Kazuo Makimoto

Autoregulation of cochlear blood flow

SummaryThe cochlear blood flow of healthy adult guinea pigs was measured with a laser Doppler flowmeter and flow dynamics were anaylzed on the basis of autoregulation. Angiotensin Il infusion was used to raise blood pressure, while phlebotomy was done to lower blood pressure. The characteristics of autoregulation of cerebral blood flow and muscular blood flow were also investigated. Cochlear blood flow was considered to have some autoregulation but was less than brain blood flow, which showed significant regulation. Muscular blood flow seemed to have no similar regulatory mechanism.

Effect of Lidocaine Injection on EOAE in Patients with Tinnitus

In the present study, evoked otoacoustic emissions (EOAEs) were measured in 30 patients with tinnitus before and after intravenous lidocaine injection (1 mg/kg). For EOAE recordings, 1 kHz tone burst stimuli were used. Intravenous lidocaine injection resulted in suppression of tinnitus in 22 (73%) ears, and changes of EOAE amplitude (increase or decrease) in 18 (60%) ears. Of the 18 ears with EOAE amplitude changes, tinnitus disappeared or decreased in 17 (94%) ears. In 12 ears without changes of EOAE amplitude, tinnitus was suppressed in only 5 (42%). Changes in latency were not detected in any of the ears. These results indicate that there is a relationship between the effect of lidocaine in tinnitus suppression and changes in cochlear micromechanics caused by lidocaine.

Recurrent laryngeal papillomatosis developing into laryngeal carcinoma with human papilloma virus (HPV) type 18 : a case report

We report a case of recurrent laryngeal papillomatosis which developed into laryngeal squamous cell carcinoma 11 years after the first diagnosis. Interestingly, we could identify HPV type 18 DNA in the carcinoma tissue using the polymerase chain reaction (PCR). Other known risk factors of irradiation, smoking, exposure to chemical agents, or a hereditary tendency to malignant tumours were not present in this case. Our finding suggests that HPV type 18 is another aetiological agent for laryngeal carcinoma.

Observations of cochlear blood flow dynamics using the laser Doppler flowmeter.

SummaryThe cochlear blood flow of normal adult guinea pigs was measured by a laser Doppler flowmeter. The validity of this flowmeter was ascertained by its specificity for blood flow and its sensitivity to blood flow changes. Angiotensin II was infused into the animals and asphyxia was induced. The responses of the cochlear blood flow showed a close correlation with those of the systolic blood pressure. These results suggest a passive aspect in the physiology of cochlear blood circulation. On the other hand, there was a negative correlation between the responses of auricular skin blood flow and those of systolic blood pressure to a certain dose range of angiotensin II. To clarify the specific details of inner ear blood flow, further studies of the hemodynamics of the inner ear blood circulation should be continued under various experimental conditions.

Effects of nitric oxide synthase inhibitor on cochlear blood flow

We observed in rats the changes in cochlear blood flow (CoBF) and cutaneous blood flow of the abdominal wall (AbBF) after the administration of the NO synthase inhibitor, N-nitro-L-arginine-methyl ester (L-NAME). Ten minutes after i.v. infusion of L-NAME (0.2, 1, 5, 10 mg/kg), L-arginine, which is a substrate of NO, was infused (100 mg/kg) i.v. Employing a laser Doppler flowmeter, the changes in blood flow were recorded from the basal turn of the right cochlea or the abdominal wall and blood pressure (BP) was recorded from the left femoral artery simultaneously. Vascular conductance (VC) was calculated from CoBF/mean BP (cochlear VC) or AbBF/mean BP (abdominal VC). The findings in rats generally agreed with those in guinea pigs [Brechtelsbauer et al., Hear. Res. 77 (1994) 38-42]. Intravenous infusion of L-NAME produced a dose-dependent depression of cochlear VC at 0.2 mg/kg (-18.9), 1 mg/kg (-37.9%), 5 mg/kg (-45.8%) and 10 mg/kg (-48.3%). AbBF also decreased after infusion of L-NAME (5 mg/kg) but to a lesser degree (-41.1% in VC) with no significance compared to CoBF (5 mg/kg). Infusion of L-arginine partially reversed the CoBF decrease caused by L-NAME. The group of 0.2 mg/kg infusion of L-NAME showed the largest degree of recovery with L-arginine, while the 10 mg/kg group showed the smallest. The decrease in AbBF did not recover substantially with L-arginine, the degree being less than that of each group in the CoBF experiment. It was suggested that the NO/soluble guanylate cyclase/cGMP system is more active in the cochlear microcirculation. With the round window (RW) application of 1% L-NAME (2 microl), cochlear VC was decreased by 21.6%, which was closest to that of the 0.2 mg/kg group of L-NAME i.v. infusion. The cochlear VC depression after local application of L-NAME did not show any recovery (-0.3%) by RW application of 5% L-arginine (2 microl) 25 min after L-NAME application; a slight gradual increase was observed when a higher concentration (20%) of L-arginine was applied to the RW. We propose that i.v. infusions of L-NAME and L-arginine primarily affect the precapillary arteriole of the spiral modiolar artery which effectively regulates microcirculation as a resistance vessel, and that RW application affects the vessels of the lateral wall, not the spiral modiolar artery because of the difficulty of substance diffusion.

The effect of batroxobin on cochlear blood flow.

Cochlear blood flow is considered to be closely related to cochlear function. Among several etiologic factors implicated in inner ear diseases, disturbance of local blood flow is held to be one of the most important. With this in view, various pharmaceuticals are currently being used to increase local blood flow in patients with inner ear diseases. In the control of blood flow there are three major factors; systemic blood pressure (perfusion pressure), vascular tone, and blood viscosity. Batroxobin (BX) was developed to increase local blood flow by lowering blood viscosity through defibrinogenation; it is used in the treatment of thrombosis and occasionally for the treatment of sudden deafness. In the present study, we observed the effect of BX on cochlear blood flow in guinea pigs, using a laser Doppler flowmeter, and measured the blood fibrinogen concentration after BX infusion. There was an obvious increase in cochlear blood flow during the observation period of 3 h after 10 BU/kg were infused, and a slight increase when 2 BU/kg were infused. Blood fibrinogen levels decreased dramatically by 30 min after BX infusion (10 BU/kg), and the extremely low level attained was maintained throughout the 3-h observation period. Hemorrhage from the surgically opened ear was noted in 2 animals during the experiment and rectal bleeding in one.

Relationship between cochlear blood flow and perilymphatic oxygen tension.

SummaryTo clarify the characteristics of the blood circulation in the cochlea, we correlated cochlear blood flow and perilymphatic oxygen tension at various blood pressures. Cochlear blood flow was measured in guinea pigs by laser Doppler flowmetry, and perilymphatic oxygen tension by polarography. Blood pressure changes were induced by angiotensin II injection, trimetaphan camsylate injection and blood withdrawal. Cochlear blood flow generally paralleled systemic blood pressure, indicating a close correlation. In contrast, perilymphatic oxygen tension was slower to increase and decrease. However, when systemic blood pressure was lowered more gradually, perilymphatic oxygen tension did not show the same lag. These findings indicate that perilymphatic oxygen tension parallels systemic blood pressure when changes induced are slower and in a physiological range.

Spontaneous Otoacoustic Emissions in Humans With Endolymphatic Hydrops

Objective/Methods The origin and clinical implications of spontaneous otoacoustic emissions (SOAEs) have not been well revealed. To investigate the relationship between the ear with endolymphatic hydrops and SOAE, SOAEs were measured in 31 patients with unilateral endolymphatic hydrops and 10 volunteers with normal hearing levels that had less than 25 dB hearing level (HL) on average for five frequencies (0.25, 0.5, 1, 2, and 4 kHz).

Comparative effects of glycerol and Urografin on cochlear blood flow and serum osmolarity.

Glycerol, an osmotic diuretic, has been used for the diagnosis and treatment of endolymphatic hydrops. Hearing improvements in hydropic ears are attributed to its dehydrating effect. In addition to this effect, glycerol also increases cochlear blood flow. Urografin, another hyperosmotic agent used for vasography, is similarly known to increase local blood flow. The present study compared these two hyperosmotic agents, glycerol and Urografin, in their effects on cochlear blood flow and serum osmolarity. Laser Doppler flowmetry on the lateral wall of the cochlea revealed that the increase in cochlear blood flow with a 30-min infusion (0.025 ml/min) of 76% Urografin continued for a longer time than with a 30-min infusion (0.025 ml/min) of 50% (v/v) glycerol. The significant increases appeared at 20 and 30 min after the infusion with the former; 10, 20, 30, 40, 50 and 60 min after the infusion with the latter. Intravenous infusion of these agents also caused elevation in serum osmolarity. This elevation was appreciably greater with Urografin infusion (maximal increase: about 30 mOsm on average) than with glycerol infusion (maximal increase: about 6 mOsm on average), and the former elevation appeared to be longer lasting than the latter. These differences were ascribed to differences between glycerol and Urografin with respect to the creation of an osmotic gradient across the capillary walls of cochlear blood vessels. Since glycerol penetrates the interstitial space and moves into inner ear fluids, the gradient may decline faster. It would be assumed that a higher concentration of the hyperosmotic agent in the capillary blood causes more vasodilatation and lowering of blood viscosity. Alternatively, direct action of these agents on the vascular wall may affect some biological processes, leading to vasodilatation in different degrees and durations with different agents. Hearing improvement with glycerol administration in hydropic ears was also discussed from the perspective of cochlear blood flow.

Effects of Hyperventilation and Hypoventilation on Cochlear Blood Flow and Endocochlear Direct-Current Potential

To understand the importance of oxygen transport to the inner ear tissue, we studied, in guinea pigs, the relationship between cochlear blood flow and endocochlear direct-current potential (EP) under different respiratory conditions. EP, a functional parameter of the stria vascularis, was recorded by a microelectrode inserted into the lateral wall of the chochlea. To measure the cochlear blood flow (CoBF), we employed laser Doppler flowmetry and recorded the flow with a probe placed on the same spot on the lateral wall. During 3 min of asphyxia, CoBF and systemic blood pressure showed irregular biphasic increases, while the EP decreased to reach a negative value. In the hypoxemia experiment, which was induced by stepwise reduction of the respiratory rate to 60%, increases in CoBF and blood pressure were evident during hypoventilation with an intermediate position of EP in the positive range. The mechanisms of these increases in two parameters are discussed from the viewpoints of sympathicotonic activity in the autonomic nervous system and the vasodilating action of CO2 during hypercapnia. In the hyperoxemia experiment, which was induced by stepwise increase in the respiratory rate to 140%, CoBF and blood pressure were found to decrease during hyperventilation with no significant change of EP. The decrease in blood pressure was considered to be due to the increase in intrathoracic pressure caused by the increased rate of artificial respiration. As for the concomitant decrease in CoBF, chemical regulation of PCO2 in the vascular bed of the lateral wall of the cochlea was thought to be a contributory factor.