Randal S. Blank

Platelet-derived growth factor-BB-induced suppression of smooth muscle cell differentiation

Previously, we demonstrated that treatment of postconfluent quiescent rat aortic smooth muscle cells (SMCs) with platelet-derived growth factor (PDGF)-BB dramatically reduced smooth muscle (SM) alpha-actin synthesis. In the present studies, we focused on the expression of two other SM-specific proteins, SM myosin heavy chain (SM-MHC) and SM alpha-tropomyosin (SM-alpha TM), to determine whether the actions of PDGF-BB were specific to SM alpha-actin or represented a global ability of PDGF-BB to inhibit expression of cell-specific proteins characteristic of differentiated SMCs. SM-MHC and SM-alpha TM expression were assessed by one- or two-dimensional gel electrophoretic analysis of proteins from cells labeled with [35S]methionine, as well as by Northern analysis of mRNA levels. Synthesis of both SM-specific proteins was decreased by 50-70% in PDGF-BB--treated cells as compared with cells treated with PDGF vehicle. Treatment of cells with 10% fetal bovine serum, which produced a mitogenic effect equivalent to that of PDGF-BB, decreased SM-MHC synthesis by 40% but increased SM-alpha TM synthesis. SM-MHC and SM-alpha TM mRNA expression was decreased by 80% at 24 hours in PDGF-BB--treated postconfluent SMCs, whereas treatment with 10% fetal bovine serum did not decrease the expression of SM-alpha TM mRNA but did inhibit SM-MHC mRNA expression by 36%. Consistent with the absence of detectable PDGF alpha-receptors on these cells, PDGF-AA had no effect on either mitogenesis or expression of SM-MHC or SM-alpha TM.(ABSTRACT TRUNCATED AT 250 WORDS)

A Retinoic Acid–Induced Clonal Cell Line Derived From Multipotential P19 Embryonal Carcinoma Cells Expresses Smooth Muscle Characteristics

Despite intense interest in understanding the differentiation of vascular smooth muscle, very little is known about the cellular and molecular mechanisms that control differentiation of this cell type. Progress in this field has been hampered by the lack of an inducible in vitro system for study of the early steps of smooth muscle differentiation. In this study, we describe a model system in which multipotential mouse P19 embryonal carcinoma cells (P19s) can be induced to express multiple characteristics of differentiated smooth muscle. Treatment of P19s with retinoic acid was associated with profound changes in cell morphology and with the appearance at high frequency of smooth muscle alpha-actin-positive cells that were absent or present at extremely low frequency in parental P19s. A clonal line derived from retinoic acid-treated P19s (9E11G) stably expressed multiple characteristics of differentiated smooth muscle, including smooth muscle-specific isoforms of alpha-actin and myosin heavy chain, as well as functional responses to the contractile agonists phenylephrine, angiotensin II, ATP, bradykinin, histamine, platelet-derived growth factor (PDGF)-AA, and PDGF-BB. Additionally, 9E11G cells expressed transcripts for MHox, a muscle homeobox gene expressed in smooth, cardiac, and skeletal muscles, but not the skeletal muscle-specific regulatory factors, MyoD and myogenin. Results demonstrate that retinoic acid treatment of multipotential P19 cells is associated with formation of cell lines that stably express multiple properties of differentiated smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

The endothelial glycocalyx: Emerging concepts in pulmonary edema and acute lung injury

The endothelial glycocalyx is a dynamic layer of macromolecules at the luminal surface of vascular endothelium that is involved in fluid homeostasis and regulation. Its role in vascular permeability and edema formation is emerging but is still not well understood. In this special article, we highlight key concepts of endothelial dysfunction with regards to the glycocalyx and provide new insights into the glycocalyx as a mediator of processes central to the development of pulmonary edema and lung injury.

Fiberoptic Intubation: An Overview and Update

Fiberoptic intubation (FOI) is an effective technique for establishing airway access in patients with both anticipated and unanticipated difficult airways. First described in the late 1960s, this approach can facilitate airway management in a variety of clinical scenarios given proper patient preparation and technique. This paper seeks to review the pertinent technology, clinical techniques, and indications for and complications of its use. The role of FOI in airway management algorithms is discussed. Evidence is presented comparing FOI to other techniques with regard to difficult airway management. In addition, we have reviewed the literature on training processes and skill development in FOI.

Intraoperative Lung-Protective Ventilation Trends and Practice Patterns: A Report from the Multicenter Perioperative Outcomes Group.

BACKGROUND:The use of an intraoperative lung-protective ventilation strategy through tidal volume (TV) size reduction and positive end-expiratory pressure (PEEP) has been increasingly investigated. In this article, we describe the current intraoperative lung-protective ventilation practice patterns and trends. METHODS:By using the Multicenter Perioperative Outcomes Group database, we identified all general endotracheal anesthetics from January 2008 through December 2013 at 10 institutions. The following data were calculated: (1) percentage of patients receiving TV > 10 mL/kg predicted body weight (PBW); (2) median initial and overall TV in mL/kg PBW and; (3) percentage of patients receiving PEEP ≥ 5 cm H2O. The data were analyzed at 3-month intervals. Interinstitutional variability was assessed. RESULTS:A total of 330,823 patients met our inclusion criteria for this study. During the study period, the percentage of patients receiving TV > 10 mL/kg PBW was reduced for all patients (26% to 14%) and in the subpopulations of obese (41% to 25%), short stature (52% to 36%), and females (39% to 24%; all P values <0.001). There was a significant reduction in TV size (8.90–8.20 mL/kg PBW, P < 0.001). There was also a statistically significant but clinically irrelevant difference between initial and overall TV size (8.65 vs 8.63 mL/kg PBW, P < 0.001). Use of PEEP ≥ 5 cm H2O increased during the study period (25%–45%, P < 0.001). TV usage showed significant interinstitutional variability (P < 0.001). CONCLUSIONS:Although decreasing, a significant percentage of patients are ventilated with TV > 10 mL/kg PBW, especially if they are female, obese, or of short stature. The use of PEEP ≥ 5 cm H2O has increased significantly. Creating awareness of contemporary practice patterns and demonstrating the efficacy of lung-protective ventilation are still needed to optimize intraoperative ventilation.

Management of One-lung Ventilation: Impact of Tidal Volume on Complications after Thoracic Surgery.

Background:The use of lung-protective ventilation (LPV) strategies may minimize iatrogenic lung injury in surgical patients. However, the identification of an ideal LPV strategy, particularly during one-lung ventilation (OLV), remains elusive. This study examines the role of ventilator management during OLV and its impact on clinical outcomes. Methods:Data were retrospectively collected from the hospital electronic medical record and the Society of Thoracic Surgery database for subjects undergoing thoracic surgery with OLV between 2012 and 2014. Mean tidal volume (VT) during two-lung ventilation and OLV and ventilator driving pressure (&Dgr;P) (plateau pressure − positive end-expiratory pressure [PEEP]) were analyzed for the 1,019 cases that met the inclusion criteria. Associations between ventilator parameters and clinical outcomes were examined by multivariate linear regression. Results:After the initiation of OLV, 73.3, 43.3, 18.8, and 7.2% of patients received VT greater than 5, 6, 7, and 8 ml/kg predicted body weight, respectively. One hundred and eighty-four primary and 288 secondary outcome events were recorded. In multivariate logistic regression modeling, VT was inversely related to the incidence of respiratory complications (odds ratio, 0.837; 95% CI, 0.729 to 0.958), while &Dgr;P predicted the development of major morbidity when modeled with VT (odds ratio, 1.034; 95% CI, 1.001 to 1.068). Conclusions:Low VT per se (i.e., in the absence of sufficient PEEP) has not been unambiguously demonstrated to be beneficial. The authors found that a large proportion of patients continue to receive high VT during OLV and that VT was inversely related to the incidence of respiratory complications and major postoperative morbidity. While low (physiologically appropriate) VT is an important component of an LPV strategy for surgical patients during OLV, current evidence suggests that, without adequate PEEP, low VT does not prevent postoperative respiratory complications. Thus, use of physiologic VT may represent a necessary, but not independently sufficient, component of LPV.

Approaches to Refractory Hypoxemia in Acute Respiratory Distress Syndrome: Current Understanding, Evidence, and Debate

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) cause substantial morbidity and mortality despite our improved understanding of lung injury, advancements in the application of lung-protective ventilation, and strategies to prevent ventilator-induced lung injury. Severe refractory hypoxemia may develop in a subset of patients with severe ARDS. We review several approaches referred to as “rescue” therapies for severe hypoxemia, including lung-recruitment maneuvers, ventilation modes, prone positioning, inhaled vasodilator therapy, and the use of extracorporeal membrane oxygenation. Each shows evidence for improving oxygenation, though each has associated risks, and no single therapy has proven superior in the management of severe hypoxemia. Importantly, increased survival with these strategies has not been clearly established.

Anesthesia for Esophageal Surgery

Patients presenting for esophageal surgery frequently have comorbidities including cardiopulmonary disease which should be evaluated per published ACC/AHA guidelines. Particular attention should be paid to symptoms and signs of esophageal obstruction, gastroesophageal reflux disease (GERD), and malnutrition which may affect the risk of perioperative complications. Postoperative pain control strategies are dictated by the surgical approach to the esophagus. Use of thoracic epidural analgesia in patients undergoing transthoracic esophageal surgery provides optimal pain control, permits early patient extubation and mobilization, and may improve outcomes. Patients presenting for esophageal surgery commonly have pathology which increases their risk of regurgitation and aspiration. This is particularly true for patients with achalasia and other motor disorders of the esophagus, patients with high-grade esophageal obstruction, and those with severe GERD. Consideration should be given to pharmacologic prophylaxis, awake or rapid sequence induction in a head-up position, and appropriate postoperative care, including gastric drainage. Excessive perioperative intravenous fluid administration, especially crystalloid, may lead to exaggerated fluid shifts toward the interstitial space causing increased complications such as poor wound healing, slower return of GI function, abdominal compartment syndrome, impaired anastomotic healing, increased cardiac demand, pneumonia, and respiratory failure. The ideal fluid regimen for major esophageal surgery should be individualized, optimizing cardiac output and oxygen delivery while avoiding excessive fluid administration. Patients presenting for emergent repair of esophageal disruption, rupture or perforation may present with hypovolemia, sepsis, and shock. Anesthetic management strategies should be based on the severity of these presenting conditions and the nature of the planned procedure. Esophageal anastomotic leak is a frequent complication associated with high morbidity and mortality and is likely to be a function of numerous surgical, systemic, and possibly anesthetic factors. Since anastomotic integrity is dependent upon adequate blood flow and oxygen delivery, the development of anastomotic leak may be related to intraoperative management variables, particularly systemic blood pressure, cardiac output, and oxygen delivery and may thus be modifiable by anesthetic management.

Essential Anatomy and Physiology of the Respiratory System and the Pulmonary Circulation

Knowledge of the clinical anatomy and function of the respiratory system is essential for the safe, efficient, and appropriate perioperative management of intubation, mechanical ventilation, and anesthesia for the thoracic surgical patient. The lung has ten (third generation airway) bronchopulmonary segments on the right and eight segments on the left that are readily identifiable by fiberoptic bronchoscopy (two segmental bronchi on the left are considered “fused”). The anesthetic employed, both general and regional, will impact the control of respiration, reactivity of the airways, and the patient’s ability to maintain their airway, take a deep breath, and cough. Dynamic influences of ventilatory pattern, posture, body habitus, agitation or pain, and inflammation can cause “air trapping” and drastically reduce alveolar ventilation. The compliance and resistance of the respiratory system will change during the course of surgery, especially those procedures requiring one-lung ventilation, and may necessitate frequent adjustments of the ventilator to optimize gas exchange and reduce lung injury. Many drugs employed during cardiothoracic surgery will impact the lung’s intrinsic mechanisms to match ventilation to perfusion matching either directly on hypoxic pulmonary vasoconstriction (HPV) or indirectly by altering cardiac output or vascular resistance.

Penetrating ascending aortic atherosclerotic ulcer.

A 60-yr-old female with a history of obesity, hypertension, and reactive airway disease presented with chest pain, back pain, and a recent syncopal event. The patient was in shock with evidence of cardiac tamponade. Computed tomography angiogram (CTA) showed “a hemorrhagic pericardial effusion and Type A intramural hematoma with linear defect of the anterior surface of the aortic root consistent with small dissection flap.” The patient was emergently taken to the operating room. Transesophageal echocardiogram (TEE) confirmed cardiac tamponade, good ventricular function, and mild aortic valvular insufficiency. A lesion was seen in aortic valve longaxis view at the anterior aspect of the sino-tubular junction (Fig. 1) (Video 1, see Supplemental Digital Content 1, http://links.lww.com/AA/A28, modified midesophageal aortic valve long-axis view in real-time shows a lesion [white arrow] at the anterior aspect of the sino-tubular junction, suggestive of dissection flap). In the aortic valve short-axis view, the same lesion appeared atheromatous with ragged edges and a central depression. It protruded into the aortic lumen and was located between the left and right coronary cusps (Fig. 2) (Video 2, see Supplemental Digital Content 2, http://links.lww.com/AA/A29, midesophageal aortic valve short-axis view in realtime demonstrates the lesion [white arrow] between the left and right coronary cusps; it is atheromatous with irregular borders). The aortic wall was minimally