© 2006 European Society of Cardiology
Type II diabetic mice exhibit contractile dysfunction but maintain cardiac output by favourable loading conditions
Laboratory of Experimental Cardiac Surgery K.U. Leuven, Provisorium I, Minderbroedersstraat 17, 3000 Leuven, Belgium
* Corresponding author. Tel.: +32 16 337298; fax: +32 16 337855. E-mail address: paul.herijgers{at}med.kuleuven.be
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Abstract |
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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.
Key Words: Contractility • Diabetes • Obesity
Received September 20, 2005; Revised November 29, 2005; Accepted March 8, 2006
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