Diabetes increases the risk of ventricular arrhythmias. Rats with streptozotocin-induced diabetes were randomized to treatment with …
DILTIAZEM TREATMENT ATTENUATES ELECTROPHYSIO-
LOGIC ABNORMALITIES DURING DIABETIC CARDIO-
MYOPATHY
Véronique A Lacombe, 1,4 John D Bonagura,2,4 Arun Sridhar, 1,4 David S
Feldman3,4 And Cynthia A Carnes 1,4
1Division of Pharmacy Practice and Administration, College of Pharmacy;
2Department of Veterinary Clinical Sciences; 3Department of Internal
Medicine; 4Davis Heart and Lung Research Institute The Ohio State
University, Columbus, OH
Diabetes increases the risk of ventricular arrhythmias Furthermore,
impaired ventricular relaxation diastolic dysfunction is found in the
majority of asymptomatic patients with well-controlled diabetes mellitus
and preserved systolic function Specific therapeutic strategies for this
diabetic population are not well defined The potential beneficial effect
of diltiazem DILT, a widely prescribed calcium channel blocker, to treat
cardiomyopathy and arrhythmia has not been investigated in diabetes We
hypothesized that impaired calcium handling may contribute to
electrophysiologic abnormalities during diabetes and we evaluated the
effect of chronic DILT treatment in a model of
diabetes displaying isolated
diastolic dysfunction
Rats with streptozotocin-induced diabetes were randomized to treatment with
either diltiazem or vehicle control for 8 weeks Electrocardiograms ECG
were measured at baseline and at 8 weeks after the onset of diabetes
Ventricular myocytes were isolated for measurements of action potential
duration APD by perforated patch whole cell recordings 35 05oc
ECGs in diabetic rats revealed increased QRS amplitude and QTc interval,
suggesting that repolarization of the ventricle was affected Diabetes
significantly prolonged APD compared to controls, and afterdepolarizations
occurred in diabetic myocytes Chronic treatment with diltiazem normalized
APD in DILT-treated diabetic compared to diabetic rats Furthermore,
chronic treatment with DILT significantly reduced the occurrence of
afterdepolarizations
These data demonstrate that diabetic animals have increased predisposition
for ventricular arrhythmias Furthermore, diltiazem had a beneficial effect
on electrophysiological parameters in this model of diabetic
cardiomyopathy We suggest that reducing calcium influx may
decrease
cytosolic calcium overload, which subsequently decreases the incidence of
cellular arrhythmias and normalizes action potentials during diabetes
Supported by the American Heart Association, National and Ohio Valley
Affiliate, and by the Davis Heart Lung Research Institute Thematic grant
program Bridging Fellowship to VA Lacombe
Source:martin.amedd.army.mil
