Review of the presented cases
The two cases presented in this article are part of a group of nearly 54 dogs with various degrees of pulmonary hypertension
(15 were severe) studied over two and a half years at the Virginia-Maryland Regional College of Veterinary Medicine. The prognosis
and cardiac changes in the 54 dogs parallel the underlying severity of the pulmonary hypertension problem. The presented cases
represent the severe form of pulmonary hypertension and reveal the difficulty in identifying the problem before it becomes
irreversible. In addition, there is the challenge of understanding the pathophysiology in each case. Control of pulmonary
vascular resistance and pressure is a finely tuned and complex system that can become imbalanced in many ways. To appropriately
treat animals with the more severe forms of pulmonary hypertension, comprehensive physiologic monitoring could be of great
benefit; however, the invasive procedures needed to monitor intracardiac pressures, cardiac output, and vascular resistance
may be difficult to accomplish in critically ill patients.
At necropsy, the two dogs in this study had no evidence of heartworm disease or major pulmonary embolism. There was evidence
of in situ thrombosis in the Labrador retriever.
Presumably, the pulmonary vascular hypertension in these dogs was related secondarily to pulmonary parenchymal disease. Both
dogs had pathologic evidence of inflammatory pulmonary disease; however, the chronicity is open to question, particularly
in the 14-year-old mixed-breed dog. This dog presented with an acute history of dyspnea and coughing and was referred quickly
to Virginia Tech. The Labrador retriever had a much more chronic history and was referred many months after initial presentation
to the referring veterinarian. The severity of the laryngeal paralysis and accompanying hypoxia could have played an important
role in this animal's clinical course and development of pulmonary hypertension. Clearly, both dogs had documented hypoxemia,
and it is well-known that this can promote pulmonary vasoconstriction; however, beyond the direct effect of hypoxia-induced
vasoconstriction through potassium and calcium availability to the vascular smooth muscle cells, it is not known what other
vascular control factors might have been disturbed. Disequilibrium of the vasoconstrictors and vasodilators that were discussed
above could have played a principal role, but assessing this is not easily done in the clinical setting.
It is tempting to speculate on what effect abnormal pulmonary vascular function might have on other vessels. The systemic
vessels, including the coronary arteries, are controlled in a manner similar to the pulmonary vessels. Perhaps the disequilibrium
in the pulmonary vessels might liberate substances or trigger mechanisms that could influence systemic vessels. For example,
endothelin is a potent vasoconstrictor with a long half-life and is important in pulmonary vascular control. Increased production
of this circulating substance could cause constriction of systemic vessels, including the coronary arteries. Coronary vasoconstriction
concurrent with a stressed right ventricle in a dog with severe pulmonary hypertension could be devastating. The frequent
and long-standing premature ventricular contractions seen in the Labrador retriever could have been the result of reduced
coronary blood flow associated with a stressed right ventricle trying to deal with an enormously increased afterload.
Finally, these two cases illustrate the challenge of trying to successfully treat the severe form of pulmonary hypertension.
By examining the original group of 15 severe cases (including the two in this report), it is apparent that such dogs have
a grave prognosis, irrespective of the therapeutic plan, and usually survive a few days to a few weeks.
Dealing with severe pulmonary hypertension in dogs is rewarding from the recognition perspective. The technology behind echocardiography,
including transesophageal studies, is constantly improving, and it will become easier to recognize the vascular and cardiac
manifestations of pulmonary hypertension. The frustrating aspect of this problem is to understand the pathogenesis and pathophysiology.
While we assume that pulmonary parenchymal disease precedes pulmonary vascular disease, this is not always obvious. Some dogs
have no physical or radiographic signs of pulmonary parenchymal disease but have severe pulmonary hypertension. The lack of
necropsy studies in many cases makes final judgments about parenchymal disease difficult at best.
Developing a rational therapeutic plan is essential in these cases, and providing oxygen is clearly a reasonable step. However,
the complex cascade of events involved in controlling pulmonary vascular tone could easily be disturbed in a number of ways.
In the clinical setting, there is no practical way to evaluate the pulmonary vascular tone or assay the substances that play
a principal role in controlling pulmonary vascular tone, so each case becomes an experiment in finding a plan that will substantially
reverse the pulmonary hypertension.
A better understanding of nonheartworm pulmonary hypertension in dogs will result from appropriate research. Further characterization
of parenchymal diseases of the lung as well as a comprehensive evaluation of the pulmonary vascular abnormalities will be
critical. Assays of control substances and histochemical studies of the pulmonary vessels may be particularly rewarding. Progress
is being made through multispecies studies, and this is likely to continue. In time, the treatment and management of canine
pulmonary hypertension may be less empirical and more rational.
R. Lee Pyle, VMD, MS, DACVIM (cardiology)
Jonathan Abbott, DVM, DACVIM (cardiology)
Heidi MacLean, DVM
Department of Small Animal Clinical Sciences
Virginia-Maryland Regional College
of Veterinary Medicine
Blacksburg, VA 24061
1. Johnson, L. et al.: Clinical characteristics of 53 dogs with Doppler-derived evidence of pulmonary hypertension: 1992-1996. J. Vet. Intern. Med. 13 (5):440-447; 1999.
2. Salvi, S.S: Alpha1-adrenergic hypothesis for pulmonary hypertension. Chest
115 (6):1708-1719; 1999.
3. Rich, S.: Pulmonary hypertension. Heart Disease: A Textbook of
Cardiovascular Medicine (E. Braunwald et al., eds.). W.B. Saunders, Philadelphia, Pa., 2001; pp 1908-1935.
4. Kienle, R.D.; Kittleson, M.D.: Pulmonary arterial and systemic arterial hypertension. Small Animal Cardiovascular Medicine (M.D. Kittleson; R.D. Kienle, eds.). Mosby, St. Louis, Mo., 1998; pp 433-448.
5. McLaughlin, V.V.; Rich, S.: Cor pulmonale. Heart Disease: A Textbook of
Cardiovascular Medicine (E. Braunwald et al., eds.). W.B. Saunders, Philadelphia, Pa., 2001; pp 1936-1954.
6. Klinger, J.R.; Hill, N.S.: Right ventricular dysfunction in chronic obstructive pulmonary disease. Chest
99 (3):715-723; 1991.
7. Atkins, C.E.: The role of noncardiac disease in the development and precipitation of heart failure. Vet. Clin. North Am. (Small Anim. Pract.) 21 (5):1035-1080; 1991.
8. Zhao, L. et al.: Sildenafil inhibits hypoxia-induced pulmonary hypertension. Circulation
104 (4):424-428; 2001.
9. Michelakis, E. et al.: Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: Comparison
with inhaled nitric oxide. Circulation
105 (20):2398-2403; 2002.
10. Atkins, C.E.: Cardiac manifestations of systemic and metabolic disease. Textbook of Canine and Feline Cardiology (P. Fox et al., eds.). W.B. Saunders, Philadelphia, Pa., 1999; pp 757-780.