BACKGROUND: Cardiomyopathy in type II diabetes is incompletely understood. The leptin receptor-deficient (db/db) mouse is a well-accepted model of type II diabetes. To date, left ventricular contractility has not been studied in animal models of type II diabetes with in vivo load-independent parameters. AIM: To determine cardiac function in db/db mice in vivo. METHODS: Cardiac function in 12- and 24-week-old db/db and wild-type mice was assessed using a microtip-pressure-conductance catheter. RESULTS: Left ventricular contractile dysfunction, measured by load-independent parameters (preload recruitable stroke work, end-systolic elastance, dP/dt-V(ed)), is present in diabetic mice from age 24 weeks onwards. Despite this contractile dysfunction, the conventional parameters cardiac output, ejection fraction and dP/dt(max) were maintained, which was due to an increased preload and decreased afterload. Ventriculo-arterial coupling was increased and mechanical efficiency significantly reduced in db/db mice. CONCLUSION: Our results demonstrate that, despite impaired cardiac contractility and mechanical efficiency, cardiac output is maintained in db/db mice by favourable loading conditions and that in vivo load-independent measurements are necessary to fully characterize cardiac performance in animal models of pathophysiological states.
BACKGROUND:Cardiomyopathy in type II diabetes is incompletely understood. The leptin receptor-deficient (db/db) mouse is a well-accepted model of type II diabetes. To date, left ventricular contractility has not been studied in animal models of type II diabetes with in vivo load-independent parameters. AIM: To determine cardiac function in db/db mice in vivo. METHODS: Cardiac function in 12- and 24-week-old db/db and wild-type mice was assessed using a microtip-pressure-conductance catheter. RESULTS:Left ventricular contractile dysfunction, measured by load-independent parameters (preload recruitable stroke work, end-systolic elastance, dP/dt-V(ed)), is present in diabeticmice from age 24 weeks onwards. Despite this contractile dysfunction, the conventional parameters cardiac output, ejection fraction and dP/dt(max) were maintained, which was due to an increased preload and decreased afterload. Ventriculo-arterial coupling was increased and mechanical efficiency significantly reduced in db/db mice. CONCLUSION: Our results demonstrate that, despite impaired cardiac contractility and mechanical efficiency, cardiac output is maintained in db/db mice by favourable loading conditions and that in vivo load-independent measurements are necessary to fully characterize cardiac performance in animal models of pathophysiological states.
Authors: Vincent G Demarco; David A Ford; Erik J Henriksen; Annayya R Aroor; Megan S Johnson; Javad Habibi; Lixin Ma; Ming Yang; Carolyn J Albert; John W Lally; Caleb A Ford; Mujalin Prasannarong; Melvin R Hayden; Adam T Whaley-Connell; James R Sowers Journal: Endocrinology Date: 2012-11-09 Impact factor: 4.736
Authors: Eduardo S Fricovsky; Jorge Suarez; Sang-Hyun Ihm; Brian T Scott; Jorge A Suarez-Ramirez; Indroneal Banerjee; Moises Torres-Gonzalez; Hong Wang; Irina Ellrott; Lisandro Maya-Ramos; Francisco Villarreal; Wolfgang H Dillmann Journal: Am J Physiol Regul Integr Comp Physiol Date: 2012-08-08 Impact factor: 3.619