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One of the main limiting factors in the performance of devices based on two-dimensional (2D) materials is Fermi level pinning at the contacts, which creates Schottky barriers (SBs) that increase contact resistance and, for most transition metal dichalcogenides (TMDs), limit hole conduction. A promising method to mitigate these problems is surface charge transfer doping (SCTD), which places fixed charge at the surface of the material and thins the SBs by locally shifting the energy bands. We use a mild O 2 plasma to convert the top few layers of a given TMD into a substoichiometric oxide that serves as a p-type SCTD layer. A comprehensive experimental study, backed by TCAD simulations, involving MoS 2 , MoSe 2 , MoTe 2 , WS 2 , and WSe 2 flakes of various thicknesses exposed to different plasma times is used to investigate the underlying mechanisms responsible for SCTD. The surface charge at the top of the channel and the gate-modulated surface potential at the bottom are found to have competing effects on the channel potential, which results in a decrease in the doping-induced threshold shift and an increase in minimum OFF state current with increasing thickness. Additionally, an undoped channel region is shown to mitigate carrier injection issues in sufficiently thin flakes. Notably, the band movements underlying the SCTD effects are independent of the particular semiconductor material, SCTD strategy, and doping polarity. Consequently, our findings provide critical insights for the design of high-performance transistors for a wide range of materials and SCTD mechanisms including TMD devices with strong hole conduction.

Cranial microsurgery is an essential procedure for accessing the brain through the skull that can be used to introduce neural probes that measure and manipulate neural activity. Neuroscientists have typically used tools such as high-speed drills adapted from dentistry to perform these procedures. As the number of technologies available for neuroscientists has increased, the corresponding cranial microsurgery procedures to deploy them have become more complex. Using a robotic tool that automatically performs these procedures could standardize cranial microsurgeries across neuroscience laboratories and democratize the more challenging procedures. We have recently engineered a robotic surgery platform that utilizes principles of computer numerical control (CNC) machining to perform a wide variety of automated cranial procedures. Here, we describe how to adapt, configure and use an inexpensive desktop CNC mill equipped with a custom-built surface profiler for performing CNC-guided microsurgery on mice. Detailed instructions are provided to utilize this 'Craniobot' for performing circular craniotomies for coverslip implantation, large craniotomies for implanting transparent polymer skulls for cortex-wide imaging access and skull thinning for intact skull imaging. The Craniobot can be set up in <2 weeks using parts that cost <$1,500, and we anticipate that the Craniobot could be easily adapted for use in other small animals.

Chemical doping constitutes an effective route to alter the electronic, chemical, and optical properties of two-dimensional transition metal dichalcogenides (2D-TMDs). We used a plasma-assisted method to introduce carbon-hydrogen (CH) units into WS 2 monolayers. We found CH-groups to be the most stable dopant to introduce carbon into WS 2 , which led to a reduction of the optical bandgap from 1.98 to 1.83 eV, as revealed by photoluminescence spectroscopy. Aberration corrected high-resolution scanning transmission electron microscopy (AC-HRSTEM) observations in conjunction with first-principle calculations confirm that CH-groups incorporate into S vacancies within WS 2 . According to our electronic transport measurements, undoped WS 2 exhibits a unipolar n-type conduction. Nevertheless, the CH-WS 2 monolayers show the emergence of a p-branch and gradually become entirely p-type, as the carbon doping level increases. Therefore, CH-groups embedded into the WS 2 lattice tailor its electronic and optical characteristics. This route could be used to dope other 2D-TMDs for more efficient electronic devices.

A defect-controlled approach for the nucleation and epitaxial growth of WSe 2 on hBN is demonstrated. The WSe 2 domains exhibit a preferred orientation of over 95%, leading to a reduced density of inversion domain boundaries (IDBs) upon coalescence. First-principles calculations and experimental studies as a function of growth conditions and substrate pretreatment confirm that WSe 2 nucleation density and orientation are controlled by the hBN surface defect density rather than thermodynamic factors. Detailed transmission electron microscopy analysis provides support for the role of single-atom vacancies on the hBN surface that trap W atoms and break surface symmetry leading to a reduced formation energy for one orientation of WSe 2 domains. Through careful control of nucleation and extended lateral growth time, fully coalesced WSe 2 monolayer films on hBN were achieved. Low-temperature photoluminescence (PL) measurements and transport measurements of back-gated field-effect transistor devices fabricated on WSe 2 /hBN films show improved optical and electrical properties compared to films grown on sapphire under similar conditions. Our results reveal an important nucleation mechanism for the epitaxial growth of van der Waals heterostructures and demonstrate hBN as a superior substrate for single-crystal transition-metal dichalcogenide (TMD) films, resulting in a reduced density of IDBs and improved properties. The results motivate further efforts focused on the development of single crystal hBN substrates and epilayers for synthesis of wafer-scale single crystal TMD films.

Over the last few decades, a plethora of tools has been developed for neuroscientists to interface with the brain. Implementing these tools requires precisely removing sections of the skull to access the brain. These delicate cranial microsurgical procedures need to be performed on the sub-millimeter thick bone without damaging the underlying tissue and therefore, require significant training. Automating some of these procedures would not only enable more precise microsurgical operations, but also facilitate widespread use of advanced neurotechnologies. Here, we introduce the "Craniobot", a cranial microsurgery platform that combines automated skull surface profiling with a computer numerical controlled (CNC) milling machine to perform a variety of cranial microsurgical procedures on mice. The Craniobot utilizes a low-force contact sensor to profile the skull surface and uses this information to perform precise milling operations within minutes. We have used the Craniobot to perform intact skull thinning and open small to large craniotomies over the dorsal cortex.

Mobility is a critical parameter that is routinely used for benchmarking the performance of field-effect transistors (FETs) based on novel nanomaterials. In fact, mobility values are often used to champion nanomaterials since high-performance devices necessitate high mobility values. The current belief is that the contacts can only limit the FET performance and hence the extracted mobility is an underestimation of the true channel mobility. However, here, such misconception is challenged through rigorous experimental effort, backed by numerical simulations, to demonstrate that overestimation of mobility occurs in commonly used geometries and in nanomaterials for which the contact interface, contact doping, and contact geometry play a pivotal role. In particular, dual-gated FETs based on multilayer MoS 2 and WSe 2 are used as case studies in order to elucidate and differentiate between intrinsic and extrinsic contact effects manifesting in the mobility extraction. The choice of 2D layered transition metal dichalcogenides (TMDCs) as the semiconducting channel is motivated by their potential to replace and/or coexist with Si-based aging FET technologies. However, the results are equally applicable to nanotube- and nanowire-based FETs, oxide semiconductors, and organic-material-based thin-film FETs., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Structural defects govern various physical, chemical, and optoelectronic properties of two-dimensional transition-metal dichalcogenides (TMDs). A fundamental understanding of the spatial distribution and dynamics of defects in these low-dimensional systems is critical for advances in nanotechnology. However, such understanding has remained elusive primarily due to the inaccessibility of (a) necessary time scales via standard atomistic simulations and (b) required spatiotemporal resolution in experiments. Here, we take advantage of supervised machine learning, in situ high-resolution transmission electron microscopy (HRTEM) and molecular dynamics (MD) simulations to overcome these limitations. We combine genetic algorithms (GA) with MD to investigate the extended structure of point defects, their dynamical evolution, and their role in inducing the phase transition between the semiconducting (2H) and metallic (1T) phase in monolayer MoS 2 . GA-based structural optimization is used to identify the long-range structure of randomly distributed point defects (sulfur vacancies) for various defect densities. Regardless of the density, we find that organization of sulfur vacancies into extended lines is the most energetically favorable. HRTEM validates these findings and suggests a phase transformation from the 2H-to-1T phase that is localized near these extended defects when exposed to high electron beam doses. MD simulations elucidate the molecular mechanism driving the onset of the 2H to 1T transformation and indicate that finite amounts of 1T phase can be retained by increasing the defect concentration and temperature. This work significantly advances the current understanding of defect structure/evolution and structural transitions in 2D TMDs, which is crucial for designing nanoscale devices with desired functionality.

Over the past decade, the field of two-dimensional (2D) layered materials has surged, promising a new platform for studying diverse physical phenomena that are scientifically intriguing and technologically relevant. Contacts are the communication links between these 2D materials and the three-dimensional world for probing and harnessing their exquisite electronic properties. However, fundamental challenges related to contacts often limit the ultimate performance and potential of 2D materials and devices. This article provides a comprehensive overview of the basic understanding and importance of contacts to 2D materials and various strategies for engineering and improving them. In particular, we elucidate the phenomenon of Fermi level pinning at the metal/2D contact interface, the Schottky versus Ohmic nature of the contacts and various contact engineering approaches including interlayer contacts, phase engineered contacts, and basal versus edge plane contacts, among others. Finally, we also discuss some of the relatively under-addressed and unresolved issues, such as contact scaling, and conclude with a future outlook.

Physics of monolayer and few-layer transition metal dichalcogenides (TMDs) and chemistry of few-layer TMDs have been well studied in recent years in the context of future electronic, optoelectronic, and energy harvesting applications. However, what has escaped the attention of the scientific community is the unique chemistry of monolayer TMDs. It has been demonstrated that the basal plane of multilayer TMDs is chemically inert, whereas edge sites are chemically active. In this article, we experimentally demonstrate that the edge reactivity of the TMDs can be significantly impeded at the monolayer limit through monolayer/substrate interaction, thus making the monolayers highly resistant to electrooxidation and corrosion. In particular, we found that few-layer flakes of MoS 2 and WS 2 exfoliated on conductive TiN substrates are readily corroded beyond a certain positive electrode potential, while monolayer remnants are left behind unscathed. The electrooxidation resistance of monolayers was confirmed using a plethora of characterization techniques including atomic force microscope (AFM) imaging, Raman spectroscopy, photoluminescence (PL) mapping, scanning/transmission electron microscope (S/TEM) imaging, and selected area electron diffraction (SAED). It is believed that strong substrate monolayer interaction compared to the relatively weak interlayer van der Waals interaction is responsible for the superior monolayers chemical stability in highly corrosive oxidizing environments. Our findings could pave the way for the implementation of monolayer transition metal disulfides as superior anticorrosion coating which can have a significant socioeconomic impact.

In this paper, we report high-performance monolayer thin-film transistors (TFTs) based on a variety of two-dimensional layered semiconductors such as MoS 2 , WS 2 , and MoSe 2 which were obtained from their corresponding bulk counterparts via an anomalous but high-yield and low-cost electrochemical corrosion process, also referred to as electro-ablation (EA), at room temperature. These monolayer TFTs demonstrated current ON-OFF ratios in excess of 10 7 along with ON currents of 120 μA/μm for MoS 2 , 40 μA/μm for WS 2 , and 40 μA/μm for MoSe 2 which clearly outperform the existing TFT technologies. We found that these monolayers have larger Schottky barriers for electron injection compared to their multilayer counterparts, which is partially compensated by their superior electrostatics and ultra-thin tunnel barriers. We observed an Anderson type semiconductor-to-metal transition in these monolayers and also discussed possible scattering mechanisms that manifest in the temperature dependence of the electron mobility. Finally, our study suggests superior chemical stability and electronic integrity of monolayers even after being exposed to extreme electro-oxidation and corrosion processes which is promising for the implementation of such TFTs in harsh environment sensing. Overall, the EA process proves to be a facile synthesis route offering higher monolayer yields than mechanical exfoliation and lower cost and complexity than chemical vapor deposition methods.

In this paper we provide insight into an anomalous corrosion process, referred to as electroablation (EA), which converts multilayer flakes of transition metal diselenides like MoSe 2 into their corresponding monolayers when micromechanically exfoliated on a conductive electrode and subsequently subjected to a high anodic potential inside a conventional electrochemical cell. Photoluminescence intensity maps and scanning transmission electron microscopy (STEM) images confirmed the single crystalline nature and 2H-hexagonal lattice structure of the remnant monolayer MoSe 2 flakes, indicating the superior corrosion stability of the monolayers compared to that of the bulk counterpart. It is noted that the EA technique is a low-cost alternative for high-yield synthesis of single crystalline monolayer MoSe 2 at room temperature. We also found that the dynamics of such an electro-oxidation-mediated and self-limiting corrosion process differs significantly for MoSe 2 and WSe 2 . While we were able to engineer the corrosion conditions for the EA process to obtain monolayers of MoSe 2 , our attempts to obtain monolayers of WSe 2 were largely unsuccessful. Finally, we constructed a phenomenological physical chemistry framework to explain such anomalous corrosion processes in transition metal diselenides.

Nanosensor arrays have recently received significant attention due to their utility in a wide range of applications, including gas sensing, fuel cells, internet of things, and portable health monitoring systems. Less attention has been given to the production of sensor platforms in the μW range for ultra-low power applications. Here, we discuss how to scale the nanosensor energy demand by developing a process for integration of nanowire sensing arrays on a monolithic CMOS chip. This work demonstrates an off-chip nanowire fabrication method; subsequently nanowires link to a fused SiO 2 substrate using electric-field assisted directed assembly. The nanowire resistances shown in this work have the highest resistance uniformity reported to date of 18%, which enables a practical roadmap towards the coupling of nanosensors to CMOS circuits and signal processing systems. The article also presents the utility of optimizing annealing conditions of the off-chip metal-oxides prior to CMOS integration to avoid limitations of thermal budget and process incompatibility. In the context of the platform demonstrated here, directed assembly is a powerful tool that can realize highly uniform, cross-reactive arrays of different types of metal-oxide nanosensors suited for gas discrimination and signal processing systems.

Neurotransmitter release in chemical synapses is fundamental to diverse brain functions such as motor action, learning, cognition, emotion, perception, and consciousness. Moreover, improper functioning or abnormal release of neurotransmitter is associated with numerous neurological disorders such as epilepsy, sclerosis, schizophrenia, Alzheimer's disease, and Parkinson's disease. We have utilized hysteresis engineering in a back-gated MoS 2 field effect transistor (FET) in order to mimic such neurotransmitter release dynamics in chemical synapses. All three essential features, i.e., quantal, stochastic, and excitatory or inhibitory nature of neurotransmitter release, were accurately captured in our experimental demonstration. We also mimicked an important phenomenon called long-term potentiation (LTP), which forms the basis of human memory. Finally, we demonstrated how to engineer the LTP time by operating the MoS 2 FET in different regimes. Our findings could provide a critical component toward the design of next-generation smart and intelligent human-like machines and human-machine interfaces.

Background: Bereavement services are central to high-quality end-of-life care, however, little is known about how frequently and why such bereavement services are used and not used. We examined family caregiver reports about how often they used bereavement services, predictors of their use, and reported reasons for not using bereavement services., Methods: Prospective cohort study of family caregivers (n = 161) of patients with cancer enrolled with hospice between October 1999 and September 2001. We conducted bivariate and multivariable analyses to determine predictors of bereavement service use, adjusted for a broad range of factors including caregiving experiences, major depressive disorder (MDD), relationship with the deceased, and demographic factors. We used content analysis to summarize responses to open-ended questions concerning why individuals did not use bereavement services., Results: We found that approximately 30% of family caregivers used bereavement services in the year postloss, and the majority of these caregivers used services in the first 6 months postloss. Even among bereaved caregivers with MDD, less than half (47.6%) used bereavement services. Factors associated with using bereavement services included being a spouse caregiver, younger age, having MDD at study enrollment, witnessing highly distressing events pertaining to the patient's death, having assisted the patient with more Instrumental Activities of Daily Living (IADLs) prior to the patient's death, having greater availability of instrumental support for oneself, and physician communication with the caregiver about the patient's prognosis before the patient's death. The most common given reason for nonuse was the perception that bereavement services were not needed or would not help., Conclusion: Addressing caregiver receptivity to bereavement services will be an important aspect of increasing appropriate use of such services. Future studies might examine specific interventions for reducing barriers and increasing receptivity to bereavement service use.

Objectives: We tested whether acute hormone therapy reduces ambulatory electrocardiographic ischemia in postmenopausal (PMP) women with unstable angina (UA)., Background: Endothelial dysfunction contributes to the pathophysiology of UA. Acute estrogen administration improves endothelial function in PMP women with coronary artery disease and increases coronary artery blood flow., Methods: Two hundred ninety-three PMP women with UA (mean age 69.7 years), treated with standard anti-ischemic therapy, were enrolled within 24 h of symptom onset. In a double-blind fashion, subjects were randomized to receive intravenous followed by oral conjugated estrogen for 21 days, intravenous estrogen followed by oral conjugated estrogen plus medroxyprogesterone for 21 days or placebo. The primary end point was the number of ambulatory electrocardiographic ischemic events over the first 48 h. Clinical events were also determined over six months of follow-up., Results: Electrocardiographic ischemia did not differ among the three randomized groups. The mean number of ischemic events per patient over 48 h was 0.74 for estrogen, 0.86 for estrogen plus progesterone and 0.74 for the placebo groups (p = 0.87). The percentage of patients with ischemic events and the mean duration of ischemia did not differ between hormone- and placebo-treated patients. In-hospital and six-month rates of adverse clinical events were also similar among the three randomized groups., Conclusions: Acute hormone therapy does not reduce ischemia in PMP women with UA when added to standard anti-ischemic therapy.

Patients with systemic hypertension and coronary artery disease (CAD) often manifest abnormalities at rest in left ventricular (LV) diastolic function and reduced exercise tolerance. It is possible that abnormalities in filling persist during exercise and are partially related to abnormal exercise tolerance. We examined rest and exercise peak filling rate (PFR) to determine if changes in PFR during exercise influence exercise performance. We studied 20 patients with systemic hypertension who had no evidence of CAD (negative thallium-201 stress imaging) and 15 patients with prior myocardial infarction, preserved ejection fraction, and no ischemia by thallium-201 stress imaging. Results were compared with 20 normal subjects. All 55 subjects had rest and exercise radionuclide angiograms Peak workload, exercise time, and LV ejection fraction were reduced in subjects with CAD (57 +/- 24 W, 7.41 +/- 2.91 min, and 60 +/- 9%) compared with subjects with hypertension (72 +/- 21 W, 9.69 +/- 3.03 min, and 70 +/- 6%, p <0.05) and controls (80 +/- 30 W, 10.82 +/- 3.50 min, and 67 +/- 6%, p <0.05). PFR at rest was reduced in CAD subjects (2.40 +/- 0.70 end-diastolic volume per second [EDV/s]) compared with those with hypertension (2.89 +/- 0.70 EDV/s, p <0.02) and controls (3.23 +/- 0.52 EDV/s, p <0.0002). The increments in PFR during exercise were reduced in CAD patients (+1.76 +/- 0.95 EDV/s) compared with hypertensive subjects (+2.93 +/- 1.7 EDV/s) and controls (+3.22 +/- 1.4 EDV/s, p <0.05). The increment in PFR during exercise was related to exercise performance (r = 0.49, p <0.0002). These findings suggest that alterations in LV diastolic filling during exercise are important determinants of exercise performance.

We compared exercise test results to a physiologic depiction of stenosis severity, coronary flow reserve (CFR), measured with a Doppler guide wire in 35 patients with single-vessel coronary disease. Group 1 (n = 21) had abnormal CFR, and group 2 (n = 14) had normal CFR. In group 1, 14 of 21 had ST-segment depression versus 3 of 14 in group 2 (p < 0.01). Exercise treadmill time (Bruce protocol) was normalized to the age- and sex-predicted time. Exercise time and normalized exercise time were less in group 1 (5.6 +/- 2.3 vs 9.9 +/- 1.8 min and 0.82 +/- 0.32 vs 1.25 +/- 0.23, p < 0.00001). Having either ST-segment depression or a normalized exercise time <1 during exercise had a 95% sensitivity, 71% specificity, and 86% predictive accuracy in identifying abnormal CFR. Coronary stenoses and minimal lumen diameter were similar in groups 1 and 2. By using stepwise logistical regression analysis, exercise time and ST-segment depression predicted CFR with a total r2 of 0.51. Minimal lumen diameter did not significantly add to the model. Exercise test variables, ST-segment depression, and exercise time are predictive of the physiologic significance of coronary lesions.

Coronary flow reserve (CFR) is a critical measurement in the assessment of the coronary circulation. The development of this physiologic variable in animal and human studies is reviewed. Human studies documenting the limitations of coronary angiography, especially in the setting of severe diffuse coronary artery disease, are analyzed. Furthermore, the important variables that must be accounted for when CFR is measured are examined. With this background, the application of CFR in a variety of clinical settings and the development and use of the Doppler FloWire for its measurement are discussed.

Antihypertensive therapy in hypertensive patients with left ventricular (LV) hypertrophy causes hypertrophy regression and improved diastolic filling. Whether similar changes occur in hypertensive patients with diastolic dysfunction and no hypertrophy is unknown. We determined the effect of antihypertensive therapy of LV geometry and function in hypertensive patients without hypertrophy. In 18 mild to moderate hypertensive patients without significant hypertrophy, baseline echocardiograms and rest and exercise and radionuclide angiograms were performed. Subjects were treated for 8 to 12 months with the calcium channel blocker felodipine and then restudied 2 weeks after treatment withdrawal. Blood pressure normalized with treatment (165 +/- 22/98 +/- 9 to 128 +/- 12/80 +/- 5 mm Hg, p <0.001) and returned to pretreatment levels after therapy withdrawal. Rest ejection fraction and peak oxygen consumption and cardiac outputs were unchanged after treatment, but rest peak filling rate increased (2.63 +/- 0.57 to 3.11 +/- 0.95 end-diastolic volume/second, p <0.05). Ejection fraction increased with exercise only after treatment (64 +/- 5% at rest to 71 +/- 8% at peak exercise, p <0.05). LV mass index was unchanged (97 +/- 18 to 101 +/- 23 g/m2), but relative wall thickness declined (0.41 +/- 0.05 to 0.37 +/- 0.05) and LV end-diastolic dimension increased (4.9 +/- 0.4 to 5.2 +/- 0.4, p = 0.01). Blood pressures control in hypertensive patients without hypertrophy leads to improved peak filling rates and remodeling with decreased relative wall thickness. Improved diastolic function can occur without alterations in LV mass.

The right ventricle has a prominent role in determining overall cardiac function. Thus an accurate measurement of right ventricular (RV) function is important. Radionuclide angiography has advanced our ability to measure RV function. In this way, it has furthered our understanding of the pathophysiology of disease states involving the right ventricle. This article reviews the current methods of measuring RV function by radionuclide angiography. The physiology of normal RV function is discussed. Then several common disease states in which RV dysfunction is prominent are addressed.

In hypertensive patients with hypertrophy, abnormal peak filling rate (PFR) is related to a decline in left ventricular (LV) ejection fraction (EF) during supine exercise. Because an increased LV preload is more common during upright exercise, we determined this relation during upright and supine exercise. In 20 hypertensive patients, rest and exercise radionuclide angiography in the supine and upright positions, as well as echocardiography, were performed and compared with 20 age-matched controls. At rest in the supine and upright positions, blood pressure, LVEF, and PFR were 164 +/- 20/94 +/- 10 and 164 +/- 24/94 +/- 10 mm Hg, 65 +/- 8% and 65 +/- 6%, and 2.77 +/- 0.59 and 2.70 +/- 0.52 end-diastolic volumes/s, respectively. PFR was reduced compared with controls (3.29 +/- 0.3 and 3.27 +/- 0.27 end-diastolic volumes/s, supine and upright). LV mass index was normal (94 +/- 19 g/m2). LVEF increased during upright but not during supine exercise in the hypertensives. Four patients had a decline in each position versus none of the controls. There was no relation between the change in LVEF and rest PFR. In patients with mild to moderate hypertension without extensive hypertrophy, abnormal filling rates were present but did not correlate with the change in LVEF with exercise.

Background: A decline in left ventricular (LV) ejection fraction in response to mental stress and exercise is regarded as an indicator of myocardial ischemia. In patients with LV dysfunction, the ejection fraction is sensitive to afterload, which increases during stress. Thus, the effects of mental stress and exercise on LV systolic function in patients with cardiomyopathy were examined., Methods: The ambulatory nuclear VEST (Capintec, Inc., Ramsey, N.J.) was used to monitor LV ejection fraction in patients with cardiomyopathy (10 idiopathic and 9 ischemic). Patients underwent a series of mental stress tests (serial 7s, Stroop color, and Paced auditory addition) and treadmill exercise. Heart rate, systolic blood pressure, and LV ejection fraction were measured., Results: Mental stress and exercise increased heart rate and systolic blood pressure. For idiopathic cardiomyopathy, LV ejection fraction decreased during serial 7s, Stroop color, Paced auditory addition and exercise by -8% +/- 6%, -7% +/- 5%, -7% +/- 3%, -9% +/- 10%, respectively. For ischemic cardiomyopathy, LV ejection fraction declined by -4% +/- 3%, -7% +/- 5%, -6% +/- 3%, -2% +/- 6% during the same stress tests. There was no difference between the idiopathic and ischemic groups. Each patient showed a 5% or greater decline in LV ejection fraction during one mental stress test. There was an inverse relation between changes in LV ejection fraction and systolic blood pressure during all mental stress tests and exercise (r = -0.47, p < 0.0001)., Conclusions: In patients with depressed baseline systolic function, the decline in systolic function during mental stress and exercise could be related in part to increases in LV afterload.

Study Objective: Right ventricular (RV) ejection fraction is load sensitive, varying inversely with pulmonary artery pressure. We tested whether this relationship exists in dilated cardiomyopathy., Design: Retrospective chart review., Setting: Tertiary care referral medical center., Patients: In 25 patients with cardiomyopathy referred for heart transplant evaluation (left ventricular ejection fraction 27 +/- 12%), hemodynamics, radionuclide angiograms, and Doppler echocardiograms were obtained initially (study A) and 8 +/- 8 months later (study B)., Results: Right ventricular ejection fraction was 40 +/- 17% on study A and 41 +/- 16% on study B, with a wide range of change between studies (+38 to -28%). Pulmonary artery systolic pressure (PASP) and right atrial pressure increased (52 +/- 9 to 61 +/- 10 mm Hg and 10 +/- 4 to 14 +/- 4 mm Hg, respectively, p < 0.05). There was no relation between PASP and RV ejection fraction (n = 50, r = -0.02, p = 0.87). Also, there was no relation between changes in PASP and RV ejection fraction (n = 25, r = 0.25, p = 0.15) between study A and B. However, there was a significant relation between interstudy changes in PASP and RV ejection fraction (n = 14, r = -0.71, p = 0.005) and end-systolic volume (n = 14, r = 0.53, p < 0.05) in patients in whom the degree of tricuspid regurgitation was either none or mild on both study A and B., Conclusions: In patients with cardiomyopathy, RV ejection fraction cannot be used as a noninvasive marker of pulmonary hypertension. Owing to variation in tricuspid regurgitation, alterations in pulmonary artery pressure over time may not lead to the expected change in RV ejection fraction or end-systolic volume.

Objectives: This study attempted to determine the utility of early rest-redistribution thallium-201 imaging in detecting residual myocardial viability after myocardial infarction., Background: The early detection of myocardial viability after myocardial infarction would have clinical relevance., Methods: Thirty-one patients with acute myocardial infarction had early (mean [+/- SD] 2 +/- 1 day) rest-redistribution thallium-201 imaging followed by radionuclide and coronary angiography. Late studies included stress-redistribution-reinjection thallium-201 imaging or radionuclide angiography, or both. Viability was defined by the rest thallium-201 scan as an initial mild rest defect or any defect that demonstrated redistribution., Results: Group 1 (n = 15) was predicted to have viable and Group 2 (n = 16) nonviable myocardium in the infarct zone. Group 1 patients were more likely to have a patent infarct-related artery (15 of 15 vs. 10 of 16, p < 0.03), higher initial ejection fraction (61 +/- 12% vs. 53 +/- 9%, p < 0.05), higher infarct wall motion score (p < 0.0001) and fewer abnormal thallium-201 segments (p < 0.0001). On follow-up studies, ejection fraction improved in Group 1 (from 57 +/- 13% to 66 +/- 10%, p < 0.05, n = 9) and deteriorated in Group 2 (from 53 +/- 10% to 46 +/- 8%, p < 0.05, n = 13). On late stress testing with thallium-201 reinjection, Group 1 patients had fewer abnormal segments (p < 0.03) and higher infarct zone counts during exercise (p < 0.05) and after reinjection (p < 0.05) than Group 2 patients., Conclusions: If confirmed by larger studies, early rest-redistribution thallium-201 imaging may be a useful technique for identifying residual viability after myocardial infarction.

The relationship between maximal exercise tolerance and resting radionuclide indexes of left ventricular systolic and diastolic function were evaluated in 20 ischemic and 44 idiopathic cardiomyopathy patients with New York Heart Association class 2-4 chronic congestive heart failure. Left ventricular ejection fraction, peak systolic ejection rate, peak diastolic filling rate, time to peak filling from end-systolic volume, and fractional filling in early diastole were measured from the radionuclide ventriculogram. All patients underwent symptom-limited exercise testing with on-line measurement of oxygen consumption. In the ischemic group, all of the radionuclide indexes correlated poorly with maximal exercise oxygen consumption (VO2max) except the peak systolic ejection rate which correlated modestly (r = 0.58, p < 0.05). Peak systolic ejection rate was significantly lower (p < 0.01) as were the peak diastolic filling rate and fractional filling in the first third of diastole (p < 0.05) in ischemic patients with marked exercise intolerance (VO2max < or = 14 mL/kg/min) compared with those with preserved exercise tolerance (VO2max > 14 mL/kg/min). In the idiopathic group, none of the radionuclide indexes correlated well with VO2max; and all indexes were similar in patients with and without marked exercise intolerance. These data suggest that (1) resting left ventricular ejection fraction poorly predicts maximal exercise capacity in both ischemic and idiopathic cardiomyopathy and (2) resting peak systolic ejection rate, peak diastolic filling rate, and fractional filling in early diastole may predict exercise tolerance in ischemic but not idiopathic cardiomyopathy.

Objectives: The purpose of this study was to compare measures of coronary flow reserve by an intracoronary Doppler guide wire with results of stress single-photon emission computed tomographic (SPECT) thallium-201 imaging in patients with intermediate coronary artery disease (40% to 70% stenosis)., Background: Visual assessment of the coronary arteriogram as a means of predicting the physiologic significance of intermediate coronary stenoses is inaccurate. Coronary flow reserve is a reliable marker of the functional importance of a coronary lesion. The recent development of an intracoronary Doppler guide wire permits routine assessment of coronary flow reserve distal to coronary artery stenoses., Methods: We prospectively evaluated coronary flow reserve in 30 subjects with intermediate stenoses using an intracoronary Doppler guide wire during elective coronary angiography. Patients subsequently underwent stress SPECT thallium-201 testing, and the blinded interpretations were correlated. Coronary flow reserve in a control group with normal coronary arteries classified our sample into group 1 (abnormal flow reserve, < 2.0) and group 2 (normal flow reserve, > or = 2.0)., Results: As defined, the coronary flow reserve of 16 vessels in group 1 was diminished in comparison to that of 19 vessels in group 2 (p = 0.0001). Qualitative and quantitative analysis of stress SPECT thallium-201 images confirmed perfusion defects in 15 of 16 vascular territories in group 1 in contrast to 1 of 19 regions in group 2. The sensitivity, specificity and overall predictive accuracy of Doppler-determined coronary flow reserve for stress SPECT thallium-201 results were 94%, 95% and 94%, respectively., Conclusions: In appropriately selected patients with intermediate coronary artery stenoses, Doppler guide wire determination of lesion significance provides equivalent data to those acquired by stress SPECT thallium-201 imaging.

A hypercoagulable state exists after orthotopic liver transplantation. This hematologic abnormality may predispose patients to coronary thrombosis and unstable angina. The incidence of postoperative myocardial ischemia in such patients is unknown. Suitable electrocardiograms and clinical events of consecutive patients undergoing orthotopic liver transplantation (n = 45) and major intraabdominal surgery (n = 28) during a 3-month period at a major university teaching hospital and transplant center were examined retrospectively. Clinical myocardial ischemia or ischemic electrocardiographic changes, or both, occurred in 6 transplant patients compared with no patient in the nontransplant or comparison group. In 4 of the 6 patients with dramatic electrocardiographic changes and ischemic events, coronary arteriography failed to demonstrate significant obstructive disease. It is concluded that severe myocardial ischemia may occur in patients after orthotopic liver transplantation in the absence of significant coronary disease. A hypercoagulable state may predispose to coronary thrombosis in this setting, providing insight (and a future model for study) into the development of unstable angina.

Right ventricular (RV) function influences left ventricular (LV) diastolic filling in various clinical and experimental models. The influence of RV systolic function on LV diastolic performance was examined in patients with severe RV pressure overload. Eighty-two patients with pulmonary vascular or parenchymal disease who were referred for heart-lung or lung transplant evaluation were studied. All patients had radionuclide angiography from which RV ejection fraction and LV peak filling rate were measured. Most patients (n = 51) had right-sided cardiac catheterization. In 24 patients (group 1), RV ejection fraction was < 30%, whereas in 58 (group 2), it was > 30%. Mean pulmonary artery pressure was greater in group 1 than in 2 (57 +/- 16 vs 34 +/- 20 mm Hg; p < 0.0001). Pulmonary artery wedge pressure was also greater in group 1 than in 2 (14 +/- 9 vs 7 +/- 2 mm Hg; p < 0.0001), whereas peak filling rate was decreased (2.16 +/- 0.88 vs 2.97 +/- 0.79 end-diastolic volumes/s; p < 0.0001). LV ejection fraction was normal in all patients. There was an inverse relation between RV ejection fraction and pulmonary artery wedge pressure (r = 0.45; p < 0.001; SEE 5.3). There was a direct relation between RV ejection fraction and LV peak filling rate (r = 0.49; p < 0.0001; SEE 1.34). In patients with RV pressure overload, RV systolic function is related to LV diastolic performance. This effect is most likely mediated by ventricular interdependence.

Right ventricular ischemia occurs in experimental models of pulmonary hypertension. We analyzed right ventricular size and function and 201Tl uptake to determine if there was a relationship between 201Tl uptake and systolic function in 19 patients with pulmonary artery hypertension who were being evaluated for heart-lung transplantation. All patients had dipyridamole stress 201Tl scintigraphy, radionuclide angiography and echocardiography. In nine patients (Group 1), right ventricular ejection fraction was < 30% (mean 22% +/- 8%). In 10 patients (Group 2) it was > 30% (mean 45% +/- 11%). In Group 1, right ventricular 201Tl uptake in the lateral wall after dipyridamole was increased compared to Group 2 (40% +/- 7% versus 28% +/- 15% counts/pixel, p < 0.05) while left ventricular free wall uptake was similar. The ratio of right to left ventricular 201Tl uptake was increased in Group 1 versus Group 2 (0.81% +/- 0.30% versus 0.49% +/- 0.18%, p < 0.05). At 4 hr, right ventricular free wall 201Tl clearance was comparable, 51% +/- 13% versus 51% +/- 18% in Groups 1 and 2, respectively. No patient had perfusion abnormalities. Right ventricular ejection fraction was inversely related to dipyridamole stress right ventricular 201Tl uptake, r = -0.49, p < 0.03, s.e.e. = 13.6. Right ventricular 201Tl uptake was directly related to right ventricular wall thickness (r = 0.56, p = 0.18, s.e.e. = 10.4). Therefore, patients with more severe right ventricular systolic dysfunction have greater 201Tl uptake after dipyridamole stress, suggesting increased myocardial mass and possibly blood flow in response to hypertrophy. Patients with the most marked hypertrophy have impairment of right ventricular systolic function, independent of ischemia.

Echocardiographic automated border detection can provide on-line estimates of left ventricular cavity area by differentiating blood from tissue backscatter characteristics. The objective of this study was to assess the ability of short-axis measurements of left ventricular cavity area by automated border detection to determine left ventricular function by comparing these measurements to radionuclide measures of ejection fraction in the same patients. Eighty-eight consecutive patients, aged 53 +/- 14 years, underwent automated border detection studies within 2 hours of radionuclide ventriculography. Short-axis imaging with automated border detection was attempted at basal, midpapillary muscle, and apical levels. Maximal left ventricular length was also measured from apical 4- and 2-chamber views by standard imaging. Fractional area change--(end-diastolic area-end-systolic area)/end-diastolic area--was determined at each short-axis level. Volumes and ejection fractions were calculated using: volume = 5/6 (midventricular area).length. Simpson's rule for 3 short-axis measurements was calculated using: volume = (length/12) (5.basal area + 2.mid-area + 4.apical area). Technically adequate automated border detection data could be obtained on 69 patients (78%) at basal and mid-levels, and at all 3 short-axis levels in 66 patients (75%). Correlations with radionuclide ejection fraction were as follows: midventricular fractional area change--R = 0.84, SEE = 12%, y = 0.86 x - 7; area-length ejection fraction--R = 0.89, SEE = 9%, y = 0.96 x - 4; and Simpson's rule--R = 0.91, SEE = 8%, y = 0.89 x + 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Verapamil has complex influences on ventricular function owing to its direct myocardial effects, vasodilation, and reflex activation of the sympathetic nervous system. To investigate the direct myocardial effects of verapamil in humans independent of reflex sympathetic stimulation, we administered the drug to 13 recent heart transplant recipients with denervated ventricles. Hemodynamics and radionuclide angiograms were recorded at baseline, with altered loading conditions, and after intravenous (i.v.) verapamil (median dose 4 mg). Left ventricular (LV) systolic and diastolic function was analyzed by systolic pressure-volume relations (SPVR) and peak filling rate (PFR), respectively. Verapamil caused a decrease in blood pressure (BP) and heart rate (HR) with increases in right atrial pressure (RAP 6 +/- 3-8 +/- 3, p < 0.01) and pulmonary artery wedge pressure (PAWP, 9 +/- 3-11 +/- 3 mm Hg, p < 0.01) pressures. LV ejection fraction (EF) decreased (69 +/- 7-66 +/- 8%, p < 0.02) in association with an increase in LV end-systolic counts (3.45 +/- 1.27 to 4.72 +/- 1.78 kcts, p < 0.001). In 11 of 13 patients, the SPV point after verapamil administration was decreased from the line established during altered loading conditions. PFR (4.05 +/- 0.81 to 4.11 +/- 0.76 EDV/s) was unchanged. In the denervated ventricle, verapamil has negative chronotropic and inotropic effects with minimal effects on PFR.

We evaluated the hemodynamic and functional response to acute elevations in left ventricular (LV) afterload in 22 recent recipients of cardiac transplants to determine whether abnormalities in LV diastolic function influence the response to this intervention. In seven patients (group 1) LV ejection fraction decreased significantly from baseline values (> or = 5%) during methoxamine infusion, whereas in 15 patients (group 2) LV ejection fraction was maintained. Peak filling rate was lower in group 1 versus group 2 (3.36 +/- 0.46 vs 4.23 +/- 0.68 end-diastolic volumes/sec, p < 0.01). In addition, patients in group 1 did not have LV dilatation during methoxamine (percentage change in end-diastolic counts, -3.4 +/- 6.9%) and had a large increase in pulmonary artery wedge pressure. In contrast, patients in group 2 had LV dilatation (percentage change in end-diastolic counts, +10.7 +/- 14.7%) and a smaller increase in pulmonary artery wedge pressure. There was a relationship between the baseline peak filling rate and the change in LV ejection fraction during methoxamine (r = 0.65, p = 0.001). Therefore in a subset of cardiac transplant patients, abnormalities in LV filling can have an impact on the response to increased afterload.

Right ventricular ejection fraction (RVEF), a measure of systolic pump performance of the right ventricle, is frequently depressed at rest or during exercise in patients with chronic obstructive pulmonary disease (COPD). The most common cause of reduced RVEF in COPD is augmentation of right ventricular afterload, namely an increase in pulmonary artery pressure and pulmonary vascular resistance. Therapy with agents that decrease the afterload on the right ventricle have the potential to improve the systolic performance of this chamber. Oxygen, vasodilators such as hydralazine and nifedipine, theophylline, and sympathomimetics all may augment RVEF in part by reducing pulmonary vascular resistance and, in some cases, pulmonary artery pressures in patients with COPD and cor pulmonale. However, only oxygen therapy has been shown to improve survival.

Propionibacterium acnes rarely causes systemic disease. Few cases of P. acnes endocarditis have been reported. This report describes a 63-year-old man who presented with severe congestive heart failure. He had prosthetic valve endocarditis which resulted in severe acute aortic insufficiency. During surgery he was found to have complete disruption of the aorta and left ventricle with a false aneurysm encompassing the circumference of the aortic annulus. Cultures of the valve grew P. acnes. Thus, although P. acnes is a rare cause of endocarditis, it may pursue a very aggressive course, especially in the setting of a prosthetic valve.

The individual and additive effects of positive end-expiratory pressure (PEEP) and right coronary artery (RCA) occlusion on left ventricular end-diastolic pressure-volume relations (LVEDPVR) were examined in six anesthetized dogs. Right ventricular (RV) and left ventricular (LV) ejection fractions (EF), end-diastolic volume (EDV) and end-systolic volumes (ESV) were measured by thermodilution as PEEP was added before and after RCA occlusion. PEEP alone caused a decline in cardiac output, transmural left atrial pressure (LAP) (6.0 +/- 0.6 to 3.2 +/- 1.4 mm Hg, p less than 0.05), and LVEDV (49 +/- 3 to 36 +/- 4 ml, p less than 0.05). RVEDV, the mean slope (+/- SD) of the LVEDPVR (0.37 +/- 0.16 to 0.30 +/- 0.19) and LAP at a common LV volume (35 ml, V35) did not change with PEEP. RCA occlusion caused cardiac output and RVEF (38 +/- 5 to 27 +/- 5%, p less than 0.05) to decline and RVESV (25 +/- 4 to 33 +/- 6 ml, p less than 0.05) to increase. RVEDV, the slope of the LVEDPVR, and LAP at V35 were unchanged from baseline. The addition of PEEP after RCA occlusion caused cardiac output to decline further. However, unlike before occlusion, there was no change in LAP (6.5 +/- 1.3 to 5.0 +/- 1.4 mm Hg) despite a decline in LVEDV (47 +/- 3 to 29 +/- 6 ml, p less than 0.05). RVESV and RVEDV increased with PEEP after RCA occlusion as did LAP at V35. The slope of the mean LVEDPVR tended to increase (0.98 +/- 1.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal pulmonary function that causes pulmonary artery hypertension increases right ventricular work. To compensate, the right ventricle enlarges, and cor pulmonale develops. Right ventricular failure occurs when these adaptive mechanisms cannot compensate for the hemodynamic burden. The various pulmonary diseases that are associated with right ventricular overload and the physiologic responses of the right ventricle to increased afterload are discussed in this article.

In 16 closed-chest dogs the hemodynamics of ECG-coupled jet ventilation (JV) with frequencies of 1:1 (one breath for each cardiac systole) and 1:2 (one breath for every other cardiac systole) were compared to noncoupled JV and intermittent positive-pressure ventilation (IPPV). Cardiac output was similar during 1:2 coupling (1.6 +/- 0.2 L/min) and IPPV (1.6 +/- 0.2 L/min) but decreased during 1:1 coupling (1.2 +/- 0.2 L/min) and noncoupled JV (1.3 +/- 0.2 L/min), p less than 0.05. During 1:2 coupling and IPPV, systemic arterial and transmural left atrial pressures were increased, and pulmonary artery, pericardial, and right atrial pressures were decreased in comparison to the other JV modes. Pulmonary blood volume was preserved during 1:2 coupling but decreased during 1:1 coupling and noncoupled JV. Coupling at 1:2 preserves output by maintaining left ventricular preload via a decrease in right atrial pressure and subsequent maintenance of systemic venous return.

A new miniaturized nonimaging radionuclide detector (Cardioscint, Oxford, England) was evaluated for the continuous on-line assessment of left ventricular function. This cesium iodide probe can be placed on the patient's chest and can be interfaced to an IBM compatible personal computer conveniently placed at the patient's bedside. This system can provide a beat-to-beat or gated determination of left ventricular ejection fraction and ST segment analysis. In 28 patients this miniaturized probe was correlated against a high resolution gamma camera study. Over a wide range of ejection fraction (31% to 76%) in patients with and without regional wall motion abnormalities, the correlation between the Cardioscint detector and the gamma camera was excellent (r = 0.94, SEE +/- 2.1). This detector system has high temporal (10 msec) resolution, and comparison of peak filling rate (PFR) and time to peak filling (TPFR) also showed close agreement with the gamma camera (PFR, r = 0.94, SEE +/- 0.17; TPFR, r = 0.92, SEE +/- 6.8). In 18 patients on bed rest the long-term stability of this system for measuring ejection fraction and ST segments was verified. During the monitoring period (108 +/- 28 minutes) only minor changes in ejection fraction occurred (coefficient of variation 0.035 +/- 0.016) and ST segment analysis showed no significant change from baseline. To determine whether continuous on-line measurement of ejection fraction would be useful after coronary angioplasty, 12 patients who had undergone a successful procedure were evaluated for 280 +/- 35 minutes with the Cardioscint system.(ABSTRACT TRUNCATED AT 250 WORDS)

Peak filling rate is an indicator of left ventricular (LV) diastolic function. It is influenced by heart rate, loading conditions, sympathetic nervous system activity, ejection fraction and other factors. To determine the effect of altered loading conditions on peak filling rate, independent of heart rate and sympathetic nervous system activity, 12 patients were studied 3 weeks after orthotopic heart transplantation. Plasma catecholamine level, heart rate and ejection fraction were not changed by any maneuver. Nitroglycerin caused a decrease in pulmonary artery wedge pressure (9 +/- 2 to 6 +/- 1 mm Hg, p less than 0.001) and in absolute peak filling rate (46.0 +/- 3.0 to 42.8 +/- 2.5 kcts/s, p less than 0.01), but no change in normalized peak filling rate. Volume infusion increased pulmonary artery wedge pressure (9 +/- 2 to 12 +/- 2 mm Hg, p less than 0.001) and absolute peak filling rate (46.0 +/- 3.0 to 51.5 +/- 5.3 kcts/s, p less than 0.01), but peak filling rate normalized to stroke volume was unchanged. During nitroglycerin and volume infusions, there was a high correlation between changes in pulmonary artery wedge pressure and absolute peak filling rate (r = 0.82, p less than 0.001). With normalization of peak filling rate, these variables correlated less well. With methoxamine, 4 patients demonstrating systolic dysfunction had a decrease in absolute and normalized peak filling rate despite a large increase in pulmonary artery wedge pressure. The other 8 patients without systolic dysfunction had an increase in pulmonary artery wedge pressure with increased absolute but unchanged normalized peak filling rate.(ABSTRACT TRUNCATED AT 250 WORDS)

The murine-derived monoclonal antibody OKT3 has been shown to be a useful immunosuppressive agent in transplant recipients; but it may cause cardiac instability and hemodynamic findings similar to those seen in septic shock after a first dose. Eight patients who received orthotopic heart transplants and were randomized to OKT3 therapy for immunosuppression were evaluated with serial hemodynamic and radionuclide monitoring for an 8-hour period during the first dose of OKT3. Cytokines including tumor necrosis factor-alpha, interleukin-1 and -2, and interferon-gamma were measured hourly to determine the potential mechanism of action of OKT3. All patients tolerated OKT3, although most had symptoms--pyrexia, chills, dyspnea, nausea and vomiting, and fever--within an hour after the dose. All patients exhibited a biphasic hemodynamic response to the first dose of OKT3. The initial hemodynamic response was characterized by a hyperdynamic phase with involvement in cardiac function as measured by cardiac output and ejection fraction. Left ventricular ejection fraction increased from 68% +/- 10% to 79 +/- 11% and was accompanied by increases in right ventricular ejection fraction and increases in cardiac index from 2.1 +/- 1.1 to 3.8 +/- 1.3 L/min/m2. The increase in ejection fraction was accompanied by a significant decrease in systemic vascular resistance index, from 2190 +/- 740 to 1608 +/- 573 dyne.sec.cm-5. The improvement in left ventricular ejection was caused by a significant decrease in end-systolic volume index (18 +/- 9.5 to 11 +/- 7 ml/m2). This occurred within the first 2 hours after OKT3 and was followed by cardiac index and ejection fraction returning to baseline in the next 2 to 3 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

We have discussed the complex hemodynamic changes that occur throughout the respiratory cycle during spontaneous and mechanical ventilation. In patients, many cumulative factors account for the total hemodynamic burden of inspiration and expiration. Thus, the change in pleural pressure, ventilation rate, mode of ventilation, amount of spontaneous ventilation, underlying lung and cardiac disease, and intravascular volume status all affect cardiocirculatory equilibrium. In addition, in the patient with ARDS, various immune mediators that are released into the circulation will affect LV function. Knowledge of the effects discussed in this article will aid the physician in choosing therapeutic options for patients with ARDS.

Normal left ventricular systolic performance with impaired left ventricular diastolic filling may be present in a substantial number of patients with congestive heart failure (CHF). To evaluate the effect of oral verapamil in this subset, 20 men (mean age 68 +/- 5 years) with CHF, intact left ventricular function (ejection fraction greater than 45%) and abnormal diastolic filling (peak filling rate less than 2.5 end-diastolic volumes per second [edv/s]) were studied in a placebo-controlled, double-blind 5-week crossover trial. All patients underwent echocardiography to rule out significant valvular disease, and thallium-201 stress scintigraphy to exclude major active ischemia. Compared to baseline values, verapamil significantly improved exercise capacity by 33% (13.9 +/- 4.3 vs 10.7 +/- 3.4 minutes at baseline) and peak filling rate by 30% (2.29 +/- 0.54 vs 1.85 +/- 0.45 edv/s at baseline) (all p less than 0.05). Placebo values were 12.3 +/- 4.0 minutes and 2.16 +/- 0.48 edv/s, respectively (difference not significant for both). Improvement from baseline in an objective clinico-radiographic heart failure score (scale 0 to 13) was significantly greater with verapamil compared to placebo (median improvement in score: 3 vs 1, p less than 0.01). Mean ejection fraction and systolic blood pressure were unchanged from baseline; diastolic blood pressure and heart rate decreased to a small degree. Verapamil may have therapeutic efficacy in patients with CHF, preserved systolic function and impaired diastolic filling.

The effect of positive end-expiratory pressure (PEEP) on right ventricular performance and myocardial blood flow was determined in 16 dogs before and after right coronary artery (RCA) occlusion. Right ventricular ejection fraction (RVEF), end-diastolic volume (EDV) and end-ejection volume were measured by thermodilution. Right ventricular end-ejection pressure-volume relations (RVEEPVR) were determined at baseline and at 20 cm H2O PEEP, both before and after RCA occlusion. In four of the dogs, RVEEPVR were also determined at 10 cm H2O PEEP after RCA occlusion. With intact RCA flow, RVEF declined with PEEP (37 +/- 5 to 19 +/- 6%) with no significant change in EDV (50 +/- 11 to 42 +/- 11 ml) or end-ejection volume (31 +/- 7 to 36 +/- 9 ml). RVEEPVR and right ventricular myocardial blood flow were also unchanged with PEEP. After RCA occlusion, RVEF declined with PEEP (27 +/- 4 to 15 +/- 5%) in association with a significant increase in end-ejection volume (39 +/- 8 to 49 +/- 10 ml), but no change in EDV (53 to 55 ml). In addition, RVEEPVR and myocardial blood flow declined with RCA occlusion, and declined further with 20 cm H2O, but not with 10 cm H2O PEEP, after RCA occlusion. Therefore, in this experimental model, right ventricular performance was adversely affected during PEEP when right coronary blood flow was limited.

Whether mitral insufficiency is a marker of decreased left ventricular function in patients undergoing aortic valve replacement for sever aortic stenosis was examined. Hemodynamic measurements in 26 patients with pure aortic stenosis (Group 1), 17 patients with aortic stenosis and grade 1 or 2 mitral insufficiency (Group 2) and 19 control patients were compared. All patients were free of significant coronary artery disease. Ventriculograms were digitized for calculation of ejection fraction, ventricular volumes and wall stress. Despite similar aortic valve areas, Group 2 patients had more advanced symptoms. Cardiac index was comparably decreased in Group 1 (2.6 +/- 0.4 liters/min per m2) and Group 2 (2.7 +/- 0.8 liters/min per m2) compared with the control group (3.8 +/- 0.6 liters/min per m2). Left ventricular end-diastolic and end-systolic volume indexes were increased only in Group 2 (119 +/- 35 and 73 +/- 36 ml/m2, respectively). Likewise, end-systolic wall stress was increased only in Group 2 (149 +/- 54 kdynes/cm2). Ejection fraction was decreased to a greater extent in Group 2 (42 +/- 17%) than in Group 1 (59 +/- 13%) as compared with values in the control group (68 +/- 5%). Although an inverse relation existed between ejection fraction and end-systolic stress in all groups, the ejection fraction (extrapolated to end-systolic stress = 0) was decreased in Group 2, and the slope of the relation was increased in Groups 1 and 2. The end-systolic stress/end-systolic volume index ratio, an index of ventricular performance, was also decreased to a greater extent in Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

14C-Morphine was injected iv in control awake rats or in rats subjected to metabolic alkalosis or acidosis. Ten minutes later, radioactivity was determined within each of seven brain regions, after correction was made for intravascular tracer. In each region, parenchymal radioactivity was correlated positively and significantly (P less than 0.05) with arterial blood pH. Brain radioactivity was twofold to threefold greater in alkalotic rats (mean pH = 7.62) than in acidotic rats (mean pH = 7.16). The results are consistent with the pH-partition hypothesis for drug entry into the brain and indicate that morphine uptake can be increased by elevating the fraction of lipid-soluble uncharged morphine base in blood, by means of alkalosis. The observations may account for an exaggerated morphine-induced analgesia in alkalotic patients.

Thirty-six patients with diverse baseline right ventricular function were evaluated during incremental positive end-expiratory pressure (PEEP) application. Right heart pressures, cardiac output, right ventricular ejection fractions, and ventricular volumes were obtained at each PEEP level. Right ventricular peak systolic pressure-end-systolic volume relations were analyzed as an index of contractile function. Patients with severely depressed baseline right ventricular ejection fractions (30 percent or less) had an increase in end-diastolic (270 +/- 74 to 391 +/- 76 ml, 0 to 20 cm water (H2O) PEEP, p less than 0.05) and end-systolic volumes (210 +/- 70 to 321 +/- 70 ml, 0 to 20 cm H2O PEEP, p less than 0.05). These patients also had a decline in estimated right ventricular contractile function at 20 cm H2O PEEP as estimated by the slope of systolic pressure-volume relations (0.12 to 0.04 mm Hg/ml, 0 to 15 and 15 to 20 cm H2O PEEP, respectively, p less than 0.05). Patients with normal (40 percent or more) or moderately depressed (31 to 40 percent) baseline right ventricular ejection fractions had no change in right ventricular volumes or estimated contractile function. Therefore, the effect of PEEP on right ventricular function differs depending on the baseline right ventricular ejection fraction.

To assess the potential effect of hypertension on the results of thallium-201 stress imaging in patients with chest pain, 272 thallium-201 stress tests performed in 133 hypertensive patients and 139 normotensive patients over a 1-year period were reviewed. Normotensive and hypertensive patients were similar in age, gender distribution, prevalence of cardiac risk factors (tobacco smoking, hyperlipidemia, and diabetes mellitus), medications, and clinical symptoms of coronary disease. Electrocardiographic criteria for left ventricular hypertrophy were present in 16 hypertensive patients. Stepwise probability analysis was used to determine the likelihood of coronary artery disease for each patient. In patients with mid to high likelihood of coronary disease (greater than 25% probability), abnormal thallium-201 stress images were present in 54 of 60 (90%) hypertensive patients compared with 51 of 64 (80%) normotensive patients. However, in 73 patients with a low likelihood of coronary disease (less than or equal to 25% probability), abnormal thallium-201 stress images were present in 21 patients (29%) of the hypertensive group compared with only 5 of 75 (7%) of the normotensive patients (p less than 0.001). These findings suggest that in patients with a mid to high likelihood of coronary artery disease, coexistent hypertension does not affect the results of thallium-201 exercise stress testing. However, in patients with a low likelihood of coronary artery disease, abnormal thallium-201 stress images are obtained more frequently in hypertensive patients than in normotensive patients.