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Biomedical subjects

O H Frazier

Publications and source records attributed to O H Frazier.

At least 163 records · Page 9Linked to original sources

Usefulness of the QTc interval in predicting acute allograft rejection.

BACKGROUND: Endomyocardial biopsy (EMB) is the gold standard for detecting cardiac allograft rejection. However, EMB is invasive, costly, and unsuitable for frequent monitoring. Recent studies have shown that acute allograft rejection causes ventricular conduction disturbances. Therefore we tested the hypothesis that the electrocardiographic QTc interval correlates with the histopathologic degree of allograft rejection. METHODS: Between January 1994 and April 1997, 65 adult cardiac allograft recipients (mean age 52.1 +/- 1.7 years) were studied from transplantation until hospital discharge. During EMB, a 12-lead electrocardiogram was obtained. In grading acute allograft rejection, we used both the Texas Heart Institute (THI) scale and the International Society for Heart and Lung Transplantation (ISHLT) scale. 212 paired biopsy specimens and QTc intervals (mean 3.3 per patient) were obtained. We considered an increase of more than 10% of the QTc interval a rejection. RESULTS: Of the biopsy specimens 177 showed no or mild rejection (THI grade 0-5; ISHLT grade O-IIIA), and 35 showed moderate to severe rejection (THI grade 6-10; ISHLT IIIA-IV). The mean QTc interval was 449 +/- 2 msec for the first group and 517 +/- 11 msec for the second group (p = 0.0001). The correlation between the biopsy grades and the percentage of the changes in the QTc interval was r = 0.73 (p = 0.001). The QTc interval had a sensitivity of 86% (30/ 35) in predicting rejection and a specificity of 88% (1551177) in predicting the absence of rejection. CONCLUSIONS: Determination of the QTc interval is an accurate, noninvasive means of detecting acute cardiac rejection. Adoption of QTc testing may allow EMB to be used less frequently and more selectively.

Electrocardiography↗

Low serum cholesterol levels predict high perioperative mortality in patients supported by a left-ventricular assist system.

BACKGROUND: Although the use of a left-ventricular assist system (LVAS) provides circulatory support for end-stage heart failure patients awaiting heart transplantation, this procedure is accompanied by a relatively high perioperative mortality. The aim of this retrospective study was to identify those patients preoperatively which have the highest perioperative mortality. METHODS AND RESULTS: Forty-five consecutive patients undergoing LVAS implantation were evaluated for preoperative risk factors, including body mass index, hemodynamic data, and blood chemistry studies by multivariate analysis. They were divided into (1) patients who were successfully transplanted (n = 25) and (2) patients who died before transplantation (n = 20). The nonsurvivors were subclassified into patients who died within 14 days after surgery (n = 11) and patients who died after 2 weeks of device implantation (n = 9). Hemodynamic parameters were the same in both groups, but total cholesterol was significantly lower in the nonsurvivors than in the survivors (90 +/- 7 vs. 144 +/- 8 mg/dl, respectively, p < 0.0001). The sensitivity of predicting perioperative death with a serum cholesterol below 100 mg/dl was 100%, the specificity of predicting survival with a serum cholesterol above 120 mg/dl was 87%. CONCLUSION: In this small retrospective study, there was a correlation between total cholesterol levels and survival of patients with advanced heart failure on mechanical support. A cholesterol level below 100 mg/dl was accompanied by a high perioperative mortality. In contrast, a cholesterol level above 120 mg/dl was accompanied by a 87% chance of survival. The results suggest a predictive value of cholesterol which is independent of the hemodynamic status.

Biomarkers↗

Transmyocardial laser revascularization. Does it have a role in the treatment of ischemic heart disease?

Transmyocardial laser revascularization, with or without coronary artery bypass grafting, is an alternative modality for complete revascularization in selected patients with coronary artery disease. Arguably, this modality works by shunting left ventricular blood directly into the ischemic myocardium via laser-mediated transmural channels. In clinical trials, drilling of laser channels has been strongly correlated with long-term improvement of angina, but a causal relationship has not yet been documented. For now, the usefulness of transmyocardial laser revascularization and the nature of its mechanism remain controversial. Some researchers question the existence of myocardial sinusoids altogether. Others question the physiologic possibility of moving blood from the left ventricular cavity into the myocardium against a pressure gradient. Further questions concern the possible routes through which the additional blood gains access to the myocardium; the difficulty of objectively documenting improved myocardial perfusion after transmyocardial laser revascularization; and the nature of the mechanism responsible for the observed clinical benefit. This article examines the different aspects of this controversy and discusses the current status of transmyocardial laser revascularization, as well as possible future directions.

Cardiac Output↗

Cardiac transplantation for pediatric patients. With inoperable congenital heart disease.

Recent studies have reported the expanding use of transplantation as the definitive option for pediatric patients with inoperable congenital heart disease. This study compares perioperative risk factors and outcomes in pediatric patients who received heart transplants for congenital heart disease with those in pediatric patients who received heart transplants for cardiomyopathy. Retrospective data collected on 40 consecutive pediatric patients undergoing cardiac transplantation from 1 January 1990 through 31 January 1995 provided the following results: 26 patients with cardiomyopathy (mean age, 7.6 years) and 14 patients with congenital heart disease (mean age, 7.2 years) underwent heart transplantation. Between groups, no significant difference was detected in waiting time for a donor heart (cardiomyopathy = 85 days, range = 2 to 409; congenital heart disease = 126 days, range = 9 to 396; P = NS); in donor/recipient weight ratio (1.27 +/- 0.34 vs 1.27 +/- 0.28, P = NS); or in ischemic times (209 +/- 92 minutes vs 248 +/- 70 minutes, P = NS). Cardiopulmonary bypass times accounted for the only significant difference (73 +/- 21 minutes vs 102 +/- 29 minutes, P = 0.003). No significant difference was found in the number of infection episodes, total days hospitalized, rejection episodes, or incidence of transplant coronary artery disease. Forty-month actuarial survival was 88% +/- 6% and 92% +/- 7% for cardiomyopathy and congenital heart disease transplant recipients, respectively (P = NS). We conclude that post-transplantation morbidity and mortality in patients with previous congenital heart disease are not significantly different from morbidity and mortality in patients with cardiomyopathy. Transplantation should be considered an acceptable therapeutic option for patients with congenital heart disease when surgical repair of the native heart is not possible.

Adolescent↗

Improvement of reversible ischemia in severe post-transplantation coronary artery disease.

Coronary artery disease is a major cause of morbidity and mortality in patients who have undergone heart transplantation. Patients are often asymptomatic during the onset of the disease, and managing the disease is difficult. This report describes the case of a patient with post-transplantation coronary artery disease who, despite the severe, progressive appearance of the disease on angiographic examination, showed evidence of autorevascularization and collateralization.

Cardiac Catheterization↗

The HeartMate left ventricular assist system. Overview and 12-year experience.

Cardiac transplantation has become a widely accepted option for treating end-stage heart failure. As the waiting time for donor hearts grows, new generations of left ventricular assist systems are being developed for patients awaiting transplantation. Great strides have been made in the study and use of such devices, both as temporary support and (perhaps ultimately) as permanent implants. The Texas Heart Institute has been involved with the development of the HeartMate left ventricular assist systems, which have been used almost exclusively as a temporary bridge. Herein we review our 12-year clinical experience with the HeartMate left ventricular assist systems as a bridge to transplantation and as a long-term circulatory assist device that aids in cardiac repair. Trials of the HeartMate as a permanent support system for patients with end-stage heart failure who are not suitable candidates for transplantation are currently under way.

Adolescent↗

Linked pacing after heterotopic heart transplantation with concurrent left ventricular reduction of the native heart.

A 30-year-old man with dilated cardiomyopathy underwent heterotopic heart transplantation, concurrently with surgical reduction of the native left ventricle, a mitral valvuloplasty, and an apical thrombectomy. Postoperatively, the patient had hemodynamic instability that was refractory to conventional medical therapy. Temporary sequential pacing of the 2 hearts was used to induce timed counterpulsation, which resulted in marked hemodynamic improvement. To the best of our knowledge, this case involves the 1st report in the English-language literature of clinical usage of paced, linked counter-pulsation to treat acute hemodynamic compromise early after heterotopic heart transplantation.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗