Changes Of Myocardial Regional Function After Brief Periods Of Myocardial Ischemia Demonstrated By Velocity Vector Imaging

Background and ObjectivesA lot of patients get to emergency room and clinic of cardiology because of chest pain. It is great significance for timely treatment of patients how to identify chest pain induced by myocardial ischemia. ECG is the most common and convenient method to determine whether chest pain is caused by myocardial ischemia. ECG and examination of myocardial enzymes are useful to detect myocardial infarction. ECG, however, is weak to detect myocardial ischemia events when the ischemic duration was not longer than 30 min, because the non-infarction ischemic ECG changes persist for< 1 minute of reperfusion. In patients with chest pain, symptoms have usually resolved before they come to a hospital, which makes the routine diagnostic approaches such as ECG and conventional echocardiography insufficient to provide reliable evidence for diagnosis of myocardial ischemia. Although coronary angiography is gold standard in identifying chest pain caused by myocardial ischemia, it is not a routine screening method because of an invasive examination and possibility of leading to a variety of complications. In addition, since the symptoms of myocardial ischemia are not typical in more and more patients, which is induced by the aging population and increased incidence of diabetes, it is easy to lead delayed, missed or mistaken diagnosis. It, thus, is urgent to develop a convenient, efficient, and accurate method to determine myocardial ischemic event after relief of symptoms of myocardial ischemia. In recent years, a great of progresses have been made on ultrasound imaging, which may provide evidences for early diagnosis of chest pain by estimating regional dysfunction after myocardial ischemia.The changes of function, metabolism, electrical activity and a series of biological markers can be caused by a relatively severe and acute myocardial ischemia. In these changes, systolic and diastolic dysfunction appeared earlier. The abnormality of regional systolic and diastolic function persists even after restoration of perfusion, which is known as myocardial stunning. Through evaluating myocardial regional dysfunction after restoration of perfusion, not only be able to provide evidences for determining whether the chest pain caused by myocardial ischemia, but also offer the diagnostic time window of a recent ischemic event. Some researchers analyzed contractile function after ischemia by using strain imaging derived from tissue Doppler technology, and found that the abnormality of myocardial systolic function after ischemia can be used for identifying ischemic events. Tissue Doppler imaging and strain imaging derived from tissue Doppler techniques, however, are angle-dependent of ultrasound beam, which can affect accuracy and comprehensiveness of the evaluation results. Also, some studies, compared with the systolic function, have shown that abnormal diastolic function is an early signal for myocardial ischemia and seem to be a more sensitive index to ischemia. Currently, the details of functional recovery, especially in diastolic function, after various durations of ischemia remain largely unclear. In addition, it seems uncertain in regard to the ischemic injury threshold for the induction of the diastolic or systolic stunning. Therefore, through studying the abnormality of myocardial regional function after ischemia myocardial ischemia that can make the myocardial ischemia memory to come true.In addition, When ischemia causes myocardial stunning, there are a series of biomechanical changes in regional myocardium. Through precisely evaluating these changes, not only do we deepen our knowledge of mechanism of myocardial stunning, but also may provide evidence for the diagnosis of myocardial ischemia. In past years, people had recognized myocardial stunning involving both systolic and diastolic properties. However, myocardial function was consisted of contraction, diastolic function and torsion. The muscle of heart is consisted of subendocardial myocardium, mid-myocardium and subepicardial myocardium. In the subendocardium, the myofibres have the right-handed spiral orientation. The myofibres of middle layer have horizontal orientation. And the myofibres is left-handed helix in the subepicardium. Opposite rotation of subendocardium and subepicardium lead to left ventricular twist in cardiac cycle. Cardiac torsion is an important component of cardiac function. In systole, torsion can strengthen contraction of myocardium, and it help left ventricular filling by effect of elastic recoil in diastole. Accordingly, torsion plays an important role in maintaining normal global function.The tagging magnetic resonance imaging (MRI) is a "gold standard" for evaluating torsion of left ventricular. The MRI, however, is complicated with low temporal resolution, high cost, inconvenient operation, time-consuming and complex processing of data analysis, which have inherently led to the underuse of this technique in the clinic. Because of convenience, noninvasive feature and feasibility of bedside examination, echocardiography has a good prospect of potential application in evaluating left ventricular twist. Numbers of echocardiographic techniques have been introduced to determine regional myocardial rotation and left ventricular torsion function, such as traditional two-dimensional echocardiography, and so on. People had used tissue doppler imaging and speckle tracking imaging to evaluated torsion function after myocardial infarction. They found that global and regional myocardial torsion were decreased after myocardial infarction. No information, but, is available in regard to changes of regional myocardial torsion in stunned myocardium.Velocity vector imaging (VVI) based two-dimension strain imaging is a new technology with a few advantages sourced by its software. "Feature tracking" of the myocardium with VVI can be achieved through the combination of speckle tracking, mitral annulus motion, tissue-blood border detection, and the periodicity of the cardiac cycle using R-R intervals, thus VVI improves the accuracy of assessment. We hypothesized that VVI would be an ideal tool to characterize the time course of regional dysfunction after brief periods of myocardial ischemia and recognize recent myocardial ischemic insult.The aim of this experimental study was designed to use VVI to evaluate regional systolic and, particularly, regional diastolic function after ischemia followed by reperfusion. In addition, we detect recovery of myocardial regional rotation function in stunned myocardium by using VVI, which can deepen comprehensive understanding of changes of myocardial mechanics in myocardial stunning, and guide the treatment of myocardial stunning.Methods1.108 Wistar rats (180-250 g) were equally divided into one sham and four myocardial ischemia-reperfusion (I/R) groups. I/R models were generated by brief occlusion (3,5,10 and 15 min, respectively) of the proximal left anterior descending artery (LAD) followed by reperfusion for 240 min. Myocardial ischemia was detected by ECG. Echocardiography was performed at Pre-occlusion, Occlusion and varied time-point after reperfusion (1 to 240 min), two-dimension images were performed in the left ventricular mastoid muscle section on the short axis for VVI analysis. Regional systolic and diastolic function was estimated from peak diastolic and systolic circumferential strain rate (SRdia and SRsys) at short axis view of left ventricular, respectively. Cardiac catheter was performed to determine left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximum rising rates of left ventricular pressure (+dP/dtmax) and maximum descending rates of left ventricular pressure (-dP/dtmin) at the same time-point. Histological changes of myocardium were detected by TTC staining. In addition, the rats were euthanasia and the myocardial glycogen was determined at Occlusion and reperfusion for 1,60, 120 and 240 min.2.12 Wistar rats were randomly divided into two myocardial ischemia- reperfusion (I/R) groups (10 or 15 min) and sham group. Myocardial ischemia was induced by brief occlusion of the proximal left anterior descending artery (LAD) followed by reperfusion for 240 min. ECG was monitored continuously. Echocardiography was performed at Pre-ischemia (baseline), ischemia and varied time-point after reperfusion (1 to 240 min), two-dimension images were obtained in the left ventricular mastoid muscle section on the short axis for VVI analysis. Regional systolic function and the function of torsion were evaluated by peak systolic circumferential strain rate (SRsys) and peak rotation degree (Rot) of VVI at short axis view of left ventricular, respectively. Myocardium contrast echocardiography (MCE) was also performed in the same section at baseline, ischemia and reperfusion for 30 min. Contrast agent was continuously infused by caudal vein. Myocardial blood flow (standard A·β) of LAD bed was determined.Results 1.(1) There was no evident necrotic myocardium detected by TTC staining in four MI/R group. It showed that the MI/R model can mimic stable (3-5 min) and variant (10-15 min) angina pectoris in the study.(2) Hemodynamic changes during MI/R. During LAD occlusion in all the four ischemia groups, LVSP,+dp/dt and -dp/dt were decreased (P< 0.01). LVEDP was increased (P< 0.05). Upon reperfusion, however, all hemodynamic variables returned to values similar to pre-occlusion and did not change significantly throughout the rest of the experiment (P> 0.05).(3) Changes of myocardial regional systolic function during MI/R. SRsys in the ischemic area was decreased at the end of occlusion in all the four ischemic groups when compared to the pre-occlusion values (P< 0.001). It began to restore after reperfusion, and returned to the pre-occlusion values immediately after reperfusion in both the 3-min and 5-min ischemia groups (P> 0.05), at 120 min and 240 min in the 10-min and 15-min ischemia groups, respectively (P=0.634 and 0.755). SRsys in non-ischemic area and sham group remained stable throughout the experiment (P> 0.05).(4) Changes of myocardial regional diastolic function during MI/R. In the non-ischemia zone and sham group, SRdia remained essentially unchanged during the course of the experiment (P> 0.05). In the ischemia area, SRdia was significantly decreased at the end of occlusion in all the four ischemic groups when compared to pre-occlusion values (P< 0.001). SRdia returned to pre-occlusion level immediately after reperfusion in the 3-min ischemia group (P=0.733), and at 10 min in the 5-min ischemia groups (P=0.326). Even 240 min after reperfusion, however, SRdia did not completely recovered in both 10-min and 15-min ischemia groups (P<0.001).(5) Images of SR show that negative (systolic SR) and positive (diastolic SR) waves in the ischemic area were smaller than those in the non-ischemic area in all the four ischemic groups. After reperfusion, negative waves of ischemic area returned to the pre-occlusion level immediately in both the 3-min and 5-min ischemia groups, at 120 min and 240 min in the 10-min and 15-min ischemia groups. Positive wave of ischemic area also returned to the pre-occlusion level immediately after reperfusion in the 3-min ischemia group, and at 10 min in the 5-min ischemia groups. Nevertheless, positive waves of ischemic area did not completely restored in both 10-min and 15-min ischemia groups.(6) Changes of myocardial glycogen. myocardial glycogen was significantly depleted by the 10-15-min period of ischemia to 36% of baseline (pre-occlusion values) (P< 0.001), whereas only 19% by 3-5 min ischemia (P=0.039). After reperfusion for 240 min, levels of myocardial glycogen returning to 90% of baseline values in 3-5min ischemia group (P=0.245), but only to 69% in 10-15min ischemia group (P< 0.001).2. (1) During myocardial ischemia/reperfusion, changes of myocardial blood flow in the LAD bed. Standard A·βin the LAD bed of sham group remained stable throughout the experiment (P> 0.05). At the ischemia, standard A·βin the LAD bed was significantly decreased and smaller than the baseline in the 10 or 15-min ischemic group (P<0.01). But standard A·βin the LAD bed was returned to the baseline values in both 10-min and 15-min ischemic groups at reperfusion for 30 min (P>0.05).(2) Regional systolic dysfunction in the LAD bed during myocardial ischemia/reper- fusion. SRsys in the LAD bed was decreased at the ischemia in the two ischemic groups when compared to the baseline values (P<0.01). It began to restore after reperfusion, and returned to the baseline values after reperfusion for 120 min in the 10-min ischemic group (P=0.184), at 240 min in the 15-min ischemic groups(P=0.914), respectively. In the LAD bed of sham group, SRsys remained essentially unchanged during the course of the experiment (P>0.05).(3) During myocardium ischemia/reperfusion, changes of regional torsion in the LAD bed. Rot in the LAD bed of sham group remained stable throughout the experiment (P>0.05). In the LAD bed, Rot was significantly decreased at the ischemia in the 10-min and 15-min ischemic groups when compared to the baseline (P<0.01). Rot returned to baseline level after reperfusion for 60 min in the 10-min ischemic group (P=964), and at 120 min in the 15-min ischemic groups (P=0.736).Conclusions1. VVI could be used to estimate myocardial regional function of rat after brief period ischemia followed by reperfusion.2.10 min ischemia is enough to cause systolic myocardial stunning and the assessment of SRsys by using VVI may facilitate the detection of myocardial ischemic memory.3. The persistent time of diastolic myocardial stunning is longer than the persistent time of systolic myocardial stunning. Compared with regional systolic function, regional diastolic function is a better parameter for detecting myocardial ischemic memory, and it can prolong the diagnostic time window of recent ischemic result.4. Images of strain rate of VVI can simultaneously, intuitively, qualitatively and quantitatively show time-dependent changes of regional myocardial systolic and diastolic function after ischemia followed by reperfusion.5. Myocardial torsion stunning can be caused by 10 min ischemia. It demonstrated that myocardial stunning should include systolic, diastolic and torsion properties.6. Abnormality of regional rotation caused by 10 to 15-minischemia persisted 1 to 2 h after reperfusion, and it, which was evaluated by VVI, can provided a helpful parameter for diagnosis of recently ischemic events.