Minimally‐invasive Serial Assessment of Left‐Ventricular Pressure‐Volume Relationships in Rats: Pilot Evaluation in the Setting of Normal and Impaired Diastolic Function.

Abstract

IntroductionThe assessment of myocardial mechano‐energetic states is paramount to understand both pathological remodeling and responses to therapeutic interventions. In vivo, such state is determined by the interplay between both load‐independent functional properties (inotropy/lusitropy) and loading conditions. However, albeit most cardiac remodeling occurs over time, tools permitting the serial evaluation of load‐independent cardiac function and energetics responses in the chronic setting are limited, particularly in small animals. This pilot study established the feasibility of serial left‐ventricular (LV) pressure‐volume assessments (and derived mechano‐energetic indices) via the simultaneous integration of telemetered pressures and non‐invasive high‐resolution echocardiography in rats with either normal or acquired impaired diastolic function.MethodsHealthy (CTRL, n = 4) and obese/diabetic/hypertensive rats (ZSF1, n = 6) were instrumented with an analog telemetered (Data Sciences International) micro‐manometer catheter in the LV. Real‐time continuous LV pressures (LVP) and dimensions/volumes (via high‐resolution parasternal long‐axis transthoracic echocardiography) were measured simultaneously. In healthy rats, LV pressure‐volume relationships (LVPV) were determined under anesthesia (isoflurane) before/during inotropic (dobutamine, 5 to 10 μg/kg/min IV) and/or vascular (phenylephrine, 5 to 10 μg/kg/min IV) challenges. In the ZSF1 rats, conscious LVP and anesthetized LVPV data were collectd over the course of disease development (16 to 24 weeks).ResultsSimultaneous LV dimensions and pressures were successfully collected in all animals. LV pressures, dimensions, and derived functional indices remained independently sensitive to the pharmacological challenges. Acutely, PE increased systolic and end‐diastolic pressures (EDP) while shifting the pressure‐volume relationships to the right. DOB increased dP/dtmax and decreased EDP, while shifting the LVPV relationship to the left. Both PE and DOB increased stroke‐work, while having opposite effects in arterial elastance/load (Ea, ↑PE and ↓DOB) (see Fig. A). Meanwhile, ZSF1 rats showed progressive elevations in EDP (12.0 ± 1.6 to 17.5 ± 2.1 mmHg. P < 0.05) and Ea (0.51 ± 0.04 to 0.56 ± 0.05 mmHg/μL, P < 0.05), but preserved ejection fraction (73.5 ± 1.7 to 70.6 ± 2.0%, N.S.) and end‐diastolic dimensions (see Fig. B)ConclusionsTaken together, these experiments demonstrate that telemetered pressures and echocardiography‐derived dimensions can be successfully integrated in vivo in order to generate real‐time and serial (minimally‐invasive) LV pressure‐volume relationships in rats.Support or Funding InformationTelemetry devices were donated by DSIThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.