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DOI: 10.1055/s-0040-1705383
Human Ventricular Tissue for Experimental Studies: A New Source?
Publikationsverlauf
Publikationsdatum:
13. Februar 2020 (online)
Objectives: The possibilities for studying force development or arrhythmias in human ventricular myocardium is very limited. So far, it was only possible in tissue from explanted organs after heart transplantation. Because of a general decrease in transplant numbers and the impossibility to schedule these operations, the chance to perform experiments on human heart tissue becomes less. For that reason, most of the experiments were done with animal tissue or computer models. To break new ground, we tried to use left ventricular tissue out of an apical punch after implantation of a left ventricular assist device (LVAD).
Methods: To implant the HeartWare left ventricular assist device (HVAD) it is necessary to puncture the left ventricular apex with a coring device. This device cuts a myocardial piece with a diameter of about 2 cm out of the apex. After taking a part for pathological investigation we put the rest in a cardioplegic solution containing 2,3-butanedione-monoxime (BDM). The tissue was cut into longitudinal slices of about 1 cm length and 2 mm width. Preparations were set in an organ bath and paced at 1 Hz at 37°C. Action potentials were recorded by sharp microelectrodes. We measured isometric force generation under basal condition and after exposure to increasing concentrations of isoprenaline (10 nmol–10 μmol).
Results: Some minutes after starting stimulation 75% of the preparations (n = 6/8) started to contract. Basal force was 0.54 ± 0.18 mN. Four out of the remaining six preparations increased force upon isoprenaline from 0.74 ± 0.2 to 1.35 ± 0.38 mN (log EC50 = 7.4 ± 0.1 M). Resting membrane potential amounted to −76 ± 2.7 mV (n = 4). Action potential duration at 90% repolarization was 313 ± 10 ms (n = 4) and increased upon exposure to the potassium channel blocker E-4031 (1 μM).
Conclusion: In ventricular tissue obtained during HVAD-implantation, force and action potentials can be recorded. Basal forces were clearly smaller than found by us and others in intact right ventricular trabeculae. However, sensitivity to catecholamines was similar. APD is in the expected range and showed the well-known prolongation upon potassium channel block. Ventricular tissue obtained from an apical punch represents a promising source to study mechanic and electrical properties of human ventricular heart tissue.