Sumatriptan alleviates nitroglycerin-induced mechanical and thermal allodynia in mice.

The association between the clinical use of nitroglycerin (NTG) and headache has led to the examination of NTG as a model trigger for migraine and related headache disorders, both in humans and laboratory animals. In this study in mice, we hypothesized that NTG could trigger behavioural and physiological responses that resemble a common manifestation of migraine in humans. We report that animals exhibit a dose-dependent and prolonged NTG-induced thermal and mechanical allodynia, starting 30-60 min after intraperitoneal injection of NTG at 5-10 mg/kg. NTG administration also induced Fos expression, an anatomical marker of neuronal activity in neurons of the trigeminal nucleus caudalis and cervical spinal cord dorsal horn, suggesting that enhanced nociceptive processing within the spinal cord contributes to the increased nociceptive behaviour. Moreover, sumatriptan, a drug with relative specificity for migraine, alleviated the NTG-induced allodynia. We also tested whether NTG reduces the threshold for cortical spreading depression (CSD), an event considered to be the physiological substrate of the migraine aura. We found that the threshold of CSD was unaffected by NTG, suggesting that NTG stimulates migraine mechanisms that are independent of the regulation of cortical excitability.

Medical students' attitudes towards abortion: a UK study.

BACKGROUND: There is little research into medical students' or doctors' attitudes to abortion, yet knowing this is important, as policy makers should be aware of the views held by professionals directly involved in abortion provision and changing views may have practical implications for the provision of abortion in the future. METHODS: We surveyed 300 medical students about their views on abortion, their beliefs about the status of the fetus and the rights of the mother, their attitude towards UK law and their willingness to be involved in abortion provision as qualified doctors. RESULTS: 62% of medical students were pro-choice, 33% pro-life and 7% undecided. Students' views correlated with gender, year of study and holding a religious belief. Their beliefs about abortion, the status of the fetus and the rights of women significantly correlated with their attitudes towards the UK law and their willingness to be involved in abortion provision. Students' willingness to be involved in abortion provision was related to their views on abortion, the extent of participation required, the circumstances of the pregnancy and the stage of pregnancy. CONCLUSIONS: The percentage of pro-choice students was lower than that found in research on general practitioners' attitudes to abortion. It is unclear whether this is because students become more pro-choice as they progress through their medical career or because there is genuinely a change in attitudes to abortion.

Design and experimental results of the 1-T Bitter Electromagnet Testing Apparatus (BETA).

The Bitter Electromagnet Testing Apparatus (BETA) is a 1-Tesla (T) technical prototype of the 10 T Adjustable Long Pulsed High-Field Apparatus. BETA's final design specifications are highlighted in this paper which include electromagnetic, thermal, and stress analyses. We discuss here the design and fabrication of BETA's core, vessel, cooling, and electrical subsystems. The electrical system of BETA is composed of a scalable solid-state DC breaker circuit. Experimental results display the stable operation of BETA at 1 T. These results are compared to both analytical design and finite element calculations. Experimental results validate analytical magnet designing methods developed at the Dusty Plasma Laboratory. The theoretical steady state maxima and the limits of BETA's design are explored in this paper.

Systematic review of the effectiveness of community-based self-management interventions among primary care COPD patients.

COPD self-management reduces hospital admissions and improves health-related quality of life (HRQoL). However, whilst most patients are managed in primary care, the majority of self-management trials have recruited participants with more severe disease from secondary care. We report the findings of a systematic review of the effectiveness of community-based self-management interventions in primary care patients with COPD. We systematically searched eleven electronic databases and identified 12 eligible randomised controlled trials with seven included in meta-analyses for HRQoL, anxiety and depression. We report no difference in HRQoL at final follow-up (St George's Respiratory Questionnaire total score -0.29; 95%CI -2.09, 1.51; I2 0%), nor any difference in anxiety or depression. In conclusion, supported self-management interventions delivered in the community to patients from primary care do not appear to be effective. Further research is recommended to identify effective self-management interventions suitable for primary care populations, particularly those with milder disease.

Neutrophil migration inhibitory properties of polyunsaturated fatty acids. The role of fatty acid structure, metabolism, and possible second messenger systems.

The n-3 polyunsaturated fatty acids (PUFA) appear to have antiinflammatory properties that can be partly explained by their biological activity on leukocytes. Since leukocyte emigration is an essential component of the inflammatory response, we have examined the effects of the n-3 PUFA (eicosapentaenoic and docosahexaenoic acids) on neutrophil random and chemotactic movement. Preexposure of neutrophils for 15-30 min to 1-10 micrograms/ml PUFA reduced the random and chemotactic migration to both FMLP- and fungi-activated complement. The inhibitory effect diminished with increasing saturation and carbon chain length, and methylation abolished this activity. Arachidonic and docosahexaenoic acids were the most active fatty acids. The PUFA concentration required to inhibit migration was dependent on cell number, suggesting that the fatty acid effects on leukocyte migration in vivo may be governed by the stage of the inflammatory response. It was concluded that the PUFA rather than their metabolites were responsible for the inhibition since: (a) antioxidants did not prevent the PUFA-induced migration inhibition and the hydroxylated intermediates were less active, and (b) inhibitors of the cyclooxygenase and lipoxygenase pathways were without effect. Inhibitors of protein kinases and calmodulin-dependent enzyme system did not prevent the PUFA-induced migration inhibition, which was also independent of phospholipase D-catalyzed hydrolysis of phospholipids. It is also shown that PUFA decrease the FMLP-induced Ca2+ mobilization.

Action and object processing in aphasia: from nouns and verbs to the effect of manipulability.

The processing of words and pictures representing actions and objects was tested in 21 aphasic patients and 20 healthy controls across three word production tasks: picture-naming (PN), single word reading (WR) and word repetition (WRP). Analysis 1 targeted task and lexical category (noun-verb), revealing worse performance on PN and verb items for both patients and control participants. For Analysis 2 we used data collected in a concurrent gesture norming study to re-categorize the noun-verb items along hand imagery parameters (i.e., objects that can/cannot be manipulated and actions which do/do not involve fine hand movements). Here, patients displayed relative difficulty with the 'manipulable' items, while controls displayed the opposite pattern. Therefore, whereas the noun-verb distinction resulted simply in lower verb accuracy across groups, the 'manipulability' distinction revealed a 'double-dissociation' between patients and control participants. These results carry implications for theories of embodiment, lexico-semantic dissociations, and the organization of meaning in the brain.

Emergency percutaneous coronary intervention (PCI) for the care of patients with ST-elevation myocardial infarction (STEMI).

There is general consensus that emergency percutaneous coronary intervention (PCI) is the preferred treatment for patients with ST-elevation myocardial infarction (STEMI), so long as it can be delivered in a timely fashion, by an experienced' operator and cardiac catheterization laboratory (CCL) team. STEMI is both a functional and structural issue. Although it has been recognized since the work of pioneering cardiologists and surgeons in Spokane, Washington, that approximately 88% of patients presenting within 6 hours of onset of STEMI have an occluded coronary artery, it is the pathophysiology of myocardial necrosis, and the varied consequences of necrosis that characterize STEMI. Accordingly, experience' of both primary operator and cardiac catheterization laboratory (CCL) crew, in performing an emergency PCI for STEMI, are as much a function of experience with the treatment of complex MI patients, as experience with coronary intervention. Rapidly achieving normal coronary artery flow, at both the macro and micro vascular levels, is the recognized key to aborting the otherwise progressive wavefront' of myocardial necrosis. The time urgency of decisions (Time is muscle') make emergency PCI for patients with on-going necrosis, more like emergency room (ER) care, than like most in-hospital or outpatient care. In general, most patients with acute coronary syndromes (ACS) are currently thought to have plaque rupture and/or erosion with subsequent thrombosis and embolization. Consequences of thrombo-embolism, such as slow flow' or no-reflow' are in addition to, the structural (anatomic) considerations of PCI in stable patients (such as ostial location; bifurcation involvement; heavy calcification; tortuosity of lesion or access to it; length of disease; caliber of infarct-artery; etc.). Good quality studies have provided strong support for the specific added value of glycoprotein IIb/IIIa inhibitors (especially abciximab), dual antiplatelet therapy (the addition of the thienopyridine, clopidogrel, to aspirin use), and bare-metal stents (BMS), for a broad range of STEMI patients. The added value of drug-eluting stents (DES) to bare-metal stents (BMS), primarily in terms of reducing restenosis and repeat revascularization, is supported by several randomized trials, and a number of registries, despite its being off-label' from a regulatory standpoint. The recognition of late stent thrombosis (LST) has raised additional issues, in choosing between these two options for specific STEMI patients. The added value of a number of other mechanical approaches to coronary thrombus, such as thrombus removal devices, and/or distal protection, are more controversial, and perhaps, patient specific. Whether intravascular ultrasound guidance (IVUS) for stent use should be used for the majority, or even a specific minority, of STEMI patients, is also controversial; late-stent thrombosis provides a counter-point. The advantages of developing a network approach to STEMI care, so as to optimize the number of patients receiving timely reperfusion, have been demonstrated in Prague, Denmark, and Minneapolis, among many places. The benefits of both bivalirudin (anti-thrombin drug with efficacy against clot-bound thrombin, which does not appear to stimulate platelets) and abciximab (glycoprotein IIb/IIIa inhibitor which is antibody to platelet receptors), as PCI adjuncts generally, and for STEMI patients, in particular, are supported by multiple trials. The specific choice of administering the bolus dose of either, or both, drugs via intra-coronary (IC) injection follows the precedents' of IC thrombolytics, and IC small-vessel vasodilators for no-reflow', but it has not been tested by prospective, randomized trials. Although rapid reperfusion is the first objective, one cannot ignore the other components of the oxygen delivery chain, and the importance of each of these components to on-going delivery of oxygen to all vital organs. A balance must be struck between doing those control' things which serve to stabilize other vital components of the oxygen-delivery chain, without digressing too long from the job of re-establishing brisk coronary flow. The clinical and angiographic heterogeneity of STEMI patients and the array of available therapeutic approaches make it impossible to obtain specific randomized trial direction for many of the clinical decisions in an individual emergency PCI for STEMI. There are a range of reasonable/ appropriate therapeutic choices for a given emergent PCI performed by multiple experienced and competent operators. The treatment of STEMI, and high-risk non-STEMI, patients, by means of emergent PCI, is among the most challenging and rewarding arenas in contemporary medicine.

Language development.

Recent research suggests that our ability to learn language is innate, but not necessarily domain-specific. That is, language development appears to be based on a relatively plastic mix of neural systems that also serve other cognitive and perceptual functions. Evidence in support of this conclusion includes neural network simulations of language learning, event-related brain potential studies of normal language development, and studies of language development in several clinical populations of subjects suffering focal brain injury, specific language impairment, and contrasting forms of mental retardation.

Poly(A)-binding protein I of Leishmania: functional analysis and localisation in trypanosomatid parasites.

Regulation of gene expression in trypanosomatid parasites is predominantly post-transcriptional. Primary transcripts are trans-spliced and polyadenylated to generate mature mRNAs and transcript stability is a major factor controlling stage-specific gene expression. Degenerate PCR has been used to clone the gene encoding the Leishmania homologue of poly(A)-binding protein (Lm PAB1), as an approach to the identification of trans-acting factors involved in this atypical mode of eukaryotic gene expression. lmpab1 is a single copy gene encoding a 63 kDa protein which shares major structural features but only 35-40% amino acid identity with other PAB1 sequences, including those of other trypanosomatids. Lm PAB1 is expressed at constant levels during parasite differentiation and is phosphorylated in vivo. It is localised predominantly in the cytoplasm but inhibition of transcription with actinomycin D also reveals diffuse localisation in the nucleus. Lm PAB1 binds poly(A) with high specificity and affinity but fails to complement a null mutation in Saccharomyces cerevisiae. These properties are indicative of functional divergence in vivo.

Inhibition of proteoglycan synthesis by hydrogen peroxide in cultured bovine articular cartilage.

Oxygen-derived reactive species, generated enzymatically by the action of xanthine oxidase upon hypoxanthine, significantly inhibit proteoglycan synthesis by cultured bovine articular cartilage (Bates, E.J., Lowther, D.A. and Handley, C.J. (1984) Ann. Rheum. Dis. 43, 462-469). Here we extend these investigations and show, through the use of catalase and the specific iron chelator diethylenetriaminepentaacetic acid, that the active species involved is H2O2 and not the hydroxyl radical. Incubations of cartilage with H2O2 at concentrations of 1 X 10(-4) M and above are also inhibitory to proteoglycan synthesis. Subsequent recovery of the tissue is dependent upon the initial dose of xanthine oxidase or H2O2. Xanthine oxidase at 84 mU per incubation results in a prolonged inhibition of proteoglycan synthesis which is still apparent after 14 days in culture. Lower concentrations of xanthine oxidase (21-66 mU) are inhibitory to proteoglycan synthesis, but the tissue is able to synthesise proteoglycans at near normal rates after 3 days in culture. The inhibition of proteoglycan synthesis by 1 X 10(-4) M H2O2 is completely reversed after 5 days in culture, whereas 1 X 10(-3) M H2O2 results in a more prolonged inhibition. The synthesis of the proteoglycan core protein is inhibited, but the ability of the newly formed proteoglycans to aggregate with hyaluronic acid is unimpaired.

IL-8 is an angiogenic factor in human coronary atherectomy tissue.

BACKGROUND: Interleukin-8 (IL-8), a CXC chemokine that induces the migration and proliferation of endothelial cells and smooth muscle cells, is a potent angiogenic factor that may play a role in atherosclerosis. Previously, IL-8 has been reported in atherosclerotic lesions and circulating macrophages from patients with atherosclerosis. Therefore, we sought to determine whether IL-8 plays a role in mediating angiogenic activity in atherosclerosis. METHODS AND RESULTS: Homogenates from 16 patients undergoing directional coronary atherectomy (DCA) and control samples from the internal mammary artery (IMA) of 7 patients undergoing bypass graft surgery were assessed for IL-8 content by specific ELISA, immunohistochemistry, and in situ hybridization for IL-8 mRNA. The contribution of IL-8 to net angiogenic activity was assessed using the rat cornea micropocket assay and cultured cells. IL-8 expression was significantly elevated in DCA samples compared with IMA samples (1.71+/-0.6 versus 0.05+/-0.03 ng/mg of total protein; P<0.01). Positive immunolocalization of IL-8 was found exclusively in DCA tissue sections, and it correlated with the presence of factor VIII-related antigen. In situ reverse transcriptase polymerase chain reaction revealed the expression of IL-8 mRNA in DCA tissue. Corneal neovascular response, defined by ingrowth of capillary sprouts toward the implant, was markedly positive with DCA pellets, but no constitutive vessel ingrowth was seen with IMA specimens. Neutralizing IL-8 attenuated both the in vivo corneal neovascular response and the in vitro proliferation of cultured cells. CONCLUSIONS: The results suggest that, in human coronary atherosclerosis, IL-8 is an important mediator of angiogenesis and may contribute to plaque formation via its angiogenic properties.

Cardiogenic shock in patients with acute ischemic syndromes with and without ST-segment elevation.

BACKGROUND: Cardiogenic shock is usually considered a sequela of ST-segment elevation myocardial infarction. There are limited prospective data on the incidence and significance of shock in non-ST-segment elevation patients. This study assessed the incidence and outcomes of cardiogenic shock developing after enrollment among patients with and without ST-segment elevation in the Global Use of Strategies To Open Occluded Coronary Arteries (GUSTO)-IIb trial. METHODS AND RESULTS: Among 12,084 patients in GUSTO-IIb who did not present with cardiogenic shock, 4092 (34%) had and 7991 (66%) did not have ST-segment elevation on the enrollment ECG. Cardiogenic shock developed in 4.2% of ST-segment elevation patients compared with 2.5% of patients without ST-segment elevation (odds ratio, 0. 581; 95% CI, 0.472 to 0.715; P<0.001). Shock developed significantly later among patients without ST-segment elevation. There were significant differences in baseline characteristics between shock patients with and without ST-segment elevation: Patients without ST-segment elevation were older, more frequently had diabetes mellitus and 3-vessel disease, but had less TIMI grade 0 flow at angiography. Regardless of the initial ECG, mortality was high: 63% among patients with ST-segment elevation and 73% in those without ST-segment elevation. CONCLUSIONS: Cardiogenic shock occurs in the setting of acute ischemic syndromes regardless of whether ST-segment elevation is present. The incidence, patient characteristics, timing, clinical course, and angiographic findings differ between the 2 groups. Mortality from cardiogenic shock is similarly high among patients with and without ST-segment elevation.

Reperfusion therapy in inferior myocardial infarction.

This review summarizes the multicenter trial results of reperfusion therapy for treatment of inferior myocardial infarction. Therapy with intracoronary streptokinase or intravenous recombinant tissue plasminogen activator (rt-PA) produced higher patency rates than did intravenous streptokinase. Reocclusion was more common when the right coronary artery was the infarct-related artery, irrespective of treatment strategy. Left ventricular ejection fraction was improved compared with that in control patients, especially when the time from symptom onset was brief or when patency rates were high. Enzymatic infarct size was reduced in treated patients. A trend toward mortality reduction in treated patients was found in four studies and was statistically significant in the Second International Study of Infarct Survival (ISIS-2) trial. Precordial ST segment depression in inferior myocardial infarction is associated with values for enzyme release, left ventricular ejection fraction and mortality similar to those in anterior infarction. Patients with inferior infarction who present within 6 h of symptom onset with precordial ST segment depression should be considered candidates for intravenous thrombolytic therapy with rt-PA; immediate cardiac catheterization and possible coronary angioplasty should be limited to those who are in hemodynamically unstable condition. Patients without precordial ST segment depression who present within 3 h of symptom onset and who do not have risk factors for bleeding should also be candidates for intravenous rt-PA therapy. The prognosis of other patients with inferior myocardial infarction is so good that the issue of thrombolytic therapy remains unsettled.

Revisiting reperfusion therapy in inferior myocardial infarction.

Although thrombolytic therapy for acute myocardial infarction (MI) is recommended without regard for infarct location, treatment results are less impressive for inferior than for anterior MI because the amount of myocardium at risk is smaller and less strategically located, and the mortality risk is lower. Whereas the risks associated with anterior MI are relatively constant, high risk subsets of patients with an inferior MI can be identified by simple electrocardiographic criteria, including left precordial ST segment depression, complete atrioventricular heart block and right precordial ST segment elevation. Unfortunately, none of the placebo-controlled, randomized trials have analyzed the benefit of thrombolytic therapy for inferior MI in high risk versus low risk subsets. Thrombolytic therapy should be more successful in reducing infarct size and decreasing mortality in high risk patients with an inferior MI. Thrombolytic therapy may not decrease hospital mortality in low risk patients (baseline risk 2% to 4%) or those with symptom duration > 6 h. Whereas it is arguable whether coronary angioplasty is superior to thrombolytic therapy in anterior MI, there are no mortality data to support using angioplasty as a primary or rescue reperfusion strategy instead of thrombolytic therapy in inferior MI, unless thrombolytic contraindications are present or the patient is in cardiogenic shock.

Limitations of thrombolytic therapy for acute myocardial infarction complicated by congestive heart failure and cardiogenic shock.

As many as one quarter of patients treated with thrombolytic therapy present with congestive heart failure or cardiogenic shock. Although thrombolytic therapy has been shown to limit infarct size, preserve left ventricular ejection fraction and decrease mortality in most subgroups of patients, no apparent benefit has been demonstrated in patients with clinical left ventricular dysfunction. The lack of correlation between ejection fraction and other measurements of left ventricular dysfunction such as exercise time, cardiac output, filling pressures, activation of the neurohumoral system and regional perfusion bed abnormalities may partly explain this paradox. Alternatively, lower perfusion rates, higher reocclusion rates, associated mechanical complications or completed infarction may explain these findings. Preliminary data indicate that emergency coronary angioplasty or bypass graft surgery improves survival in selected patients with cardiogenic shock. Because these findings suggest that restoration of infarct artery patency is especially important in patients with clinical left ventricular dysfunction, additional studies are needed in these patients to investigate the potential benefit that new thrombolytic strategies, inotropic or vasodilator agents or intraaortic balloon counterpulsation might offer by augmenting coronary blood flow and improving reperfusion rates. Currently, acute mechanical revascularization should be considered for patients who present with congestive heart failure associated with hypotension or tachycardia and for patients with cardiogenic shock.

Treatment of recurrent ischemia after thrombolysis and successful reperfusion for acute myocardial infarction: effect on in-hospital mortality and left ventricular function.

To determine the effect of treatment of recurrent ischemia after reperfusion for acute myocardial infarction on in-hospital mortality and left ventricular function recovery and to identify patients at highest risk of serious consequences in the event of recurrent ischemia in this setting, 405 consecutively treated patients were studied retrospectively. All patients received intravenous thrombolytic therapy within 6 h of ST segment elevation-documented infarction and had angiographic confirmation of their reperfusion status performed within 120 min of treatment. Three hundred three patients had successful reperfusion with or without rescue angioplasty and had no recurrent ischemia (group 1), 74 patients had initially successful reperfusion but subsequent recurrent ischemia (group 2) and 28 patients had failed reperfusion (group 3). The in-hospital mortality in groups 1 to 3 was 2.0%, 14.9% and 32.1%, respectively (p less than 0.001) and the change from baseline to prehospital discharge left ventricular ejection fraction was 1.2 +/- 9.3%, -0.8 +/- 8.7% and -4.3 +/- 5.3%, respectively (p = NS). Within the recurrent ischemia group (group 2), multiple regression analysis found absence of cardiogenic shock at presentation (p = 0.002) and successful treatment initiated within 90 min of recurrent ischemia (p = 0.045) to be the only variables independently correlated with in-hospital survival. Later successful reperfusion was not associated with improved hospital survival. The timing and success of treatment did not affect recovery of global or regional left ventricular function in the patients with paired angiographic studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative study of coronary flow reserve, coronary anatomy and results of radionuclide exercise tests in patients with coronary artery disease.

A comparative assessment of regional coronary flow reserve, quantitative percent diameter coronary stenosis and exercise-induced perfusion and wall motion abnormalities was performed in 39 patients with coronary artery disease. Coronary flow reserve was determined by a digital angiographic technique utilizing contrast medium as the hyperemic agent. Percent diameter stenosis was calculated by an automated quantification program applied to orthogonal cineangiograms. Thallium-201 scintigraphy and radionuclide ventriculography were used to assess regional perfusion and wall motion abnormalities, respectively, at rest and during exercise. In Group A, 19 patients without transmural infarction or collateral vessels, coronary flow reserve was inversely related to percent diameter stenosis (r = -0.61, p less than 0.0001), and scintigraphic abnormalities occurred only in vascular distributions with a coronary flow reserve of less than 2.00. There was a strong relation among abnormal regional exercise results, stenoses greater than 50% and reactive hyperemia of less than 2.00. Patients with multivessel disease, however, often had normal exercise scintigrams in regions associated with greater than 50% stenosis and low coronary flow reserve when other regions had a lower coronary flow reserve or higher grade stenosis, or both. In Group B, 20 patients with angiographically visible collateral vessels, 12 of whom had prior myocardial infarction, coronary flow reserve correlated less well with percent diameter stenosis than in Group A (r = -0.47, p less than 0.004). As in Group A patients, there was a significant relation between abnormal exercise test results and stenoses greater than 50%. However, reactive hyperemia values were generally lower than in Group A, and positive exercise stress results were strongly correlated only with highly impaired flow reserves of 1.3 or less. In Group B patients, the coronary flow reserve of vessels with less than 50% stenosis was significantly lower than that of similar vessels in Group A patients (2.40 +/- 0.79 versus 1.56 +/- 0.43; p less than 0.0002). It is concluded that: there is a general relation between quantitative percent diameter stenosis and reactive hyperemia that is not of sufficient precision to allow accurate prediction of coronary flow reserve in individual cases; exercise scintigraphic abnormalities are usually associated with low coronary flow reserve, and the relation between these two functional tests is stronger than the relation between exercise test results and quantitative percent diameter stenosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Prospects for the use of antagonists to the platelet glycoprotein IIb/IIIa receptor to prevent post-angioplasty restenosis and thrombosis.

Despite many advances since its inception in humans in 1977, coronary angioplasty continues to be limited by the problems of abrupt arterial closure and late restenosis. Excessive platelet deposition at the site of angioplasty undoubtedly plays an important role in the pathophysiology of both of these problems. Monoclonal antibodies and snake venom-derived or synthetic peptides directed against a common protein recognition sequence on the platelet glycoprotein IIb/IIIa receptor are currently in the early stages of preclinical and clinical testing and hold promise of preventing abrupt closure and restenosis by inhibiting platelet function. Whether any of these agents will eventually be commonly used in clinical practice will depend on their effects on the complex pathophysiology of these problems and on their safety profile when administered to patients who are likely to receive other antithrombotic medications and who are instrumented for coronary angioplasty.

Thrombolysis plus aortic counterpulsation: improved survival in patients who present to community hospitals with cardiogenic shock.

OBJECTIVES: We sought to explore the potential benefit of combining intraaortic balloon counterpulsation (IABP) with thrombolysis for acute myocardial infarction (MI) complicated by cardiogenic shock. BACKGROUND: In community hospitals, this condition is usually managed with thrombolysis alone. METHODS: We reviewed the charts of 335 patients from two community hospitals who presented with acute MI and had cardiogenic shock between 1985 and 1995. RESULTS: Of 46 patients who underwent thrombolysis within 12 h of acute infarction with confirmed cardiogenic shock, 27 underwent IABP and 19 did not. Age, systolic blood pressure with shock, pulmonary artery catheter use, pulmonary capillary wedge pressure and the incidence of diabetes mellitus and anterior MI did not differ between groups. Patients treated with IABP were somewhat more likely to have prior MI and had a significantly greater cardiac index (2.0 vs. 1.5 liters/min per m2, p = 0.04). Although no deaths occurred within 2 h of presentation, patients not treated with IABP tended to die earlier (6.8 +/- 5 vs. 23.8 +/- 19 h, p = 0.13). Patients treated with IABP had a significantly higher rate of community hospital survival (93% vs. 37%, p = 0.0002), and more of them were transferred for revascularization (85% vs. 37%). Of 30 patients transferred for revascularization, 27 underwent angioplasty or bypass surgery; hospital survival was 74%. Patients treated with IABP also had a significantly higher overall hospital and 1-year survival rate (67% vs. 32%, p = 0.019). CONCLUSIONS: Survival may be enhanced and transfer for revascularization facilitated when community hospitals use both thrombolysis and IABP to treat patients with acute MI complicated by cardiogenic shock.

Abnormal coronary flow reserve and abnormal radionuclide exercise test results in patients with normal coronary angiograms.

Coronary flow reserve, exercise thallium-201 scintigraphy and exercise radionuclide ventriculography were compared in 18 patients with chest pain and angiographically normal coronary arteries. Regional exercise thallium-201 perfusion was abnormal in three patients, regional exercise wall motion was abnormal in three other patients and results of both tests were abnormal in one additional patient. Left ventricular ejection fraction responses were abnormal in five of these seven patients. The coronary flow reserve of arterial distributions with abnormal perfusion or regional dysfunction was significantly lower than that of distributions associated with normal radionuclide results (1.42 +/- 0.23 versus 2.58 +/- 0.83, p less than 0.001). All patients with abnormal scintigraphic results had low coronary flow reserve (less than 1.95) in at least one distribution. Perfusion abnormalities appeared to be more localized in the arterial distributions with the lowest flow reserve. Only two patients had low flow reserve (less than 1.95) with normal scintigraphic results; both were hypertensive. These data suggest that abnormal exercise scintigraphic findings in patients with angiographically normal coronary arteries and chest pain are indicative of true blood flow or perfusion abnormalities.