A comparison of echocardiography to invasive measurement in the evaluation of pulmonary arterial hypertension in a rat model

Abstract

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by progressive elevation in pulmonary artery pressure (PAP) and total pulmonary vascular resistance (TPVR). Recent advances in imaging techniques have allowed the development of new echocardiographic parameters to evaluate disease progression. However, there are no reports comparing the diagnostic performance of these non-invasive parameters to each other and to invasive measurements. Therefore, we investigated the diagnostic yield of echocardiographically derived TPVR and Doppler parameters of PAP in screening and measuring the severity of PAH in a rat model. Serial echocardiographic and invasive measurements were performed at baseline, 21 and 35 days after monocrotaline-induction of PAH. The most challenging echocardiographic derived TPVR measurement had good correlation with the invasive measurement (r = 0.92, P < 0.001) but also more simple and novel parameters of TPVR were found to be useful although the non-invasive TPVR measurement was feasible in only 29% of the studies due to lack of sufficient tricuspid valve regurgitation. However, echocardiographic measures of PAP, pulmonary artery flow acceleration time (PAAT) and deceleration (PAD), were measurable in all animals, and correlated with invasive PAP (r = −0.74 and r = 0.75, P < 0.001 for both). Right ventricular thickness and area correlated with invasive PAP (r = 0.59 and r = 0.64, P < 0.001 for both). Observer variability of the invasive and non-invasive parameters was low except in tissue-Doppler derived isovolumetric relaxation time. These non-invasive parameters may be used to replace invasive measurements in detecting successful disease induction and to complement invasive data in the evaluation of PAH severity in a rat model.

Estrogen Rescues Preexisting Severe Pulmonary Hypertension in Rats

“…The severity of PH at Day 21 was further confirmed by (1) the increase in lung weight (from 1.37 6 0.1 g in CTRL to 2.37 6 0.09 g in PH, Figure 1E), (2) RV hypertrophy (RV/[LV1IVS] increased from 0.23 6 0.02 in CTRL to 0.64 6 0.05 in PH, Figure 1F), (3) pulmonary arteriolar medial hypertrophy (Figure 2A), and (4) appearance of a midsystolic notch on Doppler echocardiography of pulmonary artery flow ( Figure 2B). These data clearly demonstrate the development of malignant PH by Day 21 (16) and agree with previous studies using this time point as an initiating point for therapy of advanced PH (12). Therefore, we started E2 therapy at Day 21 in one group of rats by subcutaneously implanting continuous-release E2 pellets (42.5 mg/kg/d) for 10 days from Days 21 to 30 (E2 group), and another group was left untreated to develop RV failure (RVF group) by Day 30.…”

Effects of ovariectomy on antioxidant defence systems in the right ventricle of female rats with pulmonary arterial hypertension induced by monocrotaline

“…These data agree with the study of Koskenvuo et al (2010), in which pulmonary artery pressure was measured directly by using RV catheterization. In the present study, there was a slight increase in pulmonary pressure in female rats, while this parameter D r a f t was increased by about three times in male rats, as observed in previous reports (Ishikawa et al 2009, Koskenvuo et al 2010. Thus, this suggests that the animals in the present study, at this time point, are in a mild pulmonary hypertensive state.…”

“…The RVSP was used in order to estimate systolic pulmonary artery pressure, as RVSP is similar to systolic pulmonary artery pressure. Pulmonary artery pressure (PAP) was estimated using the following equation: Mean PAP (mmHg) = 0.61 x systolic PAP + 2 (Chemla et al 2004;Koskenvuo et al 2010).…”

The Sugen 5416/Hypoxia Mouse Model of Pulmonary Hypertension Revisited: Long‐Term Follow‐Up

“…PAAT increased over the 10-week normoxic recovery in both groups, and although SuHx mice had lower PAAT than VeHx mice after 10 weeks of recovery, this difference was not significant. PAAT is known to become shorter with higher RV and PA pressure in both humans and animals, [24][25][26][27][28][29][30][31][32] and it is a useful marker of PH in small animals that do not reliably develop quantifiable tricuspid regurgitation. PAAT has been hypothesized to be shorter in PH because of the reduced compliance and increased impedance of the pulmonary arterial system, 33 and it may provide additional information about these important parameters (compliance and impedance) when compared with invasively measured RV pressure.…”