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Changes in cochlear oxygenation, microcirculation and auditory function during prolonged general hypoxia.

Changes in cochlear microcirculation and oxygenation and auditory function were examined in anesthetized guinea pigs during prolonged hypoxic ventilation (8% oxygen in nitrogen) for 1 h. Cochlear blood flow and perilymphatic oxygen partial pressure were measured using laser Doppler flowmetry and oxygen-sensitive microelectrodes. Auditory function was examined by recording cochlear microphonics, compound action potentials and auditory evoked brainstem response. Blood pressure and heart rate were monitored. During systemic hypoxia, the perilymphatic PO2 dropped on average to about 70% of the initial value. Cochlear and brainstem potentials showed a mean reduction to 75-82%. Different effects of hypoxia on cochlear blood flow were observed and included decreases as well as increases. Mean arterial blood pressure declined significantly during hypoxia, while the heart rate remained constant. The changed variables returned to normal during reventilation with room air. The findings are discussed with regard to their significance as an animal model for the study of hypoxia-induced cochlear pathophysiology.

Action Potentials↗

Alpha-adrenergic reactivity of the microcirculation in conscious spontaneously hypertensive rats.

The goal of this study was to determine the functional distribution of alpha 1- and alpha 2-adrenoceptors in the striated muscle microcirculation. Experiments were performed in intact conscious spontaneously hypertensive rats (SHR) that were provided with a dorsal microcirculatory chamber to allow microvascular diameter measurements. Administration of selective alpha 1- and alpha 2-agonists, phenylephrine and azepexole, respectively, induced different patterns of microvascular constriction. alpha 1-Adrenoceptor stimulation showed a preferential constriction of large arteries and venules. The entire arteriolar microvasculature was sensitive to alpha 2-adrenoceptor stimulation, whereas the venular vessels did not respond to azepexole. The selective alpha 1- and alpha 2-antagonists prazosin and yohimbine showed patterns of vasodilator activity comparable to those of the corresponding agonists. The specificity of the drug-induced effects was verified by comparing their effects with those of graded hemorrhage, a non-pharmacological method for blood pressure lowering. In the range of blood pressure decreases comparable to that obtained by alpha-adrenoceptor antagonists, graded hemorrhage did not influence microvascular diameters. These results show a differential functional distribution of alpha 1- and alpha 2-adrenoceptors along the microvascular tree in striated muscle of conscious SHR.

Adrenergic alpha-Agonists↗

Intravenous infusion of iloprost in arterial occlusive disease: dose-dependent effects on skin microcirculation.

Transcutaneous oxygen pressure (tcPo2), laser Doppler flux and capillary microscopy have been used to examine the forefoot skin in 5 healthy men and 8 patients with severe peripheral arterial occlusive disease in order to evaluate the dose dependent effects of iloprost on skin microcirculation. Iloprost was infused IV starting at 0.0625 ng.kg-1.min-1 and doubling the dose every 15 min up to 2 ng.kg-1.min-1. While tcPo2 at an electrode core temperature of 44 degrees C decreased in both patients and controls, there was a significant dose dependent increase in tcPo2 (37 degrees C) in the controls from 0.25 ng.kg-1.min-1. In the patients the reaction was variable: it was decreased in two and increased in 6, with a maximum either at 0.25-0.5 ng.kg-1.min-1 (n = 3) or at the highest dose (1.0 or 2.0 ng.kg-1.min-1; n = 3). Mean laser Doppler flux in both groups was increased, although the reaction was not consistent in the patients. Density of forefoot skin capillaries was reduced in 3 patients, and in the others the flow velocity was very low. During infusion of iloprost, both an increase in capillary density and blood cell velocity were observed. The effects were of variable intensity and occurred at varying doses, some appeared early and diminished as the dose was increased, and others were found only at 2 ng.kg-1.min-1. Adverse effects were numerous, extending from harmless skin flushing to mental changes and a quickly reversible attack of angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Responses of the skin microcirculation to acetylcholine and sodium nitroprusside in patients with NIDDM.

The mechanisms involved in the pathogenesis of microangiopathy occurring in non-insulin-dependent diabetes mellitus (NIDDM) are unclear. In the present study, blood flow responses to the vasodilators acetylcholine (which acts via the endothelium) and sodium nitroprusside (a smooth muscle relaxant) were evaluated in this patient group. In 14 male patients with NIDDM, treated with either diet alone (n = 6) or diet plus insulin, (mean age 59 years) and 14 age-pair-matched control subjects, forearm skin perfusion following multiple doses of iontophoretically applied 1% acetylcholine and 0.01% sodium nitroprusside was recorded by laser Doppler perfusion imaging. Basal skin blood flow was not significantly different in the diabetic group compared with the control group. The following results are expressed as drug-minus-vehicle response. Acetylcholine significantly increased forearm skin perfusion (p < 0.001, analysis of variance) in all subjects, but the vasodilatation was attenuated in the patient group compared with control subjects (0.86 +/- 0.09 vs 1.36 +/- 0.14 arbitrary units of volts (V) respectively, at the fifth measurement point, mean +/- SEM, p < 0.01). Skin perfusion significantly increased following sodium nitroprusside (p < 0.001) but was lower in patients than control subjects (0.12 +/- 0.05 vs 0.45 +/- 0.11 V, respectively, at the fifth measurement point, p < 0.01). These data suggest that endothelial and/or smooth muscle function may be impaired in the skin microcirculation of patients with NIDDM.

Acetylcholine↗

Cutaneous cytodestructive potency of lignans. I. A comparative evaluation of influence on epidermal and dermal DNA synthesis and on dermal microcirculation in the hairless mouse.

The four lignans: podophyllotoxin, 4'-demethyl-podophyllotoxin, alpha-peltatin and beta-peltatin represent the podophyllin ingredients believed to exert lesional necrosis after application to condylomata acuminata. This study comparatively evaluates cutaneous cytodestructive potency of these drugs, as evaluated by measurement of epidermal and dermal 3H-thymidine incorporation and injury of dermal microcirculation at intervals in the range of 9--168 h after application to hairless mouse skin. Influence on DNA-synthesis was measured using a disc technique for isolation of standardized skin areas followed by alkali extraction of DNA from respective tissues after separation through potassium bromide incubation. Any capillary injury was demonstrated by visual assessment of leakage of i.v. injected trypan blue to test areas. An analytical method compensating for variations in DNA synthesis in individual controls is presented. Using 0.5% preparations of the lignans, podophyllotoxin most consistently influenced the variables indicating cytodestructive effect, while 4'-demethyl-podophyllotoxin exerted the weakest degree of damage.

Animals↗

Effect of adenosine and its stabile analogue 2-chloroadenosine on cerebrocortical microcirculation and NAD/NADH redox state.

In the present study, the effects of topically applied adenosine (ADO) and its stabile analogue 2-chloroadenosine (CADO) on cerebrocortical microcirculation and NAD/NADH redox state (oxidized/reduced nicotinamide adenine dinucleotide) were investigated. Vascular volume (CVV), mean transit time of blood flow (tm), blood flow (CBF), and NADH fluorescence of the cat brain cortex were measured through a cranial window with a microscope fluororeflectometer. The reference values of CVV, tm, and CBF, measured in the artificial cerebrospinal fluid (mock CSF) which superfused brain cortex, were regarded as 100%. Adenosine and 2-chloroadenosine, in the concentration range of 10(-6) - 10(-3) M, resulted in concentration-dependent increases in CBF and NAD reduction. 10(-5) M adenosine and 2-chloroadenosine increased CBF by 49.6 +/- 5.6% and 80.4 +/- 10.3%, respectively. At a pharmacologically high concentration (10(-3) M), ADO increased CBF by 164.6 +/- 13.5%, CADO by 333 +/- 44%. At the same time, 10(-3) M ADO and CADO shifted the cortical NAD/NADH redox state by 7.9 +/- 0.4% and 12.4 +/- 0.7%, respectively toward a more reduced state. Our results, concerning the vasodilator potency of adenosine and 2-chloroadenosine, accord with available data in the literature. However, the pronounced NAD reduction obtained with these adenosine nucleosides suggests that, besides an action on vascular adenosine receptors, some other changes, such as increased substrate mobilization and possibly cAMP production, may contribute to the vasodilator effect of adenosine and 2-chloroadenosine.

2-Chloroadenosine↗

Microcirculation in the upper trapezius muscle during sustained shoulder load in healthy women--an endurance study using percutaneous laser-Doppler flowmetry and surface electromyography.

Microcirculation in the upper portion of the trapezius muscle was measured percutaneously in a group of 16 healthy women of different ages by continuous laser-Doppler flowmetry (LDF) in relation to electromyography (EMG) during an endurance test. During the measurements the subject kept her arms straight and elevated at 45 degrees in the scapular plane and held a 1-kg load in each hand as long as possible. This was followed by rest with the arms hanging and carrying no load. The 10-min recording period comprised 1-min initial rest followed by the endurance test and then recovery. Signal processing was done by computer on line. The LDF and root-mean-square (rms) EMG signals were normalized. Spectrum analyses of EMG mean power frequency (MPF) were performed. The amount of load produced was on average 2,267 (SD 939) N.m.s, i.e. shoulder torque x time expressed as Newton meter seconds, and the endurance time was 4.3 (SD 1.20) min. The rms-EMG as well as the LDF increased significantly during endurance, both when related to endurance time and to amount of load. The MPF showed no significant changes. The mean total increase in muscle blood flow was 175% of that recorded in the initial rest period. The average increase per each 10 s of contraction was 2.9%. Maximum was reached during the 1st min of recovery followed by a fall to the base level that was reached within 77 s on average. The amount of load produced and the blood flow increase was smaller than that found in a separate study of men, indicating a lower functional capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Continuous percutaneous measurement by laser-Doppler flowmetry of skeletal muscle microcirculation at varying levels of contraction force determined electromyographically.

Laser-Doppler flowmetry (LDF) and electromyography (EMG) were used simultaneously for measuring skeletal muscle blood perfusion in relation to static load and fatigue. Percutaneous single-fibre LDF and bipolar surface EMG of the trapezius muscle were performed continuously during a 10-min series of alternating periods of static contractions and rest, each of 1-min duration. The muscle was exposed to static load expressed as shoulder torque, by keeping the arms straight and elevated at 30, 60, 90 and 135 degrees. On-line computer processing of the LDF and EMG signals made possible the interpretation of the relationship between the perfusion and the activity of the muscle. The LDF and root mean square (rms)-EMG were normalized by using the average value of the serial examinations of each individual as a reference value. Spectrum analyses of EMG showed the lowest variability for median frequency (MDF) in the frequency range 10-1000 Hz and mean power frequency (MPF) at 2-1000 Hz. The LDF power spectrum density during low (muscle rest) and high (high-force muscle contraction) perfusion indicated that disturbances were small when measurements were performed during sustained static contraction with as little movement as possible. Vasomotion, i.e. rhythmic variations in the blood flow, were present and showed a frequency of 5-6 cycles.min-1. Application of a tourniquet to the upper arm caused an arrest of the microcirculation in the distally situated brachioradial muscle which was followed by a postischaemic hyperaemia upon removal of the torniquet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Microcirculation in the upper trapezius muscle during varying levels of static contraction, fatigue and recovery in healthy women--a study using percutaneous laser-Doppler flowmetry and surface electromyography.

Microcirculation in the upper portion of the trapezius muscle was measured percutaneously by continuous laser-Doppler flowmetry (LDF) during two 10-min series of alternating 1-min periods of static contraction and rest determined electromyographically (EMG). Stepwise increased contraction was induced by keeping the arms straight and elevated at 30, 60, 90 and 135 degrees, which was repeated with a 1-kg load carried in each hand. Thereafter, fatigue and recovery were recorded while the subject kept her arms straight and elevated at 45 degrees carrying the 1-kg hand load as long as possible, followed by rest with arms hanging and no load. A group of 16 healthy women of different ages was studied. Signal processing was done on line using a 386 SX computer. The LDF- and root-mean-square (rms) EMG signals were normalized. Spectrum analyses of EMG mean power frequency (MPF) and median spectrum frequency were performed. The rms-EMG increased significantly with an increase in the calculated shoulder torque (r = 0.75). Accumulated local fatigue was indicated by a decrease in MPF with increased shoulder angle and added load (r = -0.54). Blood flow increased with increased shoulder angle (r = 0.82, with hand load r = 0.62) and with increased shoulder torque (r = 0.72), and also showed a significant increase with increased EMG activity (r = 0.74). The LDF showed a negative correlation to MPF (r = -0.67), with increased values when MPF was lowered. During the endurance test, a moderate increase of LDF occurred which reached its maximum during the 1st min of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Myogenic and flow-dependent control mechanisms in the coronary microcirculation.

We have recently gained evidence that segmental coronary microvascular diameters, and therefore resistances, are controlled by myogenic and endothelial responses to pressure and flow. Furthermore, intact heart studies are demonstrating that these mechanisms may interact importantly with the metabolic mechanisms primarily governing coronary blood flow. Further studies utilizing measurement of segmental coronary microvascular diameters in isolated microvessels and in the beating heart may elucidate the nature of these interactions. Clinical studies may determine whether reversal of endothelial impairment in the diseased coronary microcirculation contributes to autoregulatory vasodilation, increases resting myocardial perfusion, and increases the threshold for myocardial ischemia during exercise.

Animals↗

Measurement by laser-Doppler flowmetry of microcirculation in lower leg muscle at different blood fluxes in relation to electromyographically determined contraction and accumulated fatigue.

Single-fibre percutaneous laser-Doppler flowmetry (LDF) of the tibialis anterior muscle was performed continuously for measurement of the microcirculation during different blood fluxes, as well as in relation to different muscle activities and fatigue determined electromyographically (EMG). The laser-Doppler power spectrum density function was studied in a frequency range of 0-8.2 Hz as representing the blood flow most selectively. Reduced blood flow from tourniquet inflation caused a decrease in signal power density, compared to that of intact blood flow at rest. During postocclusion reactive hyperaemia an increased signal power was recorded. This reached its maximum within 4.4 (SD 1.88) s after deflation of the tourniquet. The different fluxes were recorded at high sensitivity and disturbances were small. Periods of 1-min static dorsi-flexion of the foot at 10, 20, 30, 40, and 50% MVC (maximal voluntary contraction) with 1-min rest between were associated with a significant increase in LDF, the recordings obtained during the rest periods showing a tendency towards an increase. A decrease in the EMG mean power frequency (MPF) indicated accumulated fatigue. The LDF for the rest periods that followed upon continuous contractions up to the same MVC levels showed a tendency towards an increase but variability was large. With further development, these techniques may be useful in the evaluation of insufficiency of the peripheral circulation.

Adult↗

Effects of posture, hypotension and locally applied vasoconstriction on the middle ear microcirculation in anaesthetized humans.

Studies by laser-Doppler flowmetry of middle ear microcirculation changes induced by physical and chemical stimuli in the animal have only recently been made. This prospective study, performed in humans, was designed to compare the effects of a postural manoeuvre (headup tilt 30 degrees), hypotension and locally applied vasoconstriction on middle ear blood flow during anaesthesia. Circulatory changes provoked by a headup tilt of 30 degrees, and successive intravenous boluses of potent vasodilators, were compared with circulatory changes provoked by locally applied adrenaline, in ten healthy patients in good physical states undergoing middle ear surgical repair. Heart rate and direct arterial pressure were continuously recorded via a radial artery cannula. Middle ear blood flow was continuously recorded via a laser-Doppler probe placed on the promontorium cavi tympani. Metabolic parameters (partial pressure of O2 and CO2 in arterial blood, pH, arterial lactate concentrations) and arterial concentrations of propofol were measured just before and just after the experiment. Headup tilt did not modify heart rate, mean arterial pressure or middle ear blood flow. Vasodilators (nicardipine, nitroprusside, nitroglycerin) provoked a fall in arterial pressure (P < 0.0001, P < 0.0001, P < 0.019, respectively), but did not induce any significant variations in heart rate; variations occurred in middle ear blood flow (P > 0.05, not significant) which were different according to patients and agents. Locally applied adrenaline provoked a fall in the middle ear blood flow (P < 0.0012), with no effect on heart rate and arterial pressure. There were no significant changes in metabolic values, or propofol serum concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Early effects of experimental arterial subarachnoid haemorrhage on the cerebral circulation. Part I: Experimental subarachnoid haemorrhage in cat and its pathophysiological effects. Methods of regional cerebral blood flow measurement and evaluation of microcirculation.

Studies of pathophysiological changes, regional cerebral blood flow (rCBF) and cerebral microcirculation were performed in cats subjected to arterial subarachnoid haemorrhage (SAH). An original method for SAH imitating aneurysm rupture was developed. The bleeding was induced by puncturing of the internal carotid artery approached tranpresphenoidally and followed by immediate closure of the skull opening. It was found, that arterial subarachnoid bleeding elevates intracranial pressure and results in a transitory fall in cerebral perfusion pressure which is not prevented by elevation of arterial blood pressure (Cushing reflex). A depression in brain electrical activity and respiration rate were present in the course of subarachnoid haemorrhage.

Animals↗

Early effects of experimental arterial subarachnoid haemorrhage on the cerebral circulation. Part II: Regional cerebral blood flow and cerebral microcirculation after experimental subarachnoid haemorrhage.

Employing the experimental set-up and the methods described - in part I of the paper, the measurements of the regional cerebral blood flow (rCBF) and evaluation of brain microcirculation were performed. The control series provided normal values and constituted the reference for the results of the post-haemorrhagic measurements. Arterial subarachnoid haemorrhage increases transitorily the intracranial pressure to values close to the diastolic blood pressure. The rise of the blood pressure (Cushing response) is not adequate to prevent the reduction in the cerebral perfusion pressure. Cerebral blood flow diminishes after arterial subarachnoid haemorrhage during the elevation of intracranial pressure. It results in numerous, disseminated areas of reduced regional cerebral blood flow. During 4 hours following arterial subarachnoid haemorrhage global cerebral blood flow returns to normal values, while focal reductions in blood flow persist in the grey matter structures of both hemispheres. These foci are accompanied by confined areas of markedly increased regional cerebral blood flow. Disseminated foci with a reduced number of patent capillaries are found in the grey matter structures of both hemispheres 1 and 4 hours following arterial subarachnoid haemorrhage. Their number decreases during the 4 hours observation.

Animals↗

[The influence of dopamine on hemodynamics, microcirculation and renal function in patients with hypnotic drug intoxication (author's transl)].

The effect of dopamine on hemodynamics (CO, AoPm, TPR, SV, SW, CVP, PAPm, PAEDP), microcirculation (MBF, PS-product) and renal function (VU, CKI, CNa, CK, Cosm, TcH2O) was studied in 8 patients with hypnotic drug poisoning. With increasing doses of dopamine, cardiac output and heart rate increased and the peripheral resistance decreased. An augmentation of stroke volume and left ventricular stroke work was observed in the low dose range only (200--400 mug/min). With increasing doses, central venous pressure as well as mean pulmonary artery pressure and enddiastolic pulmonary artery pressure decreased. No vasoconstriction was found in muscle tissue vessels even with large doses of dopamine. This is explained by the vasoplegic properties of hypnotic drugs. In circulatory shock associated with hypnotic drug poisoning, dopamine develops only minor pressure effects in contrast to its action in circulatory shock of cardiogenic or septic shock origin. High doses of dopamine result in a significant increase in heart rate, without concomitant increase in stroke volume and blood pressure. Therefore the dosage of dopamine should not exceed 400 mug/min in these cases. A combination with small doses of norepinephrine (10--20 mug/min) seems to be more effective. Renal function tests showed variable expansion of urine volume, glomerular filtration rate, and clearances of sodium, potassium and osmotic substances. Therapy with dopamine might increase the renal elimination rate of hypnotic drugs.

Adolescent↗

Influence of intense sound stimuli on skin microcirculation.

Sound influences not only the organ of hearing but also other systems including the circulation. The purpose of the present study was to investigate the effect of strong sound on the skin microcirculation of the palmar area of the hand and of the plantar area of the foot, which are areas of dense microvasculature and rich sympathetic innervation. The laser Doppler technique was used for measuring cutaneous red cell flux (RCF). Eighteen normal subjects were studied. The results indicate that a pure tone sound of 1500 Hz, with an intensity of 100 dBA and duration 5 s, applied by earphones caused a significant decrease in RCF in 14 out of 18 subjects in the finger but not in the foot skin. A higher intensity (110 dBA) tone caused a stronger decrease of RCF in the finger. The latency and the duration of the reaction showed a dependence on the intensity of the sound, i.e. the reaction to the stronger stimulus was of shorter latency (p < 0.01) and longer duration (p < 0.05). The duration of the reaction did not show significant change when a longer stimulus of 30 s was applied. Repetitive stimuli evoked habituation (p < 0.05).

Acoustic Stimulation↗

An anatomical study of the microcirculation in the rabbit femur.

A technique is described which will allow a study of the microcirculation to a long bone such as the femur. It involves use of a silicone rubber compound (Microfil) in combination with the Spalteholz clearing technique. Preliminary results in the normal rabbit skeleton suggest that this technique can be used to study the changes in vascularity which occur under various pathological conditions.

Angiography↗