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Biomedical subjects

Patrick M McCarthy

Publications and source records attributed to Patrick M McCarthy.

At least 109 records · Page 6Linked to original sources
PubMed2002

The role of vitronectin receptor (alphavbeta3) and tissue factor in the pathogenesis of transplant coronary vasculopathy.

OBJECTIVES: This study was undertaken to test the hypothesis that transplant coronary vasculopathy (CV) is associated with increased myocardial protein expression of both tissue factor (TF) and integrin alphavbeta3. BACKGROUND: The vitronectin receptor (integrin alphavbeta3) and TF have recently been found to play a key role in apoptotic cell death and vascular endothelial cell injury. METHODS: A total of 77 heart transplant recipients underwent simultaneous endomyocardial biopsy and intravascular ultrasound (IVUS) at one year of transplant. Patients with pre-existing donor coronary atherosclerosis (n = 35) or with acute rejection (grade >1A, n = 10) at the time of the IVUS were excluded from the analysis. The remaining 32 patients constitute the cohort of the present study. A computerized biopsy score was derived based on the duration and severity of cellular rejection. Both TF and alphavbeta3 expression in the heart biopsy specimens were evaluated by immunoperoxidase histochemistry and Western blot analysis. RESULTS: Patients with CV (n = 24) had increased expression of alphavbeta3 (2.7-fold, p = 0.003) and TF (7.9-fold, p = 0.04) compared with patients without evidence of vasculopathy (n = 8). In the absence of myocardial fibrosis, alphavbeta3 expression correlated significantly with the cellular rejection score (r = 0.58, p = 0.02). CONCLUSIONS: Transplant vasculopathy is associated with increased expression of both TF and alphavbeta3. The significant correlation of alphavbeta3 with cellular rejection suggests an important role for this integrin in serving as a mechanistic link between cellular rejection and vasculopathy.

Cardiovascular Diseases↗
PubMed2002

Quantitation and distribution of beta-tubulin in human cardiac myocytes.

Increasing evidence suggests that derangements of cytoskeletal proteins contribute to alterations in intracellular signaling, myocyte function, and the coupling of myocytes to the extracellular matrix during cardiac hypertrophy and failure. Data from animal studies have shown an increased density of beta-tubulin protein in the right or left ventricle subjected to pressure overload, and have demonstrated that interfering with excess polymerization of beta-tubulin improves contractility. We tested the hypothesis that beta-tubulin is increased in human left ventricular hypertrophy and end-stage heart failure. Confocal microscopy of fluorescently labeled beta-tubulin protein revealed an increased density of the beta-tubulin network in cardiomyocytes from both hypertrophied and failing human hearts as compared to cells from nonfailing hearts. Western blot analysis on total heart homogenate showed no change in beta-tubulin when data were normalized to either actin or calsequestrin, although there was a significant increase in failing human hearts when data were normalized only for a constant amount of protein per heart. The mRNA for beta-tubulin was not changed in hypertrophied hearts, but was significantly decreased in failing human hearts. Thus, similar to animal models, we have shown that the density of the microtubular network within the cardiomyocyte is increased in end-stage failing human hearts. We have also shown for the first time that beta-tubulin density is increased in cells from hypertrophied human hearts. Although the functional implications of this finding in the human heart remain to be explored, data from animal studies suggest that increased beta-tubulin protein contributes to cardiac dysfunction.

Animals↗
PubMed2002

Atrial fibrillation: current surgical options and their assessment.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with morbidity and mortality. Traditional surgical treatment of AF is the Cox-Maze III procedure, a complicated operation. New surgical approaches include alternate energy sources (radiofrequency, microwave, cryothermy) and simplified left atrial lesion sets. These operations cure AF in 70% to 80% of patients. This review describes contemporary and emerging surgical approaches to AF, synthesizes results of these operations, and proposes new standards for reporting results of AF treatment.

Atrial Fibrillation↗
PubMed2002

Do left ventricular assist device (LVAD) bridge-to-transplantation outcomes predict the results of permanent LVAD implantation?

BACKGROUND: Implantable left ventricular assist devices (LVADs) were designed for permanent implant, but we began their use for bridge-to-transplant (BTTx) to study their safety and effectiveness. We review our experience in order to compare the BTTx lessons learned with the outcomes and goals of permanent implants. METHODS: From December 1991 until January 2002, 264 patients received 277 LVADs for BTTx. We analyzed temporal trends in pre-LVAD patient factors and device-specific time-related complications. RESULTS: Survival to transplant was 69%. Adverse event analysis demonstrated a high risk of infections (0.56, 1.28, and 1.88 per patient at 30 days and 3 and 6 months). HeartMate devices were more prone to infection than Novacor devices (p < 0.0001). Cerebral infarctions occurred less commonly than infections (0.15, 0.25, 0.30 at 30 days and 3 and 6 months), were more common in Novacor than HeartMate (p = 0.0001), and were decreased by the new Novacor Vascutek conduit (p = 0.07), but these were still slightly higher than the HeartMate (p = 0.04). Device failures occurred in 21 instances (all but one were in HeartMate devices [p = 0.04 vs Novacor]), but have significantly decreased (p < 0.0001) in HeartMate since 1998. CONCLUSIONS: Infections and device durability limit the chronic use of the HeartMate device, but device failures are decreasing. Novacor has fewer problems with infection and durability, and the new Vascutek conduit will reduce, but not eliminate, strokes.

Cerebral Infarction↗
PubMed2002

Atricure bipolar radiofrequency clamp for intraoperative ablation of atrial fibrillation.

PURPOSE: This work reports our initial evaluation and clinical experience with the Atricure bipolar radiofrequency (RF) system for intraoperative ablation of atrial fibrillation (AF). DESCRIPTION: The Atricure system includes a bipolar RF clamp and an RF generator. Lines of conduction block are created by delivery of RF energy (75 volts, 750 milliamps) to tissue compressed between the jaws of the clamp. Energy delivery is continued until the lesion is transmural, indicated by steady and reduced conductance between electrodes in the clamp. EVALUATION: The Atricure device was used for intraoperative treatment of AF in 120 patients. Lesion sets varied, as the device was used for pulmonary vein isolation, creation of right atrial lesions, or both. There were no device-related complications. Initial incomplete pulmonary vein isolation, identified by pacing, was uncommon, occurring with very thick atrial tissue and when tightening the clamp caused tissue to become folded upon itself in the jaws or to extrude beyond the jaws of the clamp. In such cases, reapplication of the RF clamp produced complete pulmonary vein isolation. CONCLUSIONS: The Atricure bipolar RF system facilitates surgical treatment of AF. Proper application of the clamp is essential to ensure continuous transmural lesions.

Atrial Fibrillation↗
PubMed2002

Computerized scoring of histopathology for predicting coronary vasculopathy, validated by intravascular ultrasound.

BACKGROUND: Allograft coronary vasculopathy results from a complex interplay between immunologic and non-immunologic factors. We devised a computerized biopsy scoring method based on histopathology to predict the development of coronary vasculopathy. METHODS: One hundred forty heart transplant recipients underwent serial intravascular ultrasound analysis at baseline (within 1 month) and at 1 year after transplantation and were evaluated for development of coronary vasculopathy (change in coronary maximal intimal thickness, CMIT). We evaluated serial endomyocardial biopsy specimens for cellular rejection, vascular rejection, ischemia, and fibrosis. In a mathematical model, we computed a biopsy score in each patient based on the duration and severity of histopathology. RESULTS: We found a significant correlation between biopsy score (RY) and progression of coronary vasculopathy (r = 0.54, p = 0.001). Using a sensitivity analysis method, an RY value of > or =560 predicted development of coronary vasculopathy with a sensitivity of 86%, specificity of 62%, and diagnostic accuracy of 80%. Compared with patients with low-risk biopsy scores (RY < 560, n = 37), patients with high-risk biopsy scores (RY > or = 560, n = 103) had increased progression of coronary vasculopathy (CMIT, 0.59 +/- 0.29 vs 0.19 +/- 0.10 mm, p < 0.001) and worse 7-year event-free survival (60% vs 91%, p = 0.01). CONCLUSION: The biopsy score is an effective method for predicting the development of coronary vasculopathy and for predicting outcome in cardiac transplant recipients.

Adult↗
PubMed2002

Increased beta-myosin heavy chain in acute cellular rejection following human heart transplantation.

BACKGROUND: Increased expression of smooth muscle and nonmuscle myosin heavy chains has been previously reported in animal models of cardiac allograft rejection. However, altered expression of beta-myosin heavy chain in human cardiac rejection has not been determined. METHODS: Two-dimensional (2D)-gel electrophoresis of endomyocardial biopsies taken from patients with (Grade 3A, n = 6) and without (Grade 0, n = 6) acute rejection were analyzed. Increased expression of two protein spots (MW approximately 12 kDa) were identified in the presence of acute rejection and were further characterized by mass spectrometry analysis. In patients who had acute rejection, protein expression was subsequently analyzed by immunoblotting on biopsies preceding, during, and following treatment of rejection. RESULTS: Mass spectrometric analysis of the protein spots detected 6 and 22 tryptic peptides, respectively. Protein sequence database search analysis identified the first protein as beta-myosin heavy chain and the second spot consisted of proteins of unidentified nature that may represent novel proteins. Immunoblotting analysis showed 1.4 x fold increase (p < 0.01) of protein expression of beta-myosin heavy chain expression in the presence of acute rejection. CONCLUSIONS: To our knowledge, this is the first 2D-gel study to describe increased expression of beta-myosin heavy chain and other proteins of unidentified nature in association with human cardiac allograft rejection.

Adult↗
PubMed2002

Volume reduction surgery for end-stage ischemic heart disease.

The Dor procedure, or infarction excision surgery, was first used in 1984. It is a surgical treatment option for patients with end-stage ischemic heart failure. In a recently published multicenter study that included a total of 439 patients, average ejection fraction increased from 29 +/- 10% to 39 +/- 12% after surgery. In our experience, the overall survival rate 18 months after surgery is 89%, and the preoperative mortality rate is 6.6%. These results are similar to the previous reports from Dor's group, which confirmed the certain value of the surgery. Echocardiography, including intraoperative transesophageal echocardiography, plays an important role in clarifying cardiac anatomies, absolute left ventricular (LV) volumes, ejection fraction, and mitral regurgitation in patients with ischemic heart failure undergoing this surgery. With the development of ultrasound and computer technology, three-dimensional echocardiography may be preferred when evaluating the surgical results, including determination of absolute LV volumes. Communication between experienced cardiac surgeons and echocardiographers in the operating room is essential for successful outcomes and reliable evaluation of the surgery.

Cardiac Surgical Procedures↗
PubMed2002

Synergistic approaches in the surgical treatment of heart failure: complex solutions for complex problems.

In the current era, with a high incidence and prevalence of heart failure, cardiologists are developing a wide range of medical therapies for this population. Working in synergy with pharmacologic therapies, surgeons are developing several innovative surgical procedures to address mechanical problems in heart failure patients that will stabilize and reverse the complex problem of heart failure.

Atrial Fibrillation↗
PubMed2002

Aortic valve surgery in patients with left ventricular dysfunction.

Patient with advanced left ventricular dysfunction and heart failure symptoms, either secondary to severe aortic stenosis and a low transvalvular gradient, or chronic aortic insufficiency are sometimes referred for cardiac transplantation. Now, with improvements in both myocardial protection and better valve prostheses, aortic valve surgery for patients with even the most advanced ventricular dysfunction can be performed with low risk.

Adult↗
PubMed2002

Induction and maintenance of an experimental model of severe cardiomyopathy with a novel protocol of rapid ventricular pacing.

OBJECTIVE: An animal model of chronic severe heart failure is needed to evaluate new mechanical devices, surgical procedures, and medical therapies. The purpose of this study was to evaluate a unique new model of severe heart failure developed by means of a novel protocol of rapid ventricular pacing. METHODS: Heart failure was induced in 8 mongrel dogs by means of rapid ventricular pacing (230 beats/min) for 4 weeks. After a sham operation, maintenance pacing at a reduced rate (190 beats/min) was continued for another 4 weeks. RESULTS: Left ventricular systolic function was significantly reduced at week 4 and remained low at week 8, including the slope of the end-systolic pressure-volume relationship (2.4 +/- 1.0 vs 0.7 +/- 0.2 vs 0.8 +/- 0.3 mm Hg/mL [baseline vs week 4 vs week 8, respectively]), ejection fraction (63% +/- 5% vs 28% +/- 7% vs 33% +/- 5%), and cardiac output (3.1 +/- 0.7 vs 2.0 +/- 0.3 vs 2.2 +/- 0.7 L/min). Significant ventricular remodeling changes took place with increased ventricular volumes and circumferential wall stress, which were stable between weeks 4 and 8. Serum catecholamine and atrial natriuretic polypeptide levels also increased from baseline but stabilized between weeks 4 and 8. The end-diastolic pressure-volume relationship also showed stable diastolic function between weeks 4 and 8. CONCLUSIONS: Induction pacing at 230 beats/min readily created severe heart failure in all animals, and a new technique of maintenance pacing provided a consistent model of severe heart failure. This model can be used to study a variety of new interventions for heart failure.

Animals↗
PubMed2002

Does off-pump coronary surgery reduce morbidity and mortality?

OBJECTIVE: To compare hospital outcomes of on-pump and off-pump coronary artery bypass surgery. METHODS: From 1997 to 2000, primary coronary artery bypass grafting was performed in 481 patients off pump and in 3231 patients on pump. Hospital outcomes were compared between propensity-matched pairs of 406 on-pump and 406 off-pump patients. The 2 groups were similar in age (P =.9), left ventricular function (P =.7), extent of coronary artery disease (P =.5), carotid artery disease (P =.4), and chronic obstructive pulmonary disease (P =.5). However, off-pump patients had more previous strokes (P =.05) and peripheral vascular disease (P =.02); on-pump patients had a higher preoperative New York Heart Association class (P =.01). RESULTS: In the matched pairs the mean number of bypass grafts was 2.8 +/- 1.0 in off-pump patients and 3.5 +/- 1.1 in on-pump patients (P <.001). Fewer grafts were performed to the circumflex (P <.001) and right coronary (P =.006) artery systems in the off-pump patients. Postoperative mortality, stroke, myocardial infarction, and reoperation for bleeding were similar in the 2 groups. There was more encephalopathy (P =.02), sternal wound infection (P =.04), red blood cell use (P =.002), and renal failure requiring dialysis (P =.03) in the on-pump patients. CONCLUSIONS: Both off- and on-pump procedures produced excellent early clinical results with low mortality. An advantage of an off-pump operation was less postoperative morbidity; however, less complete revascularization introduced uncertainty about late results. A disadvantage of on-pump bypass was higher morbidity that seemed attributable to cardiopulmonary bypass.

Aged↗