Point:Counterpoint: Hypoxia is/is not the optimal means of reducing pulmonary blood flow in the preoperative single ventricle heart POINT: HYPOXIA IS THE OPTIMAL MEANS OF REDUCING PULMONARY BLOOD FLOW IN THE PREOPERATIVE SINGLE VENTRICLE HEART

Patients with single ventricle are often quite ill and present complex management dilemmas. The distribution of blood flow to the systemic and pulmonary circulations, which in this patient population are in parallel rather than series, depends primarily on the relative resistances of the respective vascular beds. The entire cardiac output is managed by the single ventricle and must somehow divide itself between the systemic and pulmonary circuits. As pulmonary vascular resistance decreases after birth, many of these children will suffer from overcirculation into the pulmonary circuit. In patients with ductal-dependent systemic circulation, such as hypoplastic left heart syndrome, this can result in a paucity of systemic circulation with concomitant acidosis (Fig. 1A). It was over 60 years ago that the idea of hypoxia-induced pulmonary vasoconstriction was first proposed, and this idea has been put to the test and validated many times in the past half century. In the normal heart, hypoxia to segments of lung, typically due to atelectasis or infiltrate, induces local pulmonary vasoconstriction, which minimizes ventilation-perfusion mismatching. For a patient with normal heart and lungs, this is a very effective way of limiting intrapulmonary right to left shunting of deoxygenated blood, thereby maintaining stable arterial oxygen saturations. It is generally accepted that balancing the pulmonary (Qp) and systemic blood flows (Qs) is the best way of stabilizing the circulation in patients with single ventricle. These patients, however, often respond very differently to common interventions such as the administration of oxygen and mechanical ventilation. How will the pulmonary vascular bed of a single ventricle patient respond to not just isolated lung segment hypoxia but to global hypoxia? Barnea et al. (1) developed a wonderful mathematical model of the univentricular circulation and tested it through various manipulations of cardiac output, systemic arterial and venous oxygen saturations, pulmonary venous oxygen saturations, and Qp:Qs. He demonstrated that maximal oxygen delivery to the tissues would be obtained by Qp:Qs slightly 1 and that for higher Qp:Qs ratios, oxygen delivery to the tissues would actually decrease. He also showed that with systemic arterial oxygen saturations greater than a certain value that was determined by cardiac output (typically in the 70 – 85% range), oxygen delivery falls off precipitously. Various approaches aimed at normalizing Qp:Qs by either decreasing Qp or increasing Qs have been advocated by different authors (2, 5, 6, 7, 10). Controversy exists, however, as different centers with different approaches typically have equally good results with this patient population. Determining the optimal means of reducing Qp and thereby stabilizing circulation in the univentricular heart continues to be debated, although methods that mimic the stable fetal circulation seem to be most effective. In the womb, the fetus is hypoxic with oxygen saturations between 30 and 60% (3); pulmonary vascular resistance is high, and systemic vascular resistance is low, with systemic blood flow being supplied by the ductus arteriosus. Hypoxia allows one to duplicate this stable physiology in the newborn infant (Fig. 1B). Using his mathematical model, Barnea calculated that ideal Qp:Qs balance would be obtained in patients with hypoplastic left heart syndrome by keeping arterial blood gases near the following parameters: pH 7.4, arterial partial pressure of carbon dioxide (PaCO2) 40 mmHg, with arterial partial pressure of oxygen (PaO2) 40 mmHg, and arterial saturation 75%. This, he suggests, could easily be managed by maintaining the patient in either room air, or by creating an hypoxic environment by adding additional nitrogen to lower the inspired concentration of oxygen. Reddy developed a fetal animal model of single ventricle physiology in lambs and tested various therapies aimed at altering pulmonary vascular resistance and flow and measured