Animal Model of the Univentricular Heart and Single Ventricular Physiology

The univentricular heart complexes are a fairly common and potentially lethal set of congenital cardiac anomalies. Progress in developing new therapeutics has been hampered by a lack of suitable animal models. The authors developed a stable, closed heart preparation to systematically examine potential interventions. Using neonatal piglets (3.5-6.0 kg), a 6-mm PTFE graft was anastomosed end to end to the innominate artery and end to side to the pulmonary artery. An atrial septostomy was made, using a Rashkind septostomy catheter passed transsvenously. With the same catheter, the tricuspid valve was rendered incompetent. Occlusion of the right ventricular outflow tract completed a univentricular circuit. All cardiac output exited from the left ventricle, and pulmonary blood Jow was maintained via the innominate artery-to-pulmonary artery shunt. Pressure transducers measured central venous (mid inferior vena cava), aortic, and pulmonary arterial pressures. Oximetric probes recorded systemic venous and arterial oxygen saturations. Transit-time flow probes measured total cardiac output and pulmonary flows. Systemic flow was calculated by subtracting pulmonary flow from total cardiac output. This model has been completed in 30 animals. Minimal pressure drops have been recorded across the innominate-to-pulmonary artery graft. Pulmonary flows up to 700 ± 52 mL/min were seen. Total cardiac outputs are as high as 1370 ± 88 mL/min. Mean ratios of pulmonary to systemic flow (QI/Qs ratio) range from 1.29 ±0.08 to 0.41 ± 0.09. The model allows for full continuous monitoring of systemic and pulmonary pressures and flows and for accurate characterization of the physiological effects of respiratory and pharmacological interventions. In addition, mechanical constriction of the graft may allow direct alteration of the QI/QS ratio, with determination of an optimum value for this ratio.