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Biomedical subjects

A Just

Publications and source records attributed to A Just.

At least 37 records · Page 2Linked to original sources
PubMed1999

Stimulation of the renin-angiotensin system by endothelin subtype A receptor blockade in conscious dogs.

Previous studies in dogs have shown additive or even synergistic effects of combined angiotensin-converting enzyme inhibition and either nonselective endothelin subtype A/B (ETA/B) or selective endothelin subtype A (ETA) receptor blockade on renal vascular resistance and mean arterial blood pressure. A possible mechanism underlying this interaction may be a stimulation of the renin-angiotensin system during endothelin (ET) receptor blockade. We therefore investigated whether plasma renin activity and renin release are regulated by the ETA receptor. Experiments were made in conscious, chronically instrumented dogs receiving either saline or the selective ETA receptor antagonist LU 135252 (10 mg/kg IV). Eighty to 100 minutes after the administration of LU 135252 (n=5), heart rate (99+/-7 versus 81+/-6 bpm; P<0.05) and renal blood flow (327+/-40 versus 278+/-36 mL/min; P<0.05) were increased significantly, whereas mean arterial blood pressure tended to be lower (93+/-5 versus 105+/-7 mm Hg). These changes were associated with a 2-fold increase in plasma renin activity (0.74+/-0.12 versus 0.37+/-0.10 ng angiotensin I per milliliter per hour; P<0.05). Measurements of renin release at various renal perfusion pressures (n=5) with the use of a vascular occluder implanted around the left renal artery revealed that ETA receptor blockade did not alter renin release at resting renal perfusion pressure (78+/-25 versus 71+/-39 U/min) but strongly enhanced the sensitivity of pressure-dependent renin release <80 mm Hg approximately 2.2-fold. In conclusion, selective ETA receptor blockade is associated with a stimulation of the circulating renin-angiotensin system, which results from both a sensitization of pressure-dependent renin release and a larger proportion of blood pressure values falling into the low pressure range, where renin release is stimulated. These find-ings strengthen the view that ET and the renin-angiotensin system closely interact to regulate vascular resistance and provide a physiological basis for synergistic hypotensive effects of a combined blockade of both pressor systems.

Animals↗
PubMed1999

Interaction between nitric oxide and endogenous vasoconstrictors in control of renal blood flow.

The level of renal blood flow (RBF) is controlled by opposing vasoconstrictor and vasodilator influences. In a recent investigation in normotensive dogs, we found that combined blockade of endothelin type A (ET(A)) receptors and angiotensin II formation induces marked increases in RBF that were much larger than the effects of blocking either system alone. The aim of the present study was to determine the contribution of nitric oxide (NO) to this vasodilator response. Experiments were made in 6 conscious, chronically instrumented dogs subjected to 5 different experimental treatments on separate days. Blockade of ET(A) receptors alone by the selective antagonist LU 135252 had only minor effects on RBF compared with time-control experiments. Additional blockade of angiotensin II formation by angiotensin-converting enzyme inhibition with trandolaprilat caused a substantial increase of RBF by approximately 50%. This vasodilation was entirely suppressed when NO formation was prevented by inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester HCl. However, when during NO synthase inhibition renal vascular NO concentrations were clamped at control levels by infusing the NO donor S-nitroso-N-acetyl-D, L-penicillamine, the vasodilator response to combined blockade of ET(A) receptors and angiotensin II formation was completely restored (DeltaRBF approximately 60%). These results indicate that the vasodilation after combined ET(A) receptor blockade and angiotensin-converting enzyme inhibition is not mediated by an increase in NO release but results from the unmasking of the tonic influence that is normally exerted by constitutively released NO. Accordingly, the tonic activity of endothelial NO synthase appears to be of major importance in the physiological regulation of renal vascular resistance by determining the vasomotor responses to endothelin and angiotensin II.

Angiotensin II↗
PubMed1999

Influence of catheter position and equipment-related factors on the accuracy of intravascular ultrasound measurements.

BACKGROUND: Intravascular ultrasound (IVUS) is frequently used as an adjunct to coronary angiography to guide revascularization procedures and, more recently, to estimate atherosclerotic plaque volumes. Although accuracy of IVUS imaging and analysis is crucial for these measurements, available data are scarce. The purpose of this in vitro study is to determine the extent to which transducer position and equipment-related factors influence measurement accuracy. METHODS: Cross-sectional views of tubular vessel phantoms (diameter 2-14 mm) were acquired using 3.2 French catheters in coaxially centered, eccentric and oblique positions. Catheters were sequentially connected to two different ultrasound systems (A and B) to estimate equipment-related variability. In system B, two software versions were used to analyze ultrasound images. Longitudinal views of phantom segments were reconstructed to document transducer misplacement. RESULTS: Oblique transducer positioning resulted in a non-linear overestimation of phantom areas that was independent of lumen size and also resulted in dramatic distortions of three-dimensionally reconstructed phantom geometry. Eccentric positioning did not significantly influence measurement accuracy. In coaxial positioning, differences between measured and true areas increased non-linearly from 0.36 to 4.5 mm2 in system B and in a linear fashion from -0.01 to 2.68 mm2 in system A with increasing phantom diameters. Relative differences decreased from 11.4% to 2.9% with increasing reference areas in system B (positive off-set error). When using updated software in system B, the off-set error was negative and relative error diminished from -1.34% to 0.44% with increasing phantom size. CONCLUSION: Transducer position and equipment-related factors influence the accuracy of intravascular ultrasound, which may lead to misinterpretation of vessel size and geometry even in straight vessel segments. Transducer position may be controlled by the reconstruction of longitudinal images. Ultrasound equipment should be calibrated before using it for quantitative measurements.

Cardiac Catheterization↗
PubMed1998

Buffering of blood pressure variability by the renin-angiotensin system in the conscious dog.

1. The renin-angiotensin system (RAS) participates in the compensation of major blood pressure disturbances such as haemorrhage and is involved in the tonic long-term (> 1 day) maintenance of mean arterial blood pressure (MABP). Since its contribution to the short-term (< 1 h) buffering of normal blood pressure variability is not known, this was investigated in resting conscious dogs. 2. The regulatory efficiency and the response time of the RAS were studied by an acute step reduction of renal artery pressure to 70 mmHg for 1 h using a suprarenal aortic cuff. After a delay of at least 100 s, MABP rose exponentially by 22 +/- 5 mmHg in normal dogs (n = 4), by 6 +/- 3 mmHg after angiotensin converting enzyme (ACE) inhibition (n = 4), and by 25 +/- 5 mmHg after ganglionic blockade (n = 4). MABP returned to control after release of the cuff with similar time courses. The time constants of the MABP responses were in the range of 20 min. Thus, possible feedback oscillations of the RAS would be expected around 0.0025 Hz (1/(4 x 100 s)); a buffering effect would be possible below this frequency. 3. Blood pressure variability was investigated by spectral analysis of MABP from 3.75 h recordings in the frequency ranges of 0.002-0.003 Hz (feedback oscillations) and below 0.002 Hz (buffering effect). 4. ACE inhibition (n = 7) decreased MABP by 11 +/- 2 mmHg (P < 0.05), but in both frequency ranges integrated spectral density was not affected. ACE inhibition also failed to significantly change spectral density in either of the two frequency ranges under the following conditions: (1) during ganglionic blockade (n = 7), (2) during a low-sodium diet (except for a very slight elevation below 0.002 Hz) (n = 7), and (3) when the fall of MABP induced by ACE inhibition was compensated by an angiotensin II infusion (n = 7). 5. It is concluded that in spite of its high regulatory efficiency with an adequate response time the RAS does not directly contribute to the short-term buffering of blood pressure variability, nor does it give rise to feedback oscillations under normal resting conditions. Even if the RAS is stimulated by sodium restriction its contribution to short-term blood pressure buffering is only marginal.

Angiotensin II↗
PubMed1998

Renal haemodynamic responses to exogenous and endogenous adenosine in conscious dogs.

1. Adenosine has been suggested to be the mediator of a metabolic feedback mechanism which transfers acute changes in the tubular load into opposite changes in renal blood flow (RBF). The goal of the present experiments was to assess the importance of endogenously formed adenosine as a 'homeostatic metabolite' during short-term changes in metabolic demand. 2. In nine chronically instrumented conscious foxhounds, both the direct effects of adenosine injections (10, 30 and 100 nmol) into the renal artery and the temporal changes of RBF after short renal artery occlusions (15, 30 and 60 s duration), the most widely used experimental model to study the metabolic feedback mechanism in vivo, were studied. 3. Intrarenal bolus injections of adenosine (10, 30 and 100 nmol) induced dose-dependent decreases of RBF (RBF: -34 +/- 5, -59 +/- 4 and -74 +/- 4 %, respectively). This vasoconstrictor effect of adenosine was significantly larger (RBF: -51 +/- 4, -68 +/- 4 and -83 +/- 3 %, respectively) when the dogs received a low salt diet. 4. The post-occlusive responses were characterized by a transient hyperaemia with no detectable drop of RBF below the preocclusion level. The post-occlusive responses were affected neither by changes in local angiotensin II levels, nor by intrarenal infusions of hypertonic NaCl or blockade of A1 adenosine receptors. 5. When intrarenal adenosine levels were elevated by infusion of the adenosine uptake inhibitor dipyridamole, a transient, although weak, post-occlusive vasoconstriction was detected. 6. In summary, the present data demonstrate that adenosine acts as a potent renal vasoconstrictor in the conscious dog. The endogenous production of adenosine during short-lasting occlusions of the renal artery, however, appears to be too small to induce a post-occlusive vasoconstrictor response of RBF. These results suggest that a metabolic feedback with adenosine as 'homeostatic metabolite' is of minor importance in the short-term regulation of RBF in the conscious, unstressed animal.

Adenosine↗
PubMed1998

Autoregulation of renal blood flow in the conscious dog and the contribution of the tubuloglomerular feedback.

1. The aim of this study was to investigate the autoregulation of renal blood flow under physiological conditions, when challenged by the normal pressure fluctuations, and the contribution of the tubuloglomerular feedback (TGF). 2. The transfer function between 0.0018 and 0.5 Hz was calculated from the spontaneous fluctuations in renal arterial blood pressure (RABP) and renal blood flow (RBF) in conscious resting dogs. The response of RBF to stepwise artificially induced reductions in RABP was also studied (stepwise autoregulation). 3. Under control conditions (n = 12 dogs), the gain of the transfer function started to decrease, indicating improving autoregulation, below 0.06-0.15 Hz (t = 7-17 s). At 0.027 Hz a prominent peak of high gain was found. Below 0.01 Hz (t > 100 s), the gain reached a minimum (maximal autoregulation) of -6.3 +/- 0.6 dB. The stepwise autoregulation (n = 4) was much stronger (-19.5 dB). The time delay of the transfer function was remarkably constant from 0.03 to 0.08 Hz (high frequency (HF) range) at 1.7s and from 0.0034 to 0.01 Hz (low frequency) (LF) range) at 14.3 s, respectively. 4. Nifedipine, infused into the renal artery, abolished the stepwise autoregulation (-2.0 +/- 1.1 dB, n = 3). The gain of the transfer function (n = 4) remained high down to 0.0034 Hz; in the LF range it was higher than in the control (0.3 +/- 1.0 dB, P < 0.05). The time delay in the HF range was reduced to 0.5 s (P < 0.05). 5. After ganglionic blockade (n = 7) no major changes in the transfer function were observed. 6. Under furosemide (frusemide) (40 mg + 10 MG h-1 or 300 mg + 300 mg h-1 i.v..) the stepwise autoregulation was impaired to -7.8 +/- 0.3 or 6.7 +/- 1.9 dB, respectively (n = 4). In the transfer function (n = 7 or n = 4) the peak at 0.027 Hz was abolished. The delay in the LF range was reduced to -1.1 or -1.6 s, respectively. The transfer gain in the LF range (-5.5 +/- 1.2 or -3.8 +/- 0.8 dB, respectively) did not differ from the control but was smaller than that under nifedipine (P < 0.05). 7. It is concluded that the ample capacity for regulation of RBF is only partially employed under physiological conditions. The abolition by nifedipine and the negligible effect of ganglionic blockade show that above 0.0034 Hz it is almost exclusively due to autoregulation by the kidney itself. TGF contributes to the maximum autoregulatory capacity, but it is not required for the level of autoregulation expended under physiological conditions. Around 0.027 Hz, TGF even reduces the degree of autoregulation.

Animals↗
PubMed1998

Catheter-related infections in long-term catheterized dogs. Observations on pathogenesis, diagnostic methods, and antibiotic lock technique.

BACKGROUND: Intravascular catheters are associated with severe infections in patients, but only few reports on this problem in animal research exist. OBJECTIVE: We report on catheter-related bacterial colonization and its consequences in long-term catheterized animals. MATERIAL AND METHOD: Foxhounds were instrumented with intravascular catheters and flow probes to study the regulation of renal blood flow and pressures. RESULTS: After flushing the catheters, alterations in renal blood flow were observed and these could be related to bacterial colonization of intravascular catheters with Pseudomonas species. After attention had been focused on aseptic technique in all experimental phases and prophylactic antibiotic lock instituted, the occurrence of Pseudomonas bacteremia ceased, and the magnitude and incidence of catheter-related colonization and infection by Pseudomonas species dropped considerably. CONCLUSION: The catheter-related colonization that occurred spontaneously in these animals resembled findings in animal experiments in which catheter-related infections were deliberately induced as well as observations made with regard to catheter-related infections in patients. This report emphasizes the importance of asepsis when working with animals with long-term intravascular catheters. We suggest that monitoring for this complication, e.g., by means of catheter cultures at the time of removal, should routinely be part of protocols for animal experiments using long-term intravascular catheters.

Animals↗
PubMed1997

[Classification of hemodynamic changes in renal artery stenosis using cine magnetic resonance phase contrast flow measurements].

PURPOSE: To evaluate the use of high-temporal resolution cine MR phase-contrast flow measurements for assessment of flow dynamics in renal artery stenosis (RAS). MATERIAL AND METHODS: In a dog model, cine MR flow measurements were validated by comparing the MR flow data to an invasive transit-time ultrasound reference technique for different degrees of RAS. Cardiac-gated MR flow curves were recorded in 56 renal arteries of 28 patients with a temporal resolution of at least 32 ms. In all cases RAS was confirmed by digital subtraction angiography (DSA). Abnormalities of flow dynamics were assessed in the calculated flow curves using the MR parameters mean flow, maximum velocity, and time to systolic maximum. RESULTS: By means of the MR blood flow parameters high-grade stenoses (> 50%, n = 23) were detected with sensitivity of 100% and specificity of 94% with reference to DSA. The overall differentiation between stenoses (n = 37) and non-stenosed vessels (n = 19) revealed a sensitivity of 87% and a specificity of 100%. CONCLUSION: Analysis of cardiac-gated MR flow curves provides a non-invasive method to assess the hemodynamic significance of RAS and thus allows a functional evaluation in relation to the morphologic characteristics of the stenosis.

Adolescent↗
PubMed1997

Energy expenditure and quantitative oxidation of nutrients in rats (Rattus norvegicus) kept in different thermal environments and given two levels of dietary fiber.

A study was performed to investigate the effect of environmental temperature (16 degrees C, 24 degrees C or 32 degrees C) and dietary fiber (DF) on energy expenditure and quantitative oxidation of nutrients in rats. Forty-eight male rats, initial body weight 90-105 g, were allocated to eight groups in two series. The rats kept at 24 degrees C was repeated in both series. Low and high fiber diets (56 vs. 257 g DF/kg dry matter) were studied in 6-week balance experiments. The rats in all groups were offered the same amount of air-dried food. Indirect calorimetry was used to measure the energy metabolism. The difference in heat production (HP) calculated by RQ and CN methods was < 2% and was not affected by environmental temperature and DF. The relation between fat and protein oxidation changed from 1.54 to 1.00 when the ambient temperature changed from 16 degrees C to 32 degrees C. The contribution of carbohydrate oxidation to total HP was lowest at 16 degrees C, whereas the fat and protein oxidation was highest at 16 degrees C. The oxidation of nutrients was not influenced by DF. The additional energy retained at the higher temperatures had a constant ratio between fat and protein, i.e., 70:30. At an energy retention of 65.8 kJ/kg0.75 d or less, body fat is mobilized and only protein deposited. Because of higher HP, rats living in the cold environment used more fat as substrate for HP than rats kept in warmer environments. The cold environment results in an increase in the amount of interscapular brown adipose tissue, but no significant difference was found between DF levels.

Adipose Tissue, Brown↗
PubMed1997

Renal artery stenosis: grading of hemodynamic changes with cine phase-contrast MR blood flow measurements.

PURPOSE: To analyze the blood flow dynamics in renal artery stenosis with high-temporal-resolution cine phase-contrast magnetic resonance (MR) flow measurements. MATERIALS AND METHODS: Cine phase-contrast MR flow measurements were invasively validated with real-time intraoperative transit-time ultrasound (US). In 23 patients, 48 renal artery stenoses were confirmed at digital subtraction angiography. Cardiac-gated cine phase-contrast MR flow measurements were obtained in 32-msec intervals, and flow curves were calculated for the whole cardiac cycle. Hemodynamic parameters evaluated included the decrease in mean flow and the delay and reduction in the systolic velocity maximum due to decrease in or absence of the early systolic peak. RESULTS: Overall differentiation between renal artery stenosis (n = 31) and nonstenosed vessels (n = 17) with cine phase-contrast MR revealed a sensitivity of 90% and specificity of 94% compared with findings at digital subtraction angiography. High-grade stenoses (>50%, n = 19) were detected with cine phase-contrast MR with sensitivity of 100% and specificity of 93%. CONCLUSION: Quantitative and qualitative analysis of cardiac-gated cine phase-contrast MR flow velocity curves provided a highly accurate method to detect hemodynamic abnormalities in patients with suspected renal artery stenosis.

Adolescent↗
PubMed1997

Noninvasive analysis of renal artery blood flow dynamics with MR cine phase-contrast flow measurements.

It was the aim of this study to quantify the measurement of pulsatile flow in the renal artery with the noninvasive magnetic resonance cine phase-contrast (MRCPC) method and combine it with the simultaneous assessment of pulsatile flow with a transit-time ultrasound (TTUS) flowmeter. In seven foxhounds with a chronically implanted precalibrated TTUS flow probe, MRCPC flow measurements were made in the renal artery with a temporal resolution of 32 ms. Mean and pulsatile flow signal were compared by the simultaneous ipsi- or contralateral measurement of the renal blood flow signal by both methods (TTUS and MRCPC). In addition, comparative MRCPC and TTUS flow measurements were made with artificial renal artery stenosis and after the administration of angiotensin II. The mean flow data assessed by the noninvasive MRCPC flow measurements showed an excellent correlation with corresponding TTUS recording (r = 0.99). The MRCPC flow signal displayed a waveform of the renal artery flow profile that was very similar to the TTUS flow pulse. The hemodynamic changes induced by angiotensin II or due to renal artery stenosis were also reliably detected by MRCPC. MRCPC provides a reliable noninvasive method for the quantification of mean blood flow and the assessment of the pulsatile flow signal in the renal artery and proves to be sensitive to hemodynamic changes of pathophysiological importance. Alternatively, the method may be used for studies in physiology that demand a noninvasive approach.

Angiotensin II↗
PubMed1997

Very low frequency oscillations in arterial blood pressure after autonomic blockade in conscious dogs.

The aim of this study was to investigate spontaneous variability of arterial blood pressure in conscious foxhounds in the absence of direct sympathetic and parasympathetic influences. Autonomic blockade was achieved by administration of the ganglionic blocking agent hexamethonium (n = 7). In contrast to the control group (n = 7), marked oscillations with a cycle length of 100 s (0.01 Hz) were observed. The relationship of the power densities of the oscillation band (0.01 +/- 0.005 Hz) to the total power increased threefold (0.213 +/- 0.007 vs. 0.057 +/- 0.005; P < 0.01). The 0.01-Hz oscillations typically commenced after some delay. To test whether the absence of the mechanoreceptor afferents was responsible for these fluctuations, we investigated an additional group of foxhounds that were subjected to total baroreceptor and cardiopulmonary receptor denervation (n = 7). Neither in this protocol, nor in a group subjected to denervation and ganglionic blockade (n = 6), did we observe sustained oscillations in this frequency range. Since the oscillations were not seen after combined afferent (mechanoreceptor denervation) and efferent (ganglionic) blockade, central oscillators as a source of the oscillations can be ruled out. A simple model of a circulating pressoric factor may explain the fluctuations, provided that there is a time delay between the stimulus and the release or action of the factor. The findings suggest that a circulating factor accounts for the 0.01-Hz oscillations, which is dependent on intact pathways from the cardiac receptors or baroreceptors to the central nervous system. This hypothesis is put forward since cardiopulmonary and baroreceptor denervation blocked the oscillations seen after ganglionic blockade.

Animals↗
PubMed1997

Nitric oxide and renal autoregulation.

Blockade of NO synthesis reduces mean RBF by about 30%. The GFR is slightly reduced or not changed at all. The autoregulatory capacity for both RBF and GFR in response to static or dynamic pressure changes is not affected. This suggests that under normal conditions, the renal vasculature is subject to a strong continuous influence by endogenous NO, which determines the mean RBF. However, although the tubuloglomerular feedback and myogenic response may be modulated by NO, the accuracy of the renal haemodynamic autoregulation as well as the mean GFR seem to be kept independent of the influence on mean RBF.

Animals↗
PubMed1996

Blood-pressure variability is buffered by nitric oxide.

The baroreflex constitutes the only hitherto known buffer of rapid blood pressure oscillations. In order to investigate the influence of nitric oxide (NO) and the sinoaortic and cardiopulmonary baroreflex pathways on the dynamic properties of blood pressure control, we determined the power spectra of 24-h blood pressure time series of conscious dogs. This was done in the intact state (n = 6), during blockade of NO synthesis via the false substrate NG-nitro-L-arginine ((L-NNA), 16.5 +/- 2 mg/kg body weight i.v., n = 5) and in animals devoid of baroreceptor reflexes (n = 5). After L-NNA, blood pressure (BP) increased by roughly 20 mmHg to 137 +/- 6 mmHg (P < 0.01), heart rate decreased from 97 +/- 6 to 68 +/- 3 beats/min (P < 0.01). The power of blood pressure variations within the frequency range 0.1-0.5 Hz was tripled by L-NNA (P < 0.05). By comparison total sinoaortic and cardiopulmonary denervation increased power of slower oscillations ( < 0.1 Hz) by a factor of 4.7 (P < 0.05). Thus, NO and the baroreceptor reflex both play an important role as physiological blood pressure buffers, NO for rapid (0.1-0.5 Hz) and the baroreflex for slower fluctuations ( < 0.1 Hz).

Animals↗
PubMed1996

[Neurologic complications in a case of Werner syndrome].

A 39 year old caucasian man was admitted in 1994 to the neurological department with a left pure motor hemiplegia that appeared suddenly. This patient showed typical features of Werner's syndrome. He had a hoarse voice, a diffuse muscle weakness and atrophy in the upper and lower limbs with chronic ulcers on the legs. His scalp and public hair were sparse. Cranial MRI revealed several lesions in the white matter, low signal intensity on T1 weighted images and high signal on T2 weighted images. Cerebrospinal fluid (CSF was inflammatory with hypercytosis and proteinorachia was 0.50 g/l with synthesis of IgG. Sural nerve biopsy revealed muscle atrophy and the loss of myelinated fibers. Thus, central and peripheral nervous systems were affected in this case.

Adult↗