Rapid ventricular pacing of dogs to heart failure: biochemical and physiological studies

Abstract

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 .cntdot. min-1 .cntdot. 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 < 0.05). Dogs with heart failure also had (i) 69% lower norepinphrine 9232 .+-. 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 < 0.05). No differences between groups were observed for isozyme patterns and ATPase activity of myosin. The pacing-induced alterations in left ventricular norepinephrine and sarcoplasmic reticular and myofibrillar Ca ATPase best correlated with in vivo physiological alterations. Biochemical alterations produced by rate overload were similar to those reported for volume or pressure overload.