was effective in reducing ischemia‐induced VAs . Sympathetic activation could increase the level of oxidative stress and apoptosis . Our previous study also revealed a possible relevance between the cardiac autonomic nervous system and inflammation .…”

Effect of endurance exercise training on morphological changes in rat heart tissue following experimental myocardial infarction

“…Isoprenaline is a synthetic catecholamine and betaadrenergic receptor agonist that upon oxidation, generates highly toxic free radicals and stimulates membrane phospholipids peroxidation and severe myocardial membrane damage. It is reported that high levels of circulating catecholamines cause cardiac toxicity (19,20). Isoprenaline or isoproterenol-induced myocardial injury represents the occurrence of oxidative damage, lipid peroxidation, LV hemodynamic and function changes following hypertrophy, inflammatory cells infiltration, fibrous and tissue necrosis.…”

“…Isoprenaline-induced infarction, causes significant metabolical and morphological disorders in the heart muscle of laboratory animals, particularly rats, and shows biochemical and structural changes leading to cell damage and necrosis. Morphological changes observed in the coronary arteries may be justified by the mismatch between the oxygen supply and cardiac muscle demands after coronary hypotension and over activity of cardiac muscle result from isoprenaline (20). Studies have shown that the capacity to secrete catecholamine in response to stimuli such as exercise, hypoglycemia and hypoxia is very high (21).…”

“…In addition, it is known that reperfusion after ischemia leads to increased production of ROS, mitochondrial permeability and cardiovascular death (26). Thus, according to the intolerance of exercise and oxygen uptake reduction (VO2) in patients with MI (27), and also with regard to the incidence of hypoxia, coronary hypotension, cardiac hyperactivity and excessive oxidative stress, as well as reperfusion following isoprenaline-induced ischemia (20,22,26), it seems that the accumulation of the effects of endurance exercise training and isoprenaline and stress of more dealing with electric shock sticks in training group rats, in the beginning of the exercise protocol in the present study creates more damage in cardiac tissue of endurance training group rats compared with the control group. Therefore, it is likely that the extent of damage in the endurance training group was more than the control group at the first.…”

The Beneficial Effects of Electro-acupuncture at PC6 (Neiguan-point) of Gene and Protein Expressions of Classical Inward-rectifier Potassium Channels in Myocardial Ischemic Rats

“…ISO, a β-agonists, which propel heart rate acceleration, can expand blood vessels and increase the pulse pressure, but large doses of ISO can cause the increase of myocardial oxygen consumption and sharp decline in myocardial blood flow and MI injury [39,40]. And this injury was similar to the process of acute MI in human [42]. And this injury was similar to the process of acute MI in human [42].…”