الفهرس 
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Abstract
Mortality associated with acute myocardial infarction (AMI) is still a leading cause of death in both developing and developed countries. The effect of early treatment with ß-blockers in reducing mortality and ischemic events after AMI is well known. The beta blocker; carvedilol; is an effective antianginal and antihypertensive agent and significantly limits infarct size in animal models. Carvedilol has previously been demonstrated to be beneficial in patients with AMI. However, the overall success of beta blockers is limited, and usually adverse reaction is clear. As such, it is important to evaluate new therapeutic modalities in addition to standard medical therapy.
Metabolic agents are a new class of drugs that directly modify the use of energy substrates in the heart, lessening ischaemic injury and improving cardiac performance during ischaemia. One of these metabolic agents is carnitine. Increasing evidences also demonstrate that oxidative stress plays an important role in experimental models of MI. Thymoquinone, the main volatile oil constituent of Nigella sativa seed, is reported to possess strong antioxidant properties. The protective effect of carvedilol-carnitine combination, and carvedilol-thymoquinone combination on myocardium was investigated using isoprenaline (ISO)-induced myocardial infarction (MI) model in rats.
Firstly, the effect of a single dose of drugs on ISO (250 mg/kg, S.C.)-induced MI was investigated; resembling acute MI treatment. Image analysis was carried out and levels of diagnostic marker enzymes in plasma, cardiac glutathione and lipid peroxides were measured. Injection of ISO caused animal mortality (46%), 60% infarction size, significant reduction in cardiac GSH level, and increased levels of diagnostic marker enzymes in plasma and lipid peroxidation in heart tissue.
Treatment with carvedilol, carnitine, or thymoquinone significantly prevented ISO-induced cardiac toxicity as evidenced by reduced mortality, reduced myocardial infarction size, decreased serum enzymes, and maintained myocardial antioxidant status at near normal status. While combination of carvedilol with either carnitine, or thymoquinone, didn’t show significant difference from carvedilol group.
Secondly, the effect of daily administration of drug combination for 2 weeks started 24 hours following ISO injection (250 mg/kg S.C.) was investigated. Tissue pathology, heart weight, collagen content, and serum TNF-α were assessed. ISO induced focal area of fibrosis, increased heart weight, increased collagen content, but didn’t affect TNF-α level. Thymoquinone didn’t show any significant difference from ISO group. Carnitine, and carvedilol showed significant protection against post-MI change. Combination of carvedilol with thymoquinone didn’t show significant difference from carvedilol group, while, carnitine showed histopathological improvement when added to carvedilol.
from the results we conclude that, adding carnitine or thymoquinone to carvedilol didn’t show additional beneficial effect compared to carvedilol alone against ISO-induced AMI. Regarding post MI remodeling, carvedilol-carnitine shows potential additive effect, while combination of carvedilol with thymoquinone didn’t show beneficial effect compared to carvedilol alone. In addition, our results show that thymoquinone represents a potential cardioprotective agent aginst acute ISO-induced MI, while no protective effect was observed aginst post-MI remodeling.