Hemodynamic Characterization Of Pulmonary Artery Hypertension In A Rat

Abstract

Introduction: Hemodynamic characterization of Pulmonary Artery (PA) hypertension helps to reveal progression of disease of pulmonary vasculature with constrictive remodeling of pulmonary arterioles, leading to right ventricle (RV) dysfunction and right sided HF failure. In this preclinical methodology article, surgical access, controlled mechanical ventilator set up and direct open chest measurements of PA hypertension is described, employing a rat model. Chronic PA injury was induced by single dose of monocrotaline (MCT).
 Methods & Aims: Setting of controlled mechanical volume ventilation (CMVV) was adjusted to limit its influence on RV preload and LV afterload in the instance of chronic pulmonary disease. Volume-ventilation setting of tidal volume and respiration rate was based on body weight. Isoflurane monoanesthesia was used without any premedication. PA pressures were compared using single and dual pressure catheter at 3-weeks post injury. Initially, single pressure catheter was positioned in the PA to assess data quality, while advanced data comparison (RV and PA pressures) during PA hypertension were made using dual pressure catheter. PA access was performed using “high” RV needle-stab, adjacent to the anatomical area of the PA outflow.
 Results: Introduction of single pressure catheter was successful and collected data during RV systole and diastole did not produce any major pressure artefacts. Final position in the main PA was guided by using visual cues i.e. distance of pressure sensor on the catheter, accompanied by simultaneous data recording from that location. In case of dual pressure catheter, RV and PA pressure data were successfully collected. During PA hypertension, systolic ranges were (41-52 mmHg) vs. naive (25-30 mmHg); diastolic (21-27 mmHg) vs. (9-14 mmHg); n=4. In PA hypertension, high afterload pressures complicated RV ejection, with PAP cresting about 1mmHg higher than the maximal RVP. During further assessment, RV ejection was complicated by higher PA dicrotic notch pressures, at the end of systole; for hypertension (37-41 mmHg) vs. naïve (16-21mmHg), n=4.
 Conclusions: This study revealed that good rat pressure data could be collected from the main trunk of PA using an open chest supported by CMVV. In future, hemodynamic influence of respiratory pump in close chest setting and its influence on chronic PA hypertension needs to be analyzed using solid state pressure catheter. To accomplish this, pressure catheter design should be based on rat’s RV and its outflow anatomy.