PubMed Health⌕ Search

Biomedical subjects

G Nieman

Publications and source records attributed to G Nieman.

9 recordsLinked to original sources
PubMed2001

Evidence of increased matrix metalloproteinase-9 concentration in patients following cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response, which can result in acute lung injury known as "postperfusion syndrome." Neutrophil activation with concomitant serine protease release has been implicated in the pathogenesis of "postperfusion syndrome." Increased plasma levels of neutrophil elastase (NE) have been demonstrated in patients undergoing CPB, and it is well documented that both NE and matrix metalloproteinase-9 (MMP-9) have a synergistic role in pulmonary injury. We, therefore, hypothesized that plasma levels of MMP-9 would be elevated in patients after CPB. Human plasma was obtained after informed consent from eight patients undergoing CPB. Plasma was collected at the start of CPB, 5 minutes after the initiation of CPB, and at the termination of CPB (156 +/- 17 min). All samples were analyzed by both standard enzyme-linked immunosorbent assay (ELISA) and gelatin zymography for MMP-9 (free and total enzyme) concentration. Data were expressed as means +/-SE and assessed by analysis of variance (ANOVA). Plasma MMP-9 concentration was significantly increased at the end of CPB (191 +/- 30.4 ng/mL; p <.05) as compared to both the start of CPB (28.3 +/- 13.2 ng/mL) and 5 minutes after the initiation of CPB (44.3 +/- 15.4 ng/mL). Patients undergoing CPB show an increase in serum MMP-9 levels. Prior studies utilizing an animal model of "postperfusion syndrome" have shown that inhibition of MMP-9 and NE prevented pulmonary injury following CPB. The results of the current study suggest that such an approach may also have merit in the clinical setting of cardiopulmonary bypass.

Adult↗
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↗
PubMed1999

Systemic inflammation induced by cardiopulmonary bypass: a review of pathogenesis and treatment.

The acute respiratory distress syndrome (ARDS) is a severe alteration in lung structure and function that develops secondary to a traumatic stimulus. When ARDS develops following cardiopulmonary bypass (CPB) it is know as postpump syndrome (PPS). ARDS can be caused by a single massive insult ("hit"); however, sequential minor insults ("hits") are more common clinically. The concept of multiple sequential insults causing ARDS has been termed the "two-hit" model of ARDS. The purpose of this article is to summarize our studies testing the hypothesis that PPS is caused by multiple sequential insults. To confirm our hypothesis, we developed a porcine model of "two-hit" PPS. Our model was composed of sequential benign insults, with CPB as the "first hit" and low dose of endotoxin as the "second-hit." It is our hypothesis that the mechanism of PPS is CPB-induced priming of polymorphonuclear leukocytes (PMNs) ("first-hit") with subsequent PMN activation by a second insult ("second-hit") such as endotoxin. Our model confirms this clinically relevant postulate, and we provide strategies to disrupt the inflammatory cascade leading to PPS.

Cardiopulmonary Bypass↗
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↗
PubMed1990

Distribution of extravascular lung water after acute smoke inhalation.

Anesthetized dogs with thoracotomy were injected with Evans blue dye and were exposed acutely (5 min) to wood smoke inhalation. Thin slices from freeze-dried samples were photographed and assessed for periarterial and perivenous cuff area and for blue coloration with a score of 0 to 5. Bloodless extravascular lung water (EVLW) was also measured. The smoke-exposed animals were compared with controls and with animals exposed to alloxan or to high-pressure-induced pulmonary edema. EVLW at 2 h after smoke (6.46 +/- 0.80) was above control value (4.30 +/- 0.63) but not different from the alloxan (6.13 +/- 0.70) or high-pressure (6.88 +/- 1.30) groups. Despite the similarity in EVLW in the edematous lungs, there were marked differences in the intensity of blue color and size of cuffing around arteries and veins: the smoke, alloxan, and high-pressure groups had blue color scores of 1.0 +/- 0.1, 2.9 +/- 0.3, and 0.3 +/- 0.1, respectively. These scores indicated a large increase in microvascular permeability to proteins in the alloxan group, a moderate increase in the smoke group, and minimal change in the high-pressure group. The perivascular cuff area was largest in the alloxan group and moderate in the smoke and high-pressure groups. The cuff area was higher for arteries than for veins in all groups except the 0.5-h smoke group. We conclude that smoke inhalation causes a moderate increase in permeability and EVLW compared with alloxan. The extravascular lung water accumulates preferentially around the arteries, but the size of the perivascular cuff is not similar for all causes of pulmonary edema.

Alloxan↗
PubMed1990

High alveolar surface tension increases clearance of technetium 99m diethylenetriamine-pentaacetic acid.

The effect of high alveolar surface tension on alveolar epithelial permeability was studied in anesthetized closed-chest mongrel dogs. Alveolar surface tension was elevated by displacement of pulmonary surfactant from the alveolar hypophase by the aerosolized detergent dioctyl sodium sulfosuccinate (OT). After measurement of baseline hemodynamics, arterial blood gases, and airway pressure, the dogs were separated into groups: Group I inhaled a 1% solution of OT (15 mg/kg) in a vehicle of equal parts saline and ethanol; group II inhaled the same volume of vehicle without OT. The pulmonary clearance of technetium 99m diethylenetriamine-pentaacetic acid (99mTc-DTPA) (half-time in minutes) was studied immediately after aerosol (OT and vehicle) delivery and compared with that of historical control values. No change was seen in arterial blood gases and airway pressure after vehicle inhalation, whereas OT caused a marked fall in arterial oxygen tension and increase in airway pressure. Vehicle inhalation effected only a slight increase in DTPA clearance, whereas OT significantly reduced half-time over control and group II. These data suggest that high alveolar surface tension increases alveolar epithelial permeability.

Aerosols↗
PubMed1984

High-frequency jet ventilation versus conventional ventilation after surfactant displacement in dogs.

High-frequency jet ventilation (HFJV) was compared with conventional ventilation (CV) after surfactant displacement with diocytyl sodium sulfosuccinate (OT) via ultrasonic nebulization. After aerosol delivery, dogs were separated into 3 groups and followed for 2 h. Ventilator settings were not changed in group I (CV) and group II (HFJV) after OT delivery. In group III, drive pressure was increased to 40 psi. Adequacy of oxygenation varied directly with peak inspiratory pressure (PIP) rather than airway pressure (Paw) in both HFJV and CV. In all groups, immediately after OT administration PaO2 decreased and there was a slight increase in Paw; PIP was significantly elevated only in groups I and III. Two hours later, PaO2 had returned to baseline in groups I and III, but had not improved significantly in group II. Paw remained the same in all groups. These data demonstrate that in noncompliant lungs, oxygenation is not improved unless a high PIP is used to establish the critical opening pressures needed to rerecruit alveoli. In this noncompliant lung model, HFJV was not effective at low Paw values, and thus offered no apparent advantage over CV.

Animals↗
PubMedDate not supplied

Effect of acute smoke inhalation on angiotensin converting enzyme, plasminogen activator, and angiotensin-II in the dog.

Smoke inhalation injuries in humans are associated with many uncontrolled variables which impact on the lung and make the cause of the pulmonary response difficult to assess. In this report, an established model of smoke inhalation injury in the dog was used to study the early responses of tissue and serum angiotensin-converting enzyme (ACE), tissue plasminogen activator (PLA), and plasma angiotensin II. Animals were exposed to smoke from burning sawdust and kerosene for five minutes. The hemodynamic and pulmonary mechanical responses were typical with a rise in pulmonary artery pressure, pulmonary vascular resistance, and venous admixture (shunt fraction) while dynamic compliance fell. Within five minutes of smoke exposure, lung ACE declined without any change in serum ACE. Lung PLA dropped one hour after injury. Plasma angiotensin II increased within 30 minutes without evidence for systemic hypertension. These early enzymatic changes substantiate the presence of pulmonary endothelial damage known to occur in this form of chemical injury. These changes may condition the lung's physiologic response to the injury and to additional stresses which are multiple when smoke inhalation occurs in conjunction with a cutaneous burn.

Angiotensin II↗