Biomedical subjects

A Paskanik

Publications and source records attributed to A Paskanik.

9 recordsLinked to original sources

PubMed1999

Matrix metalloproteinase inhibitor prevents acute lung injury after cardiopulmonary bypass.

BACKGROUND: Acute lung injury (ALI) after cardiopulmonary bypass (CPB) results from sequential priming and activation of neutrophils. Activated neutrophils release neutral serine, elastase, and matrix metalloproteinases (MMPs) and oxygen radical species, which damage alveolar-capillary basement membranes and the extracellular matrix, resulting in an ALI clinically defined as adult respiratory distress syndrome (ARDS). We hypothesized that treatment with a potent MMP and elastase inhibitor, a chemically modified tetracycline (CMT-3), would prevent ALI in our sequential insult model of ALI after CPB. METHODS AND RESULTS: Anesthetized Yorkshire pigs were randomized to 1 of 5 groups: control (n=3); CPB (n=5), femoral-femoral hypothermic bypass for 1 hour; LPS (n=7), sham bypass followed by infusion of low-dose Escherichia coli lipopolysaccharide (LPS; 1 microgram/kg); CPB+LPS (n=6), both insults; and CPB+LPS+CMT-3 (n=5), both insults plus intravenous CMT-3 dosed to obtain a 25-micromol/L blood concentration. CPB+LPS caused severe lung injury, as demonstrated by a significant fall in PaO(2) and an increase in intrapulmonary shunt compared with all groups (P<0.05). These changes were associated with significant pulmonary infiltration of neutrophils and an increase in elastase and MMP-9 activity. CONCLUSIONS: All pathological changes typical of ALI after CPB were prevented by CMT-3. Prevention of lung dysfunction followed an attenuation of both elastase and MMP-2 activity. This study suggests that strategies to combat ARDS should target terminal neutrophil effectors.

Acute Disease↗

PubMed1999

Multiple sequential insults cause post-pump syndrome.

BACKGROUND: We hypothesize that post-pump syndrome (PPS) following cardiopulmonary bypass (CPB) can be caused by multiple minor insults and that the mechanism of PPS is a priming and subsequent activation of polymorphonuclear (PMN) leukocytes. In this study extensive pathophysiologic and morphometric assessment was undertaken in a porcine model of sequential insult PPS. METHODS: Pigs were anesthetized, placed on a ventilator, instrumented for measurements of hemodynamic function, and separated into five groups: (1) Control (n = 4)--surgery only, (2) CPB (n = 4)--placed on femoral-femoral hypothermic (28 degrees C) bypass for 1 h, (3) LPS (n = 6)--underwent sham CPB followed by infusion of low dose endotoxin [E. coli lipopolysaccharide (LPS-1 microg/kg)], (4) Heparin + protamine + LPS (HP + LPS, n = 4)--were heparinized without CPB for 1 h, following which protamine and LPS were infused and (5) CPB + LPS (n = 8)--subjected to both CPB and LPS. RESULTS: Only CPB + LPS resulted in acute respiratory distress typical of PPS as indicated by a significant decrease in PaO2 and increase in intrapulmonary shunt fraction (p<0.05). CPB + LPS significantly increased tissue density and the number of sequestered monocytes and PMNs (p<0.05) above all other groups. Alveolar macrophages (AM) increased equally in all groups receiving LPS. CONCLUSIONS: CPB primes the inflammatory system causing pulmonary PMN sequestration without lung injury. Exposure to an otherwise benign dose of endotoxin results in activation of the sequestered PMNs causing PPS. This study confirms that PPS can be caused by multiple minor insults.

Animals↗

PubMed1998

Exogenous surfactant and positive end-expiratory pressure in the treatment of endotoxin-induced lung injury.

OBJECTIVE: To evaluate the efficacy of treating endotoxin-induced lung injury with single dose exogenous surfactant and positive end-expiratory pressure (PEEP). DESIGN: Prospective trial. SETTING: Laboratory at a university medical center. SUBJECTS: Nineteen certified healthy pigs, weighing 15 to 20 kg. INTERVENTIONS: Pigs were anesthetized and surgically prepared for hemodynamic and lung function measurements. Animals were randomized into four groups: a) Control pigs (n = 4) received an intravenous infusion of saline without Escherichia colilipopolysaccharide (LPS); b) the LPS group (n = 5) received an intravenous infusion of saline containing LPS (100 microg/kg); c) the PEEP plus saline group (n = 5) received an intravenous infusion of saline containing LPS. Two hours after LPS infusion, saline was instilled into the lung as a control for surfactant instillation, and the animals were placed on 7.5 cm H2O of PEEP; d) the PEEP plus surfactant group (n = 5) received an intravenous infusion of saline containing LPS. Two hours following LPS infusion, surfactant (50 mg/kg) was instilled into the lung and the animals were placed on 7.5 cm H2O of PEEP. PEEP was applied first and surfactant or saline was instilled into the lung while maintaining positive pressure ventilation. All groups were studied for 6 hrs after the start of LPS injection. At necropsy, bronchoalveolar lavage was performed and the right middle lung lobe was fixed for histologic analysis. MEASUREMENTS AND MAIN RESULTS: Compared with LPS without treatment, PEEP plus surfactant significantly increased PaO2 (PEEP plus surfactant = 156.6 +/- 18.6 [SEM] torr [20.8 +/- 2.5 kPa]; LPS = 79.2 +/- 21.9 torr [10.5 +/- 2.9 kPa]; p<.05), and decreased venous admixture (PEEP plus surfactant = 12.5 +/- 2.0%; LPS = 46.9 +/- 14.2%; p< .05) 5 hrs after LPS infusion. These changes were not significant 6 hrs after LPS infusion. PEEP plus surfactant did not alter ventilatory efficiency index (VEI = 3800/[peak airway pressure - PEEP] x respiratory rate x PacO2), or static compliance as compared with LPS without treatment at any time point. Cytologic analysis of bronchoalveolar lavage fluid showed that surfactant treatment significantly increased the percentage of alveolar neutrophils as compared with LPS without treatment (PEEP plus surfactant = 39.1 +/- 5.5%; LPS = 17.4 +/- 6.6%; p< .05). Histologic analysis showed that LPS caused edema accumulation around the airways and pulmonary vessels, and a significant increase in the number of sequestered leukocytes (LPS group = 3.4 +/- 0.2 cells/6400 micro2; control group = 1.3 +/- 0.1 cells/6400 micro2; p < .05). PEEP plus saline and PEEP plus surfactant significantly increased the total number of sequestered leukocytes in the pulmonary parenchyma (PEEP plus surfactant = 8.2 +/- 0.7 cells/6400 micro2; PEEP plus saline = 3.9 +/- 0.2 cells/6400 micro2; p <.05) compared with the control and LPS groups. CONCLUSIONS: We conclude that PEEP plus surfactant treatment of endotoxin-induced lung injury transiently improves oxygenation, but is unable to maintain this salutary effect indefinitely. Thus, repeat bolus dosing of surfactant or bolus treatment followed by continuous aerosol delivery may be necessary for a continuous beneficial effect.

Animals↗

PubMed1998

Aerosolized surfactant improves pulmonary function in endotoxin-induced lung injury.

Surfactant dysfunction is a primary pathophysiologic component in patients with adult respiratory distress syndrome (ARDS). In this study we tested the efficacy of aerosolized surfactant (Sf ) replacement in a severe lung injury model of endotoxin-induced ARDS. Twenty-one certified healthy pigs were anesthetized, surgically prepared for measurement of hemodynamic and lung function, then randomized into one of four groups: (1) control (n = 5), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 6), infused with Escherichia coli LPS (100 microgram/kg) without positive end- expiratory pressure (PEEP) and ventilated with a nonhumidified gas mixture of 50% N2O and 50% O2; (3) LPS + PEEP (n = 4), infused with LPS, placed on PEEP (7.5 cm H2O), and ventilated with a humidified gas mixture; and (4) LPS + PEEP + Sf (n = 6), infused with LPS, placed on PEEP, and ventilated with aerosolized Sf (Infasurf, ONY, Inc.). All animals were studied for 6 h. Arterial PO2 significantly decreased in both the LPS and LPS + PEEP groups (LPS + PEEP = 74 +/- 19 mm Hg; LPS = 74 +/- 19 mm Hg, p < 0.05) while venous admixture (Q S/Q T) increased in these groups (LPS + PEEP = 43.3 +/- 3.9%; LPS = 47.7 +/- 11%, p < 0.05) as compared with the control group. PEEP + Sf reduced the fall in PO2 (142 +/- 20 mm Hg) and rise in Q S/Q T (15.1 +/- 3.6%) caused by LPS. Delayed induction of PEEP (2 h following LPS) did not significantly improve any parameter over the LPS group without PEEP in this ARDS model. LPS without PEEP (3.4 +/- 0.2 cells/6,400 micrometer2) caused a marked increase in the total number of sequestered leukocytes in the pulmonary parenchyma as compared with the control group (1.3 +/- 0.1 cells/6,400 micrometer2). LPS + PEEP + Sf (2.3 +/- 0.2 cells/6,400 micrometer2) significantly decreased while LPS + PEEP significantly increased (4.0 +/- 0.2 cells/6,400 micrometer2) the total number of sequestered leukocytes as compared with the LPS without PEEP group. In summary, aerosolized surfactant replacement decreased leukocyte sequestration and improved oxygenation in our porcine model of endotoxin-induced lung injury.

Aerosols↗

PubMed1996

Superoxide dismutase (SOD) prevents hypotension after hemorrhagic shock and aortic cross clamping.

To determine if superoxide dismutase (SOD) administration attenuates injury caused by supraceliac aortic cross clamping, a randomized controlled study on 12 taconic rats was performed at the university hospital research center at Syracuse, New York. All animals were anesthetized and placed on a ventilator through a tracheotomy. Surgical preparation included catheterization of carotid and femoral arteries, and the jugular vein. A midline laparotomy was performed through which the supraceliac aorta was exposed and isolated. Animals were allowed to stabilize after surgery and baseline measurements [systemic pressure (Psys), central venous pressure, and blood gases] were recorded. Then, animals were subjected to 60 minutes of hemorrhagic shock (mean Psys = 35 mm Hg), followed by 45 minutes of supraceliac aortic cross clamping. After the release of the aortic cross clamp, shed blood was reinfused. After stabilization, all animals were monitored for 60 minutes. Rats were separated into two groups: the experimental group (n = 6) that received intravenous SOD before and during aortic cross clamping, and the control group (n = 6) that received an equivalent volume of saline at the same time periods. No difference was detected in overall arterial pH, partial arterial carbon dioxide pressure, or base excess at any time period between the groups. A significant increase in Psys was measured in the experimental group compared with the control group from the time of aortic cross-clamp release until the experiment was terminated. One hour after aortic cross-clamp release, the Psys for the experimental group was 69.2 +/- 10.6 mm Hg vs. 36.7 +/- 3.8 mm Hg for the control group (P < 0.05). These data demonstrate that superoxide dismutase significantly improves postaortic cross-clamp Psys. This suggests that oxygen-derived free radicals play a role in postaortic cross-clamp hypotension.

Animals↗

PubMed1995

Segmental pulmonary vascular resistance following wood smoke inhalation.

OBJECTIVES: To locate the specific site (i.e., pulmonary arteries, veins, or capillaries) of increased pulmonary vascular resistance after wood smoke inhalation and to demonstrate whether the prostanoids, thromboxane B2 or 6-keto-prostaglandin F1 alpha, play a role in these vascular resistance changes. DESIGN: Prospective, randomized, controlled trial. SETTING: Laboratory at a university medical center. SUBJECTS: Five mongrel dogs. INTERVENTIONS: The isolated canine left lower lobe preparation was used to measure changes in the pressure drop across the pulmonary arteries, veins, and capillaries. The left lower lobe was surgically isolated and perfused by a pump primed with autologous blood. The arterial and venous occlusion technique and the vascular pressure-flow relationship were used to assess changes in pulmonary vascular resistance. After baseline measurements, the left lower lobe was exposed to wood smoke for 2.5 mins and measurements were repeated. MEASUREMENTS AND MAIN RESULTS: Smoke exposure caused an immediate (5 mins post-inhalation) increase in the total pressure gradient across the lobe (baseline = 9.8 +/- 0.5 torr [1.3 +/- 0.06 kPa]); smoke inhalation = 24.3 +/- 3.9 torr [3.24 +/- 0.5 kPa]; p < .05). Total pressure drop was partitioned longitudinally into pressure drops across arteries, veins, and the middle vessels. The increase in total pressure drop was associated with a moderate increase in the pressure drop across the middle vessels (baseline = 1.1 +/- 0.2 torr [0.14 +/- 0.02 kPa]; smoke inhalation = 5.2 +/- 1.1 torr [0.69 +/- 0.14 kPa]; p < .05); a large increase in the pressure drop across the veins (baseline = 4.8 +/- 1.3 torr [0.64 +/- 0.17 kPa]; smoke inhalation = 20.7 +/- 3.4 torr [2.7 +/- 0.45 kPa]; p < .05), and no significant change in the pressure drop across the arteries (baseline = 3.7 +/- 0.4 torr [0.49 +/- 0.05 kPa]; smoke inhalation = 4.8 +/- 0.5 torr [0.64 +/- 0.06 kPa]; p = NS). Increases in the pressure drop across the middle and venous vessels were transient and no longer significantly different from baseline 15 mins after smoke inhalation. Similarly, analysis of the pulmonary artery/blood flow data demonstrated that the mean slope and pressure intercept were greater than baseline only at 5 mins postsmoke inhalation (p < .05). Thromboxane B2 did not significantly change from baseline values after smoke exposure and prostaglandin F1 alpha demonstrated a slight but significant decrease 30 mins postsmoke. Pulmonary edema was measured gravimetrically (wet/dry weight ratio) and smoke significantly increased lung water in the left lower lobe (wet/dry weight ratio = 6.55 +/- 0.4) as compared with the normal left upper lobe (wet/dry weight ratio = 4.97 +/- 0.2). CONCLUSIONS: We conclude that smoke causes an intense but transient increase in the pressure drop across the venous segment that may accelerate the formation of pulmonary edema, which is not mediated by changes in thromboxane B2 or prostaglandin F1 alpha.

Analysis of Variance↗

PubMed1990

Surfactant displacement by plasma lavage results in pulmonary edema.

The effects of plasma lavage on pulmonary surfactant and edema were studied in anesthetized open-chest dogs. After instrumentation and baseline measurements, citrated autologous plasma (1.5 ml/kg) was lavaged into each lung (n = 6). A control group was administered the same dose of buffered saline solution (n = 4). Hemodynamic parameters, blood gases, and lung compliance were monitored for 2 hours after lavage. Surfactant function, assessed with a Wilhelmy balance, and extravascular lung water measured gravimetrically were determined at the end of the experiment. Immediately after plasma lavage, a nonsegmental atelectasis was observed on the lung surface. Little change was seen in vascular pressures or cardiac output in either group, whereas partial pressure of oxygen in arterial blood and static compliance fell significantly after plasma lavage. Two hours after lavage, a large amount of white foam was observed in both large and small airways in the plasma group. Plasma but not saline lavage elevated surface tension minimum in pulmonary tissue. Airway foam contained functional surfactant; addition of plasma to normal surfactant on the Wilhelmy balance did not inhibit surfactant function. Extravascular lung water was increased in the plasma compared with the saline lavage group. These data suggest that plasma usurps surfactant from the alveolar hypophase rather than inhibiting its ability to lower surface tension. Because little change was measured in vascular pressures and it is unlikely that autologous plasma increases vascular permeability, we conclude that the edema was the result of high alveolar surface tension.

Animals↗

PubMed1983

Effect of positive end-expiratory pressure on lung water in pulmonary edema caused by increased membrane permeability.

Pulmonary edema caused by increased membrane permeability was created in dogs by alloxan and infusion of saline solution. Pulmonary extravascular water volume was measured gravimetrically using the supernatant hemoglobin concentration to estimate red cell mass in the calculation of residual pulmonary blood volume. Three groups were studied for two hours: a control group, a group given alloxan and mechanical ventilation without positive end-expiratory pressure (PEEP), and a group given alloxan and mechanical ventilation with 10 cm H2O of PEEP. After two hours, alloxan caused moderately severe pulmonary edema in the two experimental groups, but PEEP had no effect on the accumulation of pulmonary extravascular water volume. No sustained differences in pulmonary or systemic hemodynamics were present throughout two hours of pulmonary edema. The pulmonary shunt was increased in the group without PEEP but was similar in the control group and the group with PEEP. No significant changes in alveolar dead space were noted among the three groups.

Alloxan↗

PubMed1981

Portal hemodynamics in dogs during mechanical ventilation with positive end-expiratory pressure.

The effects of 10 and 15 cm H2O positive end-expiratory pressure (PEEP) on portal vein flow (PVF), superior mesenteric artery flow (SMAF), and cardiac output (CO) were studied. Portal vein pressure (PVP) and the intraluminal pressure gradient between portal vein and intrathoracic inferior vena cava (PVP-CVP) were also measured. PEEP caused a fall in CO and SMAF, and the fall in each was proportionately the same. PVF also fell and a linear correlation between PVF and SMAF during PEEP was observed. Although PVP increased relative to atmosphere, no increase in transmural PVP and no change in PVP-CVP gradient was observed with PEEP. These data suggest that the major effect of PEEP on portal hemodynamics is a reduction in portal flow secondary to the reduction of arterial inflow into the gut. These hemodynamic changes do not appear to be the result of an increase in resistance to protal flow at the liver but rather the result of PEEP reducing cardiac output.

Animals↗