We investigated the hypothesis that a cardioprotective, antiarrhythmic effect might be obtained by brief ischemia of a remote part of the body before ischemia of the heart. Regional ischemia (RI) was induced in isolated Langendorff-perfused rat hearts: group I, 30-min RI and reperfusion (control hearts; n = 18); group II, 5-min RI before 30-min RI (a reference group of “classic” ischemic preconditioning; n = 12); and group III, ischemic preconditioning with in vivo 10-min limb ischemia (LI) before 30-min RI in the perfused heart ( n = 20). A significant decrease in reperfusion arrhythmia was found in groups II and III compared with group I ( P < 0.02). Release of norepinephrine (NE) and prostacyclin was higher in hearts from animals pretreated with LI ( P < 0.05). Prostacyclin increased in all groups at minute 1 of reperfusion, but there was no correlation to the antiarrhythmic effect. NE increased at the beginning of reperfusion after 30 min of ischemia; this release was significantly diminished after preconditioning with LI ( P < 0.05). We further investigated the role of NE in preconditioning with LI using drug interventions. Pretreatment with exogenous NE protected against tachyarrhythmia. Reserpine given 24 h before LI partially abolished the antiarrhythmic effect of LI preconditioning. However, the α1-adrenoreceptor blocker prazosin did not prevent the effect of LI preconditioning on either ischemic or reperfusion tachyarrhythmia. Therefore, brief ischemia of an extremity protects against reperfusion tachyarrhythmia. One of the humoral mediators involved in this response appears to be NE; others remain to be identified.
Potential long-term cardioprotection was investigated in an extensive experimental study. Lactobacillus cultivation components (LCC) were administered intravenously in anesthetized rats 1, 7, and 21 days before global ischemia (GI). GI was produced by full stop flow in isolated Langendorff-perfused hearts for 20 min and was followed by reperfusion. Control animals were injected with saline. LCC reduced reperfusion tachyarrhythmia significantly and improved functional recovery of the ischemized rat heart. These beneficial effects were associated with reduction of release of norepinephrine (NE) and prostacyclin at the first minute of reperfusion, activation of myocardial catalase, and overexpression of 70-kDa heat stress protein (HSP-70) at ischemia and reperfusion (P < 0.05). This cardioprotection was documented up to 21 days after a single injection of LCC. Thus Lactobacillus cultivation components are new nontoxic materials that produce marked long-term cardioprotection against ischemia-reperfusion damage. This effect is attributed to an activation of the cellular defense system, manifested by activation of the antioxidant pathway and by expression of protective proteins. NE is involved in this process, and the data also suggest a role for prostacyclin in this model of cardioprotection. The potential of LCC and related compounds working through similar mechanisms in the prevention and therapy of various ischemic heart syndromes should be explored.
We studied the effects of short-term global ischemia and reperfusion on ANP secretion from Langendorff-perfused rat hearts compared with isolated ventricles. Effects of regional ischemia, with or without increased atrial pressure, were examined in Langendorff-perfused and working heart models. Five minutes of global ischemia were associated with elevated levels of atrial natriuretic peptide (ANP) in the coronary effluent immediately and for approximately 10 min after resumption of reperfusion, resulting in a net hormone excess of 23 +/- 5 ng/g wet wt. The ventricles produced on the average 11% ANP compared with the whole heart, and their contribution of to postischemic ANP overflow was approximately proportional to their basal production. In Langendorff-perfused hearts, regional ischemia increased the concentration of ANP in the coronary effluent 51 +/- 11%, whereas the secretion rate (per minute) decreased 18 +/- 5%. In the presence of atrial distension in the working heart model, a trend for increase in ANP secretion was apparent. We conclude that global ischemia, even of brief duration, has an independent stimulatory effect on ANP release, the ischemic atrium being responsible for most of the excess. Regional ischemia, when not accompanied by atrial distention, reduces the ANP secretion rate during the ischemic period. Heart failure secondary to ischemia stimulates ANP secretion, but this response seems to be both delayed and attenuated compared with atrial stretch alone.
Oral administration of Lactobacillus produces marked cardioprotection against ischemia-reperfusion injury. This effect is attributed to activation of the cellular defense system, manifested by activation of the antioxidant pathway, and by expression of protective proteins. Norepinephrine is involved in this process. The results of this study suggest that Lactobacillus, which is generally considered safe, could serve as a basis for the development of a new agent for preventive therapy of various ischemic heart syndromes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.