Vestibular control of intermediate- and long-term cardiovascular responses to experimental orthostasis.

Sustained orthostasis elicits the elevation of arterial blood pressure (BP) via sympathetic activation in conscious Wistar rats for at least 2 hours. We tested the hypothesis whether vestibular apparatus plays a role in BP and heart rate (HR) control in response to prolonged gravitational stress. BP and HR responses to 45 degrees head-up for either 2 or 24 hours were monitored by telemetry. Vestibular lesions (VL) were performed by a modified microsurgical-chemical technique. Horizontal BP and HR were not influenced by VL preceding 2-hour tilt. VL abolished the sustained 2-hour BP response to head-up tilt (8.3+/-0.9 mm Hg relative to horizontal values) while suppressed HR transiently only. VL eliminated diurnal BP fluctuations and decreased HR in horizontal position for 24 hours. Head-up tilt for 24 hours increased BP and HR progressively in intact animals, raising their daily average value by 5.6+/-0.7 mm Hg and 22.2+/-6 BPM, respectively. VL resulted in an initial BP rise followed by progressive BP reduction in response to long-term head-up tilt (4+/-2.2 mm Hg) without eliminating the tachycardia (34.4+/-5.4 BPM). Thus, blockade of labyrinthine inputs attenuates the BP responses elicited by both intermediate and long-term gravitational stress of orthostatic type. However, other sensory inputs derived from non-vestibular cues (e.g. proprioceptive, visual, visceral, cutaneous etc.) seem to be effective enough to maintain BP normal.

Does long-term experimental antiorthostasis lead to cardiovascular deconditioning in the rat?

Microgravity or simulated microgravity induces acute and chronic cardiovascular responses, whose mechanism is pivotal for understanding of physiological adaptation and pathophysiological consequences. We investigated hemodynamic responses of conscious Wistar rats to 45? head-down tilt (HDT) for 7 days. Arterial blood pressure (BP) was recorded by telemetry. Heart rate (HR), spectral properties and the spontaneous baroreflex sensitivity (sBRS) were calculated. Head-up tilt (HUT) was applied for 2 h before and after HDT to assess the degree of any possible cardiovascular deconditioning. Horizontal control BP and HR were 112.5+/-2.8 mmHg and 344.7+/-10 bpm, respectively. HDT elicited an elevation in BP and HR by 8.3 % and 8.8 %, respectively, in less than 1 h. These elevations in BP and HR were maintained for 2 and 3 days, respectively, and then normalized. Heart rate variability was unchanged, while sBRS was permanently reduced from the beginning of HDT (1.01+/-0.08 vs. 0.74+/-0.05 ms/mmHg). HUT tests before and after HDT resulted in BP elevations (6.9 vs. 11.6 %) and sBRS reduction (0.44 vs. 0.37 ms/mmHg), respectively. The pressor response during the post-HDT HUT test was accompanied by tachycardia (13.7 %). In conclusion, chronic HDT does not lead to symptoms of cardiovascular deconditioning. However the depressed sBRS and tachycardic response seen during the post-HDT HUT test may indicate disturbances in cardiovascular control.

fMLP-induced respiratory burst and the intracellular Ca2+ signal are not interrelated in neutrophils.

Reactive oxygen intermediate (ROI) production and the development of the intracellular (IC) Ca2+ ([Ca2+]i) signal by formyl-Met-Leu-Phe (fMLP) stimuli were investigated in neutrophils. When the concentration was varied between 2.3 nM-2.3 microM, ROI production and the [Ca2+]i signal showed different fMLP concentration dependencies. ROI production increased continuously with increasing fMLP concentrations, while the [Ca2+]i signal responses reached a plateau around 230 nM fMLP. Moreover, when a consecutive, 2.3 microM fMLP stimulus was applied 10 min after the first fMLP stimulus, the intensity of the ROI production and that of the [Ca2+]i signal showed a variable dependence on the fMLP concentration of the first stimulus. An initial fMLP dose of 2.3 nM and 23 nM sensitized the cells regarding their ROI production and [Ca2+]i signals. After a first fMLP stimulus of 230 nM, the second stimulus produced an increased [Ca2+]i signal, while no ROI production could be activated. A strong fMLP stimulus of 2.3 microM desensitized the cells regarding both [Ca2+]i signal and ROI production. However, even in these desensitized cells, a high level of ROI production could be evoked by other stimuli like PMA or opsonized zymosan. The differences observed between the fMLP concentration dependence of ROI production and the [Ca2+]i signal strongly suggest that these two phenomena are not interrelated.

Transdifferentiation of polymorphonuclear neutrophils: acquisition of CD83 and other functional characteristics of dendritic cells.

Polymorphonuclear neutrophils (PMN) are in the first line of defense against bacterial infections. They are considered to be end-differentiated cells undergoing constitutive apoptosis within hours after release from the bone marrow. During pathological events, however, their life span is extended in conjunction with morphological and functional alterations indicative of a transdifferentiation of mature PMN. To further characterize differentiated PMN, the alterations seen in vivo were reproduced by cultivating PMN of healthy donors with either gamma-interferon, granulocyte/macrophage colony stimulating factor, or a combination thereof. Thus cultivated cells escaped from apoptosis, and protein synthesis was induced, notably of the major histocompatibility complex (MHC) class II antigens, CD80 and CD86. Moreover, CD83, thought to be specific for dendritic cells was synthesized, while typical markers of PMN, including CD66b, CD11a/CD11b/CD11c, CD15, CD18 were preserved. A profound alteration of both cellular morphology and of function was seen: the cultivated PMN lost their chemotactic activity but had acquired the ability to present to T-cells a peptide antigen in a MHC class II restricted manner. The data lead to the conclusion that mature PMN can differentiate further to cells with characteristics of DCs, thereby connecting PMN to the specific T-cell response.

Azurophil granules are heterogeneous with respect to mobilization induced by different concentrations of fMLP.

Azurophil granules of neutrophils beyond their already known heterogeneity of beta-glucuronidase and myeloperoxidase enzyme contents are heterogeneous with respect to a spontaneous or low concentration (2.3 or 23 nM) of formyl-Met-Leu-Phe-induced mobilization. This suggests that the heterogeneity of azurophil granules is manifested in their functions too.

Endothelialization of biosynthetic vascular prostheses after laser perforation.

OBJECTIVE: This study was undertaken to investigate the feasibility of transmural capillary ingrowth into the inner surface of biosynthetic vascular prostheses (Omniflow, BioNova, Melbourne, Australia) through perforations created by an excimer laser, thus inducing an endothelial cell coverage. METHOD: Biosynthetic vascular prostheses (Omniflow, 10 cm length, 6 mm diameter) were perforated with an excimer laser (diameter of the holes 50 to 100 microm, distance 4 mm) and implanted into the carotid arteries of eight sheep. They were compared to untreated Omniflow prostheses implanted at the contralateral side. Three months after implantation the prostheses were explanted and evaluated by gross morphology, histologic examination, scanning electron microscopy, and immunohistochemical staining for factor VIII to identify endothelial cells. RESULTS: All grafts remained patent. Gross morphologic examination revealed no significant difference in the thrombus-free surface between perforated and untreated prostheses. However, scanning electron microscopy showed endothelial cells in the midgraft portion of all perforated prostheses, whereas collagen fibers, fibrin meshwork, and activated platelets formed the inner layer in six of eight untreated Omniflow prostheses. Transmural capillary ingrowth in the laser group was verified by positive factor VIII staining for endothelial cells in the laser channels. CONCLUSION: Spontaneous endothelialization of biosynthetic vascular prostheses can be achieved by transmural capillary ingrowth through perforations in the wall of the prostheses in an experimental sheep model.