Pulmonary Vascular Resistance and Pulmonary Hypertension

Pulmonary artery pressure can rise because pulmonary vascular load increases, left atrial pressure rises, or more blood flows through the lungs. These mechanisms often coexist. Interpreting pressure alongside flow and downstream pressure helps explain the problem and its response to treatment.

12.1 A Low-Pressure Circulation With Substantial Reserve

The pulmonary circulation receives the entire effective right ventricular output. Blood flows through a large network of parallel vessels. Because many pathways carry blood at the same time, the network normally accommodates that output with a relatively small pressure difference between the pulmonary artery and left atrium.

The vessels also change as flow and pressure increase. Recruitment means that additional vascular pathways participate effectively in flow. Distension means that vessels already carrying blood become wider. Both increase the capacity of the network, although their relative contributions depend on the initial vascular pressures, lung volume, and other conditions.

This flexibility helps the pulmonary circulation accommodate exercise. More blood passes through the lungs each minute, and pulmonary artery pressure rises. The pressure increase is limited by the ability of the vascular network to expand and conduct more flow. A rigid tube with a fixed diameter would behave differently.

Reeves and colleagues examined published human exercise measurements using a distensible-vessel model. Their analysis showed how vascular distensibility helps explain the pressure response to increasing flow. This was a model-based interpretation of exercise physiology, not a way to measure an unstable ICU patient's vascular reserve from one resting pressure. 1

Obstruction, remodeling, compression, or vasoconstriction can reduce the capacity to accommodate flow. A larger pressure rise may then be required to move the same additional volume through the lungs. The right ventricle must generate that pressure while maintaining stroke volume.

A satisfactory resting pulmonary pressure therefore does not prove that reserve is normal. Conversely, a pressure rise during a large flow increase does not by itself demonstrate new vasoconstriction. Recruitment and distension can also lower calculated resistance without any active relaxation of vascular smooth muscle. Interpret the change in pressure with flow, downstream pressure, and the clinical setting.

12.2 Calculating Pulmonary Vascular Resistance

Pulmonary vascular resistance, or PVR, relates the mean pressure difference across the pulmonary circulation to pulmonary blood flow:

Mean pulmonary artery pressure, abbreviated mPAP, describes the average pressure at the arterial end of this circulation. Pulmonary artery wedge pressure, or PAWP, estimates left atrial pressure when the measurement is valid. It is also called pulmonary artery occlusion pressure. Subtracting PAWP from mPAP estimates the pressure drop across the pulmonary vessels. This difference is the transpulmonary gradient.

Dividing that gradient by flow shows how much pressure difference accompanies each unit of pulmonary flow. With pressure in mm Hg and flow in L/min, PVR is expressed in Wood units. One Wood unit equals 1 mm Hg·min/L.

For an illustrative calculation, let mPAP be 30 mm Hg, PAWP 10 mm Hg, and cardiac output 5 L/min. First find the pressure difference:

30 − 10 = 20 mm Hg

Then divide by flow:

20 ÷ 5 = 4 Wood units

The same resistance can be expressed in dyn·s·cm⁻⁵. Multiply the value in Wood units by 80:

4 × 80 = 320 dyn·s·cm⁻⁵

This conversion changes the units, not the physiology. These assumed values explain the arithmetic and are not treatment targets.

Now consider a second patient with the same mPAP of 30 mm Hg and output of 5 L/min, but a PAWP of 20 mm Hg:

30 − 20 = 10 mm Hg

10 ÷ 5 = 2 Wood units

Both patients have the same pulmonary artery pressure. In the second patient, more of that pressure reflects the higher downstream pressure, while the pressure drop across the pulmonary vessels is smaller. Pulmonary artery pressure alone cannot distinguish these situations.

PVR describes the relationship at the measured operating state. It does not show whether obstruction, remodeling, compression, or active vasoconstriction produced that relationship. When vessels distend or recruit as flow changes, the calculated value may also change.

The denominator must represent pulmonary flow. Without a significant shunt, cardiac output is generally suitable. With a shunt, pulmonary and systemic flows can differ. Using systemic flow when pulmonary flow is required can produce the wrong PVR even if both pressure measurements are accurate.

12.3 Resistance Does Not Describe the Whole Right Ventricular Load

PVR uses mean pressures and mean flow. The right ventricle ejects in pulses. It must accelerate blood, expand the pulmonary arteries, and interact with pressure waves traveling through the circulation. These processes contribute to afterload but are not fully described by PVR.

Pulmonary arterial compliance describes how much vascular volume increases for a given pressure increase. More compliant arteries can accept additional blood with a smaller pressure rise. Less compliant arteries require a larger pressure increase to accommodate a comparable volume.

A common clinical approximation divides stroke volume by pulmonary artery pulse pressure. Pulse pressure is systolic minus diastolic pulmonary artery pressure. For an illustrative stroke volume of 60 mL and pulse pressure of 30 mm Hg:

60 ÷ 30 = 2 mL/mm Hg

This is an estimate of the compliance of the arterial system. Blood continues leaving the arteries during ejection, and pressure waves also affect the waveform. The calculation is therefore an approximation rather than a direct measurement of one arterial wall's stiffness.

Two patients with similar PVR can have different arterial compliance and different pressure patterns during ejection. Their right ventricles may consequently face different pulsatile loads. Assessing how ventricular performance matches pulmonary load requires more than a resistance value.

Downstream pressure also influences this relationship. Tedford and colleagues analyzed catheterization datasets and found that higher wedge pressure was associated with lower pulmonary arterial compliance at a given resistance. This increased pulsatile loading helps explain why left-heart disease can stress the right ventricle beyond raising mean pulmonary pressure. 2

During treatment, stroke volume, heart rate, resistance, and compliance may change together. A narrower pulmonary artery pulse pressure could reflect improved compliance, but it could also reflect less blood ejected with each beat. A lower mean pressure could likewise reflect reduced flow. Pair the waveform with stroke volume and right ventricular assessment before calling either change beneficial.

12.4 Lung Volume, Alveolar Pressure, and Vascular Zones

Pulmonary vessels sit within a lung that changes volume and pressure with every breath. Alveolar vessels are influenced by expanding alveoli and the pressure within them. Extra-alveolar vessels are influenced by the surrounding tissue and the traction that lung expansion exerts on their walls.

At high lung volume, distended alveoli can narrow vessels within their walls. At low lung volume, reduced tissue traction can narrow extra-alveolar vessels. Collapse can also reduce the pathways effectively carrying blood. Pulmonary vascular resistance can therefore rise at either extreme of lung volume.

Flow also depends on the relationship between local arterial, venous, and alveolar pressures. These pressures must be compared at the same location and against a common reference. The classic vascular zones describe three useful arrangements.

In zone 3, arterial pressure exceeds venous pressure, and venous pressure exceeds alveolar pressure. Vessels remain open through the region. The arterial-to-venous pressure difference is the principal pressure difference driving flow.

In zone 2, arterial pressure exceeds alveolar pressure, but alveolar pressure exceeds venous pressure. The higher surrounding alveolar pressure constrains the downstream portion of the vascular pathway. Flow becomes more dependent on the arterial-to-alveolar pressure difference. Lowering venous pressure further need not produce the increase in flow expected from an ordinary rigid tube.

In zone 1, alveolar pressure exceeds arterial pressure. Vascular compression can severely restrict or stop flow through the affected pathway. The presence and extent of such regions depend on the actual pressure and ventilation conditions.

West, Dollery, and Naimark demonstrated these relationships in isolated perfused lungs by altering vascular and alveolar pressures. Their experiments established a mechanical framework for regional pulmonary flow. The zones describe local pressure relationships, not permanently fixed horizontal anatomical compartments. 3

Gravity, posture, blood volume, ventilation, and disease change these relationships. Recruitment in one region can coexist with overdistension in another. Increasing PEEP may improve flow through previously collapsed lung while increasing compression elsewhere. Observe the overall response through respiratory mechanics, gas exchange, pulmonary pressures, and forward flow.

12.5 Hypoxic Pulmonary Vasoconstriction

When an alveolar region becomes poorly oxygenated, nearby small pulmonary arteries constrict. This is hypoxic pulmonary vasoconstriction. Its purpose differs from the vasodilation commonly produced by local hypoxia in systemic tissues.

Constriction reduces blood flow to a poorly ventilated region and redirects some of that flow toward better-ventilated lung. More blood can then encounter alveoli capable of oxygenating it. This improves ventilation–perfusion matching, although it cannot fully correct a large shunt or extensive lung disease.

The consequence changes when hypoxia is widespread. Few well-ventilated regions remain available to receive redirected blood. Vasoconstriction then increases resistance across much of the pulmonary circulation. The right ventricle must generate more pressure to maintain flow. A useful regional response can therefore become a cause of increased overall right ventricular load.

Motley and colleagues documented pulmonary artery pressure responses during short periods of induced hypoxia in humans. Their early physiological work helped establish that changing oxygen availability alters pulmonary vascular behavior. It does not define one predictable pressure response for every hypoxemic ICU patient. 4

Carbon dioxide, acid–base status, lung volume, and vasoactive signaling modify the response. In critical illness, hypoxia may coexist with endothelial injury, vascular obstruction, and mechanical compression. Improving oxygenation removes one potential influence but may leave others unchanged.

Drug delivery also affects perfusion distribution. An inhaled vasodilator mainly reaches ventilated regions. It may increase flow preferentially where gas exchange is possible. A systemic vasodilator can also reach vessels supplying poorly ventilated lung and may weaken the redistribution produced by hypoxic vasoconstriction. Oxygenation can then worsen even if resistance falls.

The result depends on the drug, disease, ventilation distribution, and circulatory response. Measure oxygenation and forward flow as well as pulmonary pressure. A pressure reduction, better oxygenation, and higher cardiac output are separate observations; none guarantees the others.

12.6 Current Hemodynamic Definitions

Pulmonary hypertension is defined by a resting mPAP greater than 20 mm Hg measured at right heart catheterization. PAWP and PVR then distinguish how downstream pressure and the pressure drop across the pulmonary vessels contribute. The 2022 ESC/ERS guidelines and the 2024 World Symposium report use the patterns in Table 12.1. 5, 6

A precapillary pattern combines pulmonary hypertension with PAWP of 15 mm Hg or less and PVR greater than 2 Wood units. A postcapillary pattern has PAWP greater than 15 mm Hg. Postcapillary disease is called isolated when PVR is 2 Wood units or less, and combined when PVR is greater than 2 Wood units.

Table 12.1. Resting hemodynamic patterns of pulmonary hypertension. All rows require mPAP greater than 20 mm Hg.

If mPAP is elevated but both PAWP and PVR remain within the lower ranges shown, the pattern is unclassified. Increased pulmonary flow can produce this arrangement. It requires investigation of the flow state and possible shunts rather than automatic assignment to pulmonary arterial hypertension.

These cutoffs support diagnostic classification. They are not resuscitation targets or sharp biological boundaries. A PAWP just above 15 mm Hg does not describe a fundamentally different circulation from one just below it. Measurement uncertainty, fluid administration, diuresis, and surrounding pressure can shift an apparent category.

A precapillary pattern is also not synonymous with pulmonary arterial hypertension, or PAH. Several different diseases produce precapillary hemodynamics. PAH is one clinical category among them and requires an appropriate diagnostic evaluation.

In an unstable ventilated patient, the measured pattern may include reversible effects of shock, gas exchange, ventilation, and treatment. Identify the immediate physiology, but do not turn one acute measurement into a definitive chronic diagnosis. Classification must be connected to the patient's history and investigations.

12.7 Clinical Classification Adds the Cause

Hemodynamic classification describes the pressure–flow pattern. Clinical classification identifies the disease responsible. Similar catheter measurements can arise from different diseases and require different treatment.

Group 1 is pulmonary arterial hypertension. Group 2 is pulmonary hypertension associated with left-heart disease. Group 3 is associated with lung disease or hypoxia. Group 4 includes chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions. Group 5 contains conditions with unclear or multiple mechanisms. 5, 6

The group reflects the predominant clinical cause. Elevated PVR with a low PAWP can occur in PAH, severe lung disease, or chronic thromboembolic obstruction. Those two numbers cannot distinguish among these diagnoses. Lung function, imaging, the history, and other appropriate investigations supply the missing explanation.

Left-heart disease can also coexist with an additional pulmonary vascular component. Long-standing elevation of left atrial pressure may be accompanied by pulmonary vascular remodeling and higher PVR. This can produce combined postcapillary and precapillary hemodynamics without converting the clinical diagnosis into group 1 PAH.

Acute illness often adds several influences. A patient with chronic left-heart disease may develop pneumonia and hypoxic vasoconstriction. Mechanical ventilation may add vessel compression or alter venous return. Right ventricular dysfunction may then reduce flow. The measured PVR reflects the resulting state but cannot assign a separate percentage to each mechanism.

The time course helps identify what may be reversible. Acute pulmonary embolism is different from chronic thromboembolic pulmonary hypertension. A new hypoxic increase in load differs from established vascular remodeling. Earlier imaging, prior catheter measurements, and the current presentation help separate chronic disease from acute changes.

A useful classification connects the numbers to a defensible disease explanation. That explanation determines which treatment evidence applies and which further investigations could change management.

12.8 Measurement Quality Can Change the Diagnosis

PVR is calculated from three measurements, so an error in any input changes the result. Zero and level the pressure system appropriately. Confirm that each waveform represents the intended chamber or vessel. Obtain pressure and flow measurements under comparable respiratory and treatment conditions.

A valid wedge measurement requires appropriate catheter position and arterial occlusion. Incomplete occlusion can leave a contribution from pulmonary artery pressure. Overwedging or an unsuitable regional pressure relationship can also produce a misleading tracing. Examine the waveform rather than accepting the monitor's PAWP label as proof of a valid measurement.

PAWP estimates left atrial pressure under suitable conditions. Left ventricular end-diastolic pressure, or LVEDP, measures ventricular pressure at a particular point in the cardiac cycle. The two are related but are not interchangeable. Mitral valve disease, large atrial pressure waves, and measurement timing can separate them.

Hemnes and colleagues found clinically meaningful disagreement between PAWP and LVEDP in a large cohort undergoing concurrent right and left heart catheterization. Their findings show how measurement choice and interpretation can affect pulmonary hypertension classification. Disagreement requires investigation; it does not mean that one value should automatically replace the other. 7

Respiratory pressure adds another distinction. End-expiratory measurement can improve consistency, but PEEP, auto-PEEP, or active expiration may leave surrounding pressure elevated at that point. A pressure measured relative to atmosphere is not necessarily the pressure distending the chamber or vessel. Transmural pressure is the inside pressure minus surrounding pressure.

Large respiratory swings may require interpretation across several respiratory cycles rather than reliance on one end-expiratory point. Use an appropriate, consistent method and document it. Subtracting the airway PEEP directly from every vascular pressure is not a reliable correction because pressure transmission depends on lung and chest wall mechanics.

Output error changes the denominator. If flow is underestimated, calculated PVR is overestimated for the same pressure gradient. Thermodilution and Fick methods have different limitations. Shunts, important regurgitation, and use of an assumed oxygen consumption can complicate interpretation. Review discordant results in the context of the method and circulation.

Finally, synchronize the measurements. Combining pressures from before a major intervention with output measured afterward may create a calculation that describes neither state. Extra decimal places cannot compensate for uncertain inputs or mismatched timing.

12.9 Acute Pulmonary Loading in the ICU

Acute pulmonary loading can have vascular, mechanical, and downstream causes. Pulmonary embolism obstructs vascular pathways. ARDS can combine vascular injury, hypoxic vasoconstriction, microvascular obstruction, and abnormal inflation. Elevated left atrial pressure adds a downstream contribution to pulmonary artery pressure.

The right ventricle's reserve determines whether it can maintain flow against the new load. Adequate adaptation raises pressure generation enough to sustain ejection. If adaptation is insufficient, more blood remains after systole and the chamber dilates. Tricuspid regurgitation and ventricular interdependence can then reduce effective forward flow further.

Systemic pressure may fall as left ventricular filling decreases. This reduces the pressure supporting right ventricular coronary perfusion. Meanwhile, pressure generation and dilation increase myocardial oxygen requirements. The imbalance can impair contraction and reinforce the fall in output.

A falling pulmonary artery pressure during this sequence can be misleading. If output falls and venous pressure rises, the lower pulmonary pressure may reflect a ventricle losing its ability to eject. That differs from a pressure fall accompanied by higher flow and less congestion.

Use the time course to guide assessment without letting timing become proof of causation. Deterioration after a ventilator change prompts examination of overdistension and venous return. It also requires consideration of other acute causes. A pulmonary pressure rise with pulmonary edema requires left-heart assessment as well as investigation of the pulmonary vessels.

Describe the response to treatment through the same connected observations: pulmonary pressure, cardiac output, systemic pressure, oxygenation, and right ventricular size and function. Together they help distinguish reduced pulmonary load from declining pressure generation.

12.10 Treatment Evidence Depends on the Disease

A high PVR may make vasodilation seem an obvious solution, but the clinical result depends on the cause. Drug effects on systemic pressure, ventilation–perfusion matching, and left-heart filling also influence benefit or harm. Resistance alone cannot select a treatment.

If left atrial pressure is elevated, increasing pulmonary flow may deliver more blood to a left heart that cannot accept it without a further pressure rise. Pulmonary congestion may worsen. This is one reason evidence from PAH cannot simply be transferred to pulmonary hypertension associated with left-heart disease.

In SIOVAC, Bermejo and colleagues randomized patients with persistent pulmonary hypertension after successful correction of valvular heart disease to sildenafil or placebo. Sildenafil produced worse composite clinical outcomes. The trial demonstrates the risk of assuming that a drug used for PAH benefits a different disease population. It does not establish the mechanism of every adverse event. 8

Treatment effects also differ within pulmonary hypertension associated with lung disease. In INCREASE, Waxman and colleagues studied inhaled treprostinil in selected patients with pulmonary hypertension associated with interstitial lung disease. Six-minute walking distance improved over 16 weeks compared with placebo. This supports a specific treatment in a defined chronic disease population, not a treatment for acute ICU shock. 9

The PERFECT trial tested inhaled treprostinil in pulmonary hypertension associated with COPD. It was stopped early because the safety assessment found an unfavorable balance of benefit and harm, including more serious adverse events and a possible mortality signal. Early termination limited efficacy assessment. These findings do not support extending the INCREASE result to PH associated with COPD. 10

These trials do not supply one rule for every pulmonary vasodilator or every rescue situation. They show why the disease, route, treatment, and endpoint must match the evidence. A chronic exercise outcome and an immediate change in ICU hemodynamics answer different questions.

Identify the disease and reversible contributors before selecting support. Define the intended benefit and reassess whether it occurs. Higher forward flow, adequate systemic pressure, acceptable oxygenation, and less congestion provide a more useful assessment than a lower pulmonary pressure alone.

12.11 A Worked Bedside Interpretation

Consider an illustrative patient with pulmonary edema and circulatory failure. Right heart catheterization shows mPAP of 40 mm Hg, PAWP of 24 mm Hg, and cardiac output of 4 L/min. First calculate the pressure drop across the pulmonary circulation:

40 − 24 = 16 mm Hg

Then relate that pressure drop to flow:

16 ÷ 4 = 4 Wood units

The patient has elevated pulmonary artery pressure, elevated downstream pressure, and elevated calculated PVR. Now apply the definitions. The mPAP is above 20 mm Hg, PAWP is above 15 mm Hg, and PVR is above 2 Wood units. If the measurements are valid, this is a combined postcapillary and precapillary hemodynamic pattern.

That pattern does not establish PAH. The high PAWP makes the left atrial pressure contribution central to the assessment. Review left ventricular filling and valve function, the right ventricle, ventilation, gas exchange, and possible vascular obstruction. Chronic disease and reversible acute influences may coexist.

Suppose a later measurement shows mPAP of 32 mm Hg, PAWP still 24 mm Hg, and output of 2 L/min. Repeat the same calculation:

32 − 24 = 8 mm Hg

8 ÷ 2 = 4 Wood units

PVR is unchanged. The pressure gradient has halved, but so has the flow used as the denominator. Pulmonary artery pressure is lower while cardiac output has fallen from 4 to 2 L/min. That pressure fall cannot establish successful unloading.

The reduced flow needs an explanation. Worsening right ventricular ejection, altered filling, treatment effects, and measurement error are possibilities. Check the waveforms and confirm that the pressures and output describe the same state. The calculations clarify what changed; they do not identify its cause automatically.

A favorable response would include better systemic flow and perfusion at acceptable pulmonary and systemic pressures. Reduced congestion and satisfactory gas exchange would strengthen that interpretation. The purpose of PVR is to connect pressure to flow so that the clinical response is understood more accurately.

References

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2. Tedford RJ, Hassoun PM, Mathai SC, et al. Pulmonary capillary wedge pressure augments right ventricular pulsatile loading. Circulation. 2012;125(2):289–297. doi:10.1161/CIRCULATIONAHA.111.051540.

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7. Hemnes AR, Opotowsky AR, Assad TR, et al. Features associated with discordance between pulmonary arterial wedge pressure and left ventricular end diastolic pressure in clinical practice: implications for pulmonary hypertension classification. Chest. 2018;154(5):1099–1107. doi:10.1016/j.chest.2018.08.1033.

8. Bermejo J, Yotti R, García-Orta R, et al. Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial. Eur Heart J. 2018;39(15):1255–1264. doi:10.1093/eurheartj/ehx700.

9. Waxman A, Restrepo-Jaramillo R, Thenappan T, et al. Inhaled treprostinil in pulmonary hypertension due to interstitial lung disease. N Engl J Med. 2021;384(4):325–334. doi:10.1056/NEJMoa2008470.

10. Nathan SD, Argula R, Trivieri MG, et al. Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results. Eur Respir J. 2024;63(6):2400172. doi:10.1183/13993003.00172-2024.