The silent killer: pulmonary hypertension (Proceedings)


The silent killer: pulmonary hypertension (Proceedings)

Aug 01, 2011

Pulmonary hypertension (PH) is defined by a systolic pulmonary artery pressure greater than 25 mmHg. The incidence of PH is difficult to define due to lack of clinical awareness, non-specific clinical signs, and difficulty in confirming the diagnosis. Unfortunately, many patients with PH are diagnosed late in the course of disease when irreversible vascular pathology has developed. PH results from many diseases and pathophysiologic mechanisms, and most commonly occurs secondary to chronic cardiopulmonary disease.

The vascular endothelium mediates vascular tone and remodeling through release of several neurohormonal factors, and endothelial injury plays a key role in development of PH. Normally, there is a balance between locally acting vasodilators including prostacyclin (PGI2) and nitric oxide (NO) versus potent vasoconstricting substances including thromboxane, endothelin-I (ET-1), and angiotensin II (AT-II). Endothelial dysfunction in PH contributes to smooth muscle cell proliferation (increased ET-I, AT-II, reduced NO), increased production of vasoconstrictor mediators including ET-1 and AT-II, and decreased synthesis of vasodilating substances including PGI2 and NO.

Classification of PH through hemodynamic and pathophysiologic mechanisms helps to guide interventional treatment. Mean pulmonary artery pressure (MPAP) is related to pulmonary blood flow (PBF) and pulmonary vascular resistance (PVR) by the equation MPAP= (PVR x PBF) + pulmonary capillary wedge pressure (PCWP). Abnormalities of any component of this equation can cause PH.

Pre-capillary PH occurs due to abnormalities of the pulmonary arterial vascular bed and is characterized by increased systolic, mean, and diastolic PAP, increased PVR, and normal PCWP. PVR is closely related to total cross sectional area of the small muscular arteries and arterioles. Given the high-capacitance of the pulmonary vasculature, ≥ 50% of the pulmonary vasculature must be destroyed before PH develops. Diseases that cause pre-capillary PH include: primary pulmonary hypertension (PPH), Eisenmenger syndrome, chronic pulmonary disorders, pulmonary thromboembolism (PTE), and peripheral pulmonary artery branch stenosis. PPH is ill-defined in veterinary medicine. PTE is a secondary condition. Immune mediated hemolytic anemia (IMHA), neoplasia, cardiac disease, protein-losing nephropathy or enteropathy, hyperadrenocorticism, disseminated intravascular coagulation, sepsis, trauma, and recent surgery are associated with PTE in dogs and cats. Eisenmenger syndrome is an irreversible, obliterative pulmonary vascular disease that results from severe left to right shunting congenital heart disease that reverse to shunt right to left. Chronic respiratory disorders may result in PH in some individuals through hypoxic pulmonary vasoconstriction, extramural compression of the pulmonary arterioles, and destruction of pulmonary microvasculature. In absence of pulmonary arterial pathologic changes (plexiform lesions, necrotizing arteritis, hyalinizing fibrosis), PH due to hypoxic vasoconstriction may be dynamic and respond to therapeutic intervention.

In post-capillary PH, PAP passively increases due to elevated PCWP. PA diastolic pressure is within 5 mmHg of the PCWP, and PVR is normal. Left sided congestive heart failure (CHF) is the most common cause of increased PCWP and may result from severe mitral valve disease, dilated cardiomyopathy, or diastolic heart disease. A mixed hemodynamic response may be seen with chronic elevations in PCWP and consists of a disproportionate elevation in PA pressures in comparison to elevated PCWP. The mechanism for increased PVR in response to elevated PCWP is not entirely clear but likely involves endothelin-1 release, endothelial dysfunction and abnormal pulmonary vasodilatory reserve. Based on clinical experience, a low percentage of dogs with severe mitral regurgitation likely have a mixed hemodynamic response of PH.

Pulmonary blood flow (PBF) can be increased selectively by left to right shunting congenital heart diseases (ASD, VSD, PDA) and some patients are at risk for development of Eisenmengers physiology. PBF is also increased by high output cardiac disease (arteriovenous fistula, chronic anemia, and hyperthyroidism), however most patients do not develop recognizable PH. Pneumonectomy leads to selective increases in pulmonary blood flow, but PH is not recognized as a complication in dogs.

Cor pulmonale is an adaptive mechanism by which the right ventricle responds to PH resulting from chronic pulmonary disease. The most common cause of cor pulmonale in veterinary medicine is heartworm disease in dogs. PH leads to acquired pressure overload of the right ventricle characterized by concentric hypertrophy and chamber dilation. RV myocardial failure may occur due to inadequate reduction of wall stress and may be worsened by myocardial ischemia from reduced right coronary artery perfusion pressure. The extent of concentric hypertrophy and dilation of the RV ventricle depends on the age of the animal, the severity and duration of pressure overload, and the time course of progression.