Many important observations and discoveries in heart physiology have been made possible using the isolated heart method of Langendorff. Nevertheless, the Langendorff’s method has some limitations and disadvantages such as the vulnerability of the excised heart to contusions and injuries, the probability of preconditioning during instrumentation, the possibility to induce tissue oedema, and a high oxidative stress, leading to the deterioration of the contractile function. To avoid the preceding drawbacks associated to the use of a whole heart, we have alternatively used beating mouse cardiac syncytia cultured in vitro in order to assess possible ergotropic, chronotropic, and inotropic effects of drugs. To achieve the preceding aim, we have developed a method based on image processing analysis to evaluate the kinematics and the dynamics of that drug-stimulated beating syncytia starting from the video registration of their contraction movement. In this manner, in comparison with the physiological no-drug condition, we have observed progressive positive ergotropic, positive chronotropic, and positive inotropic effects of 10 microM isoproterenol (beta-adrenergic agonist) and early positive ergotropic, negative chronotropic, and positive inotropic effects of 10 microM phenylephrine (alpha-adrenergic agonist), followed by a late phase with negative ergotropic, positive chronotropic, and negative inotropic trends. The present method permitted a systematic study of in vitro beating syncytia, producing results coherent with previous works. As consequence, it could be used in in vitro studies of beating cardiac patches, as alternative to the Langendorff’s heart in biochemical and pharmacological studies, and, especially, when the Langendorff’s technique is inapplicable (e.g., in studies about human cardiac syncytium in physiological and pathological conditions, patient-tailored therapeutics, and syncytium models derived from induced pluripotent/embryonic stem cells with genetic mutations). Furthermore, the method could help, in heart tissue engineering and bioartificial heart researches, to “engineer the heart piece by piece”. In particular, the proposed method could be useful in the identification of a suitable cell source, in the development and test of “smart” biomaterials, and in the design and use of novel bioreactors and microperfusion systems.

Video evaluation of kinematics and dynamics of the beating cardiac syncytium: an alternative to the Langendorff's method

FASSINA, LORENZO;MAGENES, GIOVANNI
2012-01-01

Abstract

Many important observations and discoveries in heart physiology have been made possible using the isolated heart method of Langendorff. Nevertheless, the Langendorff’s method has some limitations and disadvantages such as the vulnerability of the excised heart to contusions and injuries, the probability of preconditioning during instrumentation, the possibility to induce tissue oedema, and a high oxidative stress, leading to the deterioration of the contractile function. To avoid the preceding drawbacks associated to the use of a whole heart, we have alternatively used beating mouse cardiac syncytia cultured in vitro in order to assess possible ergotropic, chronotropic, and inotropic effects of drugs. To achieve the preceding aim, we have developed a method based on image processing analysis to evaluate the kinematics and the dynamics of that drug-stimulated beating syncytia starting from the video registration of their contraction movement. In this manner, in comparison with the physiological no-drug condition, we have observed progressive positive ergotropic, positive chronotropic, and positive inotropic effects of 10 microM isoproterenol (beta-adrenergic agonist) and early positive ergotropic, negative chronotropic, and positive inotropic effects of 10 microM phenylephrine (alpha-adrenergic agonist), followed by a late phase with negative ergotropic, positive chronotropic, and negative inotropic trends. The present method permitted a systematic study of in vitro beating syncytia, producing results coherent with previous works. As consequence, it could be used in in vitro studies of beating cardiac patches, as alternative to the Langendorff’s heart in biochemical and pharmacological studies, and, especially, when the Langendorff’s technique is inapplicable (e.g., in studies about human cardiac syncytium in physiological and pathological conditions, patient-tailored therapeutics, and syncytium models derived from induced pluripotent/embryonic stem cells with genetic mutations). Furthermore, the method could help, in heart tissue engineering and bioartificial heart researches, to “engineer the heart piece by piece”. In particular, the proposed method could be useful in the identification of a suitable cell source, in the development and test of “smart” biomaterials, and in the design and use of novel bioreactors and microperfusion systems.
2012
9781621008439
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/270303
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