Enrico Camporesi - Academia.edu (original) (raw)

Papers by Enrico Camporesi

European Journal of Applied Physiology, 2001

Treatment with hyperbaric O2 (HBO) ameliorates ischemia-reperfusion (I/R) injury. Since tumor nec... more Treatment with hyperbaric O2 (HBO) ameliorates ischemia-reperfusion (I/R) injury. Since tumor necrosis factor-α (TNF-α) plays an important role in I/R injury, we hypothesized that the effect of HBO in I/R injury may be due to its ability to inhibit TNF-α production. In this study, one group of rats received HBO during 60 min of ischemia (HBO group, n=9), while control rats endured the same procedure but did not receive HBO (non-HBO, n=9). A group of sham-operated control rats (SHAM, n=6) underwent laparotomy without occlusion of the artery and HBO treatment. Intestinal I/R led to an increase in serum TNF-α concentration to [mean (SEM)] 165 (32) pg/ml (P<0.01 vs SHAM rats). HBO attenuated this increase [34 (9) pg/ml; P<0.05 vs non-HBO group]. Intestinal I/R also resulted in a marked increase in lung myeloperoxidase content [0.62 (0.04) U/g vs 0.17 (0.02) U/g of SHAM rats, P<0.01]. HBO suppressed this increase [0.40 (0.04) U/g, P<0.05 vs non-HBO rats]. HBO ameliorated the injury to the intestine and lung. The number of neutrophils sequestered in the lung was reduced in HBO rats compared to non-HBO rats [6.4 (0.9) neutrophils/per oil field and 10.9 (2) neutrophils/per oil field, respectively; P<0.05]. These findings demonstrate that HBO inhibits TNF-α production during intestinal I/R, and this reduced TNF-α production may be attributed to the beneficial effects of HBO.

Anesthesia and Analgesia, 1994

Methylnaltrexone (MNTX) is a quaternary derivative of naltrexone. It does not cross the blood-bra... more Methylnaltrexone (MNTX) is a quaternary derivative of naltrexone. It does not cross the blood-brain barrier and, thus, it reverses peripherally mediated effects of morphine without blocking its centrally located analgesic effects. The effects of MNTX on morphine-induced depression of hypoxic ventilatory response are unknown. We evaluated the efficacy of MNTX, compared with naloxone, in reversing this effect. On three sessions separated by a week, 10 healthy male volunteers received morphine, 0.125 mg/kg, as a bolus at 20 min after completing a control hypoxic ventilatory challenge. At 60 min, naloxone, 5 micrograms/kg, MNTX, 0.3 mg/kg, or placebo was administered in a randomized double-blind order. Four isocapnic hypoxic ventilatory challenges were conducted: 0 min (control), 40 min (postmorphine), and 80 and 120 min (postreversal) and the hypoxic respiratory responses were recorded. Morphine administration was associated with a significant depression in hypoxic responses: The slope of the response (L/min/Spo2) and the predicted ventilation at 80% O2 saturation (VE80) (L/min) decreased significantly in the three sessions (P &amp;amp;amp;amp;amp;lt; 0.05). Naloxone injection reversed the respiratory depression at 80 min (85% of the control value of the slope and 89% of VE80), whereas MNTX and placebo did not. At 120 min, the slope (69%) and VE80 (80%) after naloxone administration were not significantly different from control. MNTX slope (69%) was not statistically different from the control, whereas VE80 (70%) was still depressed (P &amp;amp;amp;amp;amp;lt; 0.05). Placebo slope and VE80, at 120 min, remained lower than the control (P &amp;amp;amp;amp;amp;lt; 0.05). These data show that MNTX is not as effective as naloxone for reversal of morphine-mediated depression of respiration during acute hypoxia.

Pflugers Archiv-european Journal of Physiology, 1996

The effect of endogenous nitric oxide (NO) on the pulmonary hypoxic vasoconstriction was studied ... more The effect of endogenous nitric oxide (NO) on the pulmonary hypoxic vasoconstriction was studied in isolated and blood perfused rat lungs. By applying the occlusion technique we partitioned the total pulmonary vascular resistance (PVR) into four segments: (1) large arteries (R a), (2) small arteries (R a′), (3) small veins (R v′), and (4) large veins (R v). The resistances were evaluated under baseline (BL) conditions and during; hypoxic vasoconstriction and acetylcholine (Ach) which was injected during hypoxic vasoconstriction. After recovery from hypoxia and Ach, N ω-nitro-L-arginine (L-NA) was added to the reservoir and the responses to hypoxia and Ach were reevaluated. Before L-NA, hypoxia caused significant increase in the resistances of all segments (P < 0.05), with the largest being in R a and R a′. Ach-induced relaxation during hypoxia occurred in R a, R a′ and R v′ (P < 0.05). L-NA did not change the basal tone of the pulmonary vasculature significantly. However, after L-NA, hypoxic vasoconstriction was markedly enhanced in R a, R a′, and R v′ (P < 0.01) compared with the hypoxic response before L-NA. Ach-induced relaxation was abolished after L-NA. We conclude that, in rat lungs, inhibition of NO production during hypoxia enhances the response in the small arteries and veins as well as in the large arteries. The results suggest that hypoxic vasoconstriction in the large pulmonary arteries and small vessels is attenuated by NO release.

Clinical and Experimental Pharmacology and Physiology, 2003

1. We investigated the effect of hyperbaric oxygenation (HBO 2 ) pretreatment on the production o... more 1. We investigated the effect of hyperbaric oxygenation (HBO 2 ) pretreatment on the production of exhaled nitric oxide (ENO) and the expression of lung inducible nitric oxide synthase (iNOS) by Escherichia coli lipopolysaccharide (LPS)induced shock in an experimental rat model.

Systemic hypotension during sepsis is thought to be due to nitric oxide (NO) overproduction, but ... more Systemic hypotension during sepsis is thought to be due to nitric oxide (NO) overproduction, but it may also be due to acidosis. We evaluated in healthy rats the consequences of acid infusion on NO and blood pressure. Sprague-Dawley rats were anesthetized, and ventilated with room air. The animals were randomized into four groups. Group 1 (C, n = 10) received only normal saline at rates comparable to the other groups. Group 2 (A1, n = 10) received hydrochloric acid at 0.162 mmol in the first 15 to 30 min, followed by a continuous infusion of 0.058 mmol/h for 5 h. Group 3 (AG+A1, n = 6) was pretreated with aminoguanidine (AG, 50 mg/kg), and HCl was infused as above. Group 4 (A2, n = 7) received HCl at twice the rate used in A1. Nitric oxide concentration in the exhaled gas (ENO), blood gases, and mean arterial pressure were measured every 30 min. Acid infusion in A1 caused the pH to fall gradually from 7.43 +/- 0. 01 to 7.13 +/- 0.05. This moderate decrease in pH was associated with a marked increase in ENO (1.6 +/- 0.3 to 114.2 +/- 22.3 ppb), an increase in plasma nitrite/nitrate (17.3 +/- 3.7 to 35.2 +/- 4.3 microM), and a significant decrease in blood pressure (110.5 +/- 6.3 to 63.3 +/- 15.0 mm Hg). Furthermore, acidosis caused lung inflammation, as suggested by the increase in lung myeloperoxidase activity (282.2 +/- 24.7 to 679.3 +/- 57.3 U/min/g) and lung injury score (1.7 +/- 0.2 to 3.5 +/- 0.6). Acidosis after AG pretreatment was associated with a similar change in pH, but the increase in ENO, nitrite/nitrate, and systemic hypotension were prevented. Furthermore, lung injury was attenuated by AG, as suggested by a lower myeloperoxidase activity, though lung injury score was not altered. In this model, moderate acidosis causes increases in NO, hypotension, and lung inflammation. Lung inflammation and injury are due in part to acidosis and NO production. This is the first report to show a direct effect of chronic acidosis on NO production and lung injury. These results have profound implications on the role of acidosis on NO production and lung injury during sepsis.

Critical Care Medicine, 1998

To evaluate the effect of treatment with a combination of nitric oxide synthase inhibitors and in... more To evaluate the effect of treatment with a combination of nitric oxide synthase inhibitors and inhaled nitric oxide on systemic hypotension during sepsis. Prospective, randomized, controlled study on anesthetized animals. A cardiopulmonary research laboratory. Forty-seven male adult Sprague-Dawley rats. Animals were anesthetized, mechanically ventilated with room air, and randomized into six groups: a) the control group (C, n=6) received normal saline infusion; b) the endotoxin-treated group received 100 mg/kg i.v. of Escherichia coli lipopolysaccharide (LPS, n=9); c) the third group received LPS, and 1 hr later the animals were treated with 100 mg/kg i.v. Nw-nitro-L-arginine (LNA, n=9); d) the fourth group received LPS, and after 1 hr, the animals were treated with 100 mg/kg i.v. aminoguanidine (AG, n=9); e) the fifth group received LPS and 1 hr later was treated with LNA plus 1 ppm inhaled nitric oxide (LNA+NO, n=7); f) the sixth group received LPS and 1 hr later was treated with aminoguanidine plus inhaled NO (AG+NO, n=7). Inhaled NO was administered continuously until the end of the experiment. Systemic mean blood pressure (MAP) was monitored through a catheter in the carotid artery. Mean exhaled NO (ENO) was measured before LPS (T0) and every 30 mins thereafter for 5 hrs. Arterial blood gases and pH were measured every 30 mins for the first 2 hrs and then every hour. No attempt was made to regulate the animal body temperature. All the rats became equally hypothermic (28.9+/-1.2 degrees C [SEM]) at the end of the experiment. In the control group, blood pressure and pH remained stable for the duration of the experiment, however, ENO increased gradually from 1.3+/-0.7 to 17.6+/-3.1 ppb after 5 hrs (p< .05). In the LPS treated rats, MAP decreased in the first 30 mins and then remained stable for 5 hrs. The decrease in MAP was associated with a gradual increase in ENO, which was significant after 180 mins (58.9+/-16.6 ppb) and reached 95.3+/-27.5 ppb after 5 hrs (p< .05). LNA and AG prevented the increase in ENO after LPS to the level in the control group. AG caused a partial reversal of systemic hypotension, which lasted for the duration of the experiment. LNA reversed systemic hypotension almost completely but only transiently for 1 hr, and caused severe metabolic acidosis in all animals. The co-administration of NO with AG had no added benefits on MAP and pH. In contrast, NO inhalation increased the duration of the reversal in MAP after LNA, alleviated the degree of acidosis, and decreased the mortality rate (from 55% to 29%). In this animal model, LPS-induced hypotension was alleviated slightly and durably after AG, but only transiently after LNA. Furthermore, co-administration of NO with AG had no added benefits but alleviated the severity of metabolic acidosis and mortality after LNA. We conclude that nitric oxide synthase (NOS) inhibitors, given as a single large bolus in the early phase of sepsis, can exhibit some beneficial effects. Administration of inhaled NO with NOS inhibitors provided more benefits in some conditions and therefore may be a useful therapeutic combination in sepsis. NO production in sepsis does not seem to be a primary cause of systemic hypotension. Other factors are likely to have a major role.

Journal of Laboratory and Clinical Medicine, 2001

Journal of Surgical Research, 1997

Acute hemorrhage is associated with a variety of physiologic and metabolic alterations, including... more Acute hemorrhage is associated with a variety of physiologic and metabolic alterations, including vascular hyporeactivity and endothelial cell dysfunction. The lung is a major target organ during hemorrhagic shock. The effect of acute hemorrhage on NO production in the lung is not well described. In the present study we examined the effect of acute hemorrhage on exhaled NO (NOe), and studied how changes in blood volume and flow affect NOe. Anesthetized and mechanically ventilated rabbits were used. The effect of acute hemorrhage by slow exsanguination on NOe was examined using chemiluminescence. Because hemorrhagic shock is associated with decreased pulmonary blood flow, we established an isolated lung preparation perfused with autologous blood (Hct = 17.4%) and studied the effect of pulmonary flow rate on NOe independent of metabolic changes. In order to separate the effect of flow from the effect of changes in blood volume, we examined the effect of flow in isolated lungs perfused with a blood-free albumin solution (PAS). In the isolated lung, ventilation was similar to that used in the intact animal, and temperature, pH,pCO2, andPO2were kept normal. Prior to exsanguination, baseline NOe in the intact animal was 24 ± 3 ppb. At 5, 10, 15, and 20 min after initiating the hemorrhage, NOe rose to 31 ± 3, 51 ± 7, 94 ± 10, and 154 ± 16 ppb, respectively (P< 0.05). During baseline conditions in the blood-perfused isolated lungs (200 ml/min), NOe was 35 ± 3 ppb. When flow was decreased to 70 and 0 ml/min, NOe increased to 37 ± 3 and 56 ± 6 ppb, respectively (P< 0.001). During baseline conditions in the PAS-perfused lungs (70 ml/min), NOe was 94 ± 13 ppb and was unaffected by changes in flow. The perfusion pressure in the isolated lungs was in the normal range. Reduction in blood flow rate in the isolated lung was associated with less than twofold increase in NOe. This was attributed to reduction in red blood cell volume and not due to changes in blood flow rate. Reduction in flow in the intact animal during hemorrhage generated more than threefold increase in NOe, suggesting that neurohumoral mediators, in addition to changes in flow, play an important role in determining NOe in the intact condition. NOe began to rise immediately after exsanguination began, and therefore may be a useful early marker of acute hemorrhagic shock and hypovolemia. This information may be useful in the intensive care setting.

Anesthesia and Analgesia, 1995

Reversal of heparin anticoagulation with protamine may be associated with acute pulmonary vasocon... more Reversal of heparin anticoagulation with protamine may be associated with acute pulmonary vasoconstriction. The specific site of pulmonary vasoconstriction has not been determined. This study was designed to determine the site of protamine-induced pulmonary vasoconstriction and the role of nitric oxide (NO) after protamine injection. Pigs were anesthetized and instrumented with catheters for monitoring pulmonary arterial, systemic arterial, and central venous pressures. Pulmonary capillary pressure was estimated using the arterial occlusion concept, while left atrial pressure was estimated from the equilibrium wedge pressure. Hemodynamic measurements were made during baseline, before and after heparin (200 U/kg), at peak pressure response after protamine injection (2 mg/kg), and 10 and 30 min thereafter. In the control group, pulmonary vascular resistance (PVR) values during baseline and after heparin were identical (2.7 +/- 0.4 mm Hg.L-1.min-1). At peak protamine response (1-2 min) PVR increased to 8.0 +/- 1.6, but returned to baseline value after 10 min (2.8 +/- 0.3) and remained stable for 30 min (2.2 +/- 0.3). The increase in PVR after protamine was primarily due to an increase in venous resistance from 1.0 +/- 0.2 to 4.9 +/- 1.4 mm Hg.L-1.min-1, and a much smaller increase in arterial resistance from 1.7 +/- 0.3 to 3.4 +/- 0.6 mm Hg.L-1.min-1. A second group was treated with nitrow-L-arginine (LNA, 20 mg/kg) to inhibit NO release, and then heparin and protamine were administered as in the first group. Heparin had no effect on pressures, but protamine increased PVR by the same magnitude as in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal of Gynecologic Surgery, 1992

The objective of this work was to determine whether the volume of Hyskon administered during oper... more The objective of this work was to determine whether the volume of Hyskon administered during operative and diagnostic hysteroscopy could be correlated with Hyskon blood levels in order to predict a threshold for toxicity and to investigate the action ofHyskon on the intrinsic ...

Anesthesia and Analgesia, 1990

Pentamorphone is a novel, potent opiate with rapid onset and short duration of action that has be... more Pentamorphone is a novel, potent opiate with rapid onset and short duration of action that has been reported to produce analgesia with limited depression of ventilation. We quantified the effects of pentamorphone (0.08, 0.24, and 0.60 micrograms/kg, IV) on ventilatory responses to hypercapnia and hypoxia in 12 healthy volunteers. Normoxic hypercapnia and isocapnic hypoxia were induced through a rebreathing method. During each test we recorded ventilation (VE), end tidal carbon dioxide tension (PETCO2), and arterial oxygen saturation (SO2) using a pulse oximeter. Using linear regression analysis of the relationships between VE and PCO2 during hypercapnia and VE and SO2 during hypoxia, we determined the slope (slope CO2) and intercept (V55), both at PCO2 55 mm Hg, and the slope (slope O2) and intercept (V80) at SO2 80%. Pentamorphone produced dose-related reductions in the ventilatory responses to both hypercapnia and hypoxia. Maximal depression occurred 15 min after injection of pentamorphone with all doses; the highest dose (0.60 micrograms/kg) produced 48% and 53% reductions in slope CO2 and V55, and 42% and 22% reductions in slope O2 and V80, respectively, relative to parallel saline controls. The respiratory depressant actions of pentamorphone were short-lived, as all parameters returned to baseline levels within 45 min. Testing was continued for 180 min after injection, but no delayed ventilatory effects were detected, and minimal side effects were reported, even at the highest dose. The findings confirm previous reports that pentamorphone has limited ventilatory depressant effects in humans in doses that (in other studies) have been associated with clinically effective analgesia.

Anesthesia and Analgesia, 1989

We evaluated the analgesic properties of 14-beta-n-pentylaminomorphinone (pentamorphone), a new m... more We evaluated the analgesic properties of 14-beta-n-pentylaminomorphinone (pentamorphone), a new morphinan derivative, in 23 male volunteers divided into 6 groups who were given either placebo (1 per group) or 0.015, 0.03, 0.06, 0.12, 0.24, 0.48 microgram.kg-1 pentamorphone intravenously. Analgesia was evaluated by the maximal tolerance to a spring-loaded rod on the tibia and manubrium. Analgesic assessments and arterial blood samples were taken prior to and at set time intervals following drug administration. Pentamorphone produced a linear increase in pain tolerance with increasing dose as well as a dose-dependent depression of ventilation. Pentamorphone had no effect on blood pressure or heart rate in the doses used. Plasma histamine levels at 5 minutes were not elevated with any of the dosages. Pentamorphone appears to be an analgesic with clinically tolerable side effects in the range 0.12 to 0.24 microgram.kg-1 that merits further evaluation under clinical conditions.