Abstract
Background: Diabetes mellitus is a metabolic syndrome that adversely affects all parts of the body especially
cardiovascular system. Dipeptidyl peptidase-4 (DPP-4) is a multifunctional protein and its inhibition has diverse
effects. DPP-4 inhibition was shown to improve survival rate after myocardial infarction in mice. Beneficial
myocardial metabolic effects of DPP-4 inhibitors have been observed in experimental models. Cardiovascular
outcome trials of DPP-4 inhibitors show variable adverse cardiovascular events.
Objective: This experimental study was aimed to study the direct cardiovascular effects of DPP-4 Inhibitors on
chronotropicity (Heart Rate,HR), inotropicity (Apical Force and; dP/dt(max), ECG and Coronary Flow(C.F) and
detect its potential useful and harmful effects on cardiovascular parameters.
Methods: The effects of graded doses (10-9 - 10-6M) of Sitagliptin (S) and Vildagliptin(V) were observed on
retrograde perfused isolated rabbit hearts with warm Krebs-Henseliet solution on Radnoti working heart system.
Fifty four(54) rabbits were grouped into nine groups i.e ; I(S1), II(S2), III(S3), IV(S4), V(S5), VI(S6), VII(V1), and
VIII(V2) and IX(V3) each comprising of six animals(n=6).Effects of experimental drugs were observed on
chronotropicity(HR), inotropicity (Apical Force and Peak rate of rise of LVP i.e; dP/dt(max) and Coronary
flow(CF). The results were statistically analyzed with Graph Pad Grism and wherever necessary paired or unpaired
“t” test was applied.
Conclusion: Sitagliptin and Vildagliptin both have suppressant effects on HR. Sitagliptin has positive and
Vildagliptin had negative inotropic effects. Both drugs (10-8 - 10-6M); decrease coronary flow but have no significant
effect on ECG
A.S.A.Bhatti, Aliya Shabbir, Abdul Waheed Shehzad, M.A.Bhatti. (2019) Non Incretin Effects of DPP-4 Inhibitors: Comparative Stud, Journal of Shalamar Medical and Dental College, volume 1, issue 1.
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