Pulmonary vascular disease (Proceedings)

Pulmonary vascular disease or pulmonary vascular obstructive disease (PVOD). is a catch-all term for conditions that affect the pulmonary circulation. These conditions are of particular importance to as they may result in severe respiratory dysfunction. As a review, the pulmonary and systemic circulation are in series, with the cardiac output of the left and right heart (in the absence of cardiac shunt) being equal. However the pressure in the pulmonary vasculature is low in relation to the systemic circulation, with the mean pulmonary arterial pressure averaging less than 15 mmHg and a systolic pressure of < 25 mmHg at rest and less the 30 mmHg during exercise. Elevated pulmonary pressures result in syncope, weakness and fatigue, and may ultimately result in right heart failure. Knowledge of normal intra-cardiac pressure is essential to recognize the effects of disease

NORMAL CARDIAC AND VASCULAR PRESSURES

Strain on the right heart is assessed by measurement of the pulmonary vascular resistance (PVR), which is defined as the [mean pulmonary arterial pressure-mean left atrial pressure (or pulmonary capillary wedge pressure)]/cardiac output. Increasing PVR is associated with increased work for the right ventricle. If R heart pressures exceed left heart pressure in the presence of an intra-cardiac shunt, there will be right to left shunting.

In simplicity, two things can go wrong with the pulmonary vasculature that will affect the pressures. The first is a clot or clots may lodge in the pulmonary vasculature, while the second is that there is vasoconstriction or hypertrophy of the pulmonary arteries.

Pulmonary thromboembolism (PTE) is a more clinical recognized cause of pulmonary dysfunction in critically ill dogs and to a much lesser extent, the critically ill cats. As an overview, in order for a thrombus to form, there should be disruption in one or more aspect of the Virchow's triad which includes vascular damage, blood stasis and hypercoagulability. A thrombus is defined as a blood clot that forms in situ, while an embolus is a clot that lodges somewhere after first forming in another site. It is often unclear as to the initial source of the clot; thus, the term thromboembolism is used. In human medicine it is widely appreciated that thrombi form in the deep veins, include the iliacs and occasionally the leg veins. It is by far less clear where they come from in dogs and cats. It seems possible that they are forming in veins, however; despite the advances in diagnostic imaging, it is rare that one is visualized.

A number of risk factors have been associated with PTE in dogs, but as a general rule, critical illness and trauma are common sources.

Diagnosis of PTE is typically based upon an acute onset of respiratory distress in a patient at risk. Other differential diagnosis include aspiration pneumonia, acute respiratory distress syndrome (ARDS), and volume overload. Thoracic radiographs may document oligemia. Angiography is considered the goal standard, but is uncommonly performed. CT and echocardiography are particularly useful for identifying these conditions, with echo able to document right ventricular failure from PTE (eg. Massive PTE) and CT being useful to visualize the thrombi in pulmonary arteries.

Evolving questions in veterinary medicine include questioning the need for and the type of prophylaxis. There have been no well-designed studies to try to answer these questions. However, it is my opinion that in all critically ill dogs, prevention should be at least considered. Methods to prevent thrombi include heparin (Unfractionated versus low-molecular weight) and aspirin or clopidogrel (Plavix).

Pulmonary hypertension is a global term for anything that results in increases in the pulmonary arterial pressures. PTE may result in pulmonary hypertension, but for this discussion we will consider the disease separately. Specific diseases that may result in include primary pulmonary hypertension, which is pulmonary hypertension without an underlying cause identified. It is thought to be most common in small breed elderly female dogs. Clinical signs include shortness of breath, exercise intolerance, syncope and ascites. Cor Pulmonale is defined as the developed of right sided heart failure due to pulmonary hypertension due to lung disease. Common lung diseases that are associated with cor pulmonale include chronic bronchitis/'COPD" and pulmonary fibrosis. Eisenmeger syndrome (or physiology) is a specific form of pulmonary vascular disease associated with a intracardiac shunt, often a VSD or large ASD. In this case, the initial shunting is left to right, but over time, the volume overload to the pulmonary vasculature hypertrophies, and as the pressure increases above that in the LV, right to left shunting ensures. This is a relatively common complication of large left to right shunting defects. Dogs and cats will tend to present at 1-2 year or older with signs more often attributable to neurological sequelae of either hyperviscosity due to polycythemia or stroke.

Two relatively rare conditions that may exist in animals are portopulmonary hypertension and hepatopulmonary syndrome; these are considered the major pulmonary vascular complication of hepatic disease. Other sources of respiratory distress, including large volume ascites or pleural effusion, pneumonia, congestive heart failure or chronic obstructive pulmonary disease (COPD) are also common in people with hepatic disease.

Portopulmonary hypertension is characterized by portal hypertension in association with pulmonary hypertension (mean pulmonary arterial pressure > 25 mmHg at rest or > 30 mmHg during exercise.. An estimated 2-10% of people with cirrhosis will have PPHTN. The mechanism for the development of pulmonary hypertension seems to be independent of portal hypertension although portal hypertension not liver disease per se is required for the development of PPHTN. Hypotheses include high cardiac output resulting in shear stress on the pulmonary vasculature, which may result in the proliferation of endothelial and smooth muscle cells and subsequent pulmonary arterial hypertension. High cardiac output is associated with portal hypertension and liver disease due in part to splanchnic volume overload and bowel-wall congestion which subsequently causes the release of endotoxin and cytokines.

Most individuals with PPHTN have only mild to moderate changes, but in some individuals disease may progress to severe pulmonary hypertension. Genetic components are thought to perhaps explain why despite similar hemodynamic changes, only a small percentage of patients develop PPHTN. Interestingly PPHTN does not improve following liver transplantation and in fact severe PPHTH is a contraindication to transplantation. Other treatments are directed toward standard management of hepatic dysfunction and pulmonary hypertension, including intravenous infusion of epoprostenol or orally active pharmaceuticals such as bosentan or sildenafil.

Hepatopulmonary syndrome is the other clinical pulmonary vascular anomaly associated with liver disease. In human medicine, HPS is defined by the triad of 1) hepatic dysfunction 2) arterial hypoxemia and 3) evidence of intrapulmonary shunt. Intrapulmonary shunt, as seen in the dog of this report, is most commonly identified by saline bubble contrast documenting spontaneous contrast in the left side of the heart 2-4 seconds after appearance in the right heart. This delay in contrast is reflective of the intrapulmonary shunting of the blood, as opposed to the immediate appearance of bubbles supported intra-cardiac shunting. Arterial hypoxemia typically identified by arterial blood gas analysis include demonstration of an increased A-a gradient although in pediatric patients, pulse oximetry may be employed as a secondary option. Hypoxemia is often more pronounced in a standing position and improves when a patient is recumbent. The incidence of PPHTN and HPS in veterinary medicine remain to be determined.

Evaluating pulmonary vascular dysfunction

A variety of tests can provide usually information regarding the pulmonary vasculature. However, since the most important question to answer is "is the right heart functionally well", the most practical test to use in the echocardiogram. In animals with significant pulmonary vascular disease of any sort, subjective and objective echocardiograph data is useful. Subjective information includes recognition that as the normal LV pressure is much higher than the normal RV pressure, is there is septal flattening, this will suggest that there is increased RV pressures, and limitation of volume delivery to the left heart. The right heart may look hypertrophied. It is important to exclude pulmonary stenosis as a cause of right heart changes prior to incriminating the pulmonary vasculature, but this is typically easily done. If available, and if there is a tricuspid regurgitant jet, Doppler may be use to estimate systolic pulmonary artery pressures using the Bernoulli equation, with the estimated pressures = 4 x velocity2

Other testing that might be warranted is the cardiac catheterization, this is considered the gold standard for evaluation of pulmonary pressures, but its use requires advanced training and specialized equipment. Chest radiographs are advisable in all cases of suspected cardiac or pulmonary dysfunction; however the findings may be non-specific. Other advanced imaging, include CT thoracic scanning may be advised for lung disease, and may be coupled with angiography. In animals where disease is less well defined, post-mortem biopsy may also be helpful in establishing etiology and helping future patients.

Treatment of pulmonary vascular disease

As with all diseases, treatment of the underlying condition is most likely to result in clear benefit. However, provided that cure is not a possibility, options include anticoagulants, and cardiac/pulmonary medications.

Anticoagulation in the short term is often most easily accomplished with intravenous heparin as a CRI; however, LMWH (eg. fragmin or lovenox) may be equally efficacious. Long-term term, common anticoagulant include anti-platelet drugs such as aspirin (0.2-5 mg/kg per day-) or clopidogrel (less clear dosing..) are popular. Unfractionated heparin is not practical for long term use at home, although the LMWH are good (but pricy). Coumadin is a popular anticoagulant in people, but relies on frequent monitoring and may be quite challenging in dogs

Key Point- strongly consider anticoagulant in all dogs with pulmonary vascular disease, not just those with historical PTE. This is important because blood flow (stasis component of the Virchow's triad) is affected by pulmonary hypertension and even small PTE may be synergistic with pulmonary hypertension. Cardiopulmonary medications that might be useful include supplemental oxygen (which is a potent vasodilator), sildenafil and pimobendan.

References upon request.