Biomedical subjects

O H Frazier

Publications and source records attributed to O H Frazier.

At least 397 records · Page 22Linked to original sources

PubMedDate not supplied

Simultaneous evaluation of cardiac wall motion and myocardial ischemic injury by measurement of electrical impedance.

The authors devised a new method to simultaneously evaluate cardiac wall motion and myocardial ischemic injury by measurement of myocardial electrical impedance. This method is based on the principle that electrical properties of the myocardium are affected by intra- or extracellular structure. Impedance was assessed by measuring voltage while a constant alternating current (0.4 mA, 50 kHz) was being applied to the myocardium by way of an electrode that had two parallel 6 mm long needles. In five dogs, an electrode was placed in the left ventricular wall, adjacent to a pair of ultrasonic crystals that were used to estimate regional wall thickness. To change regional contractility and to induce ischemic injury, the left anterior descending coronary artery was ligated. The impedance waveforms were observed to be synchronized with cardiac contraction, and changes in impedence correlated well with changes in wall thickness. Dyskinetic movements in the ischemic myocardium could also be detected through assessment of the impedance waveform. During the first 2 hr, the average value of impedance increased significantly, from 254 +/- 38 omega-cm to 329 +/- 13 omega-cm (P < 0.005), and then decreased, indicating a correlation with the progression and irreversibility of ischemic injury. This simple technique may eventually allow us to simultaneously assess cardiac wall motion and myocardial ischemia in humans.

Animals↗

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Progress in the development of the ABIOMED total artificial heart.

The ABIOMED implantable total artificial hearts in the final phase of engineering development. The system has a compact electrohydraulically driven energy converter sandwiched between two blood pumps, an internal electronics pack, an internal battery, a transcutaneous energy transmission coil for power transmission, and external wearable electronics pack and battery. The current effort is to complete development of the system during 1996 in preparation for formal pre clinical testing of the device. In vivo studies with the current thoracic unit (ABH II) have achieved 108 days of survival verifying the thermal, physiologic, and hematologic compatibility of the system. The abdominal implantable electronics pack showed no thermal dissipation problem. System improvements include scaling down the size of the thoracic unit, and efficiency enhancement in the power and hybrid electronics. The new system (ABH III) retains the flow capacity of greater than 10 L/min. Size reduction results in an atrial to sternal dimension that would fit 98% and 75% of men and women, respectively.

Animals↗

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Hospital charges for conventional therapy versus left ventricular assist system therapy in heart transplant patients.

An important goal of a left ventricular assist system (LVAS) is to provide long-term, safe, cost-effective mechanical circulatory support. The Heartmate LVAS (Thermo Cardiosystems, Inc., Woburn, MA), used in recent clinical trials as a bridge to transplantation, has proven extremely reliable for long periods, and its use has improved the survival rates in patients who subsequently received a donor heart. Patients who have been implanted with an LVAS often have significantly improved physical status and can leave the intensive care unit (ICU) and be treated at less expense elsewhere in the hospital. In this preliminary report, the authors analyzed hospital charges for three groups of patients: heart transplant patients who received conventional medical therapy before transplantation (Group 1), transplant patients who received in-hospital LVAS therapy (Group 2), and one patient who awaited transplantation at home while undergoing LVAS support. Group 1 patients (n = 6) received intraaortic balloon pump (IABP) support and inotropic therapy in an ICU before transplantation. Group 2 (n = 6) patients were receiving IABP support and inotropic therapy when the LVAS was implanted and eventually underwent heart transplantation. The length of hospital stay in Group 1 (51 days) was significantly shorter than in Group 2 (185 days). Mean hospital charge in Group 1 was $5,150/day; in Group 2, $3,178/day. The patient living at home incurred an average medical expense of $27/day. Although LVAS supported patients remain in the hospital much longer than do medically treated patients, their average daily in-hospital charges are much less. If the LVAS could be used as an alternative to transplantation, it might offer not only a longer, better quality life, but also a potential cost savings to patients with end-stage heart failure.

Adolescent↗

PubMedDate not supplied

Exercise capacity recovers slowly but fully in patients with a left ventricular assist device.

Left ventricular assist devices (LVAD) are used increasingly as bridges to cardiac transplantation. The typical LVAD candidate is a bedridden, critically ill, New York Heart Association (NYHA) Class IV patient with congestive heart failure (CHF) who is dependent upon intravenous, inotropic, and, in many cases, intra-aortic balloon support. The LVAD provides the potential for pre transplant rehabilitation by allowing the patient to become ambulatory, and by improving muscle tone, muscle mass, and nutritional status before transplantation. However, whether the abnormal exercise capacity of these patients improves after implantation has not been elucidated. The purpose of the present study was to evaluate the exercise capacity of patients with CHF after LVAD implantation (n = 10) using peak oxygen consumption during maximal exercise (MVO2), and comparing the results with those of a group of NYHA Class III patients with CHF (n = 14). After 2 months of implantation, MVO2 of the patients with LVAD was 12.8 +/- 0.3 ml/kg/min, which was comparable to that of the NYHA Class III patients with CHF (12.5 +/- 0.5 ml/kg/min). Four of 10 patients with LVAD were monitored for more than 5 months when MVO2 rose to 15.4 +/- 1.0 ml/kg/min (p < 0.05 vs NYHA Class III). In conclusion, the exercise capacity of patients with LVAD recovers slowly but significantly after 5 months of implantation, promising the potential for complete recovery from heart failure in patients supported with an LVAD.

Adult↗

PubMedDate not supplied

A comparison between intraperitoneal and extraperitoneal left ventricular assist system placement.

The HeartMate left ventricular assist system (LVAS) is being used with increasing frequency as a bridge to heart transplantation and for long-term support of chronic heart failure patients who are not transplant candidates. The surgical techniques and anatomic placement of the HeartMate are factors in minimizing complications that occur during long-term use. Device related bleeding, infection, and other intraabdominal complications are serious adverse events associated with the position of the LVAS. Clinical data from 48 HeartMate supported patients were analyzed retrospectively to determine differences in serious complication rates between intraperitoneal (IP) and extraperitoneal (EP) LVAS placement. The LVAS was placed IP in 37 patients (77%) and EP in 11 patients (23%). The occurrence of postoperative bleeding that required reoperation was 57% in the IP group and 64% in the EP group. Device related bleeding was 8% in the IP group and 29% in the EP. Neither difference in bleeding rate was statistically significant. The overall infection rate during the entire period of LVAS support was similar between groups (IP, 45.7%; EP, 46.2%; p = 0.25); however, device related infection occurred more often in the EP group (46%; IP, 14%; p = 0.025). All patients who recovered from LVAS implantation experienced mild early satiety, but were otherwise free of intra-abdominal complications. The transplantation rate was 64% for the IP group and 78% for the EP group. IP LVAS placement may offer additional protection against device related infections.

Adult↗

PubMedDate not supplied

Retrospective analysis of infection in patients undergoing support with left ventricular assist systems.

Infection is a problem in patients undergoing support with left ventricular assist systems. To better understand the nature of this problem, we retrospectively analyzed data on 56 patients supported by the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist system. Infection was defined as fever > 38 degrees C, white blood count > 12,000 cells/ml, and a need for antimicrobial therapy. Of the 56 patients, 25 (41%) had an infection. Device related infections (as determined by positive culture from driveline, housing, or inflow or outflow tract) occurred in eight patients (14.3%). The most common sites of infection were the respiratory system (42.4%), the central venous catheter (27.8%), and blood (18.3%). Of the positive cultures, 84% were bacterial and 16% fungal. There were no positive viral cultures. Positive cultures from left ventricular assist system related sites made up only 8.7% of the total. All but one of the patients with device related infections survived to transplantation. The long-term survival rate for patients in this group after transplantation was 77.8%. Two patients required surgical revision of the driveline because of infection. Both were free of infection postoperatively. Patients who stayed in the intensive care unit for longer periods had a greater risk of infection (uninfected, 35 days; infected, 78 days). In conclusion, although infection is a problem in patients undergoing support with left ventricular assist systems, it does not preclude survival to transplantation or alter the survival rate after transplantation.

Adolescent↗

PubMedDate not supplied

Long-term mechanical circulatory support system reliability recommendation: American Society for Artificial Internal Organs and 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.

Clinical Trials as Topic↗

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Neurohormonal changes after implantation of a left ventricular assist system.

In patients with left ventricular dysfunction, neurohormonal levels are valuable indicators of the severity of heart disease and prognosis. For patients with severe left ventricular dysfunction, left ventricular assist systems (LVAS) are effective as short-term bridges to heart transplantation and are currently being investigated for long-term use. Unknown, however, are the effects of mechanical unloading of the left ventricle on neurohormone levels during the initial weeks after LVAS implantation, and whether these changes are similar to the neurohormonal level decreases observed after cardiac transplantation. This study was undertaken to determine the effect of LVAS support on plasma norepinephrine (PNE) levels during the initial weeks after device implantation. The PNE levels in five consecutive patients with left ventricular dysfunction were measured within 1 week after LVAS implantation and every week thereafter for 5 weeks. Significant decreases in PNE levels were observed after 3 weeks of LVAS support. After 5 weeks of LVAS support, PNE levels had decreased to near normal. For patients with severe left ventricular dysfunction, the improved prognosis after LVAS support may be due in part to the normalization of neurohormonal levels. The findings indicate that PNE levels may be of value in determining whether a patient can be weaned from LVAS support.

Aged↗

PubMedDate not supplied

Evaluation of a physiologic pulsatile pump system for neonate-infant cardiopulmonary bypass support.

An alternate physiologic pulsatile pump (PPP) system was designed and evaluated to produce sufficient pulsatility during neonate-infant open heart surgery. This hydraulically driven pump system has a unique "dual" pumping chamber mechanism. The first chamber is placed between the venous reservoir and oxygenator and the second chamber between the oxygenator and patient. Each chamber has two unidirectional tricuspid valves. Stroke volume (0.2-10 ml), upstroke rise time (10-350 msec), and pump rate (2-250 beats per minute [bpm]) can be adjusted independently to produce adequate pulsatility. This system has been tested in 3-kg piglets (n = 6), with a pump flow of 150 ml/kg/min, a pump rate of 150 bpm, and a pump ejection time of 110 msec. After initiation of cardiopulmonary bypass (CPB), all animals were subjected to 25 minutes of hypothermia to reduce the rectal temperatures to 18 degrees C, 60 minutes of deep hypothermic circulatory arrest (DHCA), then 10 minutes of cold perfusion with a full pump flow, and 40 minutes of rewarming. During CPB, mean arterial pressures were kept at less than 50 mm Hg. Mean extracorporeal circuit pressure (ECCP), the pressure drop of a 10 French aortic cannula, and the pulse pressure were 67+/-9, 21+/-6, and 16+/-2 mm Hg, respectively. All values are represented as mean+/-SD. No regurgitation or abnormal hemolysis has been detected during these experiments. The oxygenator had no damping effect on the quality of the pulsatility because of the dual chamber pumping mechanism. The ECCP was also significantly lower than any other known pulsatile system. We conclude that this system, with a 10 French aortic cannula and arterial filter, produces adequate pulsatility in 3 kg piglets.

Animals↗

PubMedDate not supplied

A genetically engineered, nonthrombogenic cellular lining for LVADs: in vitro preconditioning before in vivo implantation.

Because of the clinical success of left ventricular assist devices (LVADs) used for short-term "bridge to transplant" and the limited availability of donor organs, heart assist devices are being considered for long-term implantation as an alternative to heart transplantation. In an effort to improve biocompatibility, our laboratory has developed a nonthrombogenic cellular lining from genetically engineered smooth muscle cells (GE-SMC) for the Thermocardiosystems Heartmate LVAD. Smooth muscle cells have been transduced with the gene for endothelial nitric oxide synthase (NOS III) and produce NO at concentrations that reduce platelet deposition and smooth muscle cell proliferation when tested in vitro. In this investigation, the adhesive capabilities of GE-SMC linings were examined. An in vitro circulatory loop was designed to expose cell lined LVADs to in vivo operating conditions. Cumulative cell loss from cell lined LVADs was less than 10% after 24 hours of flow. Using a protocol for "preconditioning" the cell lining within the mock circulatory loop, the first implantation of an LVAD containing a genetically engineered SMC lining was successfully implemented in a bovine model. Results from this 24 hour study indicate that the flow-conditioned cellular lining remained intact with no evidence of thromboembolization and only minimal changes in coagulation studies.

Animals↗

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Pulsatile and nonpulsatile flows can be quantified in terms of energy equivalent pressure during cardiopulmonary bypass for direct comparisons.

The purpose of this study was to quantify and compare pulsatile and nonpulsatile pressure and flow waveforms in terms of energy equivalent pressure (EEP) during cardiopulmonary bypass in a neonatal piglet model. EEP is the ratio of the area under the hemodynamic power curve and the flow curve. Piglets, mean weight of 3 kg, were used in physiologic pulsatile pump (n = 7), pulsatile roller pump (n = 6), and nonpulsatile roller pump (n = 7) groups. Data (waveforms of the femoral artery pressure, pump flow, and preaortic cannula extracorporeal circuit pressure) were collected during normothermic cardiopulmonary bypass at 35 degrees C (15 minutes on-pump), before deep hypothermic circulatory arrest (pre-DHCA) at 18 degrees C, and after cold reperfusion and rewarming (post-DHCA) at 36 degrees C. The pump flow rate was 150 ml/kg/min in all three groups. During pulsatile perfusion, the pump rate was 150 bpm in both pulsatile groups. Although there was no difference in mean pressures in all groups, EEP and the percentage increase of pressure (from mean pressure to EEP) of mean arterial pressure and preaortic cannula extracorporeal circuit pressure were higher with pulsatile perfusion compared with nonpulsatile perfusion (p < 0.001). In particular, the physiologic pulsatile pump group produced significantly higher hemodynamic energy compared with the other groups (p < 0.001). These results suggest that pulsatile and nonpulsatile flows can be quantified in terms of EEP for direct comparisons, and pulsatile flow generates higher energy, which may be beneficial for vital organ perfusion during cardiopulmonary bypass.

Animals↗

PubMedDate not supplied

Monitoring regional cerebral oxygen saturation using near-infrared spectroscopy during pulsatile hypothermic cardiopulmonary bypass in a neonatal piglet model.

Impairment of cerebral oxygenation in neonates and infants after hypothermic nonpulsatile cardiopulmonary bypass (CPB) support is well documented. The objectives of this study were: 1) using a neonatal piglet model to continuously monitor the regional cerebral oxygen saturation (rSO2) by near-infrared spectroscopy during pulsatile hypothermic CPB; and 2) to quantify the pulsatile flow in terms of energy equivalent pressure (EEP). After initiation of CPB, all piglets (n = 5) were subjected to 15 minutes of core cooling, reducing the rectal temperature to 25 degrees C, followed by 60 minutes of hypothermic CPB, then 10 minutes of cold reperfusion, and 30 minutes of rewarming. During CPB, mean arterial pressures (MAPs) and pump flow rates were maintained at 40-45 mm Hg and 150 ml/kg/min, respectively. During normothermic CPB, the rSO2 was significantly increased, compared with the pre-CPB level (56.8 +/- 5.2% vs. 41.8 +/- 5.5%, p < 0.01). At the end of cooling, the rSO2 level was 76.8 +/- 8.6% (p < 0.001 vs. pre-CPB). After 60 minutes of hypothermic CPB and 30 minutes of rewarming, the rSO2 level was decreased to 38.6 +/- 4.2%, which was not significantly different compared with the pre-CPB level. The average increase in pressure (from MAP to EEP) was 5 +/- 1%, and the average increase in extracorporeal circuit pressure (from ECCP to EEP) was 13 +/- 2%. This extra pressure may help to provide better regional cerebral oxygen saturation. During pulsatile CPB, there was no rSO2 deficiency in this high flow model. Near-infrared spectroscopy responded well to changes in rSO2 during different stages of these experiments and might be a helpful tool for intraoperative monitoring.

Animals↗

PubMedDate not supplied

A bovine model for detecting high intensity transient signals originating from mechanical heart valves.

In patients with mechanical heart valves (MHVs), transcranial Doppler methods commonly detect high intensity transient signals (HITS) representing microemboli. These microemboli, which are presumably gaseous, may cause stroke and cognitive deterioration. A bovine model was therefore developed for studying the relationship between mitral MHV induced HITS and potential etiogenic factors. We placed an 18 mm, 4 MHz Doppler probe in the brachiocephalic artery to detect MHV induced microbubbles at baseline (rest) and under 9 other conditions. To elucidate the gas composition (CO2 or N2) of the microbubbles, we administered 1%, 3%, and 5% CO2, and 100% O2. To determine effect of the heart rate, we paced the heart at 120, 160, and 180 bpm. To alter the myocardial contractility, we gave dobutamine and esmolol. Two independent, blinded observers counted the HITS from recorded doppler spectra. HITS were defined by an initial unidirectional spectral deviation, a signal power of >8 dB relative to the background power, and lack of a cyclic appearance. The electrocardiogram, aortic and LV pressures, and LV dP/dt were obtained telemetrically. The calves were studied 4 to 6, 8 to 10, and 12 to 14 weeks postoperatively, after which the animals were sacrificed at an approximate 4 month study duration, and a postmortem evaluation of the heart and the main viscera was performed. In all, 27 HITS recordings were made in 10 calves. Myocardial contractility was the only factor to significantly affect HITS frequency; the heart rate and blood gas concentrations had minimal effect on HITS frequency. Our bovine model will be useful for assessing valve designs, as well as the mechanism of HITS, the composition of the microemboli, and their possible pathophysiologic effects on the kidneys and brain.

Adrenal Glands↗

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Infection and thrombosis in total artificial heart technology: past and future challenges--a historical review.

On the basis of animal testing and a single clinical implant during the 1960s, development of the total artificial heart (TAH) began in earnest in the 1970s. The goal was to produce a pump that could treat biventricular heart failure or any other condition that necessitated removal of the patient's native heart. The early TAHs were pneumatically powered, with externalized drivelines. After undergoing in vivo evaluation in hundreds of sheep and calves at several centers (mainly the Utah Heart Institute), these pumps were implanted in humans, initially for permanent cardiac replacement and later for bridging to transplantation. In both the in vivo experimental setting and the clinical setting, infection and thrombosis were problematic, infection being encountered much more frequently than thrombosis in clinical cases. To minimize these problems, four research groups, funded by NIH, began in 1988 to develop permanent, transcutaneously powered, totally implantable, electromechanical TAHs. For the first time, TAH technology was able to minimize infection and thrombosis, as confirmed by current in vivo studies. These new TAHs will undergo preclinical, pre-IDE studies this year and clinical trials in the near future. This article briefly reviews the evolution of TAH technology, with an emphasis on the prevention and management of infection and thrombosis.

Animals↗

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Infectious complications associated with ventricular assist systems.

Infectious complications during support with a ventricular assist system (VAS) can cause severe morbidity and mortality, affecting nearly one-half of all VAS recipients. Because of the lack of a uniform definition of infection, the incidence of this complication is hard to determine accurately. It is approximately 50% for patients being supported by an implantable VAS as a bridge to heart transplantation and 28% for patients supported by an external, short-term VAS. Infections can be classified according to the involvement or noninvolvement of the implanted device and according to the severity of the infection. Severe infections involving the implanted device may preclude heart transplantation for some patients, but numerous patients with milder infections have undergone successful transplantation. Numerous factors predispose VAS patients to infection. Postoperative bleeding necessitating re-operation is an important contributing factor. Endotracheal tubes, intravascular catheters, and other indwelling tubes necessary for the care of postsurgical patients are also common routes of contamination. Control of infection may be improved with new VAS designs, antibiotic impregnated drivelines, and innovative therapies such as antibiotic beads. The next generation of VASs should be inherently less susceptible to infection because of their smaller size, reduced thrombogenicity, and better flow characteristics. In addition to more effective antibiotics, improved VAS designs that incorporate transcutaneous energy transmission systems may reduce infectious complications and allow safe, long-term VAS support.

Equipment Design↗

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Biventricular support with the Jarvik 2000 axial flow pump: a feasibility study.

Patients with congestive heart failure who are supported with a left ventricular assist device (LVAD) may experience right ventricular dysfunction or failure that requires support with a right ventricular assist device (RVAD). To determine the feasibility of using a clinically available axial flow ventricular assist device as an RVAD, we implanted Jarvik 2000 pumps in the left ventricle and right atrium of two Corriente crossbred calves (approximately 100 kg each) by way of a left thoracotomy and then analyzed the hemodynamic effects in the mechanically fibrillated heart at various LVAD and RVAD speeds. Right atrial implantation of the device required no modification of either the device or the surgical technique used for left ventricular implantation. Satisfactory biventricular support was achieved during fibrillation as evidenced by an increase in mean aortic pressure from 34 mm Hg with the pumps off to 78 mm Hg with the pumps generating a flow rate of 4.8 L/min. These results indicate that the Jarvik 2000 pump, which can provide chronic circulatory support and can be powered by external batteries, is a feasible option for right ventricular support after LVAD implantation and is capable of completely supporting the circulation in patients with global heart failure.

Animals↗

PubMedDate not supplied

Prolonged controlled hemorrhagic shock in a swine model: is there a role for mechanical circulatory assistance?

Outcomes of mechanical circulatory assistance during hemorrhagic shock were evaluated in a swine model. Pigs were bled to a mean arterial pressure of 35 mm Hg (group I, n = 3) or 40 mm Hg (group II, n = 5; group III, n = 5), maintained there for 30 minutes, and then resuscitated with fluids alone (groups I and II) or fluids plus mechanical circulatory assistance (group III). Mean blood loss was greater in group I than in groups II or III (1,037 +/- 212 vs. 862 +/- 387 ml vs. 681 +/- 117 ml, respectively; I vs. III, p < 0.05) and survival was shorter (230 +/- 25.5 min vs. 709 +/- 251 min vs. 662 +/- 428 min, respectively; I vs. II or III, p < 0.05). Cardiac arrhythmia caused death in most cases. Mean biochemical parameters increased progressively in all cases. Left anterior descending coronary artery flow stayed relatively constant in group II but increased in group III. Superior mesenteric artery flow returned to baseline in group II but increased in group III. Cardiac output was similar in groups II and III, but SGOT levels significantly differed (750 +/- 135 U/L vs. 359 +/- 157 U/L; p < 0.005). These results suggest that the swine model will be useful for studying ways to improve outcomes after prolonged hemorrhagic shock.

Animals↗

PubMedDate not supplied

Myocardial hemodynamics, physiology, and perfusion with an axial flow left ventricular assist device in the calf.

The Jarvik 2000 axial flow left ventricular assist device (LVAD) is used clinically as a bridge to transplantation or as destination therapy in end-stage heart disease. The effect of the pump's continuous flow output on myocardial and end-organ blood flow has not been studied experimentally. To address this, the Jarvik 2000 pump was implanted in eight calves and then operated at speeds ranging from 8,000 to 12,000 rpm. Micromanometry, echocardiography, and blood oxygenation measurements were used to assess changes in hemodynamics, cardiac dimensions, and myocardial metabolism, respectively, at different speeds as compared with baseline (pump off, 0 rpm) in this experimental model. Microsphere studies were performed to assess the effects on heart, kidney, and brain perfusion at different speeds. The Jarvik 2000 pump unloaded the left ventricle and reduced end-diastolic pressures and left ventricular dimensions, particularly at higher pump speeds. The ratio of myocardial oxygen consumption to coronary blood flow and the ratio of subendocardial to subepicardial blood flow remained constant. Optimal adjustment of pump speed and volume status allowed opening of the aortic valve and contribution of the native left ventricle to cardiac output, even at the maximum pump speed. Neither brain nor kidney microcirculation was adversely affected at any pump speed. We conclude that the Jarvik 2000 pump adequately unloads the left ventricle without compromising myocardial metabolism or end-organ perfusion.

Animals↗