Noninvasively and invasively measured pulsatile haemodynamics with graded arterial stenosis.

Pulsatile haemodynamics associated with graded degrees of experimentally produced stenosis were studied in the canine femoral artery. Invasively determined pulsatile blood flow and noninvasively determined blood velocity with Doppler ultrasound were measured an average of 1.3 and 2.3 cm proximal to the stenosis, respectively. Pulsatile blood pressure was measured 0.6 cm proximal and 3.7 cm distal to the stenosis. With increasing severity of stenosis there were progressive increases in the femoral artery hydraulic input impedance moduli and in the ratio of the impedance moduli to the zero harmonic impedance (or total resistance). This resulted in: a) a progressive reduction in the Fourier harmonic moduli and pulsewave amplitudes of flow, velocity, and distal pressure; b) a progressive increase in the fifth-seventh proximal pressure harmonic moduli; but c) little change in mean proximal pressure or its first 4 harmonic moduli. The data confirm the well known phenomena of a 'critical stenosis' in that there is little decrease in resting mean blood flow until there is a 70 to 80 stenosis (area reduction). Also the oscillatory portions of the femoral artery data were more sensitive to the changes in stenosis than were the nonoscillatory parameters, which confirms previously reported findings from the thoracic aorta. However, the femoral artery haemodynamics exhibited a greater amount of frequency dependent behaviour than the thoracic aorta which is probably the result of a more complex interaction of reflections from the stenosis and from the periphery in the femoral artery than in the thoracic aorta. The sensitive changes in oscillatory haemodynamics may provide a useful basis for noninvasive and invasive physiological assessment of human peripheral atherosclerotic stenosis and of experimental stenosis in animals.

Pulse wave velocity and morphological changes associated with early atherosclerosis progression in the aortas of cynomolgus monkeys.

To determine the time course of changes in arterial stiffness and corresponding morphology during atherosclerosis progression, we determined pulse wave velocity (PWV) in cynomolgus monkeys fed atherogenic (test) and control diets over an 18-month period. At 6-month intervals, thoracic and abdominal aortic PWVs were determined with a pressure transducer retracted down the aorta in 5 cm increments. Iliac artery PWV was determined from the abdominal aortic pressure to a noninvasive femoral pulse. Groups of individual cardiac cycles, triggered by the ECGs, were sampled on a computer and the velocities (PWV) of the pulse wave fronts were calculated. There was no significant difference between groups until 18 months when test animal PWVs in the thoracic (7.44 +/- 0.83 m X s-1) and abdominal (8.52 +/- 0.67 m X s-1) aorta were significantly greater than those of controls (5.02 +/- 0.51 and 6.24 +/- 0.53 m X s-1, respectively), indicating increased arterial stiffness. There was no change in iliac PWV, 10.96 +/- 0.74 m X s-1 for 18-month test compared with 9.44 +/- 0.89 m X s-1 for controls. Constant infusion of nitroprusside and noradrenaline lowered and raised blood pressure and PWV in all groups, and PWV changes due to drug-induced pressure changes were greater in atherosclerotic than in control arteries. Systolic pressure of 18-month test and pulse pressure of 12- and 18-month test groups were significantly greater than controls under all drug conditions, also indicating increased vessel stiffness. Morphometric evaluation of histological aortic cross sections revealed early, noncomplicated atherosclerosis showing gradual increases in the ratio of intimal to medial cross-sectional area in the thoracic (1.24 +/- 0.30 after 18 months) and abdominal (1.70 +/- 0.42 after 18 months) aortas, compared with control ratios of essentially zero. The fraction of the internal elastic lamina covered with atherosclerotic lesions, and maximal intimal thickness also showed significant increases during the test diet period. These data show that early atherosclerosis resulted in aortic but not iliac stiffening which was detected by increased PWV before development of significant stenotic lesions.

Right heart function during prosthetic left ventricular assistance in a porcine model of congestive heart failure.

A left ventricular assist device was used to produce a 90% reduction in peak systolic left ventricular pressure in pigs with congestive heart failure, and the resultant effects on right ventricular function were determined. Initially, eight farm pigs underwent rapid ventricular pacing at 230 beats/min for 7 days to produce congestive heart failure. When compared with an independent series of normal pigs, cardiac output in the paced animals was 33.3% less (2.2 +/- 0.2 versus 3.3 +/- 0.5 L/min; p less than 0.05), left ventricular end-diastolic pressure was elevated (13.8 +/- 3.5 versus 6.6 +/- 1.8 mm Hg; p less than 0.05), and the slope of the right ventricular global stroke work curve was significantly depressed (0.004 +/- 0.001 versus 0.033 +/- 0.003 joules/mm Hg; p less than 0.05). Next, the left ventricular assist device was connected between left ventricular apex and ascending aorta and left ventricular pressure was reduced from 92.0 +/- 3.8 to 10.5 +/- 2.2 mm Hg, while systemic arterial pressure was maintained constant. This led to a further impairment in cardiac output (-14%), mean arterial pressure (-15%), and the slope of the right ventricular global stroke work curve (-50%). Under each condition, right ventricular preload recruitable stroke work and end-systolic pressure-dimension relationships were studied in three different regions on the right ventricle during both steady-state and transient inferior vena caval occlusion. In the right ventricular septal-free wall dimension, left ventricular pressure unloading resulted in a 47.5% +/- 5.4% (p less than 0.05) reduction in the slope and 20.1% +/- 4.8% (p less than 0.05) increase in the dimension intercept of the preload recruitable stroke work relationship. There was also a 44.6% +/- 4.8% (p less than 0.05) reduction in the slope and 15.6% +/- 2.8% (p less than 0.05) increase in the dimension intercept of the end-systolic pressure-dimension relation. These slope changes plus reductions in cardiac output and in global stroke work, which are indicative of impaired right ventricular function during left ventricular pressure unloading in the congestive heart failure pigs, are not seen in normal hearts, whereas the intercept changes associated with leftward septal shift are present in both. These results suggest that anatomic ventricular interactions have a more significant role in heart failure than in the normal heart in determining overall right ventricular function during left ventricular assist device support.

Effects of acute right ventricular ischemia on ventricular interactions during prosthetic left ventricular support.

Systolic ventricular interactions may be partially responsible for right ventricular failure that sometimes occurs during clinical use of prosthetic left ventricular assist devices. In this hypothesis, it is proposed that the left ventricular assist device reduces left ventricular pressure and its contribution to right ventricular performance, thus impairing right ventricular output. On the other hand, these effects may be small compared with other causes of right ventricular failure such as ischemia. To test the systolic interaction hypothesis in the normal and ischemic right ventricle, we used a left ventricular assist device to pressure unload the left ventricle of anesthetized pigs, and we compared its effect on right heart function before and after 2 minutes of acute right coronary artery occlusion as a model of right heart failure. Pigs were instrumented for measurements of septal to left ventricular and right ventricular free wall dimensions with ultrasonic crystals, ventricular chamber pressures, and cardiac output with a pulmonary artery blood flow probe. Without right ventricular ischemia, the left ventricular assist device produced an 80% +/- 6% reduction in left ventricular pressure-time integral while maintaining aortic pressure. This resulted in a leftward septal shift with an 11.6% +/- 1.8% decrease in left ventricular septal-to-free wall dimension and a 12.5% +/- 2.4% increase in right ventricular septal-to-free wall dimension, with no changes in right ventricular cardiac output or stroke work. In contrast, right coronary artery occlusion alone produced right heart failure, with a 50% +/- 6% reduction in right ventricular global stroke work and 26% +/- 6% and 27% +/- 3% reductions in cardiac output and right ventricular peak systolic pressure, respectively. This right heart failure persisted during left ventricular unloading with the left ventricular assist device, which resulted in further leftward septal shifting and unchanged but still depressed stroke work and flow output. These findings support the hypothesis that a preexisting pathologic condition is the dominant factor in determining right ventricular function during prosthetic left ventricular support and that direct anatomic interactions play a minor role.

In vivo evaluations of a new thromboresistant polyurethane for artificial heart blood pumps.

To reduce the risk of thromboembolic complications in prosthetic blood pumps, we have developed a new segmented polyurethane elastomer. This material is unique because its mechanical properties for long-term durability and surface properties for biocompatibility have been separated and developed in two distinct materials. Improved thromboresistance is then obtained by a 1% concentration of a new polymeric surface-modifying additive blended with the base polyurethane before fabrication of the blood pump. To evaluate this material in vivo, we performed 10 implants, in calves, of the Pierce-Donachy prosthetic ventricle with blood-pumping sacs and cannulas fabricated from the new surface-modifying additive copolymer blend (Thoratec's BPS-215M). In four control implants the blood sacs and cannulas were fabricated from Ethicon's Biomer segmented polyurethane, which is the present clinical standard for most artificial hearts and circulatory support devices. The blood pumps were connected from the apex of the left ventricle to the descending aorta in male Holstein calves weighing 82 to 108 kg and were driven pneumatically in the full-to-empty mode with flows averaging 5 to 6 L/min. Each calf was medicated with aspirin and dipyridamole throughout the study period and was electively put to death after 4 weeks for evaluation of explanted blood sacs and for examination of the kidneys for infarction. All 10 explanted blood sacs made with the surface-modifying additive copolymer blend were shiny and completely free of thrombus. Three of the four explanted Biomer blood sacs showed visible red thrombus, and all four showed small areas of white thrombus. The average surface area of the Biomer blood sacs covered with thrombus was 45 +/- 32 mm2. Use of a semiquantitative scale to assess renal infarction demonstrated that nine of 10 animals with a surface-modifying additive copolymer blend blood sac had infarction less severe than the mean infarct score of the animals with a Biomer sac. The surface-modifying additive copolymer blend has excellent mechanical and physical properties necessary for use in artificial heart blood pumps. From these experiments, we conclude that the surface-modified polyurethane blend is superior to Biomer polyurethane in blood compatibility and in freedom from thromboembolic risk. This material is now approved by the Food and Drug Administration for investigational device exemption studies in the Pierce-Donachy prosthetic ventricle.

Importance of preoperative liver function as a predictor of survival in patients supported with Thoratec ventricular assist devices as a bridge to transplantation.

UNLABELLED: Patient selection is crucial for the success of ventricular assist devices as a bridge to heart transplantation. PURPOSE: The objective of this study was to identify preoperative markers for survival and end-organ recovery in patients having a ventricular assist device. METHODS: A retrospective study was performed on 32 severely ill patients with end-stage cardiac failure being mechanically bridged to heart transplantation with the Thoratec Ventricular Assist Device System (Thoratec Laboratories Corporation, Pleasanton, Calif) in a single center between 1984 and 1995. The preoperative cardiac index averaged 1.6 L/min per square meter with a pulmonary capillary wedge pressure of 29 mm Hg. Because of a high incidence of hepatic or renal dysfunction, or both (total bilirubin: 3.5 +/- 6.2 mg/dL; creatinine: 2.0 +/- 1.3 mg/dL), biventricular support was used in most patients (28/32). A total of 30 preoperative and 4 perioperative variables were evaluated for their association with survival and liver recovery. RESULTS: Nineteen patients (59.4%) survived to transplantation and 13 died. All 19 patients undergoing transplantation were discharged alive with a 1-year survival of 94.4%. All patients without liver recovery died of multiorgan failure. Direct and indirect bilirubin measurements were the only significant predictors for survival to discharge (P = .036, .045); all other factors failed to show significance. As direct bilirubin levels increased (normal range, 3 times normal, and >3 times normal), patient survival decreased (82 %, 56%, and 33 %, respectively). In addition, bilirubin and liver enzyme levels before insertion of the assist device were significantly associated with liver recovery during support with the device. CONCLUSION: In our patient population with ventricular assist devices, liver function is the most predictive factor of patient survival in bridging to transplantation.

Preoperative and postoperative comparison of patients with univentricular and biventricular support with the thoratec ventricular assist device as a bridge to cardiac transplantation.

OBJECTIVES: The goal of this study was to determine whether there are differences in populations of patients with heart failure who require univentricular or biventricular circulatory support. METHODS: Two hundred thirteen patients who were in imminent risk of dying before donor heart procurement and who received Thoratec left (LVAD) and right (RVAD) ventricular assist devices at 35 hospitals were divided into three groups: group 1 (n = 74), patients adequately supported with isolated LVADs; group 2 (n = 37), patients initially receiving an LVAD and later requiring an RVAD; and group 3 (n = 102), patients who received biventricular assistance (BiVAD) from the beginning. RESULTS: There were no significant differences in any preoperative factors between the two BiVAD groups. In the combined BiVAD groups, pre-VAD cardiac index (BiVAD, 1.4 +/- 0.6 L/min per square meter, vs LVAD, 1.6 +/- 0.6 L/min per square meter) and pulmonary capillary wedge pressure (BiVAD, 27 +/- 8 mm Hg, vs LVAD, 30 +/- 8 mm Hg) were significantly lower than those in the LVAD group, and pre-VAD creatinine levels were significantly higher (BiVAD, 1.9 +/- 1.1 mg/dl, vs LVAD, 1.4 +/- 0.6 mg/dl). In addition, greater proportions of patients in the BiVAD groups required mechanical ventilation before VAD placement (60% vs 35%) and were implanted under emergency conditions than in the LVAD group (22% vs 9%). The survival of patients through heart transplantation was significantly better in patients who had an LVAD (74%) than in those who had BiVADs (58%). However, there were no significant differences in posttransplantation survival through hospital discharge (LVAD, 89%; BiVAD, 81%). CONCLUSION: Patients who received LVADs were less severely ill before the operation and consequently were more likely to survive after the operation. As the severity of illness increases, patients are more likely to require biventricular support.

Preoperative predictors of survival in patients with Thoratec ventricular assist devices as a bridge to heart transplantation. Thoratec Ventricular Assist Device Principal Investigators.

Approximately two-thirds of patients implanted with ventricular assist devices recover sufficiently to requalify for heart transplantation, and the other one-third die of complications that are often secondary to delayed ventricular assist device implantation and subsequent end-organ failure. To determine whether any preoperative predictors of survival exist, univariate statistics and multivariate stepwise logistic regression analysis were performed on pre-ventricular assist device demographics, hemodynamics, and blood chemistry in 186 patients receiving Thoratec ventricular assist devices (Thoratec Laboratories Corp., Berkeley, Calif.) while awaiting transplantation. The duration of circulatory support averaged 19.6 days (maximum, 226 days). One hundred thirty-seven patients (74%) received biventricular support, 47 received isolated left ventricular assist devices, and two received right ventricular assist devices. The average blood flow was 5.0 +/- 0.9 L/min. One hundred eighteen patients (63%) ultimately received heart transplants, of whom 96 patients were discharged. Age, gender, weight, and diagnosis were not related to survival, nor were preoperative cardiac index, pulmonary capillary wedge pressure, intraaortic balloon pumps, or cardiac arrests. Pre-ventricular assist device creatinine levels (p = 0.24) and total bilirubin levels (p = 0.09) were not significant, but blood urea nitrogen level (p = 0.02) and previous operations (p = 0.05) were related to survival, using univariate techniques. Patients with cardiac operations more than 30 days previously had the lowest survival-to-transplantation (39%) compared with patients with no previous operations (67%) or operations within the previous 30 days (61%). Blood urea nitrogen level was the only parameter found to be significant (p = 0.016) in a multivariate model.(ABSTRACT TRUNCATED AT 250 WORDS)

A new skeletal muscle linear-pull energy convertor as a power source for prosthetic circulatory support devices [corrected].

Previous studies show that stimulated skeletal muscle wrapped around the heart or a blood pumping pouch can provide partial circulatory assistance. However, skeletal muscle is accustomed to pulling in direct tension, and power obtained from using the muscle in wraparound configurations is very inefficient. Therefore we have developed a new skeletal muscle-powered, linear-pull energy convertor for powering a wide range of implanted devices, including circulatory support blood pumps such as counterpulsation devices or complete prosthetic ventricles. This energy convertor system is powered by a skeletal muscle such as the latissimus dorsi, which is stimulated with a pulse generator. With the muscle left intact and in situ as much as possible, its insertion at the humerus is removed and reattached to a small-cylinder hydraulic energy convertor that is firmly attached to the ribs. Mechanical force in direct tension from the muscle is converted to high-pressure, low displacement; hydraulic energy (at approximately 200 psi). The output of this hydraulic energy convertor is connected by a small-diameter tube to a hydraulic actuator to drive the pusher plate of an implantable ventricular assist device located in the thoracic cavity or abdomen or another suitable blood pump. Preliminary in vitro tests from an engineering model of the Thoratec muscle-powered ventricular assist device show flow outputs of 5.2 L/min at a mean arterial pressure of 99 mm Hg. The muscle-powered ventricular assist device is a specific application designed to provide completely implantable circulatory support as an alternative to heart transplantation. It will enable patients to experience a quality of life free from batteries and the electrical power-conditioning hardware required with electromechanical systems.

Recovery of major organ function in patients awaiting heart transplantation with Thoratec ventricular assist devices. Thoratec Ventricular Assist Device Principal Investigators.

The time course of recovery of hepatic and renal function was determined in 193 patients receiving Thoratec ventricular assist devices while awaiting transplantation at 41 hospitals in eight countries. The duration of circulatory support averaged 26 days (maximum 248 days) and the average ventricular assist device blood flow index was 2.7 +/- 0.5 L/min/m2 compared with a preoperative cardiac index of 1.4 +/- 0.7 L/min/m2. Renal and hepatic function improved in most patients in 1 to 3 weeks of support. When comparing patients with the longest durations on the ventricular assist device (60 to 248 days) to patients with the shortest durations (< 7 days), laboratory values were significantly improved: creatinine (-29%, from 1.7 +/- 1.2 to 1.2 +/- 0.5 mg/dl), blood urea nitrogen (-32%, from 37 +/- 27 to 25 +/- 14 mg/dl), serum glutamic-oxaloacetic transaminase (-81%, from 397 +/- 702 to 76 +/- 45 IU) and total bilirubin (-79%, from 7.0 +/- 8.6 to 1.5 +/- 0.7 mg/dl). However, the posttransplantation survival through hospital discharge was not significantly different: 88% (14 of 16) for patients supported for at least 60 days and 86% (43 of 50) for patients who underwent transplantation after only 1 week of support. Therefore renal and hepatic function improve during ventricular assist device support, but the survival rate after transplantation is not related to duration and is comparable to that of conventional heart transplantation for short or long periods of ventricular assist support. Although it is clearly important not to proceed to transplantation in patients with irreversible organ failure who have ventricular assist devices, these data suggest that as long as the patient is on the path to recovery, the outcome is basically the same as for patients who have full recovery of renal and hepatic function.

Multicenter experience with the thoratec ventricular assist device in children and adolescents.

BACKGROUND: Patient size is 1 determinant in selecting a mechanical circulatory support device. The current pulsatile ventricular assist devices (VADs) were designed primarily for average-sized adults. The flexibility of the Thoratec VAD, however, has encouraged physicians to use it in a significant number of intermediate-sized older children and adolescents. METHODS: We conducted a retrospective study in 58 children and adolescents <18 years (41 boys, 17 girls) who had been supported with the Thoratec VAD in 27 centers worldwide as of December 1999. Mean patient age was 13.8 years (range, 7 to 17 years), and mean patient weight and body surface area were 51.6 kg (range, 17 to 93 kg) and 1.5 m(2) (range, 0.7 to 2.1 m(2)), respectively. RESULTS: Thirty-five patients (60%) survived to transplantation and 6 (10%) to recovery of the native heart, respectively; 38 were discharged from the hospital (66%). In the transplanted group, post-transplantation survival was 97%. Patient age and size were not associated with significantly increased risk for death or adverse events. Fifteen patients (27%) had 18 neurologic events during support, and 6 of these were fatal. Left atrial cannulation proved a risk factor for neurologic complications. CONCLUSIONS: The Thoratec VAD has successfully been used in a large number of children and adolescents with similar morbidity and mortality results as with adults. The risk of neurologic complications may be increased, particularly in patients cannulated in the left atria.

Graded compression stockings: custom vs noncustom.

Graded compression stockings of the leg (high pressure at the ankle and low pressure at the thigh) seem to help the return of venous blood to the heart and reduce the incidence deep-vein thrombosis and pulmonary emboli in supine patients. Recent advances allow noncustom stockings to be chosen for mesomorphic patients by leg length and calf circumference yet deliver the desired level of graded compression. To test the hypothesis that custom-tailored and noncustom, low-modulus. circular-knit stockings are equally efficient, a Doppler instrument and recorder were used to continually monitor femoral-vein velocity both when the patient had the stocking on and after it was removed. The changes in venous velocity after removal of custom and noncustom stockings were similar (-19% and -27%, respectively). In the five patients with whom both types of stocking were evaluated, the changes were -24% for custom and -22% for noncustom stockings. Using Laplace's law and measuring the tension created by a given stretch (circumference), low-modulus stockings were shown to deliver a more uniform pressure over a greater range of leg circumference than did high-modulus stockings. These results justify the use of noncustom, low-modulus, circular-knit elastic stockings to increase femoral-vein velocity in supine, mesomorphic patients.

Univentricular and biventricular Thoratec VAD support as a bridge to transplantation.

As of October 1991, the Thoratec ventricular assist device (VAD) system has been used in 154 transplant candidates who were in imminent risk of dying before donor heart procurement at 39 medical centers in 10 countries. The VAD system consists of a prosthetic ventricle with a 65-mL pumping chamber made from Thoratec's BPS-215M polyurethane, cannulas for atrial or ventricular inflow and arterial outflow connections, and a pneumatic drive console. The devices can be used for partial or complete support of the pulmonary, systemic, or both circulations. In all patients (average age, 42 years; range, 11 to 64 years), the pumps were placed in a paracorporeal position on the anterior abdominal wall and connected to the heart and great vessels by cannulas crossing the chest wall. Biventricular support was used in 120 patients (78%) and isolated left VADs were used in 34. Average flow rate was 5.0 +/- 0.9 L/min for the left VAD and 4.3 +/- 0.8 L/min for the right VAD. The most frequent complications were bleeding (42% incidence, 7% mortality) and infection (36% incidence, 8% mortality). Ninety-eight patients (65%) recovered sufficiently to undergo heart transplantation after 8 hours to 226 days of support (average, 17.5 days), and 3 are waiting on VADs for transplantation. Eighty-two patients who received transplants have been discharged. This is an 84% early post-transplantation survival and a 54% overall survival. The actuarial survival 1 year after transplantation is 82%, comparable with that of conventional heart transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

A versatile intracorporeal ventricular assist device based on the thoratec VAD system.

BACKGROUND: As patients are supported for longer durations with paracorporeal Thoratec left ventricular and biventricular assist devices (longest durations: 515 and 457 days, respectively), there is a need for implantable options. METHODS: We are developing a small, simple, and versatile intracorporeal ventricular assist device (IVAD) for left, right, or biventricular support as an alternative to the large, implantable, pulsatile left ventricular assist device (LVAD) systems available today. The new device is based on the Thoratec paracorporeal VAD that has been used in more than 1,400 patients weighing from 17 to 144 kg and for durations exceeding 1 year including patient discharge (using the portable driver). RESULTS: The IVAD has the same blood flow path and Thoralon polyurethane blood pumping sac as the paracorporeal VAD, but the housing is a smooth contoured, polished titanium alloy. The IVAD has a new sensor to detect when the pump is full and empty, and is controlled with the Thoratec TLC-II portable VAD driver, which is a small, briefcase-sized, battery-powered, pneumatic control unit. A small flexible (9 mm OD) percutaneous pneumatic driveline for each VAD is tunneled out of the body from the LVAD or right VAD in a pre- or intraperitoneal position. Small size and simplicity are the major advantages of the new device. The IVAD weight (339 g) and implanted volume (252 mL) are approximately one-half that of the current implantable pulsatile electromechanical LVAD systems. CONCLUSIONS: The small size of the IVAD should not only allow support of a large range of patient sizes and body habitus, but also provide options for implantable left, right, or biventricular support. By implanting only the mechanically simple blood pump, the more complex control unit is external, where it can be serviced and replaced without surgery. The IVAD with the portable driver will be a viable alternative to large implanted electromechanical systems and should address a larger segment of the physically diverse patient population.

A new method of monitoring recovery and weaning the Thoratec left ventricular assist device.

BACKGROUND: Recent scientific and clinical data suggest that chronic mechanical ventricular unloading may lead to myocardial recovery. Evaluating and monitoring patients for myocardial recovery and the optimal methods of weaning the left ventricular assist device are not well defined. METHODS: Six patients with advanced heart failure and severe mitral regurgitation have undergone successful bridge to recovery using a Thoratec left ventricular assist device. Data that details their monitoring for myocardial recovery and weaning from the left ventricular assist device were prospectively collected. RESULTS: Clinical data collected during the recovery phase included chest roentgenogram, echocardiography, plasma norepinephrine, tumor necrosis factor-alpha, bioimpedance, and cardiopulmonary exercise testing (peak oxygen consumption). Normalization of these variables with a 10% increase in the peak oxygen consumption was obtained before weaning. The Thoratec device rate and percent systole were manipulated to allow gradual reloading of the ventricle. The weaning process occurred for more than 5 to 10 days to allow time for observation of the ventricle and its response to the increasing workload. CONCLUSIONS: Select patients with advanced congestive heart failure and severe mitral insufficiency can benefit from mechanical device support. We describe our technique of monitoring for myocardial recovery using clinical variables. Our technique of weaning allows for gradual reloading of the ventricle and a longer period of observation before device removal. Additional research is needed to determine which variables will accurately predict long-term myocardial recovery and the optimal weaning method.

Urodynamic study of 15 patients with postmicturition dribble.

Fifteen patients presenting with postmicturition dribbling as their only symptom were studied in the urodynamic laboratory. Seven of these patients had no urodynamic abnormality but left a significant bulbar residue after micturition. Five patients had normal detrusor function but failed to milk back contrast from the prostatic urethra during voluntary interruption of the steam. Two of these also had a small amount of bulbar residue. The remaining three had unstable detrusor function. One had classic bladder neck obstruction. One had a bulbar residue and the other failed to milk back properly. Despite the various mechanisms for postmicturition dribble, the management is the same in all cases. The patient is instructed to press the bulbar urethra manually in the perineum after micturition and evacuate the residue, and symptomatic relief is almost always obtained. Urodynamic studies in these patients are not justified unless this maneuver fails to alleviate the symptoms.

The thoratec ventricular assist device: a paracorporeal pump for treating acute and chronic heart failure.

The Thoratec Ventricular Assist Device (VAD) System (Thoratec Laboratories, Pleasanton, CA) is a paracorporeal pump that can provide univentricular or biventricular assistance for patients with heart failure. The system consists of a prosthetic ventricle that has a blood-pumping chamber of Thoralon (Thoratec Laboratories) polyurethane, cannulas for univentricular or biventricular support, and either a hospital-based pneumatic drive console or a portable battery-powered drive unit. For biventricular assistance, 2 pumps are used. The Thoratec voluntary registry indicates that, as of May 2000, this system had been implanted in 1,376 patients, mainly for bridging to transplantation (828 patients) or postcardiotomy support (195 patients); the remaining 353 patients received a hybrid configuration of the device or had incomplete information, so they are not included in this analysis. In the 828 bridge-to-transplant patients, the Thoratec system provided biventricular assistance in 472 cases, left ventricular assistance in 326 cases, and right ventricular assistance in 30 cases for up to 515 days. During the support period, the cardiac index increased significantly from 1.4 +/- 0.8 L/min/m2 to 3.0 +/- 0.5 L/min/m2 (with biventricular assistance and left ventricular cannulation). Sixty percent of the 828 patients underwent transplantation, and the posttransplant survival rate was 86%. In the 195 patients who needed postcardiotomy support, VADs were used for up to 80 days for cardiac recovery. Thirty-eight percent of the patients were weaned from the VAD, and 59% of the weaned group were discharged from the hospital. In addition, 49 postcardiotomy patients were considered for transplantation; of these, 32 received a transplant and 23 were discharged. Patient mobility is being improved by the use of a portable driver. The Thoratec VAD is suitable for a wide range of applications, and efforts are underway to facilitate patient mobility and allow hospital discharge. An intracorporeal version of the VAD, which is currently under development, will help achieve these goals.

Megestrol acetate: promises and pitfalls.

Recent reports suggest that effective antiretroviral therapy, resulting in a plasma HIV load that has been reduced to undetectable levels, may itself prevent HIV- and opportunistic infection-associated weight loss and lead to substantial weight gain. Although these data are encouraging, it is clear that a significant proportion of patients will require, in addition, specific treatment for HIV-associated wasting. Megestrol acetate, in the dosage range of 400 to 800 mg/day, is a useful appetite stimulant for the prevention and treatment of HIV-associated wasting, particularly in women. Patients need to be advised of possible adverse effects and monitored closely. Megestrol acetate stimulates weight gain mostly through an increase in body fat and is therefore most effective in combination with a muscle-building exercise program, where appropriate, and an anabolic agent (steroid or growth hormone) to maintain or increase lean body mass.

Characterization and work optimization of skeletal muscle as a VAD power source.

Powering a ventricular assist device (VAD) with skeletal muscle in a linear configuration will require the understanding of basic muscle mechanics and efficient use of available power. Accordingly, a mathematical model incorporating aspects of the Hill equation has been developed. This model relates whole muscle length, force, velocity, and time during cyclic contraction to investigate coupling with a hydraulically actuated VAD. Parameters of the model have been determined from in vivo isometric and isotonic measurements of electrically stimulated pig latissimus dorsi with the humerus insertion reattached to a hydraulic loading system. The in vivo results show an exponential passive force-length relationship and active isometric forces increasing from 2 to 8 kgf over a 5 cm change in length. The maximum shortening velocity extrapolated from isotonic data in 85 cm/sec. With the experimentally determined parameters, the model system of differential equations was optimized computationally. Predicted maximum cycle work and corresponding muscle force are nonlinear functions of contraction duration; an increase in duration yields little improvement in work output for longer contraction times. The model helps clarify VAD system design parameters for optimal muscle coupling; for example, the model predicts that operating at maximum instantaneous power does not optimize stroke work.

Effects of left ventricular pressure unloading during LVAD support on right ventricular contractility.

The effects of left ventricular pressure (LVP) unloading with a left ventricular assist device (LVAD) on right ventricular (RV) end-systolic pressure volume relationships were studied. A Thoratec (Berkeley, CA) LVAD was implanted in open chest anesthetized pigs via apical cannulation, and an electromagnetic flow probe and computer controlled pneumatic occluder were attached to the pulmonary artery. RV and left ventricular (LV) pressures were measured with Millar catheters, and changes in RV volume during ejection were determined by integrating the flow signal. As an index of contractility, RV maximal systolic elastance (Emax) was calculated as the slope of the end systolic, pressure volume relationship between an isovolumic beat and a series of transiently occluded beats at different times in the ejection phase. After an 83 +/- 15% decrease in LV pressure time integral during LVAD pumping, there were no significant changes in cardiac output, mean systemic arterial pressure, or in RV dP/dtmax. Most important, RV Emax during LVAD unloading (0.63 +/- 0.16 mmHg/ml) was unchanged from control (0.62 +/- 0.10 mmHg/ml). Therefore, in the normal intact porcine heart, the effective contractility of the right ventricle is not altered by significant LV pressure unloading produced with a LVAD.