Proteome-Based Study Of Differential Expression Of Serum Transferrin In Patients With Preload Failure And Corresponding Animal Model

Objective: In addition to traditional cardiopulmonary exercise,invasive cardiopulmonary exercise test(iCPET)provides extra hemodynamic monitoring and blood gas analysis.Practitioners described pathophysiological status including exercise-induced pulmonary arterial hypertension,exercise-induced heart failure with preserved ejection fraction and preload failure via application of iCPET.However,studies aim at these status are restricted by mass medical resource consumption and economic burden of iCPET.This study directs to explore differential expressed serum proteins of patients with preload failure and provide a feasible animal model that mimics hemodynamic feature of iCPET patients.Methods: This study includes clinical research and animal experiment.Clinical research: patients attended to the department of vascular-cardiology of First Affiliated Hospital of Chongqing Medical University with unexplained dyspnea were suggested iCPET.Sample from non-symptom healthy individuals were used as control.Serum sample of these patients were analyzed by two-dimensional gel electrophoresis-mass spectroscopy and Elisa.Animal experiment: adult SD rats were divided into preload failure group and control group.Self-made catheter was placed into right atrium and fixed to skin near puncture site under anesthesia.Tail ends were connected to pressure sensor.Succinylcholine and atropine were injected to preload failure group before exercise in order to reduce venous blood return and increase heart rate,therefore reduced preload,while control group were injected with saline.Both groups were trained before formal experiment.Results: Twenty-three patients were diagnosed preload failure,and serum samples were collected from 18 patients.Two-dimensional gel electrophoresis-mass spectroscopy showed that patients presents higher serum transferrin comparing to healthy controls,520316±158660 vs326554±49346,p < 0.01.Elisa results were consistent with two-dimensional gel electrophoresis-mass spectroscopy,64.2±1.3 vs47.9±6.9,p<0.001.Among iCPET results and base line features,cardiac output augmentation(r=-0.572,p=0.01),peak stroke volume(r=-0.553,p=0.026)were negative related to serum transferrin;left ventricular ejection fraction(r=0.521,p=0.046)were positive related to serum transferrin.Animal experiment: in quiescent condition,right atrial pressure of to control group showed no significant difference preload failure group(2.08±1.44 vs 2.06±1.47 mm Hg,p=0.991).At peak exercise load,control rat had higher right atrial pressure than preload failure group(6.22±2.90 vs1.22±0.75 mm Hg,p=0.007).Right atrial pressure augmentation(4.15±1.89vs-0.85±1.25 mm Hg,p<0.001).Conclusion: Serum transferrin elevated significantly in preload failure patients,which has the potential of to be the diagnostic biomarker.Succinylcholine and atropine properly mimic hemodynamic features of preload failure including low right atrial pressure and right atrial pressure augmentation.This model may provide support for future studies.