Thyrotropin-releasing hormone (TRH) stimulates pituitary thyrotropin synthesis and release and also regulates autonomic nervous system functions by acting as a neuromodulator and neurotransmitter. In experimental animals a stimulation of ventilation by thyrotropin-releasing hormone was shown when applied at central nervous system sites that affect respiratory motor output. It was the goal of our study to investigate the respiratory properties of thyrotropin-releasing hormone on basal and stimulated (i.e. CO2-rebreathing) conditions following systemic thyrotropin-releasing hormone application in healthy humans. Thyrotropin-releasing hormone (200 micrograms, 400 micrograms intravenous) initiated a rapid short lasting rise of minute volume, ventilatory air-flow and alveolar oxygen tension under steady state breathing (P less than 0.001). Breathing frequency was less affected, heart rate rose concomitantly (P less than 0.001). While breathing with increasing concentrations of carbon dioxide, minute volume was higher under thyrotropin-releasing hormone than under placebo alone. Further effects (e.g. nausea, dizziness, palpitations) mostly appeared later than respiratory changes and thus may not be responsible for their initiation. Our findings prove systemic thyrotropin-releasing hormone to be a strong respiratory stimulant in man. Response in respiratory output was also accompanied by central nervous system-effects (e.g. dizziness, restlessness, augmented vigilance). The mode of thyrotropin-releasing hormone effects on respiration after peripheral administration is still speculative. An augmented sympathetic output or a direct receptor mediated action at central nervous system sites may be responsible, while a peripheral effect cannot be excluded.

Human CRH (hCRH), which acts as a major neuroregulator within the hypothalamic-pituitary-adrenal axis, is also a respiratory stimulant. The broad distribution of CRH receptors in brain areas involved in respiratory regulation is consistent with this finding. This study was designed to investigate whether ACTH or cortisol mediates the respiratory stimulation effect of CRH. Bolus injection of 100 micrograms hCRH induced significant respiratory stimulation in all 10 normal subjects studied. hCRH given after the administration of 2 mg dexamethasone, which greatly reduced plasma cortisol levels, had the same respiratory effect on respiration. Thus, increase in plasma ACTH and cortisol concentrations are probably not involved in the respiratory analeptic effect of CRH.

The square of ultrasound transmission velocity in a material is correlated to the modulus of elasticity, which is an indicator of its mechanical properties. This might make the measurement of ultrasound transmission velocity useful in the noninvasive diagnosis of bone diseases. Bone, however, is not an isotropic material but is architecturally structured. The aim of our study was to investigate and especially to quantify the influence of architecture in cortical bone on ultrasound transmission velocity. Twenty-two rectangular, flat specimens of cortical bone were prepared from diaphysis of fresh pig radius. Ultrasound transmission velocity was measured parallel and perpendicular to direction of Haversian channels. It was found to be 3647 +/- 41 m/s parallel to and 2821 +/- 29 m/s perpendicular to Haversian channels respectively (p < 0.001). Our results clearly indicate that there is an important influence of architecture in cortical bone on ultrasound transmission velocity which has to be taken into account in its clinical use.

In both human and animal studies a stimulatory effect of corticotropin-releasing hormone (CRH) on respiration and on cognitive parameters has been demonstrated. Our own studies employing human CRH (hCRH) iv in healthy volunteers and different groups of patients have shown hCRH to be a safe drug. We prospectively studied the clinical effects of a standardized dose of 100 μg hCRH iv in 12 elderly patients following major abdominal surgery who remained comatose and were under prolonged respirator therapy over a mean period of 37 days. Cardio-respiratory parameters, blood gas values, plasma cortisol and catecholamines were evaluated before and 30 min following hCRH injection. Furthermore, vigilance was tested using a score system. Ventilation was markedly enhanced following hCRH injection while the cardiovascular parameters were only moderately affected. Vigilance was augmented in all subjects and improved impressively in five patients. The changes were of great benefit for the patients treated and supported their respirator weaning procedures and mobilization training.

To study facial flush after systemic administration of human corticotropin-releasing hormone (hCRH) we injected 100 micrograms hCRH intravenously to ten healthy young men. The increase in facial temperature was measured by infrared camera. A significant increase in facial temperature of 1.39 degrees C +/- 0.3 was found within 7 min in all patients, which lasted up to 60 min, although facial flushing was visible in only 50% (5/10) of the probands. In a second experiment 100 micrograms hCRH was then administered to seven other healthy young men. Intra- and extracerebral blood flow velocity changes in the medial cerebral artery (MCA) and external carotid artery (ECA) were measured after hCRH administration by use of Doppler sonography. We found a decrease of intracerebral blood flow which was caused by hyperventilation and was reversible following 6% CO2 hyperventilation during a second injection of 100 micrograms hCRH. Blood flow velocity in the ECA increased by 111.5 +/- 32.9% (compared to baseline level), lasted up to 60 min after hCRH injection, and was not reversible by 6% end-tidal CO2 ventilation. We thus demonstrated that the direct vasodilatory effect of hCRH involves the ECA-supplied vascular territory only. The intracerebral vasoconstrictory effect represents the result of hyperventilation following hCRH injection. The data thus clearly suggest an interaction of hCRH and the vascular endothelium of the ECA, causing a marked blood flow velocity increase and facial flushing.