Prolonged exposure to hand-transmitted vibration can cause debilitating neural and vascular dysfunction in humans. It is unclear whether the pathophysiology involves simultaneous or sequential injury of arteries and nerves. The mechanism of vibration injury was investigated in a rat tail model, containing arteries and nerves structurally similar to those in the human hand. Tails were selectively vibrated for 1 or 9 days with the remainder of the animal at rest. One vibration bout of 4 h/day, 60 HZ, 5 g (49 m/s(2)) acceleration, injured endothelial cells. Injury was signaled by elevated immunostaining for NFATc3 transcription factor. Electron microscopy revealed that vibration for 9 days produced loss and thinning of endothelial cells, with activated platelets coating the exposed subendothelial tissue. Endothelial cells and arterial smooth muscle cells contained double membrane-limited, swollen processes indicative of vasoconstriction-induced damage. Laser doppler surface recording demonstrated that 5 min of vibration significantly diminished tissue blood perfusion. These findings indicate that early injury involves vasoconstriction and denuding of the arterial endothelium.

The effects of single 4-hr bouts of continuous 30, 60, 120, and 800 Hz tail vibration (49 m/sec 2 , root mean squared) were compared to assess frequencyamplitude-related structural damage of the ventral caudal artery. Amplitudes were 3.9, 0.98, 0.24, and 0.0055 mm, respectively. Vibrated, sham-vibrated, and normal arteries were processed for light and electron microscopy. The Curry rat tail model of hand-arm vibration (Curry et al. Muscle Nerve 2002; 25:527-534) proved well-suited for testing multiple frequencies. NFATc3 immunostaining, an early marker of cell damage, increased in smooth muscle and endothelial cells after 30, 60, and 120 Hz but not 800 Hz. Increased vacuolization, which is indicative of smooth muscle contraction, occurred for all frequencies except 800 Hz. Vacuoles increased in both endothelial and smooth muscle cells after 60 and 120 Hz. Only 30 Hz showed pronounced smooth muscle cell vacuolization along the internal and external elastic membranes, suggesting stretch-mediated contraction from the large amplitude shear stress. Discontinuities in toluidine blue staining of the internal elastic membrane (IEM) increased for all frequencies, indicating vibration-induced structural weakening of this structure. Patches of missing IEM and overlying endothelium occurred in ϳ 5% of arteries after 60, 120, and 800 Hz. The pattern of damage after 800 Hz suggests that the IEM is disrupted because it resonates at this frequency. Vibration acceleration stress and smooth muscle contraction appear to be the major contributors to arterial damage. The pattern of vibrationinduced arterial damage of smooth muscle and endothelial cells is frequencyamplitude-dependent.

Prolonged hand-transmitted vibration exposure in the workplace has been recognized for almost a century to cause neurodegenerative and vasospastic disease. Persistence of the diseased state for years after cessation of tool use is of grave concern. To understand persistence of vibration injury, the present study examined recovery of nerve conduction velocity and structural damage of myelinated axons in a rat tail vibration model. Both 7 and 14 days of vibration (4 h/day) decreased conduction velocity. The decrease correlated directly with the increased percentage of disrupted myelinated axons. The total number of myelinated axons was unchanged. During 2 months of recovery, conduction velocity returned to control level after 7-day vibration but remained decreased after 14-day vibration. The rat tail model provides insight into understanding the persistence of neural deficits in hand-arm vibration syndrome.

A rat-tail vibration model of hand-arm vibration was employed to test whether preemptive administration of nifedipine (5 mg/kg) to block vasoconstriction prevents vibration-induced arterial damage. The tails of vibrated and nifedipine-pretreated vibrated Sprague-Dawley rats were exposed continuously to 4 h of 60-HZ vibration at 49 m/s(2) rms. In nonvibrated anesthetized rats, the ventral tail arteries were bathed for 15 min in situ in 1 mM epinephrine or 1 mM norepinephrine to induce structural changes indicative of intense vasoconstriction. Arteries were processed for light and electron microscopy 45 min after treatment. Compared to sham control, 4-h vibration significantly (P < 0.01) reduced lumen size, generated endothelial disruption (7.0 +/- 2.6%), elevated nuclear factor of activated T cells c3 (NFATc3) expression in endothelial and smooth muscle cells, and increased smooth muscle cell vacuolization. The findings demonstrate that blockage of vibration-induced vasoconstriction with nifedipine prevents acute vascular damage. Smooth muscle and endothelial cells structurally altered by vasoconstriction are rendered susceptible to damage by vibration.

Cranial suture fusion in the murine model is not an "all-or-none" phenomenon. The posterior frontal suture, previously thought to be completely fused on day 45 by histological analysis, showed variable fusion along the length of the suture by both methods. Quantitative assessment of the percentage of bone within the posterior frontal and sagittal sutures and morphologic assessment of these sutures demonstrated similar findings by both methods. Whereas thorough histologic evaluation of an entire suture would be extremely labor intensive and impractical, these findings help to validate microcomputed tomography as a rapid and reliable method of examining the entire suture in murine models.