An Experimental study of Macroangiopathy, a common complication of Diabetes Mellitus, with Ayurveda perspective
Prof. Ojha S. N.
Dr. D.Y Patil college of ayurved and research centre Pimpri pune 18
► The prevalence of macroangiopathy is increased in Diabetes Mellitus.
► Endothelial cell injury is thought to be an early event leading to atherosclerosis which may be initiated by several factors including molecular, receptorial and cellular factors provide a continuous mechanism of vascular damage.
► Dhamanipratichaya (Atherosclerosis), Kaphaja nanatmaja vikar, is responsible for diabetic angiopathy and in turn cardiovascular complications like IHD or vatika hridroga
Madhumeha (Diabetes Mellitus)
Grathita rakta (Thrombosis)
Atibhaya Shokadi (Stress)
Vyan vata (Receptorial factor)
Dhamani or srotodushti (Endothelial wall injury)
►The study of a simple experimental model of myocardial injury in animals was considered of value.
►Myocardial necrosis can be induced in experimental animals by various means.
►As the rabbits have a coronary arterial pattern akin to human, it was felt worthwhile to test the feasibility of producing myocardial ischaemia in them by slow iv administration of isoprenaline and simultaneously recording ECG events.
►To evaluate the curative effect of Parawata-Shakrit in induced myocardial ischaemia in rabbits before the use of drug in man.
MATERIAL & METHODS
Test article – Fecal matter of Pigeon
Characteristic – Yellowish brown powder
Test system – Rabbit
Strain – Albino
Body weight range – 1 to 1.5 kg.
Number of animals – Per group – 6
Total number of group – 3
►Albino rabbits of either sex weighing 1 to 1.5 kg. were divided into 3 groups
►Each group consists of six rabbits
►All 18 rabbits sedated by diazepam, I.V.
Group I :- Control group
Rabbits of this group were infused by isoprenaline (2mg/kg) dissolved in 25ml of normal saline through marginal ear vein at rate of 4 drops per minute for a period of 2 hrs. for two consecutive days under diazepam (I.V. 2mg/kg) sedation.
Group II :- Treatment group
Animals of this group were treated with Parawata – Shakrit powder suspension (1gm/kg P.O.) at 3 hrs. and 12 hrs. after the completion of second dose of isoprenaline infusion on second day.
Group III :- Treatment group
Animals were treated with Parawata-Shakrit powder suspension (1gm/kg P.O.) at 24 hrs. and 36 hrs. after the completion of second dose of isoprenaline infusion on second day
►The blood was collected from each animal for testing of AST, Sugar, Cholesterol and Clotting time.
►The twelve leads ECG was recorded in each animals on day-0, day-1, day-2, day-3, day-4 and day-5, ECG of day-0 was taken as normal ECG, on day-1 & day-2 ECG was taken immediate after completion of isoprenaline infusion.
►Animals were observed for clinical features related to overstimulation of sympathetic nervous system, viz heart rate, breathlessness, discomfort, foaming, lacrimation urination and defecation.
►On fifth day of isoprenaline infusion the animals belonging to each group were sacrified. Heart was dissected and preserved in 10% formal dehyde solution. The biopsy of heart was carried out to study gross and microscopic pathological changes.
Gr-I Day-2 ECG
Gr – I Day – 4 ECG
Gr – I Day – 5 ECG
Gr – II Day – 2 ECG
Gr – II Day – 3 ECG
Gr – II Day – 4 ECG
Gr – II Day – 5 ECG
Gr – III Day – 2 ECG
Gr – III Day – 3 ECG
Gr – III Day – 4 ECG
Gr – III Day – 5 ECG
Discussion and Conclusion
►The characteristic features of distress and shock following the isoprenaline infusion was observed in rabbits in this study, were similar to clinical features seen in AMI in human.
►Dwivedi et al (1987) have also reported a quick onset of such reactions due to iv administration of isoprenaline in rabbits.
►Trolese Mongheal et al (1977) have also reported marked cardioaccelaration within 30 seconds of the infusion of isoprenaline in dogs.
►In this study iv infusion of isoprenaline at dose of 2mg/kg to rabbits resulted in progressive and pronounced abnormalities in ECG recording.
►The presence of deep and widened Q-wave, ST segment elevation or depression & T-wave inversion were present in ECG of rabbits following the isoprenaline infusion.
►Tachycardia was also noted in all ECG
►Increase in SGOT level which reflects the severity of myocardial damage.
►In group II, treated with Parawata Shakrit (1gm/kg orally) following the second dose of isoprenaline infusion at 3 hrs. & 12 hrs., significant beneficials effects were observed on ECG findings
►ECG of day 3, 4 & 5 revealed small Q wave, normal ST segment and T-wave.
►In one animal T-wave inversion was persisting up to day 5, but ST segment was normal.
►Microscopic study also revealed the less severity of myocardial ischaemia in comparison with control group.
►In groups-III, the animals were treated with Parawata-Shakrita (1gm/kg P.O.), following the second dose of isoprenaline infusion at 24 hrs. and 36 hrs. showed good response in reduction of induced myocardial ischaemia.
►ECG finding of day 4 & day 5 revealed almost normal findings.
►There was normal ST segment & microscopic study, indicates the reduction in myocardial ischaemia as compared to control group
►The effects of drug in reducing the Myocardial ischaemia is less in group III than group II, but reduction was significant.
►As per comparative study with other available thrombolytic drugs, as mentioned in text, this drug was observed effective even after 24 hrs. of onset of myocardial ischaemia.
►Ischaemia occurs due to increased demand of oxygen & decreased supply, it is observed (Haft J I 1972) that catecholamine may produce the intravascular platelet aggregation & subsequently thrombus formation Parawata Shakrita by inducing fibrinolytic or thrombolytic mechanism may reperfuse the area.
►Vasodilation may be another mechanism through which drug may exert its action.