Trevor Gerlach, DVM, Diplomate ACVIM (Cardiology)
The pulmonary vasculature is a low-pressure, low-resistance system that is responsible for gas exchange, acid-base regulation, and synthesis, activation, and degradation of enzymes/hormones. Blood flow through this system is determine by the pressure gradient and the resistance. Flow and resistance are inversely related, and the most influential variable in determining resistance is vessel radius (the smaller the radius, the larger the resistance). Local production of substances such as nitric oxide and prostacyclin (PGI2) leads to vasodilation. Hypoxia and the production and release of thromboxane, endothelin, and/or serotonin cause vasoconstriction. Under normal circumstances, the pulmonary arterial pressure is maintained at <30mmHg/20mmHg (systolic/diastolic).
While several disease processes can lead to pulmonary hypertension (PH), three main mechanisms are recognized: 1) over-circulation, 2) increased pulmonary vascular resistance, and 3) increased pulmonary venous pressure. Over-circulation is generally caused by left to right shunting from congenital heart defects (ex: patent ductus arteriosus, septal defects). The increased flow leads to reflex and metabolite-induced vasoconstriction that eventually causes hypertrophy and fibrosis of the arterial walls. Diseases that cause increased vascular resistance include chronic lower airway disease (ex: collapsing airways, bronchitis, allergies) and heartworm disease. Endothelial and/or alveolar damage from these inflammatory states lead to altered production and release of vasoactive substances. Increased pulmonary venous pressure is the most common mechanism for the development of PH in our patients. Elevated left atrial pressure from degenerative valve disease or dilated cardiomyopathy is transmitted to the pulmonary vasculature leading to increased pulmonary venous and arterial pressure. Further, reactive hypoxic vasoconstriction from pulmonary edema and neurohormonal activation (sympathetic tone and renin-angiotensin-aldosterone) causes vasoconstriction of pulmonary vessels. Pulmonary hypertension is classified as mild if the systolic pressure is <50mmHg, moderate if <80mmHg, and severe if 80mmHg or above.
Clinical signs associated with PH include coughing, hyperpnea, exercise intolerance, and collapse/syncope. Physical exam findings often include a murmur, crackles, weak femoral pulses, increased jugular pulses, cyanosis, and effusion (pleural or abdominal). The gold standard for diagnosis of PH is cardiac catheterization, which is rarely performed in animals given the requirement of general anesthesia. Non-invasive diagnosis requires echocardiography, while thoracic radiographs, electrocardiography, and lab work (ex: blood gas analysis, CBC/biochemistry, thromboelastography, urinalysis, cardiac biomarkers) can also aid in the diagnosis when coupled with clinical signs.
Treatment is aimed at addressing the underlying cause (i.e. heartworm disease, allergies, hypercoagulable states) and reducing pulmonary arterial pressure. Phosphodiesterase inhibitors (ex: sildenafil) and nitric oxide precursors (ex: L-arginine) are the most widely used medications. Platelet inhibitors (ex: clopidogrel, aspirin) and tyrosine kinase inhibitors serve as adjunct therapies in some cases. Prostacyclin analogues and endothelin antagonists are widely used in human medicine but are cost prohibitive in veterinary medicine at this time. The prognosis depends on the underlying cause, but sildenafil therapy has been shown to significantly improve survival and quality of life in several studies.