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The pericardium, which surrounds the heart, provides a unique enclosed volume and a site for the delivery of agents to the heart and coronary arteries. While strategies for targeting the delivery of therapeutics to the heart are lacking, various technologies and nanodelivery approaches are emerging as promising methods for site specific delivery to increase therapeutic myocardial retention, efficacy, and bioactivity, while decreasing undesired systemic effects. Here, we provide a literature review of various approaches for intrapericardial delivery of agents. Emphasis is given to sustained delivery approaches (pumps and catheters) and localized release (patches, drug eluting stents, and support devices and meshes). Further, minimally invasive access techniques, pericardial access devices, pericardial washout and fluid analysis, as well as therapeutic and cell delivery vehicles are presented. Finally, several promising new therapeutic targets to treat heart diseases are highlighted., (Copyright © 2019. Published by Elsevier B.V.)

Objective: Four-dimensional flow cardiovascular magnetic resonance may improve assessment of hemodynamics in patients with aortic dissection. The purpose of this study was to evaluate the feasibility and accuracy of 4-dimensional flow cardiovascular magnetic resonance assessment of true and false lumens flow., Methods: Thirteen ex vivo porcine aortic dissection models were mounted to a flow loop. Four-dimensional flow cardiovascular magnetic resonance and 2-dimensional phase-contrast cardiovascular magnetic resonance measurements were performed, assessed for intraobserver and interobserver variability, and compared with a reference standard of sonotransducer flow volume measurements. Intraobserver and interobserver variability of 4-dimensional flow cardiovascular magnetic resonance were also assessed in 14 patients with aortic dissection and compared with 2-dimensional phase-contrast cardiovascular magnetic resonance., Results: In the ex vivo model, the intraobserver and interobserver measurements had Lin's correlation coefficients of 0.98 and 0.96 and mean differences of 0.17 (±3.65) mL/beat and -0.59 (±5.33) mL/beat, respectively; 4-dimensional and sonotransducer measurements had a Lin's concordance correlation coefficient of 0.95 with a mean difference of 0.35 (±4.92) mL/beat, respectively. In patients with aortic dissection, the intraobserver and interobserver measurements had Lin's concordance correlation coefficients of 0.98 and 0.97 and mean differences of -0.95 (±8.24) mL/beat and 0.62 (±10.05) mL/beat, respectively; 4-dimensional and 2-dimensional flow had a Lin's concordance correlation coefficient of 0.91 with a mean difference of -9.27 (±17.79) mL/beat because of consistently higher flow measured with 4-dimensional flow cardiovascular magnetic resonance in the ascending aorta., Conclusions: Four-dimensional flow cardiovascular magnetic resonance is feasible in patients with aortic dissection and can reliably assess flow in the true and false lumens of the aorta. This promotes potential future work on functional assessment of aortic dissection hemodynamics., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

The application of three-dimensional (3D) printing enables the creation of material objects from digital images by depositing layers of plastic material into 3D structures and can be used for training, education, and surgical planning. We report two patients with large complex cardiac tumors where 3D technology was utilized to analyze the tumor size, location, and extension more precisely, allowing better preoperative planning and decision making., (© 2016 Wiley Periodicals, Inc.)

Background: 3D stereolithographic printing can be used to convert high-resolution computed tomography images into life-size physical models. We sought to apply 3D printing technologies to develop patient-specific models of the anatomic and functional characteristics of severe aortic valve stenosis., Methods and Results: Eight patient-specific models of severe aortic stenosis (6 tricuspid and 2 bicuspid) were created using dual-material fused 3D printing. Tissue types were identified and segmented from clinical computed tomography image data. A rigid material was used for printing calcific regions, and a rubber-like material was used for soft tissue structures of the outflow tract, aortic root, and noncalcified valve cusps. Each model was evaluated for its geometric valve orifice area, echocardiographic image quality, and aortic stenosis severity by Doppler and Gorlin methods under 7 different in vitro stroke volume conditions. Fused multimaterial 3D printed models replicated the focal calcific structures of aortic stenosis. Doppler-derived measures of peak and mean transvalvular gradient correlated well with reference standard pressure catheters across a range of flow conditions (r=0.988 and r=0.978 respectively, P<0.001). Aortic valve orifice area by Gorlin and Doppler methods correlated well (r=0.985, P<0.001). Calculated aortic valve area increased a small amount for both methods with increasing flow (P=0.002)., Conclusions: By combing the technologies of high-spatial resolution computed tomography, computer-aided design software, and fused dual-material 3D printing, we demonstrate that patient-specific models can replicate both the anatomic and functional properties of severe degenerative aortic valve stenosis., (© 2015 American Heart Association, Inc.)

Background: The aim of this study was to test the accuracy of an automated 3-dimensional (3D) proximal isovelocity surface area (PISA) (in vitro and patients) and stroke volume technique (patients) to assess mitral regurgitation (MR) severity using real-time volume color flow Doppler transthoracic echocardiography., Methods and Results: Using an in vitro model of MR, the effective regurgitant orifice area and regurgitant volume (RVol) were measured by the PISA technique using 2-dimensional (2D) and 3D (automated true 3D PISA) transthoracic echocardiography. The mean anatomic regurgitant orifice area (0.35±0.10 cm(2)) was underestimated to a greater degree by the 2D (0.12±0.05 cm(2)) than the 3D method (0.25±0.10 cm(2); P<0.001 for both). Compared with the flowmeter (40±14 mL), the RVol by 2D PISA (20±19 mL) was underestimated (P<0.001), but the 3D peak (43±16 mL) and integrated PISA-based (38±14 mL) RVol were comparable (P>0.05 for both). In patients (n=30, functional MR), 3D effective regurgitant orifice area correlated well with cardiac magnetic resonance imaging RVol r=0.84 and regurgitant fraction r=0.80. Compared with cardiac magnetic resonance imaging RVol (33±22 mL), the integrated PISA RVol (34±26 mL; P=0.42) was not significantly different; however, the peak PISA RVol was higher (48±27 mL; P<0.001). In addition, RVol calculated as the difference in automated mitral and aortic stroke volumes by real-time 3D volume color flow Doppler echocardiography was not significantly different from cardiac magnetic resonance imaging (34±21 versus 33±22 mL; P=0.33)., Conclusions: Automated real-time 3D volume color flow Doppler based 3D PISA is more accurate than the 2D PISA method to quantify MR. In patients with functional MR, the 3D RVol by integrated PISA is more accurate than a peak PISA technique. Automated 3D stroke volume measurement can also be used as an adjunctive method to quantify MR severity.

We present the first system for measurement of proximal isovelocity surface area (PISA) on a 3D ultrasound acquisition using modified ultrasound hardware, volumetric image segmentation and a simple efficient workflow. Accurate measurement of the PISA in 3D flow through a valve is an emerging method for quantitatively assessing cardiac valve regurgitation and function. Current state of the art protocols for assessing regurgitant flow require laborious and time consuming user interaction with the data, where a precise execution is crucial for an accurate diagnosis. We propose a new improved 3D PISA workflow that is initialized interactively with two points, followed by fully automatic segmentation of the valve annulus and isovelocity surface area computation. Our system is first validated against several in vitro phantoms to verify the calculations of surface area, orifice area and regurgitant flow. Finally, we use our system to compare orifice area calculations obtained from in vivo patient imaging measurements to an independent measurement and then use our system to successfully classify patients into mild-moderate regurgitation and moderate-severe regurgitation categories.

Objective: The proximal isovelocity surface area (PISA) method is useful in the quantitation of aortic regurgitation (AR). We hypothesized that actual measurement of PISA provided with real-time 3-dimensional (3D) color Doppler yields more accurate regurgitant volumes than those estimated by 2-dimensional (2D) color Doppler PISA., Methods: We developed a pulsatile flow model for AR with an imaging chamber in which interchangeable regurgitant orifices with defined shapes and areas were incorporated. An ultrasonic flow meter was used to calculate the reference regurgitant volumes. A total of 29 different flow conditions for 5 orifices with different shapes were tested at a rate of 72 beats/min. 2D PISA was calculated as 2pi r(2), and 3D PISA was measured from 8 equidistant radial planes of the 3D PISA. Regurgitant volume was derived as PISA x aliasing velocity x time velocity integral of AR/peak AR velocity., Results: Regurgitant volumes by flow meter ranged between 12.6 and 30.6 mL/beat (mean 21.4 +/- 5.5 mL/beat). Regurgitant volumes estimated by 2D PISA correlated well with volumes measured by flow meter (r = 0.69); however, a significant underestimation was observed (y = 0.5x + 0.6). Correlation with flow meter volumes was stronger for 3D PISA-derived regurgitant volumes (r = 0.83); significantly less underestimation of regurgitant volumes was seen, with a regression line close to identity (y = 0.9x + 3.9)., Conclusion: Direct measurement of PISA is feasible, without geometric assumptions, using real-time 3D color Doppler. Calculation of aortic regurgitant volumes with 3D color Doppler using this methodology is more accurate than conventional 2D method with hemispheric PISA assumption.

Objectives: Our goal was to prospectively compare the accuracy of real-time three-dimensional (3D) color Doppler vena contracta (VC) area and two-dimensional (2D) VC diameter in an in vitro model and in the clinical assessment of mitral regurgitation (MR) severity., Background: Real-time 3D color Doppler allows direct measurement of VC area and may be more accurate for assessment of MR than the conventional VC diameter measurement by 2D color Doppler., Methods: Using a circulatory loop with an incorporated imaging chamber, various pulsatile flow rates of MR were driven through 4 differently sized orifices. In a clinical study of patients with at least mild MR, regurgitation severity was assessed quantitatively using Doppler-derived effective regurgitant orifice area (EROA), and semiquantitatively as recommended by the American Society of Echocardiography. We describe a step-by-step process to accurately identify the 3D-VC area and compare that measure against known orifice areas (in vitro study) and EROA (clinical study)., Results: In vitro, 3D-VC area demonstrated the strongest correlation with known orifice area (r = 0.92, p < 0.001), whereas 2D-VC diameter had a weak correlation with orifice area (r = 0.56, p = 0.01). In a clinical study of 61 patients, 3D-VC area correlated with Doppler-derived EROA (r = 0.85, p < 0.001); the relation was stronger than for 2D-VC diameter (r = 0.67, p < 0.001). The advantage of 3D-VC area over 2D-VC diameter was more pronounced in eccentric jets (r = 0.87, p < 0.001 vs. r = 0.6, p < 0.001, respectively) and in moderate-to-severe or severe MR (r = 0.80, p < 0.001 vs. r = 0.18, p = 0.4, respectively)., Conclusions: Measurement of VC area is feasible with real-time 3D color Doppler and provides a simple parameter that accurately reflects MR severity, particularly in eccentric and clinically significant MR where geometric assumptions may be challenging.

We describe the development of a cardiac flow model and imaging chamber to permit Doppler assessment of complex and dynamic flow events. The model development included the creation of a circulatory loop with variable compliance and resistance; the creation of a secondary regurgitant circuit; and incorporation of an ultrasound imaging chamber to allow two-dimensional (2D) and three-dimensional (3D) Doppler characterization of both simple and complex models of valvular regurgitation. In all, we assessed eight different pulsatile regurgitant volumes through each of four rigid orifices differing in size and shape: 0.15 cm(2) circle, 0.4 cm(2) circle, 0.35 cm(2) slot and 0.4 cm(2) arc. The achieved mean (and range) hemodynamic measures were: peak trans-orifice pressure gradient 117 mm Hg (40 to 245 mm Hg), trans-orifice peak Doppler velocity 560 cm/s (307 to 793 cm/s), Doppler time-velocity integral 237 cm (111 to 362 cm), regurgitant volume 43 mL (11 to 84 mL) and orifice area 0.32 cm(2) (0.15 to 0.4 cm(2)). The model was designed to optimize Doppler signal quality while reflecting anatomic structural relationships and flow events. The 2D color Doppler, 3D color Doppler and continuous wave Doppler quality was excellent whether the data were acquired from the imaging window parallel or perpendicular to the long-axis of flow. This model can be easily adapted to mimic other intracardiac flow pathology or assess future Doppler applications.

The 2-dimensional (2D) color Doppler (2D-CD) proximal isovelocity surface area (PISA) method assumes a hemispheric flow convergence zone to estimate transvalvular flow. Recently developed 3-dimensional (3D)-CD can directly visualize PISA shape and surface area without geometric assumptions. To validate a novel method to directly measure PISA using real-time 3D-CD echocardiography, a circulatory loop with an ultrasound imaging chamber was created to model mitral regurgitation (MR). Thirty-two different regurgitant flow conditions were tested using symmetric and asymmetric flow orifices. Three-dimensional-PISA was reconstructed from a hand-held real-time 3D-CD data set. Regurgitant volume was derived using both 2D-CD and 3D-CD PISA methods, and each was compared against a flow-meter standard. The circulatory loop achieved regurgitant volume within the clinical range of MR (11 to 84 ml). Three-dimensional-PISA geometry reflected the 2D geometry of the regurgitant orifice. Correlation between the 2D-PISA method regurgitant volume and actual regurgitant volume was significant (r(2) = 0.47, p <0.001). Mean 2D-PISA regurgitant volume underestimate was 19.1 +/- 25 ml (2 SDs). For the 3D-PISA method, correlation with actual regurgitant volume was significant (r(2) = 0.92, p <0.001), with a mean regurgitant volume underestimate of 2.7 +/- 10 ml (2 SDs). The 3D-PISA method showed less regurgitant volume underestimation for all orifice shapes and regurgitant volumes tested. In conclusion, in an in vitro model of MR, 3D-CD was used to directly measure PISA without geometric assumption. Compared with conventional 2D-PISA, regurgitant volume was more accurate when derived from 3D-PISA across symmetric and asymmetric orifices within a broad range of hemodynamic flow conditions.

In totally implantable ventricular assist device systems, measuring flow rate of the pump is necessary to ensure proper operation of the pump in response to the recipient's condition or pump malfunction. To avoid problems associated with the use of flow probes, several methods for estimating flow rate of a rotary blood pump used as a ventricular assist device have been studied. In the present study, we have performed a chronic animal experiment with two NEDO PI gyro pumps as the biventricular assist device for 63 days to evaluate our estimation method by comparing the estimated flow rate with the measured one every 2 days. Up to 15 days after identification of the parameters, our estimations were accurate. Errors increased during postoperation days 20 to 30. Meanwhile, their correlation coefficient r was higher than 0.9 in all the acquired data, and estimated flow rate could simulate the profile of the measured one.

The pericardial space is being investigated as a reservoir for local drug delivery to the heart and coronary arteries. Intrapericardial drug delivery is currently limited because the pericardial space is normally small and difficult to access by standard pericardiocentesis without invasive surgery or risk of cardiac injury. Clinical trials are being conducted to evaluate a novel, minimally invasive, pericardial access device (PerDUCER, Comedicus Inc., Columbia Heights, Minn.). As of October 26, 1998, 12 clinical trials have been completed on patients undergoing cardiac surgical procedures. In all patients, a stab incision was made 1" subxiphoid and a 17G angled cannula, with preloaded guidewire, was advanced into the mediastinal space. After cannula removal, a 19F sheath/dilator was inserted over the wire. In eight patients, a median sternotomy was performed and the position of the sheath over the anterior pericardium (PC) was visually verified. Four patients underwent a closed-chest, fluoroscopy-assisted procedure. In all patients, the PerDUCER was inserted into the chest, via the sheath, and positioned over the PC. The PC was captured by suction and a bleb was formed within a side-hole on the PerDUCER tip. A sheathed needle was advanced, puncturing the isolated bleb of PC. A guidewire was advanced through the needle into the pericardial space and the PerDUCER was removed. Guidewire insertion was successful in 10 patients (7 on first attempt, 3 on second) without adverse hemodynamic effects or arrhythmia. Other than the guidewire insertion site, there was no evidence of injury to the PC or the heart. These initial clinical trials suggest that the PerDUCER may provide safe, rapid and effective percutaneous insertion of a guidewire into the normal pericardial space.

Sodium nitroprusside, a potent vasodilator, was evaluated for its effect on platelet aggregation in stenosed and endothelium-injured coronary arteries in a canine model. Twenty-five anesthetized dogs were studied; coronary blood flow velocity was continuously monitored. Recurrent intracoronary platelet aggregation and dislodgment (indicated by cyclic variations in coronary blood flow) were induced by mechanically injuring and stenosing the left anterior descending coronary artery. Sodium nitroprusside was administered either intrapericardially or intravenously 30 min after cyclic flow variations were established. Intrapericardial administration of saline (control) did not affect cyclic flow variations in any of 6 tested dogs. Sodium nitroprusside abolished cyclic flow variations in all 7 dogs (100%) when given intrapericardially and in 5 to 7 dogs (71%) when given intravenously (compared to intrapericardial salines, p < 0.01). A smaller dose of sodium nitroprusside was required to abolish cyclic flow variations when given intrapericardially than when given intravenously (1.6 +/- 0.5 micrograms.kg-1.min-1 vs 4.8 +/- 0.8 micrograms.kg-1.min-1, p < 0.01). The mean aortic pressure was reduced by 10 to 20 mmHg after intrapericardial sodium nitroprusside administration and by 30 to 40 mmHg after intravenous sodium nitroprusside administration. To investigate the mechanism of protection by sodium nitroprusside, NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthetase, was used to induce cyclic flow variations in mildly injured and stenosed left anterior descending coronary arteries in 5 dogs. Intrapericardial sodium nitroprusside abolished the cyclic flow variations in all 5 dogs. Then oxyhemoglobin, an inhibitor of nitric oxide, was administered into the left anterior descending coronary arteries of these dogs, and it restored the sodium nitroprusside-abolished cyclic flow variations in all 5 dogs. Thus, sodium nitroprusside protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured canine coronary arteries, probably by the action of nitric oxide, and it is more effective and hemodynamically safer when administered intrapericardially than when administered intravenously.

The left atrium and the left ventricular apex are the most commonly used sites of inflow cannulation for postcardiotomy left ventricular support. A new cannulation technique that requires only an ascending aortotomy is introduced. This procedure can be undertaken with equipment present in any cardiac operating room and may prove to cause fewer complications than conventional cannulation techniques.

To determine the extent to which different electrocardiographic systems account for differences in reported incidence of perioperative myocardial ischemia, the authors simultaneously recorded in 109 patients undergoing coronary artery bypass grafting (CABG) the V5 or modified CM5 lead on five ECG systems by means of a specially constructed common V5 lead. The systems included a Spacelabs Alpha 14 Model Series 3200 ECG Cardule at bandwidths of 0.05-125 Hz and 0.5-30 Hz (a typical operating room monitor), a Marquette Electronics MAC II ECG at 0.05-40 Hz and 0.05-100 Hz (a standard ECG), and a Del Mar Holter recorder at 0.1-100 Hz. Relative ST-segment position and incidence of new ischemia compared to the preoperative ECG were determined in 109 sets of preinduction traces and 877 sets of intraoperative traces. ST-segment position on the three recording systems conforming with the American Heart Association (AHA) low-frequency response recommendations (0.05 Hz) were similar. Compared to the standard ECG, ST-segment position on the Spacelabs at 0.5-30 Hz was consistently more negative. Displacement on the Holter was consistently less negative and less positive. By the 0.1-mV displacement criterion for diagnosis of myocardial ischemia on any one ECG system, 16.5% of patients on arrival and 32.1% of patients intraoperatively suffered new myocardial ischemia. Based on the operating room monitor, arrival and intraoperative ischemia were present in 15.6 and 27.5% of patients, respectively. Ischemia at the same periods was less frequent by the standard ECG system (5.5 and 12.8%, respectively) and least frequent by the Holter recorder (4.6 and 8.3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The success of heart-lung transplant experiments in subprimate models has been limited because most techniques include total pulmonary denervation, which causes respiratory problems, blood loss, and subsequent death. Using 20 subprimates (12 domestic swine and 8 mongrel dogs), we tested a heterotopic heart-single lung transplant method intended to preserve unilateral pulmonary innervation and to reduce blood loss. After native right pneumonectomy, the donor heart and right lung were transplanted en bloc. Anastomotic sites included the right primary bronchus, the superior vena cava, and the aorta. Selective left bronchial intubation and partial occlusion techniques eliminated the need for cardiopulmonary bypass and mediastinal dissection. All 10 recipient animals survived the operation, and the need for blood transfusions was minimal (1.1 +/- 0.7 [mean +/- SD] units/procedure). Donor and native lung function, assessed by selective left atrial blood gases, were similar: mean PO(2) was 229 +/- 31 mmHg and 180 +/- 25 mmHg, respectively; and mean PCO(2), 36 +/- 13 mmHg and 38+/-2 mmHg, respectively. Nine recipients were weaned from mechanical ventilation with a mean PCO(2) of 38+/-4 mmHg. Preserving unilateral pulmonary innervation allows normal respiration, and minimizing blood loss increases operative survival. Our method of heterotopic heart-single lung transplantation is reliable and could provide a functional heart-lung allograft for conducting future experimental studies of heart-lung transplantation.

This study attempts to quantitate post-infarction cardiogenic shock IABP dependence in instances of massive myocardial infarction with the use of hemodynamic indices plotted over time-course trajectories. Mortality is predicted when age and hemodynamic performance are also considered. It appears that post-infarction IABP dependence can be quantitated and that such information can be useful in considering diagnostic and therapeutic alternatives during the course of IABP support and cardiogenic shock. The analysis suggests that such IABP-dependent patients could be considered for therapeutic alternatives. They do not expire during the first 50 hours of IABP support and neither improve nor deteriorate during the second 50 hours of support. They remain in Class B without the occurrence of life-threatening ventricular dysrhythmias for a sufficient time for cardiac catheterization to determine the appropriateness of corrective procedures.

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.

A long-term, implantable, electrically actuated left ventricular assist system (THI/Gould LVAS) is being developed and characterized in vitro and in vivo for utilization in patients with end-stage heart disease. This system consists of five major components: a long-term, implantable blood pump (THI E-type ALVAD); an electrical-mechanical energy converter (Gould Model V); a control unit with batteries; a volume compensation system; and an external power supply and monitoring unit. Two of these components (blood pump and electrical-mechanical energy converter) have been integrated, and are undergoing chronic in vivo evaluations in calves. Thus far, 44 pneumatically and electrically actuated THI/Gould LVAS evaluations have been performed. This experience has resulted in greater than 6.5 years of actuation in vivo, with durations exceeding 1 year. System in vivo performance in terms of durability, mechanical reliability, hemodynamic effectiveness, and biocompatibility has been satisfactory. Demonstration of long-term (2-year) effectiveness in supporting the circulation is the ultimate goal.

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.

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.

Serial hemodynamic measurements were obtained before, during, and after nitroprusside therapy over a 24 hour period in 19 patients requiring intra-aortic balloon pumping (IABP) for successful weaning from cardiopulmonary bypass. Nitroprusside, administered in doses ranging from 0.5 to 5 micrograms/kg/min, effected significant reductions in mean aortic pressure and systemic vascular resistance within 20 to 30 minutes. Mean aortic pressure decreased from 108 +/- 22 mm Hg to 85 +/- 27 mm Hg (p less than 0.005). Systemic vascular resistance decreased from 2,705 +/- 1,072 to 1,942 +/- 823 dynes sec cm-5 (p less than 0.005). 2n response to nitroprusside-induced decreases in left venticular afterload, cardiac indes increased from 1.83 +/- 0.58 to 2.04 +/- 0.54 L/min/m2 (p less than 0.025). Pulmonary capillary wedge pressure (PCW), right atrial pressure, right and left ventricular minute work indices, and the rate-pressure products did not change, indicating that nitroprusside administration during IABP further increased cardiac output without increasing ventricular filling pressure, ventricular work, or indices of myocardial oxygen consumption. The data suggest that nitroprusside, in conjunction with volume loading to optimal preload levels (PCW = 15 to 18 mm Hg), augments ventricular performance in postcardiotomy low-output syndrome by lowering impedance to left ventricular ejection through a direct dilator effect on vascular smooth muscle, without a direct effect on cardiac muscle. Thus it is a valuable pharmacologic adjunct during mechanical (IABP) support of the failing circulation.

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.

Blood compatibility is a major objective in the development of long-term, implantable circulatory assist (left ventricular assist devices) and replacement (total artificial heart) devices. An important problem in experimental studies in animals has been the propensity for calcification to occur at the blood/material interface. Presented is a summary of our experience (27 studies) with blood pump calcification and a review of the current literature regarding this complication.

Between August and December 1983, the Texas Heart Institute Transplantation Service performed 10 cardiac transplants. All hearts were removed at outside hospitals and transported to the Heart Institute. Adequate return of cardiac function occurred in all groups after ischemic times of 58.5 minutes for hearts procured within Houston (range, 56-62 minutes) and 152 minutes for those procured in other cities (range, 130-179 minutes). Eight of the transplant patients are alive and well following operation. Distal procurement has more than doubled the number of suitable organs, and offers considerable potential for expansion of the transplant program.

Intra-aortic balloon pumping (IABP) has been utilized in our institution in over 600 patients for the treatment of postcardiotomy low-output syndrome, with a 59% survival rate. Volume loading and pharmacologic treatment have played integral roles in the overall treatment of this syndrome. This investigation documents the hemodynamic effectivenss of combined nitroprusside/dopamine therapy in patients who required IABP for weaning from cardiopulmonary bypass. Serial hemodynamic measurements were made before and during infusion of nitroprusside (0.5 to 5.0 microgram/kg/min) and after combined nitroprusside/dopamine (7.5 micrograms/kg/min) therapy in 10 patients during IABP. Prior to pharmacologic therapy, cardiac index was 1.6 +/- 0.4 L/min/m2 and systemic vascular resistance (SVR) was 2,774 +/- 932 dynes sec cm-5. After nitroprusside infusion, cardiac index increased to 1.8 +/- 0.5 L/min/m2 (NS) and SVR decreased to 1,957 +/- 791 dynes sec cm-5 (p less than 0.01). The simultaneous infusion of nitroprusside and dopamine resulted in further augmentation of cardiac index to 2.5 +/- 0.5 L/min/m2 (p less than 0.01) and an additional reduction of SVR to 1,439 +/- 358 dynes sec cm-5 (p less than 0.02). In addition, pressure-rate-product, an index of myocardial oxygen demand, was decreased by nitroprusside (p less than 0.02) but was not significantly altered by both agents. This study provides a rationale for the combined use of nitroprusside/dopamine in postcardiotomy low-output syndrome necessitating IABP when SVR is greater than 2,000 dynes sec cm-5 and cardiac index is less than 2.0 L/min/m2.

The conceptual design and development of a long-term, low-profile intracorporeal left ventricular assist device is a multifaceted project involving a series of technical, anatomic and physiologic considerations. Patients with severe left ventricular failure refractory to all other forms of therapy could benefit from such a device. Prior to fabrication of such a blood pump, consideration must be given to physiologic parameters of the projected patient population. The pump must be designed to meet physiologic demands and yet conform to the anatomic constraints posed by the patient population. We measured the body surface area (BSA) of a group of patients (n=50) and found the mean BSA for this group to be 1.804 +/- 0.161 m(2). Using 25 ml/m(2) as a stroke volume index indicative of left ventricular failure and a stroke volume index of 45 ml/m(2) as normal, distributions of stroke volumes (normal and in left ventricular failure) were plotted for a potential population and demonstrated that 63% of the projected population can be returned to normal by a pump with a stroke volume >/= 83 ml. Cadaver fitting studies established that 73% of the potential population can accommodate an ALVAD 10.8 cm in diameter. In-vitro tests demonstrated that a pump stroke volume >/= 83 ml could be achieved by the proposed pump with a 15 mmHg filling pressure at rates up to 125 B/min. A pusher-plate stroke of 0.56 inches would be necessary to provide a stroke volume >/= 83 ml. The percent of the patient population that could be served was determined by excluding those in whom the pump would not fit or in whom it would provide less than a normal resting stroke volume. Approximately 73% of the projected patient population would accommodate this pump and be returned to normal circulatory dynamics.

The effects of an abdominal left ventricular assist device (ALVAD) on subendocardial oxygen supply/demand ratios as reflected by diastolic pressure-time index/tension-time index (DPTI/TTI) were investigated in calves. Control DPTI/TTI ratios were 1.09 plus or minus 0.12 (mean plus or minus SD). With ALVAD actuation the ratios increased to 5.73 plus or minus 3.2. Following circumflex coronary artery occlusion, control ratios decreased to 0.04 plus or minus 0.05 in the ischemic area and 0.97 plus or minus 0.20 in the nonischemic areas. With ALVAD actuation in the presence of circumflex occlusion, the depressed ratios were increased to 1.37 plus or minus 0.39 in the ischemic zone and 9.71 plus or minus 2.5 in the nonoccluded segments. Subendocardial oxygen supply/demand ratios were significantly improved by ALVAD assistance following induced subendocardial ischemia.

This study describes five programs that may be used on compact, low-cost programmable calculators with adequate memory and sufficient numbers of program steps to compute cardiorespiratory variables. These short programs are especially useful in the operating room and at the bedside.

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.

Total THI/Gould LVAS experience includes 59 pneumatically and electrically-actuated blood pump evaluations (in calves, goats and sheep), including 23 studies with the Gould Model V energy converter. This experience has resulted in greater than 8 cumulative years of actuation, in vivo, including electrically-actuated LVAS durations up to 6 mos.

Our laboratories are engaged in the design of a clinically-oriented electrically actuated long-term intracorporeal (abdominal) left ventricular assist device ("E-type" ALVAD) or partial artificial heart. This infradiaphragmatic blood pump is designed to be powered by implantable electrical to mechanical energy converter systems. THE FOLLOWING ANALYSES WERE UNDERTAKEN TO: [List: see text] The proposed "E-type" ALVAD should be capable of pumping 4-7 liters per minute at heart rates of 75-100 beats per minute during rest, and 10 liters per minute at rates of 120 beats per minute during moderate exercise. These performance levels should be exceeded with a maximum device stroke volume of 85-90 ml and a mean pump inflow (filling) impedance of

Comparisons of the physiologic bases of intraaortic balloon and extracorporeal or implantable left ventricular assist device or partial artificial heart pumping in experimental and clinical setting are made. The concepts and first principles common and unique to both of these forms of mechanical circulatory support are presented with emphasis on the similarities and important differences. Intraaortic balloon counterpulsation is examined as an intravascular, volume displacement device in series with the systemic circulations. Left ventricular assist devices are analyzed as extravascular in-series or parallel volume-capturing/ejecting devices and as true blood pumps which can be implanted. The interrelated mechanisms of synchronous, diversion/counterpulsation/diastolic augmentation are discussed in relation to quantitative indices of myocardial ischemia, myocardial oxygen supply/demand ratios, the Sarnoff theorem and the Laplace relationship, vis à vis ventricular unloading/impedance reductions. Some of the many clinical settings of IABP are mentioned, along with hydraulic considerations which allow non-invasive determination of stroke volume during clinical IABP mechanical circulatory support. Cardiogenic shock/left ventricular failure/low cardiac output are defined in terms of failure to generate pressure and displace volume and deficits of ejection fraction and stroke volume. Vasodilator therapy (nitroprusside), IABP, and LVAD are then viewed as escalating methods of reversing these deficits. Finally, pressure volume loops of the human left ventricle are compared with those of LVADs, experimentally and clinically, to indicate that LVADs can function and support the circulation during all low output states including ventricular fibrillation and standstill. Representative hemodynamic traces (Fig. 5 and 6) obtained during clinical LVAD trials in man are included to illustrate these theoretical and practical considerations. The use of LVADs in any instance of IABP inadequacy is implicit and inferred.

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.