The majority clinical cases of pulmonary hypertension (PH) result from left heart failure (LHF). Some patients with venous PH induced by the left heart pressure overload develop increase in resistance in the arterial part of the lung circulation (reactive PH). We focused to design rat model of LHF which develops reactive PH.
Left heart pressure overload was induced in adult male Wistar rats by inserting a polyethylene tubing into the ascending aorta through the right carotid artery. Three weeks later experimental animals were studied (group E, N=6) and compared to the controls (N=6). The left ventricle end-diastolic pressure was elevated in the group E (1.340.07 vs. 0.410.13 mmHg in the controls; p<0.0001). Mean pulmonary arterial blood pressure (PAP) was increased in the group E (22.90.7 vs. 16.91.0 mmHg in the controls; p<0.05). Weight of the right ventricle relative to body weight was bigger in the group E (220.127.116.11-4 vs. 18.104.22.168-4 in the controls; p<0.05).
Participation in the arterial segment of the pulmonary circulation to elevated PAP was measured by double occlusion method, in isolated PSS-perfused lungs. Pressure drop across the arterial portion of the vasculature was 9.01.2 mmHg vs. 5.00.5 mmHg in the controls; p<0.01.
Contribution of vasoconstriction to elevated vascular resistance was determined by measurement of the pressure-flow (P/Q) relationship, in PSS-perfused lungs. The slope of the P/Q relationship was bigger in the group E (0.1120.003 mmHg.mL-1.min-1) than in the controls (0.0460.002 mmHg.mL-1.min-1; p<0.0001), but dropped to a value not different from the controls (0.0440.001 mmHg.mL-1.min-1) after adding sodium nitroprusside (20 mM). In lung histology, 74% of small pulmonary vessels (group E) had muscularized media (24% in controls; p<0.01).
We present a clinically relevant model of reactive PH induced by LHF which consists of pulmonary vasoconstriction and vascular remodeling.
Grants: GAUK 210216, GACR 13-01710S and 17-11223S