MTX Treatment Does Not Improve Outcome in Mice with AMI

Pharmacology ◽  
2020 ◽  
pp. 1-7
Author(s):  
Lisa Dannenberg ◽  
Kajetan Trojovsky ◽  
Aysel Ayhan ◽  
Carolin Helten ◽  
Saif Zako ◽  
...  
Keyword(s):  
Systolic Function ◽  
Structural Parameters ◽  
Wild Type ◽  
Cardiac Damage ◽  
Artery Ligation ◽  
Serum Amyloid P ◽  
Artery Disease ◽  
Cardiac Outcome ◽  
Amyloid P

<b><i>Background:</i></b> Targeting inflammation in patients with coronary artery disease and/or acute myocardial infarction (AMI) is a matter of debate. Methotrexate (MTX) is one of the most widely used immunosuppressants. Cardiovascular Inflammation Reduction Trial (CIRT) recently failed to demonstrate reduced cardiovascular events in MTX-treated patients. However, it is not known if long-term MTX treatment improves cardiac outcome in AMI. Therefore, in this study, we investigated the postischemic phase in MTX-treated mice undergoing AMI. <b><i>Methods:</i></b> Wild-type mice received MTX medication intraperitoneally for 2 weeks. Afterward, AMI was induced by transient left anterior ascending artery ligation. Postischemic cardiac damage after 24 h was assessed. <b><i>Results:</i></b> MTX treatment did not affect infarct size as compared to control (IS/AAR: Con 76.20% ± 12.37%/AAR vs. MTX 73.51 ± 11.72%/AAR, <i>p</i> = 0.64). Moreover, systolic function and structural parameters did not differ between groups (<sub>24h</sub>ejection fraction: Con 36.49 ± 3.23% vs. MTX 32.77 ± 2.29%, <i>p</i> = 0.41; <sub>24h</sub>LVID; d: Con 3.57 ± 0.17 mm vs. MTX 3.19 ± 0.13 mm, <i>p</i> = 0.14). Platelets were increased by MTX (Con 1,442 ± 69.20 × 10<sup>3</sup>/mm<sup>3</sup> vs. MTX 1,920 ± 68.68 × 10<sup>3</sup>/mm<sup>3</sup>, <i>p</i> &#x3c; 0.0001). White blood cell and RBC as well as rate of monocytes, granulocytes, lymphocytes, and serum amyloid P levels were equal. <b><i>Conclusion:</i></b> MTX medication did not improve postischemic cardiac damage in a murine model of AMI. Future trials are needed to identify and investigate other anti-inflammatory targets to improve cardiovascular outcome.

scholarly journals Impact of subclinical coronary artery disease on the clinical outcomes of carotid endarterectomy

2017 ◽  
Vol 126 (5) ◽  
pp. 1560-1565 ◽  
Author(s):  
Hyunwook Kwon ◽  
Dae Hyuk Moon ◽  
Youngjin Han ◽  
Jong-Young Lee ◽  
Sun U Kwon ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Clinical Outcomes ◽  
Primary Endpoint ◽  
Coronary Revascularization ◽  
Perioperative Period ◽  
Long Term Outcomes ◽  
Cardiac Damage ◽  
Artery Disease

OBJECTIVEControversy persists regarding the optimal management of subclinical coronary artery disease (CAD) prior to carotid endarterectomy (CEA) and the impact of CAD on clinical outcomes after CEA. This study aimed to evaluate the short-term surgical risks and long-term outcomes of patients with subclinical CAD who underwent CEA.METHODSThe authors performed a retrospective study of data from a prospective CEA registry. They analyzed a total of 702 cases involving patients without a history of CAD who received preoperative cardiac risk assessment by radionuclide myocardial perfusion imaging (MPI) and underwent CEA over a 10-year period. The management strategy (the necessity, sequence, and treatment modality of coronary revascularization and optimal perioperative medical treatment) was determined according to the presence, severity, and extent of CAD as determined by preoperative MPI and additional coronary computed tomography angiography and/or coronary angiography. Perioperative cardiac damage was defined on the basis of postoperative elevation of the blood level of cardiac troponin I (0.05–0.5 ng/ml) in the absence of myocardial ischemia. The primary endpoint was the composite of any stroke, myocardial infarction, or death during the perioperative period and all-cause mortality within 4 years of CEA. The associations between clinical outcomes after CEA and subclinical CAD were analyzed.RESULTSConcomitant subclinical CAD was observed in 81 patients (11.5%). These patients did have a higher incidence of perioperative cardiac damage (13.6% vs 0.5%, p < 0.01), but they had similar primary endpoint incidences during the perioperative period (2.5% vs.1.8%, p = 0.65) and similar estimated 4-year primary endpoint rates (13.6% vs 12.4%, p = 0.76) as the patients without subclinical CAD. Kaplan-Meier survival analysis showed that the 2 groups had similar rates of overall survival (p = 0.75).CONCLUSIONSPatients with subclinical CAD can undergo CEA with acceptable short- and long-term outcomes provided they receive selective coronary revascularization and optimal perioperative medical treatment.

scholarly journals Hydrogen Sulfide Treatment Improves Post-Infarct Remodeling and Long-Term Cardiac Function in CSE Knockout and Wild-Type Mice

2020 ◽  
Vol 21 (12) ◽  
pp. 4284 ◽  
Author(s):  
Leigh J. Ellmers ◽  
Evelyn M. Templeton ◽  
Anna P. Pilbrow ◽  
Chris Frampton ◽  
Isao Ishii ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Gene Deletion ◽  
Coronary Artery Ligation ◽  
Wild Type ◽  
Artery Ligation ◽  
Treatment Groups ◽  
Expression Of Genes

Hydrogen sulfide (H2S) is recognized as an endogenous gaseous signaling molecule generated by cystathionine γ-lyase (CSE) in cardiovascular tissues. H2S up-regulation has been shown to reduce ischemic injury, and H2S donors are cardioprotective in rodent models when administered concurrent with myocardial ischemia. We evaluated the potential utility of H2S therapy in ameliorating cardiac remodeling with administration delayed until 2 h post-infarction in mice with or without cystathionine γ-lyase gene deletion (CSE−/−). The slow-release H2S donor, GYY4137, was administered from 2 h after surgery and daily for 28 days following myocardial infarction (MI) induced by coronary artery ligation, comparing responses in CSE−/− with wild-type (WT) mice (n = 5–10/group/genotype). Measures of cardiac function and expression of key genes associated with cardiac hypertrophy, fibrosis, and apoptosis were documented in atria, ventricle, and kidney tissues. Post-MI GYY4137 administration reduced infarct area and restored cardiac function, accompanied by reduction of the elevated ventricular expression of genes mediating cardiac remodeling to near-normal levels. Few differences between WT and CSE−/− mice were observed, except CSE−/− mice had higher blood pressures, and higher atrial Mir21a expression across all treatment groups. These findings suggest endogenous CSE gene deletion does not substantially exacerbate the long-term response to MI. Moreover, the H2S donor GYY4137 administered after onset of MI preserves cardiac function and protects against adverse cardiac remodeling in both WT and CSE-deficient mice.

Abstract 2870: Influence Of The Vkorc1 And Cyp2c9 Genotypes On The Frequency Of Bleeding And Maintenance Warfarin Dose In Russian Population

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Ekaterina Kropacheva
Keyword(s):  
Prosthetic Heart Valve ◽  
Warfarin Dose ◽  
Female Gender ◽  
International Normalized Ratio ◽  
Bleeding Complications ◽  
Wild Type ◽  
Bleeding Events ◽  
Venous Thromboembolic ◽  
Artery Disease

Purpose: Warfarin (W) is a highly effective drug for prevention and treatment of arterial and venous thromboembolic disorders. Bleeding is the most important complication of the oral anticoagulation. We investigated the genetic predictors of the bleeding complications in patients on long-term adjusted-dose W therapy. Methods: The study included 86 pts (46 male), age 62,8±10,6(SD) years receiving long-term W therapy (international normalized ratio (INR) 2-3). The observation duration was from 1 month to 1 year. CYP2C9 (CYP2C9*2 and CYP2C9*3), VKORC1 G3673A genotypes were identified by the polymerize chain reaction. The indications for W therapy were: atrial fibrillation-83,7% (CHADS2 2±1,3);deep venous thrombosis-7%; LV thrombus-4,65%; prosthetic heart valve-4,65%. Arterial hypertension had 62% of pts, coronary artery disease (CAD)- 26%, congestive heart failure (NYHA II-IV)- 30%, previous ischemic stroke-12% and diabetes- 8%. Results: The frequency of VKORC1 GG, VKORC1 GA and VKORC1 AA were 31%, 55% and 14 %, respectively. The frequency of CYP2C9*1, CYP2C9*2 and CYP2C9*3 were 67,8%, 15,5% and 14,3%. 2 pts (2,4%) had CYP2C9*2/*3 genotype. The mean W daily dose was the highest in wild-type pts ( CYP2C9*1/*1 and VKORC1 GG genotypes together): 7±2,18 mg/day as compared with pts with only one: 5,1±1,85 mg/day (p=0,006) or combination of a VKORC1 and a CYP2C9 polymorphism: 3,4±1,37 mg/day (p=0,03). The carriers of the combination of VKORC1 and CYP2C9 polymorphism demonstrated higher frequency of the INR fluctuation (INR>3) as compared with wild-type pts: 81% vs 38% (p=0,03). Only the carriers of the combination of GA/AA and CYP2C9*3 genotypes had higher frequency of bleedings as compared with wild-type pts: 67% vs 12,5% (p=0,03), respectively. The possession of the VKORC1 AA and/or CYP2C9*3 genotypes, mean INR>2,5 during observation period, female gender and CAD were predictors of bleeding events according to the multivariate discriminant analysis (p<0,00001). Conclusions: The carriers of the combination of VKORC1 and CYP2C9 polymorphism required lower maintenance W dose and demonstrated more INR fluctuations. Only the carriers of the combination of VKORC1 GA/AA and CYP2C9*3 genotypes demonstrated more bleedings. The possession of VKORC1 AA and/or CYP2C9*3 genotypes was one of the predictors of bleeding events on W therapy.

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