Performance of an abdominal left ventricular assist device during induced tachycardias and dysrhythmias.

Experiments were designed to assess the performance of an intracorporeal (abdominal) left ventricular assist device (ALVAD) in the presence of induced tachycardias, multiple premature ventricular contractions (PVC's), and ventricular fibrillation in calves. Performance criteria were the degree of left ventricular unloading and the per cent cardiac output assumed by the ALVAD. During synchronous pumping, left ventricular unloading was complete and the entire cardiac output was captured by the device. During induced tachycardias up to rates of 120 beats per minute, these degrees of performance were maintained. At rates in excess of 120 beats per minute, performance declined due to decreased biologic stroke volumes and prosthetic filling times. In the presence of induced PVC's, performance during synchronous pumping decreased because of erratic R-wave sensing. Left ventricular unloading was complete but irregular, and the total cardiac output was captured. When asynchronous pumping was utilized, mean left ventricular systolic pressures increased, but total cardiac output was still captured. During induced ventricular fibrillation, ALVAD actuation maintained cardiac outputs equal to control values for periods up to 5 1/2 hours. These experiments indicate that, during normal sinus rhythm, synchronous pumping is optimal; asynchronous pumping is optimal during complex dysrhythmias; and either can be utilized to support the circulation with varying degrees of left ventricular unloading.

Prognostic indices for survival during postcardiotomy intra-aortic balloon pumping. Methods of scoring and classification, with implications for left ventricular assist device utilization.

To define more clearly a salvageable patient for possible utilization of a left ventricular assist device prior to multiple organ failure and irretrievability during postcardiotomy intra-aortic balloon pumping (IABP), we made prospective and retrospective analyses to determine prognostic indices for survival. Serial left ventricular function curves (IABP on-off), scoring methods, hemodynamic and renal function tracking trajectories, survival versus nonsurvival data envelopes, and classification methods were developed and used. All patients requiring postcardiotomy IABP support who were in Class A survived; 80 percent of the patients in Class B survived. All patients who remained in Class C for 12 hours or more following operation with IABP support died. These preliminary analyses suggest that the postcardiotomy IABP-supported patient with a score of less than 6 who remains in Class C for 12 hours or more is at the highest possible risk and is a probably candidate for more effective support with a left ventricular assist device.

Development and evaluation of electrically actuated abdominal left ventricular assist systems for long-term use.

A long-term, totally implantable, electrically actuated, abdominally positioned left ventricular assist system (ALVAS) is being developed, characterized in vitro, and evaluated in vivo for utilization in patients with end-stage cardiac failure refractory to conventional therapeutic techniques. The first two major subsystems of the ALVAS (the pusher-plate blood pump and electrical-mechanical energy converters) have been integrated and are undergoing in vitro characterization and long-term in vivo evaluations in calves. Duration of these studies has exceeded 6 months. System performance in terms of hemodynamic effectiveness, mechanical reliability, and biocompatibility has been excellent and no untoward effects have been observed. Long-term effectiveness of the ALVAS remains to be established in continuing experiments, with a 2 year period of clinical use as an ultimate goal.

An intracorporeal (abdominal) left ventricular assist device. Initial clinical trials.

We have initiated clinical trials with an intracorporeal (abdominal) partial artificial heart and ten preterminal postcardiotomy patients have been studied. During profound left ventricular failure, the device captures the entire cardiac output from the apex of the left ventricle at low pressures (20 to 40 mm Hg) and ejects (at 80 to 150 mm Hg) into the infrarenal abdominal aorta; the biological aortic valve opens only intermittently and the entire systemic circulation is pump generated. The device is six to ten times more effective than intra-aortic balloon pumping in man and has maintained systemic perfusion during clinical asystole and ventricular fibrillation. We have documented that the profoundly depressed postcardiotomy left ventricle, initially incapable of ejection, can recover during total left ventricular unloading with the abdominal left ventricular assist device support over a seven-day period.

An abdominal left ventricular assist device: preclinical studies.

An abdominally positioned left ventricular assist device (ALVAD) has been evaluated in our most recent series of 25 calves weighing 99 plus or minus 12 kg. The ALVAD is a pneumatically actuated bladder pump, positioned subdiaphragmatically and connected between the left ventricular apex and the infrarenal abdominal aorta. The mean survival time in the calves was 41 days and the longest 65 days. The major effects of the pump are reduction of all indices of left ventricular work and increases in systemic perfusion. In the awake, unanesthetized calf, left ventricular pressure, dP/dt, and stroke work were decreased while peak aortic pressure, stroke volume, and cardiac output increased. These effects were corroborated at cardiac catheterization two to four weeks postoperatively; left ventriculograms also showed increases in ejection fraction. These data demonstrate the ALVAD's effectiveness in assuming left ventricular function and support over extended periods. The device has been developed for short-term postoperative clinical use in patients with reversible left ventricular failure.

Production of controlled reversible left ventricular failure in calves using intracoronary lidocaine hydrochloride: a useful method of evaluating left ventricular assist devices.

The experimental production of stable, controlled, short-term left ventricular failure is valuable in the evaluation of implantable circulatory support systems. Acute or chronic left ventricular failure produced by occlusion or embolization of coronary arteries results in muscle dysfunction and degrees of failure that may be difficult to control. The effects of varying amounts of intracoronary lidocaine were studied during short- and long-term evaluations of intracorporeal left ventricular assist pumping. In 8 Hereford calves the left main coronary artery was cannulated with an intracoronary catheter in open and closed chest preparations. Dose-related negative inotropic effects were noted when lidocaine was injected at individual doses of 50, 75, and 100 mg. Following 100 mg doses, mean aortic pressure, cardiac output, and maximum rate of rise of left ventricular pressure decreased; left ventricular end-diastolic pressure increased fourfold. Similar effects were noted with short continuous infusions of lidocaine. The initial responses to injection or continuous infusions, if effective, were noted within 40 to 60 seconds. Several episodes of failure could be produced with either method following recovery periods of 10 to 15 minutes. In all instances, actuation of a left ventricular assist device immediately reversed the hemodynamic effects of the pharmacologically induced failure.

Infusion therapy devices: selection, cost and maintenance.

Each healthcare facility must formulate and justify their policies and procedures for providing infusion therapy. The materials manager and/or central supply manager should be involved in this process. Each facility must address and define its own specific applications and justify the decisions within the respective medical, nursing, technical and administrative staffs. Furthermore, the facility's policy and procedures should not be static. They must be reviewed and upgraded at regular intervals because of the changes in medical technology and pharmacology. Proper understanding of the definitions addressed in this article will assist in simplifying committee decisions and provide for a more comprehensive and rational policy.

Taking charge of high-tech equipment purchases.

Today's rising operating costs and declining revenues have focused attention on the importance of materiel managers in influencing their hospital's struggle to balance fiscal responsibility with the need to remain in step with advancing technology. This change in the status has left some materiel managers still struggling to find ways to fulfill the expectations of their hospital's administration and many members of the staff. One way materiel managers can respond is by taking the lead in establishing a strategic planning mechanism for capital equipment purchases; by insisting that equipment purchase decisions be made in the context of the whole hospital; by insisting that purchase decisions look beyond price to return on investment; and by insisting that each acquisition be a worthwhile, long-term investment for the hospital. The obvious justification for these demands is that they make economic sense.

Failure of general anesthesia to potentiate propranolol activity.

To determine whether halothane and morphine, commonly used during anesthesia for cardiac operations, potentiate the beta blocking activity of propanolol, hemodynamic changes induced by five incremental doses of propranolol (10, 20, 50, 120, 200 microgram/kg) were measured during halothane, 1 per cent, in oxygen, and morphine, 4 mg/kg. Against a background of contant beta stimulation by infusion of isoproterenol, 0.1 microgram/kg/min, and vagal blockade by atropine, 3 mg, propranolol produced significant dose-related decreases in heart rate, cardiac index, stroke volume index, and left ventricular dp/dtmax and significant increases in mean aortic pressure, systemic vascular resistance, and pulmonary capillary wedge pressure. Compared with basal anesthesia with pentobarbital, 15 mg/kg, neither morphine nor halothane increased sensitivity to any measured effect of propranolol expressed as the slope of the log dose-response relationship. It is concluded that the beta blocking activity of propranolol is not potentiated by morphine and halothane anesthesia but, rather, their effects are additive.

Peripheral effects of cardiovascular drugs during total artificial heart pumping in the awake unanesthetized calf.

Effects of various drugs, such as Isuprel, Neo-synephrine, aminophylline and quinidine, have been evaluated and compared in both control and TAH calves. In the control calves, the cardiac effects of these drugs were overlapped by vascular effects. But in the TAH calves, pure vascular effects have been clearly shown. 1) The peripheral effects of Dibenzyline and Inderal were evaluated in the TAH calves. 2) From these results, it has been concluded that the TAH animal is a useful model for the study of the peripheral vascular response to drugs in awake, unanesthetized subjects.

Dynamic alveolar mechanics as studied by videomicroscopy.

The in vivo morphology of rat alveoli has been recorded and studied on videotape. The dynamic internal structure has been compared to that observed by histologic section from lung rapidly frozen with liquid nitrogen. The irreversible nature of local alveolar wall movement has been demonstrated in animals ventilated both with and without positive end-expiratory pressure (10 cm water) by parametrically comparing the distances between two sets of paired points measured sequentially across internal alveolar surfaces at intervals of 0.017 sec. Geometric hysteresis was significantly less in the animals ventilated with positive end-expiratory pressure. This hysteresis can be explained by irreversibility in alveolar surface area apart from any irreversible dependence on surface tension. Sharp reverses and rapid changes in geometric hysteresis suggest that the length-tension properties of elastic tissue within the alveolar wall and interface forces from adjacent alveoli are important determinants of local alveolar wall motion and pulmonary hysteresis.

Chronic evaluations of ventricular ejection phase dynamics during abdominal left ventricular assist device (ALVAD) pumping in the awake, unanesthetized calf.

In 1974, between 2 and 8% of the 50,000 adult patients undergoing cardiac surgery in this country succumbed in the early post-operative period from left ventricular failure, despite various methods of pharmacologic and/or mechanical support. Our laboratories have concentrated on the development, modification, evaluation, and validation of an abdominally positioned left ventricular assist device which has the potential of reducing these mortalities. Continuous testing in animals, for periods exceeding 2 mos, satisfied reliability, durability and longevity requirements. The cumulative results of these investigations were reviewed at the National Heart and Lung Institute on August 21, 1975. Authorization for clinical trials of the device according to specific criteria and protocols46 was approved on November 1, 1975. The ALVAD is now in the early stages of clinical testing. The results of the current experiments demonstrate that ventricular outflow impedance and prosthetic inflow impedance are the major determinants of left ventricular assist device hemodynamic effectiveness. By markedly reducing outflow impedance, the ALVAD profoundly lowers ventricular pressure-work and oxygen demands while simultaneously increasing ventricular performance and maintaining or augmenting systemic perfusion. Moreover, our studies indicate that improved device designs (intended for intermediate and long-term implantation) and maximal performance can be achieved by focusing on these central determinants.

Molecular, microscopic, microstructural and mechanical methods of analyzing pseudoneointimal linings within partial artificial hearts in man and the calf.

Ex vivo molecular, microscopic (cellular), microstructural and mechanical methods have been utilized to evaluate biologic, blood-interfacing linings (pseudoneointimal) formed on textured, fibril-flocked pumping surfaces within abdominal left ventricular assist devices (ALVADs) on partial artificial hearts. Thus far, seventeen human and twenty bovine pseudoneointimal linings (1--28 day pumping durations) have been evaluated by these methods. The results indicate that pseudoneointima begins developing within 24 hours after contact of the pumping surface with blood and is well developed at five days. The linings exhibit surface immunofluorescent fibrinogen activity, viable surface macrophages and histiocytes and scattered erythrocytes at ALVAD removal. Structurally similar linings (20 micrometer to 500 micrometer in thickness) develop in calves and in man. Mechanically, pseudoneointima is a stable, adherent, highly compliant, isotropic structural material. It is linearly elastic and strain-rate independent, with small viscous energy losses under physiologic strains. The methods employed for the evaluation of pseudoneointima provide useful information to determine the suitability of textured or rough surfaces for blood interfacing. The cumulative results indicate that the textured surface approach is useful for intermediate-term clinical ALVAD utilization.

Evaluation of cardiac function and venous return curves in awake, unanesthetized cialves with an implanted total artificial heart.

1) The implanted TAH offers a method of evaluating the effects of varying physiologic demands cardiac output and venous return. 2) Cardiac output and venous return measurements offer a method of evaluating system design of the device and driving and control-logic improvements in awake, unanesthetized animals. 3) The obtained cardiac function and venous return curves suggest that the present TAH is less responsive to increases in right atrial pressure than the natural heart, but is still completely controlled by venous return. Therefore, it is extremely important to make every effort to eliminate any factor causing excessive venous return.

Intra-aortic balloon pumping: theory and practice. Experience with 325 patients.

Intra-aortic balloon pumping to support the failing circulation is now an accepted therapeutic modality. The device is simple. Insertion can be accomplished rapidly and efficiently in emergency rooms, coronary care units, cardiac catheterization suites and operating rooms, preoperatively, intraoperatively and postoperatively. The hemodynamic effects are immediate and predictable, and the accruing clinical results show increasing survival and hospital discharge rates. In these institutions, mechanical support of the circulation by this and more advanced methods has been formalized within the responsibility of a Circulatory Support Service. The purpose of this report is to summarize some observations and analyses which have been made during care of 325 consecutive postcardiotomy and/or postinfarction cardiogenic shock patients. Historical, theoretical, basic, and applied aspects and current results are included. Foremost are the straightforward concepts of considering the heart as a pump, the failing heart as a failing pump and intra-aortic balloon pumping as a temporary intravascular, auxiliary pump, capable of stabilizing or reversing that failure if utilized early in its evolution.

RIGHT AND LEFT VENTRICULAR HEMODYNAMIC INDICES AS PREDICTORS OF THE NEED FOR AND OUTCOME OF POST-CARDIOTOMY MECHANICAL INTRAAORTIC BALLOON PUMP SUPPORT.

Preoperative cardiac catheterization data of 21 patients requiring intraaortic balloon pumping (IABP) for weaning from cardiopulmonary bypass were analyzed and compared with similar data in 28 patients who underwent nearly similar operative procedures, but did not require IABP for weaning. Cardiac index (CI) and systemic vascular resistance (SVR) were found to have predictive value for the need of IABP for weaning from cardiopulmonary bypass and differentiated survival from non-survival. Left ventricular end diastolic pressure (LVEDP) was not found to be predictive. Ejection fraction (EF) was significantly lower in those who required IABP than those who did not; EF did not predict the outcome. Pulmonary capillary wedge pressure ([unk]), pulmonary artery pressure ([unk]) and pulmonary vascular resistance (PVR) were predictive of the need for IABP, but not the outcome. Left ventricular minute work index (LVMWI) was significantly lower in those requiring IABP, right ventricular minute work index (RVMWI) was predictive of survival with IABP. Together, LVMWI and RVMWI were predictive of the need for and outcome of IABP following cardiopulmonary bypass. Twenty-seven of 28 control RVMWI's were normal. No patient requiring IABP had depressed RVMWI's preoperatively. Elevated preoperative RVMWI's were associated with 80% survival with postcardiotomy IABP; normal RVMWI's were associated with a 56% survival with post-cardiotomy IABP. Elevated preoperative RVMWI's reflected moderate to maximal right ventricular compensatory capacity in response to depressed left ventricular function. Normal preoperative RVMWI's in the presence of depressed LVMWI's were indicative of decreased right ventricular compensatory capacity in post-cardiotomy IABP-support settings. Right ventricular function is as important as left ventricular function as a prognosticator for the need and outcome of IABP support of the failing post-cardiotomy circulation.

CLINICAL TRIALS OF THE ABDOMINAL LEFT VENTRICULAR ASSIST DEVICE (ALVAD): PROGRESS REPORT.

An abdominal left ventricular assist device (ALVAD) is undergoing controlled clinical trials in our institution. The ALVAD is pneumatically-actuated, synchronously or asynchronously with an external console and is interposed between the apex of the left ventricle and the infrarenal abdominal aorta. It is an order of magnitude more effective than conventional intraaortic balloon pumping. Thus far, we have implanted this pump in 21 patients (15 males and six females). The average age has been 50. The duration of cardiopulmonary bypass with intensive pharmacologic support and IABP until ALVAD implantation has been nearly 4 hours. The plasma hemoglobins prior to ALVAD implantation have averaged 168 mg%. The platelet counts at implantation have averaged 68,000 mm(3). The average duration of ALVAD support has been in excess of one day and the longest trial extended for one week. We have been able to remove the pump after ventricular recovery in two instances and effected cardiac allografting in one instance of ALVAD dependency. We have found that (1) the profoundly depressed left (and right) ventricles can recover if totally supported with this device; (2) the device can function in the presence of ventricular fibrillation and/or standstill; (3) the device can effectively replace both left and right ventricular function in the presence of normal pulmonary vascular resistance and microcirculatory hemodynamics; and (4) in the presence of impending multiple organ failure, procrastination in use is to be avoided.