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T J Ruigrok

Publications and source records attributed to T J Ruigrok.

At least 37 records · Page 2Linked to original sources
PubMed1998

Brain death-induced alterations in myocardial workload and high-energy phosphates: a phosphorus 31 magnetic resonance spectroscopy study in the cat.

BACKGROUND: Hemodynamic deterioration resulting from brain death-induced myocardial left ventricular dysfunction may preclude heart donation. A reduced myocardial high-energy phosphate content, assessed by biopsy specimens, has been suggested to be responsible for this phenomenon. By applying phosphorus 31 magnetic resonance spectroscopy, in vivo myocardial high-energy phosphate metabolism can be studied continuously. METHODS: Twelve cats were sedated, intubated, ventilated, and studied for 240 minutes. Heart rate, arterial blood pressure, and arterial blood gases were monitored. Central venous pressure was kept constant. Myocardial work was expressed as rate-pressure product (RPP=heart rate x systolic arterial blood pressure). After sternotomy a radio frequency surface coil was positioned onto the left ventricle. A parietal trephine hole was drilled, and an inflatable balloon was inserted. The animal was placed into a 4.7 T horizontal 40 cm bore magnet interfaced to a spectrometer. Brain death (n=6) was induced by rapid inflation of the balloon; the six other cats served as a sham-operated control group. 31P spectra were obtained in 30 seconds, with ventilation and arterial blood pressure curve triggering. The phosphocreatine/to/adenosine triphosphate ratio, as an estimator of energy metabolism, was calculated. RESULTS: Brain death was established within 30 seconds after inflation of the balloon. Changes in RPP were characterized by a triphasic profile with a maximum increase from 19.3+/-1.4 x 10(3) to 87.5+/-8.1 x 10(3) mm Hg x min(-1) (p < .0001 vs control group) at 2 minutes after inflation of the balloon. Subsequently, RPP decreased and was normalized at 15 minutes after inflation. The third phase was characterized by hemodynamic deterioration, which became significant at 180 minutes and resulted in mean arterial pressure of 71+/-12 mm Hg (p < .05 vs control group) at the end of the experimental period. RPP deteriorated to 14.6+/-2.0 x 10(3) mm Hg x min(-1) (p < .05 vs control group) at 240 minutes. Because the heart rate remained constant during the third phase, the decrease in RPP was caused by a decrease in systolic arterial blood pressure. The initial phosphocreatine/adenosine triphosphate ratio of 1.65+/-0.16 varied to 1.52+/-0.06 at 2 minutes, and to 1.73 +/-0.17 (all values NS vs control group and vs initial ratio) at 240 minutes. CONCLUSIONS: The energy status of the heart is not affected by brain death. Therefore brain death-induced hemodynamic deterioration is not caused by impaired myocardial high-energy phosphate metabolism.

Adenosine Triphosphate↗
PubMed1997

Ultrastructural study of the GABAergic and cerebellar input to the nucleus reticularis tegmenti pontis.

The nucleus reticularis tegmenti pontis is an intermediate of the cerebrocerebellar pathway and serves as a relay centre for sensorimotor and visual information. The central nuclei of the cerebellum provide a dense projection to the nucleus reticularis tegmenti pontis, but it is not known to what extent this projection is excitatory or inhibitory, and whether the terminals of this projection contact the neurons in the nucleus reticularis tegmenti pontis that give rise to the mossy fibre collaterals innervating the cerebellar nuclei. In the present study the nucleus reticularis tegmenti pontis of the cat was investigated at the ultrastructural level following anterograde and retrograde transport of wheat germ agglutinin coupled to horseradish peroxidase (WGA-HRP) from the cerebellar nuclei combined with postembedding GABA immunocytochemistry. The neuropil of this nucleus was found to contain many WGA-HRP labeled terminals, cell bodies and dendrites, but none of these pre- or postsynaptic structures was double labeled with GABA. The vast majority of the WGA-HRP labeled terminals contained clear spherical vesicles, showed asymmetric synapses, and contacted intermediate or distal dendrites. Many of the postsynaptic elements of the cerebellar afferents in the nucleus reticularis tegmenti pontis were retrogradely labeled with WGA-HRP, while relatively few were GABAergic. We conclude that all cerebellar terminals in the nucleus reticularis tegmenti pontis of the cat are nonGABAergic and excitatory, and that they contact predominantly neurons that project back to the cerebellum. Thus, the reciprocal circuit between the cerebellar nuclei and the nucleus reticularis tegmenti pontis appears to be well designed to function as an excitatory reverberating loop.

Animals↗
PubMed1997

Acute increase of myocardial workload, hemodynamic instability, and myocardial histological changes induced by brain death in the cat.

Brain death-related hemodynamic instability may preclude donor heart procurement. The relationships between the initial changes of myocardial workload, hemodynamic deterioration, and myocardial histological changes caused by acute induction of brain death are unclear. Cats (n = 15) were submitted to brain death by rapid inflation of an intracranial balloon. A further 12 cats served as a sham-operated control group. The changes in heart rate, mean arterial blood pressure, systolic and diastolic arterial blood pressure, left ventricular developed pressure, LV dP/dtmax, rate-pressure product (RPP), and circulating noradrenaline and adrenaline were studied during 240 min after the induction of brain death. Central venous pressure was kept constant. The hearts were histologically examined afterward. Electrocerebral activity disappeared within 30 sec after balloon inflation. At 3 min, noradrenaline and adrenaline levels had increased 75- and 40-fold, respectively, compared to pre-induction levels. The hemodynamic response was characterized by an early and rapid increase of hemodynamic variables at 2.9 +/- 0.2 min. This was followed by a second phase of normalization or deterioration. Two distinct subgroups (n = 9) became hemodynamically unstable (HDU), characterized by a systolic arterial blood pressure < 90 mm Hg, at 108 +/- 29 min, and progressively deteriorated to 67 +/- 8 mm Hg at 240 min after inflation of the balloon. The hemodynamic variables of the other, hemodynamically stable (HDS), subgroup (n = 6) normalized at 60 min after inflation. Hemodynamic deterioration of the HDU subgroup compared to the HDS subgroup was significant at 10 min after induction of brain death. The maximum values of RPP were similar in the two subgroups. Respiratory and metabolic variables at the end of the experiment were not different in both subgroups. Histological evidence of myocardial damage was present in 73% (11/15) of the brain dead cats and absent in the control group. The histological changes were identified both in hearts of HDU (6/9) and HDS (5/6) cats. In the cat, no relationships were demonstrated between the acute increase of myocardial workload, the occurrence of hemodynamic deterioration, and myocardial histological changes after rapid induction of brain death. These results may contribute to the discussion whether hemodynamic instability of the donor is an appropriate exclusion criterion for heart transplantation.

Animals↗
PubMed1997

The role of the Na+ channel in the accumulation of intracellular Na+ during myocardial ischemia: consequences for post-ischemic recovery.

To further elucidate the role of the Na+ channel in the ischemic accumulation of intracellular Na+ (Na+i), 200 microM lidocaine was included in the perfusate for 5 min prior to 30 min of ischemia in isolated rat hearts paced at 5 Hz. Na+i and high-energy phosphates were measured, using 23Na-NMR with the shift reagent TmDOTP5- and 31P-NMR, respectively. Control values of phosphocreatine (PCr) and ATP were 14.1 +/- 1.5 mM and 7.7 +/- 0.7 mM, respectively (all data: mean +/- S.D.). During lidocaine perfusion the rate pressure product (RPP) decreased by approximately 50% and Na+i declined from 11.5 +/- 1.5 mM to 9.8 +/- 2.1 mM. During ischemia Na+i in lidocaine hearts rose to 17.9 +/- 2.5 mM v 28.4 +/- 1.7 mM in control hearts (P<0.05). In hearts in which extracellular Ca2+ was lowered prior to ischemia to reach a similar RPP decrease as in lidocaine hearts, Na+i rose to 26.3 +/- 3.0 mM during ischemia (P<0.05 v lidocaine, N.S. v control). Lidocaine did not affect the decline of PCr during ischemia (to 0.5 +/- 0.5 v 0.7 +/- 0.8 mM in lidocaine and control hearts, respectively) but significantly attenuated the initial decrease of pH(i) (6.06 +/- 0.07 v 5.76 +/- 0.04 after 20 min, P<0.01), attenuated the initial decline of ATP (3.3 +/- 1.3 v 1.5 +/- 0.9 mM after 20 min, P<0.05) and delayed the time to onset of contracture. However, at the end of ischemia pH(i) (5.73 +/- 0.04 and 5.78 +/- 0.05) and ATP (1.2 +/- 0.6 and 0.9 +/- 0.8 mM) were not significantly different. At 30 min of reperfusion Na+i was 14.9 +/- 2.6 mM in lidocaine hearts v 20.0 +/- 3.1 mM in controls. PCr (9.6 +/- 2.3 v 4.9 +/- 0.9 mM, P<0.05) and ATP (3.0 +/- 0.6 v 1.8 +/- 0.6 mM) recovered better in lidocaine hearts. Furthermore, developed and end-diastolic pressure recovered better in lidocaine hearts. In conclusion, Na+ influx during ischemia occurs, at least partly, via the Na+ channels, and blocking this channel during ischemia improves post-ischemic functional and metabolic recovery.

Animals↗
PubMed1997

Cholinergic innervation and receptors in the cerebellum.

We have studied the source and ultrastructural characteristics of ChAT-immunoreactive fibers in the cerebellum of the rat, and the distribution of muscarinic and nicotinic receptors in the cerebellum of the rat, rabbit, cat and monkey, in order to define which of the cerebellar afferents may use ACh as a neurotransmitter, what target structures are they, and which cholinergic receptor mediate the actions of these pathways. Our data confirm and extend previous observations that cholinergic markers occur at relatively low density in the cerebellum and show not only interspecies variability, but also heterogeneity between cerebellar lobules in the same species. As previously demonstrated by Barmack et al. (1992a,b), the predominant fiber system in the cerebellum that might use ACh as a transmitter or a co-transmitter is formed by mossy fibers originating in the vestibular nuclei and innervating the nodulus and ventral uvula. Our results show that these fibers innervate both granule cells and unipolar brush cells, and that the presumed cholinergic action of these fibers most likely is mediated by nicotinic receptors. In addition to cholinergic mossy fibers, the rat cerebellum is innervated by beaded ChAT-immunoreactive fibers. We have demonstrated that these fibers originate in the pedunculopontine tegmental nucleus (PPTg), the lateral paragigantocellular nucleus (LPGi), and to a lesser extent in various raphe nuclei. In both the cerebellar cortex and the cerebellar nuclei these fibers make asymmetric synaptic junctions with small and medium-sized dendritic profiles. Both muscarinic and nicotinic receptor could mediate the action of these diffuse beaded fibers. In the cerebellar nuclei the beaded cholinergic fibers form a moderately dense network, and could in principle have a significant effect on neuronal activity. For instance, the cholinergic fibers arising in the PPTg may modulate the excitability of the cerebellonuclear neurons in relation to sleep and arousal (e.g. McCormick, 1989). Studies on the distribution of cholinergic markers in the cerebellum have proven valuable besides the issue whether cholinergic mechanism play a role in the cerebellar circuitry, because they illustrate a complexity of the cerebellar anatomy that extends beyond its regular trilaminar and foliar arrangement. For instance, AChE histochemistry has been shown to preferentially stain the borders of white matter compartments (the 'raphes', Voogd, 1967), and therefore is useful in topographical analysis of the cortico-nuclear and olivocerebellar projections (Hess and Voogd, 1986; Tan et al., 1995; Voogd et al., 1996; see Voogd and Ruigrok, 1997, this Volume). ChAT-immunoreactivity, at least in rat, appears to be a good marker to outline the morphological heterogeneity of mossy fibers, and m2-immunocytochemistry could be used to label (subpopulations of) Golgi cells, subsets of mossy fibers and, in the rabbit, a specific subset of Purkinje cells (Jaarsma et al., 1995).

Acetylcholine↗
PubMed1997

Cerebellar nuclei: the olivary connection.

This chapter gives an overview of the relation between the inferior olive and the cerebellar nuclei based on tracing and electrophysiological experiments in rats and cats. The olivary and cerebellar nuclear masses appear to maintain a precise topographical relationship. The olivary projection to the cerebellar nuclei is strictly contralateral, originates as climbing fiber collaterals, and is excitatory. The cerebellar projection to the inferior olive is exactly reciprocal to the olivonuclear projection, but, in addition, also has a variable but definite ipsilateral component, and has been demonstrated to be GABAergic. Stimulation and lesion experiments carried out in cat imply that the cerebellar nucleo-olivary pathway may be involved in regulating the oscillatory capabilities of olivary cells and as such may also have an effect on the synchrony of olivary firing. Subsequent stimulation experiments performed in rats suggests that synchronous firing of olivary neurons may result in profound effects in cerebellar nuclear neurons.

Animals↗
PubMed1997

Climbing fibre collaterals contact neurons in the cerebellar nuclei that provide a GABAergic feedback to the inferior olive.

The inferior olive provides climbing fibres to Purkinje cells in the cerebellar cortex and gives off axon collaterals to the cerebellar nuclei. The cerebellar nuclei contain GABAergic neurons that provide an inhibitory projection to the inferior olive and excitatory neurons that influence behaviour through various other premotor nuclei in the brainstem and diencephalon. Whether the olivary axon collaterals innervate the GABAergic neurons in the cerebellar nuclei is unknown. In the present study we investigated this projection in mice at the ultrastructural level using post-embedding GABA immunocytochemistry and anterograde and retrograde tracing of biotinylated dextrane amine and gold-lectin. It is demonstrated that the olivary axon collaterals do not only innervate non-GABAergic neurons in the cerebellar nuclei, but also GABAergic nucleo-olivary cells, thus establishing a direct feedback loop to the inferior olive.

Animals↗
PubMed1996

Metabolic adaptation during a sequence of no-flow and low-flow ischemia. A possible trigger for hibernation.

BACKGROUND: Myocardial hibernation is an adaptive phenomenon occurring in patients with a history of acute ischemia followed by prolonged hypoperfusion. METHODS AND RESULTS: We investigated, in isolated rabbit heart, whether a brief episode of global ischemia followed by hypoperfusion maintains viability. Four groups were studied; group 1,300 minutes of aerobia; group 2,240 minutes of total ischemia and 60 minutes of reperfusion; group 3, 10 minutes of total ischemia, 230 minutes of hypoperfusion (90% coronary flow reduction), and 60 minutes of reperfusion; and group 4, 240 minutes of hypoperfusion followed by reperfusion. In group 3, viability was maintained. Ten minutes of ischemia caused quiescence, a fall in interstitial pH (from 7.2 +/- 0.01 to 6.1 +/- 0.8), creatine phosphate (CP), and ATP (from 54.5 +/- 5.0 and 25.0 +/- 1.9 to 5.0 +/- 1.1 and 15.3 +/- 2.5 mumol/g dry wt, P < .01). Subsequent hypoperfusion failed to restore contraction and pH but improved CP (from 5.0 +/- 1.1 to 20.1 +/- 3.4, P < .01). Reperfusion restored pH, developed pressure (to 92.3%), and NAD/NADH and caused a washout of lactate and creatine phosphokinase with no alterations of mitochondrial function or oxidative stress. In group 4, hypoperfusion resulted in progressive damage. pH fell to 6.2 +/- 0.7, diastolic pressure increased to 34 +/- 5.6 mm Hg, CP and ATP became depressed, and oxidative stress occurred. Reperfusion partially restored cardiac metabolism and function (47%). CONCLUSIONS: A brief episode of total ischemia without intermittent reperfusion maintains viability despite prolonged hypoperfusion. This could be mediated by metabolic adaptation, preconditioning, or both.

Adaptation, Physiological↗
PubMed1996

Locomotion coincides with c-Fos expression in related areas of inferior olive and cerebellar nuclei in the rat.

Rats that had been walking on a rotating drum for a period of 75 min, demonstrated expression of the immediate early gene c-Fos in specific areas of the inferior olive and cerebellar nuclei. Non-walking control rats did not show consistent Fos-like immunoreactive labelling in these nuclei. Fos-like immunoreactive olivary neurons were consistently found in the caudolateral parts of the dorsal accessory olive and in its dorsal fold, and within specific areas of the medial accessory and principal olives. In the cerebellar nuclei, immunoreactive cells were found in the medial part of the anterior interposed nucleus, in the interstitial cell groups, and within specific parts of the medial, posterior interposed, and lateral nuclei. The lateral vestibular nucleus as well as the ventral part of the magnocellular red nucleus also displayed positive neurons. Most of these positive areas are known (1) to be related to the spinal cord and (2) to be anatomically linked. These results are in line with a presumptive role of the olivo-cerebellar system in ongoing movement control.

Animals↗
PubMed1996

Morphological correlates of bilateral synchrony in the rat cerebellar cortex.

Simultaneous recordings of the left and right crus IIA of the cerebellar cortex in the rat have demonstrated that Purkinje cells of both sides can be activated synchronously by their climbing fibers. Because climbing fibers arise exclusively from the contralateral inferior olive (IO), this physiological finding seems to contradict the anatomy. To define the structural basis responsible for the bilateral synchrony, we examined the possibilities that bilateral common afferent inputs to the IO and interolivary connections form the underlying mechanisms. The bilaterality of the major afferents of the olivary regions that project to crus IIA was studied using Phaseolus vulgaris leucoagglutinin as an anterograde tracer. We found that the excitatory and inhibitory projections from the spinal trigeminal nucleus and dorsolateral hump of the interposed cerebellar nucleus to the transition area between the principal olive and dorsal accessory olive were bilateral. A second possible mechanism for bilateral synchrony, which is the possibility that axons of olivary neurons provide collaterals to the contralateral side, was investigated using biotinylated dextran amine as an anterograde tracer. Labeled axons were traced and reconstructed from the principal olive and dorsal and medial accessory olive up to the entrance of the contralateral restiform body. None of these axons gave rise to collaterals. The possibility that neurons in the left and right IO are electronically coupled via dendrodendritic connections was investigated by examining the midline region of the IO. The neuropil of the left and right IO is continuous in the dorsomedial cell column. Examination of Golgi impregnations of this subdivision demonstrated that (1) many dendrites cross from one side to the other, (2) neurons close to the midline give rise to dendrites that extend into both olives, and (3) dendrites of neurons in the dorsomedial cell column frequently traverse into adjacent olivary subdivisions such as the medial accessory olive and the transition area between the principal olive and dorsal accessory olive. Sections immunostained for dendritic lamellar bodies or GABAergic terminals showed the same pattern: the neuropils of the dorsomedial cell columns on both sides form a continuum with each other as well as with the neuropil of other adjacent olivary subdivisions. Ultrastructural examination of the dorsomedial cell column demonstrated that the midline area includes many complex glomeruli that contain dendritic spines linked by gap junctions. To verify whether the complex spike synchrony observed between left and right crus IIA could indeed be mediated in part through coupled neurons in the dorsomedial cell column, we recorded simultaneously from crus IIA areas and from left and right vermal lobule IX, which receives climbing fibers from the dorsomedial cell column. In these experiments we demonstrated that the climbing fibers of all four areas, i.e., the left and right crus IIA as well as the left and right lobule IX, can fire synchronously. The present results indicate that synchronous climbing fiber activation of the left and right crus IIA in the rat can be explained by (1) bilateral inputs to the transition areas between the principal olive and dorsal accessory olive and (2) dendrodendritic electrotonic coupling between neurons of the left and right dorsomedial cell column and between neurons of the dorsomedial cell column and adjacent olivary subdivisions.

Animals↗
PubMed1996

Metabolic and functional consequences of successive no-flow and sustained low-flow ischaemia; a 31P MRS study in rat hearts.

Recently, a model of acute hibernation, based on successive no-flow and low-flow ischaemia in the isolated rabbit heart has been described. In the present study this model was used in isolated rat hearts. 31P NMR was used to follow the time course of intracellular pH (pHi) and high-energy phosphates; mechanical activity of the heart was assessed simultaneously. Control hearts were subjected to 180 min of low-flow ischaemia and 60 min of reperfusion (group A). In the acute hibernation group, low-flow was preceded by 5 min of no-flow ischaemia (group B). In group A contracture developed during low-flow. The time to onset of contracture was 51 min (range: 28 to 123 min). In group B, contracture did not occur during low-flow ischaemia (P < 0.01): recovery of left ventricular developed pressure and end-diastolic pressure was significantly better during the first 15 min of reperfusion (P < 0.05). In group A pHi decreased from 7.06 +/- 0.04 to 6.64 +/- 0.14 during the first 30 min of low-flow. After contracture developed in this group two pHi values were measured amounting to 6.33 +/- 0.15 and 6.86 +/- 0.05 at the end of low-flow. At the end of reperfusion pHi was 6.29 +/- 0.05 and 7.09 +/- 0.06. In group B, pHi decreased from 7.08 +/- 0.03 to 6.55 +/- 0.03 during no-flow ischaemia. During low-flow ischaemia, pHi increased to 6.73 +/- 0.05 and remained constant. During reperfusion pHi recovered to 7.06 +/- 0.03. In group A and B phosphocreatine (PCr) levels at the end of low-flow ischaemia amounted to 13 +/- 8% and 26 +/- 6% of pre-ischaemic levels, respectively. During reperfusion, PCr recovery was better in group B: 67 +/- 12% v 23 +/- 11% (P < 0.05). In group A and B, ATP levels at the end of low-flow ischaemia were 5 +/- 10% and 19 +/- 9%, respectively. The rate of ATP depletion during low-flow ischaemia was initially similar in both groups, but between 45 and 90 min ATP depletion still continued in group A, while this had leveled off in group B (P < 0.01). During reperfusion no significant changes in ATP were observed. We propose that increased glucose transport and glycolytic flux are able to maintain ionic homeostasis and diastolic function when low-flow ischaemia is preceded by a short period of no-flow ischaemia.

Animals↗
PubMed1995

Lack of a bilateral projection of individual spinal neurons to the lateral reticular nucleus in the rat: a retrograde, non-fluorescent, double labeling study.

The projection of spinal neurons to the lateral reticular nucleus of the rat was investigated with a non-fluorescent double retrograde tracing technique. Either a gold-lectin tracer or cholera toxin-b-subunit was injected into the lateral reticular nucleus on each side of the brain. Retrogradely labeled neurons were encountered bilaterally throughout the spinal cord. Double labeled neurons, however, were seldom seen (< 2% of the total number of labeled neurons) and those that were of passing fibers. It is concluded that most spinoreticular neurons project to either the ipsi- or contralateral lateral reticular nucleus, suggesting that each side receives a unique spinal input.

Animals↗
PubMed1995

Connections of the lateral reticular nucleus to the lateral vestibular nucleus in the rat. An anterograde tracing study with Phaseolus vulgaris leucoagglutinin.

Efferent projections from the lateral reticular nucleus in the rat were investigated with anterograde transport of Phaseolus vulgaris leucoagglutinin. Besides the well known mossy fibre connections to the cerebellar cortex and collaterals to the cerebellar nuclei, a substantial bilateral projection to the lateral vestibular nucleus was found. Terminal arborizations found within this nucleus appeared to detach from the reticulocerebellar fibres in the cerebellar white matter and enter the lateral vestibular nucleus from dorsally. This projection may have functional relevance for the control, by ascending spinal pathways, of the descending lateral vestibulospinal tract.

Animals↗