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Biomedical subjects

J E Rosenthal

Publications and source records attributed to J E Rosenthal.

At least 19 recordsLinked to original sources

A simplified urinary incontinence score for the evaluation of treatment outcomes.

There are no standardized definitions for anti-incontinence therapy outcomes. The present study was conducted to evaluate whether the incorporation of several non-invasive outcome measures into a new score may serve as a meaningful outcome instrument. Ninety-four consecutive sphincteric incontinent women who underwent a pubovaginal sling by a single surgeon were enrolled. All patients underwent a full clinical evaluation, including pre- and post-operative questionnaires, 24-hour voiding diary, and 24-hour pad test. Surgery outcomes were classified twice: First, by analyzing the patient questionnaire, voiding diary, and pad test separately, according to previously published criteria, and second, by combining the three outcome tools into a new response score. The new score was constructed in a simple, easy-to-remember format and divided into five categories: cure, good response, fair response, poor response, and failure. All patients were evaluated at least 1 year post-operatively. Comparison of the old and new classifications suggests that the new response score provides a more accurate evaluation of the surgical outcomes. Although 64 to 69% of the patients were originally classified as cure according to the old classification, only 44.7% were re-classified as cure by the strict criteria employed in the new score. Furthermore, the response score also differentiates between various degrees of clinical improvement (i.e., good, fair, or poor response). Twenty-five (26.6%) patients, most of whom were previously classified as cure, were re-classified as good response, whereas 20 others were re-classified as fair (13. 9%), or poor (7.4%) response. Seven (7.4%) patients were re-classified as surgical failures. All were diagnosed pre-operatively as having complex sphincteric incontinence. Specific failure rates were therefore 11.3% for complex and 0% for simple cases. In conclusion, the suggested post-operative response score incorporates in a user-friendly format three popular outcome tools (i.e., 24-hour diary, 24-hour pad test, and patient questionnaire) and seems to reflect the surgical results more accurately. Further studies are needed to assess its validity and reproducibility in other treatment modalities. Neurourol Urodynam. 19:127-135, 2000.

Adult↗

Results of pubovaginal sling for stress incontinence: a prospective comparison of 4 instruments for outcome analysis.

PURPOSE: Presently to our knowledge there are no standardized techniques to assess outcomes after surgery for stress incontinence. We performed a prospective blinded study to assess the correlation among physician and patient assessments, and a validated 24-hour pad test and voiding diary. MATERIALS AND METHODS: A total of 84 women were evaluated before and after pubovaginal sling for stress incontinence with a voiding diary, pad test and symptom questionnaire (patient assessment) administered by a blinded third party. The operating surgeon evaluated the patient using history, physical examination, pad test and voiding diary but was blinded to results of the outcome questionnaire. Preoperative focused neurourological examination and video urodynamics confirmed stress incontinence. Patients were assessed at least 1 year postoperatively. We compared patient assessment (cured, improved, failure) to the outcome of the pad test, voiding diary and physician assessment. The physician and questioner were blinded to each other. We considered patients with a pad test of 0 to 2 ml. as cured, 50% or more volume reduction as improved and less than 50% volume reduction as failure. Postoperative assessment did not differentiate between stress and urge incontinence. The kappa coefficient was used for statistical comparison. RESULTS: Average patient age was 58 years and average followup for the entire group was 4 years. Agreement among the 4 instruments to assess outcome was excellent (k >0.9) with respect to cured/improved versus failure but only good for cured versus improved versus failure (k >0.5). CONCLUSIONS: Outcomes following incontinence surgery may vary depending on how the analysis was performed, patient selection, definition of success and so forth. Our results indicate that a pad test and voiding diary are reliable and should be part of the normal followup after pubovaginal sling for sphincteric incontinence. When these tests are used in conjunction with defined parameters of success, there is excellent agreement with patient feelings in regard to success or failure of surgery. Nevertheless, these instruments and methods are imperfect at best.

Adult↗

Ambulatory blood pressure and Holter monitoring of emergency physicians before, during, and after a night shift.

BACKGROUND: Occupational stress may affect measured hemodynamic and electrocardiographic variables. Data describing the physiologic effects of work on the emergency physician (EP) are sparse. OBJECTIVE: To determine whether blood pressure (BP) and heart rate variability (HRV) of the EP are affected during a night shift in the ED. METHODS: This prospective study evaluated BP and HRV in attending EPs at an urban academic medical center for a 24-hour period during which a night shift was scheduled. Participants were fitted with an oscillometric ambulatory BP device and a Holter monitor at 1500 hours on the day of a night shift. The monitors were worn continuously before, during, and after a night shift (2300-0700) in the ED and were removed at 1500. Systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), heart rate (HR), measures of HRV, and occurrence of cardiac dysrhythmias were evaluated. Comparisons were made for ED and non-ED awake periods and non-ED sleep periods. RESULTS: Twelve participants completed the study. Eight (67%) subjects were men and 4 (33%) were women. Age ranged from 28 to 40 years (mean 34.1+/-4.1). Results were analyzed using repeated-measures ANOVA. An elevation of mean DBP (5.5 mm Hg+/-4.37; p < 0.05; 95% CI 1-10) during night shift activity was seen. A trend toward elevation of SBP, MAP, and HR was discernible. HRV measures indicated a significant relative increase in sympathetic vs parasympathetic tone and an increase in HR of prework and work compared with postwork. Dysrhythmias observed included sinus tachycardia, sinus bradycardia, sinus pause, atrial premature beats, atrial couplets and triplets, supraventricular tachycardia, and premature ventricular contractions. CONCLUSIONS: The elevation of DBP during a night shift suggests that these patterns of BP variability are activity- or stress-related rather than a result of a true diurnal variation. HRV analysis suggests that sympathetic tone is heightened both before work and during work. The implications of such findings to the health of the EP warrant further investigation.

Adult↗

QT interval dispersion in healthy subjects and survivors of sudden cardiac death: circadian variation in a twenty-four-hour assessment.

Twenty-four-hour acquisition of QT dispersion (QTd) from the Holter and the circadian variation of QTd were evaluated in 20 survivors of sudden cardiac death (SCD), in 20 healthy subjects, and in 14 control patients without a history of cardiac arrest who were age, sex, diagnosis and therapy matched to 14 SCD patients. Computer-assisted QT measurements were performed on 24-hour Holter recordings; each recording was divided into 288 5-minute segments and templates representing the average QRST were generated. QTd was calculated as the difference between QT intervals in leads V1 and V5 for each template on Holter. The 24-hour mean QTd was significantly greater in SCD patients (40 +/- 28 ms) than in healthy subjects (20 +/- 10 ms) and control patients (15 +/- 5 ms) (p <0.05). There was a circadian variation in QTd with greater values at night (0 to 6 A.M.) than at daytime (10 A.M. to 4 P.M.) in healthy subjects (25 +/- 13 vs 15 +/- 8 ms, p <0.001) and control patients (18 +/- 10 vs 12 +/- 4 ms p <0.05), whereas in SCD patients there was no significant difference between night and day values (45 +/- 31 vs 37 +/- 28 ms, p = NS). It is concluded that QTd measured by Holter was greater in SCD patients than in healthy subjects and matched control patients during the entire day. QTd has a clear circadian variation in normal subjects, whereas this variation is blunted in SCD patients. QTd measured on Holter differentiates survivors of cardiac arrest and may be a useful tool for risk stratification.

Adult↗

Evaluation of five QT correction formulas using a software-assisted method of continuous QT measurement from 24-hour Holter recordings.

To evaluate and compare QT correction formulas in healthy subjects, we used 24-hour Holter monitoring because it allows the assessment of QT intervals over a large range of rates. Computer-assisted QT-interval measurements were obtained from 21 subjects. QT-RR relations for individuals and the group were fitted by regression analysis to 5 QT prediction formulas: simple Bazett's, modified Bazett's, linear (Framingham), modified Fridericia's and exponential (Sarma's). There were no significant differences in mean squared residuals between formulas. When using individually calculated regression parameters, each formula gave good or acceptable QT correction over the entire range of RR intervals. Simple Bazett's formula (which uses no regression parameters) was unreliable at high rates. Akaike information criteria rank was: Sarma's, Framingham, modified Bazett's, Fridericia's, and simple Bazett's. When group-based regression parameters were applied to individuals, no formula had a clear advantage over simple Bazett's. We conclude that any formula that invokes regression parameters unique to each individual provides satisfactory QT correction. Determination of these parameters requires long-term recording to obtain an adequate range of rates. Group-based regression parameters give poor correction. When individual parameters cannot be determined, as in a 12-lead electrocardiogram, no formula provides an advantage over the familiar simple Bazett's.

Electrocardiography, Ambulatory↗

Diurnal pattern of QTc interval: how long is prolonged? Possible relation to circadian triggers of cardiovascular events.

OBJECTIVES: This study sought to evaluate the range and variability of the QT and corrected QT (QTc) intervals over 24 h and to assess their pattern and relation to heart rate variability. BACKGROUND: Recent Holter monitoring data have revealed a high degree of daily variability in the QTc interval. The pattern of this variability and its relation to heart rate variability remain poorly characterized. METHODS: We developed and validated a new method for continuous measurement of QT intervals from three-channel, 24-h Holter recordings. Average RR, QT, QTc and heart rate variability were measured from 5-min segments of data from 21 healthy subjects. RESULTS: Measurement of 6,048 segments showed mean (+/- SD) RR, QT and QTc intervals of 830 +/- 100, 407 +/- 23 and 445 +/- 16 ms, respectively (mean QTc interval for men 434 +/- 12 ms, 457 +/- 10 ms for women, p < 0.0001). The average maximal QTc interval was 495 +/- 21 ms and the average QTc range 95 +/- 20 ms. The maximal QTc interval was > or = 500 ms in 6 subjects and > or = 490 ms in 13. The 95% upper confidence limit for the mean 24-h QTc interval was 452 ms (men 439 ms, women 461 ms). The RR, QT and QTc intervals and the high frequency component of heart rate variability were greater during sleep. Both the QTc interval and the variability between hourly minimal and maximal QTc intervals reached their circadian peak shortly after awakening, before declining to daytime levels. CONCLUSIONS: The maximal QTc interval over 24 h in normal subjects is longer than heretofore thought. Both QT and QTc intervals are longer during sleep. The QTc interval and QTc variability reach a peak shortly after awakening, which may reflect increased autonomic instability during early waking hours, and the time of the peak value corresponds in time to the period of reported increased vulnerability to ventricular tachycardia and sudden cardiac death. These findings have implications regarding the definition of QT prolongation and its use in predicting arrhythmias and sudden death.

Adult↗

Lactate enhances sodium channel conductance in isolated guinea pig ventricular myocytes.

Myocardial hypoxia and ischemia result in the production of lactate. To study the effect of lactate on the rapid Na+ current (INa), we used the whole cell voltage-clamp technique in enzymatically isolated guinea pig ventricular myocytes. Experiments were conducted at 16 degrees C. Extracellular Na+ concentration ([Na+]o) was maintained in control and test solutions and extracellular pH was 7.4. Lactate (4-10 mM, either sodium lactate or lactic acid) augmented INa in each of eight experiments, increasing the peak Na+ conductance from 75.4 to 84.7 nS (13-16% at all test voltages in the linear portion of the conductance curve). The voltage dependence of steady-state availability and the time course of inactivation remained unchanged. The increase in peak Na+ conductance was concentration dependent, with an apparent dissociation constant of 1.8 mM and Hill coefficient of 1.8. Lactate in the range of 1-10 mM did not significantly reduce the Ca2+ activity of test solutions. These effects of lactate were still observed in Mg(2+)-free test solutions and when the buffering capacity of internal solution was reinforced by increasing N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid concentration from 5 to 20 mM. In conclusion, lactate enhances INa via a mechanism that does not involve chelation of Ca2+ or Mg2+ or changes in intracellular pH. These effects of lactate on the Na+ channel might alter electrophysiological properties during myocardial ischemia and could protect the heart from ischemia-induced conduction abnormalities or, alternatively, could lead to arrhythmias.

Analysis of Variance↗

Relation between QT and RR intervals during exercise testing in atrial fibrillation.

The ability to predict the RR-QT relation over a range of heart rates was evaluated in 10 patients with atrial fibrillation (AF) and in 10 control subjects in sinus rhythm. The data from each subject were fitted by regression into 3 QT prediction formulas (the square root formula of Bazett, the cube root formula of Fridericia and the exponential formula of Sarma) applied in standard form and modified with a weighted average of the preceding 5 RR intervals. The goodness-of-fit of each formula was evaluated using mean square residual and Akaike information criterion. For AF, the mean square residuals did not differ among the 3 standard QT prediction formulas (Bazett 624 +/- 274, Fridericia 625 +/- 274 and Sarma 611 +/- 267) and among the 3 modified QT prediction formulas (Bazett 507 +/- 325, Fridericia 496 +/- 255 and Sarma 495 +/- 328). The weighted average modification produced a significant decrease in mean square residuals for all 3 equations (p less than 0.05) in all patients. These findings were confirmed by Akaike information criterion. Goodness-of-fit in sinus rhythm was similar to previously published reports, and significantly better than the fit for AF (p less than 0.0001). For 9 of the 10 patients with AF, sinus rhythm electrocardiograms were obtained and the above regression equations were used to predict QT intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of catecholamines on intracellular pH in sheep cardiac Purkinje fibres.

1. It has been reported that catecholamines affect intracellular pH (pHi) in a number of tissues, generally by altering the kinetics of the Na(+)-H+ exchanger. We postulated that catecholamines might affect pHi in cardiac tissue. We tested this in resting sheep cardiac Purkinje fibres by measuring transmembrane potential and pHi with standard and H(+)-sensitive microelectrodes. 2. Adrenaline and the beta-adrenergic agonist isoprenaline, both 5.0 x 10(-6) M, resulted in depolarization and intracellular acidification (adrenaline, 0.03 +/- 0.01 pH units, n = 8, P = 0.005; isoprenaline, 0.08 +/- 0.01 pH units, n = 17, P = 0.0001). The alpha-adrenergic agonist phenylephrine, at concentrations up to 200 microM, had no significant effect on membrane potential or pHi. 3. Isoprenaline significantly attenuated the half-time (t0.5) for pHi recovery from intracellular acidification induced via the NH4Cl pulse technique. Isoprenaline also attenuated the hyperpolarization that is normally seen at the onset of pHi recovery. Phenylephrine slightly reduced the t0.5 for recovery, although the reduction did not reach statistical significance. 4. Forskolin, 7.5-10 x 10(-5) M, an agent that raises intracellular cyclic adenosine 3',5'-monophosphate (cyclic AMP), also induced depolarization and acidification, similar to that induced by adrenaline and isoprenaline. 5. In the presence of the Na(+)-H+ exchange blocker 5-dimethyl amiloride, 2-6 x 10(-5) M, isoprenaline-induced acidification was blunted but not abolished. When administered in Na(+)-free Tyrode solution, isoprenaline-induced acidification was also not abolished. Buffering power, tested using the NH4Cl method, was not decreased by isoprenaline, but rather, was slightly increased. Reversal of H+ driving force across the cell membrane from the normally inward direction to outward (achieved by increasing pHo to 8.3-8.5 and depolarizing the membrane with 10 mM K+ solutions) did not prevent intracellular acidification from occurring in the presence of isoprenaline. When glycolysis was inhibited by a 60 min exposure to glucose-free solution containing 5.5 mM 2-deoxyglucose, acidification by isoprenaline was nearly abolished. 6. We conclude that, in resting sheep Purkinje fibres, beta- but not alpha-adrenergic stimulation results in intracellular acidification and depolarization, probably mediated via an increase in cyclic AMP. beta- but not alpha-adrenergic stimulation slows the rate of recovery from intracellular acidification and blunts the hyperpolarization associated with this recovery. 7. The intracellular acidification appears to be due both to partial inhibition of Na(+)-H+ exchange and to stimulation of glycolysis by beta-adrenergic agents.

Animals↗

Electrophysiological effects of anti-free radical interventions in canine Purkinje fibers.

To assess whether free radicals affect the characteristic sequence of events in an in vitro model of ischemia and reperfusion, isolated canine cardiac Purkinje fibers were exposed to anti-free radical agents, superoxide dismutase 50 U/ml; catalase 600 U/ml; mannitol 2 mM and 20 mM and combined superoxide dismutase, catalase, and mannitol 20 mM. Fibers were superfused for 60 min with altered Tyrode's solution which mimicked some conditions of ischemia (glucose-free, containing lactate, equilibrated with 90% N2-10% CO2), and then re-exposed to normal, oxygenated Tyrode's solution. Anti-free radical agents alone had no electrophysiological effects. Ischemic conditions resulted in moderate depolarization in most preparations (10 control; 43 treated) but in severe depolarization, to less than -60 mV, in some (3 control, 11 treated). Re-exposure to normal, oxygenated solution resulted in prompt initial hyperpolarization followed by marked depolarization, and finally by recovery to baseline maximum diastolic potential. Anti-free radical agents had not effect on maximum diastolic potential during exposure to ischemic conditions or on initial hyperpolarization following re-exposure to oxygenated solution. Preparations that became severely depolarized during exposure to ischemic conditions were not protected by anti-free radical interventions from developing marked depolarization following re-exposure to oxygenated solution. However, in fibers only moderately depolarized by the ischemic conditions, all anti-free radical interventions except mannitol, 2 mM significantly attenuated depolarization following re-exposure to oxygenated solution. Anti-free radical interventions significantly reduced the number of preparations that became markedly depolarized (to less than -65 mV) during re-exposure to oxygenated solution (except for mannitol, 2 mM). Agents had no effect on the occurrence of abnormal automaticity; the occurrence of inexcitability was reduced, but not significantly, except when all agents were used in combination. The results suggest that free radical production may contribute to electrophysiological abnormalities when Purkinje fibers are re-exposed to oxygenated Tyrode's solution after they have been exposed to ischemic conditions.

Action Potentials↗

Reflected reentry in depolarized foci with variable conduction impairment in 1 day old infarcted canine cardiac tissue.

A recent study in 1 day old infarcted canine cardiac tissue demonstrated that variations in entrance and exit characteristics of depolarized spontaneous foci could profoundly affect their expression, resulting in behaviors such as modulated parasystole and entrainment, second and third degree exit block "autoentrainment" and annihilation (abrupt termination) of spontaneous activity. Foci with exit and entrance delay should also allow the occurrence of reflected reentry. To test this, the left circumflex coronary artery was ligated and, after 1 day, simultaneous microelectrode impalements were made in infarcted and uninfarcted portions of isolated ventricular preparations. Preparations were stimulated from the uninfarcted portions. Reflected reentry was demonstrated in 5 of 11 preparations. It occurred when exit conduction delay resulted in reexcitation of the focus or, alternatively, when entrance conduction delay resulted in reexcitation of extrafocal tissue. Reflection occurred in which the action potentials were reexcited during phase 2 or 3, resulting in prolongation of action potential duration (type I), and in which reexcitation occurred after full or nearly full repolarization, resulting in a closely coupled extrasystole (type II). Electrotonic modulation and reflection could coexist, the type of behavior depending on the phase relation between focal and extra-focal action potentials. An example is illustrated in which type I reflection occurred only when preceding driven activity induced overdrive suppression of exit conduction from the focus. The results suggest that, in infarcted tissue, entrance and exit conduction delays to depolarized foci may form the basis for the occurrence of reflected reentry.

Action Potentials↗

Contribution of depolarized foci with variable conduction impairment to arrhythmogenesis in 1 day old infarcted canine cardiac tissue: an in vitro study.

To assess the roles of entrance and exit block after canine myocardial infarction, single stage coronary artery ligations of canine circumflex coronary arteries were performed. After 1 day, atria and ventricles were paced using single stimuli and trains. After isolation, simultaneous microelectrode impalements were made in infarcted and uninfarcted tissue. Spontaneous foci, when identifiable, were always located in infarcted tissue. They could frequently be triggered by one or more driven beats, and their activity could often be terminated ("annihilated") by a properly timed beat. Foci with varying combinations of entrance and exit conduction impairment were observed. Variations in conduction characteristics altered the manifest arrhythmic pattern. With partial entrance block and intact exit conduction, foci could be electrotonically modulated and entrained into regular patterns. Activity that emerged from a focus with sufficient conduction delay could modulate the focus, and entrain it to discharge at a slower rate ("autoentrainment"). The results suggest that modulated parasystole may contribute to arrhythmogenesis after canine myocardial infarction and that variations in entrance and exit characteristics of depolarized foci may result in variable and complex arrhythmic patterns.

Animals↗

Contribution of variable entrance and exit block in protected foci to arrhythmogenesis in isolated ventricular tissues.

Automatic foci with membrane potentials in the range characterized by depolarization-induced automaticity exhibit entrance block. The present study demonstrates a role of variable entrance and exit block in arrhythmogenesis. We studied canine interventricular septa with the right bundle branch exposed, isolated false tendons and isolated feline papillary muscle using standard microelectrode techniques. Foci of automaticity were produced either by focal application of electric current or by exposure of the preparations to Tyrode's solution containing 1.5-2.0 mM KCl. Foci induced by mild depolarization exhibited entrance block with exit conduction and were subject to electrotonic modulation. With greater depolarization, varying degrees of exit block developed. Various rhythms, including Wenckebach periodicity, resulted. Delayed emergence of electrotonically accelerated activity led to closely coupled extrasystoles resembling reentrant activity. Exit conduction in some preparations was facilitated by enhanced normal pacemaker activity (membrane potentials -- 70 mV or greater) in tissue peripheral to the focus. Also, when there were two sites of automaticity separated by an area of depressed conduction, intermodulation between the two automatic regions generated complex arrhythmias. Shifts in maximum diastolic potential also changed conduction and led to changes in arrhythmic patterns. In some experiments, focal automaticity was terminated by single stimuli. We conclude that complex and variable behavior of automatic foci may result in activity with characteristics previously attributed to other arrhythmic mechanisms.

Animals↗

Inotropic and electrophysiologic effects of amrinone in untreated and digitalized ventricular tissues.

The purposes of this study were to determine whether amrinone induces oscillatory afterpotentials (OAP) or aftercontractions (AC) in Purkinje tissue or myocardium, to determine whether a relationship exists between the production of OAP or AC and the inotropic effects of amrinone and to determine possible effects of amrinone on the oscillations and the positive inotropic effect produced by digitalis. Isolated canine papillary and trabecullar muscles, as well as false tendons, were exposed to 5.3 X 10(-4) M amrinone. Some of the preparations had been pretreated with acetylstrophanthidin (AS) in a dose just sufficient to induce OAP or AC. Standard electrophysiologic techniques were used to record transmembrane action potentials. Developed tension also was recorded. Amrinone by itself did not induce OAP or AC in myocardium or false tendons. This was true even when the resting membrane potential of the false tendons was reduced by means of focal current application. Amrinone increased the amplitude of AS-induced oscillations in both myocardium and false tendons. Amrinone increased strength of contraction of untreated myocardium at all basic cycle lengths and of AS-treated myocardium, especially at shorter basic cycle lengths. Amrinone decreased strength of contraction both of untreated and AS-treated false tendons at all basic cycle lengths. The results suggest that there may be important differences in the mechanisms of action of amrinone and digitalis.

Aminopyridines↗

Automaticity and entrance block induced by focal depolarization of mammalian ventricular tissues.

Isolated canine interventricular septa were studied with standard microelectrode techniques. Focal automaticity was induced by applying depolarizing current through an extracellular pipet in contact with the right bundle branch (RBB) of the ventricular specialized conducting system. Automaticity appeared with depolarization to transmembrane potentials of -50 mV or less. The spontaneous activity was neither depressed nor accelerated when overdrive suppression was attempted. Activity originating within the focus propagated into fully polarized surrounding tissue. However, entrance block, phasically related to the spontaneous cycle length, was an intrinsic property of these foci. Early premature beats initiated outside the focus failed to enter the focus, but the resulting electrotonus delayed the next automatic beat. Late premature beats captured and thereby accelerated the focus. Thus, the automatic foci could be extrafocal activity. Consequently, continous pacing at various rates precipitated complex rhythms with fixed coupling. Similar foci with exit conduction, entrance block, and electrotonic modulation also were demonstrated in focally depolarized papillary muscles in feline septal preparations. The unique properties of focally depolarized areas in which spontaneous activity is generated at low membrane potentials provide a mechanism capable of generating a wide array of arrhythmias.

Animals↗

Regulation of intracranial pressure in rat, dog, and man.

Intracranial resistance and compliance were assessed in the cerebrospinal fluid system of rat, dog, and man by means of low-volume, short-duration infusions of artificial CSF into the subarachnoid space. A family of pressure/time response curves was obtained for each species: at low flow rates, steady-state pressure elevations were associated with normal neurological function; at high flow rates, rapid linear pressure elevations were associated with marked neurological dysfunction. From these curves a mathematical model was developed which describes transport and pressure-dependent valvelike characteristics of the CSF outflow resistance. This resistance shows a progressive phylogenetic change in rat, dog, and man which increasingly enhances the species' abilities to vent fluid from the intracranial cavity into the venous circulation. Arachnoid villi appear to be the major structures modulating sustained, nonlethal elevations of intracranial pressure.

Animals↗