scholarly journals Cardioprotective effect of fingolimod against calcium paradox-induced myocardial injury in the isolated rat heart

2021 ◽  
Author(s):  
Fatma Alatrag ◽  
Matthew Amoni ◽  
Roisin Kelly-Laubscher ◽  
Asfree Gwanyanya
Keyword(s):  
Infarct Size ◽  
Transient Receptor Potential ◽  
Diastolic Pressure ◽  
Myocardial Infarct ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Hemodynamic Parameters ◽  
Transient Receptor Potential Melastatin ◽  
Ventricular Tissue

Fingolimod (FTY720) inhibits Ca<sup>2+</sup>-permeable, Mg<sup>2+</sup>-sensitive channels called transient receptor potential melastatin 7 (TRPM7), but its effects on Ca<sup>2+</sup> paradox (CP)-induced myocardial damage have not been evaluated. We studied the effect of FTY720 on CP-induced myocardial damage, and used other TRPM7 channel inhibitors nordihydroguaiaretic acid (NDGA) and Mg<sup>2+</sup> to test if any effect of FTY720 was via TRPM7 inhibition. Langendorff-perfused Wistar rat hearts were treated with FTY720 or NDGA and subjected to a CP protocol consisting of Ca<sup>2+</sup> depletion followed by Ca<sup>2+</sup> repletion. Hearts of rats pre-treated with MgSO<sub>4</sub> were also subjected to CP. Hemodynamic parameters were measured using an intraventricular balloon, and myocardial infarct size was quantified using triphenyltetrazolium chloride stain. TRPM7 proteins in ventricular tissue were detected using immunoblot analysis. FTY720, but not NDGA, decreased CP-induced infarct size. Both FTY720 and NDGA minimized the CP-induced elevation of left ventricular end-diastolic pressure, but only FTY720 ultimately improved ventricular developed pressure. Mg<sup>2+</sup> pre-treatment had effect neither on CP-induced infarct size, hemodynamic parameters during CP, nor the level TRPM7 protein expression in ventricular tissue. Overall, FTY720 attenuated CP-induced myocardial damage, with potential therapeutic implications on Ca<sup>2+</sup>-mediated cardiotoxicity. However, the cardioprotective mechanism of FTY720 seems to be unrelated to TRPM7 channel modulation.

scholarly journals New Interventional Therapies beyond Stenting to Treat ST-Segment Elevation Acute Myocardial Infarction

2021 ◽  
Vol 8 (9) ◽  
pp. 100
Author(s):  
Pablo Vidal-Calés ◽  
Pedro L. Cepas-Guillén ◽  
Salvatore Brugaletta ◽  
Manel Sabaté
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
St Segment Elevation ◽  
St Segment

Myocardial infarction remains the principal cause of death in Europe. In patients with ST-segment-elevation myocardial infarction (STEMI), a promptly revascularization with primary percutaneous intervention (PCI) has transformed prognosis in the last decades. However, despite increasing successful PCI procedures, mortality has remained unchanged in recent years. Also, due to an unsatisfactory reperfusion, some patients have significant myocardial damage and suffer left ventricular adverse remodeling with reduced function—all that resulting in the onset of heart failure with all its inherent clinical and socioeconomic burden. As a consequence of longer ischemic times, distal thrombotic embolization, ischemia-reperfusion injury and microvascular dysfunction, the resultant myocardial infarct size is the major prognostic determinant in STEMI patients. The improved understanding of all the pathophysiology underlying these events has derived to the development of several novel therapies aiming to reduce infarct size and to improve clinical outcomes in these patients. In this article, based on the mechanisms involved in myocardial infarction prognosis, we review the new interventional strategies beyond stenting that may solve the suboptimal results that STEMI patients still experience.

scholarly journals Left ventricular unloading during reperfusion does not limit myocardial infarct size.

Circulation ◽  
1990 ◽  
Vol 81 (4) ◽  
pp. 1374-1379 ◽  
Author(s):  
D M Van Winkle ◽  
T Matsuki ◽  
N M Gad ◽  
M C Jordan ◽  
J M Downey
Keyword(s):  
Infarct Size ◽  
Myocardial Infarct ◽  
Left Ventricular ◽  
Myocardial Infarct Size

scholarly journals Mechanically Unloading the Left Ventricle Before Coronary Reperfusion Reduces Left Ventricular Wall Stress and Myocardial Infarct Size

Circulation ◽  
2013 ◽  
Vol 128 (4) ◽  
pp. 328-336 ◽  
Author(s):  
Navin K. Kapur ◽  
Vikram Paruchuri ◽  
Jose Angel Urbano-Morales ◽  
Emily E. Mackey ◽  
Gerard H. Daly ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Wall Stress ◽  
Left Ventricular ◽  
Left Ventricular Wall ◽  
Myocardial Infarct Size ◽  
Ventricular Wall ◽  
Coronary Reperfusion

Cardioprotection with esmolol-based cardioplegia for non-infarcted and infarcted rat hearts

2021 ◽  
Author(s):  
Alexander B Veitinger ◽  
Audrey Komguem ◽  
Lena Assling-Simon ◽  
Martina Heep ◽  
Julia Schipke ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Lactate Production ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Cardioplegic Arrest ◽  
Blood Cardioplegia ◽  
Rat Hearts

Abstract OBJECTIVES Esmolol-based cardioplegic arrest offers better cardioprotection than crystalloid cardioplegia but has been compared experimentally with blood cardioplegia only once. We investigated the influence of esmolol crystalloid cardioplegia (ECCP), esmolol blood cardioplegia (EBCP) and Calafiore blood cardioplegia (Cala) on cardiac function, metabolism and infarct size in non-infarcted and infarcted isolated rat hearts. METHODS Two studies were performed: (i) the hearts were subjected to a 90-min cardioplegic arrest with ECCP, EBCP or Cala and (ii) a regional myocardial infarction was created 30 min before a 90-min cardioplegic arrest. Left ventricular peak developed pressure (LVpdP), velocity of contractility (dLVP/dtmax), velocity of relaxation over time (dLVP/dtmin), heart rate and coronary flow were recorded. In addition, the metabolic parameters were analysed. The infarct size was determined by planimetry, and the myocardial damage was determined by electron microscopy. RESULTS In non-infarcted hearts, cardiac function was better preserved with ECCP than with EBCP or Cala relative to baseline values (LVpdP: 100 ± 28% vs 86 ± 11% vs 57 ± 7%; P = 0.002). Infarcted hearts showed similar haemodynamic recovery for ECCP, EBCP and Cala (LVpdP: 85 ± 46% vs 89 ± 55% vs 56 ± 26%; P = 0.30). The lactate production with EBCP was lower than with ECCP (0.6 ± 0.7 vs 1.4 ± 0.5 μmol/min; P = 0.017). The myocardial infarct size and (ECCP vs EBCP vs Cala: 16 ± 7% vs 15 ± 9% vs 24 ± 13%; P = 0.21) the ultrastructural preservation was similar in all groups. CONCLUSIONS In non-infarcted rat hearts, esmolol-based cardioplegia, particularly ECCP, offers better myocardial protection than Calafiore. After an acute myocardial infarction, cardioprotection with esmolol-based cardioplegia is similar to that with Calafiore.

Abstract 300: Topical Application of IcyHot Reduces Myocardial Infarct Size in Rodents by a TRPA1-dependent Mechanism

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Yun Wu ◽  
Yao Lu ◽  
Eric R Gross
Keyword(s):  
Infarct Size ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion Injury ◽  
Calcium Influx ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Sprague Dawley ◽  
Area At Risk ◽  
Reactive Aldehydes

Toxic reactive aldehydes are formed during ischemia-reperfusion. The ion channel transient receptor potential ankryin 1 (TRPA1) is irreversibly modified by reactive aldehydes which can cause calcium influx and cell death. Here we tested whether topically applied creams containing a reversible TRPA1 agonist could reduce myocardial infarct size. Male Sprague-Dawley rats 8-10 weeks age were subjected to an in vivo myocardial ischemia-reperfusion model of 30 minutes of left anterior descending (LAD) coronary artery ischemia followed by 2 hours reperfusion. Prior to ischemia, rats were untreated or had 1g of cream applied to the abdomen. The creams tested were IcyHot, Bengay, Tiger Balm, or preparation H (Fig. 1A). Hearts were negatively stained for the area at risk and the infarct size was determined by using TTC staining (Fig. 1B). A subset of rodents prior to receiving IcyHot also received an intravenous bolus of the TRPA1 antagonist TCS-5861528 (1mg/kg) or AP-18 (1mg/kg). Interestingly, both IcyHot and Bengay reduced myocardial infarct size compared to untreated rodents (Fig. 1C and 1D IcyHot: 41±3%*, Bengay: 50±2%* versus control 62±1%, n=6/group, *P<0.001). Both preparation H and Tiger Balm failed to reduce myocardial infarct size (Tiger Balm: 63±2%, preparation H 59±2%). Giving a TRPA1 antagonist prior to IcyHot also blocked the reduction in infarct size. Our additional data also indicates the methyl salicylate (mint) in IcyHot and Bengay is the agent that limits myocardial infarct size. Since IcyHot and Bengay are safely used by humans, targeting TRPA1 by using products such as these could be quickly translatable and widely used to reduce ischemia-reperfusion injury.

Abstract 16538: Circulating Ketone Levels are Associated With Myocardial Infarct Size and Left Ventricular Function in Patients Presenting With St-Elevation Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Marie Sophie L de Koning ◽  
B. D Westenbrink ◽  
Solmaz Assa ◽  
Dirk J van Veldhuisen ◽  
Robin P Dullaart ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ejection Fraction ◽  
Left Ventricular Function ◽  
Infarct Size ◽  
Ventricular Function ◽  
Myocardial Infarct ◽  
Left Ventricular ◽  
St Elevation Myocardial Infarction ◽  
Myocardial Infarct Size ◽  
St Elevation

Background: Circulating ketone bodies (KB) are increased in patients with heart failure, corresponding with increased utilization of KB as a cardiac fuel. Whether circulating KB are increased in patients presenting with ST-elevation myocardial infarction (STEMI) and whether this is associated with infarct size is unknown. Methods: KB were measured in 379 non-diabetic participants of the Glycometabolic Intervention as Adjunct to Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction (GIPS) III trial (Clinicaltrial.gov Identifier: NCT01217307). Non-fasting plasma concentrations of the KB beta-hydroxybutyrate, acetoacetate, acetone were measured at presentation, 24 hours and 4 months after STEMI presentation using nuclear magnetic resonance spectroscopy. Associations of circulating KB with myocardial infarct size and left ventricular ejection fraction (both detected with MRI at 4 months after STEMI) were determined using multivariable linear regression analyses. Results: Circulating KB were higher at baseline (total KB 520 [315-997](median [IQR], μmol/L), compared to 206 [174-246] at 24 hours and 166 [143-201] at 4 months ( P <0.001 for all)). KB at 24 hours were positively associated with enzymatic infarct size, HbA1C and beta-blocker use. KB at 24 hours were independently associated with MRI outcomes at 4 months. Higher KB was associated with larger myocardial infarct size (total KB: standardized β=0.17, 95%-confidence interval (CI) (0.04-0.31), P =0.012) and lower ejection fraction (standardized β=-0.15, 95%-CI (-0.29- -0.009), P =0.037). Conclusion: Circulating KB are increased in patients with STEMI and are independently associated with myocardial infarct size and left ventricular function after 4 months of follow-up. The increase in circulating KB may reflect maladaptive changes of myocardial metabolism during the acute phase.

Reduction of Myocardial Necrosis after Glycosaminoglycan Administration: Effects of a Single Intravenous Administration of Heparin or N-Acetylheparin 2 Hours before Regional Ischemia and Reperfusion

1996 ◽  
Vol 1 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Michael R. Gralinski ◽  
Edward M. Driscoll ◽  
Gregory S. Friedrichs ◽  
Michael R. DeNardis ◽  
Benedict R. Lucchesi
Keyword(s):  
Infarct Size ◽  
Regional Blood Flow ◽  
Myocardial Infarct ◽  
Myocardial Necrosis ◽  
Final Analysis ◽  
Study Groups ◽  
Left Ventricular ◽  
Coagulation System ◽  
Myocardial Infarct Size ◽  
Area At Risk

Background We determined if a single administration of heparin or nonanticoagulant N-acetylheparin could reduce myocardial injury resulting from a 90-minute occlusion of the left circumflex coronary artery (LCX) and 6 hours of reperfusion in the anesthetized canine. Methods and Results Heparin (2 mg/kg), N-acetylheparin (2 mg/kg), or vehicle, 0.9% sodium chloride (control), was administered intravenously to separate groups of animals 2 hours before LCX occlusion. To ensure parity of LCX ischemia, only animals with ischemic zone regional blood flow < 0.16 mL/min/g tissue were included in the final analysis. Hemodynamics did not differ among the three study groups. Infarct size as a percentage of the left ventricular area at risk was obtained for each group. Myocardial infarct size was 43.0 ± 3.9% in the vehicle, 28.8 ± 5.8% in the heparin ( P < .05 vs vehicle) and 24.7 ± 4.6% ( P < .05 vs vehicle) in the N-acetylheparin-treated animals. Conclusion Pretreatment with heparin or its nonanticoagulant derivative, N-acetylheparin, provides significant protection to the regionally ischemic and reperfused canine myocardium independent of either plasma glycosaminoglycan concentration or alterations in the coagulation system.

The Effect Of Fibrinolysis In The Early Stage Of Acute Myocardial Infarction

1981 ◽  
Author(s):  
K Genth ◽  
J Frank ◽  
J Schaefer ◽  
V Korten ◽  
D Heene
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Infarct Size ◽  
Ventricular Function ◽  
Early Stage ◽  
Myocardial Infarct ◽  
Interventricular Septum ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Time To Peak

The influence of streptokinase (SK) on myocardial infarct size and left ventricular function after acute myocardial infarction was investigated. 21 patients with myocardial infarction received SK (SK-group), 27 patients underwent conventional therapy (C-group). In both groups therapy started within 8 hours after onset of chest pain. In the SK-group initially 250 000 IU were administered intravenously, followed by a maintenance dose of 100 000 IU/h, lasting 15 hours. Blood samples at 8 hours intervals were collected for 3 days for serial CPK-analysis to calculate infarct size (I=∫f(t)×dt×K×bw). M-mode echocardiography was taken before start of t her a py and after 15, 24, 48 and 72 hours. AOP and heart rate were recorded continuously. Infarct size was 47±12g in the SK-group and 84±25g in the C-group (p<0.05). The average time to peak blood CPK-activity was 24 hours in the SK-group and 40 hours in the C-group. Peak CPK-level was significantly higher (p<0.5) in the SK-group (841±160U/l) than in the C-group (532±13 8 U / l ) . In 16 patients of the SK-group short periods of ventricular tachycardia were recorded during the period of fibrinolysis. Before therapy all patients showed abnormal motion of the posterior left ventricular wall and/or the interventricular septum, detected by echocardiography. 14 patients showed after fibrinolysis an improved or normalized motion.The results indicate that early fibrinolysis may reopen the occluded coronary artery. Reperfusion of the ischemic perfusion area may salvage jeo pardized myocardium, therefore infarct size was reduced and ventricular function improved.

Isoflurane-induced preconditioning is attenuated by diabetes

2002 ◽  
Vol 282 (6) ◽  
pp. H2018-H2023 ◽  
Author(s):  
Katsuya Tanaka ◽  
Franz Kehl ◽  
Weidong Gu ◽  
John G. Krolikowski ◽  
Paul S. Pagel ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Area At Risk ◽  
End Tidal

Volatile anesthetics stimulate, but hyperglycemia attenuates, the activity of mitochondrial ATP-regulated K+ channels. We tested the hypothesis that diabetes mellitus interferes with isoflurane-induced preconditioning. Acutely instrumented, barbiturate-anesthetized dogs were randomly assigned to receive 0, 0.32, or 0.64% end-tidal concentrations of isoflurane in the absence or presence of diabetes (3 wk after administration of alloxan and streptozotocin) in six experimental groups. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium staining) was 29 ± 3% ( n = 8) of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 ± 2 and 13 ± 1% during 0.32 and 0.64% concentrations; n = 8 and 7 dogs, respectively). Diabetes alone did not alter infarct size (30 ± 3%; n = 8) but blocked the protective effects of 0.32% (27 ± 2%; n = 7) and not 0.64% isoflurane (18 ± 3%; n = 7). Infarct size was directly related to blood glucose concentrations in diabetic dogs, but this relationship was abolished by higher concentrations of isoflurane. The results indicate that blood glucose and end-tidal isoflurane concentrations are important determinants of infarct size during anesthetic-induced preconditioning.

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