Comparison of two sulfonylureas with high and low myocardial KATP channel affinity on myocardial infarct size and metabolism in a rat model of type 2 diabetes

Purpose Insulin-like growth factor-1 (IGF-1) has been associated with both protective and detrimental effects on the development of ischemic heart disease. The relationship between IGF-1 levels and major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients remains unclear. This study aimed to investigate the relationship between IGF-1 admission levels in hyperglycemic ACS patients and: (1) MACE over a 5 years follow-up, (2) type 2 diabetes at discharge, and (3) post-ACS myocardial infarct size and dysfunction. Methods This was a post hoc analysis of the BIOMArCS-2 randomized controlled trial. From July 2008 to February 2012, 276 ACS patients with admission plasma glucose level between 140 and 288 mg/dL were included. Records of the composite of all-cause mortality and recurrent non-fatal myocardial infarction were obtained during 5 years follow-up. Venous blood samples were collected on admission. IGF-1 was measured batchwise after study completion. Oral glucose tolerance test was performed to diagnose type 2 diabetes, whereas infarct size and left ventricular function were assessed by myocardial perfusion scintigraphy (MPS) imaging, 6 weeks post-ACS. Results Cumulative incidence of MACE was 24% at 5 years follow-up. IGF-1 was not independently associated with MACE (HR:1.00 (95%CI:0.99–1.00), p = 0.29). Seventy-eight patients (28%) had type 2 diabetes at discharge, and the highest quartile of IGF-1 levels was associated with the lowest incidence of diabetes (HR:0.40 (95%CI:0.17–0.95), p = 0.037). IGF-1 levels were not associated with post-ACS myocardial infarct size and dysfunction. Conclusions IGF-1 carries potential for predicting type 2 diabetes, rather than long-term cardiovascular outcomes and post-ACS myocardial infarct size and dysfunction, in hyperglycemic ACS patients.

Download Full-text

Vitamin E reduces myocardial infarct size in type 2 diabetes

The FASEB Journal ◽

10.1096/fasebj.20.5.a1153-c ◽

2006 ◽

Vol 20 (5) ◽

Author(s):

Grace Frances Davis‐Gorman ◽

Raoul Gonzales ◽

Zoe Cohen ◽

Paul F. McDonagh

Keyword(s):

Type 2 Diabetes ◽

Vitamin E ◽

Infarct Size ◽

Myocardial Infarct ◽

Myocardial Infarct Size

Download Full-text

Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus

World Journal of Diabetes ◽

10.4239/wjd.v9.i9.149 ◽

2018 ◽

Vol 9 (9) ◽

pp. 149-156 ◽

Cited By ~ 3

Author(s):

Vladislav A Zykov ◽

Taisiia P Tuchina ◽

Denis A Lebedev ◽

Irina B Krylova ◽

Alina Y Babenko ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Infarct Size ◽

Myocardial Infarct ◽

Myocardial Infarct Size ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Download Full-text

Functional capacity in a rat model of heart failure: impact of myocardial infarct size

Experimental Physiology ◽

10.1113/ep086076 ◽

2017 ◽

Vol 102 (11) ◽

pp. 1448-1458 ◽

Cited By ~ 4

Author(s):

Vítor Scotta Hentschke ◽

Lucas Capalonga ◽

Douglas Dalcin Rossato ◽

Júlia Luíza Perini ◽

Jadson Pereira Alves ◽

...

Keyword(s):

Heart Failure ◽

Infarct Size ◽

Functional Capacity ◽

Rat Model ◽

Myocardial Infarct ◽

Myocardial Infarct Size

Download Full-text

Abstract 17348: Necrostatin 7 Limits Myocardial Infarct Size and Reduces Cardiac Remodeling After Permanent Coronary Occlusion in Rats

Circulation ◽

10.1161/circ.130.suppl_2.17348 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Yuri Dmitriev ◽

Sarkis Minasian ◽

Anna Dracheva ◽

Andrey Karpov ◽

Svetlana Chefu ◽

...

Keyword(s):

Infarct Size ◽

Rat Model ◽

Coronary Occlusion ◽

Ventricular Remodeling ◽

Ischemia Reperfusion Injury ◽

Myocardial Infarct ◽

Ischemia Reperfusion ◽

Morphological Characteristics ◽

Left Ventricular ◽

Myocardial Infarct Size

Background: Reduction of irreversible myocardial ischemia-reperfusion injury (IRI) remains important. One of the promising strategies aimed at myocardial IRI alleviation is modulation of programmed cell death (PCD) pathways. PCD mode displaying morphological characteristics of necrosis, and amenable to pharmacological manipulation is referred to as necroptosis. Necroptosis inhibitor necrostatin-1 has been shown to exert cardio- and neuroprotective effects. In the present work, the effect of necrostatin-7 (Nec-7) on myocardial injury in the rat model of permanent coronary occlusion was studied. Methods: Male Wistar rats (n = 19) were anesthetized with pentobarbital. The animals were subjected to permanent coronary occlusion (PCO) and intraperitoneal (i.p.) Nec-7 administration 1 h prior to PCO at a dose of 14.5 mg/kg in dimethyl sulfoxide (DMSO) or DMSO alone at a dose of 3.1 g/kg. Control rats were treated with saline. Three weeks after PCO, serum levels of NT-proBNP were measured, and histological outcomes were assessed. The infarct size (IS, %) and infarct length (IL, mm) were analyzed morphometrically. Results: DMSO caused significant reduction in serum NT-proBNP level vs. Control (0.3 ± 0.19 vs. 0.5 ± 0.22 ng/ml, p = 0.001), while Nec-7 further decreased NT-proBNP level in comparison with DMSO (0.2 ± 0.14 ng/ml, p = 0.008 vs. DMSO). Compared with Control, DMSO reduced adverse left ventricular remodeling, as evidenced by reduction in IS (16.0 ± 2.92 and 12.9 ± 1.72%, p = 0.015) and IL (6.2 ± 0.89 and 3.8 ± 0.35 mm, p = 0.008). Nec-7 treatment resulted in additional reduction of both IS and IL vs. DMSO group (9.0 ± 4.91 % and 2.9 ± 1.62 mm, respectively; p = 0.013 and p = 0.011 vs. DMSO, respectively). Conclusion: Nec-7 has cardioprotective properties, reducing myocardial wall stress and myocardial remodeling in the rat model of myocardial infarction.

Download Full-text

Sarcolemmal and Mitochondrial Adenosine Triphosphate– dependent Potassium Channels

Anesthesiology ◽

10.1097/00000542-200006000-00033 ◽

2000 ◽

Vol 92 (6) ◽

pp. 1731-1739 ◽

Cited By ~ 98

Author(s):

Wolfgang G. Toller ◽

Eric R. Gross ◽

Judy R. Kersten ◽

Paul S. Pagel ◽

Garrett J. Gross ◽

...

Keyword(s):

At Risk ◽

Infarct Size ◽

Adenosine Triphosphate ◽

Katp Channel ◽

Myocardial Infarct ◽

Katp Channels ◽

Left Ventricular ◽

Myocardial Infarct Size ◽

Area At Risk ◽

Mitochondrial Katp Channels

Background Volatile anesthetic-induced preconditioning is mediated by adenosine triphosphate-dependent potassium (KATP) channels; however, the subcellular location of these channels is unknown. The authors tested the hypothesis that desflurane reduces experimental myocardial infarct size by activation of specific sarcolemmal and mitochondrial KATP channels. Methods Barbiturate-anesthetized dogs (n = 88) were acutely instrumented for measurement of aortic and left ventricular pressures. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle (0.9% saline) or the nonselective KATP channel antagonist glyburide (0.1 mg/kg intravenously) in the presence or absence of 1 minimum alveolar concentration desflurane. In four additional groups, dogs received 45-min intracoronary infusions of the selective sarcolemmal (HMR 1098; 1 microg. kg-1. min-1) or mitochondrial (5-hydroxydecanoate [5-HD]; 150 microg. kg-1. min-1) KATP channel antagonists in the presence or absence of desflurane. Myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively. Results Desflurane significantly (P < 0.05) decreased infarct size to 10 +/- 2% (mean +/- SEM) of the area at risk as compared with control experiments (25 +/- 3% of area at risk). This beneficial effect of desflurane was abolished by glyburide (25 +/- 2% of area at risk). Glyburide (24 +/- 2%), HMR 1098 (21 +/- 4%), and 5-HD (24 +/- 2% of area at risk) alone had no effects on myocardial infarct size. HMR 1098 and 5-HD abolished the protective effects of desflurane (19 +/- 3% and 22 +/- 2% of area at risk, respectively). Conclusion Desflurane reduces myocardial infarct size in vivo, and the results further suggest that both sarcolemmal and mitochondrial KATP channels could be involved.

Download Full-text