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Keywords:

  • coronary blood flow;
  • left anterior descending coronary artery;
  • monocrotaline;
  • pulmonary hypertension;
  • pulmonary artery dilatation

Summary

Background:  Many patients with pulmonary hypertension (PH) have symptoms of angina without evidence of occlusive coronary artery disease. For the first time, this study addresses the influence of progressively increasing pulmonary artery pressure (PAP) on left anterior descending artery flow in a rat model of PH. The role of pulmonary artery dilatation, septal wall motion abnormality, cardiac output or diastolic blood pressure in determining coronary blood flow (CBF) during PH was determined.

Methods:  Pulmonary hypertension was induced in 6-week-old female nude rats (n = 44) using monocrotaline. Animals underwent right heart catheterization and echocardiography, and blood pressure measurement was taken at baseline, 21 and 35 days.

Results:  A total of 103 echocardiographic studies were carried out at three fixed time points in rats with variable PAP. CBF decreased from 46·6 ± 14·3 to 24·7 ± 12·3 cm s−1 (P<0·001) over time. Pulmonary artery diameter increased from 2·30 ± 0·19 to 2·83 ± 0·30 mm (P<0·001), and left ventricular (LV) cardiac output decreased from 143 ± 23 to 78 ± 30 ml min−1 (P<0·001). Using observed solution estimates of 0·00170 (P = 0·0005) and −1·75 (P = 0·006) for these variables, we calculated that CBF increased by 5·90 cm s−1 (15·6%, CI: 14·5–17·1%) or decreased by −4·86 cm s−1 (−12·9%, CI: −14·1–11·9%) for every standard deviation increase in LV cardiac output or pulmonary artery diameter, respectively. CBF decreased significantly with increasing PAP. Pulmonary artery diameter and LV cardiac output appear to be independent determinants of coronary flow in PH.

Conclusions:  Coronary flow reduction in murine PH has potential to be clinically meaningful and should therefore further studied in a clinical trial.