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Inspired Therapeutics (Merritt Island, FL) is developing a mechanical circulatory support (MCS) system designed as a single driver with interchangeable, extracorporeal, magnetically levitated pumps. The NeoMate system design features an integrated centrifugal rotary pump, motor, and controller that will be housed in a single compact unit. Conceptually, the primary innovation of this technology will be the combination of disposable, low-cost pumps for use with a single, multi-functional, universal controller to support multiple pediatric cardiopulmonary indications. In response to the paucity of clinically available pediatric devices, Inspired Therapeutics is specifically targeting the underserved neonate and infant heart failure (HF) patient population first. In this article, we present the development of the prototype Inspired Therapeutics NeoMate System for pediatric left ventricular assist device (LVAD) support, and feasibility testing in static mock flow loops (H-Q curves), dynamic mock flow loops (hemodynamics), and in an acute healthy ovine model (hemodynamics and clinical applicability). The resultant hydrodynamic and hemodynamic data demonstrated the ability of this prototype pediatric LVAD and universal controller to function over a range of rotary pump speeds (500-6000 RPM), to provide pump flow rates of up to 2.6 L/min, and to volume unload the left ventricle in acute animals. Key engineering challenges observed and proposed solutions for the next design iteration are also presented., Competing Interests: This study was supported by a National Institutes of Health SBIR grant 1R43HL144214-01 (PI Dasse). Drs. Monreal, Koenig, and Slaughter were co-investigators on the NIH SBIR phase I grant (1R43HL144214-01) subcontract with Inspired Therapeutics. Dr. Dasse and Mr. Gellman were PI and Co-I, respectively, on the NIH SBIR phase I grant (1R43HL144214-01) and are employed by Inspired Therapeutics. Dr. Monreal is supported in part by a gift from Robert M. Prizant to the Legacy Foundation of Kentuckiana. Dr. Koenig is co-founder of Cor Habere and MAST developing medical devices supported by NIH SBIR phase I grants (R43HL142337-01, R43HL142385-01, R43HL152894-01); however, these affiliations and funded projects are unrelated to the subcontract with Inspired Therapeutics and independent of the work presented in this manuscript. Dr. Slaughter is co-founder of Cor Habere and MAST developing medical devices supported by NIH SBIR phase I grants (R43HL142337-01, R43HL142385-01, R43HL152894-01) and consultant with Magenta Medical; however, these affiliations and funded projects are unrelated to the subcontract with Inspired Therapeutics and independent of the work presented in this manuscript. Mr. Morello was a consultant on the NIH SBIR phase I grant (1R43HL144214-01) subcontract with Inspired Therapeutics and is employed by Veritium Research. Dr. Prina was a consultant on the NIH SBIR phase I grant (1R43HL144214-01) with Veritium Research LLC. Dr. Prina was also a paid consultant of VADovations Inc and Oregon Institute of Technology through his previous company Applimotion. None of these additional affiliations are related to the work presented in this manuscript. Dr. Tompkins was an engineer on the NIH SBIR phase I grant (1R43HL144214-01) as a graduate student at the University of Louisville and is a consultant for Inspired Therapeutics LLC. Additionally, Dr. Tompkins is a co-owner of MAST LLC, engineer with Cor Habere Corp., and consultant with VADovations Inc.; however, none of these additional affiliations are related to the work presented in this manuscript. Dr. Huang has a research grant from Gilead Sciences, serves as a consultant for GE Healthcare, and has ownership at Microsensor Labs and Degranin Therapeutics. Mr. Gellman is a consultant to Paragonix Technologies, Inc.; Vivante Health, Inc.; and Cardiac Assist Holdings, which are unrelated to to work presented in this manuscript. Dr. Dasse is the CEO and co-Founder of Inspired Therapeutics LLC and serves as PI on the NIH SBIR Phase I grant (1R43HL144214-01) that supported prototype development and feasibility testing presented in this manuscript. In addition, Dr. Dasse is a co-investigator on NIH SBIR phase I grant (R43HL142385-01) and consultant on NIH SBIR grant (R43HL158430), which are unrelated to this manuscript. He is also President and COO of VADovations Inc, and serves as a consultant to BiVACOR Inc, CH-Biomedical USA Inc, Jarvik Heart International, and Vortronix Medical, LLC, Teal Health Inc. CAH Holdings LLC, and “The Kidney Project” affiliated with the University of California San Francisco and Vanderbilt University, which are unrelated to this manuscript. Dr. Dasse serves on the Board of Directors for Makana Therapeutics and Artio Medical, which are unrelated to this manuscript.

In the US, the most significant morbidity and mortality associated with non-valvular atrial fibrillation (NVAF) is embolic stroke, with 90% of thrombus originating from the left atrial appendage (LAA). Anticoagulation is the preferred treatment for the prevention of stroke in NVAF patients, but clinical studies have demonstrated high levels of non-compliance and increased risk of bleeding or ineligibility for anticoagulation therapy, especially in the elderly population where the incidence of NVAF is highest. Alternatively, stroke may be preventing using clinically approved surgical and catheter-based devices to exclude or occlude the LAA, but these devices continue to be plagued by peri-device leaks and thrombus formation because of residual volume. To overcome these limitations, Cor Habere (Louisville, KY) and the University of Louisville are developing a LAA closure device (StrokeShield) that completely occludes and collapses the LAA to minimize the risk of stroke. The StrokeShield device is a collapsible occluder (nitinol reinforced membrane) that completely covers the LAA orifice with an expandable conical coil anchor that attaches to the myocardium. The device is designed for catheter-based delivery and expands to completely occlude the LAA orifice and collapse the LAA. The primary advantages of the StrokeShield system are a completely sealed LAA (no peri-device flow or residual space) and smooth endothelialized connection to the left atrial wall with minimal risk of cardiac bleeding and tamponade. We tested proof-of-concept of a prototype StrokeShield device in acute (n = 2) and chronic 60-day (n = 2) healthy canine models. Acute results demonstrated that the conical coil securely attached to the myocardium (5N pull-out force) and the Nitinol umbrella fully deployed and covered the LAA ostium. Results from the chronic implants demonstrated long-term feasibility of device placement with no procedural or device-related intra- or post-operative complications, secure placement and correct positioning of the device with no device migration. The device successfully occluded the LAA ostium and collapsed the LAA with no interference with the mitral valve, circumflex coronary artery, or pulmonary veins. Necropsy demonstrated no gross signs of thrombus or end-organ damage and the device was encapsulated in the LAA. Histology demonstrated mature neointima covering the device with expected foreign body inflammatory response. These early positive results will help to guide the iterative design process for the continued development of the StrokeShield system., Competing Interests: Financial • Two US patents awarded related to the research presented in this manuscript, and a third University of Louisville (UofL) invention disclosure was filed February 1, 2021, but is not presented in this manuscript Slaughter MS, Giridharan GA, Sobieski MA, Soucy KG, and Koenig SC. Atrial appendage closure device and related methods (US Patent 10,531,878 awarded January 14, 2020) Slaughter MS, Giridharan GA, Sobieski MA, Soucy KG, and Koenig SC. Atrial appendage closure device and related methods (US Patent 10,898,202 awarded January 26, 2021) Slaughter MS, Monreal G, Koenig SC, Jimenez J, Tompkins L. Left Atrial Appendage (LAA) device, delivery tool, and related methods (UofL Invention Disclosure no. 21038, filed February 1, 2021) • Research presented in this manuscript was funded as an internal project subaward (PI: Guruprasad Giridharan) from a 5-yr Coulter Foundation grant awarded to University of Louisville (PIs: Robert Keynton, PhD and Mark Slaughter, MD) • Co-authors Jimenez, Koenig, Slaughter are co-founders of Cor Habere (Louisville KY), and are continuing the research and development of the StrokeShield system (LAA device) presented in this manuscript. Note: Cor Habere was founded after the research and development presented in this manuscript had been completed. • Cor Habere was awarded a NIH SBIR phase I grant (R43HL142337-01) to continue development of the StrokeShield system (LAA device, delivery tool) but none of the work supported by the SBIR phase I grant is presented in this manuscript. Co-authors (Giridharan, Koenig, Slaughter) were awarded US Patent 10,531,878 (January 14, 2020) and US Patent 10,898,202 (January 26, 2021). All of the co-authors are continuing with the development of the StrokeShield device and are listed as co-inventors on our recent UofL invention disclosure (no. 21038, filed Feb 1, 2021) and co-investigators of NIH SBIR phase I grant (R43HL142337-01, awarded Sep 30, 2019). This information does NOT alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Less invasive circulatory support devices have been developed that require anastomosis to a peripheral artery. The Symphony Heart Assist System (Abiomed, Inc, Danvers, Mass) is a volume-displacement pump sewn to the subclavian artery to provide partial circulatory support. The surgical configuration produces nonphysiologic blood pressure and bidirectional flow in the subclavian artery. Our objective was to identify effects of altered hemodynamics on arterial structure and function., Methods: In calves (n = 23; 80-100 kg), the Symphony pump was sewn end-to-side to the carotid artery. Acutely, carotid blood pressure and flow were recorded to evaluate hemodynamic changes. After medium-term support (1-4 weeks), carotid artery was studied. Histologic and molecular assays evaluated architectural changes. Quantitative real-time polymerase chain reaction evaluated gene expression of matrix metalloproteinase (MMP)-2, MMP-9, and connective tissue growth factor. In vitro carotid arterial-ring studies evaluated physiologic responses., Results: During Symphony support, carotid arterial pressure was 200/15 mm Hg. Antegrade flow increased significantly (P < .05) from 1.40 ± 0.32 to 4.29 ± 0.33 L/min. Flow during native cardiac diastole reversed completely from 0.25 ± 0.05 to -4.15 ± 0.38 L/min in carotid artery proximal to the anastomosis. After medium-term support, the carotid artery was significantly dilated with significantly thinner tunica media and thicker tunica adventitia than in control carotid arteries. MMP-9 gene expression decreased significantly, connective tissue growth factor gene expression increased significantly, and collagen, elastin, and total extracellular matrix increased significantly. Endothelial cells were significantly hypertrophied and produced significantly more von Willebrand factor. Endothelial apoptosis increased significantly. Platelet-endothelial interactions decreased significantly. Endothelial-independent contraction decreased significantly, whereas endothelial-dependent relaxation increased modestly., Conclusions: Assisted circulation with a left ventricular assist device triggered arterial remodeling that allowed a peripheral artery to accommodate the altered hemodynamics of a novel partial-support pump. Further delineation of remodeling pathways may be of significance for the emerging field of partial circulatory support., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Left ventricular assist device support produces a bleeding diathesis. Evidence suggests a major role for von Willebrand factor (vWF). We examined vWF metabolism in a preclinical model of short-term mechanical circulatory support., Methods: In 25 calves (weight, 80-110 kg), the inflow/outflow graft of the Symphony Heart Assist System was sewn end-to-side to the carotid artery. Support was initiated (acute, n = 4; 1 week, n = 16; 2 weeks, n = 5). Acutely, carotid artery pressure and flow were measured to evaluate the hemodynamic changes near the anastomosis. At baseline and after ≤2 weeks of support, platelet aggregometry with adenosine 5'-diphosphate, collagen, and ristocetin was performed. Gel electrophoresis and wet immunoblotting qualitatively evaluated vWF multimers and quantified plasma ADAMTS-13, the vWF-cleaving protease. Carotid arterial rings near the anastomosis were studied with immunohistochemical staining for ADAMTS-13 and were cultured to quantify endothelial ADAMTS-13 production. Fluorescent resonance energy transfer was used to evaluate the enzymatic activity of ADAMTS-13 in the plasma and in supernatant from cultured carotid arterial rings. Plasma interleukin-6, which inhibits ADAMTS-13 activity, was measured using an enzyme-linked immunosorbent assay., Results: During support, statistically significant (P < .05) changes in the carotid endothelium arterial hemodynamics were observed. The highest molecular weight vWF multimers were absent, and the vWF-ristocetin platelet aggregation pathway was significantly impaired. A modest but significant increase in plasma ADAMTS-13 protein and activity was observed. ADAMTS-13 decreased significantly in the carotid near the anastomosis but increased significantly in supernatant from cultured carotid arterial rings. The plasma interleukin-6 levels did not change significantly., Conclusions: Hemodynamic activation of vWF and increased plasma ADAMTS-13 activity may have reduced high-molecular-weight vWF multimers and thereby impaired the vWF-platelet aggregation pathway. Additional delineation of these pathways may improve management of left ventricular assist device-associated bleeding., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The anatomic and physiologic constraints for pediatric cavopulmonary assist differ markedly from adult Fontan circulations owing to smaller vessel sizes and risk of elevated pulmonary resistance. In this study, hemodynamic and hemolysis performance of a catheter-based viscous impeller pump (VIP) to power the Fontan circulation is assessed at a pediatric scale (∼15 kg) and performance range (0-30 mm Hg)., Methods: Computer simulation and mock circulation studies were conducted to assess the hydraulic performance, acute hemodynamic response to different levels VIP support, and the potential for vena caval collapse. Computational fluid dynamics simulations were used to estimate VIP hydraulic performance, shear rates, and potential for hemolysis. Hemolysis was quantified in a mock loop with fresh bovine blood., Results: A VIP augmented 4-way total cavopulmonary connection flow at pediatric scales and restored systemic pressures and flows to biventricular values, without causing flow obstruction or suction. VIP generated flows up to 4.1 L/min and pressure heads of up to 38 mm Hg at 11,000 rpm. Maximal shear rate was 160 Pa, predicting low hemolysis risk. Observed hemolysis was low with plasma free hemoglobin of 11.4 mg · dL(-1) · h(-1)., Conclusions: A VIP will augment Fontan cavopulmonary flow in the proper pressure and flow ranges, with low hemolysis risk under more stringent pediatric scale and physiology compared with adult scale. This technology may be developed to simultaneously reduce systemic venous pressure and improve cardiac output after stage 2 or 3 Fontan repair. It may serve to compress surgical staging, lessening the pathophysiologic burden of repair., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: An ectopic coronary artery that courses between the aortic root and the pulmonary trunk may lead to sudden cardiac death, especially in athletes. It has been speculated that during exercise, compression of the coronary artery between the great vessels may impair coronary blood flow and produce myocardial ischemia and fatal arrhythmia. However, this hypothesis cannot be tested in humans, and little experimental data exist to explain this phenomenon. To this end, in a calf with an anomalous left coronary artery that coursed from the right sinus of Valsalva between the great vessels, we assessed for myocardial ischemia during pharmacologically induced tachycardia and hypertension., Methods: We identified a juvenile male calf (103 kg) with an anomalous left coronary artery from the right sinus of Valsalva that coursed between the great vessels. Via thoracotomy, the animal was instrumented for hemodynamic measurements. Intravenous dobutamine increased heart rate and myocardial metabolic demands. Intravenous phenylephrine produced arterial hypertension and increased myocardial metabolic demands. Fluorescent-labeled microspheres were used to map regional myocardial blood flow, and hemodynamics were recorded during each condition. Masson's trichrome staining for fibrosis, wheat-germ agglutinin staining for myocyte size, terminal deoxynucleotidyl transferase dUTP nick end-label staining for apoptosis, and isolectin-B4 staining for capillary density were performed., Results: For the first time, empiric data documented that an ectopic coronary artery produced myocardial ischemia during elevated myocardial metabolic demands. Left coronary artery resistance increased in a cardiac cycle-dependent pattern that was consistent with systolic compression between the great vessels. Increased cardiac fibrosis, myocyte hypertrophy, cardiac apoptosis, and capillary density indicated that regional ischemic, inflammatory-mediated myocardial remodeling was present., Conclusions: These findings confirm the proposed mechanism of sudden death and support early surgical repair of coronary arteries that course between the aortic root and the pulmonary trunk., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Introduction: Platelet adhesion and activation are a significant source of clinical complications. Preventing foreign surface-platelet interaction may improve biocompatibility of implantable medical devices. This study evaluated efficacy of novel technique for electrically modifying surface of conductive biomaterial and attaching blood components to prevent thrombogenesis. Specifically, this new surface modification technology, Forcefield (ATS Medical, Inc, Minneapolis, Minn), was designed to prevent platelet adhesion on pyrolytic carbon. A modulated low-voltage current is directly applied to pyrolytic carbon surfaces to stimulate adherence of a layer of charged proteins from circulating blood components that is resistive to platelet deposition., Methods: Feasibility of Forcefield technology was tested in line with cardiopulmonary bypass circuit in patients undergoing standard cardiac surgery (n = 6). Forcefield treatment was applied to segment of pyrolytic carbon with 15 minutes (n = 3) and 30 minutes (n = 3) of electrically stimulated exposure time, and resulting segments were compared with untreated pyrolytic carbon segment. Platelet adhesion confluence was then quantified by scanning electron microscopy., Results: Confluence of the Forcefield-treated pyrolytic carbon segments (3.3% ± 2.2%) was significantly reduced relative to untreated pyrolytic carbon control segments (81.7% ± 24%, P < .001). There were no discernible differences in cell confluence with Forcefield-treated segments as function of exposure time (15 or 30 minutes)., Conclusions: Forcefield technology may enable modification of pyrolytic carbon surfaces to prevent platelet adhesion and thrombogenesis of implanted medical devices, including heart valves, stents, catheters, and ventricular assist devices, and may eliminate the need for anticoagulant and antiplatelet therapies., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Left ventricular assist devices are increasingly used to treat patients with advanced and otherwise refractory heart failure as bridge to transplant or destination therapy. We evaluated a new miniaturized left ventricular assist device that requires minimal surgery for implantation, potentially allowing implantation in earlier stage heart failure., Methods: HeartWare (Miami Lakes, Fla) developed transapical miniaturized ventricular assist device. Acute (n = 4), 1-week (n = 2), and 30-day (n = 4) bovine model experiments evaluated hemodynamic efficacy and biocompatibility of the device, which was implanted through small left thoracotomy with single insertion at apex of left ventricle without cardiopulmonary bypass. The device outflow cannula was positioned across the aortic valve. The international normalized ratio was maintained between 2.0 and 2.5 with warfarin. Hemodynamic, echocardiographic, fluoroscopic, hematologic, and blood chemistry measurements were evaluated., Results: The device was successfully implanted through the left ventricular apex in all 10 animals. The device was operated at 15,000 ± 1000 rpm (power consumption, 3.5-6.0 W). The device maintained normal end-organ perfusion with no significant hemolysis (0-30 mg/dL). There were no pump failures or device-related complications. At autopsy, no abnormalities were seen in endocardium, aortic valve leaflets, or aortic root. There was no evidence of thromboembolism or abnormalities in any peripheral end organs., Conclusions: We successfully demonstrated feasibility of a novel intraventricular assist device that can be completely implanted through left ventricular apex. This transapical surgical approach eliminates needs for sternotomy, device pocket, cardiopulmonary bypass, ventricular coring, and construction of an outflow graft anastomosis., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Left ventricular assist devices (LVADs) constitute a recent advance in heart failure (HF) therapeutics. As the rigorous experimental assessment of LVADs in HF requires large animal models, our objective was to develop a bovine model of cardiomyopathy. Male calves (n = 8) were used. Four animals received 1.2 mg/kg intravenous doxorubicin weekly for seven weeks and four separate animals were studied as controls. Doxorubicin-treated animals were followed with weekly echocardiography. Target LV dysfunction was defined as an ejection fraction ≤ 35%. Sixty days after initiating doxorubicin, a terminal study was performed to determine hemodynamic, histological, biochemical, and molecular parameters. All four doxorubicin-treated animals exhibited significant (P < 0.05) contractile dysfunction, with target LV dysfunction achieved in three animals. Doxorubicin-treated hearts exhibited significantly reduced coronary blood flow and interstitial fibrosis and significantly increased apoptosis and myocyte size. Gene expression of atrial natriuretic factor increased more than 3-fold. Plasma norepinephrine and epinephrine levels were significantly increased early and late during the development of cardiomyopathy, respectively. We conclude that sequential administration of intravenous doxorubicin in calves induces a cardiomyopathy with many phenotypic hallmarks of the failing human heart. This clinically-relevant model may be useful for testing pathophysiologic responses to LVADs in the context of HF.

Objective: We sought to investigate differences in indices of pulsatility between patients with normal ventricular function and patients with heart failure studied at the time of implantation with continuous-flow or pulsatile-flow left ventricular assist devices., Methods: Eight patients with normal ventricular function and 22 patients with heart failure were studied. A high-fidelity aortic and left ventricular pressure catheter was inserted retrograde through the aortic valve into the left ventricle, and transit-time flow probes were placed on the aorta and device outflow graft. Hemodynamic waveforms were recorded at native heart rate before cardiopulmonary bypass and over a range of device flow rates controlled by adjusting beat rate or rpm. These data were used to calculate vascular input impedance and 2 indices of vascular pulsatility: energy-equivalent pressure and surplus hemodynamic energy., Results: At low support levels, pulsatile support restored surplus hemodynamic energy to within 2.5% of normal values, whereas continuous support diminished surplus energy by more than 93%. At high support levels, pulsatile support augmented surplus energy by 49% over normal values, whereas continuous support further diminished surplus energy by 97%. Pulsatile support diminished vascular impedance from baseline failure values, whereas continuous support increased impedance. Vascular impedances at baseline for patients undergoing pulsatile and continuous support and during pulsatile support revealed normal vascular compliance, whereas impedance during continuous support indicated a loss of compliance (or "stiffening") of the vasculature., Conclusion: These results suggest that selection of device type and flow rate can influence vascular pulsatility and input impedance, which might affect clinical outcomes.

Effects of prescribed doses of ketamine five minutes after application and influences of transesophageal echocardiography (TEE) on left ventricular, systemic arterial, and baroreflex responses were investigated to test the hypothesis that ketamine and/or TEE probe insertion alter cardiovascular function. Seven rhesus monkeys were tested under each of four randomly selected experimental conditions: (1) intravenous bolus dose of ketamine (0.5 ml), (2) continuous infusion of ketamine (500 mg/kg/min), (3) continuous infusion of ketamine (500 mg/kg/min) with TEE, and (4) control (no ketamine or TEE). Monkeys were chronically instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to measure aortic flow. These measures were used to calculate left ventricular function. A 4-element Windkessel lumped-parameter model was used to estimate total peripheral resistance and systemic arterial compliance. Baroreflex response was calculated as the change in R-R interval divided by the change in mean aortic pressure measured during administration of graded concentrations of nitroprusside. The results indicated that five minutes after ketamine application heart rate and left ventricular diastolic compliance decreased while TEE increased aortic systolic and diastolic pressure. We conclude that ketamine may be administered as either a bolus or continuous infusion without affecting cardiovascular function 5 minutes after application while the insertion of a TEE probe will increase aortic pressure. The results for both ketamine and TEE illustrate the classic "Hawthorne Effect," where the observed values are partly a function of the measurement process. Measures of aortic pressure, heart rate, and left ventricular diastolic pressure should be viewed as relative, as opposed to absolute, when organisms are sedated with ketamine or instrumented with a TEE probe.

Background and Purpose: Cardiac and arterial responses to prescribed doses of propofol and etomidate in rhesus monkeys were compared., Methods: Intravenously administered induction doses of propofol (2 mg/kg of body weight) or etomidate (1 mg/kg) followed by continuous intravenous infusions of propofol (200 microg/kg/min) or etomidate (100 microg/kg/min) were administered. Left ventricular and right atrial access catheters were implanted for long-term use, along with a transit-time flow probe on the ascending aorta, and pericardial electrocardiogram leads. A dual sensor 3-F micromanometer was used to measure left ventricular pressure and aortic pressure, and an active redirectional transit-time probe measured aortic flow. Noordergraaf's four-element model was used to estimate total peripheral resistance and systemic arterial compliance., Results: Significant (P < 0.01) decreases in mean arterial pressure, heart rate, and myocardial contractility were accompanied by an increase in systemic arterial compliance associated with propofol and etomidate. Only minimal changes in left ventricular diastolic pressure, cardiac output, stroke volume, and total peripheral resistance were found for both drugs. The changes associated with propofol are comparable to results in human beings, whereas the changes associated with etomidate did not agree with results of published human studies., Conclusion: The significant cardiovascular alterations associated with both agents were attributed to reductions in heart rate, although the possibility exists that negative inotropic effects may have had a role.

Objective: Flow probes have been introduced as a non-invasive means of anastomotic quality assessment in off-pump coronary artery bypass graft (CABG). Flow waveform morphology cannot reliably be assessed visually unless severe anastomotic stenosis is present ( > 90%). We applied spectral analysis techniques to determine whether the frequency content of graft flow can improve the surgeon's ability to detect anastomotic errors., Methods: Forty-six mammary to left anterior descending artery (LAD) anastomoses were created in mongrel dogs during off-pump CABG surgery. Graft flow was measured using transit-time flow probes with the LAD closed, and the mammary graft patent and with varying degrees of stenosis. The degree of anastomotic stenosis was created by an artificial stitch and verified by random postoperative angiography. Spectral analysis of the graft flow waveforms was performed. Differences in the magnitude and phase components of the graft flow for the first five harmonics were determined for the varying anastomosis test conditions. Differences were determined using analysis of variance and least square means techniques., Results: The magnitude of the fundamental (zeroth) harmonic was statistically different in the internal mammary artery (IMA) with 0-25% stenosis compared to IMA with 50-75% stenosis (P < 0.01 ). Further, the magnitude of the first, second, and fourth harmonics were statistically different in IMA with 0-25% compared to IMA with 75% (P < 0.01). The phase of the first harmonic was statistically different in IMA with 25% stenosis than IMA with 50% stenosis (P < 0.01 ). No differences in interaction between the LAD and IMA for all ranges of stenosis were detected (P > 0.50)., Conclusion: Spectral analysis of graft flow waveforms may be beneficial in detecting lesser degrees of anastomotic stenosis (i.e. < 90%) compared to traditional visual assessment of mean graft flow and/or graft flow waveform morphology.

Objective: The intra-operative assessment of the quality of anastomosis in minimally invasive coronary artery bypass surgery (CABG) is critical. Recent investigations demonstrated that flow probes used intra-operatively to assess anastomotic errors may give the surgeon a false sense of confidence as only severely stenotic anastomoses (>90%) could be reliably detected. We developed a neural network system using graft flow data and assessed its potential to improve anastomotic error detection., Methods: Mammary to LAD grafts (n = 46) were constructed in mongrel dogs off-pump. Continuous beat-to-beat graft flow was recorded using transit-time flow probes. Various degrees of anastomotic stenoses (0-100%) were created by an additional suture. The degree of anastomotic stenosis was confirmed by postoperative angiography. A learning vector quantization neural network was created using heart rate, mean aortic pressure, mean systolic, maximum systolic, minimum systolic, mean diastolic, maximum diastolic, minimum diastolic, and mean graft flows. In addition, a spectral analysis of the flow waveforms was performed and the magnitude and phase of the first five harmonics were used to further develop the neural network., Results: The neural network pattern recognition system was 94% accurate in detecting any stenosis >50%. To validate the model, a testing set was used with 20% of the data values, and the accuracy remained at 100% above chance alone., Conclusion: Pattern recognition of transit-time flow probe tracings using neural network systems can detect anastomotic errors significantly better than the surgeon's visual assessment, thereby improving the clinical outcome of minimally invasive CABG.

Objective: Partial left ventriculectomy has been introduced as an alternative surgical therapy to heart transplantation. We performed a single-center, retrospective analysis of all patients with idiopathic dilated cardiomyopathy who underwent partial left ventriculectomy or heart transplantation or who were listed for transplantation to determine operative mortality rate, 12-month survival, freedom from death on the heart transplantation waiting list, and freedom from death or need for relisting for heart transplantation., Methods: Patients who had partial left ventriculectomy (October 1996 to April 1998) were retrospectively compared with patients who were listed for heart transplantation (January 1995 to April 1998). Survival was assessed after the surgical procedure (partial left ventriculectomy vs heart transplantation) and from time of listing for heart transplantation to assess the additional impact of waiting list deaths. Freedom from death or relisting for heart transplantation was also compared., Results: There was no difference in age or United Network for Organ Sharing status between the 2 groups. Twenty-nine patients with idiopathic dilated cardiomyopathy were listed for heart transplantation; 17 patients underwent transplantation, 6 patients died while on the waiting list, and 6 patients remain listed. One patient died after heart transplantation, and 1 patient required relisting. Sixteen patients had partial left ventriculectomy; 10 patients are in improved condition, 2 patients died (1 death early from sepsis and 1 death from progressive heart failure), and 4 patients required relisting for heart transplantation. Operative survival was 94% after partial left ventriculectomy and 94% after heart transplantation (P =.92). Postoperative 12-month Kaplan-Meier survival was 86% after partial left ventriculectomy and 93% after heart transplantation (P =.90). Twelve-month Kaplan-Meier survival after listing for heart transplantation was 75% due to death while on the waiting list (P =.76). Freedom from death or need for relisting for heart transplantation was 56% after partial left ventriculectomy and 86% after transplantation (P =.063)., Conclusion: Operative and 12-month survival after partial left ventriculectomy and heart transplantation were comparable. However, despite their initial improvement, many patients who underwent partial left ventriculectomy required relisting for transplantation. Although partial left ventriculectomy is associated with acceptable operative and 12-month survival, it may prove to serve better as a bridge to transplantation in patients with idiopathic dilated cardiomyopathy rather than definitive therapy, given the number of patients who required relisting for transplantation.

We assessed the acute cardiovascular changes of partial left ventriculectomy (PLV) in a patient with idiopathic dilated cardiomyopathy (IDCM) without mitral regurgitation. Acutely, PLV reduced left ventricular (LV) end-diastolic dimension and volume while increasing LV ejection fraction and cardiac output due to increased HR and SV. Substantial increases in LV filling pressure, possibly due to high LV end-systolic and diastolic elastances, were of concern clinically and the mechanism(s) of change remain unclear. However, one year follow-up showed remarkable improvements in NYHA and VO2 max while maintaining reduced LV volume, increased LVEF, and trivial MR.

Objective: Flow probes are being used for intraoperative assessment of anastomotic quality during off-pump coronary artery bypass grafting (CABG). We conducted a survey with the cooperation of 19 international surgeons to assess the ability of surgeons to detect anastomotic errors by evaluating mean flow and flow waveform morphology., Material and Methods: Mongrel dogs underwent mammary to left anterior descending (LAD) grafting. Mean graft flow and flow wave morphology for varying degrees of anastomotic stenoses were recorded using transit-time flow probes. A questionnaire consisting of ten different recorded flow tracings and the corresponding mean flows were given to 20 surgeons from around the world. The surgeons were asked to determine the degree of stenosis and whether they would re-do the anastomosis based upon the mean flow and the flow tracings., Results: All of the 19 surgeons that responded were able to clearly identify a highly stenotic graft (>90% stenosis). However, 24% would re-do a fully patent anastomosis, 58% accepted an anastomosis with moderate stenosis, and 72% accepted anastomoses with severe stenosis., Conclusions: Evaluation of flow tracing morphology and/or mean flows can be used to reliably detect nearly occluded anastomoses (>90% stenosis). However, surgeons should be cautious in assessing anastomoses with lesser degrees of stenosis, as they may be more difficult to reliably interpret.

Background: Anastomotic quality is currently the critical issue in minimally invasive coronary surgery. Although little is known about its effectiveness, surgeons routinely assess grafts intraoperatively using flow probes. This study was designed to determine whether mean flow and the pattern of flow tracing in internal mammary artery grafts obtained with a transit-time flow probe are reliable indicators of anastomotic quality., Methods: Mongrel dogs (n = 14, 30 to 35 kg) underwent off-pump left, right, or left and right internal mammary artery to left anterior descending artery anastomosis (23 grafts). Moderate to severe degrees of stenosis were created at the anastomosis by an additional suture. Internal mammary artery graft flow was measured before and after the stenosis was created with the left anterior descending artery occluded. Angiography was performed at random postoperatively to validate the degree of stenosis. Mean flow and flow tracing morphology were compared under various degrees of stenosis., Results: There were no significant differences in mean graft flow or the morphology of the flow tracing between patent (<15%), mild (<25%), moderate (<50%), and moderately severe (<75%) stenosis. However, mean graft flow decreased (p < 0.05) with severe stenosis (>75%)., Conclusions: Although differences in mean graft flow and graft flow morphology were detectable in anastomoses with severe stenosis (>75%), they were indistinguishable in anastomoses with mild (<25%) to moderately severe (<75%) stenosis. Flow measurement techniques are valuable tools intraoperatively, but surgeons should exercise caution in their interpretation.

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

Theoretical concepts hold that blood in the gravity-dependent portion of the body would relocate to more cephalad compartments under microgravity conditions. The result is an increase in blood volume in the thoracic and cardiac chambers. This increase in central volume shift should result in an increase in central atrial filling pressures. However, experimental data has been somewhat contradictory and nonconclusive to date. Early investigations of peripheral venous pressure and estimates of central venous pressure (CVP) from these data did not show an increase in CVP in the microgravity condition. However, CVP recorded in human volunteers during the parabolic flight by Norsk revealed an increase in CVP during the microgravity state. On the June 1991 STS 40 shuttle mission, a payload specialist wore a fluid line that recorded CVP during the first few hours of orbital insertion. These data revealed decreased CVP. When this CVP catheter was tested during parabolic flight in four subjects, two subjects had increased CVP recordings and two other subjects had decreased CVP measurements. In April 1991, our laboratory performed parabolic flight studies in several chronic-instrumented baboon subjects. It was again noted that centrally recorded right atrial pressure varied with exposure to microgravity, some animals having an increase and others having a decrease. Thus, data presently available has demonstrated a variable response in the mechanism not clearly defined. In April 1992, we determined a test hypothesis relating the possible mechanism of these variable pressure responses to venous pressure-volume relationships.