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P K Dillon

Publications and source records attributed to P K Dillon.

9 recordsLinked to original sources
PubMed1991

A new model for studying ischemia-reperfusion injury in hamster cheek pouch.

The cheek pouch was prepared as a single layer and attached to a two-piece Lucite chamber that was filled with bicarbonate buffer (pH 7.35, equilibrated with 95% N2-5% CO2). Two microcirculatory areas were circumscribed in the cheek pouch by equilateral triangular chambers. Each chamber was made of 90-microns thick Mylar sheet (2 mm wide, 18 mm long). A cover slip was used as the chamber top. Ischemia was induced by applying pressure to the cover slip. The experimental area was reperfused after 1 h of ischemia by releasing the pressure. The other area served as control. One hour of reperfusion after 1 h of ischemia caused a significant increase in the number of leukocytes adhering to postcapillary venules (PCVs) per 100 microns vessel length in the ischemic area relative to the values in the control area (7.8 +/- 2.5 vs. 3.7 +/- 1.3, respectively, for PCVs 10-19.9 microns diam; and 10.9 +/- 2.8 vs. 6.2 +/- 1.8 for PCVs 20-29.9 microns diam; P less than 0.01 for both comparisons). The results demonstrate the adequacy of the model to investigate leukocyte adhesion to endothelium in ischemia-reperfusion. Because blood flow is maintained in most of the pouch, our model should also be useful for identifying possible interactions between ischemic and nonischemic areas in the microcirculation.

Animals↗
PubMed1990

Acute microcirculatory effects of platelet-activating factor.

Using the hamster cheek pouch preparation and intravital microscopy and fluorometry methods, we quantitated the dose-response effects of topically applied platelet-activating factor (PAF) on microvascular permeability, vessel diameter and leukocyte adhesion and investigated the biochemical pathways of this compound. Permeability alterations were assessed by the clearance of macromolecules. PAF increased macromolecular clearance in a dose-dependent manner with the maximum effect being obtained at 10(-7) M. Maximal vasoconstriction was induced by 10(-5) M PAF. Interestingly, PAF at 10(-9) M induced extensive adhesion of leukocytes to postcapillary endothelium, but did not produce changes in either vessel diameter or permeability. To elucidate the biochemical pathways of PAF activity, several inhibitors of the arachiodonic acid cascade and receptor blockers were employed. Dexamethasone and kadsurenone attenuated the clearance response to PAF, while indometacin, OKY-046 (a thromboxane A2 synthase inhibitor), and chlorpheniramine did not. Indometacin and OKY-046 prevented vessel diameter changes. Our results demonstrate that (1) PAF produces a dose-related extravasation of macromolecules, (2) leukotrienes may be responsible for the increased clearance of macromolecules caused by PAF, (3) PAF-induced vasoconstriction is mediated by thromboxane, (4) PAF stimulates leukocyte adhesion in an inverse dose relationship, and (5) responses to PAF are at least partially mediated by receptor interactions.

Animals↗
PubMed1989

Dexamethasone attenuates microvascular ischemia-reperfusion injury in the rat cremaster muscle.

We examined the effect of dexamethasone (DXM) pretreatment on microvascular transport of macromolecules in ischemia-reperfusion injury. The rat cremaster muscle was splayed, placed in a Lucite intravital chamber, and suffused with bicarbonate buffer. The clearance of fluorescein isothiocyanate-dextran 150 (FITC-Dx 150) was measured as an index of microvascular transport. After determination of baseline data, the muscle was made ischemic for 2 hr by clamping its vascular pedicle, and subsequently reperfused for 2 hr. Ischemia-reperfusion produced a marked increase in clearance of FITC-Dx 150. After an initial peak of 13 times baseline value clearance fell to approximately 4 times baseline level 30 min into the reperfusion period. Clearance increased slowly throughout the remainder of the experiment, reaching 6 times baseline after 2 hr of reperfusion. The treated animals received DXM 3 hr prior to and immediately preceding the pedicle clamping. DXM reduced macromolecular clearance significantly after the first 30 min of reperfusion, and prevented the increase in clearance over time. After an initial peak, clearance values fell to near twice baseline in DXM-treated animals, and remained at this level for the 2 hr of reperfusion. Our data demonstrate that DXM attenuates the alternations in microvascular macromolecular transport produced by ischemia-reperfusion injury.

Analysis of Variance↗
PubMed1988

Effect of platelet-activating factor on leukocyte adhesion to microvascular endothelium. Time course and dose-response relationships.

The hamster cheek pouch microcirculation was used to investigate the effects of platelet-activating factor (PAF) on leukocyte adhesion to microvascular walls by means of intravital microscopy. PAF was applied topically at concentrations ranging from 10(-11) to 10(-5) M. An inverse relationship between PAF concentration and number of adhering white cells per 100-microns length was found in venules ranging in diameter from 10 to 60 microns (grouped into 10-microns intervals). Importantly, the PAF-induced adhesion of leukocytes lasted for the 3-h experimental period. We postulate that induction of leukocyte adhesion to venular endothelium is an important role of PAF in inflammatory processes.

Animals↗
PubMed1988

Vasoconstrictor effects of platelet-activating factor in the hamster cheek pouch microcirculation: dose-related relations and pathways of action.

Platelet-activating factor (PAF) has been implicated as a potential mediator of inflammatory processes. In this study, we quantified the effects of PAF on vessel diameter in a microvascular bed and investigated the biochemical pathways of this compound. The hamster cheek pouch microcirculation was observed with intravital microscopy. Experiments were video-recorded and analyzed with an image shearing device. Vasoconstriction was the predominant vasomotor response to PAF. PAF (10(-10) -10(-5) M) was applied topically to the pouch for 3 minutes. Arterioles ranging in size from 8 to 15 micron were the most sensitive, and they constricted completely in response to PAF 10(-7) and 10(-5) M. Arterioles 21-40 micron in diameter constricted to 12-17% of control after PAF at 10(-7) and 10(-5) M, respectively; they reopened to about 70% of their control value after a few minutes and remained near that size throughout the experiment. Arterioles 41-60 micron in diameter constricted to about 20% control size in response to 10(-7) and 10(-5) M PAF, and by the end of the experiment, these vessels had returned to about 90% control size. To determine the pathways of PAF actions, inhibitors of the arachidonic acid cascade and receptor blockers were used. Dexamethasone, indomethacin, OKY-046 (a thromboxane A2 synthetase inhibitor), and kadsurenone (a PAF-receptor blocker) blocked the vasoconstrictor response to PAF. Our experiments demonstrate that PAF-produced arteriolar constriction in a microvascular bed is 1) dose-related, 2) dependent upon vessel size, 3) largely due to thromboxane A2 activity, and 4) mediated by PAF-receptor interactions.

Animals↗
PubMed1988

Effect of platelet-activating factor on microvascular permselectivity: dose-response relations and pathways of action in the hamster cheek pouch microcirculation.

Platelet-activating factor (PAF) has recently been described as a mediator of inflammatory processes. In this study, we quantitated the dose-response effects of topically applied PAF on microvascular permselectivity and investigated the biochemical pathways of this compound. Permselectivity alterations were assessed by measuring the clearance of macromolecules with fluorescein isothiocyanate dextran 150 (FITC-dx 150) as a tracer. The microvascular bed of the hamster cheek pouch served as a model. PAF was found to induce leakage of macromolecules from postcapillary venules. Control FITC-dx 150 plasma clearance (+/- SEM) was 72 +/- 10 nl/90 min. Clearances of 61 +/- 10 474 +/- 145, 622 +/- 57, 301 +/- 86, and 142 +/- 3 nl/90 min were obtained at PAF concentrations of 10(-9), 10(-8), 10(-7), 10(-6), and 10(-5) M, respectively. A one-way analysis of variance showed that the population means were not equal. Multiple comparison by the Student-Newman-Keuls test demonstrated that the clearances obtained with 10(-8), 10(-7), and 10(-6) M were significantly greater than controls. Significant differences existed between 10(-7) M PAF and 10(-9), 10(-6), and 10(-5) M PAF. In an effort to elucidate the biochemical pathways of PAF activity, several inhibitors of the arachidonic acid cascade and receptor blockers were used. Dexamethasone and kadsurenone attenuated the clearance response to PAF in a statistically significant manner, while indomethacin, OKY-046, and chlorpheniramine were without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Dose-response relationships between platelet activating factor and permeability--surface area product of FITC-dextran 150 in the hamster cheek pouch.

Changes in vascular permeability to FITC-dextran 150 associated with topical application of platelet activating factor (PAF) in the hamster cheek pouch preparation were calculated using a mathematical model (Baxter et al., Microvasc. Res. 34:336, 1987). Least square estimates of apparent permeability-surface area product (PS) and interstitial diffusion coefficient (D) were calculated from the data and the mathematical model using a Marquart optimization algorithm. Calculated PS products varied with applied PAF concentration while the best-fit estimate of apparent D remained constant at 10.5 X 10(-10) cm2/s. Average baseline PS was 16.5 X 10(-8) ml/s. PS increased to 45.2 X 10(-8) ml/s and 52.3 X 10(-8) ml/s with application of 10(-8)M and 10(-7)M PAF, respectively. A further increase in PAF concentration to 10(-6)M decreased the calculated PS product to 30.5 X 10(-8) ml/s. PAF is a potential modulator of macromolecular permeability in the microcirculation. This is the first study which quantitates the changes in PS of FITC-dextran 150 as a function of PAF concentration.

Animals↗
PubMedDate not supplied

Effects of ischemia-reperfusion injury on microvascular permeability in skeletal muscle.

Microvascular permeability changes (using FITC-dextran 150 clearance as an index) produced by ischemia-reperfusion (I-R) were investigated in the rat cremaster muscle. I-R produced significant sustained increases in microvascular permeability to macromolecules. Pretreatment with dexamethasone and verapamil reduced this I-R effect. Leukopenia also afforded protection to the microcirculation. It was concluded that changes occurring during ischemia are major causative components of the ischemia-reperfusion damage.

Animals↗