Ezequiel J. Molina

Emergency Department Thoracotomy for Penetrating Injuries of the Heart and Great Vessels: An Appraisal of 283 Consecutive Cases From Two Urban Trauma Centers

BACKGROUND Historically, patients with penetrating cardiac injuries have enjoyed the best survival after emergency department thoracotomy (EDT), but further examination of these series reveals a preponderance of cardiac stab wound (SW) survivors with only sporadic cardiac gunshot wound (GSW) survivors. Our primary study objective was to determine which patients requiring EDT for penetrating cardiac or great vessel (CGV) injury are salvageable. METHODS All patients who underwent EDT for penetrating CGV injuries in two urban, level I trauma centers during 2000 to 2007 were retrospectively reviewed. Demographics, injury (mechanism, anatomic injury), prehospital care, and physiology (signs of life [SOL], vital signs, and cardiac rhythm) were analyzed with respect to hospital survival. RESULTS The study population (n = 283) comprised young (mean age, 27.1 years +/- 10.1 years) men (96.1%) injured by gunshot (GSW, 88.3%) or SWs (11.7%). Patients were compared by injury mechanism and number of CGV wounds with respect to survival (SW, 24.2%; GSW, 2.8%; p < 0.001; single, 9.5%; multiple, 1.4%; p = 0.003). Three predictors-injury mechanism, ED SOL, and number of CGV wounds-were then analyzed alone and in combination with respect to hospital survival. Only one patient (0.8%) with multiple CGV GSW survived EDT. CONCLUSION When the cumulative impact of penetrating injury mechanism, ED SOL, and number of CGV wounds was analyzed together, we established that those sustaining multiple CGV GSWs (regardless of ED SOL) were nearly unsalvageable. These results indicate that when multiple CGV GSWs are encountered after EDT, further resuscitative efforts may be terminated without limiting the opportunity for survival.

Outcomes after emergency department thoracotomy for penetrating cardiac injuries: a new perspective.

Previous reports have described penetrating cardiac injuries as the anatomic injury with the greatest opportunity for emergency department thoracotomy (EDT) survival. We hypothesize that actual survival rates are lower than that initially reported. A retrospective review of our EDT experience was performed. Data collected included injury mechanism and location, presence of measurable ED vital signs, initial ED cardiac rhythm, GCS, method of transportation, and survival. Logistic regression analysis identified predictors of survival. Ninety-four of 237 patients presented penetrating cardiac injuries after EDT. Eighty-nine patients (95%) were males. Measurable ED vital signs were present in 15 patients (16%). Cardiac injuries were caused by GSW in 82 patients (87%) and SW in 12 patients (13%). Fifteen patients (16%) survived EDT and were taken to the operating room, while eight patients (8%) survived their entire hospitalization. All survivors were neurologically intact. Survival rates were 5% for GSW and 33% for SW. Mechanism of injury (SW), prehospital transportation by police, higher GCS, sinus tachycardia, and measurable ED vital signs were associated with improved survival. In urban trauma centers where firearm injuries are much more common than stabbings, the presence of a penetrating cardiac injury may no longer be considered a predictor of survival after EDT.

Reverse remodeling is associated with changes in extracellular matrix proteases and tissue inhibitors after mesenchymal stem cell (MSC) treatment of pressure overload hypertrophy

Changes in ventricular extracellular matrix (ECM) composition of pressure overload hypertrophy determine clinical outcomes. The effects of mesenchymal stem cell (MSC) transplantation upon determinants of ECM composition in pressure overload hypertrophy have not been studied. Sprague–Dawley rats underwent aortic banding and were followed by echocardiography. After an absolute decrease in fractional shortening of 25% from baseline, 1 × 106 MSC (n = 28) or PBS (n = 20) was randomly injected intracoronarily. LV protein analysis, including matrix metalloproteinases (MMP‐2, MMP‐3, MMP‐6, MMP‐9) and tissue inhibitors of metalloproteinases (TIMP‐1, TIMP‐2, TIMP‐3), was performed after sacrifice on postoperative day 7, 14, 21 or 28. Left ventricular levels of MMP‐3, MMP‐6, MMP‐9, TIMP‐1 and TIMP‐3 were demonstrated to be decreased in the MSC group compared with controls after 28 days. Expression of MMP‐2 and TIMP‐2 remained relatively stable in both groups. Successful MSCs delivery was confirmed by histological analysis and visualization of labelled MSCs. In this model of pressure overload hypertrophy, intracoronary delivery of MSCs during heart failure was associated with specific changes in determinants of ECM composition. LV reverse remodeling was associated with decreased ventricular levels of MMP‐3, MMP‐6, MMP‐9, TIMP‐1 and TIMP‐3, which were upregulated in the control group as heart failure progressed. These effects were most significant at 28 days following injection. Copyright

Improvement in hemodynamic performance, exercise capacity, inflammatory profile, and left ventricular reverse remodeling after intracoronary delivery of mesenchymal stem cells in an experimental model of pressure overload hypertrophy

OBJECTIVES In a rat model of pressure overload hypertrophy, we studied the effects of intracoronary delivery of mesenchymal stem cells on hemodynamic performance, exercise capacity, systemic inflammation, and left ventricular reverse remodeling. METHODS Sprague-Dawley rats underwent aortic banding and were followed up by echocardiographic scanning. After a decrease in fractional shortening of 25% from baseline, animals were randomized to intracoronary injection of mesenchymal stem cells (MSC group; n = 28) or phosphate-buffered saline solution (control group; n = 20). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of inflammatory markers were performed before the rats were humanely killed on postoperative day 7, 14, 21, or 28. RESULTS Injection of mesenchymal stem cells improved systolic function in the MSC group compared with the control group (mean +/- standard deviation: maximum dP/dt 3048 +/- 230 mm Hg/s vs 2169 +/- 97 mm Hg/s at 21 days and 3573 +/- 741 mm Hg/s vs 1363 +/- 322 mm Hg/s at 28 days: P < .001). Time to exhaustion was similarly increased in the MSC group compared with controls (487 +/- 35 seconds vs 306 +/- 27 seconds at 28 days; P < .01). Serum levels of interleukins 1 and 6, tumor necrosis factor-alpha, and brain natriuretic peptide-32 were significantly decreased in animals treated with mesenchymal stem cells. Stem cell transplantation improved left ventricular fractional shortening at 21 and 28 days. Left ventricular end-systolic and end-diastolic diameters were also improved at 28 days. CONCLUSIONS In this model of pressure overload hypertrophy, intracoronary delivery of mesenchymal stem cells during heart failure was associated with an improvement in hemodynamic performance, maximal exercise tolerance, systemic inflammation, and left ventricular reverse remodeling. This study suggests a potential role of this treatment strategy for the management of hypertrophic heart failure resulting from pressure overload.

Novel Experimental Model of Pressure Overload Hypertrophy in Rats

BACKGROUND We studied a novel animal model of pressure overload hypertrophy in transition to heart failure following ascending aortic constriction. We sought to assess chronologic changes in hemodynamic parameters, echocardiographic signs of left ventricular (LV) remodeling, exercise tolerance, and profiles of systemic and local inflammation. MATERIALS AND METHODS A cohort of Sprague Dawley rats underwent aortic constriction proximal to the innominate artery and were followed by echocardiography. A group of animals were euthanized 20 wk after aortic constriction, before any detectable decline in fractional shortening (normal fractional shortening (FS) or control group; n = 6). When additional animals reached an absolute 25% decline in fractional shortening, they were randomized to be euthanized on d 0 (25% downward arrow FS group; n = 5), or d 21 (>25% downward arrow FS group; n = 6). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of systemic and local inflammatory markers was performed at each time interval. RESULTS An absolute decline of 25% in FS after aortic constriction was observed between 24 and 28 wk for most animals. The transition from compensated to decompensated hypertrophy was associated with markedly decreased dP/dt(max) and dP/dt(min), increased LV end-systolic diameter and LV end-diastolic diameter, stabilization of LV free wall diameter, decreased exercise performance and up-regulation in expression of interleukin-1, interleukin-6, tumor necrosis factor-alpha, and atrial natriuretic peptide. All animals developed heart failure. CONCLUSIONS This study demonstrates that proximal aortic constriction in young rats represents an excellent experimental model of pressure overload hypertrophy that may be useful for testing the efficacy of novel therapies for the treatment of heart failure.

Pleomorphic adenoma of the submandibular gland

Pleomorphic adenomas of the submandibular glands are exceedingly rare tumors in the pediatric practice. Patients usually present with a painless and mobile mass without any other associated symptoms. Radiologic studies are usually unable to differentiate benign from malignant tumors in most cases. Recurrences are rare with complete en bloc excision of the tumor and the submandibular gland. Except for the rare cases of malignant transformation, the prognosis is excellent.

Pre-transplant obesity in heart transplantation: Are there predictors of worse outcomes?

Objective. Morbid obesity is increasingly observed in patients being evaluated for heart transplantation and represents a relative contraindication. We sought to evaluate the influence of pre-transplant obesity on morbidity and mortality after heart transplantation. Design. We retrospectively reviewed 90 consecutive patients with preoperative obesity (BMI ≥ 30) and 90 age matched patients with normal weight (BMI 19 – 26) who underwent heart transplantation at our institution between January 1997 and December 2005. Results. Morbidly obese patients experienced higher rates of pre-transplant diabetes (29% vs 15%, p < 0.05) and prolonged waiting time before transplantation (191.4±136.1 vs 117.4±143.2 days, p < 0.001). There were no significant differences in post-operative complications including rejection and major and minor infections. There was no difference in actuarial survival between the obese and control groups after a mean follow-up of 4.26±2.95 years (p = 0.513, log-rank statistic 0.452). Causes of death did not differ. Cox proportional hazard analysis revealed increased association of peripheral vascular disease (HR 31.718, p = 0.001), and pre operative inotropic support (HR 33.725, p = 0.013) with increased mortality in the obese group. Conclusions. This study suggests morbid obesity does not affect survival or rates of infection and rejection after heart transplantation.

Massive right atrial myxoma presenting with syncope

A 65-year-old man presented to the emergency room following an episode of syncope. His vital signs and physical examination were unremarkable. A chest X-ray and an ECG were also normal. He was admitted to the hospital for further work-up. A computed tomography scan of his brain did not reveal any evidence of stroke, hemorrhage, or mass effect. A transesophageal echocardiogram, however, revealed tricuspid regurgitation and a right atrial mass with finger-like projections, which appeared to originate from the tricuspid valve. Left heart catheterization was performed, showing a 99% proximal right coronary artery stenosis. The patient was scheduled to undergo atrial mass resection, tricuspid valve annuloplasty, and coronary bypass. During the procedure, a large myxoma was found to be adherent to the right side of the atrial septum, adjacent to the fossa ovalis. The mass was friable and was attached to the endocardium by a pedicle. Following resection of the atrial mass and tricuspid valve annuloplasty, a single saphenous vein graft bypass to the right coronary artery was performed. The patients postoperative course was unremarkable and he was discharged home on postoperative day 6.

Improved Exercise Capacity and Reduced Systemic Inflammation After Adenoviral-Mediated SERCA-2a Gene Transfer

BACKGROUND We hypothesized that sarcoplasmic reticulum Ca2+ ATPase pump (SERCA-2a) gene delivery would have beneficial effects upon exercise capacity and markers of inflammation in the setting of heart failure. MATERIALS AND METHODS A pressure-overload model of experimental heart failure was used in rats. Following a decrease in fractional shortening of >or=25%, animals underwent intracoronary adenoviral-mediated gene transfection using SERCA-2a. Heart failure animals were randomized to receive the SERCA-2a gene, the beta galactosidase (control) gene, or followed without any further intervention. Exercise and hemodynamic testing were performed, and myocardial and systemic markers of inflammation were assayed after 7 and 21 d. RESULTS Animals receiving Ad.SERCA-2a showed an increase in exercise tolerance (499.0 +/- 14.9 versus 312.8 +/- 10.5 s, P < 0.0001) relative to Ad.Gal group. Groups treated with Ad.SERCA-2a had significantly decreased serum levels of the inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor-alpha compared with Ad.Gal-treated animals. Serum levels of atrial natriuretic peptide were decreased in animals receiving Ad.SERCA-2a compared with animals receiving Ad.Gal at day 7 (0.35 +/- 0.03 versus 0.52 +/- 0.11 pg/mL, P = 0.001). Myocardial levels of the proapoptotic protein bax were reduced in Ad.SERCA-2a -treated animals compared with those receiving Ad.Gal at day 7 (protein level/actin: 0.24 +/- 0.05 versus 0.33 +/- 0.04, P = 0.04) and day 21 (protein level/actin: 0.61 +/- 0.04 versus 0.69 +/- 0.01, P = 0.001). CONCLUSIONS Genetic modulation of heart failure using the SERCA-2a gene was associated with improvement in cardiac function and exercise capacity as well as improvements in heart-failure associated inflammatory markers.

Outcomes after heart transplantation in patients with and without pretransplant renal dysfunction

Abstract Objective. To compare long-term survival and incidence of ESRD between patients with and without preoperative renal dysfunction following heart transplantation. Design. Fifty consecutive patients with preoperative estimated GFR ≤ than 50 ml/min were compared with 50 age-matched patients with estimated GFR ≥ than 80 ml/min who underwent heart transplantation between 1994 and 1998. We investigated two primary outcomes: death and development of ESRD. We also analyzed risk factors. Results. Eight patients (16%) developed ESRD and 19 (38%) died in the control group whereas 10 patients (20%) developed ESRD and 26 (52%) died in the renal failure group during a mean follow-up period of 6.74 ± 3.31 years. Survival and time to ESRD were not significantly different. In univariate and multivariate analysis, waiting time was the only risk factor found to predict mortality but not ESRD. High cyclosporine levels were only found to be associated with lower estimated GFR (p < 0.009). Among the control group, mortality was significantly higher in the subgroup of patients that developed ≥ 50% reduction of estimated GFR at the end of the first post transplant year (p < 0.05). Conclusions. This study suggests that low pre-transplant estimated GFR may not accurately predict long-term development of ESRD.