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Control of rat glomerular microcirculation by juxtaglomerular adenosine A1 receptors.

The role of adenosine A1 receptors in the glomerular microcirculation and tubuloglomerular feedback (TGF) was studied in anesthetized Sprague-Dawley rats. TGF activity was assessed as the reduction in proximal tubular stop-flow pressure (SFP) on establishing orthograde perfusion of the loop of Henle with artificial tubular fluid at 40 nl/min. Administration of a selective A1 receptor antagonist, KW-3902 (0.5 microg/kg/min i.v.), increased fractional excretion of Na (FE(Na)) 4.3-fold without changing blood pressure, glomerular filtration rate, renal plasma flow, or filtration fraction. SFP in the absence of distal flow (SFP0) increased, and TGF-mediated SFP reduction was suppressed dose dependently [by 23 +/- 2% from an SFP0 of 34 +/- 1 mm Hg, by 15 +/- 4% from 36 +/- 2 mm Hg, and by 2 +/- 1% from 39 +/- 1 mm Hg during vehicle, low- and high-dose infusions (0.5 and 5.0 microg/kg/min), respectively]. Intratubular or peritubular capillary administration of 10(-4) M KW-3902 completely suppressed TGF without affecting SFP0. TGF suppression and elevation of SFP0 during systemic A1 blockade indicated vasodilation, both in the afferent arteriole and more proximal preglomerular vessels. Inhibition of tubular Na reabsorption combined with TGF suppression allowed the marked natriuresis. TGF suppression through systemic, luminal, and peritubular application of the drug suggest that juxtaglomerular apparatus A1 receptors are important in the control of glomerular microcirculation.

Animals↗

Brain death impairs pancreatic microcirculation.

Brain death (BD) influences the quality of donor grafts in transplantation. To evaluate the impact of BD on pancreas grafts, we investigated the influence of BD on the microcirculation and histology of the pancreas in a rat model of explosive BD. A group of Wistar rats (n=7), rendered brain dead by inflating an intracranially inserted Fogarty catheter was compared with controls (CO) using intravital epifluorescence-microscopy over 4 h after BD induction; functional capillary density (FCD), leukocyte adherence (AL) in post-capillary venules, histology and pancreatic enzymes were investigated. Four hours after BD, FCD decreased (333 +/- 11 vs. baseline 444 cm/cm2 +/- 5 SEM; p<0.01) and showed lower values than CO (388 +/- 9 p<0.01). In BD, AL was increased (628 cells/mm2 +/- 110 SEM vs. baseline 123 +/- 32, and vs. CO 180 +/- 33; p<0.001). BD caused increased histological damage (CO 1.6 score-points +/- 0.7 SD vs. BD 8.3 +/- 7.1; p<0.05). Amylase was higher in BD (p<0.05) but did not reach pathological values. We show for the first time that BD causes relevant changes in pancreatic microcirculation, histology and leukocyte endothelial interaction which might have a serious impact on the function of grafts. New strategies for preventing this damage are therefore highly desirable in order to improve the outcome of pancreas transplantation.

Amylases↗

Coronary microcirculation in essential hypertension: a quantitative myocardial contrast echocardiographic approach.

AIMS: The aims of the present study were: (a) to demonstrate whether quantitative myocardial contrast echocardiography can detect the increase in coronary flow induced by dipyridamole infusion vasodilation through the myocardial opacification due to the transit of microbubbles, both at rest and after dipyridamole induced vasodilation; (b) to explore the coronary microcirculatory function before and after dipyridamole in two different models: asymptomatic and relatively young hypertensive patients with a mild degree of left ventricular hypertrophy, and healthy controls. METHODS AND RESULTS: Two groups of strictly age-matched males were studied (case-control study): 10, relatively young and asymptomatic essential hypertensive patients with a mild degree of left ventricular hypertrophy with a normal left ventricular function, and 10 healthy controls. The main findings were: the microbubbles' appearance area was significantly lower in hypertensive patients than in controls (P<0.05) because of a significantly lower time to peak. The peak intensity at rest was higher in hypertensives than in controls (P<0.05); but the per cent increase after vasodilatory stimulus was significantly higher in controls (+71% in controls vs +31% in hypertensives; P<0.05). The microbubbles' disappearance area was comparable in both groups at rest; the per cent increase of this parameter after dipyridamole was significantly higher in controls (+124%) than in hypertensives (+90%) (P<0.05). The results achieved in this study documented that the coronary microcirculation in hypertensive patients presenting a mild degree of left ventricular hypertrophy, explored with quantitative myocardial contrast echocardiography, showed a different behaviour in comparison with controls, in the vasodilatory response to dipyridamole. CONCLUSION: The coronary microcirculation in hypertensives showed a reduced vasodilation capacity of the resistance arterioles under dipyridamole induced vasodilatation, and a possible impairment of the endothelium dependent vasodilation. This happened despite an increase in the left ventricular mass, where the relation between capillary bed distribution and hypertrophied myocardium (rarefaction phenomenon) is not completely respected.

Adult↗

Microcirculation in hyperglycemic patients with IDDM without diabetic complications--effect of low-dose angiotensin-converting enzyme inhibition.

In patients with insulin-dependent diabetes mellitus (IDDM) angiotensin-converting enzyme inhibitors (ACEI) have been demonstrated to have beneficial effects in the secondary prevention of microvascular complications. There are only few data available regarding the effect of ACEI on microcirculation in patients with IDDM without any microvascular complications. In addition, there is little knowledge about ACEI action during acute hyperglycemia. In a pilot study nine patients with IDDM without any clinical signs of diabetic complications (5 females, 4 males, aged 33.3 +/- 1.0 years, duration of diabetes 11.4 +/- 3.0 years, HbA1 7.2 +/- 0.2% [normal range 4.8-7.4%], BMI 21.4 +/- 0.5 [kg/m2]) received 1.25 mg of the ACEI ramipril (Delix, Hoechst Marion Roussel, Frankfurt) over 4 weeks. Nine healthy volunteers (4 females, 5 males, age 27.4 +/- 1.1 years, HbA1 5.9 +/- 0.2% (p < 0.01 vs patients), BMI 22.2 +/- 0.9 [kg/m2]) served as controls. Using nailfold capillaroscopy we determined capillary blood cell velocity (CapiFlow, Lawrenz Electronics, Sulzbach, Germany) before and during post-occlusive hyperemia (200 mmHg for 3 minutes) as a provocative test. Before and after treatment patients were studied during hyperglycemia (blood glucose 250-350 mg/dl). Treatment with low-dose ramipril resulted in a significant decrease in the time to peak capillary blood cell velocity during post-occlusive hyperemia (17.8 +/- 7.7 vs 57.4 +/- 12.8 s, p < 0.01) in hyperglycemic patients. This effect was absent in healthy volunteers. Hemodynamic and metabolic parameters remained unchanged throughout the study in both groups. These data demonstrate that low-dose therapy with the ACEI ramipril is able to improve microcirculation in hyperglycemic patients with type 1 diabetes mellitus also before microvascular complications are evident. Prospective studies are necessary to evaluate whether this effect might be clinically relevant in the primary prevention of diabetic microangiopathy.

Adult↗

Endothelial dysfunction: impact on epicardial coronary arteries and microcirculation.

This article examines the relationship between endothelial dysfunction and "small vessel disease." Newer technologies have facilitated the study of this issue. Using a Doppler wire and the intracoronary administration of acetylcholine and papaverine, a difference can be made between functional and chronic-trophic disturbances of the coronary reserve. Papaverine induces smooth muscle cell-mediated vasodilation, acetylcholine induces nitric oxide (NO)-mediated vasodilation. The data revealed that endothelial dysfunction may be related to disturbances in the microcirculation. In addition to those vasomotor-related properties, other factors such as antithrombotic, antiadhesive disturbances contribute to the disturbed microcirculation. Newer techniques, such as serial positron emission tomography, may yield an even better understanding of these processes.

Coronary Disease↗

New composite tissue allograft transplantation model in mouse with intravital microscopic evaluation of microcirculation.

A new mouse composite tissue allograft (CTA) transplantation model was developed to study the microcirculatory changes during acute allograft rejection and ischemia/reperfusion (I/R) injury. The donor cremaster muscle allografts were prepared as a tube flap, harvested on the common iliac vessels, transplanted to the neck region of the recipient, and anastomosed to the recipient's ipsilateral carotid artery and external jugular vein using standard end-to-end microsurgical technique. In Group 1 (n=6), the hemodynamics of cremasteric muscle microcirculation was measured in C57BL/6N mice without transplantation for baseline data. In Group 2 (n=6), isograft transplantations were performed between C57BL/6N mice. In Group 3 (n=5), allograft transplantations were performed across a high histocompatibility barrier between C3H and C57BL/6N mice. Following transplantation, cremaster muscle tube flaps were prepared for standard microcirculatory measurements of functional capillary perfusion, diameters, and red blood cell (RBC) velocities of 1 (st), 2 (nd), and 3 (rd) order arterioles and venules, and numbers of rolling, adhering, and transmigrating leukocytes and lymphocytes. Hemodynamic parameters of microcirculation did not differ significantly between the three groups. However, the number of rolling, adhering, and transmigrating polymorphonuclear leukocytes and lymphocytes was significantly increased in the allograft group ( p<0.001) as early as 2 hr following transplantation. Cremaster muscle transplantation in mice is a reliable and reproducible model with a 95 percent immediate success rate. The model offers the unique possibility of studying leukocyte-endothelial interaction during acute allograft rejection and I/R injury in mouse.

Abdominal Muscles↗

[Determination of the renal blood flow in macro- and microcirculation by means of pulse inversion imaging].

PURPOSE: To evaluate whether real-time and intermittent pulse inversion technology (PI) allows the analysis of blood flow in renal macro- and microcirculation. MATERIALS AND METHODS: The experiments were performed in a kidney perfusion phantom as an experimental model for the assessment of contrast replenishment in vascular regions of high flow velocity (medulla) and low flow velocity (cortex). During continuous infusion (0.03 ml/min) of Optison, contrast replenishment kinetics were assessed with intermittent PI at high emission power (MI: 1.3, with increasing trigger intervals) and with real-time PI at low emission power (MI: 0.09) at variable renal arterial blood flow (15 - 65 ml/min), using an HDI-5000 ultrasound unit (Philips Medical Systems). Regions of interest were placed in the major arteries of the medulla and the renal cortex to obtain replenishment curves of the macro- and microcirculation. Non-linear curve fitting was performed using the mathematical model y = A (1-e (-beta t)) with A as the parameter describing blood volume and beta as the parameter describing the speed of contrast replenishment. RESULTS: Replenishment curves could be obtained in all analyzed renal segments. For intermittent and real-time PI a strong linear correlation was found between renal arterial blood flow and A*beta (intermittent PI: cortex: R = 0.97; medulla: R = 0.98; real-time PI: cortex: R = 0.99; medulla: R = 0.96). The differences between the slopes of the regression lines (cortex: high power vs. low power, p = 0.844; medulla: high power vs. low power, p = 0.444) were not significant. CONCLUSION: Intermittent and real-time PI allows the assessment of renal blood flow in different vessel compartments.

Albumins↗

Microcirculation of the ankle after Cryo/Cuff application in healthy volunteers.

The aim of the study was to assess the combination of compression and cryotherapy (Cryo/Cuff ankle device) on parameters of ankle microcirculation in healthy volunteers over 30 min. In 21 volunteers (12 males, 29 +/- 10 years [incl. females], BMI 24 +/- 3) the Cryo/Cuff ankle device (AIRCAST, Summit, NJ, USA) was applied with continuous assessment of parameters of ankle microcirculation, such as tissue oxygen saturation (SO2), relative postcapillary venous filling pressures (rHb), and microcirculatory blood flow at 2- and 8-mm tissue depths during 30 min with the Oxygen-to-see System, a laser-Doppler-spectrophotometry-system (LEA Medizintechnik, Giessen, Germany). Superficial tissue oxygen saturation (SO2, 48 +/- 19 %) immediately dropped to 23 +/- 15 % (-52 %, p < 0.05) within the first 2 min after Cryo/Cuff activation with a consecutive slow decrease to 32 +/- 23 % (- 32 %, p < 0.05 vs. baseline) after 30 min. Deep SO2 (8 mm, 69 +/- 5 %) did not change within 30 min of Cryo/Cuff application (70 +/- 4 %, n.s.). Superficial postcapillary venous filling pressures (61 +/- 17 relative units) showed an immediate and sustained decrease after Cryo/Cuff application within four minutes to 37 +/- 18 relative units (-39 %, p < 0.05). Deep postcapillary venous filling pressures (85 +/- 20 relative units) dropped within the first four minutes of Cryo/Cuff application to 68 +/- 19 relative units (-20 %, p < 0.05). Superficial microcirculatory blood flow (21 +/- 36 relative units) decreased significantly to 7 +/- 5 relative units after 30 min (-69 %, p < 0.05 vs. baseline). Deep microcirculatory blood flow at 8 mm tissue depth (63 +/- 43 relative units) significantly decreased over the 30 min to 39 +/- 23 relative units (-47 %, p < 0.05 vs. baseline). Using the Oxygen-to-see system we could demonstrate significant effects of the Cryo/Cuff device on the ankle level in healthy volunteers with reduced superficial tissue oxygen saturation with preserved deep tissue oxygen saturation, reduced superficial and deep postcapillary venous filling pressures, and reduced superficial and deep microcirculatory blood flow as a function of time. Further clinical studies are mandatory to elucidate the effects of the Cryo/Cuff device on the microcirculatory environment in injured ankles.

Adult↗

[Coincidence of hypertensive changes of the eye fundus and regulation disorders of peripheral microcirculation: I--Skin].

In cases of arterial hypertension, funduscopy is an established method of estimating systemic vascular lesions. In this study the relation between the extent of retinal vascular changes and dynamic processes in the microcirculation of the skin was investigated by nailfold capillaroscopy in 88 patients. With increasing vascular changes a progressive loss of vasodilator reserve and transcutaneous partial pressure was observed (no morphologic changes--fundus hypertonicus II--fundus hypertonicus III). It thus appears possible to evaluate the functional state of the macro- and microcirculation by funduscopy.

Adult↗

[Effect of fenofibrate on fibrinogen concentration and blood viscosity. Consequences for myocardial microcirculation in coronary heart disease?].

The effect of fenofibrate (a clofibrate derivative) on fibrinogen concentration, blood viscosity and myocardial microcirculation was examined in 35 patients with coronary heart disease (n = 27) or hypertension (n = 8). After eight weeks' administration of 250 mg fenofibrate daily cholesterol and triglycerides levels decreased significantly, as did the fibrinogen concentration, from a mean of 300.7 +/- 75.1 mg/dl to 252.3 +/- 61.2 mg/dl (P less than 0.01). Plasma viscosity and erythrocyte aggregation were also significantly lowered (from 1.43 +/- 0.09 to 1.37 +/- 0.07 mPas and 15.0 +/- 3.1 to 13.5 +/- 2.2, respectively; P less than 0.01). In eight of twelve subjects selected from the whole group thallium myocardial scintigraphy demonstrated, after eight weeks of treatment with fenofibrate, a global (in two) or regional (in six) increase in blood flow. Reduction of fibrinogen concentration may in coronary heart disease achieve an improvement in myocardial microcirculation with decreased myocardial ischaemia.

Blood Viscosity↗

Morphologic changes in the microcirculation induced by chronic smoking habit: a videocapillaroscopic study on the human labial mucosa.

BACKGROUND: Cigarette smoking has been identified as a major risk factor for cardiovascular and pulmonary diseases. Although an impressive literature does exist on the subject, no evidence is available on morphologic changes induced with chronic smoking habit in the human microcirculation. SUBJECTS AND METHODS: One hundred healthy subjects, 50 smokers and 50 nonsmokers, underwent videocapillaroscopy of the labial mucosa. For each subject, the caliber of capillary loops, the number of visible capillary loops, the background optical transmittance, the tortuousness of capillary loops, the presence of microaneurysms, the presence of microhemorrhages, and the cumulative smoking habit (pack-year index) were noted. RESULTS: Smokers had a lower caliber of capillary loops (P <.001), with a higher number of visible capillary loops (P <.001), a lower background optical transmittance (P <.001), and a more marked tortuousness of capillary loops (P <.001). Microaneurysms and microhemorrhages were absent in nonsmokers, and 1 smoker of 3 had microaneurysms alone, and 1 smoker of 3 had both microaneurysms and microhemorrhages. A significant correlation was found between cumulative smoking habit and tortuousness of capillary loops (P <.001) and between cumulative smoking habit and total score (tortuousness score + microaneurysm score + microhemorrhage score; P <.005). CONCLUSION: Chronic smoking habit does induce significant morphologic changes in the microcirculation of the human labial mucosa, and these changes can be easily and comfortably recorded with videocapillaroscopy.

Adult↗

Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates.

BACKGROUND: We previously demonstrated that therapy with a new endothelin A receptor antagonist (ET-RA) significantly reduced mortality rates in severe acute pancreatitis (AP) in the rat without attenuating local signs of disease severity (intrapancreatic protease activation, acinar cell necrosis). This raised the question as to why ET-RA was so effective. The purpose of this study was to assess the effect of ET-RA on microcirculation (particularly capillary permeability) within and outside of the pancreas on intravascular fluid loss and extravascular fluid sequestration and on distant organ function. METHODS: Severe AP was induced in rats by standardized intraductal bile acid infusion and cerulein hyper-stimulation. Starting 6 hours (n = 24 rats) and 12 hours (n = 30 rats) after the onset of AP, animals randomly received either the ET-RA (LU-135252) or saline solution with fluid resuscitation (6 mL/kg/h Ringer's lactate). At 24 hours, animals were relaparotomized for intravital microscopic determination of capillary blood flow, leukocyte rolling, and capillary permeability in the pancreas and colon. Further monitoring included cardiorespiratory and renal parameters, hematocrit levels and quantification of ascites and pleural effusions, and acinar cell necrosis at autopsy. Groups of sham-operated healthy animals (n = 6 animals each) that had been treated according to the same protocol served as control animals. RESULTS: ET-RA treatment that was started 6 hours after AP-induction significantly decreased hematocrit levels (38% +/- 1% vs 45% +/- 2% with saline solution treatment), reduced ascites and pleural effusions (6.7 +/- 1.3 mL vs 11.9 +/- 1.3 mL), and improved urine production (4.8 +/- 0.5 mL vs 2.9 +/- 0.6 mL) and respiratory parameters. Moreover, all microcirculatory parameters were improved; in particular, capillary permeability was stabilized (158% +/- 9% vs 248% +/- 8% in the colon). These beneficial effects were also seen when therapy was delayed until 12 hours after AP induction. Pancreatic necrosis was not significantly reduced. The overall mortality rate was 12% in ET-RA-treated animals and 42% in saline solution-treated control animals (P <.05). In healthy animals ET-RA did not significantly alter the target parameters, except for a reduction of capillary permeability in the pancreas. CONCLUSIONS: Improved microcirculation and stabilized capillary permeability in ET-RA-treated animals together with reduced intravascular fluid loss and extravascular fluid sequestration and improved renal and pulmonary function (1) may explain improved survival in this model, (2) support the hypothesis that systemic disease sequelae significantly contribute to outcome in AP, and (3) suggest that ET-RA may be a promising therapeutic tool in AP because it counteracts microcirculatory disorders that contribute to pancreatitis-associated organ dysfunction even when therapy is delayed to a point at which pancreatic injury may no longer be influenced.

Acute Disease↗

Noninvasive analysis of conjunctival microcirculation during carotid artery surgery reveals microvascular evidence of collateral compensation and stenosis-dependent adaptation.

OBJECTIVE: Hemodynamically relevant internal carotid artery (ICA) stenosis is a major cause of ischemic stroke. Despite its long-term benefit, carotid endarterectomy may also be associated with severe neurologic deficits. Intraoperative and early recognition of ischemia in the region of the ICA may reduce this risk. To date, direct imaging and quantitative analysis of microvascular structures and function in the human ICA region have not been possible. We purposed to visualize and quantify ischemia/reperfusion-induced microcirculatory changes in the terminal vascular bed of the ICA in patients undergoing unilateral ICA endarterectomy. METHODS: Sequential analysis of the ipsilateral and contralateral conjunctival microcirculation was performed with orthogonal polarized spectral imaging in 33 patients undergoing unilateral ICA endarterectomy because of moderate or severe ICA stenosis (North American Symptomatic Carotid Endarterectomy Trial score, 75% +/- 13%), before clamping the ICA (baseline), during clamping of the external carotid artery and ICA, during reperfusion of the ICA (intraluminal shunt), during the second clamping of the ICA (shunt removal), after declamping (reperfusion) of the external carotid artery and ICA, and 15 to 20 minutes after the second ICA reperfusion. RESULTS: During ICA clamping for shunt placement, ipsilateral and contralateral conjunctival capillary perfusion was significantly decreased, but it was completely restored after reperfusion with carotid shunting. Reclamping of the ICA for shunt removal caused microvascular dysfunction, which was significantly less pronounced than that observed during the first clamping. The individual degree of ICA stenosis was inversely correlated with the ipsilateral and contralateral decrease in conjunctival functional capillary density during the first ICA clamping. CONCLUSIONS: These results suggest adaptive mechanisms of capillary perfusion with increasing stenosis and development of collateral compensatory circulation in the vascular region of the human ICA. Conjunctival orthogonal polarized spectral imaging during unilateral ICA reconstruction enables continuous noninvasive analysis of bilateral conjunctival microcirculation in the terminal region of the ICA and enables monitoring for efficient carotid shunt perfusion during and after endarterectomy.

Adaptation, Physiological↗

Quantifying leukocyte dynamics and plugging in retinal microcirculation of streptozotosin-induced diabetic rats.

PURPOSE: To determine leukocyte kinetics in the retinal microcirculation of streptozotosin-induced diabetic rats. METHODS: Rats were made diabetic with intraperitoneal injection of streptozotosin. For one month after injection, the alteration of the velocity and plugging of leukocytes were investigated using acridine orange, which stains leukocytes, and scanning laser ophthalmoscopy. Blood plasma protein levels, such as fibrinogen and alpha1- and alpha2- globulin, were also measured. RESULTS: Throughout the observational period, mean leukocyte velocity was similar between diabetic (1.53+/-0.45 mm/sec) and age-matched control (1.58+/-0.23 mm/sec) rats, but the coefficient of variation of the velocity in the diabetic rats was twice as large as that in the control rats. Plugging was increased in a sigmoidal fashion and saturated for 5 weeks or later. No differences were seen in plasma protein levels between groups. CONCLUSIONS: Within one month of the hyperglycemic condition, the velocities of leukocytes in capillaries were more varied and the leukocytes were plugged time-dependently. This action occurred not because the blood fibrinogen and globulin levels were altered, but because of the leukocyte-endothelium interaction. In streptozotosin-induced diabetic rats, retinopathy usually cannot be found during the fundus examination and fluorescein angiography. In the level of the microcirculation, however, some of the disorders have already occurred.

Acridine Orange↗

Macrophages and microcirculation in regressed and partially regressed irradiated choroidal and ciliary body melanomas.

PURPOSE: To investigate how tumour-infiltrating macrophages and microcirculation attributes of uveal melanomas regressed after brachytherapy and whether primarily enucleated melanomas differ. METHODS: A case-control analysis of 34 matched pairs of irradiated and nonirradiated choroidal and ciliary body melanomas with main outcome variables being area of necrosis, extravascular matrix loops and networks, tumour-infiltrating macrophages in nonnecrotic areas identified with mAb PG-M1 to the CD68 epitope, and microvascular density (MVD) determined by mAb QBEND/10 to the CD34 epitope. RESULTS: Comparison of primarily enucleated eyes to eyes with irradiated, secondarily enucleated melanomas revealed significantly more necrosis (median difference, +9%, P = 0.0012) and lower MVD (median difference, -10 counts/0.313 mm(2), P = 0.011) in the latter. In eyes managed with brachytherapy, loops and networks tended to be less frequent (P = 0.077). Number and type of macrophages were similarly distributed, being moderate to high in about 95% (P = 0.67) of the matched pairs, and intermediate to dendritic in 79% (P = 0.90). In the irradiated eyes, presence of epithelioid cells and the number and type of macrophages showed no association with microcirculation attributes, whereas in the primarily enucleated tumours, high number of macrophages was associated with high MVD (P < 0.001). CONCLUSIONS: This study suggests that regression after brachytherapy reduces MVD. The difference cannot be attributed to different numbers of tumour-infiltrating macrophages and different cell type in nonnecrotic areas of the tumour.

Blood Vessels↗

Focal damage to cochlear microcirculation measured using a non-contact laser blood flowmeter in guinea pigs.

The focal microcirculation damage induced by a photochemical reaction in the stria vascularis (SV) of the guinea pig cochlea was evaluated using a non-contact laser blood flowmeter (NCLBF) and the endocochlear potential (EP). Focal degeneration, including vascular thrombosis in the SV produced by the systemic infusion of rose bengal, and the illumination of green light in the second cochlear turn were observed with scanning and transmission electron microscopy. The NCLBF probe was placed at a position 10 mm from the cochlear surface, and the diameter of the laser light was focused to 1 mm in the green light illumination area. The change in NCLBF values induced by the loading of anoxia and administration of epinephrine agreed very well with those obtained with a conventional contact-type laser Doppler flowmeter. Significant decreases in the cochlear blood flow (CBF) (p < 0.01) and EP (p < 0.01) were observed at the site of the photochemical injury compared with the values at the non-illuminated area. CBF gradually decreased (82.0+/-7.3% at 10 min, 71.2+/-5.5% at 20 min, 64.3+/-11.2% at 30 min from the baseline, n=7), but blood pressure was stable. The EP values also decreased gradually during the first 13 min (79.9+/-3.7 mV at pre-illumination, 11.4+/-10.7 mV at 13 min, n=7). The gradual decline in the EP was comparable to the changes in the CBF. The NCLBF was useful for evaluating the haemodynamic properties of the cochlear microcirculation disorders, and this animal model is expected to be suitable for studying the pathology of focal cochlear vascular disease.

Animals↗

Effects of ventricular arrhythmia on the cerebral microcirculation in cats.

To test the widely believed but poorly proved hypothesis that the cerebral symptoms observed during ventricular arrhythmia are caused by a reduced cerebral blood supply, we examined the effects of single and multiple ectopic ventricular beats (or ventricular tachycardia of short duration) on the cerebral microcirculation. Six anesthetized cats were used. Ectopic ventricular systoles of various sequences were produced by electrically stimulating the ventricle through a bipolar needle-type electrode for 1 to 50 times at a rate of 300/min. The local cerebral blood volume (CBV) and blood flow (CBFLD) in the cortex were measured continuously employing the photoelectric and laser Doppler methods. CBV reflects the cumulative dimensions of the cerebrocortical microvessels. Ectopic ventricular contractions, as confirmed by electrocardiograms, always reduced the CBV and arterial blood pressure in a total of 104 attempts. The CBV reductions ranged from 0.20 +/- 0.03 vol% for a single ectopic beat to approximately 0.6-0.8 vol% for runs of 8 or more beats. The CBFLD reductions measured with the laser Doppler flowmeter were 10-35%. The reductions in CBV and CBFLD during the ventricular arrhythmia could be attributed to the abrupt and marked reductions in arterial blood pressure. Runs of ectopic ventricular beats have significant effects on the cerebral microcirculation, whether clinically apparent or not.

Animals↗

Hypothermia influences time course of intracranial pressure, brain temperature, EEG and microcirculation during ischemia-reperfusion.

Time-related effects of hypothermia on intracranial pressure (ICP), brain (Tbr) and rectal temperature (Tc), cortical (LDF) and subcortical microcirculation (ti-pO2) were assessed following a unilateral balloon induced epidural focal mass lesion in rats. Results of injured but normothermia animals (Group A, n = 6) were compared with hypothermia animals (Group B, n = 6). Parameters were recorded during balloon expansion (BE) to an ICP of 60 mmHg followed by a period of sustained inflation (SI) of 30+/-2 min. Animals in Group B were then cooled to 31.7+/-0.4 degrees C (Tbr) during SI. After reperfusion animals were monitored 178+/-4 min. The study protocol concluded with a rewarming phase of the hypothermic animals. Balloon expansion led to a Cushing response and flattening of the EEG. In both groups Tbr decreased during inflation of the balloon 0.5-0.8 degrees C below Tc and during SI in Group A 1.7 degrees C below Tc. During SI and reperfusion Tbr decreased below Tc in Group A but remained above Tc in Group B (p < 0.003). During sustained inflation LDF decreased in group A to 21% and in Group B to 45% of baseline values. After 178+/-4 min of reperfusion LDF reached 68% of baseline values in Group A and 97% in Group B (p < 0.001). During sustained inflation ti-pO2 showed median values of 0.8 mmHg in Group A and 5.5 mmHg in Group B. After reperfusion ti-pO2 reached normal values in both groups (p < 0.3) but ti-pO2 showed 18% higher values before rewarming. After reperfusion the secondary increase of ICP was reduced (p < 0.006) and CPP was improved by 20% in Group B. EEG restored quicker in Group B than Group A (106+/-11 min vs. 188+/-25 min). Intra-ischemic hypothermia improved cerebral microcirculation, prevented a secondary increase of ICP and improved restoration of EEG after ischemia-reperfusion.

Animals↗