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P Borgdorff

Publications and source records attributed to P Borgdorff.

At least 19 recordsLinked to original sources
PubMed2000

In vivo visualization of hemodialysis-induced alterations in leukocyte-endothelial interactions.

BACKGROUND: The aim of this study was to develop a model for hemodialysis (HD) in small animals using conventional dialysis equipment that would allow the intravital microscopic observation of leukocyte-endothelial interactions in vivo. METHODS: Cuprophan dialyzers were adapted to obtain a similar ratio of membrane area to blood volume as in clinical HD. A silicone ring was inserted into the dialyzer's inlet to limit the number of blood-perfused capillaries. Rabbits were dialyzed for one hour without a dialysate flow. RESULTS: Extracorporeal circulation with the cuprophan dialyzer resulted in a transient leukopenia and complement activation. At the nadir of leukopenia, leukocytes that rolled along the venular wall were scarcely observed, whereas rolling was abundant (54 +/- 9 per min) prior to extracorporeal circulation. The adhesion of leukocytes to the vascular endothelium was not induced. After 60 minutes, rolling of leukocytes was still reduced by 73 +/- 5.5%, despite the full recovery of circulating leukocyte counts. Extracorporeal circulation without a dialyzer also tended to reduce leukocyte rolling, although systemic leukocyte counts were not affected. CONCLUSIONS: The use of adapted conventional cuprophan hemodialyzers in rabbits yielded a transient leukopenia similar to that in clinical HD. Using intravital microscopy, we demonstrated impairment of leukocyte-endothelial interactions. In addition, our data indicate that tissues, in which leukocytes can roll and adhere, are not automatically sites of leukocyte sequestration during HD-induced leukopenia.

Animals↗
PubMed2000

Extracorporeal circulation can induce hypotension by both blood-material contact and pump-induced platelet aggregation.

OBJECTIVE: Use of extracorporeal systems in cardiopulmonary bypass and dialysis induces vascular reactions, which can lead to hypotension and lung edema. METHODS: To study the contribution of blood-material contact and use of a roller pump, as well as prevention of their adverse effects, we perfused a rat hind leg with a tube connecting a carotid and a femoral artery. RESULTS: Autoperfusion of an uncoated tube caused a fall of aortic pressure and femoral resistance to 66% +/- 16% and 76% +/- 15%, respectively, of their initial values within 2 hours, whereas in control animals without a shunt, these variables hardly changed (to 94% +/- 2.8% and 99% +/- 2.8%, respectively). Lung water content became significantly higher than that found in control animals (79.4% +/- 1.50% versus 77. 0% +/- 1.67%). If we coated the tube with albumin, these changes were largely prevented. When the coated tube was placed in a roller pump, aortic pressure and femoral resistance immediately fell to 79% +/- 17.2% and 63% +/- 13.5%, respectively, whereas lung water content did not increase. The vasodilation was caused by platelet aggregation and could be prevented with aurintricarboxylic acid, which inhibits shear-induced platelet aggregation by blocking the binding of von Willebrand factor to platelet glycoprotein Ib receptors. CONCLUSIONS: Extracorporeal circulation may induce hypotension and lung edema by means of blood-material contact. Hypotension can be prevented by coating the system with albumin but can still result from pump-induced platelet aggregation.

Animals↗
PubMed1999

Minoxidil-induced cardiac hypertrophy in guinea pigs.

To investigate whether during cardiac hypertrophy changes occur in contractile protein composition and in mechanical and energetic properties of the myocardium, contractile protein composition, isometric force and adenosine triphosphate (ATP) consumption were studied in control and hypertrophied guinea-pig hearts. Cardiac hypertrophy was induced by adding minoxidil (120 or 200 mg/l) to the drinking water. Protein analysis was performed by one-dimensional gel electrophoresis. The myosin heavy-chain (MHC) composition was determined in an enzyme-linked immunosorbent assay (ELISA). ATP consumption and force development were simultaneously measured during isometric contraction in chemically skinned trabeculae. Histochemical analysis of cross-sectional area of cardiomyocytes and interstitial space was performed on the left ventricular tissue of 200 mg/l minoxidil-treated and control guinea pigs. Minoxidil treatment (120 and 200 mg/l) significantly increased left ventricular dry weight normalized for body weight by 19 +/- 4 and 24 +/- 4%, respectively. No significant differences were found in the cellular cross-sectional area, while interstitial space was slightly decreased in minoxidil-treated hearts. In left ventricular trabeculae of 200 mg/l minoxidil-treated guinea pigs, ATPase activity was slightly less than in those of control guinea pigs, whereas force did not differ significantly. Calcium sensitivity of force and ATPase activity were not affected by minoxidil treatment. Gel electrophoresis revealed no difference in contractile protein composition, but a tendency towards a lower amount of alpha-MHC in the minoxidil-treated hearts was found in ELISA.

Adenosine Triphosphate↗
PubMed1999

Pump-induced platelet aggregation in albumin-coated extracorporeal systems.

OBJECTIVE: Coating of extracorporeal systems with heparin does not prevent platelet activation and subsequent bleeding disorders. We investigated whether this could be due to elevated shear stress caused by a roller pump. METHODS: Human or rat blood was made to flow through an uncoated or an albumin-coated medical polyvinyl chloride tube with or without a roller pump. Aggregation of platelets in the tubing was recorded continuously with a photometric device. RESULTS: Although in vitro gravitational flow in uncoated tubes caused immediate platelet aggregation and platelet loss, this remained absent in coated tubes. When the pump was started in experiments with a coated tube strong platelet aggregation was observed and platelet count fell within 5 minutes to 78% +/- 2% and 71% +/- 3% of control values in human and rat blood, respectively. In vivo, no aggregation was observed during spontaneous flow in rats with an albumin-coated tube running from the carotid artery to the femoral artery, but aggregation started as soon as the blood was pumped. Pump-induced platelet aggregation, both in vitro and in vivo, could be prevented with aurintricarboxylic acid, which specifically inhibits shear-induced platelet aggregation as has recently been shown. Pump perfusion of blood in an uncoated tube did not elicit platelet aggregation. CONCLUSIONS: Pump perfusion of blood in coated systems elicits shear-induced platelet aggregation, which may be prevented by administration of substances that block the binding of von Willebrand factor to glycoprotein Ib receptors on the platelets. The effects of pumping on platelets are masked in uncoated circuits because of the dominant influence of blood-material contact.

Albumins↗
PubMed1994

Vasodilation by shear-induced platelet aggregation in extracorporeal circuits.

Extracorporeal circulation may have adverse effects on vascular reactivity. To reduce such effects, we recently coated a tube connecting the carotid and the distal femoral artery of rats with albumin. When we partially occluded this perfusion line, the reduction of flow was followed by a marked increase, which seemed not to be caused by autoregulation but by release of a vasodilator at the site of occlusion. In the present study, we investigated whether this vasodilator could originate from platelets aggregating under the influence of increased shear stress at the site of occlusion. Blood distal to the site of occlusion indeed contained numerous platelet aggregates that were not present before occlusion. Continuous recording with a photometric device showed that aggregation in the tube started before flow increased and ended before flow decreased again. Blockade of serotonin S1- and S2-receptors with methiothepin prevented the flow response. Estimated shear stress (231 +/- 17 dyn/cm2) and shear rate (6,370 +/- 478 s-1) at the site of occlusion were of the magnitude known to elicit platelet aggregation. Others have recently demonstrated that shear-induced platelet aggregation is mediated by binding of von Willebrand factor to platelet glycoprotein Ib, which is inhibited by aurintricarboxylic acid. This drug (35 mg/kg iv) completely abolished both platelet aggregation and flow increase in our experiments. These results suggest that the vasodilation during partial tube occlusion is mediated by serotonin released from platelets that aggregate as a result of high shear stress.

Animals↗
PubMed1994

Relationship between strength of short-term systemic autoregulation and initial resistance.

The relationship between strength of short-term whole body autoregulation and peripheral resistance in the reference state (initial resistance) was investigated in 9 anesthetized closed-chest dogs and 18 anesthetized open-chest cats. Baroreflex regulation was abolished in one of three ways: barodenervation, ganglionic blockade, or setting pressure constant in the isolated carotid sinuses after vagotomy. Ascending aortic pressure and flow and venous pressure were measured in the reference state and 1-3 min after partial occlusions of the inferior vena cava. Cardiac output and peripheral resistance (ratio between arteriovenous pressure difference and cardiac output) were normalized for body weight. Strength of autoregulation was quantified by a resistance gain (Gra), defined as the ratio between change in normalized peripheral resistance and corresponding change in normalized cardiac output. A broad range of values for peripheral resistance in the reference state (Ro) was obtained as a result of the different interventions used to abolish baroreflex regulation. Arteriovenous pressure difference and normalized cardiac output during multiple vena cava occlusions in the 9 dogs and in 8 of the cats were fitted with a parabola convex to the flow axis. From the best fit, Gra was estimated. In the remaining 10 cats Gra was estimated from a single occlusion of vena cava. When data of all dogs and cats were taken together, we found a linear relationship between Gra and Ro: Gra = K1.Ro + K2. The constants K1 and K2 were 17.9 x 10(-3) min.kg.ml-1 and -14.5 x 10(-3) mmHg.min2.kg2.ml-2, respectively. The correlation coefficient was 0.9.

Animals↗
PubMed1992

Extracorporeal circuits and autoregulation: effect of albumin coating.

Autoregulation of muscle blood flow often is difficult to demonstrate when extracorporeal perfusion is used. This could be caused by contact of blood and foreign material. Accordingly, we tested whether autoregulation is preserved when the system is coated with albumin. Polyurethane tubing between the carotid and distal femoral artery of rats was partially occluded for 1-2 min. With the system uncoated (n = 6 rats) autoregulation was absent. With coated systems (n = 6 rats) the closed-loop gain (Gc) of the apparent autoregulation (0 < Gc < 1) for the pressure range from control (137 +/- 14) to 80 mmHg was 0.40 +/- 0.24 (mean +/- SD). In most cases autoregulation was preceded by a period of "superregulation": after a variable delay flow rose above control. When the distance between occluder and tip of femoral cannula was varied in another group of rats (n = 6), the delay (20-75 s) was linearly related to transit time (10-35 s) of blood. Flow increase thus seemed to be caused by a blood-borne vasodilator originating at the occlusion site and not by a myogenic or metabolic response to decreased pressure and flow. The vasodilator did not originate from the albumin coating. Partial occlusion of an extracorporeal shunt thus can increase flow to the perfused tissue when the system is coated with albumin. The reaction readily disappears when the system is not coated.

Animals↗
PubMed1991

Systemic autoregulation counteracts the carotid baroreflex.

The interaction between autoregulation and baroregulation and its effect on the gains of the short-term pressure regulatory system was studied by performing both open- and closed-loop experiments in the same five anesthetized, vagotomized dogs, and by analyzing the data making use of a new model. With carotid pressure constant (no baroregulation) the pressure-flow data were convex to the flow axis, thus indicating the presence of autoregulation. When baroregulation was present the data were convex to the pressure axis. Our model was able to fit the data as measured in both cases. From the fitting procedure the zero-flow pressure intercept Pzf, the autoregulation resistance gain Gra, and the baroregulation resistance gain Grb were estimated. Pzf was about 20 mmHg in three dogs and about zero in the other two. Average values of Gra and Grb were 13.0 +/- 3.5 mmHg min2/L2 and 0.83 +/- 0.25 min/L, respectively. The two curves which fitted the data points collected in the presence and in the absence of baroreflex intersected at a point (Qo, Po) generally different from the control point. We determined the open-loop gain, Goc = GrbQo, about the point (Qo, Po). The averaged value was 2.23 +/- 0.84. When autoregulation was neglected, the resistance gain Grb and the open-loop gain Goc obtained from the same closed-loop method were underestimated (0.32 +/- 0.15 min/L and 0.88 +/- 0.48, respectively). In the open-loop preparation the carotid sinuses were isolated and the aortic (P) versus carotid (Pca) pressure data were collected. A third-order polynomial was fitted to these data.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Endogenous adenosine enhances vagal negative chronotropic effect during hypoxia in the anaesthetised rabbit.

STUDY OBJECTIVE: Hypoxia potentiates the negative chronotropic effect of efferent vagal stimulation. A similar potentiation is evoked by exogenous adenosine. The aim of this study was to verify whether vagal potentiation during hypoxia is caused by endogenous adenosine. DESIGN: In anaesthetised rabbits the peripheral end of the right vagus was stimulated once every 20 s for 1 s, during normoxia and during systemic hypoxia, before and after adenosine receptor blockade. Hypoxia was induced by lowering oxygen content of the inspired air for 6 min. EXPERIMENTAL MATERIAL: 12 rabbits were anaesthetised with chloralose (50 mg.kg-1, intravenously) and halothane (0.3 vol%) and artificially ventilated. Reflex influences on heart rate were minimised by bilateral cervical vagotomy and administration of atenolol (1 mg.kg-1, followed by 0.25 mg.kg-1.h-1). Hypoxia was repeated before and after 8-phenyltheophylline administration (19.5 mumol.kg-1, intravenously) in seven rabbits, or before and after vehicle injection in five rabbits (time control). MEASUREMENTS AND RESULTS: The PaO2 attained at the end of the hypoxic period was 19(SEM 1) mm Hg [2.5(0.1) kPa]. Before adenosine receptor blockade, arterial pressure increased during hypoxia [14(6)mm Hg after 1 min], then decreased [7.3(8.8) mm Hg below control after 4 min]. Heart rate fell by 38.3(12.1) beats.min-1 in the last 3 min of hypoxia. Vagal negative chronotropic effect increased from -30.3(1.8) beats.min-1 during control to -58.7(4.6) beats.min-1 during the last 5 min of hypoxia, ie, a potentiation of 93.2(9)%. Administration of 8-phenyltheophylline reduced the effects of hypoxia on spontaneous heart rate and vagal bradycardia: heart rate decreased by 14.2(7.8) beats.min-1 and vagal negative chronotropic effect increased from -32.2(2.1) to -39.3(3.7) beats.min-1, ie, a potentiation of 21.5(10)%. Blood pressure showed a stronger increase [19.1(4.4) mm Hg after 2 min], but no decrease. These differences were not seen in the five control rabbits, in which hypoxia was repeated without adenosine receptor blockade. CONCLUSIONS: These results show that adenosine does play a role in hypoxia induced bradycardia and vagal potentiation.

Adenosine↗
PubMed1990

Short-term systemic autoregulation.

We studied total systemic autoregulation in closed-chest, chloralose-anesthetized dogs. Cardiac out-put (previously implanted electromagnetic flow probe on ascending aorta) and aortic pressure were varied by reducing venous return using a balloon catheter in the vena cava. Compensatory action of the baroreflex was prevented by bilateral vagotomy and isolation of both carotid sinuses. To avoid high vessel tone carotid sinus pressure was set at the original baseline value using a pressurized blood reservoir. With each balloon inflation aortic flow and aortic pressure decreased and stabilized in about 1 min. Pressure and flow were allowed to return to base-line values after each balloon inflation in an attempt to minimize the activation of slower regulatory mechanisms. The steady-state pressure-flow relations could be fitted with a sigmoidal curve. The mean quality (0 less than Q less than 1) of autoregulation in eight dogs was 0.41 +/- 0.08 (SD). Autoregulation was found in the pressure range from 42 to 140 mmHg. The early appearance of total systemic autoregulation suggests that, in the intact animal, it may counteract baroreflex control.

Animals↗
PubMed1988

Pump perfusion abolishes autoregulation possibly via prostaglandin release.

The influence of pump perfusion on autoregulation was studied in the hindleg of the halothane- and chloralose-anesthetized cat. Flow was measured with an electromagnetic flow probe in a tube between aorta and the vascularly isolated, denervated leg and varied with a calibrated occluder. Perfusion pressure was measured via a T-piece distal to the occluder. The steady-state pressure-flow relations could be fit with a sigmoidal curve. The mean closed-loop gain (0 less than Gc less than 1) for autoregulation in six cats was 0.46 +/- 0.11 (SD). When in these cats a roller pump was used, an almost linear pressure-flow relation was found (Gc = 0.01 +/- 0.09), while the resistance at control flow was decreased by 15 +/- 4%. Administration of indomethacin (5 mg/kg iv), a cyclooxygenase inhibitor, partly restored autoregulation during pumping (Gc = 0.34 +/- 0.09) and slowly increased the resistance to above its original value (20 +/- 13%). In six other cats, pump perfusion had no influence on autoregulation when started after indomethacin administration but resistance increased. This increase could not be prevented with ketanserin, a specific serotonin 2 receptor blocker. We conclude that pump perfusion abolishes autoregulation and decreases resistance via a process that involves prostaglandins. Blockade of the prostaglandin synthesis unmasks a slow vasoconstrictor influence in the bed.

Animals↗
PubMed1987

Cardiac alpha-1 adrenoceptors are not involved in heart rate control of the anaesthetized dog.

To study the possible role of cardiac postsynaptic alpha-1 adrenoceptors in heart rate control of the anaesthetized open-chest dog we injected a specific alpha-1 agonist (amidephrine) into the right coronary artery or stimulated electrically the right stellate ganglion. Reflex influences were minimized by bilateral cervical vagotomy and de-afferentiation of both stellate ganglia. Activation of alpha-2, beta- and muscarinic receptors was prevented by intravenous administration of yohimbine, propranolol and atropine, respectively. Since alpha-1 receptor stimulation could affect heart rate indirectly via coronary constriction, a continuous intracoronary infusion of adenosine (0.25 mg/kg/h) was given. Amidephrine did not affect heart rate at the lower dose (1-10 microgram). After the highest dose (100 micrograms) the maximum variation in heart rate was an increase of 2.2 +/- 1.1 bpm at 3 min after injection (mean +/- SEM; P less than 0.05). This slight cardioacceleration was simultaneous with an aortic pressure rise of 13.8 +/- 3.4 mm Hg and it was abolished by alpha-1 blockade with prazosin (1 mg/kg i.v.). After propranolol (1 mg/kg +0.5 mg/kg/h) the residual positive chronotropic effect of sympathetic stimulation (12.2 +/- 4.0 bpm) was not significantly altered (13.8 +/- 5.7 bpm) by prazosin administration. Similar results were recorded without adenosine infusion. We conclude that in the anaesthetized dog chronotropic effects directly mediated by alpha-1 adrenoceptors either do not exist or lack physiological significance.

Adenosine↗
PubMed1987

Short-term regulation of arterial pressure and the calculation of open-loop gain in the intact anesthetized dog.

Open-loop gain of the short-term systemic pressure regulation was determined under closed-loop conditions in the closed chest anesthetized dog (n = 5). For this purpose, cardiac output and mean systemic pressure were varied by ventricular pacing after the production of complete heart block. From the pressure-flow data resistance gain (the ratio of peripheral resistance change to pressure change in the steady state) was obtained by means of a simple model. The value of this gain was automatically estimated by fitting the pressure-flow relation described by the model to the experimental data. The model allows the pressure-flow relation to be straight or curved with or without a zero-flow pressure intercept. The best fit was obtained when the pressure-flow curve was convex to the pressure axis and had no intercept. When the model was linearized about the control values of pressure and flow (operating point), open-loop gain could be calculated from resistance gain. Its averaged value in the control condition, 1.63 +/- 0.45, is in agreement with values found by other investigators in open-loop conditions. During vasoconstriction open-loop gain, at the (new) operating point, increased to 2.51 +/- 0.51; during vasodilation it decreased to 1.17 +/- 0.27. Open-loop gain about an operating point thus can be determined in the intact animal from measurements of mean pressure and mean flow in the steady state.

Animals↗
PubMed1987

The inhibitory effect of fentanyl, nicomorphine and 6-nicotinoyl morphine on phrenic nerve activity in relation to their cardiovascular effects in the anaesthetized cat.

The inhibitory effects of the morphine-like drugs fentanyl, nicomorphine (3,6-dinicotinoyl morphine, Vilan) and its active metabolite 6-nicotinoyl morphine (6-NM) on phrenic nerve activity (PNA) were quantified. Therefore, the drugs were simultaneously infused into the left and right vertebral artery of anaesthetized cats. Previously we demonstrated that drugs, administered via these arteries, accumulate within the pontomedullary region, whereas only insignificant amounts reach higher brain areas and peripheral structures. The results were compared with the effects of i.v. administration. It is shown that fentanyl already inhibits PNA after 60 ng via the vertebral arteries. Nicomorphine and its metabolite have much less influence on respiration (factor 564 and 47, respectively). The difference in potency between nicomorphine and 6-NM was less after i.v. injection, indicating that nicomorphine needs metabolization in order to unfold full biological activity. Haemodynamic parameters are not affected after central administration even when PNA is almost completely depressed. After i.v. injection of relatively high doses, blood pressure falls, but probably not by an interaction with opiate receptors in the lower brain stem, since it could not be reversed by intravertebral naloxone.

Animals↗
PubMed1986

Influence of vagal cooling on cardiac output in normal and beta-blocked exercising dogs.

To study the relative influence of parasympathetic and sympathetic innervation on the early adaptation of cardiac output (CO) to exercise, we determined the time constant and amplitude of the CO change in dogs following a stepwise increase in treadmill velocity. The animals were studied during control conditions, beta-blockade, vagal blockade and combined beta-blockade and vagal blockade. To measure CO, an electromagnetic flow probe was implanted around the ascending aorta. Vagal activity was blocked with coolers, implanted around the cervical vagosympathetic trunks. The time constant during beta-blockade (12.1 s) was not different from the control situation (11.4 s), but during vagal cooling it increased significantly (16.2 s), and with combined vagal cooling and beta-blockade it rose to 20.7 s. Thus the increase in cardiac output with exercise is accelerated most by the loss of vagal tone and to a lesser degree by sympathetic activation. The amplitude of the change in CO during control was 112%. Heart rate (HR) rose by 74% and stroke volume (SV) by 22%. Beta-blockade lowered the initial CO but did not alter the percentage increase. Vagal cooling, with or without beta-blockade, caused an increased initial HR but did not influence basal CO because of a concomitant reduction in SV. Exercise now increased HR less (21% and 30%, respectively) and SV more (52% and 52%) but the increase in CO did not change significantly (87% and 97%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

An implantable nerve cooler for the exercising dog.

An implantable nerve cooler has been constructed to block cervical vago-sympathetic activity in the exercising dog reversibly. An insulated gilt brass container implanted around the nerve is perfused with cooled alcohol via silicone tubes. The flow of alcohol is controlled by an electromagnetic valve to keep nerve temperature at the required value. Nerve temperature is measured by a thermistor attached to the housing and in contact with the nerve. It is shown that, during cooling, temperature at this location differs less than 2 degrees C from nerve core temperature. Measurement of changes in heart rate revealed that complete vagal block in the conscious animal is obtained at a nerve temperature of 2 degrees C and can be achieved within 50 s. During steady-state cooling in the exercising animal nerve temperature varied less than 0.5 degree C. When the coolers after 2 weeks of implantation were removed they showed no oxydation and could be used again.

Animals↗