An animal model of dilated cardiomyopathy: characterization of dihydropyridine receptors and contractile performance.
Broad-Breasted White turkey poults exhibit a low incidence of dilated cardiomyopathy (DCM). Ejection fraction in DCM turkeys with moderate to severe dilatation was decreased from 67 +/- 5% (control, n = 20) to 42 +/- 4% (DCM, n = 12; P = 0.001). Moderate to severe DCM hearts demonstrated peak left ventricular pressure 67 +/- 4 mmHg (n = 11) vs. 156 +/- 9 mmHg (n = 10; P < 0.0001). With moderate to severe dilatation, there was normal calcium responsiveness in saponin-skinned fiber experiments. (+)[methyl-3H]-PN200-110 binding early in the course of cardiac dilatation was increased 62% (Bmax = 1,798 +/- 212 fmol/mg protein, n = 9 vs. control Bmax = 1,113 +/- 48 fmol/mg, n = 26; P < 0.0001). The concentration to reach 50% effect (EC50) for nifedipine contractile response was 0.5 log unit higher for isolated DCM muscle vs. control at the early stage of dilatation, consistent with the increase in calcium channel number identified by ligand binding. However, more advanced heart failure resulted in a decrease in number of DHP binding sites by 24% compared with control and by 53% compared with the early dilated group (Bmax, moderate dilatation = 844 +/- 71 fmol/mg, n = 7; P < 0.05). Finally, with gross dilatation, there was a second increase in calcium channel number by 40% (Bmax, severe dilatation = 1,556 +/- 201 fmol/mg, n = 7; P < 0.01) compared with control, which is an increase of 84% vs. moderate dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)
Gruver
E J
EJ
Cardiovascular Diseases Research Laboratory, Charles A. Dana Research Institute, Boston, Massachusetts.
Glass
M G
MG
Marsh
J D
JD
Gwathmey
J K
JK
D000704:Analysis of Variance; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004452:Echocardiography; D006321:Heart / Q000033:anatomy & histology / Q000503:physiopathology; D017275:Isradipine / Q000378:metabolism; D007700:Kinetics; D009124:Muscle Proteins / Q000378:metabolism*; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D014422:Turkeys; D016277:Ventricular Function, Left
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D017275:Isradipine