The Effect Of Low Dose Digitalis On Heart Rate Variability In The Early Stage Of Reperfused Acute Myocardial Infarction With Acute Heart Failure

Digitalis therapy for acute myocardial infarction (AMI) with acute heart failureremains controversial. Some non-randomized clinical observational studies before theera of reperfusion therapy indicated that the use of digitalis in AMI may increasemyocardial oxygen consumption and cardiac arrhythmias. Therefore, it is notrecommended to use digitalis in the early stage of AMI with acute heart failure. But theinformation of the use of digitalis in the early stage of reperfused AMI with acute heartfailure is rare. With the development of percutaneous coronary intervention (PCI)technology, the proportion of patients who underwent reperfusion therapy has increased.Therefore, under the background of reperfusion therapy, it is worthy to further explorethe effect and corresponding mechanism of digitalis on hemodynamic responses andleft ventricular remodeling.Autonomic imbalance characterized by increased sympathetic activity and reducedvagal tone is seen in AMI and heart failure, and it can be reflected by diminished heartrate variability (HRV). Ventricular arrhythmia and sudden cardiac death after AMI wasclosely associated with sympathetic neural remodeling. β-blockers are believed toimprove HRV and sympathetic neural remodeling after AMI, but it should be usedcautiously in acute heart failure.Previous studies have suggested that low dose digitalis not only can increasemyocardial contractility, but also has neurohumoral effect. Low dose digitalis which hasa vagal-like effect can suppress the activity of the sympathetic nervous system inchronic heart failure, and improve HRV. However, the researches of the effect ofdigitalis on autonomic nervous system (ANS) tend to focus on the areas of chronicheart failure, and the reports about the effect of early use of digitalis on ANS of AMIwith acute heart failure is rare.Deslanoside injection, called also Cedilanid, a rapidly acting cardiac glycoside, iswidely used in the treatment of acute heart failure. Cedilanid can quickly convert todigoxin in vivo, and onset time is10~30minutes with intravenous administration. Thepeak time of effect is about1~3hours, its sustainable action is2~5hours, and half-lifeis about33~36hours. The purpose of this study is to evaluate the effect of low dosedigitalis on HRV in the early stage of reperfused AMI with acute heart failure. Part1: Effects of Low Dose Digitalis on HeartRate Variability and Remodeling of Sympathetic Nervein a Model of Reperfused Acute Myocardial Infarctionwith Acute Heart Failure[Objectives]:This study was designed to investigate the effects of low dose digitalis onventricular arrhythmia, HRV and remodeling of sympathetic nerve in a model ofreperfused AMI with acute heart failure.[Methods]:Eleven Wuzhishan microswine were anesthetized and underwent occlusion of theleft anterior descending coronary artery by coronary angioplasty balloon withinterventional technique to establish a model of AMI with acute heart failure modelafter ischemic preconditioning. Eight out of the eleven microswine were survived fromthe procedure of infarction producing and underwent reperfusion by deflating theballoon after occluding for120min and then randomized into digitalis group (n=4) andcontrol group (n=4). Microswine in digitalis group were given Cedilanid injection (0.2mg) and normal saline (20ml) intravenously when those in control group were givensame volume of saline injection accordingly. The5-minutes HRV includingtime-domain and frequency-domain parameters were analyzed prior to ischemicpreconditioning, before reperfusion, before medication,2hours,3hours and24hoursafter medication. Digoxin (0.125mg q.d.) was given to the digitalis group in thefollowing days. Four microswine were sacrificed for immunohistochemistry ofgrowth-associated protein (GAP)-43to detect the remodeling of sympathetic nerves inperi-infarction area and no-infarction area at the end of the1st week and the other4atthe end of the4th week after infarction.[Results]:1. All of the eight microswine were survival to the end of the study. There was nomalignant ventricular arrhythmia requiring cardioversion therapy observed in the two groups.2. Compared with the baseline, SDNN, RMSSD and LFnorm of both groupsdecreased while the ratio of LF/HF increased after reperfusion. The above HRVparameters of control group tended to be stationary from2hours on after medication.3. Compared with the baseline, HFnorm of control group declined significantly at2hours after medication (P <0.05), and kept decreasing potential from then on. Therewas no statistically significant decline of HFnorm in digitalis group before medicationto3hours after medication (P>0.05). HFnorm of digitalis group was significantlyhigher than that of control group at2hours and3hours after medication (P <0.05), butthe difference was disappeared at24hours after medication.4. The ratio of LF/HF in control group increased significantly at2hours aftermedication (P <0.05), and increased slightly in the remaining hours. The ratio ofLF/HF in digitalis group changed slightly before medication to3hours after medication,and it was significantly lower than that of control group at2hours and3hours aftermedication (P <0.05), and it increased to the level of control group at24hours aftermedication.5. The distribution of GAP-43-positive nerve fibres seemed to be more uniformand less intensive in the digitalis group than that in the control group at the fourth weekafter AMI, but there was no statistically significant difference in the quantitativemeasurement between the two groups.[Conclusions]:Low dose digitalis didn’t increase the risk of malignant ventricular arrhythmiaand might be beneficial to recover sympatho-vagal imbalance and HRV in the earlystage of AMI with acute heart failure after reperfusion. Part2: Effect of Low Dose Digitalis onHeart Rate Variability in the Patients of ReperfusedAcute Myocardial Infarction with Acute Heart Failure[Objective]:To investigate the effect of digitalis on HRV in patients with acute heart failurefollowing AMI who underwent reperfusion therapy.[Methods]:Between January2013and December2013, a total of32consecutive patients withacute heart failure following AMI within24hours who underwent PCI in Departmentof Cardiology of Guangzhou General Hospital of Guangzhou Military Command wereenrolled in this study. The patients were randomly divided into two groups afterreperfusion therapy: digitalis group (n=17) and control group (n=15). The patients indigitalis group were given intravenously Cedilanid injection (0.2mg) with normalsaline (20ml) intravenously, and followed by Cedilanid injection (0.1~0.2mg)4~6hours later if required clinically. In the control group, the patents were given samevolume of saline injection accordingly. Electrocardiogram signals were recorded beforemedication,30minutes,3hours,6hours,12hours, and24hours after medication, andthen5minutes of Time-domain and Frequency-domain of HRV parameters wereanalyzed.[Results]:1. The general trends of HRV were appeared as follows in both groups afterreperfusion：SDNN, RMSSD, and HFnorm decreased while LFnorm and the ratio ofLF/HF increased.2. SDNN in both groups decreased after medication, and SDNN of control groupdecreased faster than that of digitalis group from30minutes to3hours after medication.SDNN of digitalis group was significantly higher than that of control group from3hours and6hours after medication (P <0.05), which decreased to the level of controlgroup from6hours to24hours after medication. 3. RMSSD in both groups decreased after medication, and there was nostatistically difference between the two groups.4. LFnorm of digitalis group increased significantly from30minutes to3hoursafter medication, and was remarkable higher than that of control group from3hours to12hours after medication (P <0.05).5. HFnorm of digitalis group increased significantly from30minutes to3hoursafter medication, and was significant higher than that of control group from3hours to24hours after medication (P <0.05).6. The ratio of LF/HF in digitalis group increased slightly from30minutes to6hours after medication (P>0.05), and was significantly lower than that of controlgroup from3hours to24hours after medication (P <0.05).[Conclusion]:Low dose digitalis reduced heart rate and might improve sympatho-vagalimbalance and HRV in the patients with AMI with acute heart failure who underwentPCI in the early stage.