scholarly journals Cardiovascular Effects of Sodium Glucose Cotransporter-2 (SGLT-2) Inhibition in the Setting of Ischemia/Reperfusion Injury

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Sam Luebbe ◽  
Hana E. Baker ◽  
Kieren J. Mather ◽  
Adam G. Goodwill ◽  
Blake R. Simon ◽  
...  
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Myocardial Infarct ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Ischemia And Reperfusion Injury ◽  
Myocardial Ischemia And Reperfusion ◽  
Sodium Glucose Cotransporter ◽  
Regional Myocardial Ischemia ◽  
Domestic Swine

Background and Hypothesis: Recent evidence indicates that sodium glucose cotransporter-2 inhibitors (SGLT2i) significantly reduce the incidence of major adverse cardiovascular events in high risk patients. However, the specific effects of SGLT2i on the cardiovascular system remain poorly defined. This study was designed to test the hypothesis that SGLT2i improves cardiac function and mitigates myocardial infarct size following regional myocardial ischemia and reperfusion injury.  Experimental Design: Lean domestic swine received placebo (n=6) or canagliflozin (n=6; 300 mg PO) 24 hours prior to and the morning of an experiment. Hemodynamics, left ventricular pressure and volume were measured in open chest, swine at baseline, during a 60 min coronary occlusion, and during a 2-hour reperfusion period. The degree of myocardial infarction was assessed by staining with 1% tetrazolium.  Results: At the onset of ischemia, SGLT2i produced a significant parallel increase in both left ventricular end diastolic (85 ± 9 mL to 129 ± 10 mL; P < 0.05) and end systolic volumes (29 ± 8 mL to 78 ± 9 mL; P < 0.01). This increase in ventricular filling was associated with significant increases in stroke volume (P < 0.05) and stroke work (P < 0.05) relative to untreated controls swine during ischemia.  SGLT2i decreased infarct size from 9.4 [Symbol] 2.1% in control swine to 3.1 [Symbol] 0.98% in SGLT2i treated swine.  Conclusion: SGLT2 inhibitors significantly improve cardiac contractile function and mitigate myocardial infarct size following regional myocardial ischemia and reperfusion injury in domestic swine.

Abstract 20587: Myocyte-Specific Over-Expression of Hdac4 Promotes Myocardial Ischemia and Reperfusion Injury

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ling Zhang ◽  
Jian Feng Du ◽  
Yu Zhao ◽  
Ting C Zhao
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Left Ventricular ◽  
Heart Weight ◽  
Ischemia And Reperfusion ◽  
Wild Type ◽  
Ischemia And Reperfusion Injury ◽  
Myocardial Ischemia And Reperfusion ◽  
Over Expression

Background: Histone deacetylases (HDACs) have been recently demonstrated to play a critical role in modulating myocardial protection and cardiomyocyte survival. However, the specific HDAC in mediating myocardial ischemia/reperfusion injury is currently unknown. Objective: The goal of this study is sought to define whether cardiac specific over-expression of HDAC4 would exacerbate myocardial ischemia and reperfusion injury. Methods: We created myocyte-specific HDAC4 transgenic mice, in which cDNA encoding HDAC4 was cloned into an expression vector encoding alpha-myosine heavy chain (the α-MHC promoter). Langendorff isovolumetrically perfused hearts from wild type (WT) control (n=5) and α-MHC-HDAC4 mice (n=5) were subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Infarct size was measured by triphenyl tetrazolium chloride staining. HDAC4 protein and activity in myocardium were determined. Results: The HDAC4 protein levels in the hearts of α-MHC-HDAC4 mice were significantly higher than those of control wild type. HDAC activity was elevated in MHC-HDAC4 mice as compared with wild type mice. In adult mice, there was no significant difference in the heart weight-body weight ratio between α-MHC-HDAC and wild-type mice. As compared to wild type mice, myocyte-specific over-expression of HDAC4 resulted in an elevation of left ventricular end-diastolic pressure (LVEDP) and reduction in the recovery of rate and pressure products (RPP) at the end of reperfusion. Furthermore, over-expression of HDAC4 increased myocardial infarct size as compared to wild type mice. Conclusions: These findings indicate that specific over-expression of HDAC4 exacerbates myocardial ischemia and reperfusion injury.

Sevoflurane Reduces Myocardial Infarct Size and Decreases the Time Threshold for Ischemic Preconditioning in Dogs 

1999 ◽  
Vol 91 (5) ◽  
pp. 1437-1437 ◽  
Author(s):  
Wolfgang G. Toller ◽  
Judy R. Kersten ◽  
Paul S. Pagel ◽  
Douglas A. Hettrick ◽  
David C. Warltier
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Myocardial Infarct ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia And Reperfusion ◽  
Time Threshold

Background Recent evidence indicates that volatile anesthetics exert protective effects during myocardial ischemia and reperfusion. The authors tested the hypothesis that sevoflurane decreases myocardial infarct size by activating adenosine triphosphate-sensitive potassium (K(ATP)) channels and reduces the time threshold of ischemic preconditioning necessary to protect against infarction. Methods Barbiturate-anesthetized dogs (n = 75) were instrumented for measurement of aortic and left ventricular pressures and maximum rate of increase of left ventricular pressure and were subjected to a 60-min left anterior descending (LAD) coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle or the K(ATP) channel antagonist glyburide (0.1 mg/kg intravenously), and 1 minimum alveolar concentration sevoflurane (administered until immediately before coronary artery occlusion) in the presence or absence of glyburide. In three additional experimental groups, sevoflurane was discontinued 30 min (memory) before the 60-min LAD occlusion or a 2-min LAD occlusion as an ischemic preconditioning stimulus was used with or without subsequent sevoflurane (with memory) pretreatment. Regional myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively. Results Vehicle (23 +/- 1% of the area at risk; mean +/- SEM) and glyburide (23 +/- 2%) alone produced equivalent effects on myocardial infarct size. Sevoflurane significantly (P &lt; 0.05) decreased infarct size (13 +/- 2%). This beneficial effect was abolished by glyburide (21 +/- 3%). Neither the 2-min LAD occlusion nor sevoflurane followed by 30 min of memory were protective alone, but together, sevoflurane enhanced the effects of the brief ischemic stimulus and profoundly reduced infarct size (9 +/- 2%). Conclusion Sevoflurane reduces myocardial infarct size by activating K(ATP) channels and reduces the time threshold for ischemic preconditioning independent of hemodynamic effects in vivo.

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 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.

Inability of Left Ventricular Decompression to Limit Myocardial Infarct Size

1993 ◽  
pp. 266-266
Author(s):  
Donna M. Van Winkle ◽  
James M. Downey
Keyword(s):  
Infarct Size ◽  
Myocardial Infarct ◽  
Left Ventricular ◽  
Myocardial Infarct Size

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.

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