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Biomedical subjects

O H Frazier

Publications and source records attributed to O H Frazier.

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

Postauricular percutaneous power delivery for permanent mechanical circulatory support.

OBJECTIVE: Percutaneous driveline infection continues to detract from both quality and length of life in patients with a left ventricular assist device. We have pursued an alternative route by using a skull-mounted percutaneous pedestal similar to cochlear implant technology. We have now used this method in patients implanted with the Jarvik 2000 heart (Jarvik Heart, Inc, New York, NY) as destination therapy for end-stage (New York Heart Association class IV) heart failure. METHODS: Four men with cardiomyopathy aged 61 to 72 years received the Jarvik 2000 heart with postauricular power delivery for permanent mechanical circulatory support. The power cable was brought through the second posterior intercostal space and routed through the neck to a percutaneous titanium implant screwed to the skull. This joins with the cable to the external controller and battery. RESULTS: In 3 patients the pedestal healed well and remained free from infection up to 1 year. The system was user friendly, and the whole external apparatus is exchangeable. The second patient had a subdural hematoma. This caused us to improve the preparation and modify the implant procedure. CONCLUSION: For widespread use, permanent implantable circulatory support requires a reliable, user-friendly device with freedom from powerline infection. Our early experience with the Jarvik 2000 heart suggests that rigid fixation and the vascularity of scalp skin promote healing and reduce the risk of driveline infection.

Aged↗
PubMed2002

Downregulation of metabolic gene expression in failing human heart before and after mechanical unloading.

BACKGROUND: We have previously shown that several metabolic genes are downregulated in the failing human heart. We now tested the hypothesis that mechanical unloading might reverse this process. METHODS: Clinical data and myocardial tissue were collected from 14 failing hearts paired for the time of implantation and explantation of a left ventricular assist device (LVAD) and compared to 10 non-failing hearts. Transcript levels for key regulators of energy metabolism and for atrial natriuretic factor (ANF) were measured by real-time quantitative RT-PCR. RESULTS: The expression of the glucose transporter 1 and 4 (GLUT1, GLUT4), muscle carnitine palmitoyl transferase-1 (mCPT-1), and uncoupling protein 3 (UCP3) were downregulated by up to 80% in the failing heart. Although LVAD treatment improved clinical markers of heart failure (decrease of left ventricular diastolic dimension and normalization of serum sodium), only UCP3 expression reversed to non-failing transcript levels following mechanical unloading. CONCLUSIONS: LVAD treatment only partially reverses depressed metabolic gene expression in the failing human heart. Reversal of depressed UCP3 expression may be an important mechanism for reducing the formation of oxygen-derived free radicals. Further studies are necessary to define the effects of mechanical unloading on post-transcriptional mechanisms.

Adult↗
PubMed2002

Reverse remodeling of the failing human heart with mechanical unloading. Emerging concepts and unanswered questions.

Anecdotal and clinical evidence suggests that mechanical unloading may restore cardiac function by inducing changes in the biological properties of the failing heart. This challenges the notion that the progression of end-stage heart failure is an irreversible process ending in either death of the patient or transplantation. Although it is still not clear how mechanical unloading of the failing heart improves cardiac function, the process likely involves adaptive responses of cardiac myocytes on the cellular, extracellular, and subcellular levels.

Heart Failure↗
PubMed2001

Metabolic gene expression in fetal and failing human heart.

BACKGROUND: Previous studies suggest that the failing heart reactivates fetal genes and reverts to a fetal pattern of energy substrate metabolism. We tested this hypothesis by examining metabolic gene expression profiles in the fetal, nonfailing, and failing human heart. METHODS AND RESULTS: Human left ventricular tissue (apex) was obtained from 9 fetal, 10 nonfailing, and 10 failing adult hearts. Using quantitative reverse transcription-polymerase chain reaction, we measured transcript levels of atrial natriuretic factor, myosin heavy chain-alpha and -beta, and 13 key regulators of energy substrate metabolism, of which 3 are considered "adult" isoforms (GLUT4, mGS, mCPT-I) and 3 are considered "fetal" isoforms (GLUT1, lGS, and lCPT-I), primarily through previous studies in rodent models. Compared with the nonfailing adult heart, steady-state mRNA levels of atrial natriuretic factor were increased in both the fetal and the failing heart. The 2 myosin heavy chain isoforms showed the highest expression level in the nonfailing heart. Transcript levels of most of the metabolic genes were higher in the nonfailing heart than the fetal heart. Adult isogenes predominated in all groups and always showed a greater induction than the fetal isogenes in the nonfailing heart compared with the fetal heart. In the failing heart, the expression of metabolic genes decreased to the same levels as in the fetal heart. CONCLUSIONS: In the human heart, metabolic genes exist as constitutive and inducible forms. The failing adult heart reverts to a fetal metabolic gene profile by downregulating adult gene transcripts rather than by upregulating fetal genes.

Acyl-CoA Dehydrogenase↗
PubMed2001

Long-term use of a left ventricular assist device for end-stage heart failure.

BACKGROUND: Implantable left ventricular assist devices have benefited patients with end-stage heart failure as a bridge to cardiac transplantation, but their long-term use for the purpose of enhancing survival and the quality of life has not been evaluated. METHODS: We randomly assigned 129 patients with end-stage heart failure who were ineligible for cardiac transplantation to receive a left ventricular assist device (68 patients) or optimal medical management (61). All patients had symptoms of New York Heart Association class IV heart failure. RESULTS: Kaplan-Meier survival analysis showed a reduction of 48 percent in the risk of death from any cause in the group that received left ventricular assist devices as compared with the medical-therapy group (relative risk, 0.52; 95 percent confidence interval, 0.34 to 0.78; P=0.001). The rates of survival at one year were 52 percent in the device group and 25 percent in the medical-therapy group (P=0.002), and the rates at two years were 23 percent and 8 percent (P=0.09), respectively. The frequency of serious adverse events in the device group was 2.35 (95 percent confidence interval, 1.86 to 2.95) times that in the medical-therapy group, with a predominance of infection, bleeding, and malfunction of the device. The quality of life was significantly improved at one year in the device group. CONCLUSIONS: The use of a left ventricular assist device in patients with advanced heart failure resulted in a clinically meaningful survival benefit and an improved quality of life. A left ventricular assist device is an acceptable alternative therapy in selected patients who are not candidates for cardiac transplantation.

Activities of Daily Living↗
PubMed2001

Sustained angina relief 5 years after transmyocardial laser revascularization with a CO(2) laser.

BACKGROUND: Although transmyocardial laser revascularization (TMR) has provided symptomatic relief of angina over the short term, the long-term efficacy of the procedure is unknown. Angina symptoms as assessed independently by angina class and the Seattle Angina Questionnaire (SAQ) were prospectively collected up to 7 years after TMR. METHODS: Seventy-eight patients with severe angina not amenable to conventional revascularization were treated with a CO(2) laser. Their mean age was 61+/-10 years at the time of treatment. Preoperatively, 66% had unstable angina, 73% had had >/=1 myocardial infarction, 93% had undergone >/=1 CABG, 42% had >/=1 PTCA, 76% were in angina class IV, and 24% were in angina class III. Their average pre-TMR angina class was 3.7+/-0.4. RESULTS: After an average of 5 years (and up to 7 years) of follow-up, the average angina class was significantly improved to 1.6+/-1 (P=0.0001). This was unchanged from the 1.5+/-1 average angina class at 1 year postoperatively (P=NS). There was a marked redistribution according to angina class, with 81% of the patients in class II or better, and 17% of the patients had no angina 5 years after TMR. A decrease of >/=2 angina classes was considered significant, and by this criterion, 68% of the patients had successful long-term angina relief. The angina class results were further confirmed with the SAQ; 5-year SAQ scores revealed an average improvement of 170% over the baseline results. CONCLUSIONS: The long-term efficacy of TMR persists for >/=5 years. TMR with CO(2) laser as sole therapy for severe disabling angina provides significant long-term angina relief.

Adult↗
PubMed2001

Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil-based formulation of cyclosporine--results at 24 months after transplantation.

BACKGROUND: The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection. The original oil-based form of cyclosporine demonstrated unpredictable absorption resulting in an increased frequency of acute and chronic rejection in patients with poor bioavailability. The primary end. points of the present, prospective, randomized multicenter, double-blind trial were to compare the efficacy of the micro-emulsion form of cycolsporine (CsA-NL) with the oil-based formulation as determined by cardiac allograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with Sandimmune CsA-(SM) in the study population. The 6-month analysis of the study showed reduced number of CsA-NL patients requiring antilymphocyte antibody therapy for rejection, fewer International Society of Heart and Lung Transplantation grade > or =3A rejections in female patients and fewer infections. Our report represents the final analysis of the results 24 months after transplantation. METHODS: A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM. Acute allograft rejection was diagnosed by endomyocardial biopsy and graded according to the International Society of Heart and Lung Transplantation nomenclature. Kaplan-Meier analysis and Fisher's exact test were used for comparisons between groups. RESULTS: After 24 months, allograft and recipient survival were identical in both groups. There were fewer CsA-NL patients (6.9%) requiring antilymphocyte antibody therapy for rejection than in the CsA-SM-treated patient group (17.7%, P=0.002). There were fewer discontinuations of study drug for treatment failures in the CsA-NL groups (7; 3.7%) compared with the CsA-SM group (18; 9.4%, P=0.037). The average corticosteroid dose was lower in the CsA-NL group (0.37 mg/kg/day) compared with the CsA-SM group (0.48 mg/kg/day, P=0.034) over the 24-month study period. Overall, there was no difference in blood pressure or creatinine between the two study groups. CONCLUSIONS: The final results of this multi-center, randomized study of two forms of cyclosporine confirmed that there were fewer episodes of rejection requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated with CsA-SM. The use of CsA-NL did not predispose these patients to a higher risk of adverse events.

Adolescent↗
PubMed2001

Implantable cardioverter defibrillator patch erosion in a heart transplant patient.

A 57-year-old man who had received an automatic implantable cardioverter defibrillator and subsequent orthotopic heart transplant presented to medical attention for hemoptysis. The hemoptysis was caused by the migration of the left ventricular patch of the automatic implantable cardioverter defibrillator, which had been left in place at the time of orthotopic heart transplant. The patch had eroded into the left lung. We recommend that implantable cardioverter defibrillators be removed completely at the time of heart transplantation to prevent subsequent complications.

Defibrillators, Implantable↗
PubMed2001

Research and development of an implantable, axial-flow left ventricular assist device: the Jarvik 2000 Heart.

Advances in technology and increased clinical need have led to the development of a new type of blood pump. The Jarvik 2000 Heart is an electrically powered, axial-flow left ventricular assist device that has been developed during the past 13 years. Unlike first-generation left ventricular assist devices, which were developed in the 1970s and were designed to totally capture the cardiac output, the Jarvik 2000 is designed to normalize the cardiac output by augmenting the function of the chronically failed heart for extended periods. Design iterations have been tested in 67 animals, and clinical trials have recently begun. Three patients have received the Jarvik 2000 as a bridge to transplantation, and 1 patient is being supported permanently outside the hospital. All 4 patients have improved from New York Heart Association functional class IV to class I, and 2 of them have been discharged from the hospital after heart transplantation. The experimental and clinical results indicate that the Jarvik 2000 can provide physiologic support with minimal complications and is reliable, biocompatible, and easy to implant.

Animals↗
PubMed2001

A multicenter, randomized, controlled trial of Celsior for flush and hypothermic storage of cardiac allografts.

BACKGROUND: A multicenter, randomized, controlled, open-label trial was conducted to evaluate the safety and efficacy of Celsior when used for flush and hypothermic storage of donor hearts before transplantation. METHODS: Heart transplant recipients were randomized to one of two treatment groups in which donor hearts were flushed and stored in either Celsior or conventional preservation solution(s) (control). Study subjects were followed for 30 days after transplantation. RESULTS: A total of 131 heart transplant recipients were enrolled (Celsior, n = 64; control, n = 67). The treatment groups were evenly distributed in donor and recipient base line characteristics. Graft loss rate was lower in the Celsior group on day 7 (3% versus 9%) and on day 30 (6% versus 13%), but the difference was not statistically significant based on 95% confidence interval analysis. No significant difference was measured between the Celsior and control groups in 7-day patient survival (97% versus 94%) and the proportion of patients with one or more adverse events (Celsior, 88%; control 87%) or serious adverse events (Celsior, 38%; control, 46%). Significantly fewer patients in the Celsior group developed at least one cardiac-related serious adverse event (13% versus 25%). CONCLUSIONS: Celsior was demonstrated to be as safe and effective as conventional solutions for flush and cold storage of cardiac allografts before transplantation.

Adult↗
PubMed2001

Myocardial tumor necrosis factor-alpha expression does not correlate with clinical indices of heart failure in patients on left ventricular assist device support.

BACKGROUND: Mechanical unloading with a left ventricular assist device (LVAD) can improve clinical indices of heart failure and alter myocardial tumor necrosis factor-alpha (TNFalpha) expression, but a correlation between clinical and molecular indices has not been established. METHODS: We enrolled 14 patients with end-stage heart failure treated with drugs and mechanical unloading in a protocol including the collection of myocardial tissue samples at LVAD implantation and explantation. Ten nonfailing donor hearts served as controls. TNFalpha expression was measured by quantitative reverse transcription polymerase chain reaction. Clinical indices of heart failure were retrospectively analyzed and correlated with myocardial TNFalpha expression. RESULTS: Left ventricular end-diastolic dimension decreased (p < 0.01) and cardiac index (p < 0.001) increased with unloading. Abnormal values of serum sodium, creatinine, blood urea nitrogen, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, and albumin showed a trend toward normalization with mechanical unloading. TNFalpha expression was increased in 5 of 14 patients and decreased with mechanical unloading in 4 of them. Surprisingly, there was no correlation between mRNA levels of TNFalpha and any of the clinical indices studied. CONCLUSIONS: Although clinical indices of heart failure improve and elevated levels of myocardial TNFalpha expression decrease with mechanical unloading, there is no correlation between the two. Thus, clinical and molecular indices of heart failure in LVAD-supported patients do not always correlate.

Adolescent↗
PubMed2001

Regression of fibrosis and hypertrophy in failing myocardium following mechanical circulatory support.

BACKGROUND: The cellular and structural changes that occur during long-term ventricular unloading leading to cardiac recovery are poorly understood. However, we have previously demonstrated that left ventricular assist device (LVAD) support leads to a significant decrease in intracardiac tumor necrosis factor-alpha (TNF-alpha), a protein capable of producing hypertrophy and fibrosis. METHODS: To further define the beneficial effects of long-term ventricular unloading on cardiac function, we determined the effect of mechanical circulatory support on fibrosis and hypertrophy in paired myocardial samples of 18 patients with end-stage cardiomyopathy obtained at the time of LVAD implantation and removal. RESULTS: We determined total collagen as well as collagen I and III by a semiquantitative analysis of positive immune-stained areas in pre- and post-LVAD myocardial samples. We found that total collagen content was reduced by 72% (p < 0.001), whereas collagen I content decreased by 66% (p < 0.001) and collagen III content was reduced by 62% (p < 0.001). Next, we determined myocyte size by direct analysis of cellular dimensions utilizing a computerized edge detection system in pre- and post-LVAD myocardial samples. We found that myocyte size decreased in all patients studied for an average reduction of 26% (33.1 +/- 1.32 to 24.4 +/- 1.64 microm, p < 0.001). CONCLUSION: These data demonstrate that long-term mechanical circulatory support significantly reduces collagen content and decreases myocyte size. We suggest that the reduction of fibrosis and hypertrophy observed may in part contribute to the recovery of cardiac function associated with long-term mechanical circulatory support.

Adult↗
PubMed2001

Online detection of myocardial ischemia by near infrared spectroscopy with a fiberoptic catheter.

BACKGROUND: The interruption of myocardial O2-supply in acute myocardial ischemia causes differences in coronary venous O2-content. In this study, the oxygenation status of coronary sinus blood is detected in myocardial ischemia by near infrared (NIR) spectroscopy. METHOD: For the intravascular application, a new fiberoptic catheter is developed. After calibration of the catheter by perfusion of blood with standardized gas mixtures in an in vitro experiment, the in vivo application was performed in 12 domestic pigs. The catheter was placed into coronary sinus and an anterior ischemia was induced by temporary occlusion of LAD. NIR graphs and hemodynamic data were obtained for 90 min ischemia and 90 min reperfusion time. RESULTS: Main NIR-spectroscopic differences between oxygenated and de-oxygenated hemoglobin took place in O2-concentrations less than 30%. Coronary sinus NIR spectra of hemoglobin-oxygen binding showed significant, reproducible differences between pre-ischemia, LAD-occlusion and reperfusion. NIR graphs also show variations related to CO2-concentration, pH and temperature. CONCLUSION: The intravascular application of NIR spectroscopy could be a reliable tool in detection and follow-up of acute myocardial ischemia and infarction.

Animals↗
PubMed2001

Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation.

BACKGROUND: Despite advances in heart transplantation and mechanical circulatory support, mortality among transplant candidates remains high. Better ways are needed to ensure the survival of transplant candidates both inside and outside the hospital. METHODS: In a prospective, multicenter clinical trial conducted at 24 centers in the United States, 280 transplant candidates (232 men, 48 women; median age, 55 years; range, 11-72 years) unresponsive to inotropic drugs, intra-aortic balloon counterpulsation, or both, were treated with the HeartMate Vented Electric Left Ventricular Assist System (VE LVAS). A cohort of 48 patients (40 men, 8 women; median age, 50 years; range, 21-67 years) not supported with an LVAS served as a historical control group. Outcomes were measured in terms of laboratory data (hemodynamic, hematologic, and biochemical), adverse events, New York Heart Association functional class, and survival. RESULTS: The VE LVAS-treated and non-VE LVAS-treated (control) groups were similar in terms of age, sex, and distribution of patients by diagnosis (ischemic cardiomyopathy, idiopathic cardiomyopathy, and subacute myocardial infarction). VE LVAS support lasted an average of 112 days (range, < 1-691 days), with 54 patients supported for > 180 days. Mean VE LVAS flow (expressed as pump index) throughout support was 2.8 L x min(-1) x m(-2). Median total bilirubin values decreased from 1.2 mg/dL at baseline to 0.7 mg/dL (P =.0001); median creatinine values decreased from 1.5 mg/dL at baseline to 1.1 mg/dL (P =.0001). VE LVAS-related adverse events included bleeding in 31 patients (11%), infection in 113 (40%), neurologic dysfunction in 14 (5%), and thromboembolic events in 17 (6%). A total of 160 (58%) patients were enrolled in a hospital release program. Twenty-nine percent of the VE LVAS-treated patients (82/280) died before receiving a transplant, compared with 67% of controls (32/48) (P <.001). Conversely, 71% of the VE LVAS-treated patients (198/280) survived: 67% (188/280) ultimately received a heart transplant, and 4% (10/280) had the device removed electively. One-year post-transplant survival of VE LVAS-treated patients was significantly better than that of controls (84% [158/188] vs 63% [10/16]; log rank analysis P =.0197). CONCLUSION: The HeartMate VE LVAS provides adequate hemodynamic support, has an acceptably low incidence of adverse effects, and improves survival in heart transplant candidates both inside and outside the hospital. The studies of the HeartMate LVAS (both pneumatic and electric) for Food and Drug Administration approval are the only studies with a valid control group to show a survival benefit for cardiac transplantation.

Cohort Studies↗
PubMed2001

[Intravascular detection of myocardial ischemia by spectrometry in the near infrared spectrum in experimental animals].

Interruption of oxygen supply in acute myocardial ischaemia reduces venous return of oxygen at the coronary sinus. In this study, the oxygen content of venous return in the coronary sinus was measured by using spectrometry in the near infrared spectrum. The authors developed a new intravascular catheter made of fibre optics. After in vitro calibration by blood flow based on a standard gas mixture used in in vitro experiment, an in vivo application in 12 domestic pigs was undertaken. The catheter was positioned in the coronary sinus and ischaemia induced by temporary occlusion of the left anterior descending artery. Recordings of the near infrared spectrum and haemodynamic data were obtained during 90 minutes' ischaemia followed by 90 minutes reperfusion. Spectrometry in the near infrared range detected a marked difference between oxyhaemoglobin and deoxyhaemoglobin, especially when the oxygen concentration was less than 30%. The near infrared spectrum of liaison between haemoglobin and oxygen in the coronary sinus shows significant and reproducible differences between pre-ischaemia occlusion of the left anterior descending artery and reperfusion. The recordings of the near infrared also show variation in CO2, pH and temperature. The authors conclude that the use of intravascular spectrometry of the near infrared spectrum could be a permanent reliable tool for detection and follow-up of acute myocardial ischaemia.

Animals↗
PubMed2001

Aortic valve implantation in the calf: a successful approach using Heartport cannulation and minimally invasive techniques.

BACKGROUND AND AIM OF THE STUDY: Aortic valve replacement (AVR) for mechanical prosthetic valvular testing has not been performed in calves because of anatomic difficulties, and sheep have traditionally been used in this situation. Hemodynamically, however, the calf constitutes an excellent model due to vigorous myocardial contractility, high stroke volumes and high cardiac output, and so has been used for preclinical evaluation of mechanical assist devices and mechanical valves in the mitral and tricuspid positions, which can be approached with relative surgical ease. Recently, a juvenile bovine model has been used to test a newly developed mechanical valve in the aortic position. METHODS: Ten calves (body weight 91+/-11 kg) underwent AVR with a 21-mm mechanical prosthesis via a small left intercostal thoracotomy with the aid of a Heartport cannulation device. A standard cardiopulmonary bypass (CPB) circuit was used. To circumvent the short bovine ascending aorta and to gain additional space to perform the aortotomy, two aortic cannulas were inserted for arterial-systemic perfusion. Nine calves each received a 21-mm experimental trileaflet aortic central flow valve prosthesis, and one calf received a 21-mm St. Jude Medical prosthesis. RESULTS: Mean CPB duration was 154.2+/-44.4 min, and mean ischemic time 80.1+/-15.9 min. Mean study duration was 42.6+/-53.7 days. Three calves were killed prematurely: two on days 2 and 7 due to complications arising from inadvertent entrapment of the right coronary artery ostium by a suture, and one on day 0 due to an accidental overdose of magnesium. Three calves, all of which had a first-version test valve, were killed electively due to valve malfunction secondary to early valvular thrombosis. Four animals (three with the final version valve and one with a standard valve as a control) survived until killed electively (range: 33-172 days). CONCLUSION: Results indicate that replacement of the native bovine aortic valve with a mechanical prosthesis can be performed safely in calves. Complication-free survival of up to six months can be achieved in the growing calf, provided that the test valve design satisfies minimum hemodynamic and coagulation criteria.

Animals↗