Antiadrenergic effects of adenosine on His-Purkinje automaticity. Evidence for accentuated antagonism.

The effects of adenosine on the human His-Purkinje system (HPS) were studied in nine patients with complete atrioventricular (AV) block. Adenosine had minimal effect on the control HPS cycle length, but in the presence of isoproterenol increased it from 906 +/- 183 to 1,449 +/- 350 ms, P less than 0.001. Aminophylline, a competitive adenosine antagonist, completely abolished this antiadrenergic effect of adenosine. In isolated guinea pig hearts with surgically induced AV block, isoproterenol decreased the HPS rate by 36%, whereas in the presence of 1,3-dipropyl-8-phenyl-xanthine, a potent adenosine antagonist, the HPS rate decreased by 48% and was associated with an increased release of adenosine. Therefore, by blocking the effects of adenosine at the receptor level, the physiologic negative feedback mechanism by which adenosine antagonizes the effects of catecholamines was uncoupled. The results of this study indicate that adenosine's effects on the human HPS are primarily antiadrenergic and are thus consistent with the concept of accentuated antagonism. These effects of adenosine may serve as a counterregulatory metabolic response that improves the O2 supply-demand ratio perturbed by enhanced sympathetic tone. Some catecholamine-mediated ventricular arrhythmias that occur during ischemia or enhanced adrenergic stress may be due to an imbalance in this negative feedback system.

Assessment of global atrial fibrillation organization to optimize timing of atrial defibrillation.

BACKGROUND: We hypothesized that frequency domain analysis of a wide bipolar interatrial electrogram describes the global organization of atrial fibrillation (AF) and should vary over time. By timing shocks to periods of high organization of AF, cardioversion efficacy should improve. METHODS AND RESULTS: A total of 15 dogs (weight, 28.2+/-3.4 kg) were rapidly paced for 48 to 72 hours to induce AF. Coil electrodes with a surface area of 1.80 cm(2) were then placed in the left and right atria to form a wide bipole. Wide bipolar electrograms were digitally filtered, and a fast Fourier transform was performed over a sliding 2-s window every 0.5 s. The organization index (OI) was calculated as the ratio of the area of the dominant peak and its harmonics to the total area of the magnitude spectrum. The atrial defibrillation threshold (ADFT(50)) was determined using a 3-ms/3-ms biphasic shock and an up-down-up protocol. Additional shocks with higher and lower energies were delivered in a random sequence to develop a distribution curve. The OI varied over time, with a mean of 0.42+/-0.03, a maximum of 0.65+/-0.07, and a minimum of 0.20+/-0.06. The OI changed rapidly, with durations of high organization (OI>0.5) ranging from 1 to 5 s. The ADFT(50) for QRS complex-synchronized shocks was 183+/-56 V, versus 142+/-49 V for shocks synchronized to an OI>0.5 (P<0.001). The distribution curve shifted leftward when shocks were synchronized to an OI>0.5. CONCLUSIONS: AF signals show a high degree of variability. Shock efficacy is increased when shocks are delivered during periods of high AF organization as determined by the OI method.

Electrical, morphological, and ultrastructural remodeling and reverse remodeling in a canine model of chronic atrial fibrillation.

BACKGROUND: In patients with recurrent persistent atrial fibrillation (AF), vulnerability to AF persists indefinitely despite presumed completion of reverse electrical remodeling within days of return to normal sinus rhythm. Atrial electrical and anatomic remodeling and reverse remodeling were studied in a canine model of chronic AF. METHODS AND RESULTS: Chronic AF was induced in 8 dogs by creating moderate mitral regurgitation and rapidly pacing the right atrium at 640 bpm for >8 weeks. Measurements performed at baseline, after establishment of chronic AF, and then at 4 hours and again at 7 to 14 days after cardioversion to sinus rhythm included atrial effective refractory periods, AF cycle lengths, left atrial dimensions, premature atrial contraction (PAC) frequency, and atrial vulnerability to atrial extrastimuli. After establishing chronic AF, atrial effective refractory period shortening, increases in spontaneous PAC frequency, increases in left atrial size with loss of contractility, and multiple ultrastructural abnormalities were demonstrated. Complete reverse electrical remodeling and decreases in PACs were observed after 7 to 14 days of sinus rhythm, but there was no resolution of anatomic and ultrastructural abnormalities. Occurrence of spontaneous AF paralleled PAC frequency, but vulnerability to AF induction persisted (75% immediately after conversion versus 63% at 4 hours and 50% at 7 to 14 days) despite reverse electrical remodeling. CONCLUSIONS: After conversion from chronic AF to sinus rhythm in this canine model, electrical remodeling occurs rapidly. However, gross and ultrastructural anatomic changes persist, as does vulnerability to induced AF. Vulnerability to AF initiation 7 to 14 days after cardioversion is more dependent on persisting structural abnormalities than on electrophysiological abnormalities.

Sustained intraatrial reentrant tachycardia: clinical, electrocardiographic and electrophysiologic characteristics and long-term follow-up.

Although intraatrial reentry has been traditionally listed as a mechanism for supraventricular tachycardia, few reports describing the clinical features of this arrhythmia exist. Nineteen patients with a clinical history of sustained supraventricular tachycardia were diagnosed as having intraatrial reentrant tachycardia. Seventeen (89%) patients of the 19 had underlying structural heart disease and 17 had echocardiographic evidence of atrial enlargement; the mean left ventricular ejection fraction was 51 +/- 16%. A history of concomitant atrial fibrillation or flutter was present in 13 patients (68%). The mean atrial cycle length during tachycardia was 326 +/- 57 ms (range 260 to 460). Fourteen patients had 1:1 atrioventricular (AV) conduction during tachycardia, of whom 50% had an RP'/RR' ratio greater than 0.5. Intravenous adenosine (dose range 37.5 to 150 micrograms/kg) and verapamil (dose range 5 to 10 mg) had no effect on atrial tachycardia cycle length in 13 of 14 and 9 of 9 patients, respectively, despite induction of second degree AV block. Type 1a antiarrhythmic drugs achieved long-term suppression of intraatrial reentrant tachycardia in only 6 patients, whereas amiodarone (326 +/- 145 mg/day) was successful in 11 patients during a 32 +/- 20 month follow-up period. The remaining two patients and one patient who later developed amiodarone toxicity either progressed to (n = 1) or had (n = 2) catheter-induced high grade AV block and were treated with long-term ventricular pacing. It is concluded that intraatrial reentrant tachycardia is often associated with structural heart disease, particularly of types that cause atrial abnormalities, but left ventricular dysfunction is not a requisite finding. Other arrhythmias are frequently observed in these patients. This arrhythmia responds poorly to type 1a antiarrhythmic drugs, but is effectively treated with amiodarone. Catheter ablation of the AV junction offers a therapeutic option for patients who are refractory to medical therapy.

Current-based versus energy-based ventricular defibrillation: a prospective study.

Defibrillation is thought to be mediated by a depolarizing current; however, the present method of defibrillation is based on delivering an empiric dose of energy to all patients. The hypothesis of this study was that for equivalent efficacy rates, a current-based defibrillation method would result in delivering less energy and peak current than would the standard energy-based method. In a group of 86 consecutive patients with ventricular fibrillation, every other patient was prospectively assigned to receive shocks according to method 1 or method 2. Method 1 was current based and delivered successive shocks of 25, 25 and a maximum of 40 A; method 2 was energy based and delivered shocks of 200, 200 and 360 joules. Patients in both groups were similar with respect to age, gender, weight, cardiac diagnosis, ejection fraction, antiarrhythmic therapy, chest circumference, chest depth and transthoracic impedance. Each method had statistically equivalent first shock (79% current-based versus 81% energy-based) and cumulative shock success rates. The mean first shock energy was 120 +/- 30 joules for patients receiving the current-based method and 200 joules for patients receiving energy-based shocks (p = 0.0001). The mean peak current was 24 +/- 2.3 and 33 +/- 5.0 A, respectively (p = 0.0001). Therefore, for equivalent first shock success rates, the energy-based method delivered 67% more energy and 38% more current than the current-based method. High transthoracic impedance (greater than or equal to 90 omega) predicted first shock failure only in patients undergoing defibrillation by the energy-based method (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Coexistence of type I atrial flutter and intra-atrial re-entrant tachycardia in patients with surgically corrected congenital heart disease.

OBJECTIVES: This study assessed the coexistence of intra-atrial re-entrant tachycardia (IART) and isthmus-dependent atrial flutter (IDAF) in patients presenting with supraventricular tachyarrhythmias after surgical correction of congenital heart disease (CHD). BACKGROUND: In patients with CHD, atrial tachyarrhythmias may result from IART or IDAF. The frequency with which IART and IDAF coexist is not well defined. METHODS: Both IDAF and IART were diagnosed in 16 consecutive patients using standard criteria and entrainment mapping. Seven patients had classic atrial flutter morphology on surface electrocardiogram (ECG), whereas nine had atypical morphology. RESULTS: A total of 24 circuits were identified. Three patients had IDAF only, five had IART only, seven had both, and one had a low right atrial wall tachycardia that could not be entrained. Twenty-two different reentry circuits were ablated. Successful ablation was accomplished in 13 of 14 (93%) IART and 9 of 10 (90%) IDAF circuits. There was one IART recurrence. The slow conduction zone involved the region of the right atriotomy scar in 12 of 14 (86%) IART circuits. No procedural complications and no further recurrences were seen after a mean follow-up of 24 months. CONCLUSIONS: Both IDAF and IART are the most common mechanisms of atrial re-entrant tachyarrhythmias in patients with surgically corrected CHD, and they frequently coexist. The surface ECG is a poor tool for identifying patients with coexistent arrhythmias. The majority of IART circuits involve the lateral right atrium and may be successfully ablated by creating a lesion extending to the inferior vena cava.

Exercise-induced ST segment elevation 2 weeks after uncomplicated myocardial infarction: contributing factors and prognostic significance.

To define the prevalence and clinical significance of exercise-induced ST segment elevation during predischarge treadmill testing after uncomplicated acute myocardial infarction confirmed by serum MB creatine kinase (CK) activity, 241 consecutive patients were prospectively investigated with quantitative exercise thallium-201 scintigraphy, rest radionuclide ventriculography and coronary angiography at 10 +/- 3 days. All patients received customary care, and in none was thrombolytic therapy or emergency coronary angioplasty employed. Eighty-two patients (34%) had exercise-induced ST segment elevation of greater than or equal to 1 mm above rest baseline. These patients were similar to the 159 patients without this finding with respect to history of prior infarction, the Norris coronary prognostic index, exercise duration, metabolic equivalents (METs) achieved and peak heart rate-blood pressure product. The frequency of inducible myocardial ischemia and extent of angiographic coronary disease was also comparable in the two groups. Findings associated with larger infarct size and transmural extent of infarction were more common in patients with exercise-induced ST segment elevation than in those without, including higher peak CK values (1,235 +/- 1,037 versus 942 +/- 915 mumol/min per liter, p less than 0.026), lower left ventricular ejection fraction (43 +/- 12 versus 51 +/- 10%, p less than 0.001), a higher prevalence of pathologic Q waves in greater than or equal to 2 contiguous infarct-related leads (80 versus 55%, p less than 0.001), more persistent thallium-201 defects (2.2 +/- 1.1 versus 1.4 +/- 1.1, p less than 0.001), abnormally increased lung uptake of thallium (33 versus 18%, p less than 0.01) and a greater number of akinetic or dyskinetic segments (3.2 +/- 2.5 versus 1.4 +/- 1.9, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective clinical, scintigraphic, angiographic and functional evaluation of patients after inferior myocardial infarction with and without right ventricular dysfunction.

To elucidate the functional and prognostic significance of right ventricular dysfunction after acute inferior wall myocardial infarction, 74 consecutive patients with inferior infarction were prospectively evaluated with gated equilibrium blood pool imaging at rest, submaximal exercise thallium-201 scintigraphy and coronary angiography before hospital discharge. In addition, symptom-limited stress thallium-201 scintigraphy was performed in 61 patients at 3 months, and all patients were followed up clinically for 23 +/- 15 months. Utilizing predetermined radionuclide angiographic criteria, 47 patients (Group I) had normal right ventricular function, 12 patients (Group II) had mild to moderate dysfunction and 15 patients (Group III) had severe right ventricular dysfunction. There were no significant differences among the groups with regard to age, history of prior myocardial infarction, peak creatine kinase values, maximal Killip functional class, number or type of in-hospital complications, left ventricular ejection fraction, prevalence of multivessel disease or the distribution and severity of disease affecting the infarct-related vessel. Exercise tolerance as assessed by treadmill time, blood pressure-heart rate product and peak work load in METS was comparable among the three groups, both before hospital discharge and at 3 month follow-up. No differences in indicators of exercise-induced ischemia were noted among the groups, including the prevalence of redistribution thallium-201 defects, ST segment depression or symptoms of chest pain. Finally, cardiac mortality, reinfarction rate and the incidence of medically refractory angina pectoris were similar in the three groups. Thus, right ventricular dysfunction after acute inferior wall myocardial infarction does not appear to limit exercise tolerance or identify a subgroup of patients at higher risk for recurrent cardiac events.

Use of a regional wall motion score to enhance risk stratification of patients receiving an implantable cardioverter-defibrillator.

OBJECTIVES: We postulated that preoperative assessment of both regional wall motion and left ventricular ejection fraction would serve as an accurate prognostic indicator of long-term cardiac mortality and functional outcome in patients treated with an implantable cardioverter-defibrillator. BACKGROUND: Long-term cardiac mortality has remained high in patients receiving an implantable cardioverter-defibrillator. The ability to risk stratify patients before defibrillator implantation is becoming increasingly important from a medical and economic standpoint. METHODS: The hypothesis was retrospectively tested in 74 patients who had received an implantable cardioverter-defibrillator. Left ventricular ejection fraction and regional wall motion score, derived from centerline chord motion analysis, were calculated for each patient from the preoperative right anterior oblique contrast ventriculogram. Wall motion score was the only significant independent predictor of long-term cardiac mortality and functional status by multivariate analysis because of its enhanced prognostic capability in patients with an ejection fraction in the critical range of 30% to 40%. RESULTS: Patients with an ejection fraction > 40% had a 3-year cardiac mortality rate of 0% compared with 25% for those with an ejection fraction of 30% to 40% and 48% for those with an ejection fraction < 30% (p < 0.05). Similarly, 75% of patients with an ejection fraction > 40% were in New York Heart Association functional class I or II during long-term follow-up compared with 59% of those with an ejection fraction 30% to 40% and 29% of those with an ejection fraction < 30%. Among patients with an ejection fraction of 30% to 40%, those with a wall motion score > 16% had a 3-year cardiac mortality rate of 0% compared with 71% of those with a wall motion score < or = 16% (p = 0.002). In addition, 86% of patients with a wall motion score > 16% were in functional class I or II during long-term follow-up compared with 13% of those with a wall motion score < or = 16% (p = 0.001). CONCLUSIONS: Long-term cardiac mortality and functional outcome in patients receiving an implantable cardioverter-defibrillator can be predicted if the left ventricular ejection fraction and regional wall motion score are measured preoperatively.

Neuron specific alpha-adrenergic receptor expression in human cerebellum: implications for emerging cerebellar roles in neurologic disease.

Recent data suggest novel functional roles for cerebellar involvement in a number of neurologic diseases. Function of cerebellar neurons is known to be modulated by norepinephrine and adrenergic receptors. The distribution of adrenergic receptor subtypes has been described in experimental animals, but corroboration of such studies in the human cerebellum, necessary for drug treatment, is still lacking. In the present work we studied cell-specific localizations of alpha1 adrenergic receptor subtype mRNA (alpha 1a, alpha 1b, alpha 1d), and alpha2 adrenergic receptor subtype mRNA (alpha 2a, alpha 2b, alpha 2c) by in situ hybridization on cryostat sections of human cerebellum (cortical layers and dentate nucleus). We observed unique neuron-specific alpha1 adrenergic receptor and alpha2 adrenergic receptor subtype distribution in human cerebellum. The cerebellar cortex expresses mRNA encoding all six alpha adrenergic receptor subtypes, whereas dentate nucleus neurons express all subtype mRNAs, except alpha 2a adrenergic receptor mRNA. All Purkinje cells label strongly for alpha 2a and alpha 2b adrenergic receptor mRNA. Additionally, Purkinje cells of the anterior lobe vermis (lobules I to V) and uvula/tonsil (lobules IX/HIX) express alpha 1a and alpha 2c subtypes, and Purkinje cells in the ansiform lobule (lobule HVII) and uvula/tonsil express alpha 1b and alpha 2c adrenergic receptor subtypes. Basket cells show a strong signal for alpha 1a, moderate signal for alpha 2a and light label for alpha 2b adrenergic receptor mRNA. In stellate cells, besides a strong label of alpha 2a adrenergic receptor mRNA in all and moderate label of alpha 2b message in select stellate cells, the inner stellate cells are also moderately positive for alpha 1b adrenergic receptor mRNA. Granule and Golgi cells express high levels of alpha 2a and alpha 2b adrenergic receptor mRNAs. These data contribute new information regarding specific location of adrenergic receptor subtypes in human cerebellar neurons. We discuss our observations in terms of possible modulatory roles of adrenergic receptor subtypes in cerebellar neurons responding to sensory and autonomic input signals, and review species differences in cerebellar adrenergic receptor expression.

The contributors to Volume 1 (1891) of The Journal of Comparative Neurology: C.L. Herrick, C.H. Turner, H.R. Pemberton, B.G. Wilder, F.W. Langdon, C.J. Herrick, C. von Kupffer, O.S. Strong, T.B. Stowell.

The concept of a truly innovative "neurology" journal germinated in the mind of Clarence Luther Herrick and then flowered, in March of 1891, as the first issue of Volume 1 of The Journal of Comparative Neurology. The other parts appeared in June, October, and December of the same year. The contributors to this volume, and their affiliations, were: C.L. Herrick (University of Cincinnati-UC), C.H. Turner (UC), B.G. Wilder (Cornell), F.W. Langdon (Miami Medical College, Cincinnati), C.J. Herrick (UC) H.R. Pemberton (Princeton), T.B. Stowell (State Normal and Training School, Potsdam), and O.S. Strong of Columbia who translated a large paper by Carl von Kupffer, the famous German anatomist. In 1890-91 some of these scientists (e.g., Wilder, Langdon, Stowell, von Kupffer) were well known and had already made notable contributions in their chosen fields. However, several were students (e.g., Turner, C.J. Herrick, Pemberton, Strong), most of whom would make important contributions in later years. The founder of JCN, Clarence Luther Herrick, by 1891 had an excellent reputation in geology and natural science and had already established a successful scientific journal. Based on the totality of their contributions, the authors of the papers that made up Volume 1 of JCN were a unique group. Textbooks that went through several editions came from Wilder, C.J. Herrick, and Strong; the latter is currently going into its 9th edition. Structures were named in recognition of the original descriptions by von Kupffer and C.L. Herrick, a type of insect behavior recognized Turner's discovery, and after their deaths several had university buildings, one a scientific club, and one a research award, named in their honor. There were also interesting and important links between these nine men. Turner and C.J. Herrick were students of C.L. Herrick, and Stowell served as a member of the Association of American Anatomists nomenclature committee which was chaired by Wilder. C.J. Herrick became a student (for his Ph.D.) of Strong's, and Strong became an associate editor of JCN under C.J. Herrick. Of the nine, two practiced medicine; Langdon in an academic setting, Pemberton in private practice. The lives of the nine scientists whose work made up Volume 1 of JCN are reviewed. Many of these individuals were notable, not only for their work in the first volume of JCN, but for their larger and enduring contributions in the biomedical sciences.

Evidence of intracerebellar collateralization of nucleocortical cell processes in a prosimian primate (Galago): a fluorescence retrograde study.

The distribution of single and/or double-labeled neurons in the cerebellar nuclei was investigated in a prosimian primate (Galago) by means of fast blue (FB) and nuclear yellow (NY) as retrograde tracers. Injections were made into spatially separate regions of cerebellar cortex on one side (zones C1-C3 in lobules IV and V and in the paramedian lobule) and into the same zones of lobules IV and V on both sides. Following unilateral injections single- and double-labeled somata were seen in the anterior (NIA) and posterior (NIP) interposed cerebellar nuclei on the same side. Single-labeled cells were, in general, more concentrated in NIA from the lobule IV-V injection and in NIP from the PML placement; double-labeled somata were about evenly distributed between NIA and NIP. Cell labeling was sparse in the contralateral NIP. Large and small somata were filled with FB, NY, or FB + NY ipsilateral to the injection sites while the majority of labeled neurons on the contralateral side had small oval- or fusiform-shaped somata. Subsequent to bilateral injections cells labeled with each tracer were concentrated in the NIA, moderate in number in the NIP, both on the ipsilateral side, and sparse in the contralateral NIP. The double labeling of cells in the present study indicates that these neurons project to spatially separated, yet possibly functionally related, areas of ipsilateral cortex. Since larger and small somata were double labeled it is possible that those cells with cerebellofugal processes to extracerebellar targets may simultaneously relay information to divergent cortical sites. In contrast, the few labeled cells seen in the contralateral NIP have small oval and fusiform somata. These neurons may be specifically involved in cerebelloolivary and olivocerebellar feedback loops.

HRP study of cerebellar corticonuclear-nucleocortical topography of the dorsal culminate lobule--lobule V--in a prosimian primate (Galago): with comments on nucleocortical cell types.

The distribution of retrogradely labeled cerebellar nucleocortical (NC) cells and anterogradely labeled corticonuclear (CN) fibers was investigated in a prosimian primate (Galago) by means of horseradish peroxidase as a tracer. Iontophoretic and pressure injections were made in the cortex of lobule V and the resultant patterns of label were determined in the cerebellar nuclei. Following iontophoretic injections in vermal (zone A), intermediate (zones C1, C3), and lateral (zone D) cortices, retrogradely labeled cells were present in medial (NM), anterior interposed (NIA), and lateral (NL) cerebellar nuclei, respectively. Larger injections that involved A-C2 zones resulted in NC label in NM, medial NIA, and throughout the posterior interposed (NIP) nucleus. Retrogradely labeled NC cells were usually found in areas of their respective nuclei that also contained anterogradely filled CN axons. In addition, retrogradely labeled cells were seen contralateral to some injection. Contralateral NC cells were found mainly in the NM and NIP and seemed to be labeled in response to injections that involved zones A, C2, and possibly x on the opposite side. No contralateral CN labeling was seen. It appears that the NC projections of lobule V follows a basic zonal (sagittal) orientation and that most are reciprocal to CN fibers arising from the same cortical area. There is evidence of zonal heterogeneity in the ipsilateral NC projection. Iontophoretic injections placed in adjacent zones resulted in markedly different numbers of retrogradely labeled NC cells in their respective nuclei. Also, after pressure injections that involved two or more adjoining zones, the number of labeled NC cells was large in one nucleus but minimal in an adjacent nucleus. These data suggest that different cerebellar cortical zones have quantitatively different NC input; this may relate to specific functional demands placed on each nucleus and its corresponding cortical zone. On the basis of their known connections, it is hypothesized that there are at least three and possibly four categories of NC cells. Ipsilateral reciprocal NC cells are found in, or on the periphery of, CN terminal fields formed by axons originating from the same cortical area to which the NC cells project. Ipsilateral nonreciprocal NC cells are located outside the CN terminal field and may even be found in an adjacent nucleus; these are fewer in number than the reciprocal population. Contralateral NC cells are found in the opposite cerebellar nuclei and appear to be topographically related to the ipsilateral contingent as well as to the injection site.(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebellar cortical efferents of the posterior lobe vermis in a prosimian primate (Galago) and the tree shrew (Tupaia).

The topographical organization of cerebellar cortical efferents of the posterior lobe vermis was studied in a prosimian primate (Galago senegalensis) and the tree shrew (Tupaia glis). Two patterns emerge; one which shows longitudinal zones of the entire vermis and a second which shows that induvidual lobules within the overall longitudinal pattern terminate in specific areas of the ipsilateral medial cerebellar nucleus (NM) and vestibular complix. The posterior lobe vermis consists of a narrow midline portion which projects bilaterally into the NM and a paramidline zone which projects only into the ipsilateral NM. These two zones are probably comparable to, and subdivisions of, Zone A of Voogd ('69). The lateral vermal zone projects primarily into the ipsilateral vestibular complex and/or interposed nuclei and appears to correspond to Zone B of Voogd ('69). Within this overall pattern individual lobules project into specific portions of the NM. From rostral to caudal (lobules VI to IX) terminal fields in the NM shift from dorsal and dorsomedial to ventral and ventrolatera. This is the inverse of the pattern of termination seen in the vestibular complex from lesions of the same lobules where from rostral to caudal (VI to IX) there are overlapping terminal fields from lateral to medial. With the exception of the narrow midline zone cerebellar corticonuclear projections of the posterior lobe vermis are ipsilateral. There is a more complex and more precise relationship between the posterior lobe vermis, NM and vestibular complex than previously suggested.

Cerebellar corticovestibular fibers of the posterior lobe in a prosimian primate, the lesser bushbaby (Galago senegalensis).

The orginization of cerebellar corticovestibular fibers was studied in a prosimian primate (Galago senegalensis) using the Fink and Heimer ('67) method. The vestibular complex of Galago is larger than in other mammals and some higher primates. Vermis lobule IX contributes the largest number of fibers to the ipsilateral vestibular complex. Lobules VI and VIII give rise to lesser, but similar, numbers of fibers which also pass into the ipsilateral vestibular nuclei. Vermis lobule VII and the paravermal and lateral cortices contribute extremely sparse numbers of fibers to the dorsal area of the ipsilateral vestibular complex. All degenerated fibers enter the vestibular nuclei through a large diffusely organized juxtarestiform body. Fibers from vermis lobule VII and the paravermal and lateral cortices terminate in dorsal areas of the ipsilateral vestibular nuclei. Vermis lobule VI projects into dorsal and lateral regions of the ipsilateral SVN, LVN and SpVN. Vermis lobules VIII and IX project into the dorsal and into progressively more central and medial regions of the ipsilateral SVN, LVN, and SpVN. This gives the clear impression of a rostro-caudal origin of fibers from the posterior lobe vermis which terminate in an overlapping lateral to medial sequence in the vestibular complex. In addition to its projection into the vestibular nuclei, lesions of vermis lobule IX also elicit degeneration in dorsal areas of the ipsilateral medullary reticular formation and in the ipsilateral parabrachial nuclei.

Cerebellar corticonuclear and corticovestibular fibers of the anterior lobe vermis in a prosimian primate (Galago senegalensis).

Efferent projections of the anterior vermis were studied in a prosimian primate (Galago senegalensis). Cerebellar corticoncuclear and corticovestibular fibers of the anterior lobe vermis are, in toto, ipsilateral. Two additional main points emerge. First, evidence is given which suggests that the cortical ara defined as vermis converges, in a rostral direction (from lobules V to I + II), as the hemispheres of these lobules become latero-medially fore-shortened. The anterior vermis is a cortical region reflected by its efferent projections and not an arbitrary median strip of cortex which is either constant in width or morphologically separated from adjacent paravermal areas. Secondly, two patterns of organization emerge concerning cortical efferents, one suggestive of longitudinal zones and a second which shows that individual lobules project mainly to specific areas of the ipsilateral NM and into portions of the vestibular complex. Three zones are recognized. A very narrow midline area which appears to project bilaterally to the NM, a wider intermediate area (homologous to zone A) related to the ipsilateral NM, and a lateral area (homologous to zone B) related mainly to the ipsilateral vestibular complex, primarily its lateral nucleus. Within this overall zonal organization individual lobules project to specific areas of the NM and vestibular complex. Lobules V and IV project to rostrodorsal and rost-ocentral NM respectively and into the dorsal LVN. Lobules III and II + I project to rostroventral-medial and rostroventral-lateral NM respectively, throughout the LVN and minimally into the SVN and SpVN. The specificity of cortico-nuclear terminations in the NM from the anterior vermis, heretofore not described for any primate, are similar, in terms of a general pattern, to that recently reported for the cat (Courville and Diakiw, '76).

Cerebellar corticonuclear fibers of the paramedian lobule of tree shrew (Tupaia glis) with comments on zones.

Following a series of lesions in dorsal (DPML) and ventral (VPML) divisions of tree shrew (Tupaia) paramedian lobule (PML), the distribution of degenerated axons within the deep cerebellar nuclei was determined using the Fink and Heimer ('67) method. Damage to PML produced axonal degeneration in lateral (NL), anterior interposed (NIA), and posterior interposed (NIP) cerebellar nuclei. No degenerated fibers could be traced to either the medial cerebellar nucleus or vestibular complex, via juxtarestiform body, from lesions in PML. Corticonuclear fibers to NL, NIA, and NIP from PML cortex are topographically organized. Subsequent to lesions of lateral DPML, axonal debris is found in rostral and medial NL, while the lateral edge of VPML projects primarily into medial NL. According to the terminology of Voogd ('69) these lateral regions of PML represent the D zone. The NIP receives corticonuclear input from a relatively wide middle area of both portions of PML, interpreted as the C2 zone. There is some evidence which suggests that medial portions of the C2 area of DPML project into more lateral areas of NIP, while lateral regions of this zone in DPML are related to more medial NIP. This projection pattern is invited for the C2 area of VPML; medial C2 to medial NIP, lateral C2 to lateral NIP. Corticonuclear fibers of PML which enter NIA appear to arise from a narrow, irregular, partially discontinuous strip of cortex located at the interface of the D and C2 areas in lateral PML and from a wider, more regular region in the most medial areas of this lobule. These represent, respectively, the C3 and C1 zones. Although an overall pattern of zones is present, there is evidence to suggest that their spatial organization differs from DPML to VPML. The zonal patterns appears to be more obvious in VPML, while this pattern for DPML is less distinct. This is interpreted as indicating that either (1) zones C1--C3 overlap to a greater degree in DPML than in VPML, or (2) zones C1 and C3 may converge in rostral DPML, partially obliterating the intervening zone C2. The different ways in which zonal terminology is applied to both corticonuclear and certain of the afferent cerebellar systems are discussed.

Secondary vestibulocerebellar projections to flocculonodular lobe in a prosimian primate, Galago senegalensis.

The organization of vestibulocerebellar projections to the flocculonodular and adjacent cortices were studied in Galago using horseradish peroxidase (HRP). Implants of HRP pellets or injections (0.14-0.95 microliter) were placed in floccular, parafloccular, nodular, and uvular cortices. Following survival times of 18-25 hours animals were killed via transcardiac perfusion of heparinized saline followed by a buffered solution of paraformaldehyde and glutaraldehyde. Tissues were processed using DAB as the chromogen. Consequent to floccular implants HRP-positive cells are found bilaterally in medial (MVN), spinal (SpVN), and superior (SVN) vestibular nuclei. Labeled neurons are present in the ipsilateral subgroup y and interstitial nucleus of the eighth nerve. The prepositus hypoglossal nuclei also contained HRP-positive somata. A column of labeled cells is present exclusively in dorsomedial MVN subsequent to injection of the paraflocculus. Injections of nodular cortex reveal a distinct bilateral projection to this cortical area. Many labeled cells are located in SpVN, MVN, SVN, subgroups x and y, the interstitial nucleus, and the ganglion of the eighth nerve. Labeled somata are concentrated in dorsal and dorsolateral SpVN and in a bandlike configuration in subgroup x. HRP-reactive cells appear to have a differential rostrocaudal distribution in MVN, while the majority of positive cells in SVN are found in central portions of the nucleus. After HRP injection into the transition area between nodular and uvular cortices, labeled neurons are present in MVN, SpVN, and the prepositus hypoglossal nucleus. A similar distribution of HRP-positive cells is seen following injections of ventral uvula; however, cells are markedly fewer in number. In no case, subsequent to injection of the flocculonodular lobe and adjacent cortices, are HRP-labeled neurons found in the lateral vestibular nucleus.