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Biomedical subjects

W F Hofman

Publications and source records attributed to W F Hofman.

At least 37 records · Page 2Linked to original sources
PubMed1988

Venous occlusion pressure and vascular permeability in the dog lung after air embolization.

Pulmonary edema has frequently been associated with air embolization of the lung. In the present study the hemodynamic effects of air emboli (AE) were studied in the isolated mechanically ventilated canine right lower lung lobe (RLL), pump perfused at a constant blood flow. Air was infused via the pulmonary artery (n = 7) at 0.6 ml/min until pulmonary arterial pressure (Pa) rose 250%. While Pa rose from 12.4 +/- 0.6 to 44.6 +/- 2.0 (SE) cmH2O (P less than 0.05), venous occlusion pressure remained constant (7.0 +/- 0.5 to 6.8 +/- 0.6 cmH2O; P greater than 0.05). Lobar vascular resistance (RT) increased from 2.8 +/- 0.3 to 12.1 +/- 0.2 Torr.ml-1.min.10(-2) (P less than 0.05), whereas the venous occlusion technique used to determine the segmental distribution of vascular resistance indicated the increase in RT was confined to vessels upstream to the veins. Control lobes (n = 7) administered saline at a similar rate showed no significant hemodynamic changes. As an index of microvascular injury the pulmonary filtration coefficient (Kf) was obtained by sequential elevations of lobar vascular pressures. The Kf was 0.11 +/- 0.01 and 0.07 +/- 0.01 ml.min-1.Torr-1.100 g RLL-1 in AE and control lobes, respectively (P less than 0.05). Despite a higher Kf in AE lobes, total lobe weight gains did not differ and airway fluid was not seen in the AE group. Although air embolization caused an increase in upstream resistance and vascular permeability, venous occlusion pressure did not increase, and marked edema did not occur.

Animals↗
PubMed1987

The effect of blood flow and diffusion impairment on pulmonary gas exchange: a computer model.

An assumption of the classical three-compartment lung model is that the physiologic shunt fraction (Qs/Qt) remains constant with changes in cardiac output (Qt). As a result, when Qt decreases, both the arterial O2 tension (PaO2) and the mixed venous O2 tension (PvO2) must also decrease. Yet observations in intact dogs with pulmonary edema and humans with the adult respiratory distress syndrome (ARDS) indicate that as Qt decreases, Qs/Qt occasionally declines while the PaO2 increases. The present study was conducted to examine these discordant observations using a computer model of pulmonary gas exchange with a diffusion impairment. A computer model of gas exchange was developed to specifically analyze the effect of changing Qt upon PaO2 and Qs/Qt in the presence of diffusion impairment. Using the classical three-compartment model of gas exchange, a diffusion impairment was inserted by a MIMIC subroutine. The results of this computer simulation indicated that in the presence of a diffusion impairment, lowering Qt caused PaO2 to increase while Qs/Qt and PvO2 decreased. These changes indicated that a diffusion impairment might account for the experimental observations of the effects of Qt on PaO2 in ARDS.

Cardiac Output↗
PubMed1987

Effects of cyclooxygenase inhibition on pulmonary vascular responses to serotonin.

The vasopressor response to graded bolus doses (50-500 micrograms) of serotonin (5-hydroxytryptamine; 5-HT) was examined in the isolated canine lower left lung lobe (LLL) perfused at constant flow with autogenous blood before and after cyclooxygenase inhibition (COI). Lobar vascular resistance (LVR) was partitioned into pre- (Ra) and postcapillary (Rv) segments by venous occlusion with lobar blood volume changes monitored gravimetrically. Before COI, 5-HT produced transient, dose-dependent increases in pulmonary arterial pressure (Ppa) of 43.8 +/- 4.8-123.0 +/- 8.5% (n = 22) and simultaneous decreases in lobar blood volume (5.5 +/- 0.5-8.2 +/- 0.6 g/100 g LLL) with nearly proportionate increases in Ra and Rv at each 5-HT dose. After the initial challenge to 5-HT, LLL's were treated either with saline (n = 7) or one of three chemically distinct cyclooxygenase inhibitors. COI with 40 microM indomethacin (n = 6) or 45 microM meclofenamate (n = 6) increased resting LVR by 36.0 +/- 8.3% (P less than 0.01; n = 12) and decreased the Ra/Rv from 1.9 +/- 0.3 to 1.1 +/- 0.2 (P less than 0.01), whereas 1 mM aspirin (n = 3) caused a fourfold increase in resting LVR without affecting Ra/Rv. After indomethacin or meclofenamate treatment, the vasopressor response to graded doses of 5-HT was markedly potentiated as Ppa increased by 71.6 +/- 7.6-207.0 +/- 24.6%. COI did not potentiate the lobar vasopressor response to graded doses (10-100 micrograms) of norepinephrine (NE, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Vascular pressure effects on lung edema formation after glass bead embolism.

The canine lung lobe was embolized with 100-micron glass beads before lobectomy and blood anticoagulation. The lobe was isolated, ventilated, and pump-perfused with blood at an arterial pressure (Pa) of about 50 (high pressure, HP, n = 9) or 25 Torr (low pressure, LP, n = 9). Rus/PVR, the ratio of upstream (Rus) to total lobar vascular resistance (PVR), was determined by venous occlusion and the isogravimetric capillary pressure technique. The capillary filtration coefficient (Kf), an index of vascular permeability, was obtained from rate of lobe weight gain during stepwise capillary pressure (Pc) elevation. The embolized lobes became more edematous than nonembolized controls, (C, n = 11), (P less than 0.05), with Kf values of 0.20 +/- 0.04, 0.25 +/- 0.06, and 0.07 +/- 0.01 ml X min-1 X Torr-1 X 100 X g-1 in LP, HP, and C, respectively (P less than 0.05). The greater Rus/PVR in embolized lobes (P less than 0.05) protected the microvessels and, although Pc was greater in HP than in controls (P less than 0.05), Pc did not differ between HP and LP (P greater than 0.05). Although indexes of permeability did not differ between embolized groups (P greater than 0.05), HP became more edematous than LP (P less than 0.05). The greater edema in HP did not appear due to a greater imbalance of Starling forces across the microvessel wall or to vascular recruitment. At constant Pc and venous pressure, elevating Pa from 25 to 50 Torr in embolized lobes resulted in greater edema to suggest fluid filtration from precapillary vessels.

Animals↗
PubMed1986

Effect of fluosol-DA infusion on pulmonary vascular permeability in the dog lung.

Oxygen-carrying perfluorocarbon (PFC) emulsions show clinical promise as blood supplements or substitutes. However, some evidence suggests that PFC emulsions may accumulate in the lungs to disrupt pulmonary function. This study was conducted to determine whether the infusion of a PFC emulsion (Fluosol-DA) would alter microvascular permeability in the isolated canine right lower lung lobe (RLL). RLL's, perfused at constant pressure with autogenous blood, were divided into three groups: Group I (n = 6), the control group, was infused with bovine serum albumin (BSA) until the BSA solution equaled 10% of the total blood volume in the perfusion system; Group II (n = 6) was infused with Fluosol-DA until the emulsion comprised 10% of the final blood volume; and Group III (n = 6) was infused with Fluosol-DA until it comprised 20% of the final blood volume. The pulmonary filtration coefficient (Kf), an index of microvascular permeability, was obtained in each group approximately 1 hour after infusion. The Kf values for the control, 10% Fluosol, and 20% Fluosol groups were 0.070 +/- 0.018, 0.127 +/- 0.024, and 0.115 +/- 0.022 ml X min-1 X mm Hg-1 X 100 gm-1, respectively, and were not significantly different (p greater than 0.05) from each other. Perfusate oncotic pressure, lobar compliance, blood gas levels, and pulmonary arterial pressure did not vary significantly among the experimental groups. Under these experimental conditions, Fluosol-DA, in blood concentrations that might be used clinically, was not associated with an increased microvascular permeability in the isolated dog lung lobe.

Animals↗
PubMed1986

Effects of arterial pressure on lung capillary pressure and edema after microembolism.

The effect of increased arterial pressure (Pa) on microvessel pressure (Pc) and edema following microvascular obstruction (100-micron glass spheres) was examined in the isolated ventilated dog lung lobe pump perfused with blood. Lobar vascular resistance (PVR) increased 2- to 10-fold following emboli when either Pa or flow was held constant. Microbead obstruction increased the ratio of precapillary to total PVR from 0.60 +/- 0.05 to 0.84 +/- 0.02 (SE) or to 0.75 +/- 0.06 (n = 6), as determined by the venous occlusion and the isogravimetric capillary pressure techniques, respectively. Isogravimetric Pc (5.0 +/- 0.7) did not differ from Pc obtained by venous occlusion (3.8 +/- 0.2 Torr, n = 6). After embolism, Pc in constant Pa decreased from 6.2 +/- 0.3 to 4.4 +/- 0.3 Torr (n = 16). In the constant-flow group, embolism doubled Pa while Pc increased only 40% (6.7 +/- 0.6 to 9.2 +/- 1.4 Torr, n = 6) with no greater edema formation than in the constant Pa groups. These data indicate poor transmission of Pa to filtering capillaries. Microembolism, even when accompanied by elevated Pa and increased flow velocity of anticoagulated blood of low leukocyte and platelet counts, caused little edema. Our results suggest that mechanical effects alone of lung microvascular obstruction cause minimal pulmonary edema.

Animals↗
PubMed1986

Prostanoid inhibition potentiates vasoconstrictor response to acetylcholine in dog lung.

We determined whether cyclooxygenase or phosphodiesterase inhibition would alter the vasomotor response to acetylcholine in the dog lung. Lower left lobes were removed and then cannulated, ventilated, and pump perfused with autogenous blood at constant flow [6.0 +/- 0.1 ml X min-1 X g-1 lower left lobe (LLL)]. LLLs were challenged with graded doses of acetylcholine (ACh) (100-1,000 nmol) into the arterial cannula before and after administration of either 40 microM indomethacin (n = 5), 1 mM aspirin (n = 4), or 1 mM theophylline (n = 5). ACh produced a dose-dependent increase in pulmonary arterial pressure (Pa) and a decrease in the upstream-to-down-stream resistance ratio (Rus/Rds). Pretreatment with either indomethacin or aspirin potentiated the Pa response to ACh while eliminating the ACh-associated decrease in Rus/Rds. Pretreatment with the phosphodiesterase inhibitor theophylline significantly antagonized the ACh pressor response and decrease in the Rus/Rds. The present study suggests that the pulmonary pressor response to ACh is enhanced with cyclooxygenase inhibition. Our results indicate that ACh stimulates pulmonary vascular muscarinic cholinoceptors to cause vasoconstriction. Additionally or as sequelae to this response, predominantly vasodilatory prostanoids appear to be released.

Acetylcholine↗
PubMed1985

Sequential cardiopulmonary changes after oleic-acid injury in dogs.

Oleic acid (OA) administered to experimental animals increases pulmonary vascular permeability and produces a condition that pathophysiologically resembles adult respiratory distress syndrome (ARDS) in humans. The present study examined the sequence of cardiorespiratory changes after OA infusion and their similarity to ARDS. After a baseline period, mechanically ventilated and anesthetized dogs were administered 0.18 ml/kg body weight OA into the pulmonary artery while hemodynamic and respiratory changes were monitored. After OA infusion, cardiac output fell by 39%, paralleling a 26% decrease in heart rate. Pulmonary vascular resistance (PVR) increased over 200% without a change in pulmonary capillary wedge pressure and initially without an increase in pulmonary artery pressure (PAP). Within 30 min after OA infusion, dynamic pulmonary compliance (Cdyn) was reduced 32% from baseline values, with a coincident increase in the alveolar-arterial PO2 gradient (P[A-a]O2) but without a significant change in the pulmonary shunt fraction (Qsp/Qt). This was followed in 30 min by a further 27% decrease in Cdyn, with a Qsp/Qt in excess of 50%. Both the hematocrit and hemoglobin concentration increased progressively after OA infusion, without a change in plasma protein concentration. The results suggest that the sequence of cardiopulmonary changes after OA injury are initially marked by a decrease in Cdyn and an increase in PVR and P(A-a)O2. This is followed by an increase in Qsp/Qt, PAP, hemoglobin concentration and PCO2. The changes appear related to progressive flooding of the alveolar air space with edema fluid. These findings parallel the sequential cardiorespiratory changes reported to occur in ARDS.

Animals↗
PubMed1985

Pulmonary fluid balance and hemodynamics after perfluorocarbon infusion in the dog lung.

Perfluorocarbon (PFC) emulsions are promising oxygen-carrying blood supplements for the treatment of shock and in organ preservation for transplantation. We used the isolated, blood-perfused, canine right lower lung lobe (RLL) to determine the effect of a PFC emulsion, Oxypherol (FC-43), upon lung fluid balance and hemodynamics. Eighteen RLLs were divided into three equal groups, one of which was infused with a bovine serum albumin (BSA) solution to 10% of the total perfusate volume, and two of which were infused with Oxypherol to 10% and 20% of the final blood volume, respectively. At 145 min after infusion, there was no significant difference among the three groups in pH, blood gases, and lobar compliance. Arterial pressure and lobar vascular resistance were significantly (p less than .05) greater in the 20% Oxypherol group than in the BSA group. PFC-related changes in lobar permeability were determined by measuring the pulmonary filtration coefficient (Kf), which was not significantly different among groups. Thus, Oxypherol did not increase microvascular permeability (i.e., lung edema).

Animals↗
PubMed1985

Albumin attenuation of oleic acid edema in dog lung depleted of blood components.

Circulating fatty acids are normally transported principally bound to serum albumin. We examined whether administering oleic acid (OA) in a concentrated albumin solution would attenuate its edemogenic potential in the isolated dog lung lobe perfused with a solution nearly depleted of blood cellular and protein components. The isolated ventilated lower left lobe (LLL) was perfused (7.3 +/- 0.6 ml X min-1 X g LLL-1) with a balanced salt solution containing 6% dextran and approximately 10% serum (vol/vol). Hourly weight gain, net LLL weight gain, and wet-to-dry weight ratio (W/D) were used as indices of extravascular lung fluid changes. Group I lobes (n = 5) were given saline, whereas both group II (n = 5) and III (n = 5) lobes were administered 1 microliter OA/kg body wt. The OA was incubated with 5 ml of albumin solution containing approximately 640 mg of bovine fatty acid-free albumin before infusion into group III lobes. Group I gained weight at rate of 10.8 +/- 0.5 g X h-1 X 100 g LLL-1 after saline, whereas group II exhibited a greater (P less than 0.005) rate of weight gain of 42 +/- 13 after OA. Group III weight gain of 8.4 +/- 0.5 g X h-1 X 100 g LLL-1 was not different (P greater than 0.05) from group I but was lower (P less than 0.005) than group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Filtration coefficient obtained by stepwise pressure elevation in isolated dog lung.

The base-line capillary filtration coefficient (Kf) obtained from rates of lobe weight gain during stepwise vascular pressure elevation is reported to be threefold greater in isolated than in intact dog lung. To further evaluate the stepwise pressure elevation technique, we obtained Kf in control and oleic acid-injured isolated lung. The left lower lung lobe was removed, placed on a balance, ventilated, and pump perfused with autogenous blood. Saline (n = 6) or oleic acid (n = 6) was infused, and rate of lobe weight gain was obtained during stepwise pressure elevation. Kf averaged 0.071 +/- 0.012 and 0.243 +/- 0.027 ml X min-1 X Torr-1 X 100 g-1 in the control and injured lobes, respectively. Stepwise pressure elevation can yield a base-line Kf in isolated lung similar to Kf's obtained from this and other gravimetric methods in intact and isolated lung. Furthermore, Kf increased severalfold following lung injury with oleic acid. The stepwise pressure elevation technique for Kf determination in isolated lung can be a useful tool for quantitating changes in vascular permeability.

Animals↗
PubMed1984

Permeability edema in dog lung depleted of blood components.

We perfused the isolated dog lung lobe with a 6% dextran (mol wt 60,000-90,000) balanced salt solution to determine the importance of blood components in lung fluid balance following injury with oleic acid (OA). The ventilated lower left lobe (LLL) was perfused at constant vascular pressure and weighed continuously as an index of transvascular fluid exchange. Each LLL was washed out with at least 600 ml of perfusate before recirculation started. All LLLs perfused with 6% dextran ion solution (group I) rapidly developed a permeability edema. The addition of 10% serum (vol/vol) from the lobe donor to the 6% dextran ion solution greatly improved LLL stability. One group of dextran-serum perfused LLLs (group II, n = 6, control) was infused with 2.0 ml normal saline; a second group (group III; n = 5) was given 45 microliters/kg body wt OA. Group II showed a linear rate of weight gain that averaged 7.9 g X h-1 X 100 g-1 over 3 h compared with an average rate of 249 g X h-1 X 100 g-1 in group III. In contrast to no change in group II, group III exhibited a decline in PO2 (P less than 0.05), and lobar compliance (P less than 0.05) and airway fluid was evident in all lobes by 0.5 h after infusion. The wet-to-dry weight ratio was higher in group III than group II. In the near absence of blood, massive edema developed rapidly following OA. Thus normal blood components, such as platelets, leukocytes, and fibrin do not appear to be essential mediators of OA-induced permeability edema. OA appears to increase vascular permeability either by injuring the lung directly or by releasing mediators endogenous to lung tissue.

Animals↗
PubMed1981

Effects of endotracheal suction versus apnea during interruption of intermittent or continuous positive pressure ventilation.

The hypoxemia, elevated vascular pressure, and cardiac arrhythmias occurring during endotracheal suction may be related both to suction and the interruption of ventilation during suction. Although effects of suction vs. apnea have been compared in healthy patients, interruption of ventilation for purely investigational purposes precludes such a study in critically ill patients. Thus, in the present study, cardiovascular and blood gas changes attendant to endotracheal suction or equivalent periods of apnea were compared in anesthetized, paralyzed dogs in acute respiratory failure induced by oleic acid. Suction of 45-sec duration during interruption of intermittent positive pressure ventilation (IPPV) was associated with decreases in PaO2, pH, and heart rate and increases in PaCO2, cardiac output, pulmonary arterial and systemic arterial pressure. These changes were not different from those observed during interruption of ventilation (apnea) alone. Cardiovascular and blood gas changes were also similar when suction and apnea were compared during interruption of continuous positive pressure ventilation (CPPV). Neither apnea nor suction was associated with cardiac arrhythmias.

Animals↗
PubMed1981

Effects of methylprednisolone on fatty acid induced edema in the dog lung.

In animals oleic acid induces a form of lung injury similar to that observed following fat embolization in humans. In the present study, canine lower left lung lobes were isolated, ventilated, and perfused at constant pressure with heparinized, autologous blood. Weight gain, in the absence of vascular volume change, in this preparation is a sensitive indicator of edema. One group of lobes was pretreated with 5.1 mg/gm lobe wt methylprednisolone before 1 microliter/kg body wt oleic acid. An untreated group given only oleic acid served as controls. Following oleic acid, the reduction in effective lobe compliance and blood PO2 and the increase in perfusate total protein concentration were similar in both groups. Rate of lobe weight gain following oleic acid was remarkably linear in both groups but significantly lower (p less than 0.05) in lobes pretreated with methylprednisolone. The latter group showed a total weight gain of 21% compared to 34% in the controls 3 hr after oleic acid challenge. We conclude that oleic acid induces a pulmonary edema in the absence of an elevation in hydrostatic pressure. Furthermore, rate of edema formation is attenuated by methylprednisolone pretreatment.

Animals↗
PubMed1981

Oleic acid dose-related edema in isolated canine lung perfused at constant pressure.

Fatty acid embolism of the lung results in pulmonary edema. Isolated lung lobes ventilated and blood perfused at constant pressure were treated with 1 (n = 6) or 45 microliter/kg body wt (n = 6 oleic acid or saline (n = 7). Lobe weight increase linearly over 1-3 h following oleic with regression slopes indicating a more rapid rate of weight gain at the higher oleic acid dosage. Total lobe weight gain was greater in the 45 than in the 1 microliter/kg group (0.60 +/- 0.10 vs. 0.31 +/- 0.07 g/g initial lobe wt) and greater in the acid-treated lobes than in the controls (0.13 +/- 0.05 g/g initial lobe wt). Pulmonary vascular resistance increased 79% after 45 microliter/kg oleic acid but appeared unchanged following 1 microliter/kg oleic acid or saline. The decrease in arterial O2 partial pressure was greater in the 45 microliter/kg group than in the controls, 47 vs 22 Torr. High vascular pressures and increased flow velocities in patent vessels are not essential for oleic acid-associated edema, since weight increased at constant pressure perfusion. Weight gain related to oleic acid dosage suggests that oleic acid increases permeability by affecting the vascular endothelium either directly or through biochemical intermediates endogenous to the lung or blood.

Animals↗
PubMed1977

Thermorespiratory responses of shorn and unshorn sheep to mild heat stress.

Three 3-year-old ewes with surgically exteriorized carotid loops were twice exposed to ambient temperatures (Ta) of 25, 30, 35 and 40 C (at constant 40% relative humidity) for 120 min in the presence (6.6 cm) and absence (less than 0.3 cm) of fleece. Thermoregulatory responses were evaluated during the last 30 min of each exposure by measurements of rectal (Tre), 6 skin surface temperatures (Ts), respiratory frequency (f), oxygen consumption (Vo2) and respiratory evaporative heat (Er); arterial blood samples were analyzed for pH, Pco2 and HCO-3 concentration. Both shorn and unshorn sheep exhibited a progressive increase in f, Er and Ts as Ta was elevated, with the unshorn group showing a higher Er than the shorn sheep at each Ta without a significant change in heat production. Er was found to be the principal avenue of heat loss, accounting for as much as 59% of the total in the shorn sheep compared to65% for the unshorn sheep. Increases in Er were accompanied by a decline in the arterial Pco2 which was linearly related to the Ta in both shorn and unshorn sheep. These data suggest that in defending against hyperthermia, sheep appear unable to increase Er without a concurrent elevation in Va at nearly allstages of acute heat stress.

Animals↗