Biomedical subjects

S A Barman

Publications and source records attributed to S A Barman.

At least 19 recordsLinked to original sources

PubMed2000

Posterior capsular opacification with hydrogel, polymethylmethacrylate, and silicone intraocular lenses: two-year results of a randomized prospective trial.

PURPOSE: To compare the visual outcome, percentage of posterior capsular opacification, and laser capsulotomy rates with polymethylmethacrylate, silicone, and hydrogel intraocular lens implants at 1 and 2 years postoperatively. METHODS: Ninety-three eyes of 93 patients were randomized to receive a polymethylmethacrylate, silicone, or hydrogel intraocular lens implant. A standardized surgical protocol was followed by a single surgeon using phacoemulsification with capsulorhexis; any patients with surgical complications were excluded, and all patients received standardized medication and follow-up. Patients were examined at days 1 and 7, months 1, 3, and 6, and years 1 and 2 after surgery. At each assessment, best-corrected logMAR visual acuity and Pelli-Robson contrast sensitivity were measured. Posterior capsular opacification was objectively assessed by digital retroillumination imaging with the use of a dedicated software program and calculated as the percentage area of opacified capsule. Laser capsulotomy was performed if the eye had lost 2 lines of visual acuity with a clinically opaque capsule. RESULTS: At 2 years postoperatively, the mean percentage area of posterior capsular opacification for hydrogel lenses was 63%; for polymethylmethacrylate, 46%; and for silicone, 17%. Hydrogel intraocular lenses were associated with 17% more posterior capsule opacification than were polymethylmethacrylate lenses (95% confidence interval, 1-33; P =. 037) and 45% more than were silicone lenses (95% confidence interval, 33-58; P <.0001) at 2 years. Polymethylmethacrylate lenses had 28% more posterior capsule opacification than silicone lenses (95% confidence interval, 13-43; P <.0001) at 2 years. Twenty-eight percent of patients with hydrogel intraocular lenses required an Nd:YAG laser posterior capsulotomy at 2 years, compared with 14% with polymethylmethacrylate, whereas no patients with silicone lenses needed a capsulotomy (P =.014). Visual acuity was not significantly different among the three groups, but patients with silicone intraocular lenses had significantly better contrast sensitivity than those with hydrogel lenses (P =.046). CONCLUSIONS: Intraocular lenses made of this specific hydrogel were associated with a significantly higher degree of posterior capsular opacification and more laser capsulotomies than polymethylmethacrylate and silicone intraocular lenses.

Aged↗

PubMed2000

Quantification of posterior capsular opacification in digital images after cataract surgery.

PURPOSE: To describe a software program developed to provide an objective assessment of the amount of posterior capsular opacification (PCO) in high-resolution digital images of the posterior capsule after cataract surgery. METHODS: Images are analyzed by a set protocol of defining the area of the posterior capsule, removing the Purkinje light reflexes by intensity segmentation, contrast enhancement, filtering to enhance low-density PCO, and variance analysis using a co-occurrence matrix to assess texture. The accuracy of the system was tested for validity and repeatability. RESULTS: The software developed has been demonstrated to be an objective method of quantifying PCO. In validation tests, the image analysis-derived measure of PCO showed good agreement with clinically derived measures of PCO. Clinicians assessed PCO on a computer screen image and also under slit lamp examination (Pearson correlation coefficient for both methods >0.92). The entire acquisition and analysis system was demonstrated to have a confidence limit for 2 SDs of 9.8% for group data. CONCLUSIONS: This system is capable of producing an accurate and reproducible measure of PCO that is relevant to assessing techniques of PCO prevention.

Aged↗

PubMed1999

The effect of polymethylmethacrylate, silicone, and polyacrylic intraocular lenses on posterior capsular opacification 3 years after cataract surgery.

OBJECTIVE: To compare the visual outcome, neodymium:YAG (Nd:YAG) capsulotomy rates, and percentage of posterior capsular opacification (PCO) seen with polymethylmethacrylate (PMMA), silicone, and polyacrylic intraocular lens implants 3 years after surgery. DESIGN: Randomized, prospective trial. PARTICIPANTS: Ninety eyes of 81 patients were examined at a British teaching hospital. INTERVENTION: Ninety eyes were prospectively randomized to receive a PMMA, silicone, or polyacrylic (AcrySof, Alcon, Fort Worth, TX) implant. All lenses had 6-mm disc optics with PMMA haptics. A standardized surgical protocol was performed by a single surgeon using an extracapsular technique with capsulorhexis; any surgical complications were excluded and all patients had standardized postoperative medication and follow-up. MAIN OUTCOME MEASURES: Patients were seen at 6 months and 1, 2, and 3 years after surgery. At 3 years, logarithm of the minimum angle of resolution (LogMAR) visual acuity and Pelli-Robson contrast sensitivity were measured and YAG capsulotomy rates determined. Posterior capsular opacification was assessed objectively by digital retroillumination imaging using dedicated software and calculated as the percentage area of opacified capsule. RESULTS: At 3 years, the overall follow-up rate was 71%: 19 patients were available for examination with polyacrylic lens implants, 22 with silicone, and 23 with PMMA. There was a significant difference in percentage PCO at 3 years among the lens types (P = 0.0001). Polyacrylic lenses were associated with less PCO (10%) than silicone (40%) and PMMA lenses (56%). The YAG capsulotomy rate was 0% for polyacrylic, 14% for silicone, and 26% for PMMA (P = 0.05). The visual acuity and contrast sensitivity were not significantly different among the three groups if patients with age-related macular degeneration and those requiring YAG capsulotomies are excluded. CONCLUSIONS: Intraocular lenses made from polyacrylic are associated with a significantly reduced degree of PCO and lower YAG rates.

Acrylates↗

PubMed1999

Potassium channels modulate canine pulmonary vasoreactivity to protein kinase C activation.

The role of Ca2+-activated K+-channel, ATP-sensitive K+-channel, and delayed rectifier K+-channel modulation in the canine pulmonary vascular response to protein kinase C (PKC) activation was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. The PKC activators phorbol 12-myristate 13-acetate (PMA; 10(-7) M) and thymeleatoxin (THX; 10(-7) M) significantly increased pulmonary arterial and pulmonary venous resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. The Ca2+-activated K+-channel blocker tetraethylammonium ions (1 mM), the ATP-sensitive K+-channel inhibitor glibenclamide (10(-5) M), and the delayed rectifier K+-channel blocker 4-aminopyridine (10(-4) M) potentiated the pressor response to both PMA and THX on the arterial and venous segments and also further decreased pulmonary vascular compliance. In contrast, the ATP-sensitive K+-channel opener cromakalim (10(-5) M) attenuated the vasoconstrictor effect of PMA and THX on both the arterial and venous vessels. In addition, membrane depolarization by 30 mM KCl elicited an increase in the pressor response to PMA. These results indicate that pharmacological activation of PKC elicits pulmonary vasoconstriction. Closure of the Ca2+-activated K+ channels, ATP-sensitive K+ channels, and delayed rectifier K+ channels as well as direct membrane depolarization by KCl potentiated the response to PMA and THX, indicating that K+ channels modulate the canine pulmonary vasoconstrictor response to PKC activation.

Animals↗

PubMed1998

Potassium channels modulate hypoxic pulmonary vasoconstriction.

The role of Ca2+-activated K+-channel, ATP-sensitive K+-channel, and delayed rectifier K+-channel modulation in the canine pulmonary vascular response to hypoxia was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. Under normoxia, the Ca2+-activated K+-channel blocker tetraethylammonium (1 mM), the ATP-sensitive K+-channel inhibitor glibenclamide (10(-5) M), and the delayed rectifier K+-channel blocker 4-aminopyridine (10(-4) M) elicited a small but significant increase in pulmonary arterial pressure. Hypoxia significantly increased pulmonary arterial and venous resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. Tetraethylammonium, glibenclamide, and 4-aminopyridine potentiated the response to hypoxia on the arterial segments but not on the venous segments and also further decreased pulmonary vascular compliance. In contrast, the ATP-sensitive K+-channel opener cromakalim and the L-type voltage-dependent Ca2+-channel blocker verapamil (10(-5) M) inhibited the vasoconstrictor effect of hypoxia on both the arterial and venous vessels. These results indicate that closure of the Ca2+-activated K+ channels, ATP-sensitive K+ channels, and delayed rectifier K+ channels potentiate the canine pulmonary arterial response under hypoxic conditions and that L-type voltage-dependent Ca2+ channels modulate hypoxic vasoconstriction. Therefore, the possibility exists that K+-channel inhibition is a key event that links hypoxia to pulmonary vasoconstriction by eliciting membrane depolarization and subsequent Ca2+-channel activation, leading to Ca2+ influx.

4-Aminopyridine↗

PubMed1997

Canine pulmonary vasoreactivity to serotonin: role of protein kinase C and tyrosine kinase.

The role of protein kinase C- and protein tyrosine kinase-mediated signal transduction in the canine pulmonary vascular response to serotonin (5-HT) was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. 5-HT (10(-5) M) significantly increased precapillary resistance by approximately 150% and postcapillary resistance twofold and significantly decreased total vascular compliance to approximately 50% of control values by decreasing large-vessel compliance and middle-compartment compliance. The 5-HT2-receptor blocker ketanserin (10(-7) M), the protein kinase C inhibitor staurosporine (10(-7) M), the voltage-dependent Ca2+-channel blocker verapamil (10(-5) M), and the specific protein tyrosine kinase inhibitors genistein (5 x 10(-4) M) and tyrphostin 25 (5 x 10(-4) M) completely inhibited the pressor response to 5-HT, whereas the 5-HT1-receptor antagonist (-)pindolol (10(-7) M) had no significant effect on the serotonergic response. These results indicate that the canine pulmonary vascular response to 5-HT involves activation of 5-HT2 receptors and suggests that this receptor signal transduction pathway involves protein kinase C and tyrosine kinase and the activation of voltage-dependent Ca2+ channels.

Animals↗

PubMed1997

Role of calcium-activated potassium channels and cyclic nucleotides on pulmonary vasoreactivity to serotonin.

The role of Ca(2+)-activated K+ channel modulation and cyclic nucleotide second messenger signal transduction in the canine pulmonary vascular response to serotonin was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured using vascular occlusion techniques. Serotonin (10(-5) M) significantly increased precapillary and postcapillary resistance and significantly decreased total vascular compliance by decreasing large vessel compliance and middle compartment compliance. Tetraethylammonium ions (TEA+; 1 mM), an inhibitor of Ca(2+)-activated K+ channels, significantly potentiated the pressor effect to serotonin on both the pulmonary arteries and pulmonary veins. Pretreatment with the guanosine 3',5'-cyclic monophosphate (cGMP)/adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-5) M), the cell membrane-permeable analog of cAMP, dibutyryl-cAMP (10(-5) M), or the cAMP-dependent vasodilator isoproterenol (10(-5) M) inhibited the serotonergic response on both the arteries and veins, which was reversed by TEA+. In contrast, the stable membrane-permeable analog of cGMP, 8-bromo-cGMP (10(-5) M), had no effect on serotonin. These results indicate that there is a basal level of vasorelaxation in canine pulmonary blood vessels that is mediated by Ca(2+)-activated K+ channel activity and that inhibition of these K+ channels increases pulmonary vascular tone and potentiates the pulmonary vasoactive response to serotonin. Also, these data suggest that cAMP-induced pulmonary vasodilation is mediated primarily by Ca(2+)-activated K+ channels and that activation of these specific K+ channels attenuates the pressor response to serotonin. Thus an important relationship appears to exist between the cAMP second messenger system and Ca(2+)-activated K+ channels in canine pulmonary vasoreactivity.

1-Methyl-3-isobutylxanthine↗

PubMed1997

Pulmonary vasoreactivity to serotonin during hypoxia is modulated by ATP-sensitive potassium channels.

The role of ATP-sensitive K+-channel modulation in the canine pulmonary vascular response to serotonin during hypoxia was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured by using vascular occlusion techniques. Under normoxia, serotonin (10(-5) M) significantly increased precapillary and postcapillary resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. During hypoxia, the effect of serotonin was potentiated on both precapillary and postcapillary resistance and capillary pressure, as well as on microvascular compliance and large-vessel compliance. Under normoxia, the ATP-sensitive K+-channel opener cromakalim (10(-5) M) inhibited the serotonergic response on postcapillary resistance and microvascular compliance, whereas during hypoxia cromakalim inhibited the potentiated effect of serotonin on both precapillary and postcapillary resistance, capillary pressure, and both microvascular and large-vessel compliances. These results indicate that canine pulmonary vasoreactivity to serotonin is heightened under hypoxic conditions and that ATP-sensitive K+ channels modulate the pressor response to serotonin, an effect that is more pronounced during hypoxia.

Adenosine Triphosphate↗

PubMed1997

Measurement of thromboxane and prostacyclin in valvulotomized human saphenous veins.

The present study was done to determine the effect of the modified Hall valvulotome technique on endothelial injury by measuring TxB2 and 6-keto PGF1alpha, the stable metabolites of thromboxane and prostacyclin, respectively. It was hypothesized that increased levels of these cyclooxygenase products would be an excellent indicator of vascular endothelial injury in the presence of the modified Hall valvulotome. Eight segments of human distal saphenous veins were obtained, each measuring approximately 4 cm in length, with diameters of approximately 2 to 3 mm. From these original vein segments, two groups of smaller vein segments were examined, with each group consisting of eight segments, each segment measuring 2 cm in length. The first group of vein segments was designated as the control group, and the second group of vessels had a modified Hall valvulotome (2.5 mm size) inserted into each segment to simulate valvulotomy. After this procedure, all vein segments were analyzed for levels of thromboxane and prostacyclin by a standard radioimmunoassay procedure. Results from the present study indicate that the modified Hall valvulotome technique in human saphenous veins does not significantly increase the levels of the cyclooxygenase metabolites thromboxane and prostacyclin relative to control conditions. However, the ratio of TxB2 formation 6-keto PGF1alpha production was increased in the valvulotomized vessel segments, indicating possible platelet release of thromboxane. Therefore, even though there was increased thromboxane production relative to prostacyclin levels in the modified Hall valvulotome technique, it still appears that this type of valvulotomy is relatively noninsulting to the endothelial cell lining.

Endothelium, Vascular↗

PubMed1996

Pulmonary vasoreactivity to endothelin-1 at elevated vascular tone is modulated by potassium channels.

The role of K+ channels on the pressor effect of endothelin-1 (ET-1) on vascular resistance and compliance in the canine pulmonary circulation was studied by using three different K+ channel inhibitors in isolated blood-perfused dog lungs when vascular tone was elevated with U-46619: 1) 10(-6) M glibenclamide, a potent and selective blocker of ATP-sensitive K+ channels; 2) 1 mM tetraethylammonium ions (TEA), an inhibitor of Ca(2+)-dependent K+ channels; and 3) 10(-4) M 4-aminopyridine, a nonspecific inhibitor of K+ channels. The results of the present study showed that under control vascular tone, 10(-8) M ET-1 increased total vascular resistance and capillary pressure by increasing postcapillary resistance. In addition, ET-1 decreased total vascular compliance. When vascular tone was elevated, ET-1 elicited an initial transient vasodilation followed by a sustained mild vasoconstriction that was lesser in magnitude than that observed under normal vascular tone. In addition, the increases in postcapillary resistance and capillary pressure and the decrease in vascular compliance that was observed with ET-1 at normal vascular tone was not present. Pretreatment with glibenclamide, TEA, and 4-aminopyridine at elevated vascular tone significantly potentiated the pressor effect of ET-1, and TEA blocked the transient vasodilation to ET-1. These data indicate that when pulmonary vasomotor tone is elevated with U-46619, Ca(2+)-dependent K+ channels may play a significant role in mediating the vasodilator response to ET-1 while ATP-sensitive, Ca(2+)-dependent, and other voltage-activated K+ channels attenuate the pulmonary vasoconstrictor response to ET-1.

Animals↗

PubMed1996

Measurement of pulmonary blood flow by fractal analysis of flow heterogeneity in isolated canine lungs.

Regional heterogeneity of lung blood flow can be measured by analyzing the relative dispersion (RD) of mass (weight)-flow data. Numerous studies have shown that pulmonary blood flow is fractal in nature, a phenomenon that can be characterized by the fractal dimension and the RD for the smallest realizable volume element (piece size). Although information exists for the applicability of fractal analysis to pulmonary blood flow in whole animal models, little is known in isolated organs. Therefore, the present study was done to determine the effect of blood flow rate on the distribution of pulmonary blood flow in the isolated blood-perfused canine lung lobe by using fractal analysis. Four different radiolabeled microspheres (141Ce, 95Nb, 85Sr, and 51Cr), each 15 microns in diameter, were injected into the pulmonary lobar artery of isolated canine lung lobes (n = 5) perfused at four different flow rates (flow 1 = 0.42 +/- 0.02 l/min; flow 2 = 1.12 +/- 0.07 l/min; flow 3 = 2.25 +/- 0.17 l/min; flow 4 = 2.59 +/- 0.17 l/min), and the pulmonary blood flow distribution was measured. The results of the present study indicate that under isogravimetric blood flow conditions, all regions of horizontally perfused isolated lung lobes received blood flow that was preferentially distributed to the most distal caudal regions of the lobe. Regional pulmonary blood flow in the isolated perfused canine lobe was heterogeneous and fractal in nature, as measured by the RD. As flow rates increased, fractal dimension values (averaging 1.22 +/- 0.08) remained constant, whereas RD decreased, reflecting more homogeneous blood flow distribution. At any given blood flow rate, high-flow areas of the lobe received a proportionally larger amount of regional flow, suggesting that the degree of pulmonary vascular recruitment may also be spatially related.

Animals↗

PubMed1995

Effect of phorbol myristate acetate-induced lung injury on airway blood flow.

The effects of phorbol myristate acetate (PMA) induced lung injury on the pulmonary and systemic blood flow contributions to the trachea and main bronchi (upper airways) were assessed in anesthetized dogs by injecting 15 microns radiolabeled microspheres into the right and left heart, respectively. Upper airway blood flow was studied in lungs given the following treatments: (1) PMA; (2) PMA in lungs pretreated with the thromboxane synthetase inhibitor OKY-046, and (3) PMA in lungs pretreated with the antioxidant catalase. After microsphere injections, the tracheal cartilage, tracheal muscle-mucosa, and main bronchi were excised. The results of this study indicate that under normal conditions, tracheal mucosa [33-52 ml.min-1.(100 g)-1] and tracheal cartilage [18-27 ml.min-1.(100 g)-1] blood flow is primarily systemic while both the systemic [12-18 ml.min-1.(100 g)-1] and pulmonary [6-12 ml.min-1.(100 g)-1] circulations contribute substantial amounts of blood flow to the main bronchi. PMA significantly decreased the systemic blood flow contribution to the tracheal cartilage and muscle-mucosa, and both the systemic and pulmonary blood flow contributions to the main bronchi to less than 50% of control values, an effect that was inhibited by catalase, but not by OKY-046. These results suggest that the effect of PMA-induced lung injury on the pulmonary and systemic blood flow contributions to the upper airways is at least partially mediated by oxygen radical production, probably hydrogen peroxide (H2O2), but not by the production of the arachidonic acid metabolite thromboxane.

Animals↗

PubMed1995

Endothelial cell injury in the human saphenous vein: a comparative study of two valvulotomes.

Use of valvulotomes in non-reversed venous conduits carries the potential of venous endothelial cell injury. Earlier studies have shown that there is a significant decrease in the number of endothelial cells present in the human saphenous vein when employing the circular (LeMaitre) valvulotome. The present study was performed to evaluate and compare the LeMaitre and modified Hall valvulotome techniques on vascular endothelial cells from human saphenous vein. The results of the present study indicate that while both valvulotomes caused a significant decrease in the number of endothelial cells, the modified Hall instrument was less damaging to the vascular endothelium than the LeMaitre valvulotome. These results suggest that the modified Hall valvulotome technique may be more beneficial in maintaining endothelial cell function when the use of a valvulotome is warranted.

Cell Count↗

PubMed1995

Regional pulmonary blood flow during rest, tilt, and exercise in unanesthetized dogs.

We assessed the heterogeneity of regional pulmonary blood flow (PBFr), using radioactive microspheres in five unanesthetized dogs standing at rest (Rest), standing at a 45 degrees upward tilt (Tilt), and during moderate treadmill exercise (Exer). The excised lungs were cut into 1-cm3 pieces along transverse, horizontal, and longitudinal planes. Mean PBFr increased from 23.3 ml.min-1.g-1 at Rest to 57.4 ml.min-1.g-1 during Exer, but the relative dispersions were not statistically different between states (47.3-51.9%). A small but significant gravity-dependent gradient in PBFr of < or = 4.7%/cm (r2 < or = 0.118) as well as a PBFr decreasing radial gradient from the lung midpoint of < or = 7.2%/cm (r2 < or = 0.108) were present in all states. PBFr at Rest was highly correlated with those at Tilt (r2 = 0.773) and Exer (r2 = 0.888), and a variable PBFr gradient of < or = 2.5%/cm from base to apex was observed. Fractal dimensions calculated using relative dispersion as a function of aggregated sample size were not significantly different between states and were 1.132 (r2 = 0.987) at Rest, 1.121 (r2 = 0.973) at Tilt, and 1.149 (r2 = 0.986) during Exer. Thus, gravity and centripetal gradients consistently accounted for a maximal difference of only about twofold in PBFr and < 11% of overall PBFr heterogeneity in 1-cm3 samples. Recursive anatomic branching of pulmonary arteries and local mechanical factors apparently account for most of the blood flow heterogeneity in small pieces of lung.

Animals↗

PubMed1995

Effect of catecholamines on pulmonary circulation at elevated vascular tone.

The effect of catecholamine stimulation on the longitudinal resistance and compliance distribution in the canine pulmonary vasculature was evaluated under control vascular tone and after vascular tone was elevated using the thromboxane analogue U-46619. The arterial-, venous-, and double-occlusion techniques were used to measure the segmental resistances and compliances in isolated dog lung blood perfused at constant flow. The results of this study indicate that at control vascular tone the catecholamines norepinephrine and epinephrine increase pulmonary vascular resistance and decrease pulmonary vascular compliance through alpha 1- and alpha 2-receptor-mediated stimulation with precapillary alpha 1- and alpha 2-receptors and postcapillary alpha 2-receptors interacting with precapillary and postcapillary beta 2-receptors. In addition, epinephrine appears to have a greater effect on beta 2-receptors than norepinephrine. When vascular tone was elevated, the effect of norepinephrine and epinephrine on pulmonary vascular resistance was not present, which may be due to the appearance of a more pronounced vasodilatory beta 2-receptor system and an attenuation of the alpha-mediated vasoconstrictor responses. In addition, neither catecholamine had any significant effect on pulmonary vascular compliance when vascular tone was raised. These data suggest that the adrenergic-receptor systems modulating pulmonary vascular resistance and compliance in the canine pulmonary circulation are altered when vascular tone is elevated. As a result, these altered pulmonary vascular responses may affect pulmonary capillary pressure, a major determinant of lung fluid balance.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1995

Phorbol ester potentiation of canine pulmonary vasoreactivity to histamine.

The effect of phorbol myristate acetate (PMA) on canine pulmonary vasoreactivity to histamine was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured by using vascular occlusion techniques. Histamine (10(-5) M) significantly increased postcapillary resistance by venoconstriction and significantly attenuated total vascular compliance by decreasing large-vessel compliance and middle-compartment compliance. Pretreatment with the phorbol ester PMA (10(-7) M) significantly potentiated the vasoactive response to histamine and elicited an edemagenic effect in the isolated dog lung through modulation of the histaminergic vasoconstrictor effect on precapillary resistance, postcapillary resistance, and pulmonary vascular compliance. Pretreatment with the protein kinase C inhibitors staurosporine (10(-7) M) and calphostin C (10(-6) M) and the dihydropyridine Ca2+ channel blocker nifedipine (10(-5) M) significantly attenuated the effect of PMA on histaminergic-mediated vasoconstriction. The results of this study indicate that phorbol esters may exert their effect on canine pulmonary vasoreactivity predominantly through activation of protein kinase C and influx of Ca2+ through voltage-dependent Ca2+ channels.

Alkaloids↗

PubMed1995

Mechanism of action of endothelin-1 in the canine pulmonary circulation.

Possible mechanisms of action by which endothelin (ET)-1 has an effect on pulmonary vascular resistance and compliance in the canine pulmonary circulation were investigated in the isolated blood-perfused dog lung by use of vascular occlusion techniques. In the present study, ET-1 (10(-8) M) increased pulmonary vascular resistance and pulmonary capillary pressure by postcapillary vasoconstriction. In addition, ET-1 decreased total vascular compliance and middle-compartment compliance. Pretreatment with the ETA receptor antagonist BQ-610 (10(-7) M) or the protein kinase C inhibitors staurosporine (10(-6) M) and calphostin C (10(-6) M) completely blocked the pressor effect of ET-1. Elimination of extracellular calcium mobilization through voltage-dependent calcium channels by verapamil (10(-5) M) or modulation of G protein signal transduction by pertussis toxin challenge (15 micrograms/kg) had no significant effect on the ET-1-induced pulmonary vascular response. The results of the present study indicate that ET-1 causes pulmonary vasoconstriction in the canine pulmonary circulation through ETA receptor mediation and protein kinase C activation, possibly leading to intracellular calcium release. In contrast, the ET-1-induced pulmonary vascular response does not appear to involve extracellular calcium entry through voltage-dependent calcium-channel activation or pertussis toxin-sensitive G protein-signaling mechanisms.

Animals↗

PubMed1993

Effects of left atrial and airway pressures on airway blood flow.

The blood flow contributions of the pulmonary and systemic circulations to airway blood flow from the trachea down to the 5th generation airways when either 15 cmH2O positive end expiratory pressure (PEEP) or 20 mmHg left atrial pressure was applied were assessed in anesthetized dogs by injecting 15-microns radiolabeled microspheres into the right and left heart, respectively. After the microsphere injections, the animals were killed, and the tracheal cartilage, tracheal muscle-mucosa, main bronchi and the 2nd generation bronchi down to the 5th generation airways were excised and collected for radioactive counting. The results of this study showed that under normal conditions, tracheal blood flow was primarily systemic (> 95% of total tracheal blood flow) averaging 15-26 ml.min-1 x (100 g)-1, while both the pulmonary [10 ml.min-1 x (100 g)-1] and systemic circulations [15 ml.min-1 x (100 g)-1] contributed substantially to main bronchi blood flow. The systemic blood flow contribution to the lower airway generations (2nd to the 5th generation airways) stayed relatively constant, averaging 13-31 ml.min.(100 g)-1 while the pulmonary blood flow contribution increased significantly in these airway segments to a maximum of over 100 ml.min-1 x (100 g)-1 at the 5th generation. At 15 cmH2O PEEP, the systemic contribution to all of the airway segments (except the 5th generation, P < 0.09) and the pulmonary component to the main bronchi, significantly decreased (P < 0.05). In contrast, elevated left atrial pressure had little effect on the pulmonary and systemic contributions to airway blood flow. The results of this study suggest that elevated PEEP has a greater effect than elevated left atrial pressure on the systemic blood flow contribution to the airways, while the pulmonary blood flow contribution to the airways is affected very little by either of these perturbations.

Animals↗