Induction of heart failure: haemodynamic comparison of three different canine models

Abstract

We compared three methods: arteriovenous anastomosis, doxorubicin administration, and combination of anastomosis and doxorubicin, with the intention of designing a simple, stable model of chronic heart failure. Twelve dogs were divided into three groups of four. One group received carotid-jugular anastomosis (Ana series), another group received anastomosis and doxorubicin injection (A/D series), and the last group received only doxorubicin (Dox series). Animals were followed for eight weeks. Fifteen different haemodynamic parameters were tracked and compared to baseline values. After eight weeks, diastolic pressure in the right atrium increased from 3.8+/-2.0 mmHg at baseline to 5.3+/-5.9 mmHg in the Ana series, to 6.3+/-3.3 mmHg in the Dox series and to 8.0+/-2.0 mmHg in the A/D series (P<0.05 A/D vs. baseline). Systolic pulmonary wedge pressure increased from 11.6+/-2.0 mmHg at baseline to 15.5+/-3.4 mmHg in the Ana series, 14.0+/-3.7 mmHg in the Dox series and 17.3+/-4.2 mmHg in the A/D series (P = NS vs. baseline). Left ventricular ejection fraction decreased from 53.9+/-10% at baseline to 36.1+/-5.6% in the Ana series (P<0.05 vs. baseline), 31.5+/-5.4% in the Dox series (P<0.05 vs. baseline) and 25.8+/-5.8% in the A/D series (P<0.001 vs. baseline, P<0.05 vs. Ana series and Dox series). In conclusion, eight weeks are not enough to produce stable heart failure using arteriovenous anastomosis alone. Doxorubicin administration alone produces a left ventricular failure. However, a combination of both of these interventions provides a more stable model of right-and left-sided heart failure.