الفهرس 
Material and methodsOnly 14 pages are availabe for public view
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Abstract
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The present work was performed to evaluate the effect of some non steroidal anti-inflammatory drugs on adrenaline and ouabain induced arrhythmias in anaesthetized rats, also to study the effect of imidazole (Selective thromboxane synthetase inhibitor) on adrenaline and ouabain induced arrhythmias in anaesthetized intact rats. These work was designed to investigate their effect on the prostaglandins
level in heart tissue.
In the first part of this work, in control group adrenaline were injected I.V to produce arrhythmia in anaesthetized intact rats. The minimal arrhythmogenic dose of adrenaline and minimal fibrillating dose were 20 ± 0.57 mg/kg and 40 ± 1.82 mg/kg respectively.
The second group of anaesthetized rats (no = 7) were injected I.V by acetyl salicylic acid (aspirin) 50 mg/kg, about 15 minutes prior to adrenaline injection, then the minimal arrhythmogenic dose of adrenaline and fibrillating dose were determined.
It was found that acetyl salicylic acid (aspirin)
significantly (P<0.05) increase the arrhythmogenic dose and fibrillating dose of adrenaline from 20 ± 0.57 mg/kg to 37 ± 1.56 mg/kg and from 40 ± 1.82 mg/kg to 48 ± 2.2 mg/kg respectively. This indicate that the acetyl salicylic acid
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(aspirin) have a protective effect against the adrenaline induced arrhythmias in rats.
To determine the mechanism of action of this drug, the effect of this durg on the prostaglandins level were tested on isolated rat fundus strip. In this study, it was found that the acetyl salicylic acid decreased significantly (P<0.01) the level of prostaglandins in 1 gm heart tissue from 29 ± 1.73 nanogram before treatment by to 5.6 ± 0.86 nanogram after treatment by aspirin that is to say the acetyl salicylic acid inhibite the cyclooxygenase enzyme and inhibite the conversion of arachidonic acid to prostaglandins and thromboxanes.
Also in this study, the effect of indomethacin on adrenaline arrhythmia were tested in anaethetized rats, 10 mg/kg indoomethacin was injected I.V 15 minutes prior to adrenaline injection, it was found that, indomethacin increased significantly (PC 0.01)the minimal arrhythmogenic dose and fibrillating dose of adrenaline from 20, + 0.57 mg/kg to 35 ± 1.77 mg/kg and from 40 ± 1.82 mg/kg to 50 ± 1.19 mg/kg respectively this indicate that, the indomethacin has a protective effect against adrenaline induced arrhythmia in rats also the indomethacin had been decreased significantly (P <0.01) the level of prostaglandins in 1 gm heart tissue from 29 ± 1.73 nanogram before treatment to 1.6 ± 0.05 nanogram after treatment by indomethacin. This action
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may be due to inhibition of cyclooxygenase enzyme and hence inhibition of synthesis of prostaglandins and thromboxane.
In this study imidazole a (selective thromboxane synthetase inhibitor) was tested by I.V injection of 300 ug/kg 15 minutes prior to injection of adrenaline, it was found that, the imidazole increased significantly (P <0.01) the arrhythmogenic and fibrillating dose of adrenaline from 20 + 0.57 ug/kg to 38 ± 2.92 ug/kg and from 40 ± 1.82 ug/kg to 70 ± 3.11 ug/kg respectively the above result indicate that, the imidazole have a protective effect against adrenaline arrhythmia.
Also by studying its effect on the prostaglandis level in 1gm heart tissue, it was found that imidazole decreased significantly the level of prostaglandins in 1 gm heart tissue from 29 ± 1.73 nanogram before treatment to 14.8 ± 0.82 nanogrom after treatment.
In the second part of this work, the effect of acetyl salicylic acid, indomethacin and imidazole was studied on ouabain induced arrhythmias in anaesthetized rats and also the effects of these drugs on the prostaglandins level in 1 gm heart tissue before and after treatment was determined.
The acety salicylic acid (aspirin) increased
significantly (P <0.0/) the arrhythmogenic dose and
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fibrillating dose of ouabain when injected by 50 mg/kg, 15 minutes prior to ouabain injection from 46 ± 1.13 ug/kg to 72 ± 1.84 ug/kg and from 80 ± 1.02 ug/kg to 85 ± 1.37 ug/kg respectively, that is to say the acetyl salicylic acid have a protective effect against ouabain induced arrhythmia in
anaesthetized intact rats.
The acetyl salicylic acid decreased significantly (P<0.01) the level of prostaglandins in 1 gm heart tissue from 27.8 ± 0.89 nanogram in ouabain arrhythmogenic heart before treatment to 4.3 ± 0.40 nanogram after treatment. This demonstrate that the acetyl salicylic acid (aspirin) inhibite the conversion of arachidonic acid in the heart tissue to prostaglandins and thromboxanes by inhibiting the cyclooxygenase enzyme.
The indomethacin increased significantly (PC0.01) the arrhythmogenic dose of ouabain and fibrillating dose of ouabain when injected by 10 mg/kg I.V 15 minutes prior to ouabain injection from 46 ± 1.13 ug/kg to 74 ± 1.62 ug/kg and from 80 ± 1.02 mg/kg to 82 ± 1.22 ug/kg respectively. This indicate that, the indomethacin have a protective effect against ouabain induced arrhythmias in intact rats.
The indomethacin decreased significantly (PC0.01) the level of prostaglandins in 1 gm heart tissue from 27.8 ± 0.89 nanogram in ouabain arrhythmogenic heart to 3.77 ± 0.23
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nanogram after treatment by indomethacin. This is demonstrated that, the indomethacin inhibite the cyclooxygenase enzyme and inhibite the synthesis of prostaglandins in heart tissue in case of ouabain
arrhythmia.
The imidazole (Selective thromboxane synthetase in-hibitor) increased significantly the arrhythmogenic and fibrillating dose of ouabain when injected by 300 mg/kg I.V 15 minutes prior to ouabain injection from 46 ± 1.13 mg/kg to 80 ± 1.14 mg/kg and from 80 t 1.02 mg/kg to 90 ± 1.34 mg/kg respectively. This indicate that, the imidazole have a protective effect against ouabain induced arrhythmia in anaesthetized, intact rats. The imidazole selectively inhibite the thromboxane synthetase enzyme and prevent the synthesis of thromboxane A2 in platelets which has a role in the genesis of arrhythmia.
The imidazole decreased significantly (P<0.01) the level of prostaglandins in 1 gm heart tissue in case of ouabain arrhythmia from 27.8 ± 0.89 nanogram before treatment to 17.6 ± 0.76 nanogram after treatment by imidazole. This indicate that, the imidazole may act through inhibiting the synthesis of thromboxane A2 which may be responsible for the genesis of arrhythmia in case of ouabain.
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from all results of this study, it can be concluded
that both acetyl salicylic acid (aspirin) and indomethacin
beside being antipyretics and anti-inflammatory drugs, have a protective effect in case of adrenaline and ouabain arrhythmias and reduce the level of prostaglandins in heart tissue including the thromboxane A2 which may be an important contributarY factor in the genesis of ventricular arrhythmia and fibrillation. Also imidazole (selective thromboxane synthetase inhibitor) have been found to protect the myocardium against ouabain and adrenaline arrhythmias, this indicate that the thromboxane A2 have an important role in the genesis of ventricular ectopic activity and ventricular fibrillation because TxA2 have two effects on the coronary microcirculation, firstly, it could cause local coronary vasoconstriction, by an action on vascular smooth muscle, and secondly there could be mechanical obstruction in small blood vessels as a result of TxA2 induced platelet aggregations, the result could be a further reduction in blood flow to an already compromised myocardium. this might well trigger ventricular ectopic activity.
Futher clinical evaluation of this results must await the availability of specific inhibitors of thromboxane synthetase or antagonits of thromboxane receptors for use in
patients.