lungs are able to accomplish this low-resistance circulation largely due to the fact that the length of the pulmonary circulation is smaller, and because much of the circuitry is in parallel rather than in series. If a significant anatomic defect (i.e. a hole or breach) exists between the two sides of the heart, a shunt will occur, causing blood to flow down the normal pressure gradient from the left side to the right side. The amount of blood shunted is proportional to the size of the defect, and the beat-to-beat volume of blood pumped through a left-to-right breach is a percentage of anticipated cardiac output (CO) of the left ventricle. Clinically a low index or percentage of CO ejected through a shunt is harmless; a high index or percentage of CO ejected through a left-to-right shunt heralds Eisenmenger's physiology. The left-to-right shunting of blood results in abnormally high blood flow and pressure directed to the right heart circulation, gradually leading to maladaptive changes that ultimately result in pulmonary hypertension. Increased right-sided blood volume and pressure causes a cascade of pathologic damage to the delicate pulmonary capillaries, causing them to be incrementally replaced with scar tissue. Scar (dead lung tissue) does not contribute to oxygen transfer, therefore decreasing the useful volume of the pulmonary vasculature. The scar tissue also provides less flexibility and compliance than normal lung tissue, causing further increases in pulmonary blood pressure, and the weakened heart must pump harder to continue supplying the lungs, leading to damage of more capillaries. It is because of this maladaptive response that at the onset of Eisenmenger syndrome, the damage is considered irreversible, even if the underlying heart defect is corrected after the fact. Eventually, due to increased resistance and decreased compliance of the pulmonary vessels, elevated pulmonary pressures cause the myocardium of the right heart to hypertrophy (RVH). The onset of Eisenmenger syndrome begins when right ventricular hypertrophy causes right heart pressures to exceed that of the left heart, leading to reversal of blood flow through the shunt (i.e., blood moves from the right side of the heart to the left side). As a consequence, deoxygenated blood returning from the body bypasses the lungs through the reversed shunt and proceeds directly to systemic circulation, leading to cyanosis and resultant organ damage. The defect, now a right-to-left shunt, causes reduced oxygen saturation in the arterial blood due to mixing of oxygenated blood