Andrew L. Rivard

Administration of Tauroursodeoxycholic Acid (TUDCA) reduces apoptosis following myocardial infarction in rat

Black bear bile has been used in traditional Chinese medicine to treat liver and eye related illnesses for centuries. A major constituent of bile is ursodeoxycholic acid (UDCA). Recent analysis of the cellular effects of UDCA and its taurine conjugate tauroursodeoxycholic acid (TUDCA) have demonstrated their antiapoptotic properties through regulation of Bcl-2 family and survival signaling proteins (Bax, Bad, phosphatidylinositol-3-kinase). In this study, we tested the hypothesis that TUDCA administered to rats prior to a myocardial infarction (MI) would exhibit anti-apoptotic effects and improve cardiac function. Prior to ligation of the left anterior descending (LAD) coronary artery, TUDCA (50 mg/ml, 400 mg/kg, IV) or PBS was administered to rats. Animals were sacrificed 24 hours after ligation for terminal transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) and caspase-3 activity to assess apoptosis. Additional TUDCA or PBS treated rats underwent pre-operative,1 and 4 week transthoracic ultrasounds to assess heart function by quantification of shortening fraction (SF) and infarct area. TUNEL labeling of the cardiac tissue revealed a significant reduction in apoptotic cells in rats given TUDCA prior to ischemic injury (p = 0.05). In support of reducing apoptosis, caspase-3 activity in the TUDCA treated animals also decreased (p = 0.02). By 4 weeks, a significantly smaller infarct area was present in the TUDCA group compared to the PBS group (0.05 vs. 0.13 cm(2), p = NS) and there was also an improvement in SF. The results provide evidence for TUDCA as a viable treatment for reducing apoptosis in a model of myocardial infarction. Additional studies will distinguish the functional result of improved cell survival following infarction, suggesting the potential for clinical application of this anti-apoptotic drug in treatment of acute MI.

Rat intubation and ventilation for surgical research.

Effective outcomes in cardiothoracic surgical research using rodents are dependent upon adequate techniques for intubation and mechanical ventilation. Multiple methods are available for intubation of the rat; however, not all techniques are appropriate for survival studies. This article presents a refinement of intubation techniques and a simplified mechanical ventilation setup necessary for intrathoracic surgical procedures using volatile anesthetics. The procedure is defined and complications of the procedure are elucidated that provide a justification for animal numbers needed for initiating new studies. Lewis rats weighing 178–400 g (287 ± 44) were anesthetized using Enflurane and intubated with a 16-G angiocatheter using transillumination. Mechanical ventilation (85 bpm, 2.5 mL TV, enflurane 1.5–2%) maintained adequate sedation for completion of an intrathoracic procedure. Complications of the intubation and ventilation included mortality from anesthetic overdose, intubation difficulty, pneumothorax, traumatic extubation, and ventilation disconnection. Anesthetic agents and their related effects on the rat heart and reflexes are compared. This article also underscores the importance of refinement, reduction, and replacement in the context of cardiothoracic surgery using rodent models.

Achievement of feeding milestones after primary repair of long-gap esophageal atresia.

OBJECTIVES To determine the pattern of feeding milestones following primary repair of long-gap esophageal atresia (EA). METHOD A questionnaire based upon well established feeding milestones was used. Children after long-gap EA repair, n=40, were compared from after primary repair to healthy children from birth, n=102. RESULTS The age when surveyed of the EA group and controls was different: 6.2+/-4.7 (mean+/-standard deviation) years, range 1.1-20.9, versus 2.5+/-2.4 years, range 0.0-12.1, p=0.00. The esophageal gap length in the EA group was 5.1+/-1.2 cm and age at repair was 5.5+/-5.0 months. There was no statistically significant difference between the atresia group and controls for feeding milestones; Self feeding finger foods approached significance. There was, however, greater variability in the timing of milestones in the atresia group compared to controls. Feeding milestones were negatively correlated with age at primary repair: drinking with a covered sippy cup, rho=-0.51, p=0.01 and self feeding finger foods, rho=-0.36, p=0.04 were statistically significant. Drinking from a cup correlated with gestational age, rho=0.38, p=0.04, and negatively correlated to esophageal gap length, rho=-0.45, p=0.01. CONCLUSIONS Despite delayed onset of feeding, major milestones after EA repair occurred in similar pattern to normal infants. An early referral for primary repair is beneficial for earlier acquisition of milestones for infants with long-gap EA.

Sodium polystyrene sulfonate used to reduce the potassium content of a high-protein enteral formula: a quantitative analysis

BACKGROUND Sodium polystyrene sulfonate (Kayexalate) commonly is used in treating hyperkalemia. As a cation exchange resin, it also can be used to reduce the potassium content of enteral nutrition formulas. This study evaluates the use of Kayexalate to reduce potassium in one high-protein enteral formula and describes the quantitative analysis of the product. METHODS Sodium polystyrene sulfonate and enteral formula were mixed into a slurry and allowed to settle, and then the supernatant was decanted off and tested as samples. Three sample concentrations were analyzed: a control not subjected to potassium reduction, 0.5 g of Kayexalate per mEq K+ sample, and a 1 g/mEq K+ sample. Of these samples, moisture, lipid, protein, carbohydrate, ash, and mineral content were obtained. RESULTS Compared with the control, the percentage decrease of potassium ranged from 25% to 36%, depending on the concentration of Kayexalate. A significant increase of 324% in sodium concentration was found in the 1.0 g/mEq K+ sample. Although there was no change in magnesium content, a slight increase in phosphorus, iron, and zinc was evident. CONCLUSIONS The treatment of an enteral formula with sodium polystyrene sulfonate significantly increases its sodium content, with a modest decrease in potassium content. Clinicians using this method in clinical practice should be aware of the increase in sodium content.

Porcine endothelial cells and iliac arteries transduced with AdenoIL-4 are intrinsically protected, through Akt activation, against immediate injury caused by human complement.

Vascular endothelial cells (ECs) can be injured in a variety of pathologic processes that involve activated complement. We reported previously that porcine ECs incubated with exogenous IL-4 or IL-13 are protected from cytotoxicity by human complement and also from apoptosis by TNF-α. The resistance to complement consists of an intrinsic mechanism that is lost a few days after cytokine removal. In our current study, we investigated whether transfer of the IL-4 gene into porcine ECs in vitro and into porcine vascular tissues in vivo would induce efficient and durable protection from human complement. We found that ECs transduced with adenoIL-4 or adenoIL-13 exhibited continuous production of the cytokine and prolonged protection from complement-mediated killing. IL-4 also protected ECs from activation: ECs incubated with IL-4 did not develop cell retraction and intercellular gaps upon stimulation with sublytic complement. The endothelium and subendothelium of pig iliac arteries that were transduced with the IL-4 gene were effectively protected from complement-dependent immediate injury after perfusion with human blood. However, after similar perfusion, the endothelium was immediately lost from arteries that were transduced with a control adenovirus. The protection was not due to up-regulation of the complement regulators decay accelerating factor, membrane cofactor protein, and CD59, or to reduced complement activation, but required the participation of Akt. Although our studies model protection in pig-to-primate xenotransplantation, our findings of IL-4 induction of Akt-mediated protection may be more broadly applicable to EC injury as manifested in ischemia-reperfusion, allotransplantation, and various vascular diseases.

Medical three-dimensional printing opens up new opportunities in cardiology and cardiac surgery

Advanced percutaneous and surgical procedures in structural and congenital heart disease require precise pre-procedural planning and continuous quality control. Although current imaging modalities and post-processing software assists with peri-procedural guidance, their capabilities for spatial conceptualization remain limited in two- and three-dimensional representations. In contrast, 3D printing offers not only improved visualization for procedural planning, but provides substantial information on the accuracy of surgical reconstruction and device implantations. Peri-procedural 3D printing has the potential to set standards of quality assurance and individualized healthcare in cardiovascular medicine and surgery. Nowadays, a variety of clinical applications are available showing how accurate 3D computer reformatting and physical 3D printouts of native anatomy, embedded pathology, and implants are and how they may assist in the development of innovative therapies. Accurate imaging of pathology including target region for intervention, its anatomic features and spatial relation to the surrounding structures is critical for selecting optimal approach and evaluation of procedural results. This review describes clinical applications of 3D printing, outlines current limitations, and highlights future implications for quality control, advanced medical education and training.

Three-dimensional printing for quality management in device closure of interatrial communications

We report the case of a 48-year-old male who was found to have an atrial septal defect (ASD) of the secundum type with evidence of moderate right heart load requiring elective device closure. Intraprocedural balloon-sizing showed an average stretched diameter of 16 mm. The decision was made to implant a …

Animal Models for Cardiac Research

The modern era of cardiac surgery is largely considered to have begun in the animal research laboratories. Today, animal models continue to be used for the study of cardiovascular diseases and are required for the preclinical assessment of pharmaceuticals, mechanical devices, therapeutic procedures, and/or continuation therapies. This chapter was designed to provide readers and potential investigators with important background information necessary for the process of matching an experimental hypothesis to an animal species that will serve as an appropriate model for studying a specific cardiovascular disease or for testing a given medical device. A review of the current animal models used in cardiac research is provided and arranged by disease state. Critical factors to consider when choosing an appropriate animal model including cost, reproducibility, and degree of similarity of the model to human disease are discussed. Thus, this chapter can be utilized as a practical guide for planning of research protocols.

Cardiac MRI in the isolated porcine heart reveals possible etiology of sudden right heart failure following heart transplantation.

Occurrence of immediate post-transplant heart failure in the cardiac transplant recipient is typically attributed to elevated pulmonary vascular resistance, however other etiologies may play a role. At the completion of the transplant, free air, which has collected in the donor heart, is vented via an aortotomy. Free air may rise into the right coronary artery and obstruct reperfusion of the right ventricle. Cardiac perfusion MRI may offer a method of non-invasively determining the presence of air embolus. The objectives in the pilot study were to identify steps in the donor process where free air could enter into the aortic root causing obstruction of perfusion of the coronary arteries. A change in surgical technique could then be used to eliminate a portal of entry and cardiac perfusion MRI could validate the technique. Standard cardiectomy was compared to a variation in technique in two animals. Pulmonary vein ligation was completed in the experimental model before completion of cardiectomy. Both hearts were isolated and imaged using T1-weighted FLASH sequence and gadolinium contrast via the aortic root. Cardiac perfusion MRI imaging of the heart with the unligated pulmonary vein revealed evidence of air embolus and no perfusion of the right coronary artery compared to the ligated heart. Anatomically, the right coronary artery is anterior in the mediastinum compared to the left coronary artery. Air emboli preferentially rise into the right coronary and can obstruct flow into the right heart. Cardiac perfusion MRI offers an effective method to evaluate the isolated pre-transplant heart for perfusion defects.

If you're not at the table, you're on the menu: the Florida Legislative Fellowship experience.

he Florida Radiological Society FRS) developed and funded a Legisative Fellowship in Tallahassee with he purpose to introduce organized edicine and the political process to adiology residents. Two residents, ne each from the University of outh Florida and the University of lorida, participated in the fellowhip during March 2008, while the egislature was in session. To our nowledge, the fellowship was the rst of its kind: a state-level legislative ellowship experience sponsored by a hapter of the ACR. The FRS lobbyist, Alison Dudey organized the fellowship schedle. The 3-day Tallahassee experince included meetings with state