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The Investigation of Combined Na+/Ca2+ Exchanger and the L-type Ca2+- Channel Inhibition in Langendorff-Perfused Isolated Guinea Pig Hearts


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Figure 1

The investigational protocol of the ouabain induced arrhythmia model in isolated guinea pig hearts. The bands represent the respective experimental groups: 1st row: control; 2nd row: test nisoldipine; 3rd row: test ORM-10962; 4th row: test ORM+nisoldipine. The demarcation lines represent the 3 distinct periods of the experiments: stabilization period, pre-treatment period and arrhythmia provocation period.
The investigational protocol of the ouabain induced arrhythmia model in isolated guinea pig hearts. The bands represent the respective experimental groups: 1st row: control; 2nd row: test nisoldipine; 3rd row: test ORM-10962; 4th row: test ORM+nisoldipine. The demarcation lines represent the 3 distinct periods of the experiments: stabilization period, pre-treatment period and arrhythmia provocation period.

Figure 2

Heart rate values from isolated guinea pig hearts for control and tested drugs. The bars represent mean values before (white) and after (black) treatment ± SEM.
Heart rate values from isolated guinea pig hearts for control and tested drugs. The bars represent mean values before (white) and after (black) treatment ± SEM.

Figure 3

Investigation of changes in left ventricular pressures from isolated guinea pig hearts in the control state and after drug administration. Ventricular pressure was calculated from the difference between end-systolic and end-diastolic pressures. ORM treatment showed a significant difference compared to the control (p < 0.001). The bars represent mean values before (white) and after (black) treatment ± SEM.
Investigation of changes in left ventricular pressures from isolated guinea pig hearts in the control state and after drug administration. Ventricular pressure was calculated from the difference between end-systolic and end-diastolic pressures. ORM treatment showed a significant difference compared to the control (p < 0.001). The bars represent mean values before (white) and after (black) treatment ± SEM.

Figure 4

The total arrhythmia map analysed from all hearts. The X axis shows the time after ouabain perfusion; Y axis: arrhythmia diagrams of 20 individual hearts. The hearts were divided into 4 groups: Control; Nisoldipine 30nM, ORM-10962 1 μM and 1 μM ORM+ 30nM Nisoldipine. Each of the horizontal lines represent a single heart. Time periods with the various arrhythmia stages are shown in colour: regular sinus rhythm (yellow); multiple extrasystoles (orange); bigeminy (blue): ventricular tachycardia (green): ventricular fibrillation (red).
The total arrhythmia map analysed from all hearts. The X axis shows the time after ouabain perfusion; Y axis: arrhythmia diagrams of 20 individual hearts. The hearts were divided into 4 groups: Control; Nisoldipine 30nM, ORM-10962 1 μM and 1 μM ORM+ 30nM Nisoldipine. Each of the horizontal lines represent a single heart. Time periods with the various arrhythmia stages are shown in colour: regular sinus rhythm (yellow); multiple extrasystoles (orange); bigeminy (blue): ventricular tachycardia (green): ventricular fibrillation (red).

Figure 5

The first appearance of VF in all groups after ouabain administration. The efficacy of individual inhibitors and inhibitor combinations has been evaluated against the control hearts. The bars represent mean values ± SEM, after drug or vehicle pretreatment and ouabain administration.
The first appearance of VF in all groups after ouabain administration. The efficacy of individual inhibitors and inhibitor combinations has been evaluated against the control hearts. The bars represent mean values ± SEM, after drug or vehicle pretreatment and ouabain administration.
eISSN:
2734-6382
Language:
English