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Biomedical subjects

O H Frazier

Publications and source records attributed to O H Frazier.

At least 19 recordsLinked to original sources
PubMed1997

Major histocompatibility complex class II antigen expression in rejecting cardiac allografts: detection using in vivo imaging with radiolabeled monoclonal antibody.

BACKGROUND: Increased expression of major histocompatibility complex class II (MHC-II) antigen occurs during cardiac allograft rejection. We tested the hypotheses that (1) radiolabeled antibody to MHC-II antigen allows detection of cardiac allograft rejection using nuclear imaging techniques and (2) uptake of radiolabeled antibody to MHC-II antigen correlates with severity of rejection. METHODS AND RESULTS: Thirteen beagles with cervical cardiac allografts were studied for 64+/-23 days by use of myocardial biopsy and in vivo imaging. Uptake of radiolabeled (131I [n=2], 123I [n=1], or 111In [n=10]) antibody to MHC-II increased over baseline in 7 animals that developed histological evidence of progressively worsening allograft rejection (group A), from 72.2+/-46.1 to 176.8+/-102.0 counts/pixel/mCi (P<.009). In 4 beagles without progressively worsening allograft rejection (group B), uptake was unchanged during follow-up (74.4+/-43.8 and 60.2+/-37.4 counts/pixel/mCi; P=NS). In animals studied with 111In-labeled antibody, uptake increased from 102.9+/-23.1 at baseline to 233.2+/-82.7 counts/pixel/mCi at follow-up in group A animals (P=.036), with no significant change in group B (91.1+/-34.9 and 75.9+/-24.9 counts/pixel/mCi; P=NS). Uptake of 111In-labeled antibody was 107.5+/-35.7, 135.9+/-70.8, and 307.8+/-90.1 counts/pixel/mCi in biopsy samples showing evidence of mild, moderate, and severe rejection, respectively (P=.001). Biopsy samples showing mild, moderate, and intense MHC-II expression antibody uptake had uptakes of 92.6+/-36.3, 158.5+/-54.7, and 307.8+/-90.1 counts/pixel/mCi, respectively (P=.00004). CONCLUSIONS: Radiolabeled monoclonal antibodies to MHC-II antigen can detect cardiac allograft rejection in this large mammal model of cardiac allograft transplantation, and this technique may have a potential role in the detection of rejection in patients after cardiac transplantation.

Animals↗
PubMed1997

Substrate metabolism as a determinant for postischemic functional recovery of the heart.

The mammalian myocardium meets its high energy needs through the oxidation of a variety of substrates, chiefly fatty acids. This review examines the hypothesis that efficient energy transfer in the heart occurs through a series of moiety-conserved cycles, which makes the heart an obligatory "omnivore." Ischemia results in a transformation of efficient metabolic cycles to less-efficient linear pathways. Substrate metabolism during reperfusion requires the replenishment of depleted cycles and is a major determinant for the return of contractile function. Although there is growing recognition of the concept that regulation of substrate flux through metabolic pathways is shared by several of the pathway enzymes it is apparent that glucose oxidation and glycogen resynthesis promote the return of normal contractile function in the postischemic heart. This concept is supported by clinical observations on the beneficial effects of a solution containing glucose, insulin, and potassium (GIK) for treatment of refractory left ventricular contractile failure after hypothermic ischemic arrest during cardiac surgery.

Animals↗
PubMed1997

Report of the National Heart, Lung, and Blood Institute Special Emphasis Panel on Heart Failure Research.

The SEP identified priorities to support in future basic and clinical research and pointed out directions likely to result in advances against heart failure. The list is not intended to be all-encompassing and does not address, for example, exciting lines of work already under way. Rather, the recommendations are designed to point out gaps in current knowledge not being adequately addressed and highly promising new directions. Although the incidence of heart failure continues to grow, emerging lines of research provide hope that research advances will eventually lead to more effective treatment and ultimately to prevention. This research will be well served by bringing the latest multidisciplinary approaches and the best investigators to focus on the problems of heart failure. It is hoped the efforts of distinguished expert entities such as the task force and SEP will be a useful guide in addressing the needs of the biomedical community and assisting in its success.

Animals↗
PubMed1997

Long- and short-term effects of transmyocardial laser revascularization in acute myocardial ischemia.

BACKGROUND AND OBJECTIVE: This study examined the effect of transmyocardial laser revascularization (TMLR) on infarct size and global and regional left ventricular (LV) function. STUDY DESIGN/MATERIALS AND METHODS: Acute ischemia was induced in 24 dogs by ligating the left anterior descending artery. TMLR was done through a left thoracotomy in 12 dogs. The 12 control dogs had ligation only. Global and regional LV function were measured before ligation, then at 6 hours or 3 months after ligation. We calculated the volumetric ratio of damaged myocardium to myocardium at risk (Vd/Vr). RESULTS: At 6 hours, global compensation despite regional dyskinesia was universal; Vd/Vr was the same in control and TMLR dogs. At 3 months, global function during stress was significantly higher in TMLR dogs than in control dogs (P < .05); regional contractions were synergic only in TMLR dogs; mean Vd/Vr was significantly lower in TMLR dogs. CONCLUSION: TMLR limits infarct expansion and improves long-term global and regional function after acute ischemia.

Animals↗
PubMed1997

Refractory angina pectoris in end-stage coronary artery disease: evolving therapeutic concepts.

Refractory angina pectoris in coronary artery disease is defined as the persistence of severe anginal symptoms despite maximal conventional antianginal combination therapy. Further, the option to use an invasive revascularization procedure such as percutaneous coronary balloon angioplasty or aortocoronary bypass grafting must be excluded on the basis of a recent coronary angiogram. This coronary syndrome, which represents end-stage coronary artery disease, is characterized by severe coronary insufficiency but only moderately impaired left ventricular function. Almost all patients demonstrated severe coronary triple-vessel disease with diffuse coronary atherosclerosis, had had one or more myocardial infarctions, and had undergone aortocoronary bypass grafting (70% of cases). We present three new approaches with antiischemic properties: long-term intermittent urokinase therapy, transcutaneous and spinal cord electrical nerve stimulation, and transmyocardial laser revascularization.

Aged↗
PubMed1997

Development of an implantable ventricular assist system.

BACKGROUND: This study describes the present state of progress in the development of the Jarvik 2000 ventricular assist system. METHODS: Designed for implantation in the human thorax, the system consists of a small (25 cm3, 90 g) intraventricular axial-flow blood pump that transmits power and data via internal electronics and a transcutaneous energy transfer system. The pump is powered by portable internal and external polymer lithium ion batteries. The only moving part, the pump rotor, contains a permanent magnet of a brushless direct-current motor that mounts an axial-flow impeller and partial magnetic thrust support, with blood-immersed radial and thrust bearings. The motor uses a redundant coil and electric lead design, which permits continued operation in case of wire breakage. RESULTS: Seven calves have been supported for an average of 107 days (range, 40 to 162 days) with prototypes of the Jarvik 2000 ventricular assist system. No physiologic complications have occurred. When its user is at rest, the pump produces flows of 5 to 6 L/min with a decreased arterial pulse contour. Renal and hepatic functions have remained normal throughout the duration of all studies. Mean plasma free hemoglobin levels ranged from 4.3 to 11.4 mg/dL (mean, 6.3 mg/dL) for each study. Pathologic analyses of the heart and kidneys revealed no damage related to the device. CONCLUSIONS: These studies indicate that the Jarvik 2000 ventricular assist system is feasible in animals and holds promise for long-term support of patients.

Animals↗
PubMed1997

Is an integrated approach warranted for concomitant carotid and coronary artery disease?

BACKGROUND: The management of patients with severe, concomitant coronary and carotid artery occlusive disease is controversial. METHODS: Between 1975 and 1996, 512 patients (mean age, 64.9 years; 70% male) were admitted for coronary revascularization; 316 (61.7%) had asymptomatic, severe carotid disease (stenosis > 70%) and 196 (38.3%) had symptomatic carotid disease (159 [31.1%] with transient ischemia and 37 [7.2%] with completed stroke). In group 1, coronary revascularization and carotid endarterectomy were simultaneously performed in 255 patients (49.8%) with unstable angina. In group 2 (staged approach), carotid endarterectomy was performed before coronary revascularization in 257 patients (50.2%) without unstable angina. RESULTS: Before 1986, the incidence of stroke and death was greater in group 1 (n = 149) than in group 2 (n = 156) (14 [9.4%] versus 4 [2.6%]; p < 0.01). Since 1986, outcomes in group 1 (n = 106) and group 2 (n = 101) have been similar for stroke (2 [1.9%] versus 2 [2.0%]), death (4 [3.8%] versus 3 [3.0%]), and myocardial infarction (4 [3.8%] versus 5 [5.0%]). Significant univariate and multivariate predictors of adverse outcome were primarily heart-related (reoperation, intraaortic balloon use, ejection fraction < 0.50, and angina grade 4 for death; age > 70 years and congestive heart failure for stroke). CONCLUSIONS: Despite highly selected populations, contemporary surgical results do not indicate that staged treatment of severe, concomitant coronary and carotid artery occlusive disease has an advantage over simultaneous treatment. Advances in myocardial protection and perioperative hemodynamic management may account for the low incidences of stroke and death in these operations.

Adult↗
PubMed1997

Traumatic aortic transections: eight-year experience with the "clamp-sew" technique.

BACKGROUND: Because traumatic aortic transection is associated with high mortality rates, great debate exists about the appropriate operative technique for treatment of patients who have acute traumatic aortic transection. METHODS: To determine the safety and efficacy of the "clamp-sew" method, we retrospectively reviewed our 8-year experience treating 75 patients who had aortic injuries secondary to blunt trauma. Seventy-one of these patients were treated surgically. The clamp-sew method was used in all of these operations. RESULTS: Aortic cross-clamp time averaged 24 minutes (range, 14 to 36 minutes), with 4/71 having times in excess of 30 minutes. One patient (clamp time, 28 minutes) became paraplegic. Significant associated injuries were seen in 51/75 patients (48/71 patients with operation), including intrathoracic (35 patients), orthopedic (28 patients), intraabdominal (24 patients), and central nervous system (17 patients) damage. No patient died within 24 hours of operation. Overall 30-day mortality was 12% (9/75), with 7/9 having two or more aforementioned associated injuries. Of these 7, 5 had central nervous system injuries. Two of 9 died within 30 days without two or more associated injuries: 1 Jehovah's Witness of low hemoglobin, and 1 patient of sepsis. CONCLUSIONS: Although any of several maneuvers may be appropriate in managing traumatic aortic injuries, the simple "clamp-sew" technique is a safe and effective method for the treatment of traumatic aortic transections.

Adolescent↗
PubMed1997

Mechanical support in dilated cardiomyopathy: signs of early left ventricular recovery.

BACKGROUND: Recent reports have documented left ventricular recovery in patients with dilated cardiomyopathy off-loaded long term with a left ventricular assist device. We sought to document the natural history of left ventricular recovery. METHODS: We implanted the TCI left ventricular assist device without the intention to perform transplantation in 2 patients with dilated cardiomyopathy who had been rejected for transplantation. Both were in New York Heart Association functional class IV and had renal failure. One was a diabetic. We studied left ventricular function with detailed echocardiography at 4, 6, and 8 weeks postoperatively. RESULTS: With the left ventricular assist device turned off, we observed a progressive increase in myocardial contractility beginning as early as 4 weeks after implantation and improving progressively. Histologic examination showed resolution of myocytolysis in both patients. CONCLUSIONS: Left ventricular recovery begins earlier than was previously suspected. Mechanical bridge to myocardial recovery is a potential approach to therapy for such patients.

Cardiomyopathy, Dilated↗
PubMed1997

Transmyocardial laser revascularization: results of a multicenter trial with transmyocardial laser revascularization used as sole therapy for end-stage coronary artery disease.

BACKGROUND: Transmyocardial laser revascularization was used as the sole therapy for patients with ischemic heart disease not amenable to percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. This technique uses a carbon dioxide laser to create transmyocardial channels for direct perfusion of the ischemic heart. METHODS: Since 1992, 200 patients, at eight hospitals in the United States, have undergone transmyocardial laser revascularization. The patients have a combined 1560 months of follow-up for an average of 10 +/- 3 months per patient. Their age was 63 +/- 10 years and their ejection fraction was 47% +/- 12%. Eighty-two percent had at least one previous bypass graft operation and 38% had a prior angioplasty. Preoperatively, the patients underwent nuclear single photon emission computed tomography perfusion scans to identify the extent and severity of their ischemia. These scans were repeated at 3, 6, and 12 months. Angina class, admissions for angina, and medications were recorded. RESULTS: The perioperative mortality was 9%. Angina class decreased significantly from before treatment to 3, 6, and 12 months (p < 0.001). Likewise, there was a significant decrease in the number of perfusion defects in the treated left ventricular free wall. Concomitantly, there was a significant decrease in the number of admissions for angina in the year after the procedure when compared with the year before treatment (2.5 vs 0.5 admissions per patient-year). CONCLUSION: These combined results indicate that transmyocardial laser revascularization provides angina relief, decreases hospital admissions, and improves perfusion in patients with severe coronary artery disease.

Adult↗
PubMed1997

Revascularization procedures in patients with transplant coronary artery disease.

OBJECTIVE: To assess the efficacy of revascularization in cardiac transplant patients who developed de novo coronary artery disease. METHODS: Eighteen patients underwent one or more of four methods of revascularization: percutaneous transluminal coronary angioplasty (PTCA), percutaneous transluminal coronary rotational atherectomy (PTCRA), coronary artery bypass grafting (CABG), and transmyocardial laser revacularization (TMLR). Eleven PTCA procedures were performed in 10 patients 55.3 +/- 6.6 months after transplantation. Six patients underwent PTCRA 83.3 +/- 11.2 months after transplantation. Five patients underwent CABG 54.0 +/- 12.6 months after transplantation; the mean left ventricular ejection fraction was 49.6 +/- 16.9 (20-65%); hypertrophy was present in two of these patients. One patient with distal coronary artery disease and New York Heart Association class IV symptoms underwent TMLR only. One patient underwent both CABG and TMLR because of triple vessel proximal disease, diffuse distal disease, and New York Heart Association class IV symptoms. RESULTS: PTCA was successful in 10 procedures with decrease in mean stenosis from 87.7 +/- 2.7 to 24.3 +/- 6.0%. Follow-up, at 16.9 +/- 4.0 months, showed restenosis in two patients. PTCRA was successful in all patients with a decrease in mean stenosis from 83.4 +/- 4.4 to 11.7 +/- 1.9%. Short-term follow-up did not reveal reocclusion. Two CABG patients who had hypertrophy died of heart failure 2 and 9 days after their operations. One CABG patient with excellent cardiac function died after 15 days because of pulmonary failure. In one patient, left ventricular ejection fraction improved from 35 to 50%, and he is alive 64 months later. Six months after TMLR, the New York Heart Association class in one patient improved from IV to II, and his left ventricular ejection fraction improved from 29 to 42%. The ejection fraction in the patient who underwent both CABG and TMLR improved from 20 to 56% but the patient expired 7 weeks later. CONCLUSIONS: It appears that revascularization procedures can be effective in patients with coronary artery disease after cardiac transplantation and that coronary angioplasty or atherectomy would be a therapy of choice for single proximal lesions. CABG should be used cautiously and only reserved for patients with multi-vessel disease without hypertrophy. Laser revascularization with or without bypass grafting has potential to become the therapy of choice for transplant coronary artery disease.

Angioplasty, Balloon, Coronary↗
PubMed1997

The development, evolution, and clinical utilization of artificial heart technology.

The ventricular assist device has evolved into an effective clinical tool to treat patients with severe heart failure. Left ventricular assist systems, such as the HeartMate, have demonstrated their utility as short- and long-term bridges to heart transplantation and their ability to effect a degree of ventricular recovery in some patients. These devices will soon be used more commonly as an alternative to transplantation.

Biocompatible Materials↗
PubMed1996

Sudden cardiac death in cardiac transplant recipients.

BACKGROUND: Sudden cardiac death (SCD) remains a significant cause of mortality in the general population. Its role in cardiac transplant patients-including its incidence, mechanism, potential risk factors, or influence on survival in this patient population-has not been well described. METHODS AND RESULTS: We undertook a retrospective analysis of the clinical and autopsy records of 257 patient deaths. SCD was analyzed in relation to severity and frequency of rejection episodes, clinical history of arrhythmias, coronary artery disease (CAD), hypertension, diabetes, left ventricular dysfunction, and clinical history of premorbid symptoms. A total of 25 patients were identified as having died of SCD, an incidence of 9.7%: 20% died < or = 12 months after transplantation, 80% died after > 12 months, and 20% died after > or = 60 months. Patient survival ranged from 2.5 to 138 months (mean, 45.7 months). The mean number of rejection episodes per patient was 2.6, most occurring within 12 months after transplantation. Echocardiography or multigated acquisition scan revealed an ejection fraction (EF) > or = 50% in 68% of patients; however, the presence of arrhythmias, primarily atrial, was evident in 68% of patients and was equally distributed between patients with EFs > or = 50% and EFs < 50%. CAD was present in 53% of patients (10 of 19) whose angiograms were available, and the appearance of CAD after transplantation was between 29 and 85 months (mean, 51.4 months). Of the 9 patients with normal cardiac catheterization studies, 6 with available autopsy reports had documented CAD. Autopsy data in 13 of 25 patients revealed CAD in 92% and rejection in 15% (International Society for Heart and Lung Transplantation grade > 3A). Of the deaths, 64% occurred within 3 months of the last endomyocardial biopsy, 96% had normal biopsies, and the only rejection was without hemodynamic compromise. CONCLUSIONS: SCD occurs relatively frequently in the cardiac transplant population, and CAD is present in most of the patients. Because the frequency of arrhythmias is relatively high in this group, more aggressive antiarrhythmic therapy may be beneficial for patients with allograft CAD in the prevention of SCD.

Adult↗
PubMed1996

The paradox of cytokine monitoring-predictor of immunologic activity as well as immunologic silence following cardiac transplantation.

The utility of cytokine monitoring to predict the onset of significant rejection was evaluated in 34 patients following heart transplantation. Serial blood levels of 5 cytokines involved in inflammation and immune activation(IL-1, IL-2, IL-6, IL-8, and TNF) were correlated with clinical outcome and endomyocardial biopsy scores. The majority of patients (68%) experienced a significant rejection during the study period. IL-6 and IL-8 levels were effective markers of significant rejection 2-4 days before diagnosis with EMBX. IL-6 and IL-8 levels of 15 and 1000 pg/ml predicted the onset of rejection with sensitivities of 75% and 66% and specificities of 86% and 76%, respectively. In contrast, IL-6 and IL-8 levels less than 15 and 400 pg/ml predicted a rejection-free course with sensitivities of 91% and 91% and specificities of 81% and 68%, respectively. The remaining cytokines differentiated patients experiencing a clinically unremarkable course from those experiencing mild-to-moderate rejection but did not discriminate rejection severity. IL-6 levels identified steroid and OKT3 resistance within 48 hr of antirejection therapy. IL-6 levels elevated to 197 +/- 20 pg/ml among steroid-resistant patients and normalized to 20 +/- 5 pg/ml among responders. IL-8 levels delineated OKT3 resistance. IL-8 levels rose to 3496 +/- 500 pg/ml among nonresponders, whereas levels fell to 152 +/- 50 pg/ml among responders. This study demonstrates that IL-6 and IL-8 are useful markers of rejection and therapeutic efficacy following heart transplation.

Adult↗
PubMed1996

Evolution of battery-powdered, vented left ventricular assist devices.

Battery-powered, vented left ventricular assist devices are designed to provide long-term circulatory support and an enhanced qualify of life. Their ongoing evolution into an effective clinical tool to treat patients with severe heart failure has resulted from the efforts of many, the open communication among researchers involved in the program, and the strong support from the National Institutes of Health.

Equipment Design↗
PubMed1996

Surgical treatment of multiple coronary aneurysms in an elderly man.

We report an unusual case involving a 70-year-old man with multiple coronary aneurysms, including a 5-cm aneurysm of the right coronary artery. The precise size was determined with magnetic resonance imaging, although the aneurysms were diagnosed initially on angiography. Multiple coronary aneurysms are rare in adults, The cause may have been atherosclerosis, syphilis, or collagen vascular disease, all of which cause weakening of the media. The patient underwent successful operation, including coronary artery bypass grafting.

Aged↗