Premorbid Determinants of Left Ventricular Dysfunction in a Novel Model of Gradually Induced Pressure Overload in the Adult Canine

Abstract

Background When a pressure overload is placed on the left ventricle, some patients develop relatively modest hypertrophy whereas others develop extensive hypertrophy. Likewise, the occurrence of contractile dysfunction also is variable. The cause of this heterogeneity is not well understood. Methods and Results We recently developed a model of gradual proximal aortic constriction in the adult canine that mimicked the heterogeneity of the hypertrophic response seen in humans. We hypothesized that differences in outcome were related to differences present before banding. Fifteen animals were studied initially. Ten developed left ventricular dysfunction (dys group). Five dogs maintained normal function (nl group). At baseline, the nl group had a lower mean systolic wall stress (96±9 kdyne/cm 2 ; dys group, 156±7 kdyne/cm 2 ; P <.0002) and greater relative left ventricular mass (left ventricular weight [g]/body wt [kg], 5.1±0.36; dys group, 3.9±0.26; P <.02). On the basis of differences in mean systolic wall stress at baseline, we predicted outcome in the next 28 dogs by using a cutoff of 115 kdyne/cm 2 . Eighteen of 20 dogs with baseline mean systolic stress >115 kdyne/cm 2 developed dysfunction whereas 6 of 8 dogs with resting stress ≤115 kdyne/cm 2 maintained normal function. Conclusions We conclude that this canine model mimicked the heterogeneous hypertrophic response seen in humans. In the group that eventually developed dysfunction there was less cardiac mass despite 60% higher wall stress at baseline, suggesting a different set point for regulating myocardial growth in the two groups.