Abstract 21287: Myocardial Oxygen Delivery is Progressively Impaired During Development of Pulmonary Hypertension

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Introduction: Pulmonary hypertension (PH) increases afterload of the right ventricle (RV), initially resulting in RV hypertrophy. Eventually the RV is unable to cope with the high afterload, resulting in RV failure and death. The transition of RV hypertrophy to failure is incompletely understood.

Hypothesis: The increased workload together with the RV hypertrophy increases oxygen demand of the myocardium, which is insufficiently compensated by an increase in myocardial oxygen supply through the right coronary vasculature. This mismatch between oxygen supply and demand is exacerbated during physical activity when oxygen demand increases.

Methods: PH was induced by banding of the confluent of the inferior pulmonary vein in juvenile swine (N=5), while 5 healthy swine served as controls. Swine were chronically instrumented to measure pressure in the RV, pulmonary artery, left atrium and aorta, and right coronary blood flow (CBF) rest and during graded treadmill exercise.

Results: Pulmonary venous banding (PVB) resulted in PH as evidenced by an increase in pulmonary artery pressure (PVB: 29±1 mmHg (week 5) and 39±3 mmHg (week 12); CON 20±1 mmHg and 21±1 mmHg, both P<0.05) that was accompanied by RV hypertrophy (RV/bodyweight 1.18±0.05 (CON), 1.70±0.15 (PVB), P=0.06). The relation between myocardial oxygen delivery (CBF*arterial oxygen content) and Myocardial work (heartrate*pulmonary artery pressure) was not different between CON and PVB at week 5 , but rotated downwards at week 12 weeks (Figure), indicative of a mismatch between oxygen supply and demand. Histology revealed an increase in cardiomyocyte size (717±35 vs 598±30 μm2, P<0.05), whereas capillary density and interstitial fibrosis were not changed.

Conclusions: Progression of PH leads to a mismatch between myocardial oxygen supply and demand, particularly during exercise. This mismatch between supply and demand may cause myocardial ischemia and contribute to the transition of RV hypertrophy to failure.

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