Development of Crotalaria pulmonary hypertension: hemodynamic and structural study

Abstract

In awake rats with indwelling catheters, the development of pulmonary hypertension after feeding Crotalaria spectabilis seeds is followed. Hypoxemia is excluded as a factor. Other hemodynamic changes are found before hypertension. After 7 days, pulmonary artery pressure (Ppa) is normal, 17.17 +/- 0.30 (SE) mmHg and from 14 days significantly increased (P < 0.01). Oxygen consumption (Vo2) is significantly increased by day 7 (control 22.72 +/- 2.13 ml . min-1 . kg-1; Crotalaria 42.47 +/- 2.95; P < 0.001). and cardiac index (CI) is significantly above normal after 7, 14, and 21 days (control 350 +/- 31 ml . min-1 . kg-1; 7 days Crotalaria 476 +/- 28; P < 0.02); pulmonary vascular resistance (PVR) increases to six times normal at day 33 (control 0.033 +/- 0.003 U/kg; 33 days Crotalaria 0.194 +/- 0.020; P < 0.001). The pulmonary arteries of these same rats were studied by quantitative morphometric techniques. The first change, muscle in smaller and more peripheral arteries than normal, is detected when Vo2 and CI are increased. Increased medial thickness of arteries < 200 micrometer diameter follows with Ppa rises. Even later, the larger arteries increase their media as the number of peripheral arteries falls and right ventricular hypertrophy becomes apparent, and hypertension and increased PVR are well established.

Changes in Pulmonary Hemodynamics during Normoxia and Hypoxia in Awake Rats Treated with Intratracheal Bleomycin.

“…These values are quite close to the value of 4.7 cmH2O which was reported by Meyrick et al (1980). Second, does 10% 02 breathing alter the left atrial pressure?…”

“…The system was run, refilling the spirometer with 100% 02 until a stable linear utilization of 02 and thermal equilibration were achieved (about 7 min). Oxygen consumption for five minutes, while blood was being sampled, was then determined, and VO2 was calculated, correcting the volume to STPD (Meyrick et al 1980).…”

“…Pulmonary vascular resistance (PVR) was calculated by dividing (Ppa-Ppv) by the cardiac output. For pulmonary venous pressure (Ppv), 4.7 cmH2O was used (Meyrick et al 1980). Systemic vascular resistance (SVR) was estimated by dividing Psa by cardiac output.…”

Endogenous production of ghrelin and beneficial effects of its exogenous administration in monocrotaline-induced pulmonary hypertension

“…MCT treatment results in endothelial dysfunction, medial thickness increasing, peripheral artery loss, pulmonary vasculature resistance elevation, and RV hypertrophy that mirror human PH (18,36).…”

Monocrotaline-induced pulmonary hypertension correlates with upregulation of connective tissue growth factor expression in the lung

“…It is thought to induce lung reactions such as interstitial edema, inflammation, hemorrhage and fibrosis (Kay and Heath, 1969). Since subcutaneous injection of MCT can cause PH, medial hypertrophy of the pulmonary arteries, and severe presMonocrotaline-induced pulmonary hypertension correlates with upregulation of connective tissue growth factor expression in the lung sure overload-induced right ventricular hypertrophy, MCT has been widely used to establish an animal model of PH (Meyrick et al, 1980;Ghodsi and Will, 1981).…”