Rapid ventricular pacing of dogs to heart failure: biochemical and physiological studies.
Chronic, rapid ventricular pacing produces congestive heart failure in dogs. The objectives of this study were to determine whether or not (i) in vitro myocardial biochemical alterations reported for heart failure by volume or pressure overload also occurred with heart failure due to rate overload, and (ii) these biochemical alterations were related to relevant in vivo cardiac physiologic alterations. We compared 27 dogs that were paced to advanced heart failure with 21 sham-operated dogs. Dogs with heart failure had 55% lower left ventricular ejection fraction (22.5 +/- 7.6 vs. 50.5 +/- 5.1%) and cardiac index (81 +/- 22 vs. 178 +/- 48 mL.min-1.kg-1), 287% higher pulmonary capillary wedge pressure (27.5 +/- 6.8 vs. 7.1 +/- 3.4 mmHg; 1 mmHg = 133.3 Pa), and 64% greater left ventricular diastolic area (18.4 +/- 3.7 vs. 11.2 +/- 1.3 cm2) (all p less than 0.05). Dogs with heart failure also had (i) 69% lower norepinephrine (232 +/- 139 vs. 747 +/- 220 ng/g protein), (ii) 25-50% lower activities of myofibrillar Ca ATPase (0.188 +/- 0.026 vs. 0.253 +/- 0.051 U/mg myofibrils), sarcoplasmic reticulum Ca-transport ATPase (0.155 +/- 0.074 vs. 0.288 +/- 0.043 U/mg membrane), and the glycolytic enzyme phosphofructokinase (33.4 +/- 10.0 and 47.7 +/- 15.8 U/g), (iii) 32% higher activity of the beta-oxidation enzyme hydroxyacyl-CoA dehydrogenase (11.43 +/- 1.48 vs. 8.67 +/- 1.70 U/g), and (iv) 60% higher activity of Krebs cycle oxoglutarate dehydrogenase (2.89 +/- 0.77 vs. 1.81 +/- 0.95 U/g) (all p less than 0.05). No differences between groups were observed for isozyme patterns and ATPase activity of myosin.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Brien
P J
PJ
Department of Pathology, Ontario Veterinary College, University of Guelph, Canada.
Ianuzzo
C D
CD
Moe
G W
GW
Stopps
T P
TP
Armstrong
P W
PW
D000818:Animals; D001835:Body Weight; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004452:Echocardiography; D006019:Glycolysis / Q000187:drug effects; D006333:Heart Failure / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D006334:Heart Function Tests; D006339:Heart Rate; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D009638:Norepinephrine