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Biomedical subjects

D A Murphy

Publications and source records attributed to D A Murphy.

At least 109 records · Page 6Linked to original sources

Major histocompatibility complex class I and class II expression by myocytes in cardiac biopsies posttransplantation.

A total of 85 cardiac biopsies from patients 23-265 days posttransplant were studied for the correlation of the rejection grade score with the level of major histocompatibility complex (MHC) class I and class II expression on cardiac myocytes and endothelial cells, the quantitative level of leukocytic infiltrate, and the immunophenotype of the leukocytes. Results indicate a lack of absolute correlation between rejection grade scores and levels of MHC antigen expression. Further, a lack of absolute correlation was also seen with quantitation of leukocytic infiltrates and relative levels of MHC antigen expression. Of great interest was our preliminary finding that as early as 4 weeks prior to a rejection episode scored by routine histological criteria as grade 4, cardiac biopsy from the patient demonstrated high levels of MHC class I and class II expression. Similar increases of MHC antigen expression prior to an increase in histological rejection score grades were also noted in serial biopsies of 2 other patients. These data suggest that it may be quite useful to examine levels of MHC antigens on cardiac biopsies posttransplantation as an additional parameter for monitoring of cardiac rejection episodes.

Antigens, Differentiation↗

Characterization of human cardiac infiltrating cells post transplantation. 1. Phenotypic and functional alloreactivity.

Sequential cardiac biopsies from patients post transplantation were studied for histological evidence of grades of rejection, the immunophenotype of the mononuclear cell infiltrate if present and, in addition, aliquots of the same biopsy were cultured in vitro with medium containing interleukin-2. The exuding mononuclear cells were expanded and bulk cultures and T cell lines resulting from this were evaluated phenotypically and functionally for donor specific alloreactivity. Results of these studies demonstrate: (1) No strict correlation of histological rejection grades with immunophenotype or degree of mononuclear cell infiltrate. (2) The mononuclear cell cultured from 102 biopsies yielded 47 relatively pure CD4+ T cell cultures and 12 cultures enriched for CD4+ T cells, 16 relatively pure CD8+ T cell cultures and 15 cultures enriched for CD8+ T cells, 7 cultures which consisted of dual marked CD4+ CD8+ T cells and 5 which were negative for both CD4 and CD8 but expressed CD3. (3) Of the 59 total CD4+ T cells, 6 demonstrated donor specific CTL reactivity and of the 31 CD8+ T cells, 26 demonstrated donor specific CTL activity. (4) None of the CD4+ CD8+ T cell cultures demonstrated CTL reactivity and all 5 of the CD3+ CD4- CD8- T cell cultures demonstrated potent donor specific CTL activity. (5) Of the 102 cultures, 89 showed donor specific PLT function. (6) High MHC-Class I expression by cardiac myocytes correlated with high frequency of CTL cultures. These data provide a summary of the phenotype and functional analysis of T cells in cardiac biopsy specimens and provide valuable reagents for further studies on the mechanisms involved in human cardiac allograft rejection.

Antibodies, Monoclonal↗

Anatomy of human extrinsic cardiac nerves and ganglia.

The anatomy of the human extrinsic cardiac nerves and ganglia was reinvestigated because descriptions of human cardiac innervation vary, detailed analyses of subhuman mammalian cardiac innervation reveal considerable similarities among species and the anatomic pattern of cardiac innervation observed in subhuman mammals differs significantly from those described for humans. The presence of a consistent pattern of cardiac innervation in subhuman mammals raised the question as to whether a similar pattern exists in humans. To investigate this, the cervical and thoracic autonomic nerves and ganglia were dissected in 13 embalmed and 10 autopsy cadavers. All major sympathetic cardiopulmonary nerves were found to arise from the stellate ganglia and the caudal halves of the cervical sympathetic trunks below the level of the cricoid cartilage. These sympathetic cardiopulmonary nerves usually consisted of 3 nerves on the right side and 4 on the left. In contrast to widely accepted reports, no sympathetic cardiopulmonary nerves were found to arise from the superior cervical ganglia or the thoracic sympathetic trunks inferior to the stellate ganglia. Parasympathetic cardiopulmonary nerves were found to arise from the recurrent laryngeal nerves and the thoracic vagi immediately distal to them. These nerves interconnected with sympathetic cardiopulmonary nerves anterior and posterior to the main pulmonary artery to form the ventral and dorsal cardiopulmonary plexuses. These plexuses contained relatively large discrete nerves as well as smaller interconnections. Emerging from these plexuses to innervate the ventricles were 3 distinct relatively large cardiac nerves, the right and left coronary cardiac nerves and the left lateral cardiac nerve. In addition to these 3 major nerves, small cardiac nerves arose from the plexuses and the thoracic vagi. Histologic examination of representative dissections confirmed the presence of neural tissue and identified the locations of neuronal cell bodies in these structures. Cell bodies were located in the nodose, superior cervical, middle cervical, stellate and thoracic sympathetic ganglia. The middle cervical ganglia varied in size and number. Neuronal cell bodies were found in the cervical and thoracic sympathetic trunks and in small mediastinal ganglia located along the courses of the cardiopulmonary and cardiac nerves. Marked similarities exist between the anatomy of the cardiopulmonary nerves and ganglia of humans and baboons.

Adult↗

Prevention of neurological injury during myocardial revascularization in patients with calcific degenerative aortic disease.

Neurological injury following myocardial revascularization may result from embolization of atheromatous debris from the diseased ascending thoracic aorta. Eight patients with calcified aortas who underwent elective myocardial revascularization suffered major strokes as a result of manipulation and clamping of the diseased ascending aorta during a 30-month period before July, 1981. computerized axial tomography scans demonstrated multiple cerebral infarctions in each patient. Six patients never regained consciousness and died as a result of neurological injury; 2 patients regained consciousness but were left with major neurological deficits. Later, 21 patients with calcific aortic degenerative disease underwent a specific operative protocol, designed to prevent neurological injury during elective myocardial revascularization. All 21 patients recovered without neurological complications. Specific attention to operative technique allowed this difficult group of patients with incapacitating angina and calcific degenerative aortic disease to have the benefit of coronary bypass.

Aorta, Thoracic↗

Myocardial metabolism and hemodynamic responses with fentanyl-enflurane anesthesia for coronary arterial surgery.

Ten patients for coronary vein grafting had induction of anesthesia with fentanyl (30 micrograms/kg), followed by enflurane-oxygen sufficient to decrease systolic blood pressure by 27% before intubation. Enflurane was continued in concentrations to maintain blood pressure below that with patients awake. All patients had preserved ventricular function and effective beta-blockade. Studies of hemodynamic functions and myocardial blood flow and oxygenation were done before induction, six times during anesthesia, and twice postoperatively. The blood pressure decrease on induction and before bypass was due to reduced cardiac index without decreased heart rate or systemic resistance. Stroke work index decreased 47% on induction and remained below awake level throughout. Coronary sinus blood flow decreased 26% after intubation and remained so before bypass. Without change in coronary resistance, coronary sinus oxygen content increased 30% on induction and stayed elevated before bypass. Normal lactate extraction continued after induction and increased before bypass; mean extraction decreased after bypass, with one or two hearts producing lactate in the first 24 postoperative hr. Fentanyl-enflurane-oxygen maintained a steady mild hemodynamic depression during the operation and soon afterward, which preserved myocardial oxygenation.

Anesthesia↗

Myocardial metabolism and hemodynamic responses with isoflurane anesthesia for coronary arterial surgery.

Isoflurane-oxygen was given for induction and maintenance of anesthesia to ten patients having coronary artery bypass grafts. All had preserved ventricular function without hypertension or other cardiac lesions; treatment with beta-blocking drugs was maintained until the operation in all patients. Cardiac output, arterial and central pressures, coronary sinus (CS) blood flow, arterial and CS oxygen, Hb, and lactate contents were measured before, six times during, and twice after anesthesia. On induction, systolic arterial pressure was purposely reduced 33% along with systemic resistance by increasing the concentration of isoflurane; cardiac index, heart rate, and coronary flow did not change. Coronary resistance decreased 23% and CS oxygen content increased 56%; but in three of ten patients myocardial lactate production took place, evidence of global ischemia. Induction of anesthesia was not smooth in three patients. Controlled hemodynamic depression could be maintained with isoflurane-oxygen, but the frequency of myocardial lactate production before and after perfusion was greater than with other general anesthetics. Isoflurane dilated portions of the coronary bed but, because anaerobic metabolism occurred concomitantly, the theory that redistribution of flow can take place resulting in ischemic areas of ventricle is supported.

Adult↗

Delayed closure of the median sternotomy incision.

Attempts to close a median sternotomy incision in the patient with profound cardiac or pulmonary dysfunction following a cardiac surgical procedure can result in severe hemodynamic deterioration. Delayed sternal closure in this setting may be a lifesaving technique. A method is described for delayed sternal closure that employs a temporary impermeable rubber patch sutured to the presternal fascia.

Aged↗

Preliminary observations on the effects of stimulation of cardiac nerves in man.

The dorsal mediastinal cardiac nerves were stimulated in 20 patients undergoing coronary artery bypass surgery. In no instance was an untoward effect produced in any of the patients. Stimulation of a cardiac nerve increased heart rate in eight patients and slowed heart rate in eight patients. In 12 patients stimulation of a cardiac nerve increased mean aortic pressure while in 8 patients it was decreased, even though the patients were supported by a total body perfusion pump. In 11 patients stimulation of a cardiac nerve resulted in a decrease in the coronary artery bypass graft flow, even though aortic pressure was unchanged or increased. These preliminary results suggest that individual cardiac nerves in the dorsal mediastinum of man may be capable of modifying heart rate, total peripheral vascular resistance, or coronary artery resistance. Furthermore, they demonstrate that stimulation of human dorsal mediastinal cardiac nerves can be done without untoward effects and that such stimulations may be a means to investigate the complexity of neural regulation of the human heart.

Adult↗

Improved myocardial recovery after cardioplegic arrest with an oxygenated crystalloid solution.

Possible enhancement of myocardial protection by oxygenation of a crystalloid cardioplegic solution was evaluated in a three-part study. In Part I, canine hearts underwent ischemia followed by heterogeneous cardioplegic arrest for 45 to 60 minutes. Oxygenation led to improved recovery in the left anterior descending region (47% versus 86% recovery, p less than 0.05) (15 minutes of ischemia) and in the circumflex region (9.5% versus 52% recovery, p less than 0.05) (30 minutes of ischemia). Part II was a blind prospective randomized study in 12 patients. It examined creatine kinase, myoglobin, and lactate as well as coronary sinus flow, oxygen consumption, and cardiac work 1 hour after aortic cross-clamping during atrial and during ventricular pacing. No significant difference was demonstrable between control and oxygenated solutions. In Part III, 57 coronary bypass patients were protected with a nonoxygenated solution while 94 patients received an identical oxygenated solution. Twelve-hour creatine kinase levels were similar in the nonoxygenated (9.5 +/- 16 IU, +/- standard deviation) and oxygenated (11 +/- 22 IU) groups if the cross-clamp interval was 28 minutes or less. In patients subjected to longer than 28 minutes of arrest, the 12 hour creatine kinase MB levels were more than twice as high in the nonoxygenated group (26.5 +/- 26 IU) compared to the oxygenated group (9.9 +/- 14 IU, p less than 0.05). In this canine model of heterogeneous cardioplegia and in the routine conduct of coronary bypass operations, oxygenated crystalloid cardioplegia is superior to an identical nonoxygenated solution.

Animals↗

Mediastinitis after cardiac valve operations. Impact upon survival.

Mediastinitis after cardiac valve replacement is a dreaded complication with consequent mortality estimated as high as 70%. We have reviewed 2,491 patients with cardiac valve operations to assess the impact of mediastinitis upon mortality in our institution in the past 10 years. Mediastinitis developed after valve replacement in 36 patients (1.4%). All patients required operative intervention for mediastinal infection with positive bacterial cultures. Twelve of these patients had other perioperative problems associated with a high mortality independent of mediastinitis: bacterial endocarditis not cured by valve replacement (three), recent preoperative myocardial infarction (four), triple valve disease with biventricular failure (one), and severe perioperative cerebral damage (four). Ten of these high-risk patients died (83.3%). The impact of mediastinitis upon survival is best evaluated in the remaining 24 patients without high-risk perioperative problems. Eight of these patients were managed before 1980 with débridement and irrigation as the primary treatment, with two hospital deaths (25%). Pectoral or rectus muscle flaps were frequently used after 1980 (flaps in 11 of 16 patients), leading to a significantly shorter time between diagnosis of infection and hospital discharge free of infection (62 versus 385 days, p less than 0.05). Only one of these 16 patients died. Valve re-replacement for endocarditis was performed in three of these 24 patients although 13 of 24 had positive blood cultures. Mediastinitis after valve operations in the absence of other high-risk perioperative problems can be successfully managed. Early débridement and muscle flap closure has led to a 94% survival rate in 16 patients during the past 4 years.

Adult↗

Comparison of coronary artery bypass surgery and percutaneous transluminal coronary angioplasty including surgery for failed angioplasty.

Selection and treatment of patients with ischemic heart disease is presently undergoing an evolutionary trend. Percutaneous transluminal coronary angioplasty (PTCA) has been recommended as the initial procedure for many patients with coronary artery disease and has thus redefined candidates for coronary artery bypass surgery. During our first years of experience with percutaneous angioplasty, 339 patients underwent the procedure and were compared with 338 patients who underwent isolated coronary artery bypass surgery. Patients who underwent PTCA had a shorter duration of angina and a lower number of prior myocardial infarctions and were found to have better left ventricular function (p less than 0.01). PTCA was considered initially successful in 87% (295 of 339) of patients. The most common finding at operation in those with failed angioplasty who underwent urgent or emergency revascularization was dissection of atheromatous plaque. Although the cumulative frequency of new Q waves in the entire 18-month angioplasty series was low (2.7%), the incidence was high (18%) in those with angioplasty failure and subsequent operation (N = 20) and significantly greater than in patients who had elective coronary artery bypass surgery (3.6%). Use of inotropic agents and lidocaine for ventricular arrhythmias was significantly higher in patients with unsuccessful PTCA who required operation than in those who underwent elective bypass surgery (10% vs 3% and 10% vs 1.5%, respectively; p less than 0.01). In an analysis of our entire experience between October 1980 and June 1982, 777 patients who had PTCA and 2068 patients who underwent coronary artery bypass surgery were analyzed for differences in clinical complications and early outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗