Robert E. Southard

Reversal of secondary pulmonary hypertension by axial and pulsatile mechanical circulatory support.

BACKGROUND Pulmonary hypertension associated with chronic congestive heart failure posses a significant risk of morbidity and death after heart transplantation. Isolated observations suggest that chronic ventricular unloading may lead to normalization of pulmonary pressures and thus render a patient likely to be a heart transplant candidate. METHODS This study is a retrospective analysis of 9 heart failure patients with secondary pulmonary hypertension (transpulmonary gradient [TPG] > 15 mm/Hg). Two were treated with a pulsatile left ventricular assist device (LVAD) and 7 with an axial-flow LVAD. RESULTS After LVAD support, mean pulmonary artery pressure decreased from 39 +/- 7 to 31 +/- 5 mm Hg, and the TPG decreased from 19 +/- 3 to 13 +/- 4 mm Hg (p < 0.01). The 1-year Kaplan-Meier survival curve for patients with pre-LVAD TPG > 15 mm Hg vs those with TPG < 15 mm Hg showed no difference in survival (p = 0.6). This finding was supported by analysis of a large multi-institutional cohort obtained from the Organ Procurement and Transplantation Network database, where no differences in survival were found in the same groups. CONCLUSIONS Pulmonary hypertension that is secondary to congestive heart failure, as defined by a TPG > 15 mm Hg can be reversed by the use of pulsatile and axial-flow LVADs; furthermore, post-transplant survival for patients with secondary pulmonary hypertension treated with an LVAD was no different than for those without pulmonary hypertension who received LVAD support.

Revascularization and ventricular restoration in patients with ischemic heart failure: the STICH trial

Purpose of review As techniques for the management of patients with ischemic heart failure have evolved, controversy has arisen with respect to the roles of revascularization and ventricular restoration procedures. This review addresses current thinking on the management of these patients and describes a prospective randomized trial that will have an impact on future treatment selection. Recent findings Although the basis for improved survival with coronary artery bypass grafting lies in the viability of ischemic myocardium, nuclear medicine studies and stress echocardiography have failed to adequately select for tissues that are capable of recovery. Recent studies have suggested an additional benefit to combining ventricular restoration with bypass surgery. However, the role for these techniques has not been definitively established. Summary The currently enrolling Surgical Treatment for Ischemic Heart Failure (STICH) trial promises to address these issues and thereby improve the management of patients with this disease.

A pooled analysis of posttransplant survival following combined heart-liver transplantation.

Because no single center has accumulated a large experience with this complex operation, the effectiveness of combined orthotopic heart transplantation (OHT) and orthotopic liver transplantation (OLT) in achieving long-term survival has been unknown. Cases of OHT-OLT were pooled from a U.S. transplant recipient registry and from previously published literature. Aggregate data from these sources was used for survival analysis. Thirty-six patients having undergone OHT-OLT were listed in the national registry; the one- and five-year patient survival rates of these patients were 88% and 78%, respectively. Many patients remain alive at 8+ years after transplantation. An analysis of the pooled results of previously-published cases estimated a one-year patient survival rate of 84%. In selected disease processes, OHT-OLT can correct underlying metabolic deficiencies. While rarely indicated, OHT-OLT is a successful treatment for patients with end-stage heart and liver disease, with survival comparable to that seen after isolated orthotopic heart or orthotopic liver transplantation.

Pulmonary contusion is associated with toll-like receptor 4 upregulation and decreased susceptibility to pseudomonas pneumonia in a mouse model.

ABSTRACT Pulmonary contusion is a major cause of respiratory failure in trauma patients. This injury frequently leads to immune suppression and infectious complications such as pneumonia. The mechanism whereby trauma leads to an immune-suppressed state is poorly understood. To further study this phenomenon, we developed an animal model of pulmonary contusion (PC) complicated by pneumonia and assessed the effect of PC and pneumonia on toll-like receptor expression in alveolar macrophages. Using a mouse model, PC was induced on the right lung, and pneumonia was induced with Pseudomonas aeruginosa (Pa) injected intratracheally 48 h after injury. Susceptibility to pneumonia was assessed by mortality at 7 days. Uninjured animals were used as controls. Bronchoalveolar lavage fluid and blood were assayed 48 h after injury and 24 h after Pa instillation to look at markers of systemic inflammation. Toll-like receptor expression in the initial inflammatory response was analyzed by flow cytometry. Unexpectedly, injured animals subjected to intratracheal injection of Pa at 48 h after PC demonstrated increased survival compared with uninjured animals. Bronchoalveolar lavage cytokine expression was increased significantly after Pa administration but not after PC alone. Toll-like receptor 4 expression on alveolar macrophages was significantly elevated in the injured group compared with sham but not in neutrophils. Animals subjected to PC are more resistant to mortality from infection with Pa and display an enhanced cytokine response when subsequently subjected to Pa. Increased expression of toll-like receptor 4 on alveolar macrophages and enhanced innate immunity are a possible mechanism of increased cytokine production and decreased susceptibility to pneumonia.

Polytrauma Increases Susceptibility to Pseudomonas Pneumonia in Mature Mice.

ABSTRACT Pneumonia is the most common complication observed in patients with severe injuries. Although the average age of injured patients is 47 years, existing studies of the effect of injury on the susceptibility to infectious complications have focused on young animals, equivalent to a late adolescent human. We hypothesized that mature adult animals are more susceptible to infection after injury than younger counterparts. To test this hypothesis, we challenged 6 to 8-month-old mature mice to a polytrauma injury followed by Pseudomonas aeruginosa pneumonia and compared them to young (8–10-week-old) animals. We demonstrate that polytrauma injury increases mortality from pneumonia in mature animals (sham-pneumonia 21% vs. polytrauma-pneumonia 62%) but not younger counterparts. After polytrauma, pneumonia in mature mice is associated with higher bacterial burden in lung, increased incidence of bacteremia, and elevated levels of bacteria in the blood, demonstrating that injury decreases the ability to control the infectious challenge. We further find that polytrauma did not induce elevations in circulating cytokine levels (TNF-alpha, IL-6, KC, and IL-10) 24 h after injury. However, mature mice subjected to polytrauma demonstrated an exaggerated circulating inflammatory cytokine response to subsequent Pseudomonas pneumonia. Additionally, whereas prior injury increases LPS-stimulated IL-6 production by peripheral blood leukocytes from young (8–10-week-old) mice, injury does not prime IL-6 production by cell from mature adult mice. We conclude that in mature mice polytrauma results in increased susceptibility to Pseudomonas pneumonia while priming an exaggerated but ineffective inflammatory response.

Obtaining a Surgical Airway

Encountering a patient in need of an emergent surgical airway is one of the most harrowing situations a surgeon faces. The surgeon is often called as the patient becomes hypoxic after multiple attempts at an airway. In these cases it is necessary to rapidly assess the situation and develop a plan. Therefore, the surgeon must possess an understanding of the indications for an emergent surgical airway, a detailed knowledge of the anatomy of the neck, procedural options available, and the potential complications. With this knowledge the acute care surgeon can be adequately prepared for this rare but challenging scenario.

Hirntodinduzierte aktivierung proinflammatorischer reaktionen in potentiellen spenderorganen

ZusammenfassungHintergrundEine Serie unspezifischer inflammatorischer Ereignisse, ausgelöst durch explosiven Hirntod, scheint in potentiellen Spenderorganen eine Reihe von funktionellen und immunologischen Veränderungen zu verursachen. Ziel dieser Studie ist es, den Verlauf pro-inflammatorischer Zytokine in Herz, Lunge und Niere hirntoter Tiere aufzuzeigen.MethodikBei 4 Hausschweinen wurde Hirntod durch akuten Druckanstieg über einen intrakraniell eingebrachten Foley- Katheter herbeigeführt. Weitere 4 Schweine wurden scheinoperiert und dienten somit als Kontrolltiere. Jedes Experiment wurde 6 Stunden nach Hirntodinduktion beendet und die Organe wurden entnommen. Wir bestimmten die mRNA-Expression für TNF-α, IL-1β und IL-6 mittels rt-PCR in Herz, Lunge und Niere. Die Ergebnisse werden als Relation der Dichtewerte der Zytokine zum Housekeeping-Gen β-actin in der Gelelektrophorese beschrieben.ErgebnisseDie 6h-Werte für IL-1β- und IL-6-mRNA waren in allen untersuchten Organen von hirntoten Tieren signifikant höher als in den von scheinoperierten. TNF-α mRNA-Expression war in Lungegewebe hirntoter Tiere ebenfalls signifikant höher, wohingegen in Herz- und Nierengewebe die Werte für TNF-α mRNA in der Hirntod-Gruppe eher niedriger waren als in der Kontrollgruppe (statistisch nicht signifikant).SchlussfolgerungExplosiver Hirntod führt zu Zytokininduktion in den peripheren Organen. Aufgrund unserer Ergebnisse schlussfolgern wir, dass es sich hierbei um eine organ-spezifische Regulation handelt.SummaryBackgroundOrgan dysfunction after explosive brain death has been well documented. In addition, a series of nonspecific inflammatory events may increase the intensity of the immunological host response. The aim of the present study was to monitor the course of proinflammatory cytokines in heart, lung and kidney after brain death induction.MethodsBrain death (BD) was induced in 4 pigs by inflation of an intracranial Foley catheter and separately 4 pigs were sham-operated. Each experiment was terminated 6 hours after brain death/sham operation and the organs were harvested. We determined the mRNA-expression for TNF-α, IL-1β and IL-6 in the heart, lung and kidney using rt-PCR techniques. The results are presented as absorbance intensity (Mean±SEM). β-actin was used for standardization.ResultsAfter 6 hours, IL-1β and IL-6 mRNA expression increased significantly in all investigated organs in the brain dead animals compared to sham-operated. TNF-α transcripts increased significantly only in lung, while in heart and kidney TNF-α mRNA tended even to lower values in brain dead animals.ConclusionBrain death was associated with an increase in mRNA concentration of IL-1β and IL-6 in lung, heart and kidney, while TNF-α mRNA expression was only up-regulated in lung. We suggest that brain death initiates a cascade of organ-specific inflammatory events that may play a crucial role in early graft dysfunction and rejection via a priming effect on the transplanted organ.