Effects of pranidipine, a calcium channel antagonist, in an avian model of heart failure.
We have previously demonstrated that turkey poults fed furazolidone (Fz) in high concentrations (700 ppm) develop dilated cardiomyopathy (DCM) which approximates the human condition [1-3]. We wanted to study the effects of a calcium channel blocker in an animal model with a documented decrease in beta-receptor density, increased levels of circulating catecholamines, and abnormal calcium metabolism. The effects of a third generation calcium channel blocker has not been studied in our model. We hypothesized that the model would be predictive of the human condition and provide additional insights into the potential use of Ca2+ channel blockers in the setting of DCM. In the present study, we examined the effect of pranidipine, a new dihydropyridine calcium antagonist, in the setting of DCM on the gross and microscopic morphology of the heart and the overall contractile performance of the myocardium. A state of symptomatic to mild cardiomyopathy was induced in Broad-Breasted White turkey poults by administration of Fz for three weeks. Blood pressure, heart rate, fractional shortening, and body weight were monitored and compared in DCM animals treated with pranidipine and those given a placebo. After four weeks of treatment or no treatment with pranidipine, animals were euthanized and heart weight, cardiac dimensions, and microscopic morphology were compared. Progressive left ventricular (LV) dilatation and wall thinning was prevented with pranidipine treatment. In addition, microscopic examination demonstrated myocyte hypertrophy regression in DCM animals treated with pranidipine. In DCM animals, treatment with pranidipine resulted in significantly smaller left ventricular dimensions. We conclude that the calcium channel blocker pranidipine was not detrimental to global cardiac function in animals with dilated cardiomyopathy.
Kim
C S
CS
Whitaker Cardiovascular Research Institute, University School of Medicine, Boston, MA, USA.
Matsumori
A
A
Goldberg
L
L
Doye
A A
AA
McCoy
Q
Q
Gwathmey
J K
JK
D000818:Animals; D000891:Anti-Infective Agents, Local; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000188:drug therapy*; D004095:Dihydropyridines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005664:Furazolidone; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D014422:Turkeys
D000891:Anti-Infective Agents, Local; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D005664:Furazolidone; C048161:pranidipine; D002118:Calcium