Browsing by Subject "Myocardial Ischemia"

Now showing 1 - 5 of 5
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    Early severe coronary heart disease and ischemic heart failure in homozygous familial hypercholesterolemia: A case report
    (Wolters Kluwer Health, 2018-10) Kuang, Hongyu; Zhou, Xue; Li, Li; Yi, Qijian; Shou, Weinian; Lu, Tiewei; Pediatrics, School of Medicine
    RATIONALE: Familial hypercholesterolemia (FH) is a common inherited cause of coronary heart disease (CHD) and premature death in an early age. Nevertheless, an ischemic heart failure (IHF) associated with FH seems to be rare, and an early diagnosis and therapy could influence the prognosis. PATIENT CONCERNS: In this 13-year-old girl, multiple xanthomas began to develop from the first day of birth. Until June, 2017, she was admitted to our center due to edema, oliguria, and dyspnea during exertion, which was attributed to a recent respiratory infection. DIAGNOSIS: Homozygous FH (HoFH), CHD, and IHF. INTERVENTIONS: The patient has been treated with statin, ezetimibe, aspirin, and traditional heart failure (HF) medications. In addition, the beta-blocker was simultaneously administered. OUTCOMES: Genotypes of this proband indicated homozygous mutations of low-density lipoprotein receptor (LDLR) and some co-segregated mutations, such as von Willebrand factor (VWF) and fibroblast growth factor receptors. At 6-month follow-up, we found a decreased level of plasma lipid profile, in addition to a significant improvement in 6-minute walk distance and functional class. Echocardiography indicated nonsignificant improvements in the structure and function of the heart. LESSONS: This case report indicates that HoFH can lead to dramatically progressive endothelial damages and ventricular remodeling, severe atherosclerosis, even IHF. Genetic outcomes indicate IHF with HoFH could possibly result from LDLR mutations and some co-segregated mutations influencing endothelial function and cardiovascular remodeling. In a short-term follow-up, a combination of statins, ezetimibe, aspirin, and traditional HF agents is safe and effective for IHF with HoFH, and there is a need for further identification of drugs to ameliorate endothelial function and cardiovascular remodeling which may play an important role in long-term treatment.
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    Mechanisms to enhance cardiac regeneration
    (2004) Dowell, Joshua D.
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    Mechanisms Underlying Cardiovascular Benefits of Sodium Glucose Co-Transporter-2 Inhibitors: Myocardial Substrate or Sodium/Hydrogen Exchanger?
    (2020-01) Baker, Hana Elisabeth; Tune, Johnathan D.; Basile, David; Goodwill, Adam; Kowala, Mark; Mather, Kieren; Michael, Mervyn (Dod)
    Recent clinical outcome studies demonstrate that Sodium glucose cotransporter 2 inhibitors (SGLT2i) significantly reduce major adverse cardiovascular events and heart failure outcomes in subjects with type 2 diabetes mellitus. At present, several hypotheses have been proposed to explain the observed cardiovascular benefit of SGLT2i, however, the mechanisms responsible remain to be elucidated. This investigation tested the hypothesis that SGLT2i improves cardiac function and efficiency during acute, regional ischemia/reperfusion injury via preferential shifts in myocardial substrate selection and/or inhibition of cardiac sodium/hydrogen exchanger-1 (NHE-1). Our initial investigation evaluated the effects of 24 hour pretreatment of the SGLT2i canagliflozin on cardiac contractile function, substrate utilization, and efficiency before and during regional myocardial ischemia/reperfusion injury in healthy swine. At the onset of ischemia, canagliflozin increased left ventricular end diastolic and systolic volumes which returned to baseline with reperfusion. This increased end diastolic volume was directly associated with increased stroke volume and stroke work relative to controls during ischemia. Canagliflozin also increased cardiac work efficiency during ischemia relative to control swine. No differences in myocardial substrate uptake of glucose, lactate, fatty acids or ketones were detected between groups. In separate experiments using a longer 60 min coronary occlusion, canagliflozin significantly diminished myocardial infarct size. Subsequent studies investigated the effect of an acute administration (15-30 min pre-treatment) of canagliflozin and the NHE-1i cariporide on cardiac contractile function efficiency in response to myocardial ischemia/reperfusion injury. Similar to our initial studies, canagliflozin increased diastolic filling, stroke work and improved cardiac work efficiency relative to untreated control hearts during the ischemic period. In contrast, cariporide did not alter ventricular filling volume, cardiac output or work efficiency at any time point. Additional examination of AP-1 cells transfected with wild-type NHE-1 showed dose-dependent inhibition of NHE-1 activity by cariporide, while canagliflozin had minimal effect on overall activity. This investigation demonstrates that SGLT2i improves cardiac function and efficiency during acute, regional ischemia in healthy swine. However, the present data fail to support the hypothesis that these SGLT2i-mediated improvements involve either preferential alterations in myocardial substrate utilization or the inhibition of NHE-1 activity.
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    Metabolic Syndrome Impairs Notch Signaling and Promotes Apoptosis in Chronically Ischemic Myocardium
    (Elsevier, 2014-09) Elmadhun, Nassrene Y.; Sabe, Ashraf A.; Lassaletta, Antonio D.; Chu, Louis M.; Kondra, Katelyn; Sturek, Michael; Sellke, Frank W.; Department of Cellular & Integrative Physiology, IU School of Medicine
    Objective Impaired angiogenesis is a known consequence of metabolic syndrome (MetS), however, the mechanism is not fully understood. Recent studies have shown that the Notch signaling pathway is an integral component of cardiac angiogenesis. We tested in a clinically relevant swine model the effects of MetS on Notch and apoptosis signaling in chronically ischemic myocardium. Methods Ossabaw swine were fed either a regular diet (CTL, n=8) or a high-cholesterol diet (MetS, n=8) to induce MetS. An ameroid constrictor was placed to induce chronic myocardial ischemia. Eleven weeks later, animals underwent cardiac harvest of the ischemic myocardium. Results There was down-regulation of pro-angiogenesis proteins Notch2, Notch4, Jagged2, Ang1 and ENOS in the MetS group compared to CTL. There was also up-regulation of pro-apoptosis protein Caspase8, and down-regulation of anti-angiogenesis protein pFOX03, and pro-survival proteins pP38 and HSP90 in the MetS group. Cell death was increased in the MetS group compared to CTL. Both CTL and MetS groups had similar arteriolar count and capillary density, and Notch3 and Jagged1 were both similarly concentrated in the smooth muscle wall in both groups. Conclusions MetS in chronic myocardial ischemia significantly impairs Notch signaling by down regulating Notch receptors, ligands and pro-angiogenesis proteins. MetS also increases apoptosis signaling, decreases survival signaling and increases cell death in chronically ischemic myocardium. Although short-term angiogenesis appears unaffected in this model of early MetS, the molecular signals for angiogenesis are impaired, thus suggesting that inhibition of Notch signaling may underlie decreased angiogenesis in later stages of MetS.
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    Wall motion abnormalities with low-dose dobutamine predict a high risk of cardiac death in medically treated patients with ischemic cardiomyopathy
    (Wiley, 2009-07) Maskoun, Waddah; Mustafa, Nowwar; Mahenthiran, Jothiharan; Gradus‐Pizlo, Irmina; Kamalesh, Masoor; Feigenbaum, Harvey; Sawada, Stephen G.; Medicine, School of Medicine
    BACKGROUND: Severe and extensive coronary artery disease is the underlying cause of stress-induced wall motion abnormalities (SWMA) with low-dose (10 microg/kg/min) dobutamine suggesting that these abnormalities may identify those with poor outcome. HYPOTHESIS: We assessed the prognostic value of low-dose SWMA in medically treated patients with ischemic cardiomyopathy. METHODS: Low- and peak-dose dobutamine echocardiography was performed in 235 patients with ischemic cardiomyopathy (ejection fraction 31% +/- 8%) who were treated with medical therapy. The survival of patients with low-dose SWMA (n = 33) was compared with the survival of patients without ischemia (n = 85) and those with peak-dose SWMA (n = 117). RESULTS: There were 123 cardiac deaths (52%) during follow-up of 4.1 +/- 3.3 years. Multivariate predictors of cardiac death were age (p = 0.002, hazard ratio [HR]: 1.03), diabetes (p = 0.028, HR: 1.54), New York Heart Association (NYHA) class III, IV heart failure (p = 0.001, HR: 1.94), the presence of peak dose SWMA (p < 0.001, HR: 2.59), and low-dose SWMA (p = 0.005, HR: 2.28). Survival of patients without ischemia was significantly better than those with peak-dose SWMA (p < 0.0001) and those with low-dose SWMA (p = 0.001). The survival of patients with low-dose SWMA was the same as those with peak-dose SWMA (p = 0.89). CONCLUSIONS: Low-dose SWMA is an independent predictor of cardiac mortality in medically treated patients with ischemic cardiomyopathy. Patients with low-dose SWMA are at equivalent risk to those with peak-dose SWMA.