Topographic organization of somatosensory corticotectal influences in cat

Using electrophysiological techniques, the present study demonstrated that substantial direct somatosensory cortical influences on the superior colliculus (SC) originate from three areas: a) SIV, b) para-SIV (the cortex adjacent to SIV but deeper in the anterior ectosylvian sulcus (AES) and for which no topography has yet been described), and c) the rostral suprasylvian sulcus. Influences also appeared to originate from SI and SII, but these may have been indirect. Detailed examination of the AES revealed that these corticotectal projections are topographically organized, and stimulation of a given cortical locus was observed to affect only those cells in the SC whose receptive fields overlapped those of cells at the stimulation site. A similar receptive-field register was found between the suprasylvian sulcus and the SC. Within this topographic pattern, considerable convergence was evident and an individual SC cell could be influenced from a surprisingly large cortical area. This was particularly evident within the representation of the forelimb. Thus, an SC cell with a receptive field covering the forelimb and paw could receive convergent input from many cortical cells with receptive fields covering all or restricted portions of this body region. Considerable corticotectal divergence also was observed within this general topographic scheme. For example, a given corticotectal site representing the digits sent projections to many different SC cells that included the digits within their receptive fields. These data are more consistent with a block-to-block than a point-to-point corticotectal projection. Somatosensory corticotectal projections excited only those SC cells that could also be activated by peripheral somatosensory stimuli. Similarly, the caudal AES, which contains auditory cells, excited only those SC cells activated also by peripheral auditory stimuli. Yet convergent influences from both auditory and somatosensory regions of the AES were observed in the SC cells that could be activated by both auditory and somatosensory stimuli. These data indicate that the AES is a major source of excitatory input to cells of the deep laminae of the SC. Since it is these deep laminae cells that project to premotor regions of the brain stem and the spinal cord, it is reasonable to suppose that the AES has a significant impact on the output signals of the SC that initiate the orientation responses to peripheral sensory stimulation.     

Effects of cooling somatosensory cortex on response properties of tactile cells in the superior colliculus

The corticotectal influences of somatosensory cortex were investigated by using reversible deactivation of cortex by cooling. More than half of the somatosensory superior colliculus (SC) cells studied exhibited a response depression (often not apparent qualitatively) or an elimination of responses to somatosensory stimuli during the period in which cortex was rendered inactive. Responses were restored to their initial levels by cortical rewarming. Hyperresponsiveness was never observed as a consequence of cortical cooling. Susceptibility to cooling-induced depression was not invariably linked to a specific cell type, location in the SC, or receptive-field size. Yet cells that had small receptive fields and were activated by hair displacement had the highest probability of being affected by this procedure. In some cells a contraction of the receptive field was induced by cortical cooling. This observation is consistent with previous experiments that showed that SC somatosensory receptive fields are constructed by the convergence of ascending and descending inputs and indicates that the responsiveness of specific receptive-field regions may depend on the functional integrity of cortex. Two cortical regions were found to produce cooling-induced effects in somatosensory SC cells: 1) SIV (and para-SIV), located in the anterior ectosylvian sulcus, and 2) the cortex within the rostral suprasylvian sulcus. These results indicate that somatosensory cortex, like visual cortex, plays a critical role in modulating the responses of SC cells. Apparently, the ability of both somatosensory and visual SC cells to code the presence of peripheral stimuli depends largely on the functional influences of their respective cortices. However, in contrast to previous observations on visual corticotectal influences, no specific receptive-field properties could be shown to be impressed on SC cells by somatosensory cortex.     

Prognostic judgments and triage decisions for patients with acute congestive heart failure

STUDY OBJECTIVES: To determine how well triage physicians judge the probability of death or severe complications that require treatment only available in an ICU to maintain life for patients with acute congestive heart failure (CHF). DESIGN: Prospective cohort study. SETTING: An urban university hospital, a Veteran's Administration hospital, and a community hospital. Patients or participants: Patients were those visiting the emergency department (ED) with acute CHF, excluding those who already required a treatment only available in an ICU to maintain life, and those with possible or definite myocardial infarction. Physician participants were those caring for the patients in the ED. MEASUREMENTS AND RESULTS: We performed chart reviews to ascertain whether each patient died or had severe complications develop by 4 days. We collected judgments of the probability of this outcome from the physicians taking care of the study patients in the ED. The prevalence of death or severe complications was 43 per 1,032 patients (4.2%). The mean +/- SD of physicians' judgments of the probability of this outcome was 32.1 +/- 28.4%. A calibration curve that stratified these judgments by decile demonstrated that physicians consistently overestimated this probability (p < 0.01). Physicians' judgments were only moderately good at discriminating which patients would have the outcome (receiver operating characteristic curve area, 0.715). Patients admitted to an ICU received the highest average predicted probability (56.4%), followed by those admitted to a telemetry unit (34.1%), to a regular hospital ward (29.8%), and those sent home (17.9%.) CONCLUSIONS: Physicians drastically overestimated the probability of a severe complication that would require critical care for patients with acute CHF who were candidates for ICU admission. Their judgments of this probability were associated with their triage decisions, as they should be according to several guidelines for ICU triage. Overestimation of the probability of severe complications may have lead to overutilization of scarce critical care resources. Current critical care triage guidelines should be revised to take this difficulty into account, and better predictive models for patients potentially requiring critical care should be developed.     

Effect of adenosine on atrioventricular conduction. I: Site and characterization of adenosine action in the guinea pig atrioventricular node

Adenosine has a negative dromotropic effect and modulates hypoxia-induced atrioventricular (AV) conduction delay. To further characterize the negative dromotropic effect of adenosine in the guinea pig heart, we determined the site of adenosine-induced AV conduction block; the effect of uptake and deamination of adenosine on its concentration-negative dromotropic effect, and the adenosine receptor that mediates this action. In isolated AV node preparations (n = 16), adenosine in a dose-dependent manner decreased significantly the duration and amplitude of the action potential of atrionodal and nodal cells and, in addition, markedly depressed the maximum rate of rise of the action potential of nodal cells. At high concentrations (greater than 20 microM), adenosine rendered nodal cells inexcitable. In isolated perfused hearts (n = 7), adenosine (5.7 microM) prolonged total AV conduction time by 21 +/- 2 msec. Of this prolongation, 83% was due to an increase in the nodal-to-His-bundle interval and the remaining 17% to an increase in the atrionodal to nodal interval. Infusion of adenosine to cause a 50% increase (EC50) in atria-to-His bundle (AH) interval prolongation resulted in a perfusate (arterial) adenosine concentration of 5.0 +/- 0.6 microM and effluent (venous) adenosine concentrations of 2.8 +/- 0.4 microM, i.e., an arteriovenous difference of 44% (n = 4). When adenosine uptake and deamination were inhibited with dipyridamole (0.5 microM) plus erythro-9-(2-hydroxy-3-nonyl)adenine (5 microM), respectively, the EC50s were 0.28 +/- 0.02 (perfusate) and 0.32 +/- 0.03 microM (effluent). These data indicate that when nucleoside metabolism is inhibited, arterial and venous concentrations of adenosine reach equilibrium. In an additional 10 hearts, the following rank order of potency of adenosine agonists in causing AH interval prolongation was found: N6-cyclopentyladenosine greater than N6-(L-2-phenyl-isopropyl)adenosine greater than 5'-N-ethylcarboxyamidoadenosine greater than or equal to 2-chloroadenosine greater than adenosine, which is compatible with activation of an A1-type receptor. In summary: the site of adenosine-induced AV conduction block is the nodal zone of the AV node, when adenosine uptake and deamination are inhibited, adenosine in concentrations similar to that released by hypoxia causes significant AH interval prolongation, and the adenosine receptor mediating the negative dromotropic effect of adenosine is of the A1-type.     

Results of report cards for patients with congestive heart failure depend on the method used to adjust for severity

BACKGROUND: The validity of outcome report cards may depend on the ways in which they are adjusted for risk. OBJECTIVES: To compare the predictive ability of generic and disease-specific survival prediction models appropriate for use in patients with heart failure, to simulate outcome report cards by comparing survival across hospitals and adjusting for severity of illness using these models, and to assess the ways in which the results of these comparisons depend on the adjustment method. DESIGN: Analysis of data from a prospective cohort study. SETTING: A university hospital, a Veterans Affairs (VA) medical center, and a community hospital. PATIENTS: Sequential patients presenting in the emergency department with acute congestive heart failure. MEASUREMENTS: Unadjusted 30-day and 1-year mortality across hospitals and 30-day and 1-year mortality adjusted by using disease-specific survival prediction models (two sickness-at-admission models, the Cleveland Health Quality Choice model, the Congestive Heart Failure Mortality Time-Independent Predictive Instrument) and generic models (Acute Physiology and Chronic Health Evaluation [APACHE] II, APACHE III, the mortality prediction model, and the Chadson comorbidity index). RESULTS: The community hospital's unadjusted 30-day survival rate (85.0%) and the VA medical center's unadjusted 1-year survival rate (60.9%) were significantly lower than corresponding rates at the university hospital (92.7% and 67.5%, respectively). No severity model had excellent ability to discriminate patients by survival rates (all areas under the receiver-operating characteristic curve < 0.73). Whether the VA medical center, the community hospital, both, or neither had worse survival rates on simulated report cards than the university hospital depended on the prediction model used for adjustment. CONCLUSIONS: Results of simulated outcome report cards for survival in patients with congestive heart failure depend on the method used to adjust for severity.     

Receptive field properties of somatosensory neurons in the cat superior colliculus.

In general, knowledge of the internal organization of receptive fields has played an important role in shaping current understanding of sensory physiology. Such knowledge is particularly important for understanding the function of the superior colliculus, since this structure is at once implicated in spatial localization and has relatively large receptive fields. While this issue has been addressed in the visual and auditory modalities represented in the superior colliculus, there are no previous studies of its somatosensory receptive field organization. Here, the properties of somatosensory receptive fields in the cat superior colliculus were studied quantitatively to determine whether they contain internal non-homogeneities that might aid in the determination of stimulus detail. Of special interest was the possibility that these comparatively large receptive fields would contain areas of differential excitability that could aid in spatial resolution, that within-field spatial summation and/or inhibition would be exhibited, and that the borders of the excitatory receptive field would be flanked by inhibitory regions. The data demonstrate that while inhibition beyond the receptive field borders is a rarity, these somatosensory receptive fields nearly always contain a well-defined area of maximal sensitivity within which the size of the stimulus is a critical feature in determining the magnitude of the response. These best areas are systematically distributed across receptive fields as a function of their location in the structure, and indicate that the resolution of stimulus location and size may be greater than expected on the basis of receptive field size alone.     

Effects of adenosine and adenine nucleotides on the atrioventricular node of isolated guinea pig hearts

The primary goal of this study was to determine whether the slowing of atrioventricular (AV) conduction by ATP is caused by ATP per se or is mediated by adenosine formed from ATP degradation. We assessed the effects of ATP, beta, gamma-methylene ATP, ADP, AMP, and adenosine on AV conduction time in the isolated perfused guinea pig heart. The cardiac effluent was collected and analyzed for its content of adenine nucleotides and nucleosides. Perfused ATP was rapidly and almost completely broken down to AMP and adenosine; only 2.5 +/- 0.5% of the infused ATP was recoverable in the effluent. A significant correlation was found between the effluent concentration of adenosine and atria-to-His bundle (A-H) conduction time. Compounds that altered the effect of adenosine on A-H conduction likewise altered the effect of ATP: (1) aminophylline, a competitive antagonist of adenosine, antagonized the ATP-induced A-H prolongation; (2) adenosine deaminase, the enzyme responsible for the deamination of adenosine to inosine, reduced the effect of ATP by 82%; (3) the adenosine transport blockers NBMPR and dipyridamole markedly enhanced the effect of ATP; and (4) EHNA, an inhibitor of adenosine deaminase, potentiated the effect of ATP. Furthermore, the less hydrolyzable ATP analog, beta, gamma-methylene ATP, was less potent than ATP in causing A-H prolongation. We conclude that the adenosine-like action of ATP on the guinea pig AV node requires that ATP first be degraded to adenosine.     

Prevention of myocardial intracellular edema induced by St. Thomas' Hospital cardioplegic solution.

During cardiac surgery, the heart is infused with cold crystalloid cardioplegic solutions such as St. Thomas' Hospital (StT) solution, which contains high concentrations of K+ and Mg2+. The high K+ and Mg2+ block impulse conduction and inhibit Ca2+ influx, thereby arresting the heart and reducing cardiac oxygen consumption. Nevertheless, myocardial edema and post-operative abnormalities have been noted after cardioplegia and attributed to ischemia and reflow or to hypothermia. We found, however, that cold StT (9 degrees C) was hypotonic and induced cell swelling in the absence of ischemic injury. Cell swelling in cold StT was not due to hypothermia alone, but rather was caused by KCl influx and was prevented by partially replacing Cl- with an impermeant anion. After exposure to cold StT, cells transiently shrank to less than control volume on rewarming in physiological saline (Tyrode's solution, 37 degrees C). The transient shrinkage was blocked by ouabain suggesting that Na+ loading of depolarized hypothermic cells and Na(+)-K+ pump activation on rewarming were responsible. Hypothermic ventricular cells seem to follow Donnan equilibrium, and the product of [K+] x [Cl-] in cardioplegic solutions affects cell volume in the absence of ischemic injury.     

Induction of Ventricular Fibrillation by T Wave Shocks: Observations from Monophasic Action Potential Recordings

Introduction: Shocks given during the vulnerable period of cardiac repolarization may induce ventricular fibrillation (VF). However, the relationship of the vulnerable period and the monophasic action potential (MAP) has not yet been reported in humans. The purpose of this study was, therefore, to determine how the monophasic action potential recorded from the right ventricle correlates with inducibility of VF using T wave shocks during ventricular pacing.Methods: Eleven patients undergoing implantable cardioverter defibrillator (ICD) implantation had a MAP catheter positioned in the right ventricle (RV). The local monophasic action potential duration at 90% repolarization (MAP90) duration was measured during pacing at 400 ms. VF induction was attempted by pacing at 400 ms for 10 cycles and then giving a 1.0 joule monophasic T wave shock at varying coupling intervals (CI) to the last paced stimulus. The maximum and minimum CI that induced VF were determined and mapped in relation to the MAP90 recording.Results: The average paced MAP duration was 275 ± 20ms. The minimum and maximum CI to induce VF were 255 ± 24ms and 325 ± 36ms respectively. This ranged from 93% to 118% of the MAP90 duration but because of delay in conduction time to the MAP catheter, shocks that induced ventricular fibrillation occurred between 74% and 99% of local repolarization time.Conclusion: VF is inducible with low energy T wave shocks falling during the last 25% of the right ventricular MAP90 recording. This corresponds with VF initiation during phase III repolarization.     

Is territorial expansion a mechanism for crossmodal plasticity?

Crossmodal plasticity is the phenomenon whereby, following sensory damage or deprivation, the lost sensory function of a brain region is replaced by one of the remaining senses. One of several proposed mechanisms for this phenomenon involves the expansion of a more active brain region at the expense of another whose sensory inputs have been damaged or lost. This territorial expansion hypothesis was examined in the present study. The cat ectosylvian visual area (AEV) borders the auditory field of the anterior ectosylvian sulcus (FAES), which becomes visually reorganized in the early deaf. If this crossmodal effect in the FAES is due to the expansion of the adjoining AEV into the territory of the FAES after hearing loss, then the reorganized FAES should exhibit connectional features characteristic of the AEV. However, tracer injections revealed significantly different patterns of cortical connectivity between the AEV and the early deaf FAES, and substantial cytoarchitectonic and behavioral distinctions occur as well. Therefore, the crossmodal reorganization of the FAES cannot be mechanistically attributed to the expansion of the adjoining cortical territory of the AEV and an overwhelming number of recent studies now support unmasking of existing connections as the operative mechanism underlying crossmodal plasticity.