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Biomedical subjects

T B Ferguson

Publications and source records attributed to T B Ferguson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Inhibition of inducible nitric oxide synthase prevents myocardial and systemic vascular barrier dysfunction during early cardiac allograft rejection.

NO is produced during cardiac allograft rejection by expression of inducible NO synthase (iNOS) in the rejecting heart. Recent evidence indicates that NO modulates vascular permeability under both physiological and pathophysiological conditions. The present study explored the effects of early acute cardiac allograft rejection, and specifically the effects of NO, on myocardial and systemic vascular barrier function using a quantitative double-tracer permeation method in a rat cardiac transplant model. Early allograft rejection increased albumin permeation twofold to fivefold in the allograft heart and systemic vasculature (brain, lung, sciatic nerve, diaphragm, retina, muscle, kidney, and uvea) compared with isografts and controls. There were no detectable differences in regional blood flow or hemodynamics, suggesting that increased albumin permeation resulted from increased vascular permeability. iNOS mRNA was expressed in the allograft heart and native lung and was associated with increased serum nitrite/nitrate levels. iNOS inhibition with aminoguanidine prevented or attenuated allograft heart and systemic vascular barrier dysfunction and reduced allograft serum nitrite/nitrate levels to isograft values. Aminoguanidine did not affect the mild histological changes of rejection present in allografts. These data demonstrate the novel observations that (1) endothelial barrier function is compromised in the systemic vasculature, particularly in the brain, remote from the site of allograft rejection; (2) allograft vascular barrier dysfunction is associated with increased NO production and iNOS mRNA expression in the affected tissues (eg, native lung and grafted heart); and (3) inhibition of NO production by iNOS prevents vascular barrier dysfunction in the allograft heart and systemic vasculature.

Animals↗
PubMed1996

Inhibition of inducible nitric oxide synthase attenuates established acute cardiac allograft rejection.

BACKGROUND: We previously demonstrated that continuous treatment with aminoguanidine, a selective inhibitor of nitric oxide production by inducible nitric oxide synthase, attenuated acute cardiac allograft rejection. METHODS: A rat transplant model was used to determine (1) when inducible nitric oxide synthase was expressed in the allograft heart during unmodified acute rejection and (2) whether pulse therapy with aminoguanidine attenuated the histologic changes of established acute rejection, in comparison with the effects of pulse therapy with corticosteroids. RESULTS: Inducible nitric oxide synthase messenger RNA and protein were expressed during early and late acute rejection. Pulse therapy with aminoguanidine inhibited nitric oxide production and attenuated the histologic changes of acute rejection, but not as effectively as corticosteroid therapy (rejection scores of 4.1 +/- 0.4, 2.5 +/- 0.9, and 1.4 +/- 0.6 on postoperative day 8, for untreated, aminoguanidine-, and dexamethasone-treated allografts, respectively (scale, 0 to 5; p < 0.05). CONCLUSIONS: (1) Inducible nitric oxide synthase expression first occurs during early acute allograft rejection and persists throughout rejection and (2) nitric oxide is an important effector molecule in acute rejection. Inducible nitric oxide synthase inhibition may offer a therapeutic adjunct in the management of acute rejection.

Animals↗
PubMed1996

Arrhythmia surgery.

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Arrhythmias, Cardiac↗
PubMed1995

Modulation of in vivo alloreactivity by inhibition of inducible nitric oxide synthase.

The role of nitric oxide in the immune response to allogeneic tissue was explored in an in vivo cardiac transplant model in the rat. Nitric oxide production during organ rejection was demonstrated by elevations in systemic serum nitrite/nitrate levels and by electron paramagnetic resonance spectroscopy. Messenger RNA for the inducible nitric oxide synthase enzyme was detected in the rejecting allografted heart, but not in the nonrejecting isografted heart. The enzyme was demonstrated to be biologically active by the in vitro conversion of L-arginine to L-citrulline and was immunohistochemically localized to the infiltrating inflammatory cells. Treatment with aminoguanidine, a preferential inhibitor of the inducible nitric oxide synthase isoform, prevented the increased nitric oxide production in the transplanted organ and significantly attenuated the pathogenesis of acute rejection. Aminoguanidine treatment prolonged graft survival, improved graft contractile function, and significantly reduced the histologic grade of rejection. These results suggest an important role for nitric oxide in mediating the immune response to allogeneic tissue. Inhibition of inducible nitric oxide synthase may provide a novel therapeutic modality in the management of acute transplant rejection and of other immune-mediated processes.

Amino Acid Oxidoreductases↗
PubMed1995

On the need for improved transfusion indicators in cardiac surgery.

Guidelines for transfusion practice have had limited impact in altering physician transfusion behavior in patients undergoing cardiac operations. This may be due to a lack of consensus on the relative risks and benefits of blood in these patients who are anemic, limited access to timely data that are necessary on which to base transfusion decisions, the recognition that empiric hemoglobin/hematocrit thresholds are limited clinical indicators of the need for blood, or a combination of these. We present an overview of current transfusion and blood conservation practices in this setting, along with possible approaches to guide the decision-making process by coupling the use of transfusion algorithms with point of care testing to use more physiologic indicators of the need for blood transfusion.

Algorithms↗
PubMed1995

Inhibition of inducible nitric oxide synthase ameliorates rat lung allograft rejection.

Recently, the inducible isoform of nitric oxide synthase has been shown to be an important immunomodulation molecule in allograft rejection. We have observed the production of nitric oxide during rejection and the effect of nitric oxide synthase inhibition on allograft rejection in a rat lung transplant model. Rat left lung allotransplants were performed in two strain combinations: brown Norway-to-F344 (major histocompatibility complex incompatible); and Lewis-to-F344 (minor loci incompatible) as severe and mild rejection models respectively. Syngeneic F344-to-F344 transplants were performed as a negative control. Nitric oxide production during rejection was determined by measuring the recipient's serum nitrite/nitrate levels as a stable end product of nitric oxide. The progression of rejection was evaluated radiographically and the grade of rejection was determined histologically. After operation, recipients of allotransplantation were randomly divided into two groups and received either aminoguanidine (200 mg/kg, intraperitoneal every 6 hours), a potent inducible nitric oxide synthase inhibitor, or normal saline treatment. The levels of serum nitrite and nitrate in recipients increased in the early phase of rejection in both allotransplant combinations. However, in the terminal phase of rejection, the serum nitrite/nitrate level decreased significantly compared with the peak level in the brown Norway-to-F344 recipients. The serum nitrite/nitrate levels in the syngeneic transplant recipients were normal during the entire observation period. In aminoguanidine-treated animals, serum nitrite/nitrate levels remained normal in both allograft combinations. Significant suppression of rejection in aminoguanidine-treated recipients was observed histologically and radiographically in comparison with untreated recipients in the brown Norway-to-F344 combinations. In the Lewis-to-F344 combination, aminoguanidine treatment significantly ameliorated histologic rejection but did not affect radiologic appearance. We therefore conclude nitric oxide is produced during early allograft rejection and may prove to be a marker and mediator of early rejection. The inhibition of inducible nitric oxide synthase results in significant reduction in rat lung allograft rejection.

Animals↗
PubMed1995

Swallowing dysfunction after cardiac operations. Associated adverse outcomes and risk factors including intraoperative transesophageal echocardiography.

The frequency, importance to patient outcomes, and independent predictors of postoperative swallowing dysfunction documented by barium cineradiography were examined in 869 patients undergoing cardiac operations over a 12-month period. Swallowing dysfunction was diagnosed in 34 patients (4% incidence) and was associated with documented pulmonary aspiration in 90% of these patients, increased frequency of pneumonia (p < 0.0001), need for tracheostomy (p = 0.0002), length of stay in the intensive care unit (p = 0.0001), and duration of hospitalization after the operation (p = 0.0001). Independent predictors of postoperative swallowing dysfunction determined by multivariate logistic regression included age (p < 0.001), length of tracheal intubation after the operation (p = 0.001), and intraoperative use of transesophageal echocardiography (p = 0.003). Dysfunctional swallowing after cardiac operations, a serious complication significantly related to postoperative respiratory morbidity and extended length of hospitalization, is more common in older patients. An association between intraoperative use of transesophageal echocardiography and swallowing dysfunction was also observed in our patients.

Aged↗
PubMed1995

Electrophysiologic basis, surgical development, and clinical results of the maze procedure for atrial flutter and atrial fibrillation.

After more than a decade of experimental and clinical research into the basic mechanisms underlying atrial fibrillation, we were able to develop a surgical procedure that appears to cure the arrhythmia. This surgical procedure has been used in 100 patients in our institution and in a total of approximately 130 patients by surgeons in other institutions. The surgical results have been excellent, which indicates the sophisticated electrophysiologic mapping systems are unnecessary and that the results are not surgeon-specific.

Animals↗
PubMed1994

Feasibility of intraoperative coronary angiography during hypothermic cardioplegic arrest.

Although intraoperative coronary angioplasty has the potential to enhance revascularization in selected patients undergoing coronary bypass, this technique is only rarely performed, due in part to the lack of angiographic monitoring. Accordingly, to develop angiographic techniques potentially applicable to intraoperative angioplasty, 6 conditioned dogs were placed on full cardiopulmonary bypass, the aorta was cross-clamped, and the heart arrested with cold cardioplegia solution. After 45 minutes of arrest, selective coronary angiography was performed employing catheters introduced through a proximal aortotomy. Small-volume contrast injections resulted in excellent opacification; however, the contrast agent stagnated within the coronary tree. Fortunately, intracoronary flush injection of the saline-cardioplegia solution resulted in immediate and complete contrast washout. After discontinuation of bypass, echocardiography revealed normal left and right ventricular function. Histopathologic analysis of tissue specimens from animals in which contrast was flushed documented the presence of normal coronary arteries and myocardium. These findings demonstrate methods by which intraoperative coronary angiography can be performed in the arrested heart without having adverse effects on either the cardiac function or histologic appearance. These techniques may have application for the performance of intraoperative angioplasty.

Animals↗
PubMed1994

Direct operation versus ICD therapy for ischemic ventricular tachycardia.

Now that the implantable cardioverter defibrillator is available as a therapeutic option for the management of ventricular tachycardia (VT), some argue that there no longer should be a role for direct surgical intervention for this malignant arrhythmia. Rebuttal of this argument is difficult for the following reasons: (1) there are many patients who are candidates for implantable cardioverter defibrillator therapy but not for direct VT operation, and thus direct comparisons of the two therapies is difficult; (2) implantable cardioverter defibrillator therapy by definition is palliative, but a VT operation is curative in most instances; (3) in many electrophysiologic triage algorithms, implantation of a cardioverter defibrillator and VT operation are employed as alternative, not competitive, therapies, again making direct comparisons difficult; and (4) probably most importantly, there are misconceptions in the literature regarding the risks and benefits of direct VT surgical procedures as they are currently performed. In this brief review, we examine the currently available data on both sides of this argument.

Catheter Ablation↗
PubMed1994

Should surgeons still be implanting pacemakers?

Cardiac pacing has undergone major changes in the areas of manpower, technology, and cost over the past 10 years. Arguments have been made to eliminate cardiac surgical involvement in pacing on the basis of these three areas of change: implantations are increasingly performed by nonsurgeons, surgeons have not kept up with the technologic advances in pacing, and consolidation of bradypacing resources is necessary during a time when reimbursement has declined significantly. This study examined two eras of pacing therapy at an institution where pacemaker implantation has always been performed by cardiothoracic surgeons. The purpose of the study was to critically analyze (1) the current role (if any) of cardiothoracic surgeons in delivery of pacemaker therapy and (2) the current results of cardiothoracic surgical involvement in pacemaker implantation. In 1,562 procedures performed between 1986 and 1992, the infection rate was 0.51% and the overall complication rate (both short-term and long-term) was 5.2%. During era 1 (1/1/86 to 6/30/89), 80% of implants were single-chamber and follow-up was incomplete and dependent in many instances on the referring cardiologist/internist. For the implantations performed in the second era (7/1/89 to 12/31/92) as part of an established Pacemaker Service, complete clinical and transtelephonic follow-up services were provided by this coordinated medical-surgical approach. During era 2, 53.9% of implants were dual-chamber (79% during 1992). Total and infectious complication rates remained low in era 2 despite this change in technology.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗
PubMed1994

Surgery for cardiac arrhythmias.

The field of arrhythmia surgery has changed markedly over the past several years. The increased effectiveness of catheter ablation for the treatment of supraventricular tachycardias, the increasingly common use of surgical techniques for treating atrial fibrillation, and the continued refinement of implantable cardioverter-defibrillator technology have all altered decision-making regarding the treatment of patients with medically refractory symptomatic arrhythmias. The effects that these changes have had on patient selection and therapeutic outcomes resulted in the publication of a number of articles concerning arrhythmia surgery during the past year. Several of the most important changes in the treatment of patients with supraventricular and ventricular arrhythmias are reviewed.

Defibrillators, Implantable↗
PubMed1994

Treatment of patients with prior exit block using a novel steroid-eluting active fixation lead. Model 4068 Investigators.

An increased interest has developed in active fixation leads for several reasons. Exit block is an uncommon complication that is seen with both active and passive fixation leads. Exit block has not been a significant problem with passive fixation steroid-eluting leads and has been treated with these leads. A new steroid-eluting active fixation lead was examined for its performance in patients in whom exit block had previously occurred. The lead function was evaluated prospectively in 24 patients with a history of exit block (15 ventricular and 9 atrial). The results in patients with atrial exit block are encouraging with an average chronic stimulation threshold of 0.19 msecs at 2.5 volts. Results in the ventricle are less encouraging with 3 occurrences of recurrent exit block in 15 patients; however, the remaining patients had a good mean threshold of 0.21 +/- 0.11 msecs at 2.5 volts. There were a remarkable number of non-lead related complications suggesting that this is a substantially different group than routine implantations.

Cardiac Pacing, Artificial↗
PubMed1994

The future of arrhythmia surgery.

The future of arrhythmia surgery is discussed in light of the 25 years of historical developments that have led to the present explosion in antiarrhythmic therapies and technologies. The role of the arrhythmia surgeon in these developments is outlined, along with a number of exciting near-term and far-term developments that will continue to revolutionize therapeutic interventions for arrhythmia problems.

Arrhythmias, Cardiac↗
PubMed1993

Early cardiac allograft rejection is independent of regional myocardial blood flow.

Noninvasive telemetric monitoring of canine heterotopic cardiac allograft unipolar peak-to-peak amplitude (UPPA) has permitted prospective surveillance for rejection; moreover, this technique is able to reliably detect rejection before the development of histologic evidence of myocyte necrosis. This study was performed to determine whether early cardiac allograft rejection and the accompanying decline in allograft UPPA were associated with alterations in regional myocardial blood flow (RMBF). Seven heterotopic, intrathoracic canine cardiac transplantations were performed using triple-drug immunosuppression. Native hearts and allografts were instrumented with right ventricular and left ventricular epicardial screw-in electrodes connected to subcutaneous telemeters. Daily measurement of native and graft UPPA was performed; using radioactive microspheres, native and graft RMBF were determined during the control period and when UPPA had declined by 15%, 30%, and 45%. Graft histologic status was determined by endomyocardial biopsy at the time of RMBF determination. Mean duration of the study was 19.7 +/- 3.9 days. Rejection was documented in all animals. The UPPA was stable in native hearts; UPPA declined in the allografts after the onset of rejection. A biphasic change in allograft blood flow was seen. Initially RMBF increased as UPPA declined; a 30% to 45% reduction in UPPA was associated with a 41% increase in RMBF (p = 0.028 versus allograft control). Subsequently, a significant decline in blood flow was observed for reductions in UPPA greater than 45% (0.68 +/- 0.44 versus 1.07 +/- 0.47 mL.g-1 x min-1 for a 30% to 45% decline in UPPA; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Long-term effectiveness of surgical treatment of ectopic atrial tachycardia.

OBJECTIVES: The purpose of this study was to determine the long-term clinical outcome of patients with ectopic atrial tachycardias treated surgically. BACKGROUND: Ectopic atrial tachycardia is an uncommon arrhythmia that can be symptomatic and is associated with the development of a cardiomyopathy. Management strategies are not well defined because of the paucity of data on the long-term effectiveness of pharmacologic and nonpharmacologic therapies. METHODS: The long-term clinical impact of medical and surgical therapy was determined in 15 consecutive patients with ectopic atrial tachycardia. All 15 patients were initially treated with antiarrhythmic drugs (mean 5.7 +/- 2.2 drugs/patient). An effective drug regimen was identified in only 5 (33%) of the 15 patients; the remaining 10 patients were treated surgically. In each, individualized surgical procedures were guided by computer-assisted intraoperative mapping, with atrial plaques comprising up to 156 electrodes. Focal ablation was performed in four patients and atrial isolation procedures in six. RESULTS: The 10 patients treated surgically were followed up a mean of 4 +/- 3.2 years. Ectopic atrial tachycardia recurred in one patient. A permanent pacemaker was implanted in two patients, one of whom also required reoperation for constrictive pericarditis. There were no operative deaths. Ectopic atrial tachycardia recurred in three (60%) of the five patients discharged on antiarrhythmic drug therapy during a mean follow-up interval of 6.4 +/- 4.3 years. There was one nonarrhythmic death. CONCLUSIONS: Map-guided surgery demonstrated long-term efficacy in abolishing symptoms in 9 of the 10 patients with ectopic atrial tachycardia. Results demonstrate that surgery is effective for patients with ectopic atrial tachycardias who are not easily treated with antiarrhythmic drugs.

Adolescent↗