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Charles R Bridges

Publications and source records attributed to Charles R Bridges.

At least 19 recordsLinked to original sources
PubMed2014

A needleless liquid jet injection delivery method for cardiac gene therapy: a comparative evaluation versus standard routes of delivery reveals enhanced therapeutic retention and cardiac specific gene expression.

This study evaluates needleless liquid jet method and compares it with three common experimental methods: (1) intramuscular injection (IM), (2) left ventricular intracavitary infusion (LVIC), and (3) LV intracavitary infusion with aortic and pulmonary occlusion (LVIC-OCCL). Two protocols were executed. First (n&#x2009;=&#x2009;24 rats), retention of dye was evaluated 10&#xa0;min after delivery in an acute model. The acute study revealed the following: significantly higher dye retention (expressed as % myocardial cross-section area) in the left ventricle in both the liquid jet [52&#x2009;&#xb1;&#x2009;4] % and LVIC-OCCL [58&#x2009;&#xb1;&#x2009;3] % groups p&#x2009;<&#x2009;0.05 compared with IM [31&#x2009;&#xb1;&#x2009;8] % and LVIC [35&#x2009;&#xb1;&#x2009;4] %. In the second (n&#x2009;=&#x2009;16 rats), each animal received adeno-associated virus encoding green fluorescent protein (AAV.EGFP) at a single dose with terminal 6-week endpoint. In the second phase with AAV.EGFP at 6&#xa0;weeks post-delivery, a similar trend was found with liquid jet [54&#x2009;&#xb1;&#x2009;5] % and LVIC-OCCL [60&#x2009;&#xb1;&#x2009;8] % featuring more LV expression as compared with IM [30&#x2009;&#xb1;&#x2009;9] % and LVIC [23&#x2009;&#xb1;&#x2009;9] %. The IM and LVIC-OCCL cross sections revealed myocardial fibrosis. With more detailed development in future model studies, needleless liquid jet delivery offers a promising strategy to improve direct myocardial delivery.

Animals↗
PubMed2006

Bedside tool for predicting the risk of postoperative dialysis in patients undergoing cardiac surgery.

BACKGROUND: Estimation of an individual patient's risk for postoperative dialysis can support informed clinical decision making and patient counseling. METHODS AND RESULTS: To develop a simple bedside risk algorithm for estimating patients' probability for dialysis after cardiac surgery, we evaluated data of 449,524 patients undergoing coronary artery bypass grafting (CABG) and/or valve surgery and enrolled in >600 hospitals participating in the Society of Thoracic Surgeons National Database (2002-2004). Logistic regression was used to identify major predictors of postoperative dialysis. Model coefficients were then converted into an additive risk score and internally validated. The model also was validated in a second sample of 86,009 patients undergoing cardiac surgery from January to June 2005. Postoperative dialysis was needed in 6451 patients after cardiac surgery (1.4%), ranging from 1.1% for isolated CABG procedures to 5.1% for CABG plus mitral valve surgery. Multivariable analysis identified preoperative serum creatinine, age, race, type of surgery (CABG plus valve or valve only versus CABG only), diabetes, shock, New York Heart Association class, lung disease, recent myocardial infarction, and prior cardiovascular surgery to be associated with need for postoperative dialysis (c statistic=0.83). The risk score accurately differentiated patients' need for postoperative dialysis across a broad risk spectrum and performed well in patients undergoing isolated CABG, off-pump CABG, isolated aortic valve surgery, aortic valve surgery plus CABG, isolated mitral valve surgery, and mitral valve surgery plus CABG (c statistic=0.83, 0.85, 0.81, 0.75, 0.80, and 0.75, respectively). CONCLUSIONS: Our study identifies the major patient risk factors for postoperative dialysis after cardiac surgery. These risk factors have been converted into a simple, accurate bedside risk tool. This tool should facilitate improved clinician-patient discussions about risks of postoperative dialysis.

Aged↗
PubMed2006

Impact of renal dysfunction on outcomes of coronary artery bypass surgery: results from the Society of Thoracic Surgeons National Adult Cardiac Database.

BACKGROUND: Although patients with end-stage renal disease are known to be at high risk for mortality after coronary artery bypass graft (CABG) surgery, the impact of lesser degrees of renal impairment has not been well studied. The purpose of this study was to compare outcomes in patients undergoing CABG with a range from normal renal function to dependence on dialysis. METHODS AND RESULTS: We reviewed 483,914 patients receiving isolated CABG from July 2000 to December 2003, using the Society of Thoracic Surgeons National Adult Cardiac Database. Glomerular filtration rate (GFR) was estimated for patients with the use of the Modification of Diet in Renal Disease study formula. Multivariable logistic regression was used to determine the association of GFR with operative mortality and morbidities (stroke, reoperation, deep sternal infection, ventilation >48 hours, postoperative stay >2 weeks) after adjustment for 27 other known clinical risk factors. Preoperative renal dysfunction (RD) was common among CABG patients, with 51% having mild RD (GFR 60 to 90 mL/min per 1.73 m2, excludes dialysis), 24% moderate RD (GFR 30 to 59 mL/min per 1.73 m2, excludes dialysis), 2% severe RD (GFR <30 mL/min per 1.73 m2, excludes dialysis), and 1.5% requiring dialysis. Operative mortality rose inversely with declining renal function, from 1.3% for those with normal renal function to 9.3% for patients with severe RD not on dialysis and 9.0% for those who were dialysis dependent. After adjustment for other covariates, preoperative GFR was one of the most powerful predictors of operative mortality and morbidities. CONCLUSIONS: Preoperative RD is common in the CABG population and carries important prognostic importance. Assessment of preoperative renal function should be incorporated into clinical risk assessment and prediction models.

Coronary Artery Bypass↗
PubMed2006

Invited commentary.

Explore the source record for details and available documents.

Aortic Aneurysm, Abdominal↗
PubMed2006

Guidelines for the clinical use of transmyocardial laser revascularization.

Patients with chronic, severe angina refractory to medical therapy who cannot be completely revascularized with either percutaneous catheter intervention or coronary artery bypass graft surgery (CABG) are clinically challenging. Transmyocardial laser revascularization (TMR), as sole therapy or as an adjunct to CABG, may be appropriate therapy for these patients. The recommendations are based on a review of the available evidence including expert consensus opinions. The author follows the format of the American Heart Association and the American College of Cardiology guidelines for diagnostic and therapeutic procedures. There are class I indications for sole therapy TMR and class IIA indications for TMR as an adjunct to CABG. TMR is indicated for selected patients: as sole therapy for a subset of patients with refractory angina. It also may be effective as an adjunct to CABG for a subset of patients with angina who cannot be completely revascularized surgically.

Angina Pectoris↗
PubMed2005

Uniform scale-independent gene transfer to striated muscle after transvenular extravasation of vector.

BACKGROUND: The muscular dystrophies exemplify a class of systemic disorders for which widespread protein replacement in situ is essential for treatment of the underlying genetic disorder. Somatic gene therapy will require efficient, scale-independent transport of DNA-containing macromolecular complexes too large to cross the continuous endothelia under physiological conditions. Previous studies in large-animal models have revealed a trade-off between the efficiency of gene transfer and the inherent safety of the required surgical and pharmacological interventions to achieve this. METHODS AND RESULTS: Rats and dogs underwent limb or hemibody isolation via atraumatic tourniquet placement or myocardial isolation via heterotopic transplantation. Recombinant adenovirus (10(13) particles per kilogram) or recombinant adeno-associated virus (10(14) genome copies/kg) encoding the lacZ transgene was delivered through pressurized venous infusion without pharmacological mediators. Muscle exhibited almost 100% myofiber transduction in rats and dogs by X-galactosidase staining and significantly higher beta-galactosidase levels compared with nonpressurized delivery. No significant difference was seen in beta-galactosidase levels between 100- or 400-mm Hg groups. The <50-mm Hg group yielded inhomogeneous and significantly lower transgene expression. CONCLUSIONS: Uniform scale- and vector-independent skeletal and cardiac myofiber transduction is facilitated by pressurized venous infusion in anatomic domains isolated from the central circulation without pharmacological interference with cardiovascular homeostasis. We provide the first demonstration of uniform gene transfer to muscle fibers of an entire extremity in the dog, providing a firm foundation for further translational studies of efficacy in canine models for human diseases.

Animals↗
PubMed2005

Relationship between race and mortality and morbidity after valve replacement surgery.

BACKGROUND: Previous studies have shown that black race is an independent predictor of increased operative mortality after coronary artery bypass surgery. Given the higher incidence of hypertension and hypertension-associated left ventricular hypertrophy in blacks, we hypothesized that black race might be associated with increased risk of mortality and morbidity after aortic valve replacement (AVR) or mitral valve replacement (MVR). We could not identify a previous study that used a multivariable model to evaluate the association between race and operative mortality after AVR or MVR. METHODS AND RESULTS: The Society of Thoracic Surgeons National Cardiac Database was used for a retrospective review of 3137 black and 46,249 white patients who underwent MVR alone or AVR alone from 1999 through 2002. Multivariate logistic regression was used to assess the association between race and mortality and 6 other adverse outcomes (stroke, renal failure, prolonged ventilation, prolonged postoperative stay, sternal infection, and bleeding) after adjustment for covariates. Unadjusted operative mortality for MVR only was 5.60% for blacks versus 6.18% for whites (OR 0.90 [95% CI 0.71 to 1.14]) and 4.60% for blacks versus 3.62% for whites for AVR only (OR 1.28 [95% CI 1.02 to 1.62]). After adjustment for other risk factors, black race was not a significant predictor of operative mortality after AVR or MVR; however, black race was associated with an increased risk of several complications: prolonged ventilation after AVR or MVR, postoperative stay >14 days after AVR or MVR, reoperation for bleeding after AVR, and postoperative renal failure after MVR. There was no significant association between race and the risk of stroke or deep sternal wound infection for either AVR or MVR. CONCLUSIONS: In contrast to previously published results that defined race as an independent risk factor for operative mortality after coronary artery bypass surgery, race does not appear to be a significant predictor of operative mortality after isolated AVR or MVR; however, there is evidence of an association between race and certain complications.

Black or African American↗
PubMed2005

Gender-specific practice guidelines for coronary artery bypass surgery: perioperative management.

Gender differences in coronary bypass surgery have been the focus of numerous publications in recent years. Unfortunately these publications have contradictions that leave surgeons with conflicting recommendations for care. To help resolve these inconsistencies, The Society of Thoracic Surgeons (STS) Workforce on Evidence-Based Surgery has carried out an objective review of published information in this field. The STS Workforce recognizes that there are important gender issues associated with referral bias, the impact of body size, psychosocial factors, and postoperative support, but the intent of this guideline is to focus specifically on perioperative management. As with all practice guidelines, our goal is to gather the most important information, analyze the information in a logical and unbiased fashion, and make recommendations based solely on the available evidence.

Anemia↗
PubMed2005

Efficient myocyte gene delivery with complete cardiac surgical isolation in situ.

BACKGROUND: Previously, we used cardiopulmonary bypass with incomplete cardiac isolation and antegrade administration of vector for global cardiac gene delivery. Here we present a translatable cardiac surgical procedure that allows for complete surgical isolation of the heart in situ with retrograde (through the coronary venous circulation) administration of both vector and endothelial permeabilizing agents to increase myocyte transduction efficiency. METHODS: In 6 adult dogs the heart was completely isolated with tourniquets placed around both vena cavae and cannulas and all pulmonary veins. On cardiopulmonary bypass, the aorta and pulmonary artery were crossclamped, and the heart was isolated. Crystalloid cardioplegia at 4 degrees C containing 10(13) particles of adenovirus encoding LacZ and 15 microg of vascular endothelial growth factor was infused retrograde into the coronary sinus and recirculated for a total of 30 minutes. The dogs were then weaned from cardiopulmonary bypass and allowed to recover. With a catheter, 3 control dogs underwent retrograde infusion of the same cocktail without cardiac isolation or cardiopulmonary bypass. RESULTS: Beta-galactosidase activities in the cardiopulmonary bypass group were several orders of magnitude higher in both the right and left ventricles when compared with those in the control group (P < .05). X-gal staining from the cardiopulmonary bypass group showed unequivocal evidence of myocyte gene expression globally in a significant proportion of cardiac myocytes. No myocyte gene expression was observed in the control group. CONCLUSION: A novel cardiac surgical technique has been developed. This approach with cardiac isolation and retrograde delivery of vector through the coronary sinus results in efficient myocyte transduction in an adult large animal in vivo.

Animals↗
PubMed2004

Myosin gene mutation correlates with anatomical changes in the human lineage.

Powerful masticatory muscles are found in most primates, including chimpanzees and gorillas, and were part of a prominent adaptation of Australopithecus and Paranthropus, extinct genera of the family Hominidae. In contrast, masticatory muscles are considerably smaller in both modern and fossil members of Homo. The evolving hominid masticatory apparatus--traceable to a Late Miocene, chimpanzee-like morphology--shifted towards a pattern of gracilization nearly simultaneously with accelerated encephalization in early Homo. Here, we show that the gene encoding the predominant myosin heavy chain (MYH) expressed in these muscles was inactivated by a frameshifting mutation after the lineages leading to humans and chimpanzees diverged. Loss of this protein isoform is associated with marked size reductions in individual muscle fibres and entire masticatory muscles. Using the coding sequence for the myosin rod domains as a molecular clock, we estimate that this mutation appeared approximately 2.4 million years ago, predating the appearance of modern human body size and emigration of Homo from Africa. This represents the first proteomic distinction between humans and chimpanzees that can be correlated with a traceable anatomic imprint in the fossil record.

Amino Acid Sequence↗
PubMed2004

The Society of Thoracic Surgeons practice guideline series: transmyocardial laser revascularization.

BACKGROUND: Patients with chronic severe angina refractory to medical therapy who cannot be completely revascularized with either percutaneous catheter intervention or coronary artery bypass graft surgery present clinical challenges. Transmyocardial laser revascularization, either as sole therapy or as an adjunct to coronary artery bypass graft surgery, may be appropriate for some of these patients. Although transmyocardial revascularization has consistently been demonstrated as an efficacious means of relieving angina, the mechanism of its effects are still debated, and criteria for the selection of patients for this novel therapy have not been adequately defined. METHODS: We reviewed the available evidence to allow us to make recommendations for the appropriate therapeutic applications of transmyocardial revascularization following the format of the American Heart Association and the American College of Cardiology guidelines for diagnostic and therapeutic procedures. Our recommendations were classified as class I, IIA, IIB, or III. For each recommendation we defined the level of supporting evidence as A, B, or C. RESULTS: We identified class I indications for transmyocardial revascularization as sole therapy and class IIA indications for transmyocardial revascularization as an adjunct to coronary artery bypass graft surgery with levels of evidence A and B, respectively. CONCLUSIONS: Transmyocardial laser revascularization may be an acceptable form of therapy for selected patients: as sole therapy for a subset of patients with refractory angina and as an adjunct to coronary artery bypass graft surgery for a subset of patients with angina who cannot be completely revascularized surgically.

Angina Pectoris↗
PubMed2003

From controlled trials to clinical practice: monitoring transmyocardial revascularization use and outcomes.

OBJECTIVES: We sought to examine trends in the use and outcomes of transmyocardial revascularization (TMR) in community practice. We also identified important risk factors for TMR and compared outcomes of TMR combined with coronary artery bypass graft surgery (TMR + CABG) versus bypass alone in patients receiving incomplete revascularization. BACKGROUND: Although it is approved for use as a stand-alone procedure, there are limited data on the outcomes of (TMR + CABG). METHODS: We identified 3,717 patients receiving TMR at 173 U.S. hospitals participating in the Society of Thoracic Surgeons (STS) National Cardiac Database. Baseline characteristics and outcomes in these patients were compared with those from six published randomized TMR trials. Multivariable logistic regression was used to identify clinical risk factors for mortality with TMR. Risk-adjusted mortality was also compared for TMR + CABG relative to CABG only in patients not amenable to complete traditional revascularization. RESULTS: Between January 1998 and December 2001, the number of STS hospitals performing TMR and total procedural counts increased markedly, driven predominately by more TMR + CABG cases. Overall mortality rates for TMR-alone and TMR + CABG were 6.4% and 4.2%, respectively. Operative risks were significantly higher in those patients with recent myocardial infarction, unstable angina, and depressed ventricular function. Among patients receiving incomplete revascularization, TMR + CABG was not associated with decreased mortality risk compared with CABG alone, adjusted odds ratio 1.11 (95% confidence interval 0.74 to 1.67). CONCLUSIONS: The use of TMR, and in particular, TMR + CABG, is expanding in community practice. Although procedural risks are high, there is room for optimization through improved patient selection and timing of the procedure. Further studies of TMR + CABG are needed given its growing use and unclear benefits.

Aged↗
PubMed2003

Cardiac surgery in African Americans.

Retrospective and prospective randomized studies that provide information on the influence of race on the morbidity and mortality of cardiac surgical procedures are reviewed. We intentionally focus our attention on the specific outcomes of these procedures in African Americans because African Americans have a high incidence of all-cause cardiovascular mortality and a high prevalence of a number of risk factors associated with cardiovascular mortality. Furthermore, numerous studies have confirmed that blacks, as a function of race, lack equal access to diagnostic and therapeutic invasive cardiac procedures. Here we use the terms "black" and "African American" interchangeably. In this context we interpret both terms to refer to Americans of African descent. Similarly, we use the term "white" or "Caucasian" interchangeably to refer to Americans of European descent.

Black or African American↗
PubMed2003

Cardiac surgery in nonagenarians and centenarians.

BACKGROUND: Nonagenarians and centenarians are a rapidly growing segment of the population. No previous study has used a national database to compare outcomes in these patients to those of other groups undergoing cardiac surgical procedures. STUDY DESIGN: The Society of Thoracic Surgeons National Database was used to review retrospectively 662,033 patients (5 patients more than 100 years of age; 1,092 patients 90 to 99 years; 59,576 patients 80 to 89 years; and 621,360 patients 50 to 79 years of age) who underwent cardiac surgical procedures from 1997 through 2000. These included 575,389 patients who had undergone coronary artery bypass grafting (CABG) only; 56,915 patients with CABG and concomitant mitral or aortic valve replacement or repair (CABG+VALVE); and 49,729 patients with mitral or aortic valve repair or replacement only (VALVE-only). A multivariate logistic regression model was developed to examine predictors of operative mortality in patients more than 90 years of age. RESULTS: For CABG-only patients, operative mortality was 11.8% for patients more than 90 years of age, 7.1% for those 80 to 89 years, and 2.8% for those 50 to 79 years. The incidence of renal failure and prolonged ventilation was highest among patients more than 90 years of age (9.2% and 12.2%), compared with those 80 to 89 years (7.7% and 10.5%) or 50 to 79 years (3.5% and 6.0%). For VALVE-only patients and CABG+VALVE patients operative mortality for those more than 90 years of age was 11.4% and 12.0%, respectively, compared with 8.3% and 11.5% for those 80 to 89 years and 4.3% and 7.6% for those 50 to 79 years. The major preoperative risk factors for operative mortality among patients more than 90 years of age undergoing isolated CABG were as follows (C-index, 0.68): emergent/salvage: odds ratio, 2.26; 95% confidence interval, 1.38-3.69; preoperative intraaortic balloon pump: odds ratio, 2.79; 95% confidence interval, 1.47-5.32; renal failure: odds ratio, 2.08; 95% confidence interval, 1.12-3.86; peripheral vascular disease or cerebrovascular vascular disease: odds ratio, 1.39, 95% confidence interval, 0.96-2.02; mitral insufficiency: odds ratio, 1.50; 95% confidence interval, 0.93-2.41. Approximately 57% of the nonagenarians and centenarians lacked any of the first four risk factors and had an operative mortality of 7.2%. CONCLUSIONS: Operative mortality and complication rates associated with cardiac surgical procedures are highest for nonagenarians and centenarians. But with careful patient selection, a majority of these patients have a lower risk of CABG-related mortality approaching that of younger patients.

Age Factors↗