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Biomedical subjects

I Mayers

Publications and source records attributed to I Mayers.

At least 37 records · Page 2Linked to original sources
PubMed1994

Lazaroid pretreatment preserves gas exchange in endotoxin-treated dogs.

PURPOSE: The lazaroids are a new class of potent free-radical scavengers. We tested whether U-74389G, a lazaroid, could attenuate some of the adverse cardiopulmonary effects of sepsis. METHODS: Dogs were randomized to receive either 10 mg/kg U-74389G (n = 10), or a saline control (n = 11). After baseline measurements of hemodynamics and gas exchange, they were then randomized to receive either 0.2 mg/kg endotoxin or a saline infusion. Measurements of hemodynamics and gas exchange were repeated. The study was concluded 70 minutes after endotoxin infusion and the lungs were then removed for histologic evaluation. RESULTS: In endotoxin-treated control animals, PO2 decreased (278 +/- 123 mm Hg to 67 +/- 13 mm Hg, P < .05) and intrapulmonary shunt increased (12.9% +/- 1.1% to 28.2% +/- 11.4%, P < .05) after endotoxin. Pretreatment with U-74389G attenuated the decrease in PO2 (476 +/- 61 mm Hg to 226 +/- 143) and the increase in intrapulmonary shunt (12.6% +/- 6.1% to 14.3% +/- 6.8%) observed after endotoxin. The extent of lung injury and systemic hemodynamics were similar between control or U-74389G-treated dogs. CONCLUSIONS: A free-radical-scavenger can attenuate the gas exchange defect commonly associated with endotoxin but it does not improve the derangement of systemic hemodynamics.

Analysis of Variance↗
PubMed1994

Pulmonary vascular effects of endotoxin in canine lobes pretreated with dapsone.

Endotoxin results in a granulocyte mediated loss of hypoxic pulmonary vasoconstriction (HPV). Dapsone blocks the granulocyte respiratory burst and might, therefore, preserve HPV following endotoxin. Isolated-perfused canine lobes (n = 6) were pretreated with 18 mg/kg dapsone (dapsone group), and compared to six lobes which did not receive dapsone (control group). Total pulmonary vascular resistance (Rtot) and arterial, middle (Rm), and venous segmental resistances were calculated by a vascular occlusion technique. We then administered endotoxin (2 mg/kg) and repeated measurements at 5, 30, and 90 min. The increase in Rm during 3% O2 compared to 35% O2 ventilation was used to define the presence of HPV. In the control group, following endotoxin, values of Rm did not change (P > 0.05) during 3% O2 ventilation (0.011 +/- 0.006 cm H2O/ml/min) compared with 35% O2 ventilation (0.014 +/- 0.005 cm H2O/ml/min). In the dapsone group, following endotoxin, values of Rm increased (P < 0.05) during 3% O2 ventilation (0.06 +/- 0.026 cm H2O/ml/min) compared with 35% O2 ventilation (0.03 +/- 0.015 cm H2O/ml/min). Changes in 6-keto PGF1 alpha or thromboxane B2 do not explain these observations. We conclude that in this experimental preparation, pretreatment with dapsone prevents the loss of HPV associated with endotoxin.

Animals↗
PubMed1994

Neutrophil-mediated acute lung injury after extracorporeal perfusion.

A pulmonary injury of varying severity occurs routinely after cardiopulmonary bypass. We studied the pulmonary complications of partial cardiopulmonary bypass in four groups of dogs to better define the injury and to evaluate the efficacy of two interventions (addition of a leukocyte filter or cyclooxygenase inhibition) on preservation of systemic oxygenation. All animals received a standard anesthetic (pentobarbital, morphine, and vecuronium) and, after sternotomy, three groups of animals received 3 hours of partial cardiopulmonary bypass. The animals were randomized to receive partial bypass alone (n = 6), indomethacin and bypass (n = 5), or a leukocyte filter and bypass (n = 5). A fourth group (n = 5) did not receive bypass and served as a time control. We measured blood gases and also obtained histologic samples to assess the degree of lung injury. We found that bypass alone caused a significant reduction (p < 0.05) in arterial oxygen tension 1 hour after the conclusion of bypass (175 +/- 53 mm Hg) compared with prebypass values (357 +/- 41 mm Hg). Pretreatment with indomethacin ameliorated the decrease in arterial oxygen tension from prebypass to postbypass values (477 +/- 50 mm Hg versus 339 +/- 57 mm Hg, respectively). Similarly use of a leukocyte filter reduced the decline in arterial oxygen tension from prebypass to postbypass values (440 +/- 71 mm Hg versus 311 +/- 73 mm Hg, respectively). We believe that indomethacin ameliorates the decline in systemic oxygenation associated with bypass by augmentation of hypoxic pulmonary vasoconstriction and that the leukocyte filter acted to reduce pulmonary edema and thereby minimized intrapulmonary shunt.

Animals↗
PubMed1993

Positive end-expiratory pressure increases the right-to-left shunt in mechanically ventilated patients with patent foramen ovale.

OBJECTIVE: To determine the effect of the presence of a patent foramen ovale on the right-to-left shunt in patients with respiratory failure who receive positive end-expiratory pressure (PEEP). DESIGN: Convenience sample with randomized application of PEEP. SETTING: General intensive care unit of a university teaching hospital. PATIENTS: A total of 46 mechanically ventilated patients with respiratory failure requiring an inspired oxygen concentration of at least 50% and a PEEP of at least 5 cm of H2O. INTERVENTION: Randomized application of PEEP (0 and 10 cm of H2O). MEASUREMENTS: A patent foramen ovale was detected by saline contrast transesophageal echocardiography. The alveolar-to-arterial oxygen difference and the right-to-left shunt were calculated from arterial and venous blood gas sampling. RESULTS: In patients without a patent foramen ovale (n = 39), the alveolar-to-arterial oxygen difference and the shunt fraction decreased (-50 mm Hg [95% CI, -21 to -67] and -0.05 [CI, -0.03 to -0.07], respectively) after adding PEEP (10 cm of H2O). In patients with a patent foramen ovale (n = 7), minimal changes were noted in the alveolar-to-arterial oxygen difference (4 mm Hg, P > 0.2), but the shunt fraction increased (0.05, CI, 0 to 0.09). Adding PEEP (10 cm of H2O) increased the shunt fraction in 6 of 7 (86%) patients with a patent foramen ovale, whereas the shunt increased in only 7 of 39 (18%) patients without a patent foramen ovale (P < 0.007). CONCLUSIONS: A patent foramen ovale was found in 7 of 46 patients (15%; CI, 6% to 29%) with acute respiratory failure. This condition is a common cause of lack of improvement in oxygenation with the addition of PEEP in the mechanically ventilated patient. In patients with a patent foramen ovale, the right-to-left shunt is usually increased by using PEEP.

Acute Disease↗
PubMed1993

NG-monomethyl-L-arginine does not restore loss of hypoxic pulmonary vasoconstriction induced by TNF-alpha.

Tumor necrosis factor-alpha (TNF-alpha) causes systemic hypotension, pulmonary vasodilation, and loss of hypoxic pulmonary vasoconstriction. NG-monomethyl-L-arginine (L-NMMA) inhibits nitric oxide (NO) production and prevents some systemic manifestations of TNF-alpha. We tested using an isolated perfused canine lobe whether NO also mediates the pulmonary vascular effects of TNF-alpha. Total resistance (RT) was measured during control and hypoxic ventilation over a 90-min period in six control lobes, five lobes treated with TNF-alpha (250 micrograms), six lobes treated with L-NMMA (200 mg), and five lobes treated with L-NMMA (200 mg) + TNF-alpha (250 micrograms). In the control lobes RT increased (P < 0.02) from 0.0474 +/- 0.0105 to 0.0677 +/- 0.0133 cmH2O.ml-1 x min during normoxic and hypoxic ventilation, respectively. RT decreased (P < 0.05) from a baseline of 0.0593 +/- 0.0133 to 0.0449 +/- 0.0176 cmH2O.ml-1 x min 30 min after TNF-alpha administration and did not further change during hypoxic ventilation (0.0475 +/- 0.0107 cmH2O.ml-1 x min). L-NMMA pretreatment did not prevent the TNF-alpha-induced loss of hypoxic pulmonary vasoconstriction, with values of RT unchanged from normoxic (0.0541 +/- 0.0067 cmH2O.ml-1 x min) to hypoxic (0.0545 +/- 0.0078 cmH2O.ml-1.min) ventilation (P > 0.10) in the L-NMMA + TNF-alpha group after TNF-alpha administration. We conclude that NO is not the mediator responsible for the acute pulmonary vascular effects of TNF-alpha.

Animals↗
PubMed1993

The lack of effect of routine magnesium administration on respiratory function in mechanically ventilated patients.

STUDY OBJECTIVE: We wished to determine if magnesium infusion would improve respiratory muscle function in long-term ventilated patients even in the absence of hypomagnesemia. DESIGN: Prospective study of mechanically ventilated patients using a double-blind crossover design. SETTING: A combined medical-surgical ICU of a university teaching hospital. PATIENTS: Twenty-one separate admissions to the ICU in 20 patients were studied. Patients who were selected had been intubated and mechanically ventilated for at least 6 days with the admitting diagnosis of respiratory failure. INTERVENTIONS: Twelve patients received 6 g MgSO4 intravenous (i.v.) infusion over 16 h on day 1 followed by placebo infusion on day 2. Nine patients received placebo on day 1 followed by MgSO4 (6 g i.v.) on day 2. MEASUREMENTS AND MAIN RESULTS: We measured vital capacity (VC), maximal inspiratory pressure (Pmax) and maximal expiratory pressure (Pemax) in all patients. There were no significant differences in Pimax (37 +/- 14 vs 42 +/- 20 cm H2O), Pemax (59 +/- 32 vs 61 +/- 38 cm H2O), and VC (850 +/- 460 vs 960 +/- 490 ml) comparing values before and after magnesium infusion. We could not find a subgroup of patients with a marked improvement in Pimax or Pemax. CONCLUSIONS: In patients requiring mechanical ventilation for respiratory failure, magnesium infusion is not associated with increased respiratory muscle strength. Although a trial of MgSO4 administration may be considered for patients with difficulty weaning from mechanical ventilation, it is unlikely to result in clinical improvement.

Adult↗
PubMed1992

Changes in PETCO2 and pulmonary blood flow after bronchial occlusion in dogs.

The use of PETCO2 in detecting accidental bronchial intubation was investigated. The PETCO2 was measured in six mongrel dogs after occluding the left mainstem bronchus in three conditions; pentobarbital anaesthesia, 0.8% halothane insufflation together with pentobarbital anaesthesia, and simultaneous left pulmonary artery and bronchial airway occlusion with intravenous pentobarbital anaesthesia. An external flow probe measured left pulmonary artery blood flow. The PETCO2 decreased after bronchial occlusion during pentobarbital (35 +/- 3 vs 30 +/- 5 mmHg) and halothane-pentobarbital (30 +/- 6 vs 25 +/- 6 mmHg) conditions (P less than 0.05). However, within three minutes of bronchial occlusion, the values of PETCO2 had returned to their pre-occlusion values. After five minutes of bronchial occlusion pulmonary artery blood flow in the non-ventilated lung decreased (P less than 0.05) during pentobarbital (770 +/- 533 ml.min-1 vs 575 +/- 306 ml.min-1) and halothane-pentobarbital (495 +/- 127 ml.min-1 vs 387 +/- 178 ml.min-1) conditions. Simultaneous bronchial and pulmonary artery occlusion prevented any changes in PETCO2. It was concluded that accidental one-lung ventilation results in small and transient decreases in PETCO2. A redistribution of blood flow from the non-ventilated to ventilated lung occurs which restores PETCO2 to the original values observed with two-lung ventilation.

Airway Obstruction↗
PubMed1992

Insufflated halothane increases venous admixture less than nitroprusside in canine atelectasis.

Although it generally is agreed that halothane is a pulmonary vasodilator, its effect on venous admixture and hypoxic pulmonary vasoconstriction are more controversial. The effects of 2.4% halothane on pulmonary vascular resistance and venous admixture were investigated in an isolated canine lobe made atelectatic. Halothane was administered by three different methods: insufflation, addition to the pulmonary artery blood through a bubble deoxygenator, or a combination of both techniques. Pulmonary vascular resistance was divided into arterial, venous, and middle segmental resistance by a vascular occlusion technique. Middle resistance increased with 3% O2 ventilation (0.0238 +/- 0.0092 cmH2O.ml-1.min-1) or after production of atelectasis (0.0225 +/- 0.0074 cmH2O.ml-1.min-1), compared to control ventilation in the nonatelectatic lung 0.01 +/- 0.0067 cmH2O.ml-1.min-1). Halothane by any delivery method variably decreased middle resistance, with increasing potency from addition of halothane through the bubble deoxygenator (0.0118 +/- 0.0047 cmH2O.ml-1.min-1) to halothane insufflation (0.0072 +/- 0.0058 cmH2O.ml-1.min-1), and finally to a combination of both techniques (0.0026 +/- 0.0041 cmH2O.ml-1.min-1). In contrast to vascular resistance, venous admixture in the atelectatic (8 +/- 5%) and nonatelectatic lobes (7 +/- 4%) was increased with halothane insufflation (11 +/- 4%), addition of halothane through the bubble deoxygenator (26 +/- 16%), and a combination of both techniques (22 +/- 13%). Compared to intravenous nitroprusside (26 +/- 12%), halothane insufflation was less potent in increasing venous admixture when total pulmonary vascular resistances were of similar magnitude (0.0526 +/- 0.0112 and 0.0484 +/- 0.0088 cmH2O.ml-1.min-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prostacyclin (not nitroprusside) preserves venous admixture in the injured canine lung.

OBJECTIVE: To compare the effects of a prostaglandin vasodilator (prostaglandin I2 [PGI2]) with that of sodium nitroprusside in the isolated lung during 3% and 35% oxygen ventilation. BACKGROUND AND METHODS: Pulmonary vascular resistance was divided into arterial, middle, and venous segmental resistances. Left lower lobes were injured in a patchy (atelectasis) or diffuse (oleic acid-induced edema) manner. RESULTS: Nitroprusside diminished, but PGI2 ablated, the usual increase in middle segment resistance observed during 3% oxygen ventilation in atelectatic lobes. In the oleic acid-treated lobes, both nitroprusside and PGI2 ablated the increase in middle segment resistance during 3% oxygen ventilation. During nitroprusside administration, as pulmonary vascular resistance decreased, venous admixture proportionately increased, but this correlation was lost during PGI2 administration. CONCLUSIONS: We hypothesize that exogenous PGI2 dilates the vessels most constricted by hypoxia but to a lesser degree than does nitroprusside. Therefore, increases in venous admixture may be reduced during PGI2 administration, compared with nitroprusside administration.

Animals↗
PubMed1992

Interactions of endotoxin, prostaglandins, and circulating cells upon pulmonary vascular resistance.

We studied the effects of endotoxin on total pulmonary vascular resistance (PVR) and hypoxic pulmonary vasoconstriction (HPV) in 24 isolated canine lung lobes. Group 1 lobes were perfused with whole blood; group 2 lobes with granulocyte/platelet depleted blood; group 3 lobes with whole blood and ibuprofen (12.5 mg/kg); group 4 lobes with granulocyte/platelet depleted blood and ibuprofen (12.5 mg/kg). All groups were otherwise treated in a similar manner and all received endotoxin (1 mg/kg) after baseline periods of normoxic and hypoxic ventilation. We found endotoxin increased PVR by 18% in group 1 and by 41% in group 2. Endotoxin administration inhibited HPV in group 1 but did not inhibit HPV in group 2. Ibuprofen administration prevented the increase in PVR and the loss of HPV caused by endotoxin. We conclude that endotoxin administration causes release of a lung-derived vasoconstrictor, but this is obscured by concomitant release of a granulocyte/platelet associated vasodilator. Our data also suggest that granulocytes or platelets may modulate baseline PVR by producing a nonprostaglandin vasodilator.

Animals↗
PubMed1991

Cardiopulmonary effects of an anterior mediastinal mass in dogs anesthetized with halothane.

The authors evaluated the cardiac effects of an anterior mediastinal mass to better understand the acute cardiovascular collapse that has been associated with anesthesia and positive-pressure ventilation. An 800-ml-capacity intravenous bag was placed within the anterior mediastinum of 12 dogs to simulate a mediastinal mass. After mediastinal mass inflation, the authors measured cardiac index (CI) during periods of spontaneous ventilation (SV), SV with added continuous positive airway pressure (CPAP), intermittent positive-pressure ventilation (IPPV), and continuous positive-pressure ventilation (CPPV). Similar mediastinal mass volumes resulted in similar decreases in CI during SV (169 +/- 51 to 105 +/- 10 ml.kg-1.min-1); CPAP (175 +/- 48 to 122 +/- 34 ml.kg-1.min-1); IPPV (151 +/- 15 to 93 +/- 24 ml.kg-1.min-1); and CPPV (183 +/- 56 to 117 +/- 46 ml.kg-1.min-1). The authors also found, by linear regression, that the relationship between CI and mass volume was similar during both SV and IPPV. In six dogs, transesophageal echocardiography (TEE) was used to measure ventricular short axis dimensions. The authors found that mass inflation caused left ventricular end-diastolic dimension to decrease significantly by 6 +/- 2 mm and 4 +/- 1 mm during SV or IPPV, respectively, and right ventricle dimensions to increase by 2 +/- 1 mm and 3 +/- 1 mm during SV or IPPV, respectively. The changes in chamber dimensions were similar with either SV or IPPV. These results suggest that the decrease in CI associated with a mediastinal mass results from an increase in right ventricular afterload, causing right ventricular enlargement. Subsequently, there is impingement on the left ventricle volume because of interventricular interdependence.

Anesthesia, Inhalation↗
PubMed1991

Interactions of tumor necrosis factor and granulocytes with pulmonary vascular resistance.

We studied the effects of endotoxin and tumor necrosis factor (TNF-alpha) on hypoxic pulmonary vasoconstriction (HPV) in 12 isolated perfused canine lung lobes. Group 1 lobes were perfused with whole blood, and group 2 lobes were perfused with granulocyte-depleted blood. All lobes were sequentially ventilated with control (35% O2) and hypoxic (3% O2) gas mixtures before and after receiving TNF-alpha. After TNF-alpha, group 2 lost HPV but group 1 retained HPV. After TNF-alpha, total pulmonary vascular resistance decreased in group 2 from 0.085 +/- 0.013 to 0.049 +/- 0.016 cmH2O.ml-1.min (P less than 0.05). We conclude that TNF-alpha acts as a pulmonary vascular vasodilator. In lobes perfused with whole blood, HPV is paradoxically preserved. We speculate that in the presence of cells rich in TNF-alpha receptors, i.e., granulocytes, the circulating levels of TNF-alpha are depressed and full expression of its vascular effects is blunted.

Animals↗
PubMed1991

Effects of halothane on hypoxic pulmonary vasoconstriction in canine atelectasis.

We studied the interactions of atelectasis and halothane on hypoxic pulmonary vasoconstriction using an isolated canine lobe. We divided pulmonary vascular resistance into arterial, venous, and middle segmental resistances by a vascular occlusion technique. We found that middle segmental resistance significantly increased (P less than 0.05) from 0.016 +/- 0.007 cm H2O.mL-1.min-1 during normoxic ventilation to 0.06 +/- 0.007 cm H2O.mL-1.min-1 during hypoxic ventilation. We then produced sublobar atelectasis by introducing 4.5-mm steel ball bearings into the lobar bronchus, which resulted in a significant increase (P less than 0.05) of middle segmental resistance to 0.046 +/- 0.014 cm H2O.mL-1.min-1 during normoxic ventilation and a further significant increase (P less than 0.05) to 0.084 +/- 0.02 cm H2O.mL-1.min-1 during hypoxic ventilation. Ventilation with 2.0% halothane but not 0.5% halothane prevented the increases in middle segmental resistance observed with either atelectasis or hypoxic ventilation. Values of arterial and venous segmental resistances were not similarly affected. We conclude that sublobar atelectasis increases pulmonary vascular resistance by stimulating hypoxic pulmonary vasoconstriction. Both halothane and hypoxia primarily act upon the middle vascular segment, but their effects are in opposite directions and, in the former instance, are concentration-dependent.

Analysis of Variance↗
PubMed1991

Relative roles of prostaglandins and leukotrienes in canine hypoxic pulmonary vasoconstriction.

We indirectly examined the role of prostaglandins and leukotrienes in modulation of hypoxic pulmonary vasoconstriction. We used a cyclo-oxygenase inhibitor (indomethacin) and a lipoxygenase inhibitor (diethylcarbamazine) in an in-situ canine lung lobe preparation. We measured total resistance in two control groups ventilated with either 35% O2 or 3% O2 (groups CC and HC respectively). Two additional groups treated with indomethacin (groups CI and HI), and two groups treated with the combination of indomethacin and diethylcarbamazine (groups CID and HID), were also ventilated with either 35% O2 or 3% O2 respectively. Total resistance was significantly greater in hypoxic groups compared with their respective control oxygen groups. Total resistance was greatest in group HI (0.288 +/- 0.103 cm H2O.ml-1 min-1), intermediate in group HID (0.153 +/- 0.016 cm H2O.ml-1 min-1) and lowest in group HC (0.066 +/- 0.017 cm H2O.ml-1 min-1). We concluded that cyclo-oxygenase blockade augments hypoxic pulmonary vasoconstriction by decreasing production of a vasodilating prostaglandin. Hypoxia also increases production of a vasoconstricting leukotriene in the presence of cyclo-oxygenase blockade with indomethacin.

Analysis of Variance↗
PubMed1990

Halothane inhibits hypoxic pulmonary vasoconstriction in the presence of cyclooxygenase blockade.

Using an isolated lung the effects of halothane on hypoxic pulmonary vasoconstriction (HPV) were studied in the presence of cyclooxygenase blockade. The pulmonary vasculature can be divided into arterial, middle and venous segment resistances. Analysis of the vascular pressure-flow relationship further separates resistance into a flow dependent resistance (1/slope) and a zero-flow pressure intercept (PCRIT). We ventilated six lobes with control (35 per cent O2) and hypoxic (three per cent O2) gas mixtures with the addition of either 0, 0.5, 1.0, or 2.0 per cent halothane. We found that after addition of indomethacin (5 mg.kg-1), ventilation with three per cent O2 increased total resistance by 87 per cent over baseline with the increase primarily in the middle vascular segment. During normoxic ventilation PCRIT was 7.9 cm H2O and this increased significantly with hypoxia to 11.5 cm H2O). Only 2.0 per cent halothane blocked the increases in middle segment resistance and in PCRIT. We conclude that following cyclooxygenase blockade, halothane inhibits HPV by acting on middle segment vessels.

Animals↗
PubMed1990

Vasodilators do not abolish pulmonary vascular critical closing pressure.

To examine whether the critical closing pressure (Pcrit) of the pulmonary vasculature is dependent upon vasomotor tone, we measured Pcrit in six dog lobes before and after the administration of vasodilators. We evaluated the pressure-flow (P-Q) relationship in zone 2 flow conditions in situ perfused dog lobe (control period). We calculated Pcrit as the mean extrapolated zero-flow pressure intercepts for the P-Q relationship. We also used arterial and venous occlusions under zone 3 conditions to partition pulmonary vascular resistance into arterial, middle and venous segment resistances. We then repeated all measurements following administration of papaverine (150 micrograms/ml) and sodium nitroprusside (200 micrograms/min) into the venous reservoir (vasodilator period). Resistance in all three vascular segments was significantly reduced during vasodilator conditions. Pcrit decreased from 3.68 +/- 0.76 cm H2O to 2.53 +/- 0.92 cm H2O during control and vasodilator periods respectively (P less than 0.05). The slopes of the P-Q relationships were similar during both conditions. Our data support a model in which vasomotor tone normally sets Pcrit but in which the pulmonary vasculature can exhibit the phenomenon of critical closure even with vasomotor tone pharmacologically ablated.

Animals↗