Effect of direct adrenaline infusion into isolated rat heart on the induction of ventricular tachyarrhythmias

Abstract

•In this study, hearts from 72 male Wistar albino rats were divided into two main protocols: a 40 min ischemia group (protocol A, n = 53) and 10 min ischemia group (protocol B, n = 19). Protocol A subdivided into 2 groups as a control group (n = 10) and adrenaline group (n = 43). Protocol B is subdivided into 2 groups as control group (n = 10) and adrenaline group (n = 9). Both adrenaline groups received the same dose of adrenaline.•In protocol A, ventricular tachyarrhythmia (VTA) incidence was 0 % in controls but rose to 72 % in the adrenaline group (p < 0.01). Heart rates for the control and adrenaline groups in stabilization and reperfusion were 254±45 bpm and 247 ± 66 bpm, versus 277 ± 41 bpm and 651 ± 286 bpm, respectively.•In protocol B, VTA incidence reached 100 % in both groups during reperfusion, with heart rates of 393 ± 29 bpm and 892±227 bpm for controls and 350 ± 49 bpm and 949 ± 116 bpm for the adrenaline group.•These findings suggest that direct adrenaline administration into the heart in last 5 mins of the ischemic period and the 5 mins of in the reperfusion time increases the incidence of reperfusion-induced ventricular arrhythmias up to 72 % in protocol A. Protocol B hearts showed reperfusion-induced ventricular arrhythmias with 100 % incidence in both groups.

Keywords: Direct adrenaline protocol; Epinephrine; Langendorff apparatus; Regional ischemia; Reperfusion arrhythmias; Reperfusion injury.

Graphical abstract

Fig. 1

Schematic illustration of the experimental protocols and their division of groups. Protocol A hearts subjected to 15 mins of stabilization period, 40 mins of regional ischemia period and 5 mins of reperfusion period. Protocol B hearts subjected to 10 mins of stabilization period, 10 mins of ischemia period and 5 mins of reperfusion period. The subgroups of Protocol A and B, control and adrenaline, are given in the table with the number of hearts. Green boxes indicate the time and duration of the adrenaline infusion in adrenaline groups of protocol A and protocol B.

Fig. 2

Preparation of left anterior descending artery occlusion (1a), application of occlusion (1b) and removal of occlusion (1c) on isolated beating rat heart in the Langendorff apparatus.

Fig. 3

Illustration of the aortic block of the Langendorff apparatus (Harvard Apparatus, Massachusetts, USA). Constant perfusion pressure is provided to the heart by setting the connected barometer (see barometer connection tip) to 80 mmHg and observing the continuous backflow from the aortic block to the reservoir. With this, the pressure controlled half-membrane valve supplies the pressure from the barometer to the aortic block. Direct infusion route is independent from the stopcock hence provides an administration of adrenaline at specified time and dose to the heart.

Fig. 4

ECG complexes from ECG I, ECG III, and aVF leads in millivolt (mV) from 2 isolated hearts (heart 1 and heart 2) in the protocol A adrenaline group during the reperfusion period. Electrocardiograms were captured in 2.048-second intervals.

Fig. 5

ECG strips from aVF (mV) and ECG_III leads in 4 different hearts with the indicated diagnosis. ECG 1 shows the readout diagnosed as ventricular fibrillation (VF). ECG 2 shows the readout diagnosed as monomorphic ventricular tachycardia. ECG 3 shows the readout identified as Torsades de Pointes (TdP). ECG 4 shows the readout identified as polymorphic ventricular tachycardia (PVT). ECG 1, ECG 2 and ECG 4 were obtained from protocol A hearts and ECG 3 was obtained from protocol B heart. All the ECG strips were captured in the reperfusion period. Identification of VF, PVT and TdP during the data analysis was done in accordance with the Lambeth conventions (II).

Fig. 6

Data in bar charts showing the incidence of ventricular tachyarrhythmias (VTA) of adrenaline and control groups in protocol A and protocol B hearts. “(+)” indicates the occurrence of the VTA in the bar chart. “(-)” stands for the no occurrence of VTA.

Fig. 7

Coronary flow (ml/min) of the hearts in adrenaline group in protocol A and protocol B. Boxplot graphs show the coronary flow measurements in the stabilization period and in the end of the reperfusion period. CF-1: Coronary flow in stabilization. CF-2: Coronary flow at the end of reperfusion. CI: Confidence index.

Fig. 8

Boxplots of heart rate (BPM) in adrenaline and control groups in protocol A and protocol B hearts during the stabilization period. Bpm: beat per minute.

Fig. 9

Boxplots of heart rate (BPM) in adrenaline and control groups in protocol A and protocol B hearts during the last 5 min of ischemia period. Symbol “°” indicates the single-deviated heart rate value. Bpm: beat per minute.

Fig. 10

Boxplots of heart rate (BPM) in adrenaline and control groups in protocol A and protocol B hearts during the reperfusion period. Almost all of the protocol B hearts had a reperfusion-induced VTA. Symbol “°” indicates the single-deviated heart rate value of the hearts. Bpm: beat per minute.

Fig. 11

QRS wave and QT wave intervals (ms) of the of hearts in adrenaline and control groups in protocol A and protocol B hearts during the stabilization and reperfusion period. “A Control” stands for the hearts in the protocol A control group. “A adrenaline” stands for the hearts in the protocol A adrenaline group. “B Control” stands for the hearts in the protocol B control group. “B adrenaline” stands for the hearts in the protocol B adrenaline group.