Glenn Circulation: Dynamic Physiology, Progressive Failure, Pulsatile Flow, and Fontan Risk Assessment

1. Physiologic Role of the Bidirectional Glenn Circulation

The bidirectional Glenn procedure connects the superior vena cava directly to the pulmonary arteries, allowing systemic venous blood from the upper body to reach both lungs without passing through a subpulmonary ventricle. Pulmonary blood flow through this pathway is therefore passive and is driven by the pressure gradient between the superior vena cava and the pulmonary venous atrium.

The Glenn procedure is usually performed as the second stage of palliation for a functionally univentricular heart. Before Glenn construction, pulmonary blood flow is commonly supplied by a systemic-to-pulmonary shunt, a right ventricle-to-pulmonary artery conduit, or native antegrade ventricular flow. Blood passing through these sources returns through the pulmonary veins to the heart, producing substantial preload and volume work for the systemic ventricle.

After the Glenn procedure, superior vena caval blood bypasses the heart. This reduces ventricular preload and may limit ventricular dilation, myocardial workload, and progression of systemic atrioventricular valve regurgitation. However, the circulation remains incomplete because inferior vena caval and hepatic venous blood continue to return to the heart and mix with pulmonary venous blood before entering the systemic circulation.

The Glenn circulation is therefore characterized by:

• Passive pulmonary perfusion from superior vena caval flow
• Partial systemic ventricular volume unloading
• Persistent intracardiac mixing
• Dependence on low pulmonary vascular resistance
• Sensitivity to pulmonary arterial and pulmonary venous obstruction
• Dependence on low atrial and ventricular filling pressures
• Strong interaction between cerebral blood flow, ventilation, and pulmonary blood flow

The circulation should be understood as a dynamic physiologic state rather than simply an anatomic surgical connection.

2. Determinants of Glenn Pulmonary Blood Flow and Oxygenation

In simplified terms:

Glenn pulmonary blood flow ≈ superior vena caval-to-pulmonary venous pressure gradient ÷ total pulmonary circuit resistance

Because the available pressure gradient is small, relatively modest abnormalities can substantially impair flow. Important impediments include:

• Elevated pulmonary vascular resistance
• Branch pulmonary artery stenosis or distortion
• Obstruction at the cavopulmonary anastomosis
• Pulmonary venous stenosis
• Elevated common atrial or pulmonary venous pressure
• Elevated systemic ventricular end-diastolic pressure
• Excessive positive intrathoracic pressure
• Markedly reduced superior vena caval return

Systemic oxygen saturation after Glenn palliation is not determined by pulmonary vascular resistance alone. It also depends on the proportion of total systemic venous return that is directed through the lungs.

Only superior vena caval blood is obligatorily routed through the pulmonary circulation. Inferior vena caval blood bypasses the lungs and mixes with pulmonary venous blood within the heart. Consequently, oxygenation is strongly influenced by the ratio of superior vena caval flow to total systemic venous return.

Infants have proportionally high cerebral and upper-body blood flow. The superior vena cava therefore contributes a relatively large fraction of total venous return, supporting acceptable pulmonary blood flow and oxygen saturation after Glenn palliation. With growth, a progressively greater proportion of cardiac output is distributed to the lower body and abdominal organs. Inferior vena caval return increases relative to superior vena caval return, while the proportion of total venous blood passing through the lungs decreases.

This developmental shift explains why systemic oxygen saturation may gradually decline even when the Glenn anastomosis and branch pulmonary arteries remain unobstructed.

3. The Glenn Paradox: Carbon Dioxide and Cerebral Blood Flow

Carbon dioxide has competing effects within the Glenn circulation. Hypocapnia may reduce pulmonary vascular resistance, which appears favorable for passive pulmonary perfusion. However, carbon dioxide is also a major regulator of cerebral vascular tone.

Higher arterial carbon dioxide tension produces cerebral vasodilation and increases cerebral blood flow. Because cerebral venous blood drains predominantly into the superior vena cava, increased cerebral perfusion increases superior vena caval return and therefore Glenn pulmonary blood flow.

The sequence is:

Higher PaCO₂ → cerebral vasodilation → increased cerebral blood flow → increased superior vena caval return → increased Glenn flow → improved systemic oxygenation

Conversely:

Excessive hypocapnia → cerebral vasoconstriction → reduced cerebral blood flow → reduced superior vena caval return → reduced Glenn flow → worsening desaturation

This counterintuitive relationship is the basis of the Glenn paradox. Lowering pulmonary vascular resistance does not necessarily improve oxygenation when the intervention simultaneously reduces the volume of blood entering the Glenn pathway.

In nine mechanically ventilated patients after bidirectional superior cavopulmonary anastomosis, increasing PaCO₂ from 35 mmHg to 45 and 55 mmHg increased arterial oxygenation, pulmonary blood flow, systemic blood flow, and cerebral blood flow. Pulmonary vascular resistance index did not change significantly, whereas systemic vascular resistance decreased. These findings indicate that the improvement in oxygenation was primarily related to increased blood flow rather than a measurable reduction in pulmonary vascular resistance [1]. (PubMed)

The study was small and does not justify unrestricted hypercapnia. Nevertheless, it provides direct physiologic evidence that aggressive hyperventilation and marked hypocapnia may be harmful after Glenn palliation. A PaCO₂ in the normal-to-mildly elevated range may be preferable when oxygenation is limited by inadequate superior vena caval flow rather than severe pulmonary vascular disease.

Ventilatory management must also consider intrathoracic pressure. High mean airway pressure, excessive positive end-expiratory pressure, prolonged inspiratory time, or dynamic hyperinflation may impede passive venous flow. Spontaneous breathing can augment cavopulmonary flow by generating negative intrathoracic pressure, provided that airway obstruction, agitation, acidosis, and excessive work of breathing are controlled.

4. Cerebral Oxygenation After Glenn Construction

The Glenn operation acutely increases superior vena caval and cerebral venous pressure, raising concern that cerebral perfusion or oxygen delivery may deteriorate. However, the cerebral circulation retains important autoregulatory capacity.

In a prospective observational study of 24 infants, conversion from a systemic-to-pulmonary arterial shunt circulation to a bidirectional Glenn circulation increased mean cerebral regional oxygen saturation from approximately 49% to 57%. Cerebral blood flow velocity decreased despite improved cerebral oxygenation, suggesting reduced cerebral oxygen extraction or normalization of excessive pre-Glenn cerebral flow rather than impaired cerebral perfusion [2]. (JCVA Online)

Thus, elevated central venous pressure after Glenn construction does not automatically imply inadequate cerebral oxygenation. Interpretation should incorporate arterial oxygen saturation, hemoglobin concentration, systemic blood pressure, near-infrared spectroscopy trends, transcranial Doppler findings when available, and the overall hemodynamic state.

5. Why Glenn Circulation Becomes Less Effective Over Time

5.1 Growth-Related Redistribution of Venous Return

As the child grows, lower-body blood flow increases and the superior vena caval fraction of total cardiac output decreases. Because only superior vena caval return is obligatorily oxygenated, pulmonary blood flow becomes progressively inadequate relative to total systemic flow.

The resulting sequence is:

Somatic growth → increasing inferior vena caval dominance → decreasing Glenn flow fraction → progressive systemic desaturation

This is a fundamental limitation of Glenn physiology and one reason that the procedure usually functions as an intermediate rather than definitive palliation.

5.2 Veno-Venous Collaterals

Chronically elevated superior vena caval pressure may stimulate development of collateral channels connecting the superior vena caval territory to the inferior vena cava, hepatic veins, coronary sinus, or atrium.

These collaterals decompress the superior vena cava but allow deoxygenated blood to bypass the pulmonary circulation. Large channels can substantially reduce effective pulmonary blood flow and produce progressive cyanosis.

Collateral closure may improve oxygenation when the vessel represents an unnecessary right-to-left shunt. However, embolization can be dangerous when the collateral is serving as a pressure-relief pathway in the presence of Glenn obstruction, elevated pulmonary vascular resistance, or high atrial pressure. The underlying hemodynamic cause should therefore be defined before closure.

5.3 Pulmonary Arteriovenous Malformations

Pulmonary arteriovenous malformations create intrapulmonary right-to-left shunting and progressive desaturation. Their development after cavopulmonary connection is associated particularly with exclusion or maldistribution of hepatic venous effluent from the affected lung.

The exact hepatic-derived protective factor remains incompletely defined. Nevertheless, restoration of hepatic venous blood to the pulmonary circulation at Fontan completion can lead to regression of pulmonary arteriovenous malformations when hepatic flow is distributed adequately.

Persistent unilateral malformations after Fontan completion should prompt evaluation for preferential hepatic flow streaming to the contralateral lung.

5.4 Aortopulmonary Collaterals

Aortopulmonary collaterals supply the lungs from systemic arteries independently of the Glenn pathway. They may increase oxygen saturation, but their blood returns through the pulmonary veins and adds preload to the systemic ventricle.

Substantial collateral flow can produce:

• Ventricular volume overload
• Progressive ventricular dilation
• Worsening atrioventricular valve regurgitation
• Elevated atrial and pulmonary venous pressures
• Increased Glenn pressure
• Prolonged pleural drainage
• Reduced circulatory efficiency

The physiologic consequence depends on total collateral burden rather than the mere presence of small vessels.

6. Pulsatile Glenn and Additional Antegrade Pulmonary Blood Flow

A pulsatile Glenn preserves a source of antegrade pulmonary blood flow in addition to passive superior vena caval flow. This may arise through a patent native pulmonary outflow tract, a restricted systemic-to-pulmonary shunt, or a ventricular-to-pulmonary artery conduit.

The pulmonary circulation consequently receives dual-source perfusion:

1. Passive superior vena caval flow through the Glenn connection
2. Pulsatile antegrade flow generated directly or indirectly by the ventricle

Potential benefits include improved oxygen saturation, greater pulmonary arterial growth, maintenance of pulmonary arterial pulsatility, and reduced formation of systemic-to-pulmonary collateral vessels.

In a study of 60 patients proceeding from Glenn palliation to Fontan completion, preserved antegrade flow was associated with modestly higher oxygen saturation, greater pulmonary artery growth, and fewer collateral vessels. However, these advantages did not translate into improved early outcomes after either Glenn or Fontan surgery [3]. (PubMed)

A retrospective comparison of 103 selected patients similarly found superior pulmonary artery growth with pulsatile Glenn physiology, but at the cost of a higher postoperative complication rate [4]. (ScienceDirect)

The principal disadvantage is that antegrade pulmonary blood flow returns to the heart through the pulmonary veins. It therefore partially reverses the ventricular unloading achieved by the Glenn operation. Excessive flow may cause ventricular dilation, worsening atrioventricular valve regurgitation, elevation of pulmonary venous and Glenn pressures, pleural or lymphatic complications, and reduced efficiency of the cavopulmonary pathway.

Earlier observational studies also produced conflicting results. Elimination of accessory pulmonary blood flow was associated with lower morbidity and mortality in one retrospective cohort of 92 patients [5], whereas another series of 160 patients concluded that the overall role of additional flow remained uncertain and documented early reoperations to either increase or decrease pulmonary blood flow [6]. (PubMed)

Longer-term studies remain inconsistent. In 111 patients, preservation of antegrade flow was associated with improved oxygen saturation and better long-term survival without a major difference in short-term hospital outcomes [7]. A separate multi-institutional experience involving 246 patients showed that Glenn palliation with antegrade flow could provide prolonged symptomatic palliation, with approximately 70% remaining without Fontan completion during the reported follow-up period [8]. (OUP Academic)

In contrast, a propensity-weighted analysis of 202 patients found that preserved antegrade pulmonary blood flow produced higher pre-Fontan oxygen saturation and larger pulmonary arteries but was associated with more effusion-related morbidity and worse transplant-free survival until the antegrade source was eliminated [9]. (PubMed)

These contradictory findings probably reflect differences in anatomy, pulmonary vascular development, ventricular function, the magnitude of antegrade flow, and institutional selection. The important distinction is between controlled supplemental flow and unrestricted competitive flow.

Targeted additional pulmonary blood flow may be useful in selected patients with unilateral pulmonary vascular abnormalities. A small shunt directed toward an underperfused lung, combined with control of flow to the opposite lung, improved antegrade perfusion in a retrospective series of 20 patients and allowed some to progress toward Fontan completion [10]. (PubMed)

The objective should therefore not be maximal pulmonary blood flow. The objective is adequate oxygenation and pulmonary arterial development without excessive ventricular preload or elevation of Glenn pressure.

7. High-Risk Indicators Before Fontan Completion

Fontan candidacy should not be determined by one pressure or resistance measurement. Risk is cumulative, and several moderate abnormalities may be more consequential than one isolated threshold.

Important hemodynamic and functional warning signs include:

• Pulmonary vascular resistance index around or above 3 Wood units·m²
• Persistent requirement for pulmonary vasodilator therapy
• Moderate or greater systemic atrioventricular valve regurgitation
• Moderate or greater systemic ventricular dysfunction
• Ventricular end-diastolic pressure above approximately 12 mmHg
• Elevated Glenn or mean pulmonary artery pressure
• Pulmonary venous or common atrial hypertension

Relevant anatomic and surgical factors include:

• Branch pulmonary artery stenosis or previous pulmonary artery intervention
• Pulmonary venous stenosis or previous pulmonary venous intervention
• Cavopulmonary pathway obstruction
• Restrictive atrial communication
• Major veno-venous or aortopulmonary collateral burden
• Uneven pulmonary perfusion
• Abnormal hepatic venous flow distribution

Respiratory, neurologic, functional, and syndromic conditions should also be incorporated. Chronic positive-pressure ventilation, tracheostomy, airway obstruction, diaphragmatic dysfunction, severe lung disease, impaired ambulation, and syndromes associated with pulmonary vascular, lymphatic, hepatic, or developmental abnormalities may reduce the efficiency and durability of Fontan physiology.

The available studies on carbon dioxide and antegrade pulmonary blood flow do not validate a comprehensive Fontan risk score. These findings should therefore be integrated with echocardiography, catheterization, cross-sectional imaging, respiratory assessment, functional status, and the clinical trajectory of the individual patient.

8. Clinical Integration

Evaluation of a deteriorating Glenn circulation should identify whether the dominant mechanism is:

• Inadequate superior vena caval return
• Elevated pulmonary vascular resistance
• Glenn or pulmonary arterial obstruction
• Pulmonary venous obstruction
• Elevated ventricular filling pressure
• Ventricular dysfunction or atrioventricular valve regurgitation
• Veno-venous collateral decompression
• Pulmonary arteriovenous malformations
• Excessive or inadequate antegrade pulmonary blood flow
• Major aortopulmonary collateral burden

Successful progression to Fontan completion requires more than an unobstructed Glenn anastomosis. It requires a low-resistance pulmonary vascular bed, low ventricular filling pressure, competent atrioventricular valves, balanced pulmonary perfusion, acceptable respiratory mechanics, and adequate systemic venous return.

Carbon dioxide management and antegrade pulmonary blood flow illustrate the central principle of Glenn physiology: an intervention that improves one component of the circulation may impair another. Management must therefore optimize the entire pressure-flow relationship rather than pursuing oxygen saturation, pulmonary vascular resistance, or pulmonary artery growth in isolation.

References

[1] Hoskote A, Li J, Hickey C, Erickson S, van Arsdell G, Stephens D, Holtby H, Bohn D, Adatia I. The effects of carbon dioxide on oxygenation and systemic, cerebral, and pulmonary vascular hemodynamics after the bidirectional superior cavopulmonary anastomosis. J Am Coll Cardiol. 2004;44(7):1501-1509.

[2] Bertolizio G, DiNardo JA, Laussen PC, Polito A, Pigula FA, Zurakowski D, Kussman BD. Evaluation of cerebral oxygenation and perfusion with conversion from an arterial-to-systemic shunt circulation to the bidirectional Glenn circulation in patients with univentricular cardiac abnormalities. J Cardiothorac Vasc Anesth. 2015;29(1):95-100.

[3] Gray RG, Altmann K, Mosca RS, Prakash A, Williams IA, Quaegebeur JM, Chen JM. Persistent antegrade pulmonary blood flow post-Glenn does not alter early post-Fontan outcomes in single-ventricle patients. Ann Thorac Surg. 2007;84(3):888-893.

[4] Ferns SJ, El Zein C, Multani K, Sajan I, Subramanian S, Polimenakos AC, Ilbawi MN. Is additional pulsatile pulmonary blood flow beneficial to patients with bidirectional Glenn? J Thorac Cardiovasc Surg. 2013;145(2):451-454.

[5] Mainwaring RD, Lamberti JJ, Uzark K, Spicer RL. Bidirectional Glenn: is accessory pulmonary blood flow good or bad? Circulation. 1995;92(9 Suppl):II294-II297.

[6] McElhinney DB, Marianeschi SM, Reddy VM. Additional pulmonary blood flow with the bidirectional Glenn anastomosis: does it make a difference? Ann Thorac Surg. 1998;66(2):668-672.

[7] Chen Q, Tulloh R, Caputo M, Stoica S, Kia M, Parry AJ. Does the persistence of pulsatile antegrade pulmonary blood flow following bidirectional Glenn procedure affect long-term outcome? Eur J Cardiothorac Surg. 2015;47(1):154-158.

[8] Calvaruso DF, Rubino A, Ocello S, Salviato N, Guardì D, Petruccelli DF, Cipriani A, Fattouch K, Agati S, Mignosa C, Zannini L, Marcelletti C. Bidirectional Glenn and antegrade pulmonary blood flow: temporary or definitive palliation? Ann Thorac Surg. 2008;85(4):1389-1395.

[9] Baek JS, Park CS, Choi ES, Yun TJ, Kwon BS, Yu JJ, Kim YH. The impact of additional antegrade pulmonary blood flow at bidirectional Glenn shunt on long-term outcomes. J Thorac Cardiovasc Surg. 2021;162(5):1346-1355.e4.

[10] Casella SL, Kaza AK, del Nido PJ, Lock JE, Marshall AC. Targeted increase in pulmonary blood flow in a bidirectional Glenn circulation. Semin Thorac Cardiovasc Surg. 2018;30(2):182-188.