Type II Diabetic Mice Exhibit Contractile Dysfunction but Maintain Cardiac Output by Favourable Loading Conditions

Abstract

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-Ved), is present in diabetic mice from age 24 weeks onwards. Despite this contractile dysfunction, the conventional parameters cardiac output, ejection fraction and dP/dtmax 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.