Comparison of Blood Transfusion Rates Before and After Implementation of a Quality Improvement Initiative for Transfusion Safety and Appropriateness.

This quality improvement study compares blood transfusion rates among patients at a single tertiary care hospital before and after the implementation of a transfusion training model completed by incoming resident physicians.

The multidisciplinary management of a mechanical mitral valve thrombosis in pregnancy: a case report and review of the literature.

Background: The management of anticoagulation for mechanical heart valves during pregnancy poses a unique challenge. Mechanical valve thrombosis is a devastating complication for which surgery is often the treatment of choice. However, cardiac surgery for prosthetic valve dysfunction in pregnant patients confers a high risk of maternofetal morbidity and mortality. Case summary: A 39-year-old woman in her first pregnancy at 30 weeks gestation presented to hospital with a mechanical mitral valve thrombosis despite therapeutic anticoagulation with low-molecular-weight heparin. She underwent an emergent caesarean section followed immediately by a bioprosthetic mitral valve replacement. This occurred after careful planning and organization on the part of a large multidisciplinary team. Discussion: A proactive, rather than reactive, approach to the surgical management of a mechanical valve thrombosis in pregnancy will maximize the chances of successful maternal and fetal outcomes.

Drone versus ground delivery of simulated blood products to an urban trauma center: The Montreal Medi-Drone pilot study.

BACKGROUND: Timely and safe distribution of quality blood products is a major challenge faced by blood banks around the world. Our primary objective was to determine if simulated blood product delivery to an urban trauma center would be more rapidly achieved by unmanned aerial vehicle (UAV) than by ground transportation. A secondary objective was to determine the feasibility of maintaining simulated blood product temperatures within a targeted range. METHODS: In this prospective pilot study, we used two distinct methods to compare UAV flight duration and ground transport times. Simulated blood products included packed red blood cells, platelet concentrate, and fresh frozen plasma. For each blood product type, three UAV flights were conducted. Temperature was monitored during transport using a probe coupled to a data logger inside each simulated blood product unit. RESULTS: All flights were conducted successfully without any adverse events or safety concerns reported. The heaviest payload transported was 6.4 kg, and the drone speed throughout all nine flights was 10 m/s. The mean UAV transportation time was significantly faster than ground delivery (17:06 ± 00:04 minutes vs. 28:54 ± 01:12 minutes, p < 0.0001). The mean ± SD initial temperature for packed red blood cells was 4.4°C ± 0.1°C with a maximum 5% mean temperature variability from departure to landing. For platelet concentrates, the mean ± SD initial temperature was 21.6°C ± 0.5°C, and the maximum variability observed was 0.3%. The mean ± SD initial fresh frozen plasma temperature was -19°C ± 2°C, and the greatest temperature variability was from -17°C ± 2°C to -16°C ± 2°C. CONCLUSIONS: Unmanned aerial vehicle transportation of simulated blood products was significantly faster than ground delivery. Simulated blood product temperatures remained within their respective acceptable ranges throughout transport. Further studies assessing UAV transport of real blood products in populated areas are warranted. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models.

Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II × LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis.

Cardioprotective effects of glucose and insulin administration while maintaining normoglycemia (GIN therapy) in patients undergoing coronary artery bypass grafting.

CONTEXT: Coronary artery bypass grafting (CABG) is complicated by ischemia-reperfusion injury jeopardizing myocyte survival. OBJECTIVE: The aim of the study was to investigate whether glucose and insulin administration, while maintaining normoglycemia (GIN therapy) using a hyperinsulinemic-normoglycemic clamp technique, is cardioprotective in patients undergoing CABG. DESIGN AND SETTING: We conducted a randomized controlled trial at a tertiary care university teaching hospital. PATIENTS: We studied 99 patients undergoing elective CABG. INTERVENTION: Patients were randomly assigned to receive either GIN from the beginning of surgery until 24 h after CABG (GIN, n = 49) or standard metabolic care (control, n = 50). MAIN OUTCOME MEASURES: We measured plasma concentrations of cardiac troponin I and free fatty acids, cardiac function as assessed by transesophageal echocardiography, glycogen content, glycogen synthase activity, and the expression of AMP-activated protein kinase (AMPK) and protein kinase B (AKT) in cardiomyocytes. RESULTS: Patients receiving GIN therapy showed an attenuated release of cardiac troponin I (P < 0.05) and improved myocardial function (P < 0.05). Systemic free fatty acid concentrations were suppressed (P < 0.05), whereas intracellular glycogen content and glycogen synthase activity were not altered. The AMPK activity remained unchanged during ischemia in the GIN group, whereas it increased in the control group (P < 0.05). Enhanced AKT phosphorylation before ischemia was observed (P < 0.05) in the presence of GIN. However, there was no evidence for AKT-dependent AMPK inhibition. CONCLUSIONS: GIN therapy protects the myocardium and inhibits ischemia-induced AMPK activation.

Marked differences between atrial and ventricular gene-expression remodeling in dogs with experimental heart failure.

Congestive heart failure (CHF) causes arrhythmogenic, structural and contractile remodeling, with important atrial-ventricular differences: atria show faster and greater inflammation, cell-death and fibrosis. The present study assessed time-dependent left atrial (LA) and ventricular (LV) gene-expression changes in CHF. Groups of dogs were submitted to ventricular tachypacing (VTP, 240 bpm) for 24 h or 2 weeks, and compared to sham-instrumented animals. RNA from isolated LA and LV cardiomyocytes of each dog was analyzed by canine-specific microarrays (>21,700 probe-sets). LA showed dramatic gene-expression changes, with 4785 transcripts significantly-altered (Q<5) at 24-hour and 6284 at 2-week VTP. LV gene-changes were more limited, with 52 significantly-altered at 24-hour and 130 at 2-week VTP. Particularly marked differences were seen in ECM genes, with 153 changed in LA (e.g. approximately 65-fold increase in collagen-1) at 2-week VTP versus 2 in LV; DNA/RNA genes (LA=358, LV=7); protein biosynthesis (LA=327, LV=14); membrane transport (LA=230, LV=8); cell structure and mobility (LA=159, LV=6) and coagulation/inflammation (LA=147, LV=1). Noteworthy changes in LV were genes involved in metabolism (35 genes; creatine-kinase B increased 8-fold at 2-week VTP) and Ca(2+)-signalling. LA versus LV differential gene-expression decreased over time: 1567 genes were differentially expressed (Q<1) at baseline, 1499 at 24-hour and 897 at 2-week VTP. Pathway analysis revealed particularly-important changes in LA for mitogen-activated protein-kinase, apoptotic, and ubiquitin/proteasome systems, and LV for Krebs cycle and electron-transfer complex I/II genes. VTP-induced CHF causes dramatically more gene-expression changes in LA than LV, dynamically altering the LA-LV differential gene-expression pattern. These results are relevant to understanding chamber-specific remodeling in CHF.

Contrasting gene expression profiles in two canine models of atrial fibrillation.

Gene-expression changes in atrial fibrillation patients reflect both underlying heart-disease substrates and changes because of atrial fibrillation-induced atrial-tachycardia remodeling. These are difficult to separate in clinical investigations. This study assessed time-dependent mRNA expression-changes in canine models of atrial-tachycardia remodeling and congestive heart failure. Five experimental groups (5 dogs/group) were submitted to atrial (ATP, 400 bpm x 24 hours, 1 or 6 weeks) or ventricular (VTP, 240 bpm x 24 hours or 2 weeks) tachypacing. The expression of approximately 21,700 transcripts was analyzed by microarray in isolated left-atrial cardiomyocytes and (for 18 genes) by real-time RT-PCR. Protein-expression changes were assessed by Western blot. In VTP, a large number of significant mRNA-expression changes occurred after both 24 hours (2209) and 2 weeks (2720). In ATP, fewer changes occurred at 24 hours (242) and fewer still (87) at 1 week, with no statistically-significant alterations at 6 weeks. Expression changes in VTP varied over time in complex ways. Extracellular matrix-related transcripts were strongly upregulated by VTP consistent with its pathophysiology, with 8 collagen-genes upregulated >10-fold, fibrillin-1 8-fold and MMP2 4.5-fold at 2 weeks (time of fibrosis) but unchanged at 24 hours. Other extracellular matrix genes (eg, fibronectin, lysine oxidase-like 2) increased at both time-points ( approximately 10, approximately 5-fold respectively). In ATP, mRNA-changes almost exclusively represented downregulation and were quantitatively smaller. This study shows that VTP-induced congestive heart failure and ATP produce qualitatively different temporally-evolving patterns of gene-expression change, and that specific transcriptomal responses associated with atrial fibrillation versus underlying heart disease substrates must be considered in assessing gene-expression changes in man.

Mechanisms of atrial remodeling and clinical relevance.

PURPOSE OF REVIEW: Atrial fibrillation usually occurs in the context of an atrial substrate produced by alterations in atrial tissue properties referred to as remodeling. Remodeling can result from cardiac disease, cardiac arrhythmias, or biologic processes such as senescence. Recent advances in understanding remodeling have allowed for insights into mechanisms underlying atrial fibrillation that have been transferred from experimental models to humans. This paper reviews recent progress in understanding atrial remodeling, as well as the consequent clinical insights into atrial fibrillation pathophysiology and treatment. RECENT FINDINGS: Two principal forms of remodeling have been described in animal models of atrial fibrillation: ionic remodeling, which affects cellular electrical properties, and structural remodeling, which alters atrial tissue architecture. Atrial tachycardias (particularly rapid tachyarrhythmias such as atrial flutter and atrial fibrillation) cause ionic remodeling, which decreases the atrial refractory period and promotes atrial reentry. Congestive heart failure produces atrial interstitial fibrosis, which promotes arrhythmogenesis by interfering with atrial conduction properties. Recent animal studies have provided insights into the pathways involved in remodeling, and have indicated the pathophysiological role of remodeling in specific contexts. In addition, work in animal models has provided information about pharmacological interventions that can prevent the development of remodeling. Clinical studies have shown that novel approaches to remodeling prevention identified in animal work have potential therapeutic value in man. SUMMARY: Understanding atrial remodeling has the potential to improve our appreciation of the pathophysiology of clinical atrial fibrillation and to allow for the development of useful new therapeutic approaches.