Search

A body of research published over the past 20 years has revealed much concerning the prevalence, pathophysiology, and prognosis associated with MSI while also providing promising approaches to improving event-free survival rates in those who have this form of ischemia. Although many important questions remain, we believe that the findings to date provide sufficient evidence for the planning, development, and execution of a large-scale clinical trial. Such a trial would provide for not only further testing of prognostic significance and treatment effects but also explorations into important remaining questions of pathophysiology while elaborating possible additional modalities for treatment. Our collective expertise in nuclear cardiology provides an opportunity to establish the diagnostic standardization, approach, and assessment of prognosis and treatment. We are in a position to be thought leaders of a complex clinical manifestation of ischemia that has substantial clinical impact.

Background Animal studies have shown that early stressors result in lasting changes in structure and function of brain areas involved in memory, including hippocampus and frontal cortex. Patients with childhood abuse–related posttraumatic stress disorder (PTSD) have alterations in both declarative and nondeclarative memory function, and imaging studies in PTSD have demonstrated changes in function during stimulation of trauma-specific memories in hippocampus, medial prefrontal cortex, and cingulate. The purpose of this study was to assess neural correlates of emotionally valenced declarative memory in women with early childhood sexual abuse and PTSD. Methods Women with early childhood sexual abuse–related PTSD (n = 10) and women without abuse or PTSD (n = 11) underwent positron emission tomographic (PET) measurement of cerebral blood flow during a control condition and during retrieval of neutral (e.g., “metal-iron”) and emotionally valenced (e.g., “rape-mutilate”) word pairs. Results During retrieval of emotionally valenced word pairs, PTSD patients showed greater decreases in blood flow in an extensive area, which included orbitofrontal cortex, anterior cingulate, and medial prefrontal cortex (Brodmann’s areas 25, 32, 9), left hippocampus, and fusiform gyrus/inferior temporal gyrus, with increased activation in posterior cingulate, left inferior parietal cortex, left middle frontal gyrus, and visual association and motor cortex. There were no differences in patterns of brain activation during retrieval of neutral word pairs between patients and control subjects. Conclusions These findings are consistent with dysfunction of specific brain areas involved in memory and emotion in PTSD. Regions implicated in this study of emotionally valenced declarative memory are similar to those from prior imaging studies in PTSD using trauma-specific stimuli for symptom provocation, adding further supportive evidence for a dysfunctional network of brain areas involved in memory, including hippocampus, medial prefrontal cortex, and cingulate, in PTSD.

Objective: Animal studies have suggested that early stress is associated with alterations in the hippocampus, a brain area that plays a critical role in learning and memory. The purpose of this study was to measure both hippocampal structure and function in women with and without early childhood sexual abuse and the diagnosis of posttraumatic stress disorder (PTSD). Method: Thirty-three women participated in this study, including women with early childhood sexual abuse and PTSD (N=10), women with abuse without PTSD (N=12), and women without abuse or PTSD (N=11). Hippocampal volume was measured with magnetic resonance imaging in all subjects, and hippocampal function during the performance of hippocampal-based verbal declarative memory tasks was measured by using positron emission tomography in abused women with and without PTSD. Results: A failure of hippocampal activation and 16% smaller volume of the hippocampus were seen in women with abuse and PTSD compared to women with abuse without PTSD. Women with abuse and PTSD had a 19% smaller hippocampal volume relative to women without abuse or PTSD. Conclusions: These results are consistent with deficits in hippocampal function and structure in abuse-related PTSD.

OBJECTIVE Depression has been related to poor medical prognosis in patients with coronary artery disease and to diminished quality of life after coronary artery bypass graft surgery (CABG). However, prior studies have not fully examined the impact of depression on medical outcomes after CABG. The purpose of this study was to determine the independent contribution of presurgical depression to short-term medical outcome after CABG. METHODS Medical, surgical, and psychosocial risk factors were assessed before surgery in 89 male veterans undergoing CABG. In addition, patients completed the Beck Depression Inventory. Medical, surgical, and psychological/quality-of-life outcomes were determined at 6 months of follow-up by telephone interview and review of medical records. RESULTS Of the 89 patients studied, 25 scored 10 or greater on the Beck Depression Inventory. The study population was dichotomized on the basis of this cutoff point. A medical prediction model was developed for each outcome of interest, based on the range of medical, surgical, and psychosocial risk indices assessed. The dichotomized depression index was added to these prediction models as a final step. This depression index was found to independently predict cardiac hospitalizations at 6 months (chi(2) = 4.24, p

Imagine that you are stranded at the airport. You have spent a week at the meeting you were obliged to attend only to find that your flight is overbooked. It does not help that the agent at the counter does not pick up his head to make eye contact, and when he does, it is to smile “hello” to someone else. You insist that your reservation was made in advance and your ticket is in order; apparently, it is not the same information that the computer has on file. You will miss your child’s birthday and your work is piling on your desk and you are not there! Feelings of anger, disappointment, and guilt may occur alternatively and/or collectively. Often these emotional responses may be associated with diaphoresis, palpitations, headaches, and dizziness with or without chest pain. This all-too-common experience provides just one example of how the brain, in transducing the events going on around us, draws on past experience and learning history in the mobilization of a genetically programmed stress response that prepares the body for action no longer appropriate to the times. As a result, this brain-initiated mobilization that occurs chronically throughout one’s day results eventually in end organ damage, such as that associated with diseases of the heart. It is indeed remarkable how willing we are to accept these responses to our daily lives without thought to the long-term consequences. This review explores the relationship of our response to psychosocial stress and its influence on the presence and progression of coronary artery disease (CAD), with an emphasis on the brain-heart pathways that underlie the stress-disease relationship. We will discuss psychosocial stress from initiation in the central nervous system (CNS) to effector output to the cardiovascular system. This review will discuss cardinal questions concerning affect and the neurocardiac interaction and will address the following

Myocardial ischemia is associated with reduced free fatty acid (FFA) beta-oxidation and increased glucose utilization. This study evaluated the potential of dynamic SPECT imaging of a FFA analog, p-(123)I-iodophenylpentadecanoic acid (IPPA), for detection of ischemia and compares retention of IPPA with (18)F-FDG accumulation.In a canine model of regional low-flow ischemia (n = 9), serial IPPA SPECT images (2 min per image) were acquired over 52--90 min. In a subset of dogs (n = 6), (18)F-FDG was injected after completing SPECT imaging and allowed to accumulate for 40 min before killing the animals. Flow was assessed with radiolabeled microspheres. Myocardial metabolism was evaluated independently by selective coronary arterial and venous sampling.Serial IPPA SPECT images showed an initial defect in the ischemic region (0.70% plus minus 0.03% ischemic-to-nonischemic ratio), which normalized within 48 min because of the slower IPPA clearance from the ischemic region (t(1/2) = 54.2 plus minus 3.3 min) relative to the nonischemic region (t(1/2) = 36.7 plus minus 5.6 min) (P0.05). Delayed myocardial IPPA and (18)F-FDG activities were correlated (r = 0.70; n = 576 segments), and both were maximally increased in segments with a moderate flow reduction (IPPA, 151% of nonischemic; (18)F-FDG, 450% of nonischemic; P0.05).Serial SPECT imaging showed delayed myocardial clearance of IPPA in ischemic regions with moderate flow reduction, which lead to increased late myocardial retention of IPPA. Retention of IPPA correlated with (18)F-FDG accumulation, supporting the potential of IPPA as a noninvasive marker of ischemic myocardium.

The regional distribution in brain, distribution volumes, and pharmacological specificity of the PET 5-HT(2A) receptor radiotracer [(18)F]deuteroaltanserin were evaluated and compared to those of its non-deuterated derivative [(18)F]altanserin. Both radiotracers were administered to baboons by bolus plus constant infusion and PET images were acquired up to 8 h. The time-activity curves for both tracers stabilized between 4 and 6 h. The ratio of total and free parent to metabolites was not significantly different between radiotracers; nevertheless, total cortical R(T) (equilibrium ratio of specific to nondisplaceable brain uptake) was significantly higher (34-78%) for [(18)F]deuteroaltanserin than for [(18)F]altanserin. In contrast, the binding potential (Bmax/K(D)) was similar between radiotracers. [(18)F]Deuteroaltanserin cortical activity was displaced by the 5-HT(2A) receptor antagonist SR 46349B but was not altered by changes in endogenous 5-HT induced by fenfluramine. These findings suggest that [(18)F]deuteroaltanserin is essentially equivalent to [(18)F]altanserin for 5-HT(2A) receptor imaging in the baboon.

Background —Rapid reperfusion of an occluded coronary artery salvages regional mechanical function, but this benefit may not be realized for hours or days because of postischemic stunning. Recovery from stunning is incompletely understood but may involve adaptive changes in heart glucose metabolism. Methods and Results —To examine whether reversible coronary occlusion produces sustained changes in regional glucose metabolism in vivo, we performed a 20-minute left coronary artery occlusion followed by 24 hours of open-artery reperfusion in intact rats. Coronary occlusion produced stunning of the anterolateral left ventricle that resolved over 24 hours. When examined at 24 hours, reperfused regions were fully contractile and viable by vital staining and microscopy but demonstrated 25% reduction in blood flow and 50% increased uptake of circulating glucose, as estimated by in vivo [ 13 N]NH 3 and [ 18 F]fluorodeoxyglucose (FDG) tracer uptake. Reperfused regions had largely inactive glycogen synthase, low rates of glycogen synthesis, and persistent 50% glycogen depletion but increased flux of plasma [1- 13 C]glucose into myocardial [3- 13 C]alanine, indicating preferential shunting of imported glucose away from storage and into glycolysis. Conclusions —Sustained increases in regional glycolytic consumption of circulating glucose occur during reperfusion of a limited-duration coronary occlusion. This suggests a role for glycolytic ATP in the recovery from postischemic stunning in vivo. Furthermore, [ 13 N]NH 3 /FDG regional mismatch may constitute a clinically accessible late metabolic signature of regional myocardial ischemia.

Although positron emission tomography (PET) and single photon emission computed tomography (SPECT) are increasingly used for quantitation of neuroreceptor binding, almost no studies to date have involved a direct comparison of the two. One study found a high level of agreement between the two techniques, although there was a systematic 30% increase in measures of benzodiazepine receptor binding in SPECT compared with PET. The purpose of the current study was to directly compare quantitation of benzodiazepine receptor binding in the same human subjects using PET and SPECT with high specific activity [ 11 C]iomazenil and [ 123 I]iomazenil, respectively. All subjects were administered a single bolus of high specific activity iomazenil labeled with 11 C or 123 I followed by dynamic PET or SPECT imaging of the brain. Arterial blood samples were obtained for measurement of metabolite-corrected radioligand in plasma. Compartmental modeling was used to fit values for kinetic rate constants of transfer of radioligand between plasma and brain compartments. These values were used for calculation of binding potential (BP= B max / K d ) and product of BP and the fraction of free non-protein-bound parent compound (V3′). Mean values for V3′ in PET and SPECT were as follows: temporal cortex 23±5 and 22±3 ml/g, frontal cortex 23±6 and 22±3 ml/g, occipital cortex 28±3 and 31±5 ml/g, and striatum 4±4 and 7±4 ml/g. These preliminary findings indicate that PET and SPECT provide comparable results in quantitation of neuroreceptor binding in the human brain.

A complete remote control system was constructed for production of the PET 5-HT2A ligand [18F]altanserin by nitro-for-fluoro exchange. Comparing with published methods, the key features include (1) conducting azeotropic distillation and nucleophilic displacement in an open vessel heated by a commercial microwave oven; (2) purifying the product by a single HPLC procedure and (3) removing HPLC solvent by solid phase extraction. The preparation took 114 min with 23% yield and high quality.

Background: Patients with posttraumatic stress disorder (PTSD) show a reliable increase in PTSD symptoms and physiological reactivity following exposure to traumatic pictures and sounds. In this study neural correlates of exposure to traumatic pictures and sounds were measured in PTSD. Methods: Positron emission tomography and H 2 [ 15 O] were used to measure cerebral blood flow during exposure to combat-related and neutral pictures and sounds in Vietnam combat veterans with and without PTSD. Results: Exposure to traumatic material in PTSD (but not non-PTSD) subjects resulted in a decrease in blood flow in medial prefrontal cortex (area 25), an area postulated to play a role in emotion through inhibition of amygdala responsiveness. Non-PTSD subjects activated anterior cingulate (area 24) to a greater degree than PTSD patients. There were also differences in cerebral blood flow response in areas involved in memory and visuospatial processing (and by extension response to threat), including posterior cingulate (area 23), precentral (motor) and inferior parietal cortex, and lingual gyrus. There was a pattern of increases in PTSD and decreases in non-PTSD subjects in these areas. Conclusions: The findings suggest that functional alterations in specific cortical and subcortical brain areas involved in memory, visuospatial processing, and emotion underlie the symptoms of patients with PTSD.

More than any other discipline, nuclear cardiology has contributed to understanding of myocardial viability, including the concepts of hibernation and stunning. It must be recognized, however, that these concepts are used as models to drive the process of scientific inquiry. These models may describe components of the pathophysiology of ventricular dysfunction in CAD. Integration of the models of hibernation and stunning may represent the next step toward a more complete understanding of how CAD causes ventricular dysfunction. As such, we are now poised to redirect the field of viability assessment. Although the development of improved instrumentation, new tracers, and better software are important, the areas of investigation that will have the most significant effect on cardiology as a whole are those that will elucidate the pathophysiologic components of LV dysfunction in CAD. The knowledge can then be applied to clinical processes such as viability assessment, with attention to how new techniques affect prognosis and cost of health care. The nuclear imaging community should strive to develop techniques that are complementary to “competing” technologies such as magnetic resonance imaging and echocardiography, providing incremental information. Significant contributions to these lines of investigation will require cooperative studies to achieve adequate statistical power, including collaboration with the PET community. With studies addressing both the pathophysiology and the impact on clinical outcomes of myocardial viability and its assessment, the nuclear cardiology community will have much to contribute to our understanding of CAD.

The central nervous system (CNS) effects of mental stress in patients with coronary artery disease (CAD) are unexplored. The present study used positron emission tomography (PET) to measure brain correlates of mental stress induced by an arithmetic serial subtraction task in CAD and healthy subjects. Mental stress resulted in hyperactivation in CAD patients compared with healthy subjects in several brain areas including the left parietal cortex [angular gyrus/parallel sulcus (area 39)], left anterior cingulate (area 32), right visual association cortex (area 18), left fusiform gyrus, and cerebellum. These same regions were activated within the CAD patient group during mental stress versus control conditions. In the group of healthy subjects, activation was significant only in the left inferior frontal gyrus during mental stress compared with counting control. Decreases in blood flow also were produced by mental stress in CAD versus healthy subjects in right thalamus (lateral dorsal, lateral posterior), right superior frontal gyrus (areas 32, 24, and 10), and right middle temporal gyrus (area 21) (in the region of the auditory association cortex). Of particular interest, a subgroup of CAD patients that developed painless myocardial ischemia during mental stress had hyperactivation in the left hippocampus and inferior parietal lobule (area 40), left middle (area 10) and superior frontal gyrus (area 8), temporal pole, and visual association cortex (area 18), and a concomitant decrease in activation observed in the anterior cingulate bilaterally, right middle and superior frontal gyri, and right visual association cortex (area 18) compared with CAD patients without myocardial ischemia. These findings demonstrate an exaggerated cerebral cortical response and exaggerated asymmetry to mental stress in individuals with CAD.

The term "reverse redistribution" generally refers to a pattern characterized by the appearance of a worsening or new perfusion defect on thallium-201 redistribution imaging when compared with the stress image. More recently, the term has been applied to thallium imaging with resting reinjection and to imaging with technetium99m-based tracers. Although this phenomenon was initially reported nearly 20 years ago,l, 2 the pathophysiologic mechanisms and clinical significance remain poorly understood in all but a few clinical circumstances. As such, clinicians remain confused with regard to the interpretation of studies that manifest this finding. The reasons for the persistent confusion around reverse redistribution are revealed in part by examining the literature over the past two decades. In particular, study methodology has been quite variable. Most studies have been performed with stress-redistribution thallium scintigraphy. Others studies have been performed with rest-redistribution or stress-reinjection thallium imaging, whereas other recent reports have extended the term to include technetium-99m-based tracers. Instrumentation is another source of variability, with reports of this phenomenon in both planar and single-photon emission computed tomography (SPECT) modalities. Perhaps the greatest source of variability is in the patient populations studied. Examination of the literature therefore may be best accomplished by reducing this variability by grouping studies according to one of these parameters. The most clinically relevant examination is probably that which is based on the patient population studied.

Background: Short-term depletion of plasma tryptophan has been shown to result in depressive relapse in patients with remission of major depression. Positron emission tomography and single photon emission computed tomography studies implicated the dorsolateral prefrontal cortex, orbitofrontal cortex, thalamus, and caudate nucleus in the pathogenesis of depression. The purpose of this study was to measure cerebral metabolic correlates of tryptophan depletion—induced depressive relapse. Methods: Patients diagnosed as having major depression (N=21) who clinically improved with serotonin reuptake inhibitors underwent 2 test days involving tryptophan depletion or placebo, followed 6 hours later by positron emission tomography scanning with fludeoxy-glucose F18. Brain metabolism was compared in patients with (n=7) and without (n=14) a tryptophan depletion—induced depressive relapse. Results: Tryptophan depletion resulted in a decrease in brain metabolism in the middle frontal gyrus (dorsolateral prefrontal cortex), thalamus, and orbitofrontal cortex in patients with a depletion-induced depressive relapse (but not in patients without depletion-induced relapse). Decreased brain metabolism in these regions correlated with increased depressive symptoms. Baseline metabolism was increased in prefrontal and limbic regions in relapse-prone patients. Conclusion: Specific brain regions, including the middle frontal gyrus, thalamus, and orbitofrontal cortex, may mediate the symptoms of patients with major depression.

The diagnosis of pedal osteomyelitis is onen complicated by the presence of pre-existing bony abnormalities. In this study, the utility of radiolabeled white blood cell imaging for the detection of complicated pedal osteomyelitis was evaluated. Twenty-seven men and women were prospectively enrolled and underwent plain film radiography, three-phase bone scan, and Tc-99m hexamethylpro-pylamine oxine white blood cell scintigraphy of their feet. The presence or absence of osteomyelitis was confirmed in all subjects by microbiologic and histopathologic analysis of resected bone tissue. The results indicated that white blood cell imaging was more sensitive (90%) and specific (86%) for infection than either bone scan (75% sensitive, 29% specific) or plain film radiography (55% sensitive, 57% specific). This preliminary study suggests that Tc-99m hexamethylpropylamine oxine-labeled white blood cell scintigraphy is a simple, accurate test for the detection of pedal osteomyelitis.

Background Experimental data have indicated that [ 99m Tc]- nitroimidazole (BMS-181321) is preferentially taken up in hypoxic tissue; its kinetics, however, has not been fully investigated. The purpose of this study was to address the relation between perfusate oxygen level and myocardial retention of [ 99m Tc]nitroimidazole. Methods and Results Bolus injection and constant infusion experiments were performed in Langendorff buffer–perfused rat hearts in normoxic and hypoxic conditions. Data were acquired with a pair of NaI detectors. The initial clearance rate of [ 99m Tc]nitroimidazole was approximately 20 seconds and independent of perfusate oxygen level. The slow clearance rate was greater than 3 hours in all perfusion conditions. The tissue retention of [ 99m Tc]nitroimidazole varied from 0.61±0.14% in normoxic conditions to 5.94±1.16% in the most severe hypoxic conditions. In addition, tissue retention was inversely proportional to perfusate oxygen level in a sigmoidal manner. The constant infusion experiments established that the binding rate at 25% oxygen level (1.94±0.38 mL of perfusate/min−g dry wt) was twofold of that at 40% and sevenfold at 100%. The binding rate of [ 99m Tc]nitroimidazole was independent of the perfusion sequence, suggesting irreversible binding. Conclusions These data indicate that [ 99m Tc]nitroimidazole may be a useful tracer for the identification of myocardial hypoxia. A sigmoidal relation was demonstrated for the uptake of the tracer, which suggests that a threshold level of hypoxia is necessary for the uptake of the tracer.

Technetium-99m methoxyisobutyl isonitrile (technetium-99m sestamibi [MIBI]) is distributed in the myocardium according to blood flow. Reports comparing stress rest sestamibi protocols with reinjection thallium or resting fluorodeoxyglucose (FDG), or both, in patients with coronary artery disease have shown appreciable discordance regarding myocardial viability in these settings. We performed this analysis with regard to regional comparisons within discordant segments and made comparisons in a subset of patients who underwent revascularization. Thirty-seven patients with coronary artery disease had single-photon emission computed tomography MIBI, N-13 ammonia/18FDG positron emission tomography (PET), and radionuclide ventriculography performed at rest. One hundred two segments were viable and 29 were nonviable by both MIBI and FDG. The concordance was 71%. In MIBI nonviable/FDG viable segments, most of the discordance was in the inferior wall. In MIBI nonviable discordant segments, FDG accurately predicted an increase in percent regional ejection fraction (preoperative 36% [+/- 5 SE] to postoperative 48% [+/- 5.5 SE][p < 0.0006]). MIBI underestimates myocardial viability as assessed by PET. Seventy-one percent of myocardial segments were concordant by both quantitative sestamibi single-photon emission computed tomography and FDG PET. Discordance in MIBI nonviable segments was predominantly in the inferior wall. PET can be helpful in detecting myocardial viability in patients suspected of having had MIBI nonviability in the inferior wall.

Reverse redistribution (RR) of thallium-201 has been associated with both acute and healed myocardial infarction, and with recent thrombolysis. The physiologic basis for RR in coronary artery disease (CAD) is unclear but may be related to an admixture of viable and scarred myocardium within the RR segment. We performed thallium reinjection imaging at rest to better characterize RR defects in patients with chronic CAD. We found enhanced uptake of 201Tl in 52% of RR segments after reinjection, consistent with significant regional viability that was not evident on redistribution images. We then used a logistic multiple regression analysis to determine whether RR alone or in combination with other scintigraphic findings could predict patient outcome. The results showed that severe RR was an independent predictor of patient outcome. We conclude that RR may have prognostic significance in chronic CAD.

The radionuclide measurement of diastolic performance may provide a rapid noninvasive index available in the clinical setting. These measurements may be used to detect coronary artery disease, manifestations of hypertensive heart disease, isolated diastolic heart failure, and hypertrophic cardiomyopathy. The various radionuclide methods to measure diastolic filling are influenced by technological considerations, as well as applying the results in the appropriate clinical context. The importance of these derived measurements and how they correspond to various pathophysiological presentations will be discussed.

Positron emission tomography was used to quantify changes in myocardial blood flow during mental stress in patients with and without coronary artery disease. Blunted augmentation of myocardial blood flow during mental stress was observed in regions without significant epicardial stenosis.

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.

Mental and emotional stress can provoke transient ischemia and acute coronary syndrome in vulnerable patients. Furthermore, those patients so provoked are at increased risk for recurrent cardiac events and early death. Viable psychological treatments to improve prognosis exist, and preliminary trials demonstrate their efficacy with regard to short- and long-term outcomes, as well as economic savings. These findings heighten the need for efforts directed toward the complete identification of the differential pathophysiology of mental stress-induced ischemia, with an eye toward development of diagnostic tests and establishment of risk stratification algorithms that can be applied in the clinical setting. Ongoing research in this vein is identifying unique aspects of the brain-heart relationship during mental stress that underlie the cognitive and emotional aspects of mental stress, and the "dow nwind" pathways by which distinct patterns of brain activity during mental stress can provoke otherwise silent myocardial ischemia. This research is making important contributions to the larger clinical goals associated with diagnostic testing, risk stratification, and treatment of patients at risk for mental stress-induced ischemia and poorer prognosis.

Background: Mentally stressful tasks produce myocardial ischemia in patients with chronic coronary artery disease (CAD) and changes in autonomic response have been implicated in its pathogenesis. The aim of this study was to determine whether MS-induced myocardial ischemia (MSI) assessed by concurrent non-invasive imaging of perfusion and/or function is associated with parasympathetic withdrawal. Methods: In 19 pts with chronic CAD, we performed simultaneous SPECT MPI, HRV analysis, and echocardiography (echo) at baseline and during MS. MS was performed using a mental arithmetic task. MSI was defined as MS-induced MPI defects and/or regional LV dysfunction by echo. HRV was quantified using spectral analysis. Results: Eleven (58%) of 19 pts had evidence of MS induced myocardial ischemia (8 MPI defects, 4 wall motion abnormalities by echo). High frequency (HF) power decreased significantly in those patients with MS-induced ischemia but did not change in those without MS-ischemia (see table below) * . HF Baseline (Ln msec2) HF MS (Ln msec2) MS ischemia (n = 11) 4.36 ± 0.32 3.75 ± 0.26 * No MS ischemia (n = 9) 4.68 ± 0.38 4.97 ± 0.31 * (p Among pts with MS ischemia, the greatest decrement in HF was observed in pts with MS-induced SPECT defects compared to those with MS-induced regional LV dysfunction. Patients with MS ischemia had a greater increase in rate-pressure product during MS than those without ischemia (58+20% vs. 34+20% increase, p Conclusion: Patients with MS-induced myocardial ischemia during MPI and/or echo show evidence of greater parasympathetic withdrawal. The association of parasympathetic withdrawal to MSI defined by SPECT was more robust than MSI defined by echocardiogram. Future studies using MPI are warranted to determine the precise role of sympathovagal balance in individual patients susceptible to MS ischemia.

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 (H 2 O) PEEP, p 2 O PEEP, p 2 O 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 H 2 O PEEP, respectively, p

Using a combined hemodynamic and radionuclide technique, 20 patients with varied ventricular function were evaluated during positive end-expiratory pressure (PEEP) application. Left ventricular (LV) and right ventricular (RV) ejection fractions and cardiac output were measured, and ventricular volumes were derived. Seven patients (group 1) who had an increase in LV end-diastolic volume with PEEP and 13 patients (group 2) who had the more typical response, a decrease in LV end-diastolic volume with PEEP, were identified. Compared with group 2, group 1 patients had a higher incidence of coronary artery disease (5 of 7 vs 1 of 13, p less than 0.005) and lower cardiac output (3.9 +/- 1.6 vs 9.1 +/- 3.2 liters/min, p less than 0.005), LV ejection fraction (27 +/- 13 vs 51 +/- 21%, p less than 0.05), RV ejection fraction (15 +/- 6 vs 32 +/- 8%, p less than 0.005) and peak filling rate (1.32 +/- 0.43 vs 3.51 +/- 1.70 end-diastolic volumes/s, p less than 0.05). LV and RV volumes increased and peak filling rate decreased with PEEP in group 1, whereas in group 2 LV volume decreased and RV volume and peak filling rate remained unchanged. Using stepwise regression analysis, the change in LV volume with PEEP was related directly to baseline systemic vascular resistance and inversely to baseline blood pressure. Similarly, the change in peak filling rate with PEEP was inversely related to the change in RV end-diastolic volume. Thus, the hemodynamic response to PEEP is heterogeneous and may be related to LV ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: We have previously reported an increase in symptoms of anxiety in patients with posttraumatic stress disorder (PTSD) following administration of the β2-antagonist yohimbine, which stimulates brain norepinephrine release. Preclinical studies show decreased metabolism in the neocortex and the caudate nucleus with high-dose yohimbine-induced norepinephrine release, but low levels of norepinephrine release result in an increase in metabolism in these areas. Methods: We used positron emission tomography and fludeoxyglucose F 18 to measure brain metabolism in Vietnam combat veterans with PTSD (n=10) and healthy age-matched control subjects (n=10), following administration of yohimbine (0.4 mg/kg) or placebo in a randomized, double-blind fashion. Results: Yohimbine resulted in a significant increase in anxiety in the patients with PTSD, but not in healthy subjects. There was a significant difference in brain metabolic response to yohimbine in patients with PTSD compared with healthy subjects in prefrontal, temporal, parietal, and orbitofrontal cortexes. Metabolism tended to decrease in patients with PTSD and increase in healthy subjects following administration of yohimbine. Conclusion: These findings are consistent with our previous hypothesis of enhanced norepinephrine release in the brain with yohimbine in patients with PTSD.

Ventricular wall motion abnormalities at rest aie believed to be indicative of myocardial scar and fibrous tissue. Although patients may have reversible wall motion abnormalities at rest during periods of ischemia, recent evidence suggests that reversible ventricular dysfunction can persist after a major ischerqic insu1t.Q Braunwald and Rutherford 3 distinguish between stunned and hibernating myocardium and suggest that in either situation, revascularization can reverse exercise-induced ischemic dysfunction. 4,5 However, reversal of prolonged resting ventricular dysfunction is not as clear. We report a patient with severe coronary artery disease without myocardial infarction who had complete reversal of marked left ventricular (LV) dys-function.

The effects of incremental positive end-expiratory pressure (PEEP) on right ventricular RV) function were evaluated in 36 (n = 36) ventilated patients. Positive end-expiratory pressure was increased from 0 (baseline) to 20 cm H2O in 5-cm H2O increments and RV hemodynamics and thermally derived right