In animal models of lipotoxicity, accumulation of triglycerides within cardiomyocytes is associated with contractile dysfunction. However, whether intramyocardial lipid deposition is a feature of human heart failure remains to be established. We hypothesized that intramyocardial lipid accumulation is a common feature of non-ischemic heart failure and is associated with changes in gene expression similar to those found in an animal model of lipotoxicity. Intramyocardial lipid staining with oil red O and gene expression analysis was performed on heart tissue from 27 patients (9 female) with non-ischemic heart failure. We determined intramyocardial lipid, gene expression, and contractile function in hearts from 6 Zucker diabetic fatty (ZDF) and 6 Zucker lean (ZL) rats. Intramyocardial lipid overload was present in 30% of non-ischemic failing hearts. The highest levels of lipid staining were observed in patients with diabetes and obesity (BMI>30). Intramyocardial lipid deposition was associated with an up-regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) -regulated genes, myosin heavy chain beta (MHC-beta), and tumor necrosis factor alpha (TNF-alpha). Intramyocardial lipid overload in the hearts of ZDF rats was associated with contractile dysfunction and changes in gene expression similar to changes found in failing human hearts with lipid overload. Our findings identify a subgroup of patients with heart failure and severe metabolic dysregulation characterized by intramyocardial triglyceride overload and changes in gene expression that are associated with contractile dysfunction.
Introduction: Sepsis should be included in the differential of any patient with unexplained organ dysfunction, whether or not an obvious infection is initially detected. Perioperative providers frequently care for patients with sepsis. This simulation case challenges participants to recognize and manage a presentation of postoperative sepsis, providing an opportunity to discuss the rationale behind sepsis management during debriefing. Methods: Assuming the role of an anesthesia provider, the participant takes over the care of a 62-year-old female who has just undergone cystoscopy and is extubated in the operating room (OR). The participant receives a brief handoff from the outgoing anesthesiologist while the patient awaits a postanesthesia care unit slot. The case has been uneventful, aside from intermittent hypotension responsive to IV fluids and boluses of phenylephrine. Within minutes of the handoff, the patient becomes somnolent and hypotensive. Efforts to treat hypotension eventually precipitate hypoxemia. Trainees must recognize and manage this cardiopulmonary decompensation. The scenario benefits from an OR simulation environment containing an anesthetic ventilator, anesthesia drugs and equipment, and a mannequin on an OR table. Results: Twelve residents completed the simulation scenario. Formal feedback was collected via email questionnaire from faculty instructors within 30 days of teaching each session. Discussion: Sepsis presents a diagnostic dilemma in part because no single diagnostic test rules the syndrome in or out. Multiple operational definitions of sepsis in the academic literature add to the confusion for clinicians. Our case simulation challenges perioperative providers to make a timely diagnosis and initiate appropriate treatment of sepsis.
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