Most cited article - PubMed ID 34486670
Excess ischemic tachyarrhythmias trigger protection against myocardial infarction in hypertensive rats
•In this study, hearts from 72 male Wistar albino rats were divided into two main protocols: a 40 min ischemia group (protocol A, n = 53) and 10 min ischemia group (protocol B, n = 19). Protocol A subdivided into 2 groups as a control group (n = 10) and adrenaline group (n = 43). Protocol B is subdivided into 2 groups as control group (n = 10) and adrenaline group (n = 9). Both adrenaline groups received the same dose of adrenaline.•In protocol A, ventricular tachyarrhythmia (VTA) incidence was 0 % in controls but rose to 72 % in the adrenaline group (p < 0.01). Heart rates for the control and adrenaline groups in stabilization and reperfusion were 254±45 bpm and 247 ± 66 bpm, versus 277 ± 41 bpm and 651 ± 286 bpm, respectively.•In protocol B, VTA incidence reached 100 % in both groups during reperfusion, with heart rates of 393 ± 29 bpm and 892±227 bpm for controls and 350 ± 49 bpm and 949 ± 116 bpm for the adrenaline group.•These findings suggest that direct adrenaline administration into the heart in last 5 mins of the ischemic period and the 5 mins of in the reperfusion time increases the incidence of reperfusion-induced ventricular arrhythmias up to 72 % in protocol A. Protocol B hearts showed reperfusion-induced ventricular arrhythmias with 100 % incidence in both groups.
- Keywords
- Direct adrenaline protocol, Epinephrine, Langendorff apparatus, Regional ischemia, Reperfusion arrhythmias, Reperfusion injury,
- Publication type
- Journal Article MeSH
BACKGROUND: The consequences at the molecular level and the mechanisms involved in a possible cardioprotective effect of antihypertensive treatment are not yet fully understood. Here, the efficacy of pyridostigmine (PYR) and trandolapril (TRA) as antihypertensive and antihypertrophic agents was investigated and compared in hypertensive SHR and normotensive WKY rats. In parallel, we investigated the effects of these drugs on myocardial β-adrenergic and cholinergic signaling pathways and protein expression profiles. METHODS: Age-matched male SHR and WKY rats were chronically (8 weeks) treated with PYR or TRA in drinking water. Blood pressure (BP) and heart rate (HR) were monitored telemetrically prior to tissue sampling for biochemical analysis. Baroreceptor reflex sensitivity (BRS) and methylatropine HR response as a measure of vagal tone were evaluated in separate groups of animals. RESULTS: PYR slightly lowered BP and HR in SHR rats during the dark phase of the day, while TRA effectively reduced BP during the light and dark phases without affecting HR. PYR enhanced BRS and improved vagal tone. There were no significant alterations in myocardial β-adrenergic and cholinergic signaling, with the exception of decreased forskolin-stimulated adenylyl cyclase (AC) activity in SHR rats, which was restored by TRA. Proteomic analysis revealed numerous differences induced by both treatments. Notable were changes in TGFβ-related signaling pathways as well as proteins involved in modifying hemodynamic parameters and cardiac hypertrophy. CONCLUSIONS: PYR is able to slightly decrease BP and HR in SHR rats but effectively increase BRS through vagal potentiation. The specific differences in protein expression profiles in rat myocardium induced by treatment with PYR and TRA reflect different mechanisms of action of these two agents at the molecular level.
- Keywords
- SHR and WKY rats, acetylcholinesterase, cholinergic signaling, hypertension, myocardial proteome, pyridostigmine, trandolapril,
- Publication type
- Journal Article MeSH
In 2023, six decades have elapsed since the first experimental work on the heart muscle was published, in which a member of the Institute of Physiology of the Czech Academy of Sciences participated as an author; Professor Otakar Poupa was the founder and protagonist of this research domain. Sixty years - more than half of the century - is certainly significant enough anniversary that is worth looking back and reflecting on what was achieved during sometimes very complicated periods of life. It represents the history of an entire generation of experimental cardiologists; it is possible to learn from its successes and mistakes. The objective of this review is to succinctly illuminate the scientific trajectory of an experimental cardiological department over a 60-year span, from its inaugural publication to the present. The old truth - historia magistra vitae - is still valid. Keywords: Heart, Adaptation, Development, Hypoxia, Protection.
- MeSH
- Academies and Institutes * history MeSH
- Biomedical Research * history trends MeSH
- History, 20th Century MeSH
- History, 21st Century MeSH
- Physiology history MeSH
- Cardiology history trends MeSH
- Humans MeSH
- Heart physiology MeSH
- Animals MeSH
- Check Tag
- History, 20th Century MeSH
- History, 21st Century MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Historical Article MeSH
- Review MeSH
- Geographicals
- Czech Republic MeSH
The aim of the study was to clarify the role of the interplay between hypertension and the renin-angiotensin system (RAS) in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. We hypothesized that in the late phase of hypertension with already developed signs of end-organ damage, inappropriate RAS activation could impair cardiac tolerance to I/R injury. Experiments were performed in male Cyp1a1-Ren-2 transgenic rats with inducible hypertension. The early phase of ANG II-dependent hypertension was induced by 5 days and the late phase by the 13 days dietary indole-3-carbinol (I3C) administration. Noninduced rats served as controls. Echocardiography and pressure-volume analysis were performed, angiotensins' levels were measured and cardiac tolerance to ischemia/reperfusion injury was studied. The infarct size was significantly reduced (by 50%) in 13 days I3C-induced hypertensive rats with marked cardiac hypertrophy, this reduction was abolished by losartan treatment. In the late phase of hypertension there are indications of a failing heart, mainly in reduced preload recruitable stroke work (PRSW), but only nonsignificant trends in worsening of some other parameters, showing that the myocardium is in a compensated phase. The influence of the RAS depends on the balance between the vasoconstrictive and the opposed vasodilatory axis. In the initial stage of hypertension, the vasodilatory axis of the RAS prevails, and with the development of hypertension the vasoconstrictive axis of the RAS becomes stronger. We observed a clear effect of AT1 receptor blockade on maximum pressure in left ventricle, cardiac hypertrophy and ANG II levels. In conclusion, we confirmed improved cardiac tolerance to I/R injury in hypertensive hypertrophied rats and showed that, in the late phase of hypertension, the myocardium is in a compensated phase.
- Keywords
- ANG II-dependent hypertension, AT1 receptor antagonist, P-V analysis, ischemia/reperfusion injury, renin-angiotensin system,
- Publication type
- Journal Article MeSH