The in vivo quantification of myocardial performance in rabbits: a model for evaluation of cardiac gene therapy.
Evaluating cardiac gene therapy in the intact animal requires an index of cardiac function capable of detecting regional differences in contractility in a load-independent fashion. Potentially load-insensitive measures of ventricular performance were therefore evaluated in 10 open- and closed-chested, anesthetized rabbits. LV transmural pressure and myocardial segment length were measured using micromanometry and sonomicrometry during steady-state and transient inferior vena caval occlusion, over a range of inotropic and loading conditions. For each intervention, segmental stroke work was calculated as the area within the left ventricular transmural pressure-length loops at a given end-diastolic segment length during inferior vena caval occlusion; regression analysis was applied to obtain the linear Frank-Starling relationship. In both open- and closed-chested states, these relationships were highly linear (r = 0.97 +/- 0.1) and reproducible. The slope of the linear relationship between segmental stroke work and end-diastolic segment length increased significantly with calcium and epinephrine infusions (P < 0.05 v control) but was not significantly altered by decreased afterload or increased afterload (P > 0.4). The x-intercept was not significantly altered by changes in intropy or afterload (P > 0.4). These data validate the linear Frank-Starling relationship and the slope, MW, as a load-insensitive index of contractility in the intact rabbit. This study presents a novel approach to the quantification of regional cardiac function in smaller animals.
Silvestry
S C
SC
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Taylor
D A
DA
Lilly
R E
RE
Atkins
B Z
BZ
Marathe
U S
US
Davis
J W
JW
Kraus
W
W
Glower
D D
DD
D000818:Animals; D015316:Genetic Therapy / Q000379:methods; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000628:therapy; D011817:Rabbits