| BackgroundUnder various pathophysiological conditions of patients with heart disease(such as ischemic heart disease and heart failure),left ventricular(LV) diastolic dysfunction precedes the onset of systolic dysfunction.Therefore,early diagnosis and recognition of LV diastolic dysfunction makes great sense to relief and prognosis of the symptoms. However,it is lack of methods evaluating LV diastolic function completely and simply in our country at present.LV diastolic function can be reflected through some important indices.Left ventricular end-diastolic pressure(LVEDP) and maximal decrease in velocity of left ventricular pressure(-(dP/dt)max) have been widely used in clinical,as indices evaluating the global LV diastolic function.However,more and more studies have indicated that time constant of ventricular isovolumic relaxation(τ) and chamber stiffness(K) are two ideal indices reflecting LV active and passive diastolic function respectively.However,τand K have not attracted enough attention,due to their calculations were rather complex and inconvenient.Recently,Eucker et al and Chung et al have derived two simple and convenient methods to calculateτand K,based on pressure phase plane(PPP),respectively.Considering the characteristic of P-dP/dt loop on PPP,we modified the model purposed by Chung et al,then represented chamber stiffness with Kd instead of K.Objectives1.To establish a novel method based on PPP,which can be used to calculate four important indices including LVEDP,-(dP/dt)max,τand Kd,and to emphasize on the calculation ofτand Kd,in order to provide a simple and easy approach for fast measurement of LV diastolic function in clinical.2.To analyze and compare PPP derived-τand Kd changes quantitatively on isolated rat heart during ischemia/reperfusion,and to explore the value of PPP derived-τand Kd for evaluation of left ventricular diastolic dysfunction.Methods1.Langendorff isolated rat heart perfusion,left ventricular pressure recording and data acquisitionHearts from male Sprague-Dawley rats were rapidly excised and mounted on a Langendorff apparatus for perfusion at 37℃with Krebs-Henseleit buffer at constant pressure(76 mmHg).The left atrium was opened,and a fluid filled latex balloon was inserted into the left ventricle.The balloon was connected via a short plastic tube to a pressure transducer.LV pressure was recorded and acquired by a processing system, and then imported to MATLAB 6.1(The Mathworks Inc,USA),in order to be processed with the program mentioned in this paper.2.Calculation of LVEDP,-(dP/dt)max,τand KdA MATLAB program was written to calculate LVEDP,-(dP/dt)max,τand Kd. Firstly,some pretreatments including superposition and smooth processing to LV pressure and its differential signals were performed,then P-dP/dt loops were plotted and LVEDP,-(dP/dt)max,τand Kd were calculated.The calculations ofτand Kd were our focuses in the program.3.Measurement of LDH in the coronary effluentTo assess myocardial injury,leakage of lactate dehydrogenase(LDH) during reperfusion was measured in the collected coronary effluent. 4.Observation of myocardial ultrastructure by transmission electron microscopeAfter the experiment,ultrastructure of myocardium was observed by transmission electron microscope(Philips Tecnai 10).5.Experimental ProtocolHearts(n=8) from 40 male Sprague-Dawley rats were randomly divided into five groups:(1)control:60 min-perfusion+0 min-ischemia+60 min-reperfusion; (2)ischemia 15:45 min-perfusion+15 min-ischemia+60 min-reperfusion;(3) ischemia 30:30 min-perfusion+30 min-ischemia+60 min-reperfusion;(4) ischemia 45:15 min-perfusion+45 min-ischemia+60 min-reperfusion;(5) ischemia 60:60 min-ischemia+60 min-reperfusion.Results1.Effect of ischemia on P-dP/dt loopsWith the prolonged ischemia,the shapes of P-dP/dt loops changed dramatically, and the areas of P-dP/dt loops decreased gradually;this situation was improved at 60 min after reperfusion,compared with that at 5 min after reperfusion.2.Differences of LVEDP,-(dP/dt)max,τand Kd among each group(1) LVEDP:Compared with pre-ischemia,LVEDP during reperfusion increased in a time dependent manner in each ischemic group.Compared with the same time course of the control group and ischemia 15 min group,LVEDP in ischemia 30 min group was higher at 0 min and 20 min after reperfusion(P＜0.01),and LVEDP in ischemia 45 min group and ischemia 60 min group were also higher after reperfusion(P＜0.01). Compared with the same time course of ischemia 30 min group,LVEDP in ischemia 45 min group and ischemia 60 min group were higher after reperfusion(P＜0.01). Compared with the same time course of ischemia 45 min group,LVEDP in ischemia 60 min group was higher at 60 min after reperfusion(P＜0.01).(2) -(dP/dt)max:Compared with pre-ischemia,the absolute values of-(dP/dt)max during reperfusion decreased in a time dependent manner in each ischemic group. Compared with the same time course of the control group and ischemia 15 min group, the absolute value of-(dP/dt)max in ischemia 30 min group was lower at 0 min and 20 min after reperfusion(P＜0.01);the absolute value of-(dP/dt)max in ischemia 45 min group was lower at 0 min,20 min and 40 min after reperfusion(P＜0.01);the absolute value of -(dP/dt)max in ischemia 60 min group was lower after reperfusion(P＜0.01). Compared with the same time course of ischemia 30 min group,the absolute value of -(dP/dt)max in ischemia 45 min group was lower at 0 min,20 min and 40 min after reperfusion(P＜0.01);the absolute value of-(dP/dt)max in ischemia 60 min group was lower after reperfusion(P＜0.01).Compared with the same time course of ischemia 45 min group,the absolute value of-(dP/dt)max in ischemia 60 min group was lower at 20 min,40 min and 60 min after reperfusion(P＜0.05).(3)τ:Compared with pre-ischemia,τduring reperfusion increased in a time dependent manner in each ischemic group.Compared with the same time course of the control group,τin ischemia 15 min group was higher at 0 min after reperfusion (P＜0.05);τin ischemia 30 min group was higher at 0 min and 20 min after reperfusion (P＜0.05);τin ischemia 45 min group and ischemia 60 min group were higher after reperfusion(P＜0.05).Compared with the same time course of ischemia 15 min group,τin ischemia 45 min group was higher at 0 min,20 min and 40 min after reperfusion (P＜0.01);τin ischemia 60 min group was higher after reperfusion(P＜0.01).Compared with the same time course of ischemia 30 min group,τin ischemia 45 min group was higher at 0 min,20 min and 40 min after reperfusion(P＜0.05);τin ischemia 60 min group was higher after reperfusion(P＜0.01).Compared with the same time course of ischemia 45 min group,τin ischemia 60 min group was higher at 0 min,20 min and 60 min after reperfusion(P＜0.01).(4) Kd:Compared with pre-ischemia,Kd during reperfusion decreased in a time dependent manner in each ischemic group.Compared with the same time course of the control group,Kd in ischemia 15 min group was lower at 20 min,40 min and 60 min after reperfusion(P＜0.05);Kd in ischemia 30 min group,ischemia 45 min group and ischemia 60 min group were all lower after reperfusion(P＜0.01).Compared with the same time course of ischemia 15 min group,Kd in ischemia 45 min group was lower at 60 min after reperfusion(P＜0.05);Kd in ischemia 60 min group was lower at 0 min,20 min and 60 min after reperfusion(P＜0.05).Compared with the same time course of ischemia 30 min group and ischemia 45 min group,Kd in ischemia 60 min group was lower at 0 min after reperfusion(P＜0.05).3.Changes of LDH among each groupExcept ischemia 15 min group,LDH in other ischemic groups increased significantly at 10 min and 20 min after reperfusion when compared with the control group(P＜0.05);Compared with ischemia 30 min group,LDH in ischemia 45 min group and ischemia 60 min group were even higher at 10 min and 20 min after reperfusion (P＜0.05).4.Ultrastructure changes in myocardial cells among each groupWith the prolonged ischemia,the myocardial ultrastructure became abnormally.Conclusions1.This method based on PPP,which can be utilized to the calculation of LVEDP, -(dP/dt)max,τand Kd,is sensitive and effective to the evaluation of LV diastolic function, and can be applied to the early detection of LV diastolic dysfunction.2.PPP derived-τand Kd may be promising indexes for quantitative assessment of LV diastolic function on isolated rat heart during ischemia/reperfusion,and indication of the severity of ischemia/reperfusion injury.
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