scholarly journals Cardioprotective effects of compound ALM-802 on subendocardial ischemia models

Author(s):  
I. B. Tsorin ◽  
V. V. Barchukov ◽  
M. B. Vititnova ◽  
A. M. Likhosherstov ◽  
G. V. Mokrov ◽  
...  

The investigation purpose. N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine (ALM-802 compounds) cardioprotective effect has been studied in rat models of subendocardial ischemia caused by isoproterenol and dobutamine. Material and methods. Acute subendocardial myocardial ischemia in anesthetized rats (urethane 1300 mg/kg, i.p.) was caused by infusion of isoproterenol (20 µg/kg/min i.v.) or dobutamine (80 µg/kg/min i.v.). Results. It was shown that in anesthetized rats, isoproterenol and dobutamine caused almost the same ST-segment depression in the II standard ECG lead. The compound ALM-802 (2 mg/kg i.v.), administered 2 minutes before the infusion start of isoproterenol or dobutamine, equally prevented the occurrence of ischemic changes on the ECG. Conclusion. The non-selective beta-adrenomimetic isoproterenol and the selective β1-adrenomimetic dobutamine cause subendocardial ischemia of the same intensity in anesthetized rats. The compound ALM-802 has a pronounced anti-ischemic effect on both models.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.R Bigler ◽  
F Praz ◽  
G.C.M Siontis ◽  
M Stoller ◽  
R Grossenbacher ◽  
...  

Abstract Background In patients with chronic coronary syndrome (CCS), percutaneous coronary intervention (PCI) targets hemodynamically significant stenoses, i.e., those thought to cause ischemia. The hemodynamic severity of a coronary stenosis increases with its tightness and with the myocardial mass of viable myocardium downstream of the stenosis. Besides the structural angiographic approach, assessment of functional relevance by pressure measurements (fractional flow reserve, FFR; instantaneous wave-free ratio, iFR) is recommended. However, visual angiographic assessment continues to dominate the treatment decisions for intermediate coronary lesions. Conversely, intracoronary ECG (icECG) potentially provides an inexpensive, sensitive and direct measure of myocardial ischemia. Purpose The goal of this study was to test the accuracy of intracoronary ECG during pharmacologic inotropic stress to determine coronary lesion severity in comparison to established physiologic indices (FFR/iFR) as well as with quantitatively determined percent diameter stenosis (%S) using biplane coronary angiography. Method This was a prospective, open-label study in patients with CCS. The primary study end point was the maximal change in icECG ST-segment shift during pharmacologic inotropic stress induced by dobutamine plus atropine obtained within 1 minute after the point of maximal heart rate (estimated by the formula 220 - age). IcECG was acquired by attaching an alligator clamp to the angioplasty guidewire positioned downstream of a stenosis. For the pressure-derived ratios, i.e. FFR and iFR, the coronary perfusion pressure downstream of a lesion as well as the aortic pressure were continuously recorded. Results One hundred patients were included in the study. Pearson-Correlation coefficient was significant between icECG and all three comparators (%S p<0.001, iFR p<0.001, FFR p<0.001). Using the FFR threshold of 0.80 defining coronary hemodynamic significance, ROC-analysis of the absolute icECG ST-segment shift showed an area under the curve (AUC) of 0.708±0.053 (p=0.0001, n=100, FFR<0.80 n=41). AUC for iFR was 0.919±0.030 (p<0.0001), for percent diameter stenosis it was 0.867±0.036 (p<0.0001). Conclusions During pharmacologic inotropic stress, intracoronary ECG ST-segment shift provides specific evidence for regional myocardial ischemia irrespective of the etiology and thus, provides an additional (patho-)physiologic information for decision making in borderline coronary lesions. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss Heart Foundation


2001 ◽  
Vol 95 (6) ◽  
pp. 1435-1440 ◽  
Author(s):  
Shinji Kohro ◽  
Quinn H. Hogan ◽  
Yuri Nakae ◽  
Michiaki Yamakage ◽  
Zeljko J. Bosnjak

Background Volatile anesthetics show an ischemic preconditioning-like cardioprotective effect, whereas intravenous anesthetics have cardioprotective effects for ischemic-reperfusion injury. Although recent evidence suggests that mitochondrial adenosine triphosphate-regulated potassium (mitoK(ATP)) channels are important in cardiac preconditioning, the effect of anesthetics on mitoK(ATP) is unexplored. Therefore, the authors tested the hypothesis that anesthetics act on the mitoK(ATP) channel and mitochondrial flavoprotein oxidation. Methods Myocardial cells were isolated from adult guinea pigs. Endogenous mitochondrial flavoprotein fluorescence, an indicator of mitochondrial flavoprotein oxidation, was monitored with fluorescence microscopy while myocytes were exposed individually for 15 min to isoflurane, sevoflurane, propofol, and pentobarbital. The authors further investigated the effect of 5-hydroxydeanoate, a specific mitoK(ATP) channel antagonist, on isoflurane- and sevoflurane-induced flavoprotein oxidation. Additionally, the effects of propofol and pentobarbital on isoflurane-induced flavoprotein oxidation were measured. Results Isoflurane and sevoflurane induced dose-dependent increases in flavoprotein oxidation (isoflurane: R2 = 0.71, n = 50; sevoflurane: R2 = 0.86, n = 20). The fluorescence increase produced by both isoflurane and sevoflurane was eliminated by 5-hydroxydeanoate. Although propofol and pentobarbital showed no significant effects on flavoprotein oxidation, they both dose-dependently inhibited isoflurane-induced flavoprotein oxidation. Conclusions Inhalational anesthetics induce flavoprotein oxidation through opening of the mitoK(ATP) channel. This may be an important mechanism contributing to anesthetic-induced preconditioning. Cardioprotective effects of intravenous anesthetics may not be dependent on flavoprotein oxidation, but the administration of propofol or pentobarbital may potentially inhibit the cardioprotective effect of inhalational anesthetics.


2013 ◽  
Vol 112 (9) ◽  
pp. 1293-1297 ◽  
Author(s):  
Jamshid Shirani ◽  
Shruthi Pranesh ◽  
Kimia Menhaji ◽  
Vlad Cotarlan ◽  
Alessandra Brofferio

2018 ◽  
Vol 27 (8) ◽  
pp. 1256-1268 ◽  
Author(s):  
Tianyu Li ◽  
Yunshu Su ◽  
Xiongli Yu ◽  
Durgahee S.A. Mouniir ◽  
Jackson Ferdinand Masau ◽  
...  

Stem cell transplantation represents a promising therapeutic approach for myocardial ischemia/reperfusion (I/R) injury, where cortical bone-derived stem cells (CBSCs) stand out and hold superior cardioprotective effects on myocardial infarction than other types of stem cells. However, the molecular mechanism underlying CBSCs function on myocardial I/R injury is poorly understood. In a previous study, we reported that Trop2 (trophoblast cell-surface antigen 2) is expressed exclusively on the CBSCs membrane, and is involved in regulation of proliferation and differentiation of CBSCs. In this study, we found that the Trop2 is essential for the ameliorative effects of CBSCs on myocardial I/R-induced heart damage via promoting angiogenesis and inhibiting cardiomyocytes apoptosis in a paracrine manner. Trop2 is required for the colonization of CBSCs in recipient hearts. When Trop2 was knocked out, CBSCs largely lost their functions in lowering myocardial infarction size, improving heart function, enhancing capillary density, and suppressing myocardial cell death. Mechanistically, activating the AKT/GSK3β/β-Catenin signaling axis contributes to the essential role of Trop2 in CBSCs-rendered cardioprotective effects on myocardial I/R injury. In conclusion, maintaining the expression and/or activation of Trop2 in CBSCs might be a promising strategy for treating myocardial infarction, I/R injury, and other related heart diseases.


Author(s):  
Muhammad Zohaib Siddiq ◽  
Shahid Hussain Memon ◽  
Anwar Ali ◽  
Tabassum Almas ◽  
Atiya Razzaq ◽  
...  

Background: Previous studies have established the fact that diabetic patients are predominantly inclined towards silent myocardial infarction (SMI). The objective of the present study is to determine the incidence of SMI in diabetes mellitus (DM) patients. Methodology: In this cross-sectional study, patient data was gathered on a predesigned proforma regarding the detailed history of dyspnea, DM and its duration, chest pain either present or not. Those patients who had normal ECG labeled negative for SMI, while those who had either ST-segment elevation or ST-segment deviation on resting ECG were positive for SMI. Study was conducted at the National Institute of Cardiovascular Diseases (NICVD) Karachi- Pakistan. Results: The mean age of the enrolled patients was 54.21±8.65 (40-70) years. Out of 210, majority were female (51.90%).Overall, 94(44.76%) patients were obese, 122(58.09%) were hypertensive, 90(42.85%) had dyslipidemia and 98(46.66%) diabetic patients were smokers. There were 93 (44.3%) DM patients who had SMI. Moreover, 109(51.90%) patients had a family history of myocardial ischemia. Conclusion:  The SMI incidence among diabetic patients was found higher in local population. It is proposed that diabetic patients with demonstrated cardiovascular autonomic neuropathy must be screened for the manifestation of SMI.


Sign in / Sign up

Export Citation Format

Share Document