scholarly journals Dose-dependent Effects of Esmolol-epinephrine Combination Therapy in Myocardial Ischemia and Reperfusion Injury

2019 ◽  
Vol 25 (19) ◽  
pp. 2199-2206 ◽  
Author(s):  
Yoshimasa Oyama ◽  
Justin Blaskowsky ◽  
Tobias Eckle
Keyword(s):  
Myocardial Ischemia ◽  
Combination Therapy ◽  
Infarct Size ◽  
Troponin I ◽  
Myocardial Dysfunction ◽  
Ischemia And Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Area At Risk ◽  
Myocardial Ischemia And Reperfusion ◽  
Arterial Blood

Background: Animal studies on cardiac arrest found that a combination of epinephrine with esmolol attenuates post-resuscitation myocardial dysfunction. Based on these findings, we hypothesized that esmololepinephrine combination therapy would be superior to a reported cardioprotective esmolol therapy alone in a mouse model of myocardial ischemia and reperfusion (IR) injury. Methods: C57BL/6J mice were subjected to 60 min of myocardial ischemia and 120 min of reperfusion. Mice received either saline, esmolol (0.4 mg/kg/h), epinephrine (0.05 mg/kg/h), or esmolol combined with epinephrine (esmolol: 0.4 mg/kg/h or 0.8 mg/kg/h and epinephrine: 0.05 mg/kg/h) during reperfusion. After reperfusion, infarct sizes in the area-at-risk and serum cardiac troponin-I levels were determined. Hemodynamic effects of drugs infused were determined by measurements of heart rate (HR) and mean arterial blood pressure (MAP) via a carotid artery catheter. Results: Esmolol during reperfusion resulted in robust cardioprotection (esmolol vs. saline: 24.3±8% vs. 40.6±3% infarct size), which was abolished by epinephrine co-administration (38.1±15% infarct size). Increasing the esmolol dose, however, was able to restore esmolol-cardioprotection in the epinephrine-esmolol (18.6±8% infarct size) co-treatment group with improved hemodynamics compared to the esmolol group (epinephrine-esmolol vs. esmolol: MAP 80 vs. 75 mmHg, HR 452 vs. 402 beats/min). Conclusion: These results confirm earlier studies on esmolol-cardioprotection from myocardial IR-injury and demonstrate that a dose optimized epinephrine-esmolol co-treatment maintains esmolol-cardioprotection with improved hemodynamics compared to esmolol treatment alone. These findings might have implications for current clinical practice in hemodynamically unstable patients suffering from myocardial ischemia.

Medroxyprogesterone acetate prevents the cardioprotective and anti-inflammatory effects of 17β-estradiol in an in vivo model of myocardial ischemia and reperfusion

2007 ◽  
Vol 293 (3) ◽  
pp. H1408-H1415 ◽  
Author(s):  
Erin A. Booth ◽  
Benedict R. Lucchesi
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Medroxyprogesterone Acetate ◽  
Troponin I ◽  
Hormone Replacement ◽  
In Vivo Model ◽  
Ischemia And Reperfusion ◽  
Area At Risk ◽  
Myocardial Ischemia And Reperfusion ◽  
17Β Estradiol

Previous studies demonstrated the protective effects of estrogen administration in models of cardiovascular disease. However, there is a discrepancy between these data and those from the recent clinical trials with hormone replacement therapy in menopausal women. One possible explanation for the divergent results is the addition of progestin to the hormone regimen in the Women's Health Initiative and the Heart and Estrogen/Progestin Replacement Study trials. The aim of the present study was to examine the effects of a combination of 17β-estradiol (E2, 20 μg) and medroxyprogesterone acetate (MPA, 80 μg) on infarct size in New Zealand White rabbits. Infarct size as a percentage of the area at risk was significantly reduced by administration of E2 30 min before induction of myocardial ischemia compared with vehicle (19.5 ± 3.1 vs. 55.7 ± 2.6%, P < 0.001). However, E2 + MPA failed to elicit a reduction in infarct size (52.5 ± 4.6%), and MPA had no effect (50.8 ± 2.6%). E2 also reduced serum levels of cardiac troponin I, immune complex deposition in myocardial tissue, activation of the complement system, and lipid peroxidation. All these effects were reversed by MPA. The results suggest that MPA antagonizes the infarct-sparing effects of E2, possibly through modulation of the immune response after ischemia and reperfusion.

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.

scholarly journals The Circadian PER2 Enhancer Nobiletin Reverses the Deleterious Effects of Midazolam in Myocardial Ischemia and Reperfusion Injury

2018 ◽  
Vol 24 (28) ◽  
pp. 3376-3383 ◽  
Author(s):  
Yoshimasa Oyama ◽  
Colleen Marie Bartman ◽  
Jennifer Gile ◽  
Daniel Sehrt ◽  
Tobias Eckle
Keyword(s):  
Myocardial Ischemia ◽  
Troponin I ◽  
Serum Levels ◽  
Underlying Mechanism ◽  
Treated Group ◽  
Ischemia And Reperfusion ◽  
Mrna Levels ◽  
Ischemia And Reperfusion Injury ◽  
Myocardial Ischemia And Reperfusion ◽  
Period 2

Background: Recently, we identified the circadian rhythm protein Period 2 (PER2) in robust cardioprotection from myocardial ischemia (MI). Based on findings that perioperative MI is the most common major cardiovascular complication and that anesthetics can alter the expression of PER2, we hypothesized that an anesthesia mediated downregulation of PER2 could be detrimental if myocardial ischemia and reperfusion (IR) would occur. Methods: and Results: We exposed mice to pentobarbital, fentanyl, ketamine, propofol, midazolam or isoflurane and determined cardiac Per2 mRNA levels. Unexpectedly, only midazolam treatment resulted in an immediate and significant downregulation of Per2 transcript levels. Subsequent studies in mice pretreated with midazolam using an in-situ mouse model for myocardial (IR)-injury revealed a significant and dramatic increase in infarct sizes or Troponin-I serum levels in the midazolam treated group when compared to controls. Using the recently identified flavonoid, nobiletin, as a PER2 enhancer completely abolished the deleterious effects of midazolam during myocardial IR-injury. Moreover, nobiletin treatment alone significantly reduced infarct sizes or Troponin I levels in wildtype but not in Per2-/- mice. Pharmacological studies on nobiletin like flavonoids revealed that only nobiletin and tangeritin, both found to enhance PER2, were cardioprotective in our murine model for myocardial IR-injury. Conclusion: We identified midazolam mediated downregulation of cardiac PER2 as an underlying mechanism for a deleterious effect of midazolam pretreatment in myocardial IR-injury. These findings highlight PER2 as a cardioprotective mechanism and suggest the PER2 enhancers nobiletin or tangeritin as a preventative therapy for myocardial IR-injury in the perioperative setting where midazolam pretreatment occurs frequently.

Isoflurane Produces Delayed Preconditioning against Myocardial Ischemia and Reperfusion Injury

2004 ◽  
Vol 100 (3) ◽  
pp. 525-531 ◽  
Author(s):  
Katsuya Tanaka ◽  
Lynda M. Ludwig ◽  
John G. Krolikowski ◽  
Dunbar Alcindor ◽  
Phillip F. Pratt ◽  
...  
Keyword(s):  
Single Dose ◽  
Myocardial Ischemia ◽  
Protein Expression ◽  
Infarct Size ◽  
Coronary Occlusion ◽  
Ischemia And Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Myocardial Ischemia And Reperfusion ◽  
Cox 2 ◽  
Cox 1

Background Whether volatile anesthetics produce a second window of preconditioning is unclear. The authors tested the hypothesis that isoflurane causes delayed preconditioning against infarction and, further, that cyclooxygenase (COX)-2 mediates this beneficial effect. Methods Rabbits (n = 43) were randomly assigned to receive 0.9% intravenous saline, the selective COX-2 inhibitor celecoxib (3 mg/kg intraperitoneal) five times over 2 days before coronary artery occlusion and reperfusion, or isoflurane (1.0 minimum alveolar concentration) 24 h before acute experimentation in the absence or presence of celecoxib pretreatment. Two additional groups of rabbits received a single dose of celecoxib either 30 min before or 21.5 h after administration of isoflurane. Rabbits were then instrumented for measurement of hemodynamics and underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Myocardial infarct size was measured using triphenyltetrazolium staining. Western immunoblotting to examine COX-1 and COX-2 protein expression was performed in rabbit hearts that had or had not been exposed to isoflurane. Results Isoflurane significantly (P &lt; 0.05) reduced infarct size (22 +/- 3% of the left ventricular area at risk) as compared with control (39 +/- 2%). Celecoxib alone had no effect on infarct size (36 +/- 4%) but abolished isoflurane-induced cardioprotection (36 +/- 4%). A single dose of celecoxib administered 2.5 h before coronary occlusion and reperfusion also abolished the delayed protective effects of isoflurane (36 +/- 4%), but celecoxib given 30 min before exposure to isoflurane had no effect (22 +/- 4%). Isoflurane did not alter COX-1 and COX-2 protein expression. Conclusions The results indicate that the volatile anesthetic isoflurane produces a second window of preconditioning against myocardial ischemia and reperfusion injury. Furthermore, COX-2 is an important mediator of isoflurane-induced delayed preconditioning.

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