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H van der Zee

Publications and source records attributed to H van der Zee.

At least 37 records · Page 2Linked to original sources
PubMed1986

Platelet-activating factor increases lung vascular permeability to protein.

We studied the effects of platelet-activating factor (PAF) on pulmonary hemodynamics and microvascular permeability in unanesthetized sheep prepared with lung-lymph fistulas. Since cyclooxygenase metabolites have been implicated in mediating these responses, we also examined the role of the cyclooxygenase pathway. PAF infusion (4 micrograms X kg-1 X h-1 for 3 h) produced a rapid, transient rise in pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), plasma thromboxane B2 concentration (TxB2), and pulmonary lymph flow (Qlym). The lymph-to-plasma protein concentration ratio (L/P) did not change from base line. Pretreatment with the cyclooxygenase inhibitor, sodium meclofenamate, prevented the generation of TxB2 and the hemodynamic changes but did not prevent the increase in Qlym. The estimated protein reflection coefficient decreased from a control value of 0.66 +/- 0.04 to 0.43 +/- 0.06 after PAF infusion. We also studied the effects of PAF on endothelial permeability in vitro by measuring the flux of 125I-albumin across cultured bovine pulmonary artery endothelial cells (EC) grown to confluency on a gelatinized micropore filter and mounted within a modified Boyden chemotaxis chamber. PAF (10(-8) to 10(-4) M) had no direct effect on EC albumin permeability, suggesting that the increase in permeability in sheep was not the direct lytic effect of PAF. In conclusion, PAF produces pulmonary vasoconstriction mediated by cyclooxygenase metabolites. PAF also increases pulmonary vascular permeability to protein that is independent of cyclooxygenase products and is not the result of a direct effect of PAF on the endothelium.

Animals↗
PubMed1986

Pulmonary vascular response to platelet-activating factor in awake sheep and the role of cyclooxygenase metabolites.

We examined the effects of platelet activating factor (PAF) (1.0 microgram/kg infusion for 15 min) on pulmonary hemodynamics and lung fluid balance and the role of cyclooxygenase metabolites in mediating these responses in unanesthetized sheep prepared with lung lymph fistulas. Platelet activating factor infusion resulted in immediate and transient increases in pulmonary artery pressure, pulmonary vascular resistance, and pulmonary lymph flow. The lymph-to-plasma protein concentration ratio did not change significantly from baseline. Circulating platelet and leukocyte counts decreased immediately after PAF infusion; the leukopenia was the result of a rapid decrease in both the neutrophil and mononuclear leukocyte counts. Arterial thromboxane B2 (TxB2) concentration increased after the PAF infusion, but the 6-keto prostaglandin F1 alpha (a prostacyclin degradation product) concentration did not change from baseline. A chemically similar substance, Lyso-PAF, had no effect on the pulmonary hemodynamic, lymph, and hematologic parameters or the TxB2 generation. Administration of cyclooxygenase inhibitors, meclofenamate or indomethacin, prior to PAF infusion prevented thromboxane B2 generation and attenuated the pulmonary hemodynamic response. The initial pulmonary lymph flow and transvascular protein clearance (lymph flow times lymph-to-plasma protein concentration) responses to PAF were attenuated after cyclooxygenase inhibition. However, there were time-dependent increases in pulmonary lymph flow and transvascular protein clearance in the cyclooxygenase-inhibited groups. These results indicate that PAF induces pulmonary vasoconstriction mediated by cyclooxygenase metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Effects of transient intracranial hypertension on lung fluid and protein exchange.

We determined whether a transient increase in intracranial pressure (Pic) increases lung vascular permeability and whether the increase occurs at a Pic threshold. Anesthetized sheep were prepared with lung lymph fistulas. Pic was increased by rapidly injecting 20-45 ml of freshly drawn autologous blood into the cisterna magna from a base line of 4.8 +/- 1.5 Torr to a peak mean value of either 142.0 +/- 17.6 Torr (group I, n = 5) or 70.3 +/- 3.5 Torr (group II, n = 5). Pic decreased to 34.6 +/- 2.2 Torr in group I and to 31.0 +/- 3.2 Torr in group II within 1 h and remained steady at these levels for the study. The Cushing response (i.e., marked systemic hypertension lasting 10-15 min) was elicited only in group I; changes in mean pulmonary arterial (Ppa) and mean pulmonary arterial wedge (Ppw) pressures during the first 15 min were small, pulmonary blood flow (QL) increased, and pulmonary vascular resistance (PVR) decreased only in the first 15 min after the intracisternal injection. In group II, Ppa and QL did not change significantly, but PVR increased after the increase in Pic. Both pulmonary lymph flow (Qlym) and transvascular protein clearance (CL) increased only in sheep with the Cushing response. In group III (n = 8) in which Qlym and CL increased after intracranial hypertension as in group I, the left atrial pressure was raised to increase the pulmonary capillary pressure (Pc) to determine the basis for the increases in Qlym and CL (i.e., whether vascular surface area or permeability increased). The increase in Pc produced a small increase and decrease in lymph-to-plasma protein concentration ratio, indicating that the transient increase in Pic did not increase endothelial permeability to proteins. The increases in Qlym and CL were due to increased pulmonary vascular surface area.

Animals↗
PubMed1983

Effects of cyclooxygenase and lipoxygenase inhibition on lung fluid balance after thrombin.

We examined the roles of the cyclooxygenase and lipoxygenase pathways in the alterations in lung fluid and protein exchange after pulmonary microembolism. Infusion of alpha-thrombin (T) (55 +/- 13 U/kg) immediately increased mean pulmonary arterial pressure (Ppa) and mean pulmonary vascular resistance (PVR), but both Ppa and PVR waned with time after T. Cyclooxygenase inhibition with either indomethacin or ketoprofen produced sustained increases in Ppa and PVR. The initial increases in Ppa in the cyclooxygenase-inhibited groups (CI) were matched to the control group by administering greater amounts of T. In the control group, T rapidly increased pulmonary lymph flow (Qlym) by two- to threefold, and this was associated with a steady increase in lymph-to-plasma protein concentration ratio (L/P). In contrast, in cyclooxygenase-inhibited (CI) groups, Qlym increased gradually to greater levels than in the control group, and L/P did not change. The effect on lung vascular permeability was determined by inflating a left atrial balloon catheter to raise pulmonary capillary pressure (Pc). An increase in Pc after T in the control group further increased Qlym and did not change L/P, whereas the increase in Pc after T in CI groups further increased Qlym and decreased L/P, indicating that cyclooxygenase inhibition prevented the increase in permeability. We determined whether lipoxygenase activation contributed to the increase in Qlym in CI groups by examining the effects of BW755C, an inhibitor of both cyclooxygenase and lipoxygenase pathways. BW755C resulted in the same increase in Qlym after T as in the control group, but the increase in Qlym was associated with a decrease in L/P. Therefore, inhibition of both pathways prevented the permeability increase and the greater increase in Qlym. The results indicate that cyclooxygenase and lipoxygenase pathways contribute to the increases in pulmonary transvascular fluid and protein fluxes after thrombin.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1983

Relationship of pulmonary edema after hemorrhagic shock to intravascular coagulation.

We examined the relationship between hemorrhage-induced alterations in the extravascular lung water content and the degree of intravascular coagulation in nonheparinized dogs. The severity of pulmonary edema was assessed by the extravascular lung water content to bloodless dry lung weight ratio (W/D), and the degree of intravascular coagulation in the lung was assessed by prior injection of 125I-labeled fibrinogen. Pulmonary edema developed in only 4 of 12 dogs (ie, W/D ratio of 4.86 +/- 0.12 ml/gm vs 3.21 +/- 0.056 in controls), while in others the W/D ratio of 3.23 +/- 0.11 was in the normal range. The animals that developed pulmonary edema also had increased 125I-activity in the lungs, while the activity was not increased in dogs that did not develop pulmonary edema. Pulmonary vascular resistance (PVR) increased to the same extent in both groups, while arterial pO2 decreased and venous admixture increased during hemorrhage only in dogs that developed pulmonary edema. Pulmonary blood volume decreased in dogs with pulmonary edema, and the decrease was largely confined to the dependent lung regions. The results suggest the activation of intravascular coagulation and pulmonary thromboembolization in only those dogs developing pulmonary edema. The relationship of intravascular coagulation to edema in these animals suggests that the edema was due to activation of cellular (eg, granulocytes) or humoral factors (eg, fibrin degradation products) associated with intravascular coagulation. However, most dogs subjected to hemorrhage did not have intravascular coagulation in lungs and did not develop pulmonary edema. Thus, differences in activation of intravascular coagulation may explain why pulmonary edema does not commonly occur after hemorrhage.

Animals↗
PubMed1981

Adrenoceptor control of lung fluid and protein exchange.

We studied the effects of alpha- and beta-adrenergic antagonists on lung fluid and protein exchange in anesthetized sheep. alpha-Adrenergic blockade with 2 mg/kg phentolamine caused a transient and small decrease in lung lymph flow (Qlym), which was associated with a decrease in mean pulmonary arterial pressure (Ppa); but the steady-state Qlym and mean left atrial pressure were not different from base-line values. In contrast, beta-adrenergic blockade with propranolol (2 mg/kg) caused an increase in Qlym from a base-line value of 7.7 +/- 2.2 ml/h to a steady-state value of 10.6 +/-2.3 ml/h within 2 h (P less than 0.05), which was not associated with a change in Ppa. The increase in Qlym persisted for the 4-h duration of the study. The 39% increase in Qlym after propranolol was associated with a 50% increase in transvascular protein clearance (CL), whereas in control animals the 100% increase in Qlym after left atrial hypertension was associated with only a 36% increase in CL, indicating increased transvascular transport of proteins after propranolol. The transient decrease in Qlym after phentolamine may be due to the short-lasting decreased in pulmonary microvascular pressure and vascular surface area. However, the long-lasting increases in Qlym and CL after propranolol may be due to an increase in vascular surface area and to an increase in endothelial permeability of proteins. The results suggests that beta-adrenergic receptors regulate the transendothelial transport of fluid and proteins.

Animals↗
PubMed1980

Effects of pulmonary edema on regional pulmonary perfusion in the intact dog lung.

Regional pulmonary blood flow was determined in dogs during varying degrees of pulmonary edema induced by infusing 179.2-659.4 ml/kg normal saline over 2-3 h. Pulmonary hemodynamics and regional blood flows were measured during the base-line period and at 30 min postinfusion. The degree of pulmonary edema was determined by the final extravascular lung water-to-bloodless dry lung weight ratio (W/D). In dogs developing gross alveolar edema (W/D of 10.70 +/- 0.88 vs. 3.10 +/- 0.30 in controls), the blood flow was shifted to either upper or dependent lung regions. The shift to the upper regions was associated with an increased (P < 0.05) pulmonary arterial pressure (Ppa), whereas the shift to the dependent lung was not associated with a significant change in Ppa. Breathing 100% O2 did not prevent these shifts, suggesting that they were not due to localized hypoxic pulmonary vasoconstriction. The flow distribution patterns were also not related to regional differences in edema. In contrast to the changes during fulminant edema, blood flow distribution did not change after moderate levels of pulmonary edema (W/D of 6.03 0.69), suggesting that gross alveolar flooding is required for a redistribution of pulmonary blood flow. Flow redistribution to the upper lung during airway flooding may be due to increase in Ppa, whereas the increased flow in the dependent lung during the same degree of edema may be due to "bulging" of alveolar vessels into the air spaces, secondary to a decrease in surface activity.

Animals↗
PubMed1979

Site of pulmonary edema after unilateral microembolization.

The effect of unilateral pulmonary microembolization on regional lung extravascular fluid accumulation was determined in dogs. Embolization was produced by injecting 100-micrometer-diam glass beads (0.25 g/kg) into the right pulmonary artery. After embolization of one lung, pulmonary arterial pressure (Ppa) and pulmonary vascular resistance increased (P less than 0.05) from base-line values of 11.7 +/- 1.3 to 17.9 +/- 1.3 Torr and of 3.4 +/- 0.5 to 5.5 +/- 0.5 Torr/(1/min). Blood flow to embolized lung measured with labeled microspheres decreased from 104.2 +/- 24.9 to 35.2 +/- 9.2 ml/min.g bloodless lung after embolization, whereas flow to the normal lung increased from 43.1 +/- 5.6 to 71.2 +/- 19.2 ml/min.g bloodless lung. Extravascular lung water-to-bloodless dry lung weight ratio (W/D) of 4.97 +/- 0.32 was greater (P less than 0.001) in the embolized lung than the value of 3.34 +/- 0.15 in nonembolized lung. In six dogs pretreated with 500 U/kg of heparin, a similar degree of duration of embolization and similar hemodynamic changes did not result in significant differences in W/D (3.88 +/- 0.18 in right lung vs. 3.02 +/- 0.53 in the left lung), and the right lung ratio was less (P less than 0.05) than the value in the heparinized dogs, suggesting that humoral mechanisms contribute to the genesis of pulmonary edema after regional embolization. Therefore, unilateral embolization leads to a greater increase in extravascular content in the embolized lung than in the nonembolized lung. Because Ppa was in the normal range after embolization, regional pulmonary edema may be due partly to the local release of factors that increase lung vascular permeability.

Animals↗
PubMed1979

Pulmonary transvascular fluid dynamics in sheep during hemorrhage.

The effects of hemorrhage on pulmonary hemodynamics and lung transvascular fluid dynamics were studied in sheep. We found that 2 hr of hemorrhage caused a fall in lung lymph flow (p less than 0.05) and no significant change in lymph protein concentration. The fall in lymph flow was not due to decreased vascular surface area since the regional distribution of pulmonary perfusion was not altered during hemorrhage; however, the decrease in lymph flow was associated with decrease (p less than 0.05) in the calculated pulmonary microvascular pressure. The extravascular lung water lung content per g bloodless dry lung was increased (p less than 0.05) in the hemorrhaged sheep from the control values. Pulmonary edema was not due to increased lung vascular endothelial permeability since the net transvascular protein flux was not increased. The finding that pulmonary edema occurred despite the consistent decreases in lymph flow suggests that edema may be due to hemorrhage-induced lymphatic "failure" or that edema fluid is sequestered in spaces (e.g., endothelial cells) where if cannot be drained by the lymphatics.

Animals↗