Calpain inhibition decreases oxidative stress via mitochondrial regulation in a swine model of chronic myocardial ischemia.

Introduction: Calpain overexpression is implicated in mitochondrial damage leading to tissue oxidative stress and myocardial ischemic injury. The aim of this study was to determine the effects of calpain inhibition (CI) on mitochondrial impairment and oxidative stress in a swine model of chronic myocardial ischemia and metabolic syndrome.

Methods: Yorkshire swine were fed a high-fat diet for 4 weeks to induce metabolic syndrome then underwent placement of an ameroid constrictor to the left circumflex artery.

Extracellular vesicle therapy attenuates antiangiogenic signaling in ischemic myocardium of swine with metabolic syndrome.

Objective: Our recent studies using a porcine model of metabolic syndrome (MS) and chronic myocardial ischemia show that extracellular vesicle (EV) therapy improves blood flow and arteriogenesis in ischemic myocardium, although mechanisms of these changes are unclear. We hypothesized that in the setting of MS, EV therapy would decrease antiangiogenic signaling to mediate increased blood flow to chronically ischemic myocardium.

Methods: Yorkshire swine were fed a high-fat diet for 4 weeks to induce MS, then underwent placement of an ameroid constrictor to the left circumflex artery to induce chronic myocardial ischemia.

Extracellular vesicles modulate inflammatory signaling in chronically ischemic myocardium of swine with metabolic syndrome.

Objective: Extracellular vesicle (EV) therapy has been shown to mitigate inflammation in animal models of acute myocardial ischemia/reperfusion. This study evaluates the effect of EV therapy on inflammatory signaling in a porcine model of chronic myocardial ischemia and metabolic syndrome.

Methods: Yorkshire swine were fed a high-cholesterol diet for 4 weeks to induce metabolic syndrome, then underwent placement of an ameroid constrictor to the left circumflex artery to induce chronic myocardial ischemia.

Glycemic control is not associated with neurocognitive decline after cardiac surgery.

Background: Whether perioperative glycemic control is associated with neurocognitive decline (NCD) after cardiac surgery was examined.

Methods: Thirty patients undergoing cardiac surgery utilizing cardiopulmonary bypass (CPB) were screened for NCD preoperatively and on postoperative day 4 (POD4). Indices of glucose control were examined.

Effects of High Fat Versus Normal Diet on Extracellular Vesicle-Induced Angiogenesis in a Swine Model of Chronic Myocardial Ischemia.

Background Mesenchymal stem cell-derived extracellular vesicles (EVs) promote angiogenesis in the ischemic myocardium. This study examines the difference in vascular density, myocardial perfusion, molecular signaling, and gene expression between normal diet (ND) and high fat diet (HFD) groups at baseline and following intramyocardial injection of EVs. Methods and Results Intact male Yorkshire swine fed either an ND (n=17) or HFD (n=14) underwent placement of an ameroid constrictor on the left circumflex coronary artery.

Intravenous injection of extracellular vesicles to treat chronic myocardial ischemia.

Background: Mesenchymal stem cell-derived extracellular vesicles (EVs) appear to be a very exciting treatment option for heart disease. Here, we used a swine model of chronic myocardial ischemia to evaluate the efficacy of a less-invasive method of injection of EVs via a peripheral intravenous route.

Methods: Sixteen Yorkshire swine underwent placement of an ameroid constrictor on the left circumflex (LCx) artery at age 11 weeks to induce chronic myocardial ischemia.

Lower preoperative hematocrit, longer hospital stay, and neurocognitive decline after cardiac surgery.

Background: Cardiopulmonary bypass may be associated with postoperative neurocognitive dysfunction; however, risk factors have not been clearly identified. We hypothesize that lower hematocrit levels are correlated with postoperative neurocognitive dysfunction.

Methods: A total of 30 patients underwent cardiac operations utilizing cardiopulmonary bypass and screening for neurocognitive dysfunction preoperatively and on postoperative day 4.

Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome.

Background Ischemic heart disease continues to be a leading cause of mortality in patients. Extracellular vesicles (EVs) provide a potential for treatment that may induce collateral vessel growth to increase myocardial perfusion. Methods and Results Nineteen male Yorkshire pigs were given a high-fat diet for 4 weeks, then underwent placement of an ameroid constrictor on the left circumflex artery to induce chronic myocardial ischemia.

Increased coronary arteriolar contraction to serotonin in juvenile pigs with metabolic syndrome.

Metabolic syndrome (MetS) is associated with alterations in coronary vascular smooth muscle and endothelial function. The current study examined the contractile response of the isolated coronary arterioles to serotonin in pigs with and without MetS and investigated the signaling pathways responsible for serotonin-induced vasomotor tone. The MetS pigs (8-weeks old) were fed with a hyper-caloric, fat/cholesterol diet and the control animals (lean) were fed with a regular diet for 12 weeks (n = 6/group).

Impaired coronary contraction to phenylephrine after cardioplegic arrest in diabetic patients.

Background: We have previously found that hyperkalemic cardioplegic arrest in the setting of cardiopulmonary bypass (CP/CPB) is associated with impairment of the coronary arteriolar response to phenylephrine in nondiabetic (ND) patients. We hypothesized that diabetes may alter coronary arteriolar response to alpha-1 adrenergic agonist in the setting of CP/CPB. In this study, we further investigated the effects of diabetes on the altered coronary arteriolar response to phenylephrine in patients undergoing cardiac surgery.

Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia.

Background: Mesenchymal stem cell-derived extracellular vesicles (EVs) are believed to be cardioprotective in myocardial infarct. The objective of this study was to examine the effects of human mesenchymal cell-derived EV injection on cardiac function, myocardial blood flow, and vessel density in the setting of chronic myocardial ischemia.

Methods And Results: Twenty-three Yorkshire swine underwent placement of an ameroid constrictor on their left circumflex artery.

Decreased contractile response of peripheral arterioles to serotonin after CPB in patients with diabetes.

Background: Regulation of coronary vasomotor tone by serotonin is significantly changed after cardioplegic arrest and reperfusion. The current study investigates whether cardiopulmonary bypass may also affect peripheral arteriolar response to serotonin in patients with or without diabetes.

Methods: Human peripheral microvessels (90-180 µm diameter) were dissected from harvested skeletal muscle tissues from diabetic and non-diabetic patients before and after cardiopulmonary bypass and cardiac surgery (n = 8/group).

Continuous Glucose Monitoring in the Cardiac ICU: Current Use and Future Directions.

Perioperative glucose control is highly important, particularly for patients undergoing cardiac surgery. Variable glucose levels before, during and after cardiac surgery lead to increased post-operative complications and patient mortality. [1] Current methods for intensive monitoring and treating hyperglycemia in the Intensive Care Unit (ICU) usually involve hourly glucose monitoring and continuous intravenous insulin infusions.

Glycogen synthase kinase 3β inhibition reduces mitochondrial oxidative stress in chronic myocardial ischemia.

Objectives: Glycogen synthase kinase 3β (GSK-3β) inhibition has been reported to increase microvascular density and improve myocardial blood flow in a porcine model of chronic myocardial ischemia and metabolic syndrome. Inhibition of GSK-3β can also be cardioprotective by modulating fibrosis signaling and mitochondrial-induced apoptosis. We hypothesized GSK-3β inhibition would have a beneficial effect on myocardial fibrosis and oxidative stress in a porcine model of chronic myocardial ischemia and metabolic syndrome.

Diabetes and Cardioplegia.

Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is associated with injury to the vasculature and microcirculation leading to coronary microvascular dysfunction, permeability changes and cardiac dysfunction. In the setting of cardiopulmonary bypass with cardioplegia, poorly-controlled diabetes is associated with significant changes in endothelium-dependent and independent vascular dysfunction, vascular reactivity, vascular permeability, protein expression, cell death, coronary/peripheral microcirculation and reduced vasomotor tone leading to hypotension and impaired endothelial function. The gene expression profiles after cardiopulmonary bypass with cardioplegic arrest is quantitatively and qualitatively different in patients with diabetes.

Alcohol attenuates myocardial ischemic injury.

Background: Moderate alcohol consumption is cardioprotective but the mechanism of action remains unclear. Nuclear factor κ-B regulates the expression of genes involved in inflammation, stress, and apoptosis. We used a swine model of diet-induced metabolic syndrome to investigate the effects of red wine and vodka on nuclear factor κ-B signaling and cytokine activity in chronically ischemic myocardium.

Lessons Learned From an Untreated "Benign" Thoracic Tumor.

We describe a patient with Doege-Potter syndrome (solitary fibrous tumor of the pleura presenting with hypoglycemia) and illustrate several important lessons learned from the case. Seven years after the initial diagnosis, the tumor showed significant growth and developed a high-grade undifferentiated component. Solitary fibrous tumors do grow and cannot be deemed benign.

Distinguishing persistent insulin autoantibodies with differential risk: nonradioactive bivalent proinsulin/insulin autoantibody assay.

A subset of children develops persistent insulin autoantibodies (IAA; almost always as the only islet autoantibody) without evidence of progression to diabetes. The aim of the current study was the development and characterization of the performance of a nonradioactive fluid phase IAA assay in relation to standard IAA radioassay. We developed a nonradioactive IAA assay where bivalent IAA cross-link two insulin moieties in a fluid phase.

Use of CoZmonitor in youth with type 1 diabetes.

Background: The purpose of this study was to evaluate the effectiveness of directly integrating self-monitoring blood glucose (BG) information with insulin pump therapy on overall glycemic control.

Methods: In this randomized trial, 34 youth with type 1 diabetes using insulin pump therapy were trained on the use of the Deltec Cozmo Insulin Pump. Seventeen were randomized to use the CoZmonitor Blood Glucose Module, a device that attaches to the back of the pump using FreeStyle technology to perform BG tests which read directly on the pump screen.

Improved glycemic control after long-term insulin pump use in pediatric patients with type 1 diabetes.

Background: There are currently few data available on the long-term use of continuous subcutaneous insulin infusion (CSII) (insulin pump) therapy in children.

Methods: Charts from 291 youth with type 1 diabetes (T1D) who were treated with CSII therapy for at least 1 year were reviewed. Data analysis included hemoglobin A(1c)(HbA(1c)) values, body mass index (BMI) values, and the occurrence of severe hypoglycemia (SH) or diabetic ketoacidosis (DKA) events.

Missed insulin meal boluses and elevated hemoglobin A1c levels in children receiving insulin pump therapy.

Objective: To identify possible causes of suboptimal glycemic control (ascertained by hemoglobin A1c [HbA1c] level) in youths using insulin pump therapy.

Methods: Forty-eight youths who were receiving insulin pump therapy for > or =6 months, and who were using insulin pumps and blood glucose meters with data that could be downloaded at our facility, are included in this cross-sectional study. Possible causes of suboptimal glycemic control were evaluated by using 4 information sources: 1) insulin pump data downloads; 2) glucose meter data downloads; 3) patient/family questionnaire about insulin bolusing habits, eating habits, exercise, and blood glucose testing habits; and 4) a physician questionnaire.