Cardioprotective effects of verapamil on myocardial structure and function in a murine model of chronic Trypanosoma cruzi infection (Brazil Strain): an echocardiographic study.
Verapamil has been shown to attenuate the extent of myocardial injury in murine models of chronic Trypanosoma cruzi infection. Infected mice treated with verapamil have significantly lower myocardial expression of inducible nitric oxide synthase and cytokines and substantially less inflammatory infiltrate and myocyte necrosis at necropsy. In the present study, we examined the cardiac structural and functional correlates of verapamil treatment in CD1 mice infected with the Brazil strain of T. cruzi using serial transthoracic echocardiography. There were four groups: uninfected- untreated control, uninfected-verapamil-treated, infected-untreated control, and infected-verapamil-treated. Verapamil was given in drinking water (1 gm/l) continuously from the day of infection for a total of 120 days. Mice were evaluated at baseline, 40 and 150 days p.i. Mice in the untreated-infected group compared with the mice in the infected-verapamil-treated group showed thinning of the left ventricular wall (0.84 +/- 0.02-vs-0.92 +/- 0.04, P<0.05 mm), increase in the left ventricular end-diastolic diameter (3.27 +/- 0.15-vs-2.74 +/- 0.05 mm, P<0.05) and reduction in percent fractional shortening (37 +/- 2-vs-53 +/- 4%, P<0.05). No differences in these parameters were noted among mice in the uninfected-untreated and uninfected-verapamil-treated groups. Furthermore, right ventricular dilation was more severe in mice from the infected-untreated group as compared with those in the infected- verapamil-treated group (visual grade 1.9 +/- 0.4-vs-1.0 +/- 0.2, P<0.05). At necropsy, the extent of myocardial injury, as determined histologically, was significantly greater in the infected-untreated mice. These data provide cardiac structural and functional correlates for the previously observed cardioprotective effects of verapamil in chronic chagasic cardiomyopathy.
Chandra
Madhulika
M
Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine and The Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, New York, NY 10461, USA.
Shirani
Jamshid
J
Shtutin
Vitaliy
V
Weiss
Louis M
LM
Factor
Stephen M
SM
Petkova
Stefka B
SB
Rojkind
Marcos
M
Dominguez-Rosales
Jose A
JA
Jelicks
Linda A
LA
Morris
Stephen A
SA
Wittner
Murray
M
Tanowitz
Herbert B
HB
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014355:Chagas Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000032:analysis / Q000096:biosynthesis; D004195:Disease Models, Animal; D004452:Echocardiography; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000378:metabolism*; D016276:Ventricular Function / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D003094:Collagen; D014700:Verapamil