Treating electrical storm : sympathetic blockade versus advanced cardiac life support-guided therapy.

BACKGROUND: Electrical storm (ES), defined as recurrent multiple ventricular fibrillation (VF) episodes, often occurs in patients with recent myocardial infarction. Because treating ES according to the Advanced Cardiac Life Support (ACLS) guidelines yields a poor outcome, we evaluated the efficacy of sympathetic blockade in treating ES patients and compared their outcome with that of patients treated according to the ACLS guidelines. METHODS AND RESULTS: Forty-nine patients (36 men, 13 women, mean age 57+/-10 years) who had ES associated with a recent myocardial infarction were separated into 2 groups. Patients in group 1 (n=27) received sympathetic blockade treatment: 6 left stellate ganglionic blockade, 7 esmolol, and 14 propranolol. Patients in group 2 (n=22) received antiarrhythmic medication as recommended by the ACLS guidelines. Patient characteristics were similar in the 2 groups. The 1-week mortality rate was higher in group 2: 18 (82%) of the 22 patients died, all of refractory VF; 6 (22%) of the 27 group 1 patients died, 3 of refractory VF (P<0.0001). Patients who survived the initial ES event did well over the 1-year follow-up period: Overall survival in group 1 was 67%, compared with 5% in group 2 (P<0.0001). CONCLUSIONS: Sympathetic blockade is superior to the antiarrhythmic therapy recommended by the ACLS guidelines in treating ES patients. Our study emphasizes the role of increased sympathetic activity in the genesis of ES. Sympathetic blockade-not class 1 antiarrhythmic drugs-should be the treatment of choice for ES.

Identification, distribution, and developmental changes of a melatonin binding site in the song control system of the zebra finch.

In many avian species, singing is a circadian or seasonal behavior that appears to be widely dependent on gonadal steroid hormones. To explore the possibility of a further hormone-dependent vocal control mechanism driven by the action of melatonin, we examined the binding of iodinated melatonin (IMEL) in the vocal control network of adult and juvenile (22- and 40-day-old) zebra finches. IMEL binding areas of the zebra finch brain were localized and characterized by using quantitative in vitro autoradiography. In the vocal control system, dense IMEL binding sites were restricted to the nucleus hyperstriatalis ventrale, pars caudalis (HVC). The binding of IMEL to the HVC and to visual areas, e.g., the ectostriatum and the optic tectum, was saturable and showed a single class of high-affinity binding sites with binding affinities (Kds) in the range of 5-20 pM. Competition experiments with various indols and IMEL showed that the IMEL binding site in the zebra finch brain has properties similar to the high-affinity melatonin receptor described in the chicken, in the house sparrow, and in the mammalian brain and retina. Similar to the zebra finch HVC, the HVC of other songbirds, e.g., male canaries and male house sparrows, has the most intense IMEL binding of all areas of the vocal control network. The IMEL binding in the forebrain vocal control areas of the zebra finch, but not that in the visual processing areas, was sexually dimorphic in correlation with the sexually dimorphic neuroanatomy of the forebrain vocal control areas. In the HVC, there is a developmental increase in the maximal number of binding sites for IMEL and in the protein content, so that the adult phenotype of dense IMEL binding develops between day 40 and day 80. The distribution and developmental pattern of IMEL binding in the song system suggests that melatonin has a role in the motor control of singing. Melatonin binding sites in HVC could link HVC-based song control to circadian and circannual changes in the photoperiod independent of gonadal steroids.

First somatosensory cortical columns and associated neuronal clusters of nucleus ventralis posterolateralis of the cat: an anatomical demonstration.

Microlesions (30--275 microns in diameter) were placed in VPLm of the cat and the terminal axonal degeneration in SI cortex was stained using the Fink-Heimer I technique. Following each of these microlesions, small, localized patches or subcolumns of degeneration, relatively light in density, were observed within laminae IIIb and IV of SI when viewed in the coronal plane. In addition, a few degenerating fibers ascended to lamina I. These multiple subcolumns had distinct radial boundaries and were narrow in the mediolateral plane (80--120 microns in width) but elongated rostro-caudally (2500--3000 microns in length). Localized patches of degeneration were separated at their widest points by a distance of 500 microns medio--laterally, but at various rostro--caudal levels of SI were observed to merge into larger columns of degeneration (250--400 microns) and then separate again into smaller multiple patches (i.e., a "zebra-like" pattern). Small injections of HRP into the forelimb region of area 3b or rostral area 1--2 of SI resulted in the labeling of small, discrete clusters of neurons in the ventral regions of VPLm. The clusters examined ranged in size from 140--350 microns in medio--lateral diameter and were elongated rostro--caudally (up to 500 microns in extent); virtually all cells within a cluster appeared labeled, but not equally so. A pattern of HRP labeling different from that observed following area 3b and rostral area 1--2 injections was observed following injections into more caudal regions of area 1--2 and into SII cortex. The labeling that resulted from these injections was not in the form of neuronal clusters but instead labeled cells tended to be scattered in more dorsal regions of VPLm. This scattering did not appear to be random since the labeled neurons were grouped within the same general area of VPLm. Labeling was distributed throughout a number of cell clusters, comprising only a small proportion of cells within each cluster. The pattern of labeling seen after caudal area 1--2 and SII injections differed only in its rostro--caudal extent within VPLm. SII injections generally resulted in labeling along the full rostro--caudal dimension of VPLm. A differential organization of the anatomy of thalamocortical projections to the various subdivisions of SI and to SII was noted in this study. It is postulated that the multiple, discrete patches of degeneration in laminae IIIb and IV of SI represent a portion of the somatosensory cortical columns and that the HRP-labeled clusters seen in VPLm following area 3b and rostral area 1--2 are the subcortical equivalents of these subcolumns.

Long-term antithrombotic treatment for atrial fibrillation.

Nonvalvular atrial fibrillation (AF) is the most common cardiac disorder causing stroke and systemic emboli. Recent clinical trials have clearly demonstrated the effects of antithrombotic treatment in preventing these devastating complications of AF. This review summarizes the salient findings of the first 5 published studies the Atrial Fibrillation, Aspirin, Anticoagulation Study (AFASAK) from Copenhagen, Denmark; the Boston Area Anticoagulation Trial for Atrial Fibrillation (BATAFF); the Canadian Atrial Fibrillation Anticoagulation study (CAFA); the Stroke Prevention in Non-rheumatic Atrial Fibrillation (SPINAF) study; and the Stroke Prevention in Atrial Fibrillation study (SPAF I) from the United States. These trials emphasize the unequivocal benefits of warfarin therapy compared with no treatment. SPAF II showed that aspirin is quite effective in younger patients (<75 years) who have no risk factors. The European Atrial Fibrillation Trial (EAFT) and SPAF III demonstrated that in older patients (>75 years) who had associated risk factors, warfarin therapy at the target international normalized ratio (INR) of 2-3, is the best treatment; however, a combination of low intensity fixed-dose warfarin and aspirin is ineffective. Thus, the guidelines recommended by the American College of Chest Physicians should be followed in treating patients with AF.

Daily changes in melatonin binding sites and the effect of castration.

The effect of castration and/or neonatal administration of testosterone propionate (TP) on 125I-melatonin binding and its daily changes was studied in rat anterior pituitary (AP) and in pars tuberalis/median eminence (PT/ME). In animals kept on a light/dark cycle of 12:12 h there was a marked increase in binding site density (Bmax) in the evening as compared to the morning, while there were no differences in the affinity (Kd). On a light/dark cycle of 8:16 h the daily rhythm in Bmax was abolished and the values were intermediate. Neonatal TP administration which increases the sensitivity of the reproductive axis to melatonin and photoperiodic regulations had no effect on the binding parameters in AP and in PT/ME. Castration, however, increased binding site density in AP by 85% while it had no effect on the affinity of the binding site (Kd).

Focal and diffuse metabolic changes in the spinal cord of the monkey elicited by microstimulation of differing motor cortical foci.

The pattern of projections from identified motor cortical efferent zones onto the spinal cord was examined in the monkey using a combination of microstimulation and [14C]2-deoxyglucose metabolic labeling. Regional differences were found in the branching patterns between the projections of proximal and distal forelimb foci of the motor cortex onto the spinal cord. Cortical efferent zones related to proximal movements project extensively within the spinal cord activating numerous motor nuclei. In contrast, the corticospinal projection of a distal movement zone was found to be significantly more restricted in overall rostrocaudal extent projecting with greatest density onto a small focal region of the ventrolateral horn.

Effects of menthol on peripheral nerve and cortical unit responses to thermal stimulation of the oral cavity in the rat.

Neurophysiological responses were recorded in individual fibers of the lingual and chorda tympani nerves and in single cortical neurons in the rat in response to a battery of tactile, thermal and chemical stimuli applied to the oral cavity. Two categories of thermally sensitive units were identified. Chorda tympani fibers and one type of cortical unit ('Type I') were activated by cold water stimulation but were unaffected by warm water or menthol. In contrast, lingual fibers and a different category of cortical units ('Type II') were extremely sensitive to menthol exposure. These units were cold water sensitive, however, this sensitivity was suppressed following menthol presentation.

Cortical unit responses to chemical stimulation of the oral cavity in the rat.

The gustatory sensitivity of individual cortical neurons in the rat was examined using a wide range of chemical stimuli. Several subsets of cortical taste cells were identified based on similarities in their response profiles. Although adjacent cortical neurons can differ in their responsiveness to individual tastants, some overlap in taste sensitivities is usually observed.

Modification of the projection from the sensory cortex to the motor cortex following the elimination of thalamic projections to the motor cortex in cats.

Examination of the projection from area 2 of the sensory cortex to the motor cortex revealed substantial changes following lesion of the ventrolateral nucleus of the thalamus. These observed changes were as follows. (1) The polarity of the evoked potentials elicited by area 2 stimulation reversed in the depth of the motor cortex whereas in normal animals, there was no reversal. (2) The amplitude of area 2-elicited EPSPs in the motor cortical neurons became greater following the lesion of VL. (3) The shape of the observed EPSPs was characterized by multiple peaks whereas in normal animals, the EPSPs were generally smooth and monophasic. (4) Neurons receiving a short-latency input from area 2 were distributed throughout the depths of the motor cortex whereas in normal animals, they were located only in the upper layers (layers II and III). (5) Intracellular injection of HRP revealed that the neurons receiving short-latency input were not restricted to typical stellate type cells, but also included bipolar or bitufted neurons with elongated cell bodies and polarized arborizations. These neurons were located in the superficial (II and III) as well as in the deep (V) layer. It is concluded that the elimination of thalamic input resulted in the reinforcement of the corticocortical input to the motor cortex. The subsequently observed corticocortical projection extended to neurons did not originally innervated by the association fibers. The results suggested that functional recovery following thalamic lesion is partly due to reorganization of projections from the sensory cortex to the motor cortex.

Morphological and electrophysiological study of sprouting of corticorubral fibers after lesions of the contralateral cerebrum in kitten.

The appearance of crossed corticorubral projections following ablations of the ipsilateral cortex is shown to result from the formation of new connections and is not due to the preservation of pre-existing bilateral connections. At least some of these crossed projections are collaterals of the pyramidal tract. Post-tetanic potentiation can be demonstrated both intra- and extracellularly following ipsilateral cerebral peduncle stimulation whereas no changes in excitatory postsynaptic potential amplitude are observed following contralateral cerebral peduncle stimulation.

Gustatory cortex in the rat. I. Physiological properties and cytoarchitecture.

The precise cytoarchitectural localization of taste-elicited cortical responses in the rat was studied using a combination of anatomical and physiological techniques. Multi-unit responses to tongue tactile, thermal and gustatory stimuli were recorded along 97 electrode penetrations positioned parallel to the lateral convexity of the brain and marking lesions were placed at the sites of transitions in these functional properties. Lesions made at sites that received different sensory inputs were consistently located within different cytoarchitectural subdivisions. In this manner, taste cortex in the rat was localized to the agranular insular cytoarchitectural region, in contrast to its traditional assignation to granular insular cortex. Instead, tongue temperature was found to be represented in the cortical area previously termed gustatory, i.e., in ventral granular cortex where layer IV attenuates.

Gustatory cortex in the rat. II. Thalamocortical projections.

The thalamic relay for lingual tactile, thermal, and gustatory sensibility was defined electrophysiologically in the rat. Subsequently, injections of tritiated leucine were centered in these functionally defined locations in separate series of rats. Following suitable survival periods, the brains were processed for autoradiographic tracing of axonal projections. After injections confined to the thalamic gustatory relay, labeled fibers terminated in agranular insular cortex. These results provide support for our previous experiments correlating neurophysiological localization of rat gustatory cortex and regional cytoarchitecture, and contrast with the traditional assignation of gustatory cortex to the granular insular area.

Anatomical and physiological properties of the projection from the sensory cortex to the motor cortex in normal cats: the difference between corticocortical and thalamocortical projections.

Details of the distribution of terminal sites of the projection fibers from area 2 of the sensory cortex to the motor cortex were studied and compared with the distribution of terminals from the ventrolateral (VL) nucleus of the thalamus to the motor cortex. The results obtained were as follows: Intracortical microstimulation (ICMS) in area 2 produced measurable short-latency EPSPs only in neurons located in layers II and III of the motor cortex, whereas VL stimulation produced short-latency EPSPs in neurons throughout the depths of the motor cortex. The time from the beginning to the peak of the EPSPs was not significantly different for area 2- and VL-elicited EPSPs suggesting that there was no systematic difference between effective terminal sites for both inputs. However, there was a difference when a given neuron received both inputs suggesting that there was a segregation between the two inputs within a given cell. The majority of area 2-elicited EPSPs were smooth and monophasic, but some (40%) of them showed double peaks indicating that some neurons received mono- and disynaptic inputs from area 2. Intracellular injections of HRP suggested that neurons receiving input from area 2 were predominantly multipolar non-pyramidal neurons in layers II and III whereas neurons receiving thalamic input were pyramidal as well as non-pyramidal cells. Field potentials in the motor cortex evoked by area 2 stimulation did not change polarity in the depths of the cortex and therefore, differed from the VL-evoked potentials suggesting differences in the mechanisms of generating the electrical fields. It is concluded that association fibers effective for producing EPSPs terminate primarily on non-pyramidal cells in layer II and III whereas VL fibers terminate not only on pyramidal but also on non-pyramidal cells in layers III and V. This study provided a basis for examining the modifiability of association fibers after elimination of VL input to the motor cortex which is reported in the following paper.

Effect of photoperiod on the pineal melatonin rhythm in neonatal rats.

Photoperiod already modulates pineal melatonin rhythm in neonatal rats. Pineal melatonin content was about 500 fmol during day and increased up to 2000 and 3000 fmol at night in 8- and 12-day-old rats, respectively. On long photoperiods (LD 14:10) melatonin was increased above 1000 fmol for about 8 h while on short photoperiods (LD 8:16) for 12 to 14 h. Melatonin pattern may thus transduce photoperiodic effects in neonatal rats. However, no differences in plasma LH were found in the rats kept on long and short photoperiods.

Drug effects on attack defense and escape in mice.

The relative specificity and potency of action of 32 neuropsychotropic drugs was assessed on attacks, defensive upright postures and escapes occurring in singly-housed male mice during interactions with non-aggressive strange males. Scopolamine was most potent in reducing attacks while apomorphine was most active in stimulating attacks. Defenses and escapes were inhibited most efficiently by pentobarbital and diazepam, while L-tryptophan was most active of the tested drugs in stimulating defenses and escapes. Aminooxyacetic acid and valproate inhibited both attack and defensive-escape behavior at relatively low doses. Inhibition of attacks by many drugs tested could be explained by anticholinergic, serotonergic or gabaergic effects while stimulation of attacks may be due to dopaminergic effects. Gabaergic drug actions seem to inhibit while serotonergic effects might stimulate defenses and escapes.

Ontogenesis of melatonin receptors in anterior pituitary and pars tuberalis of golden hamsters.

The ontogenesis of melatonin receptors in the anterior pituitary and pars tuberalis of the Golden hamster was studied using [125I]iodomelatonin as a ligand. The affinity of the binding site to the ligand (Kd) was in the range 21 to 54 pM and it did not change significantly during development. The concentration of the [125I]iodomelatonin binding sites in the anterior pituitary was highest in one-day-old hamsters (Bmax = 14 fmol/mg protein) and thereafter gradually decreased. In adults it reached to about 6% of the neonatal values. In contrast, the concentration of the binding sites in pars tuberalis did not change significantly during ontogenesis and it was in the range of 3 to 5 fmol/mg protein.

[The Penrose drain as a finger tourniquet: a study]. / Der Penrose-Drain als Fingertourniquet: Eine Untersuchung.

As finger tourniquets are used frequently in surgery of the hand, it is necessary to study the safety of this technique in order to prevent complications of ischemia such as described by Dove and Clifford in 1982. Finger tourniquets applied with high pressure compromise the blood flow to the finger as well as damage the digital nerves. The authors use their previously described technique for controlling the pressure beneath a penrose drain and measure the tissue pressure generated by such a technique by placing a Wick catheter along the neurovascular bundle of a cadaver finger as well as in the soft tissue of an in vivo Sprague Dowley rat hindlimb preparation. The pressures measured by this technique were consistent with what one would expect based on the estimated pressure generated by placing marks spaced 26 mm apart and stretching them the circumference of an average sized adult finger.

Assessment of coronary artery aneurysms with multiplane transesophageal echocardiography.

Coronary artery aneurysms are rare and may be difficult to detect clinically. Multiplane transesophageal echocardiography provides numerous imaging planes that may improve the assessment of coronary aneurysms and act as an adjunct to standard angiography. Five patients with angiographically detected coronary aneurysms were studied with multiplane transesophageal echocardiography and Doppler flow imaging. Transesophageal echocardiography was successful in identifying the size and characteristics of the coronary aneurysms. Doppler ultrasound identified markedly increased flow velocity in a patient with a coronary arteriovenous fistula and decreased coronary flow velocity in two patients with aneurysmal coronary arteries and intracoronary thrombus. Multiplane transesophageal echocardiography is a useful, noninvasive method of assessing coronary artery aneurysms and may act as an adjunct to angiography in identifying fistula anastomosis.

A nonfluoroscopic catheter-based mapping technique to ablate focal ventricular tachycardia.

The recent introduction of a nonfluoroscopic electroanatomical cardiac mapping system (CARTO) is an exciting development in catheter ablation treatment of cardiac arrhythmias. The system uses ultralow magnetic fields to locate a sensor positioned near the tip of a regular mapping and ablation catheter. The catheter location and electrograms are recorded and reconstructed in real-time and presented as a three-dimensional geometrical mapped color coded with the electrophysiological information. The CARTO represents an important tool to guide the ablation of patients who have focal tachycardia (e.g., right ventricular outflow tract [RVOT] tachycardia and idiopathic left ventricular [ILV] tachycardia). This study describes how the CARTO system is useful in mapping and ablating these arrhythmias. Two case illustrations, one patient with RVOT tachycardia and another with ILV tachycardia, are described in this article. The tachycardia was mapped and ablated using the new electromagnetic catheter technology creating an electroanatomical map of the arrhythmia focus for each tachycardia without fluoroscopy; both tachycardias were successfully ablated, terminated, and rendered noninducible. The CARTO system is useful in mapping and guiding the ablation of focal tachycardia and merits further study.

Ergot alkaloids inhibit 3H-naloxone binding to opiate receptors in the rat striatum and hippocampus.

The authors tested direct effect of selected ergot alkaloids (lisuride, terguride, DH-ergotoxine, DH-ergotamine and DH-ergocristine) on specific 3H-naloxone binding in the rat striatum and hippocampus. In the striatum they found that DH-ergotoxine (a substance with high affinity for noradrenergic receptors) inhibited specific 3H-naloxone binding much more strongly than lisuride and terguride (substances with a greater affinity for dopaminergic and serotoninergic receptors). DH-ergotoxine, which inhibited binding significantly more in the striatum than in the hippocampus, displayed the greatest activity. The results show differences in the degree of inhibition by the various groups of ergot alkaloids in the striatum. In the case of DH-ergotoxine there was also a difference in the degree of inhibition in the striatum and the hippocampus.