Why the study?
If-current density changes with age and pathophysiological hypertrophy, prompting investigation into its role in pathophysiological processes occurring in the heart after myocardial infarction.
Does If-current blockade with ZD7288 alter chronotropy, inotropy, and coronary flow in isolated rat hearts with acute myocardial infarction compared to sham-operated hearts?
Does If-current blockade with ZD7288 alter chronotropy, inotropy, and coronary flow in isolated rat hearts with acute myocardial infarction compared to sham-operated hearts?
If-current blockade differentially affects heart rate, contractile force, and coronary flow in isolated rat hearts depending on the presence of acute myocardial infarction.
Does not support clinical translation of ZD7288 in AMI; leaves open If-current role in infarcted myocardium.
If-current density in cardiomyocytes changes not only with age, but also with pathophysiological hypertrophy. Thus, studies of pathological conditions in experimental animal models allow us to study If-current role in pathophysiological processes occurring in the heart after myocardial infarction (MI). The objective of the study is to examine the effect of If-currents blockade on the isolated heart of rats with modelled acute myocardial infarction (AMI) and sham-operated (SO) rats. Materials and Methods. MI was reproduced by the left coronary artery ligation. The study was conducted on a Langendorff-isolated heart (ADInstruments). During AMI, the authors studied chronotropy, inotropy and its temporal characteristics, and blood supply of the rat heart. Results. It was found that the initial values of contractile force and coronary flow were significantly lower in the group with an experimental AMI model. There were no differences in heart rate and temporal characteristics of contractile force. If-current blockade (ZD7288, 10-9 M, 10-5 M) reduced the contractile force and coronary flow of the isolated heart in both experimental groups, the changes were more pronounced in the SO group. If-current blockade (10-9 M) in the SO group led to tachycardia, and in the AMI group - to bradycardia. ZD7288 (10-5 M) reduced heart rate in both groups, but in the AMI group, bradycardia was more pronounced. It is possible that the obtained dynamics is associated with a change in the if-current density in the dyscrasic myocardium. Thus, it is obvious that If-currents are not only involved in the regulation of various MI heart functions, but their role changes at different stages of experimental myocardial infarction.
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Kuptsova et al. (2022) studied this question.
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