Effects of epinephrine on the myocardial performance and haemodynamics of the isolated rat heart during moderate hypothermia--importance of calcium homeostasis.

Controversies exist concerning myocardial performance in hypothermia. We have studied the effects of epinephrine on myocardial function at various calcium concentrations in moderate hypothermia (28 degrees C) and normothermia (37 degrees C) using an isolated antegrade perfused rat heart. The maximum pressure velocity (dP/dt(max)) developed was significantly higher in normothermia compared with hypothermia and was improved by the addition of calcium in both circumstances. Peak negative pressure velocity (dP/dt(min)) was significantly higher at 37 degrees C compared with 28 degrees C, and was increased by the addition of calcium in normothermia; in contrast to hypothermia, in which no change of dP/dt(min) was observed. A reduction in cardiac output and stroke volume by hypercalcaemia was observed in hypothermia. The addition of epinephrine improved dP/dt(max) and dP/dt(min), but had a depressive effect on stroke volume and cardiac output at normal and elevated calcium concentrations. Myocardial efficiency was significantly higher during hypothermia compared with normothermia, but was impaired by epinephrine during hypothermia. The variable or even paradoxical effects of epinephrine suggest the need for careful haemodynamic monitoring and determination of calcium levels in hypothermia. The impairment of myocardial performance may be explained by impaired diastolic relaxation and calcium overload.

Fiberoptic bronchoscopy of intubated patients with life-threatening hemoptysis.

Bleeding in the tracheobronchial tree in intubated patients on an intensive care unit is a potentially life-threatening incident. The antecedent state of disease and frequent respiratory failure require immediate and effective therapeutic measures to avoid further respiratory and cardiocirculatory depression. We present our bronchoscopic management of endobronchial bleeding. Cardiorespiratory function must be maintained by modification of the mechanical ventilation and drug therapy owing to the patient's condition. Seven consecutive patients with acute endobronchial bleeding were treated with fiberoptic bronchoscopy and instillation of cold epinephrine-saline solution (1:10,000-100,000) during the period of July 1997 to December 1997. Control of bleeding was achieved after 1 to 20 (mean +/- SEM: 5.86 +/- 0.93) bronchoscopic interventions during a period of 0.5 hours to 10 days. One control bronchoscopy was performed additionally in every patient. Cardiocirculatory instability was observed in five patients. Six patients survived; one patient died of uncontrolled bleeding caused by severe pulmonary aspergillosis. Fiberoptic endobronchial epinephrine instillation is an effective therapy for life-threatening hemoptysis in critically ill patients. Widespread use of flexible bronchoscopy makes this procedure immediately applicable in critical situations. Intubated and mechanically ventilated patients with life-threatening hemoptysis especially benefit from this rapidly feasible procedure.

[Disorders of intestinal innervation as a possible cause for chronic constipation]. / Intestinale Innervationsstörungen als mögliche Ursache der chronischen Obstipation.

The gastrointestinal tract contains the largest amount of nerve cells apart from the central nervous system constituting together with glial cells the enteric nervous system (ENS). The morphology of the ENS is characterized by intramurally located ganglionated and non-ganglionated plexus of different structure. The diversity of neurotransmitters synthesized by the different nerve cell types as well as the complex neuronal circuits establish the basis for the mediation of a coordinated intestinal motility. Subsequently abnormalities of the ENS may cause severe constipation. The most acknowledged intestinal innervation disorder represents aganglionosis (Hirschsprung's disease) characterized by the absence of intramural nerve cells and the hypertrophy of nerve fiber bundles within the affected intestinal segment. Non-aganglionic intestinal innervation disorders include intestinal neuronal dysplasia (IND), hypoganglionosis and heterotopic ganglia. The pathogenesis of intestinal neuronal malformations is mainly attributed to development disorders of the ENS, in part caused by genetic defects. Furthermore, the ENS can sustain damage during the postnatal period by ischemic, inflammatory, autoimmunological processes or neurotoxic agents. The histopathological diagnosis of intestinal innervation disorders is achieved by enzyme- and immunohistochemical methods. The examination of the ENS can be carried out on mucosal, deep submucosal or full-thickness biopsies using serial transverse sections as well as on intestinal whole-mount preparations allowing a three-dimensional demonstration and assessment of the intramural plexus. Structural abnormalities of the myenteric and submucosal plexus and an abnormal content of neurotransmitters have been considered to be responsible for primary chronic constipation. However, until now no unified pathophysiological concept has been established due to the partly contradictory findings. Therefore, an important goal in patients with chronic constipation should be a detailed quantitative and qualitative assessment of the underlying neurohistopathology. The correlation of these data with functional parameters of intestinal motility may represent an useful tool for the differential diagnostic and therapeutic considerations.

Organization of the enteric nervous system in the human colon demonstrated by wholemount immunohistochemistry with special reference to the submucous plexus.

To demonstrate the normal topography and structure of the enteric nervous system (ENS) in the human colon, the colonic wall of patients (n = 10, mean age 66.3 years), who underwent abdominal surgery unrelated to intestinal motility disorders, was submitted to wholemount immunohistochemistry. The specimens were stretched out and separated into the tunica muscularis, the outer and inner portion of the tela submucosa and the tunica mucosa. Prior to the application of the neuronal marker Protein Gene Product (PGP) 9.5, the laminar preparations were pretreated with the maceration agent KOH. The plexus myentericus was composed of prominent ganglia and interconnecting nerve fiber strands (NFS) forming a polygonal network, which was denser in the descending than in the ascending colon. Nerve cells were observed within the ganglia as well as in primary, secondary and tertiary NFS. The latter ramified into the adjacent smooth muscle layers, which contained the aganglionated plexus muscularis longitudinalis and circularis. The submucous plexus comprised three nerve networks of different topography and architecture: the delicate plexus submucosus extremus consisted of parallel orientated NFS with isolated nerve cells and small ganglia and was located at the outermost border of the tela submucosa adjacent to the circular muscle layer. The plexus submucosus externus was closely associated with the plexus submucosus extremus and composed of larger ganglia and thicker NFS. The plexus submucosus internus was situated adjacent to the lamina muscularis mucosae and formed a network with denser meshes but smaller ganglia and NFS than the plexus submucosus externus. The NFS of the aganglionated plexus muscularis mucosae followed the course of the smooth muscle cells of the lamina muscularis mucosae. The honeycomb-like network of the plexus mucosus was located within the lamina propria mucosae and divided into a subglandular and a periglandular portion. Single and accumulated nerve cells were observed within the plexus mucosus as a regular feature. The findings confirm the complex structural organisation of the ENS encountered in larger mammals, in particular the subdivision of the submucous plexus into three different compartments. PGP 9.5-immunohistochemistry applied to wholemount preparations comprehensively visualized the architecture of the intramural nerve plexus in human colonic specimens. In addition to conventional cross-sections, this technique allows a subtle assessment and classification of structural alterations of the ENS in patients with colorectal motor disorders.

[Megacolon in adults--the spectrum of underlying intestinal innervation disorders]. / Megacolon beim Erwachsenen--das Spektrum zugrundeliegender intestinaler Innervationsstörungen.

The association of megacolon in adults and Hirschsprung's disease was reevaluated by the morphological assessment of the enteric nervous system. Whole-mount preparations of the resected colonic segments and an immunohistochemical treatment with the pan-neuronal marker protein gene product 9.5 allowed an optimal visualization of the entire intramural nervous plexus layers. The findings included different forms of intestinal neuronal malformations (hypoganglionosis, neuronal intestinal dysplasia, and heterotopic ganglia) apart from classic aganglionosis, thus indicating their etiologic relevance to the development of megacolon in adults.