Myocardial myoglobin deficiency in various animal models of congestive heart failure.
Myoglobin is known to protect the mechanical function of the heart from hypoxia by acting as a sarcoplasmic oxygen reservoir and shuttle. We postulated a role for myoglobin in the pathogenesis of congestive heart failure. Several models of congestive heart failure were employed to test the hypothesis, including spontaneous inherited dilated cardiomyopathy in Doberman Pinschers, and heart failure produced by rapid ventricular pacing in dogs, volume overload in chickens and furazolidone toxicity in turkeys. Myocardial myoglobin was decreased by approximately 50% for all models (P less than 0.05). In Doberman Pinschers dogs which are predisposed to the development of dilated cardiomyopathy and have mild subclinical depression of cardiac performance, myocardial myoglobin (1.05 +/- 0.22 mg/g) is approximately 50% decreased compared to healthy mongrel dogs (2.15 +/- 0.52 mg/g), approximately twice as much as dobermans with heart failure (0.47 +/- 0.25 mg/g) but similar to the concentration found in dogs paced to heart failure (1.09 +/- 0.34 mg/g). Myocardium from poultry had remarkably decreased myoglobin compared to mammals (34 +/- 4 micrograms/g) with heart failure produced either by furazolidone or salt toxicity causing a further 50% reduction. In the canine models of heart failure, myocardial myoglobin concentration was demonstrated to be correlated with biochemical and physiological indicators of myocardial performance, namely, mitochondrial and sarcoplasmic reticular ATPase activities, and cardiac output, systemic vascular resistance, pulmonary capillary wedge pressure and mean arterial pressure, respectively. Our data implicates a role for myoglobin deficiency in the pathogenesis of congestive heart failure and in the predisposition of doberman pinschers to dilated cardiomyopathy.
O'Brien
P J
PJ
Department of Pathology, Ontario Veterinary College, University of Guelph, Canada.
O'Grady
M
M
McCutcheon
L J
LJ
Shen
H
H
Nowack
L
L
Horne
R D
RD
Mirsalimi
S M
SM
Julian
R J
RJ
Grima
E A
EA
Moe
G W
GW
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002645:Chickens; D004195:Disease Models, Animal; D004285:Dogs; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006454:Hemoglobins / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000172:deficiency*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014422:Turkeys
D006454:Hemoglobins; D009211:Myoglobin; D000252:Calcium-Transporting ATPases