Everett Sd

Myocardial mechanics, energetics, and hemodynamics during intraaortic balloon and transvalvular axial flow hemopump support with a bovine model of ischemic cardiac dysfunction.

Unlike the mechanisms of intraaortic balloon pump (IABP) support, the mechanisms by which transvalvular axial flow Hemopump (HP) support benefit dysfunctional myocardium are less clearly understood. To help elucidate these mechanisms, hemodynamic, metabolic, and mechanical indexes of left ventricular function were measured during conditions of control, ischemic dysfunction, IABP support, and HP support. A large animal (calf) model of left ventricular dysfunction was created with multiple coronary ligations. Peak intraventricular pressure increased with HP support and decreased with IABP support. Intramyocardial pressure (an indicator of intramyocardial stress), time rate of pressure change (an indicator of contractility), and left ventricular myocardial oxygen consumption decreased with IABP and HP support. Left ventricular work decreased with HP support and increased with IABP support. During HP support, indexes of wall stress, work, and contractility, all primary determinants of oxygen consumption, were reduced. During IABP support, indexes of wall stress and contractility were reduced and external work increased. These changes were attributed primarily to changes in ventricular preload, and geometry for HP support, and to a reduction in afterload for IABP support. These findings support the hypothesis that both HP and IABP support reduce intramyocardial stress development and the corresponding oxygen consumption, although via different mechanisms.

Measurement of oxygen consumption and arterial-venous oxygen saturation following total artificial heart implantation.

Current algorithms for control of the total artificial heart are directed at maintaining hemodynamic homeostasis. Future control systems will also need to modify cardiac output in response to metabolic needs. This study was undertaken to evaluate oxygen metabolism monitoring as an indicator of the adequacy of organ and tissue perfusion. Following recovery from implantation of the Utah-100 pneumatic total artificial hearts, five calves (85 to 95 kg) underwent placement of fiberoptic oxymetry catheters to determine mixed venous and arterial oxygen saturations. By continuously measuring oxygen consumption with a gas analyzer, oxygen utilization and delivery were determined. In the awake calves, at-rest cardiac output was varied to produce hyperperfused and hypoperfused conditions while the adequacy of tissue perfusion was assessed with continuous mixed venous oxymetry and confirmed with serum lactate (Lact) levels. Inadequate tissue perfusion (Lact > 1.0 mmol/L) was evidenced by a mixed venous oxygen saturation <40%, oxygen delivery of < 200.0 milliliters/minute/m2), and oxygen delivery to utilization ratio of < 1.8 during the hypoperfusion conditions of the experiment. By accounting for oxygen consumption, the ratio of oxygen delivery to oxygen utilization was predictive of the adequacy of tissue perfusion. These results suggest that continuous oxygen metabolism monitoring may be useful as a physiologic control modifier to maintain total artificial heart output sufficient to meet physiologic needs, while avoiding hyperperfusion, unnecessary wear and deterioration of the implanted device due to excessive heart rates.

Characterization of natural and total artificial heart acceleration

The pulsatile nature of an implanted total artificial heart (TAH) may have several deleterious effects. To define the level of TAH impact, acceleration was measured and compared with that of the natural heart in a series of in vivo and in vitro experiments. In TAH implantations in calves, miniature accelerometers were incorporated onto the housing of a Utah-100 left ventricle. Identical accelerometers were glued to felt pledgets to obtain measurement of radial cardiac acceleration when sewn to the epicardial surface of the natural heart. Measurement of natural and artificial heart acceleration was made both intraoperatively and postoperatively in several animals. Many pumping conditions were also investigated with a similarly instrumented UVAD 85 left ventricle during in vitro testing. The peak natural heart acceleration measured was nearly 2 g both intraoperatively and at rest. Treadmill exercise or epinephrine infusion produced twice the resting peak acceleration value of the natural heart. Artificial heart peak acceleration as great as +/- 100 g was found intraoperatively and postoperatively. Peak TAH acceleration could be reduced by allowing the ventricle to fill fully prior to the start of the next systole, by allowing the ventricle to fully eject prior to the next diastole, or by using a ventricular pressurization waveform that has a smooth contour with a sinusoidal-like profile. The ability to lower TAH acceleration may lead to a reduction in undesirable consequences of TAH implantation.

Calves chronically implanted with a total artificial heart as a pharmacological model.

Pharmacological therapy for congestive heart failure includes drugs that have both inotropic and vasoactive effects, although it is sometimes difficult to differentiate between the two effects. An animal with an implanted total artificial heart (TAH) allows the investigation of the vascular effect of these drugs in the absence of the effect on the myocardium. An advantage of the TAH model is its sensitivity to changes in right and left ventricular preload and afterload. Four instrumented TAH calves were given vasoactive drugs and the response was compared to control. Epinephrine, dopamine, isoproterenol, and nitroprusside were selected because of the predictability of their responses. Epinephrine caused a significant increase in systemic vascular resistance (SVR), and dopamine caused a significant increase in Pulmonary vascular resistance (PVR) and Isoproterenol caused a significant decrease in PVR. TAH implanted calves can thus serve as a pharmacological model to study the vascular response, which may be useful in investigation of new agents with inotropic and vascular effects.

Anaerobic threshold in total artificial heart animals.

The anaerobic threshold represents an objective measure of functional capacity and is useful in assessment of pulmonary and cardiovascular dysfunction. This study determined the anaerobic threshold in total artificial heart animals and evaluated the performance of the total artificial heart system. Five animals with total artificial hearts were put under incremental exercise testing after exercise training. The intensity of exercise ranged from 2.0 to 4.5 km/hr, with an increment of 0.5 km/hr every 3 min. The anaerobic threshold was 6.72 +/- 0.84 ml/kg/min as detected by the lactate method, and 6.48 +/- 0.79 by the CO2 method. The value of the anaerobic threshold in total artificial heart animals implies that the performance capacity of a total artificial heart is not sufficient to meet the oxygen requirements of vigorously exercising skeletal muscle. The protocol does not allow for driving parameter changes during exercise, and this situation, combined with the manual mode of the control system used, was inadequate to allow the total artificial heart animals to exercise more vigorously. Using an automatic control mode might be helpful, as well as considering the relationship between indices of oxygen metabolism, such as oxygen delivery, oxygen consumption, and oxygen extraction rate, in the control algorithms in total artificial heart control systems.

Microbiologic survey of prosthetic blood pumps presterilization and poststerilization and at explant retrieval

Device-associated infection remains a major complication of implanted total artificial hearts (TAH). The possibility of microbes being introduced on the device was investigated by conducting a gross microbial assay, pre- and poststerilization, and following explant retrieval. Culture samples were obtained from the housing, base, and blood-contacting diaphragm of Utah-100 artificial ventricles. Additional samples were obtained from atrial sewing cuffs, outflow grafts, drive lines, and percutaneous leads, along with reference control samples prior to ethylene oxide sterilization (ETO). Culturing was repeated poststerilization and at device explant retrieval. Positive bacterial and fungal cultures were found in 24% of the presterilization samples; in the poststerilization samples, positive cultures were found in 6%. Following device explant retrieval, 84% of the cultures were positive. The reference control samples were positive in a limited number of the poststerilization samples. There was no correspondence of the species of micro-organisms found at the same location for each sampling condition. These data demonstrate that the surfaces of the TAH can become contaminated during fabrication. The presence of microbial activity poststerilization raises the possibility of inadequacy of the ETO protocol used with these devices, or contamination of the surgical field. Hearts at explant retrieval had cultures positive for microbes differing from those identified prior to implantation. This finding suggests that device-associated micro-organism colonization occurs through a source other than manufacturing or surgical contamination.

Oxygen metabolism in animals with total artificial hearts

The relationship between indices of oxygen metabolism has been widely used in clinical practice to evaluate the adequacy of tissue perfusion, to predict the outcome of the critically ill patient, and to evaluate the effectiveness of therapies. This study quantitated and correlated the relationship between oxygen delivery (DO2), oxygen consumption (VO2), and oxygen extraction rate (EO2) in 14 animals with total artificial hearts (TAH) to investigate the oxygen metabolism in animals with TAH during different physiologic and pathologic conditions. These 14 animals were subdivided into healthy, critical, and exercise groups. There was a physiologic dependence of DO2 to VO2 in animals in the healthy and exercise groups, whereas a pathologic dependence of VO2 to DO2 appeared to occur in animals in the critical group. Reduced or inadequate VO2 leads to organ dysfunction, shock syndrome, multiple organ failure, and finally, mortality. Providing a higher level of DO2 by restoring circulating blood volume, increasing cardiac output, raising hematocrit levels, and improving pulmonary function to achieve a higher level of oxygen extract efficiency and oxygen consumption in animals with TAH that are in a critical condition might be helpful for the treatment of complications and result in decreasing mortality. Using the relationship between indices of oxygen metabolism as a physiologic modifier for TAH control algorithms also might improve the physiologic performance and quality of life of TAH recipients.

Adaptive responses of total artificial heart animals to treadmill exercise

The hemodynamic and metabolic adaptations to exercise in five calves implanted with the Utah-100 total artificial heart (TAH) were investigated. The outputs of the left and right ventricles (LCO, RCO) were measured with a cardiac output monitoring and diagnostic unit (COMDU). Arterial and venous oxygen content (CaO2, CvO2) and blood lactate levels (Lac) were measured by blood gas analysis and enzymatic methods. Oxygen consumption (VO2), oxygen delivery (DO2), oxygen extraction rate (EO2), index of metabolic adequacy (IMA), and systemic and pulmonary vascular resistance (SVR, PVR) were calculated. The intensity of exercise was categorized into three horizontal grades: low speed (LS) 0.7-1.0 mph, medium speed (MS) 1.0-1.4 mph, and high speed (HS) 1.4-1.8 mph, each for 30 min. During LS, MS, and HS exercise, the LCO, RCO, LAP, RAP, VO2, DO2, and EO2 all increased, and the SVR and PVR decreased. During exercise, there was a positive correlation between DO2, EO2, and VO2. The blood pH, BE, SBE, and lactate levels were within normal ranges, and the IMA exceeded 1.5, denoting that tissue perfusion was adequate and anaerobic metabolism did not occur. This study implies that Utah-100 TAH animals could physiologically accommodate to exercise with an intensity of up to 1.8 mph for 30 min by increasing cardiac preload, cardiac output, oxygen delivery, and oxygen extraction rate, and by decreasing systemic and pulmonary vascular resistance without transition to anaerobic metabolism.