PubMed Health⌕ Search

Biomedical subjects

O H Frazier

Publications and source records attributed to O H Frazier.

At least 145 records · Page 8Linked to original sources
PubMed1999

Insulin improves functional and metabolic recovery of reperfused working rat heart.

BACKGROUND: Glucose, insulin, and potassium solution improves left ventricular function in refractory pump failure. Direct effects of insulin on the heart cannot be determined in vivo. We hypothesized that insulin has a direct positive inotropic effect on the reperfused heart. METHODS: Isolated working rat hearts were perfused with buffer containing glucose (5 mmol/L) plus oleate (1.2 mmol/L). Hearts were subjected to 15 minutes of ischemia and reperfused with or without insulin (100 microU/mL) for 40 minutes. Epinephrine (1 micromol/L) was added for the last 20 minutes. RESULTS: Hearts recovered 51.1% of preischemic cardiac power in the absence and 76.4% in the presence of insulin (p < 0.05). Whereas oleate oxidation remained unchanged, glucose uptake and oxidation increased during reperfusion with epinephrine (p < 0.01). This increase was significantly greater when hearts were reperfused in the presence of insulin (p < 0.01). Insulin also prevented an epinephrine-induced glycogen breakdown during reperfusion (p < 0.05). CONCLUSIONS: Insulin has a direct positive inotropic effect on postischemic rat heart. This effect is additive to epinephrine and occurs without delay. Increased rates of glucose oxidation and net glycogen synthesis are more protracted.

Animals↗
PubMed1999

Left ventricular assist system as a bridge to myocardial recovery.

BACKGROUND: Despite recent advances in medical therapy, heart transplantation, and mechanical circulatory support, the mortality of patients with congestive heart failure remains high. METHODS: Retrospective data on 5 patients were obtained from our hospital's medical records. Each patient was supported by a left ventricular assist system (LVAS) because of severe congestive heart failure. The duration of LVAS support averaged 229 days (range, 46 to 447 days). In 3 patients, the LVAS was removed electively after the patient showed recovery of myocardial function. In the other 2, it was removed because of a malfunction. RESULTS: In response to LVAS support, hemodynamic variables were significantly improved. The mean cardiac index increased from 1.45 to 2.69 L x min(-1) x m(-2) (p < 0.001) and the mean left ventricular ejection fraction increased from 0.144 to 0.288 (p < 0.025). All patients were in New York Heart Association functional class IV at LVAS implantation and class I at its explantation. One patient died of noncardiac-related causes 10 days after LVAS removal. The remaining 4 patients are alive and well 35, 33, 14, and 2 months after LVAS removal. CONCLUSIONS: In select patients with severe congestive heart failure, mechanical unloading with an LVAS can result in recovery of myocardial function. These patients can return to a normal physical status, thereby avoiding heart transplantation. More research is required to determine optimal modes of LVAS support, to predict which patients are likely to recover, and to assess long-term outcomes.

Adult↗
PubMed1999

Effects of perfusion mode on regional and global organ blood flow in a neonatal piglet model.

BACKGROUND: Organ injury (brain, kidney, and heart) has been reported in up to 30% of pediatric open heart surgery patients after conventional hypothermic non-pulsatile cardiopulmonary bypass (CPB) support with or without deep hypothermic circulatory arrest (DHCA). The effects of pulsatile (with a Food and Drug Administration approved modified roller pump) versus non-pulsatile perfusion on regional and global cerebral, renal, and myocardial blood flow were investigated during and after CPB with 60 minutes of DHCA in a neonatal piglet model. METHODS: Piglets, mean weight 3 kg, were used in both pulsatile (n = 7) and non-pulsatile (n = 7) groups. After initiation of CPB, all animals were subjected to hypothermia for 25 minutes, reducing the rectal temperatures to 18 degrees C, 60 minutes of DHCA followed by 10 minutes of cold reperfusion and 40 minutes of rewarming with a pump flow of 150 mL/kg/min. During cooling and rewarming, alpha-stat acid-base management was used. Differently labeled radioactive microspheres were injected pre-CPB, on normothermic CPB, pre-DHCA, post-DHCA, and after CPB to measure the regional and global cerebral, renal, and myocardial blood flows. RESULTS: Global cerebral blood flow was significantly higher in the pulsatile group compared to the non-pulsatile group at normothermic CPB (100.4 +/- 6.3 mL/100 gm/min versus 70.2 +/- 8.1 mL/100 gm/min, p < 0.05) and pre-DHCA (77.2 +/- 5.2 mL/100 gm/min versus 56.1 +/- 6.7 mL/100 gm/min, p < 0.05). Blood flow in cerebellum, basal ganglia, brain stem, and right and left cerebral hemispheres had an identical pattern with the global cerebral blood flow. Renal blood flow appeared higher in the pulsatile group compared to the non-pulsatile group during CPB, but the results were statistically significant only at post-CPB (94.8 +/- 9 mL/100 gm/min versus 22.5 +/- 22 mL/100 gm/min, p < 0.05). Pulsatile flow better maintained the myocardial blood flow compared to the non-pulsatile flow after CPB (316.6 +/- 45.5 mL/100 gm/min versus 188.2 +/- 19.5 mL/100 gm/min, p < 0.05). CONCLUSIONS: Pulsatile perfusion provides superior vital organ blood flow compared to non-pulsatile perfusion in this model.

Animals↗
PubMed1999

Transmyocardial laser revascularization in the patient with unmanageable unstable angina.

BACKGROUND: Transmyocardial laser revascularization (TMR) provides relief for patients with chronic angina, nonamenable to direct coronary revascularization. Unmanageable, unstable angina (UUA) defines a subset of patients with refractory angina who are at high risk for myocardial infarction and death. Patients were classified in the UUA group when they had been admitted to the critical care unit with unstable angina for 7 days with three failed attempts at weaning them off intravenous antianginal medications. METHODS: Seventy-six treated patients were analyzed to determine if TMR is a viable option for patients with unmanageable unstable angina. These patients were compared with 91 routine protocol patients (protocol group [PG]) undergoing TMR for chronic angina not amenable to standard revascularization. The procedure was performed through a left thoracotomy without cardiopulmonary bypass. These patients were followed for 12 months after the TMR procedure. Both unmanageable and chronic angina patients had a high incidence of at least one prior surgical revascularization (87% and 91%, respectively). RESULTS: Perioperative mortality (< or = 30 days post-TMR) was higher in the UUAG versus PG (16% vs 3%, p = 0.005). Late mortality, up to 1 year of follow-up, was similar (13% vs 11%, UUAG vs PG; p = 0.83). A majority of the adverse events in the UUAG occurred within the first 3 months post-TMR, and patients surviving this interval did well, with reduced angina of at least two classes occurring in 69%, 82%, and 82% of patients at 3, 6, and 12 months, respectively. The percent improvement in angina class from baseline was statistically significant at 3, 6, and 12 months. A comparable improvement in angina was found in the protocol group of patients. CONCLUSIONS: TMR carried a significantly higher risk in unmanageable, unstable angina than in patients with chronic angina. In the later follow-up intervals, however, both groups demonstrated similar and persistent improvement in their angina up to 12 months after the procedure. TMR may be considered in the therapy of patients with unmanageable, unstable angina who otherwise have no recourse to effective therapy in the control of their disabling angina.

Adult↗
PubMed1999

Sinus of Valsalva aneurysm or fistula: management and outcome.

BACKGROUND: Few large or long-term series exist regarding the management of patients with sinus of Valsalva aneurysms or fistulas (SVAFs). METHODS: Between 1956 and 1997, 129 patients presented with a ruptured (64 cases; 49.6%) or nonruptured (65 cases; 50.4%) SVAF. The patients included 88 men and 41 women, with a mean age of 39.1 years. Associated findings included a history of endocarditis (42 cases; 32.6%), a bicuspid aortic valve (21 cases; 16.3%), a ventricular septal defect (15 cases; 11.6%), and Marfan's syndrome (12 cases; 9.3%). Operative procedures included simple plication (61 cases; 47.3%), patch repair (52 cases; 40.3%), aortic root replacement (16 cases; 12.4%), and aortic valve replacement/repair (75 cases; 58.1%). RESULTS: There were five in-hospital deaths (3.9%): four due to preexisting sepsis and endocarditis and one that followed dehiscence of the repair in a patient with Marfan's syndrome. Two patients (1.6%) had strokes during the early postoperative period. The survivors were followed up for 661.1 patient-years (5.3 years/patient). The following late complications occurred: prosthetic valve malfunction (5 cases; 3.9%), prosthetic valve endocarditis (3 cases; 2.3%), SVAF recurrence (2 cases; 1.6%), thrombosis (1 case; 0.8%), and anticoagulation-related bleeding (1 case; 0.8%). CONCLUSIONS: Resection and repair of SVAF entails an acceptably low operative risk and yields long-term freedom from symptoms. Early, aggressive treatment is recommended to prevent endocarditis or lesional enlargement, which causes worse symptoms and necessitates more extensive repair.

Adolescent↗
PubMed1999

Transmyocardial laser revascularization: effect of laser parameters on tissue ablation and cardiac perfusion.

Dr. Mahmood Mirhoseini from Milwaukee, WI, transformed transmyocardial revascularization (TMR) into transmyocardial laser revascularization (TMLR) more than 2 decades ago. The controversial nature of this laser procedure and the prospect of its successful application to refractory cases of chronic debilitating angina have created spirited interest in TMLR. As a natural component of this interest, various laser modalities have been proposed and employed during the performance of the TMLR procedure both in the experimental and the clinical setting. However, it is the nature of laser-tissue interactions that is primarily responsible for the long-term fate of the channels, the angiogenesis that occurs in the vicinity of these laser channels, and the resulting increase (if any) in myocardial perfusion. These interactions with tissue are, in turn, determined by laser variables such as photonic absorption and scattering by the target tissue, pulse energy and duration, and the peak power generated. The CO2 laser has the advantages of producing high-energy pulses that create a transmural channel with a single pulse, low-peak power that minimizes structural tissue trauma, and high photonic absorption to minimize thermal damage. The holmium:YAG and excimer lasers, in turn, have the advantage of being coupled to a fiber optic catheter for transluminal endocardial delivery. Importantly, long-term clinical and perfusional data showing a cause and effect relationship between the use of TMLR and these end-points are available for the CO2 laser only. Prospective randomized trials are, therefore, warranted to delineate the use of each laser modality in relation to that of the CO2 laser in the TMLR setting.

Coronary Circulation↗
PubMed1999

A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation: decreased hyperlipidemia and hypertension with tacrolimus.

BACKGROUND: Tacrolimus-based immunosuppression seems safe and effective in liver and kidney transplantation. To assess the safety and efficacy of tacrolimus (TAC)-based immunosuppression after cardiac transplantation as well as the relative impact of tacrolimus on immunosuppression-related side effects such as hypertension and hyperlipidemia, we conducted a prospective, randomized, open-label, multicenter study of otherwise identical tacrolimus- and cyclosporine-based immunosuppressive regimens in adult patients undergoing cardiac transplantation. METHODS: Eighty-five adult patients (pts) at six United States cardiac transplant centers, undergoing their first cardiac transplant procedure, were prospectively randomized to receive either TAC-based (n = 39) or cyclosporine (CYA)-based (n = 46) immunosuppression. All pts received a triple-drug protocol with 15 pts (18%) receiving peri-operative OKT3 to delay TAC/CYA due to pre-transplant renal dysfunction. Endomyocardial biopsies were performed at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 24, and 52. The study duration was 12 months. RESULTS: Patients were mostly male (87%) Caucasian (90%) with a mean age of 54 years and primary diagnoses of coronary artery disease (55%) and idiopathic dilated cardiomyopathy (41%). There were no significant demographic differences between groups. Patient and allograft survival were not different in the two groups. The probability and overall incidence of each grade of rejection, whether treated or not, and the types of treatment required did not differ between the groups. At baseline and through 12 months of follow-up, chemistry and hematology values were similar between the groups except serum cholesterol was higher in the CYA group at 3, 6, and 12 months (239 vs 205 mg/dL, 246 vs 191 mg/dL, 212 vs 186 mg/dL, respectively, p < 0.001). Likewise, LDL-cholesterol, HDL-cholesterol and triglycerides were significantly higher in the CYA group. More CYA patients received therapy for hypercholesterolemia (71% vs 41% at 12 months, p = 0.01). There were no significant differences in renal function, hyperglycemia, hypomagnesemia, or hyperkalemia during the first 12 months. More CYA patients developed new-onset hypertension requiring pharmacologic treatment (71% vs 48%, p = 0.05). The incidence of infection was the same for the two groups (2.6 episodes/pt/12 month follow-up). CONCLUSION: Tacrolimus-based immunosuppression seems effective for rejection prophylaxis during the first year after cardiac transplantation and is associated with less hypertension and hyperlipidemia and no difference in renal function, hyperglycemia or infection incidence when compared to cyclosporine-based immunosuppression.

Adult↗
PubMed1999

The effects of pulsatile versus nonpulsatile perfusion on blood viscoelasticity before and after deep hypothermic circulatory arrest in a neonatal piglet model.

Blood trauma increases blood viscoelasticity by increasing red cell aggregation and plasma viscosity and by decreasing cell deformability. During extracorporeal circulation, the mode of perfusion (pulsatile or nonpulsatile) may have a significant impact on blood trauma. In this study, a hydraulically driven dual chamber pulsatile pump system was compared to a standard nonpulsatile roller pump in terms of changes in the blood viscosity and elasticity during cardiopulmonary bypass (CPB) and pre and post deep hypothermic circulatory arrest (DHCA). Piglets, with an average weight of 3 kg, were used in the pulsatile (n = 5) or nonpulsatile group (n = 5). All animals were subjected to 25 min of hypothermia, 60 min of DHCA, 10 min of cold reperfusion, and 40 min of rewarming with a pump flow of 150 ml/kg/min. A pump rate of 150 bpm, pump ejection time of 120 ms, and stroke volume of 1 ml/kg were used during pulsatile CPB. Arterial blood samples were taken pre-CPB (36 degrees C), during normothermic CPB (35 degrees C), during hypothermic CPB (25 degrees C), pre-DHCA (18 degrees C), post-DHCA (19 degrees C), post-rewarming (35 degrees C), and post-CPB (36 degrees C). Viscosity and elasticity were measured at 2 Hz and 22 degrees C and at strains of 0.2, 1, and 5 using the Vilastic-3 Viscoelasticity Analyzer. Results suggest that the dual chamber neonate-infant pulsatile pump system produces less blood trauma than the standard nonpulsatile roller pump as indicated by lower values of both viscosity and elasticity during CPB support.

Animals↗
PubMed1999

Defining pulsatile perfusion: quantification in terms of energy equivalent pressure.

Several clinical and animal studies have demonstrated that pulsatile perfusion is more beneficial than nonpulsatile perfusion during short or long durations of extracorporeal circulation. Other investigators, however, have been unable to document these benefits. The issue remains controversial. Central to the debate is the issue of a precise definition of pulsatile flow. To help resolve the conflict, pulsatile flow may be quantified in terms of energy equivalent pressure. This formula contains both the arterial pressure and pump flow rate, which are the 2 most critical parameters for open heart surgery. This definition establishes common criteria for assessment of the effectiveness of extracorporeal support.

Adult↗
PubMed1999

Left ventricular assist device as a bridge to partial left ventriculectomy.

In 1963, Dr Michael DeBakey successfully implanted the first left ventricular assist device. Throughout the 1970s, cardiovascular research aimed to achieve long-term circulatory support with such devices; later, as improved medical therapy decreased patients' chances of organ rejection or infection, transplantation became a viable alternative for the treatment of heart failure. At that point, left ventricular assist devices began to be used as bridges to transplantation. As left ventricular assist devices were used for longer periods of time, we realized that the ventricular function and overall health of the patients awaiting transplant improved. Used as a bridge to transplantation, left ventricular assist devices often increased a patient's chances of survival and recovery. Recently left ventricular assist devices have been used as bridges to partial left ventriculectomy (the Batista procedure). Our early experiences with this procedure in selected patients have been promising. Many patients recover to NYHA functional class I after prolonged left ventricular unloading, surgery, or both. In addition, the native heart may be saved, especially in younger patients, eliminating the need for transplantations and decreasing the strain on the limited organ donor pool.

Adult↗
PubMed1999

Heart transplantation: approaching a new century.

Although cardiac surgeons have gained considerable experience with heart transplantation during the past 30 years, this operation still presents many challenges. The number of transplant candidates continues to exceed the number of available donor hearts, and the shortage is not expected to improve. For patients fortunate enough to receive a donor heart, perioperative mortality is a serious concern. After the 1st postoperative year, the most frequent cause of death is transplant vasculopathy. Other potential complications include renal dysfunction, bleeding, infection, and allograft rejection. Despite these problems, heart transplantation remains the best hope for patients with end-stage heart failure that is unresponsive to conventional therapy. In the future, mechanical cardiac assistance and new medical treatments for end-stage heart disease may offer alternatives to heart transplantation, reducing the competition for scarce donor hearts.

Contraindications↗
PubMed1998

Nonthrombogenic, adhesive cellular lining for left ventricular assist devices.

BACKGROUND: The textured, blood-contacting surfaces of the Thermocardiosystems HeartMate left ventricular assist device (LVAD) promote the passivation of the biomaterial caused by the accumulation of an integral coagulum. Commonly, acute, postimplantation thrombocytopenia causes significant bleeding, requiring surgery or blood transfusions. Chronic complications include thromboembolic microevents that can affect central nervous system function. Pumps, explanted during donor organ transplantation, are often found to have an extensive cellular panus associated with the blood-contacting surfaces of the device. This natural cellular lining suggests a possible strategy for improving the blood biocompatibility of the HeartMate. Therefore, seeding of LVADs with cells genetically engineered to enhance their antithrombotic properties before implantation was investigated as a means to improve biocompatibility for long-term use. METHODS AND RESULTS: Bovine vascular smooth muscle cells genetically engineered to produce nitric oxide were seeded on LVAD biomaterials and exposed to elevated shear stresses to determine cell-adhesive capabilities. Comparative studies were performed with vascular endothelial cells isolated from the same vessel. To assess the thrombogenic potential of the genetically engineered smooth muscle cells, monolayers were exposed to whole blood in parallel plate flow chambers and were platelet-adhesion quantified. This procedure used scanning electron microscopy and computer image-capture software. Endothelial cell monolayers and mock-transduced smooth muscle cells were assayed in a comparative manner. LVADs were seeded with genetically engineered smooth muscle cells and maintained under cell culture conditions for 96 hours. Thereafter, seeded LVADs were incorporated into in vitro flow loops. Cell retention within the pump was determined by sampling the effluent culture medium downstream of the pump and cell counting in a Coulter counter. After 18 hours of in vitro flow, a seeded pump was implanted into the abdominal cavity of a calf and anastomosed to the apex of the heart and to the descending aorta. More genetically engineered smooth muscle cells were retained on the surface of LVAD biomaterials when they were subjected to shear stresses up to 75 dyne/cm than endothelial cells assayed in the identical manner. Adherence of platelets to the surface of smooth muscle cells was significantly reduced after their transduction with nitric oxide synthase with GTP cyclohydrolase genes. Platelet deposition on the genetically modified myocyte layers was similar to that associated with endothelial cell layers. Cell loss from cell-seeded LVADs incorporated into in vitro flow loops remained < 5% of the total cell number seeded regardless of the duration of flow. CONCLUSIONS: LVADs seeded with smooth muscle cells, transduced with the genes to optimize nitric oxide production, adhered well to the pump surface under in vitro and in vivo flow conditions.

Animals↗
PubMed1998

Jarvik 2000 heart: potential for bridge to myocyte recovery.

BACKGROUND: Mechanical bridge to left ventricular recovery is an emerging strategy for the treatment of heart failure. We sought to validate the use of a new intracardiac axial flow impeller pump for this purpose. METHODS AND RESULTS: The Jarvik 2000 Heart was implanted into 30 sheep to ascertain mechanical reliability, biocompatibility, and hemodynamic function. We attempted but failed to anticoagulate with warfarin. Elective explants with survival were performed in 3 animals to simulate bridge to recovery. Extensive autopsy studies were performed in all other animals. At speeds between 8000 and 12 000 rpm the device pumped up to 8 L/min, captured all mitral flow, and augmented cardiac output with elevation of mean arterial pressure. The pump was silent and hemolysis negligible. Nonpulsatile flow did not adversely affect neurological or renal function. Device removal proved straightforward and safe. A fractured inflow bearing occurred in 1 early model. There were no other pump failures, but power interruption occurred when the sheep chewed the cables or head-butted the percutaneous pedestal. At autopsy, there was no thromboembolism or primary thrombus formation in any device. Pump occlusion occurred in 2 sheep with bacterial endocarditis. One electively explanted pump, previously switched off for 5 months, had no thrombus in the device or vascular graft. CONCLUSIONS: The Jarvik 2000 Heart is a major advance in blood-pump technology and increases the scope of mechanical circulatory support. Reliability and ease of removal favor its use for bridge to myocyte recovery, as well as for bridge to transplantation or long-term support.

Animals↗
PubMed1998

Long-term results of triple-drug-based immunosuppression in nonneonatal pediatric heart transplant recipients.

BACKGROUND: Few reports document long-term results of pediatric cardiac transplantation in which triple therapy (cyclosporine, azathioprine, and corticosteroids) was the mainstay of immunosuppression. This report details a single center's pediatric transplant experience and analyzes the relative contributions of selected pre/posttransplant risk factors on long-term morbidity and mortality. METHODS: Retrospective data were collected for all non-neonatal pediatric transplant recipients including: presenting diagnosis, cardiac hemodynamics (particularly pulmonary vascular resistance index), donor ischemic time, occurrence of postoperative infections, episodes of allograft rejection, incidence of posttransplant lymphoproliferative disease or coronary artery disease (CAD), and overall survival. Analysis of single variables and a Cox-proportional hazards model were utilized to determine the impact of pre/posttransplant risk factors on long-term survival. RESULTS: From 1984 to 1995, 64 patients (mean age, 8.3 years), 46 of whom had cardiomyopathy and 18 who had inoperable complex congenital heart disease, underwent cardiac transplantation and received triple-drug immunosuppression. Orthotopic transplantation was performed unless the pulmonary vascular resistance index remained >6 um2 (despite use of pulmonary vasodilator). One patient required heterotopic transplantation. Average donor ischemic time was 217 min. An average of 1.2 rejection episodes/patient occurred (average follow-up period: 50 months). No patient developed posttransplant lymphoproliferative disease, but 22 patients (34%) developed CAD. Overall survival was 80%, 60%, and 57% at 1, 5, and 10 years, respectively. Of outcome variables analyzed, rejection frequency was significantly increased in patients who subsequently developed CAD, but the presence of CAD was not significantly correlated with mortality. CONCLUSION: Triple-drug-based immunosuppressive maintenance therapy in pediatric heart transplant recipients results in good long-term graft survival.

Adolescent↗
PubMed1998

Transmyocardial laser revascularization in allograft coronary artery disease.

We used transmyocardial laser revascularization to treat accelerated cardiac allograft atherosclerosis in 2 patients. One patient received transmyocardial laser revascularization as sole therapy, the other as an adjunct to coronary artery bypass grafting. The systolic function improved in both patients, although the patient who had adjunctive transmyocardial laser revascularization died of systemic infection and renal failure on postoperative day 55. The second patient is alive and well 1 1/2 years after the laser procedure. We discuss 4 other patients who received transmyocardial laser revascularization treatment elsewhere in the United States. Transmyocardial laser revascularization has the potential to become important in the treatment of transplant atherosclerosis. Randomized clinical trials are warranted to assess the efficacy of transmyocardial laser revascularization in this setting.

Coronary Artery Bypass↗
PubMed1998

Long-term mechanical circulatory support system reliability recommendation: American Society for Artificial Internal Organs and The Society of Thoracic Surgeons: long-term mechanical circulatory support system reliability recommendation.

Jointly developed by members of the American Society for Artificial Internal Organs and the Society of Thoracic Surgeons along with staff from the Food and Drug Administration, the National Heart, Lung and Blood Institute and other experts, this recommendation describes the reliability considerations and goals for Investigational Device Exemption and Premarket Approval submissions for long-term, mechanical circulatory support systems. The recommendation includes a definition of system failure, a discussion of an appropriate reliability model, a suggested in vitro reliability test plan, reliability considerations for animal implantation tests, in vitro and animal in vivo performance goals, the qualification of design changes during the Investigational Device Exemption clinical trial, the development of a Failure Modes Effects and Criticality Analysis, and the reliability information for surgeons and patient candidates. The document will be periodically reviewed to assess its timeliness and appropriateness within five years.

Animals↗