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M A Grosso

Publications and source records attributed to M A Grosso.

At least 19 recordsLinked to original sources
PubMed1992

Neutrophils contribute to TNF induced myocardial tolerance to ischaemia.

Sublethal endotoxin (ETX) pretreatment of rats induces protection from cardiac ischaemia-reperfusion injury. This protective state is associated with increased endogenous myocardial catalase activity. Since tumour necrosis factor (TNF) is one mediator of ETX effects, we hypothesized that (TNF) pretreatment of the rat (30 micrograms/kg ip) 36 h prior to cardiac ischaemia-reperfusion could induce myocardial protection. We found that TNF administration increased both myocardial tolerance to ischaemia reperfusion injury (modified Langendorff, buffer perfusion, global, normothermic ischaemia) and myocardial catalase activity at 36 h. Moreover, we found that 6 h after TNF administration, myocardial hydrogen peroxide (H2O2, assessed by aminotriazole-H2O2 inactivation of catalase) and myocardial neutrophil accumulation (assessed by histology) were both increased. When neutrophil function was inhibited either by neutrophil depletion (vinblastine) or by ibuprofen treatments of the rat before TNF, the protection previously apparent at 36 h was blocked. We conclude that TNF can induce myocardial resistance to ischaemia reperfusion injury. This protection is related to prior tissue neutrophil accumulation and concomitant increases in H2O2 levels.

Animals↗
PubMed1992

Release of von Willebrand factor antigen (vWF:Ag) and eicosanoids during acute injury to the isolated rat lung.

It has been suggested that the von Willebrand factor antigen (vWF:Ag) may be a clinical marker for pulmonary endothelial cell injury. An ELISA was developed for the measurement of rat vWF:Ag. Rat lungs were isolated and perfused with a recirculating, blood-free, physiologic salt solution. Circulating levels of vWF:Ag and the eicosanoids thromboxane B2 (TXB2) and prostaglandin 6-keto F1-alpha (6-keto PGF1 alpha) were measured before and after different forms of insult. The addition of phospholipase C (PLC) or hydrogen peroxide (H2O2) to the perfusate caused lung damage as manifested by pulmonary artery pressure increase and pulmonary edema. This was paralleled by significant release of vWF:Ag, TXB2, and 6-keto PGF1 alpha. Increased hydrostatic pressure caused pulmonary edema without vWF:Ag and eicosanoid release. The addition of vasopressin to the perfusate caused vWF:Ag release but no lung injury and no release of eicosanoids. It is concluded that in the rat model, vWF:Ag release is a nonspecific marker for lung injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Cardiac 5'-nucleotidase activity increases with age and inversely relates to recovery from ischemia.

The metabolic basis for the enhanced tolerance of immature hearts to ischemia remains to be elucidated. Loss of high-energy phosphate nucleotides occurs during ischemia/reperfusion in mature (adult) hearts through the breakdown of adenosine triphosphate, diphosphate, and monophosphate (nondiffusible) to adenosine (freely diffusible). However, previous work has shown that after ischemia nondiffusible nucleotides are better retained by immature (neonatal) hearts than by mature hearts. The enzyme responsible for the conversion of adenosine monophosphate to adenosine is 5'-nucleotidase. We therefore hypothesized lower activity of this enzyme in neonatal than in adult myocardium. The purposes of this study were (1) to document 5'-nucleotidase activities in neonatal and adult rabbit myocardium and (2) to correlate differences of 5'-nucleotidase activity with functional recovery from ischemia. Neonatal (5- to 10-day-old) and adult (4- to 6-month-old) rabbit hearts were isolated and perfused (retrograde Langendorff). A left ventricular balloon measured functional parameters. Hearts were subjected to 20 minutes of global 37 degrees C ischemia and 10 minutes of reperfusion followed by freeze clamping. Tissue homogenates were assayed for 5'-nucleotidase by the linked formation of nicotinamide-adenine dinucleotide at 340 nm (Arkesteijn method). Postischemic recovery of developed pressure was 86% +/- 3% in neonates (n = 5) versus 38% +/- 3% in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). 5'-Nucleotidase activity was 4400 +/- 1208 nmol/min/gm in neonates (n = 5) versus 13,938 +/- 830 nmol/min/gm in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). We conclude that (1) 5'-nucleotidase activity is 68% lower in neonatal than in adult myocardium and (2) functional recovery after ischemia inversely relates to 5'-nucleotidase activity.

5'-Nucleotidase↗
PubMed1991

Oxygen metabolite effects on creatine kinase and cardiac energetics after reperfusion.

Noninvasive 31P nuclear magnetic resonance measurements indicate that during the initial reperfusion phase myocardial tissue contents of phosphocreatine (PCr) recover rapidly, while ATP levels remain low and recover slowly. There is also a burst of H2O2 during the first 10 min of reperfusion, as indicated by the in vivo inactivation of catalase that occurs only when H2O2, and the inactivator 3-aminotriazole (AMT), are simultaneously present. Neither H2O2 production nor CK inactivation was discernable after ischemia alone. In excitable tissue the PCr and ATP pools are equilibrated by the enzyme creatine kinase (CK), but myocardial CK activity is decreased by 20% after reperfusion, though not by simple washout. Extrapolating from the well-known air sensitivity of CK, we find that limited exposure in vitro to small concentrations of H2O2 can markedly diminish CK activity. We postulate that failure of certain CK isoenzymes at energy-using termini may decouple the relative rates of PCr production and ATP regeneration and hence cause elevated PCr-to-ATP ratios. The assumptions of 1) CK equilibrium during the reperfusion period to calculate free ADP levels and 2) cardiac recovery deduced from the elevation of PCr levels may require reexamination.

Adenosine Triphosphate↗
PubMed1990

Induction of endogenous tissue antioxidant enzyme activity attenuates myocardial reperfusion injury.

Efforts to reduce reperfusion injury have focused on exogenous therapies; however, endogenous attenuation of reperfusion injury can be induced by a single sublethal dose of endotoxin (ETX) prior to ischemia. The purposes of this study were to investigate (i) the early neutrophil-endothelial (PMN-EC) adherence, (ii) the associated myocardial oxidant stress, (iii) the relationship of oxidant stress to antioxidant enzyme activity, and (iv) the correlation of increased antioxidant enzyme activity to myocardial recovery following ischemia/reperfusion (I-R) injury at 36 hr. Rats were administered a sublethal dose (2% of LD50) of endotoxin (500 micrograms/kg, ip, Salmonella typhimurium). At 6 hr, myocardial neutrophil accumulation (histology), hydrogen peroxide (H2O2) levels, and myocardial tissue glutathione (glutathione and oxidized glutathione) levels were determined. At 24 hr myocardial tissue glutathione levels and catalase (CAT) activity were assayed. At 36 hr, myocardial tissue superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase, and glucose-6-phosphate dehydrogenase (G-6-PD) were assayed. At 36 hr, hearts were subjected to a standard (20 min, global, 37 degrees C) ischemic insult followed by reperfusion. At 40 min of reperfusion, ventricular function was assessed (ventricular balloon; ventricular developed pressure +dP/dt, and -dP/dt).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Interleukin 1 pretreatment decreases ischemia/reperfusion injury.

Hearts isolated from rats treated 36 hr before with interleukin 1 (IL-1) had increased glucose-6-phosphate dehydrogenase (G6PD) activity and decreased hydrogen peroxide levels and injury after global ischemia (I, 20 min)/reperfusion (R, 40 min) compared with hearts from untreated rats. Hearts isolated from rats treated 6 hr earlier with IL-1 also had increased polymorphonuclear leukocytes (PMN), H2O2 levels, and oxidized glutathione (GSSG) contents compared with hearts from untreated rats. Depletion of circulating blood PMN by prior treatment with vinblastine prevented both early (from treatment 6 hr before study) IL-1-induced increases in myocardial PMN accumulation, H2O2 levels, and GSSG contents and late (from treatment 36 hr before study) increases in myocardial G6PD activity and protection against I/R. Our results indicate that IL-1 pretreatment causes an early (6 hr after IL-1 treatment) myocardial PMN accumulation and most likely an H2O2-dependent oxidative stress, which contributes to late (36 hr after IL-1 treatment) increases in myocardial G6PD activity and decreases in I/R injury.

6-Aminonicotinamide↗
PubMed1990

Hypertonic saline and dextran: impact on cardiac function in the isolated rat heart.

Hypertonic saline with dextran (HSD) has been recently introduced for prehospital resuscitation of hemorrhagic shock, and is currently undergoing clinical investigation. To determine the effect of clinically relevant amounts of hypertonic saline (7.5% NaCl) and/or 6% dextran 70 on non-ischemic and post-ischemic hearts, we infused rat hearts (Langendorff, 20 minutes global ischemia, 37 degrees, 40 minutes' reperfusion) with: 1) 0.9% NaCl (control); 2) 7.5% NaCl/dextran; 3) 7.5% NaCl; or 4) dextran. We found that 7.5% NaCl alone or with dextran depressed ventricular function (developed pressure, DP; contractility, +dP/dt; and relaxation rate, -dP/dt) in non-ischemic hearts. In contrast, equimolar (2,400 mOsm) sucrose increased myocardial contractility (+dP/dt) of non-ischemic hearts. Coronary flow was unchanged by the addition of 7.5% NaCl, dextran, or sucrose. Treatment of ischemic hearts with 7.5% NaCl/dextran, dextran alone, or sucrose improved recovery of ventricular function compared to 0.9% or 7.5% NaCl. Furthermore, dextran (but not sucrose) with or without 7.5% NaCl reduced myocardial hydrogen peroxide (H2O2) levels during ischemia and reperfusion. We conclude that when given in clinically relevant amounts in the isolated rat heart: 1) 7.5% NaCl directly depresses myocardial function; 2) 7.5% NaCl alone does not improve post-ischemic ventricular function; 3) 7.5% NaCl with dextran or dextran alone improves post-ischemic ventricular function in part by reducing myocardial H2O2; and 4) sucrose equimolar to 7.5% HSD increases ventricular function in non-ischemic and post-ischemic hearts. This investigation suggests that the post-shock benefit of HSD is unrelated to direct myocardial effects of saline but is due in part to toxic oxygen metabolite scavenging by dextran.

Animals↗
PubMed1990

Reversible lung neutrophil accumulation can cause lung injury by elastase-mediated mechanisms.

Neutrophils have been implicated in multiple models of end-organ injury. The purposes of this study were to determine whether (1) a sublethal septic insult promotes lung neutrophil accumulation, (2) this pulmonary neutrophil accumulation is reversible, (3) these accumulated neutrophils can be activated to injure lung, and (4) this pulmonary neutrophil accumulation obligates lung injury. Rats were administered low-dose endotoxin, 500 micrograms/kg, intraperitoneally, and at 6 or 12 hours, lungs were harvested and assayed for myeloperoxidase, a marker of neutrophil accumulation, and iodine 125-labeled albumin uptake, a marker of lung injury. A second set of rats were administered low-dose endotoxin and at 6 or 12 hours were given a neutrophil activator formyl-norleucyl-leucyl-phenylalanine (FNLP) 250 micrograms/kg, intravenously. At 8 or 14 hours, lungs were harvested and assayed for 125I-labeled albumin uptake. A third set of rats were administered low-dose endotoxin, and at 5 1/2 hours 30 minutes before FNLP administration, they were given a neutrophil elastase inhibitor, methyoxysuccinyl-L-alanine-L-alanine-L-proline-L-valine-chlorometh yl ketone, 2.5 mg/kg, intraperitoneally. At 6 hours rats were given FNLP, and at 8 hours lungs were harvested and assayed for 125I-labeled albumin uptake. The following results were obtained: (1) low-dose endotoxin caused a transient increase (p less than 0.05) in lung neutrophil accumulation at 6 hours, which was resolved by 12 hours; (2) lung 125I-labeled albumin uptake was unchanged both 6 and 12 hours after isolated low-dose endotoxin administration; (3) neutrophil activation increased (p less than 0.05) lung 125I-labeled albumin uptake when imposed 6 but not 12 hours after low-dose endotoxin administration; and (4) elastase inhibition decreased (p less than 0.05) the lung 125I-labeled albumin uptake promoted by endotoxin and FNLP. We conclude that sublethal endotoxemia causes a reversible lung neutrophil accumulation and that this lung neutrophil accumulation does not obligate lung injury; but activation of these accumulated neutrophils can promote lung injury, and this neutrophil-associated lung injury is mediated in part by neutrophil elastase.

Amino Acid Chloromethyl Ketones↗
PubMed1989

Albumin decreases hydrogen peroxide and reperfusion injury in isolated rat hearts.

Perfusion with human serum albumin decreased myocardial hydrogen peroxide (H2O2) levels (as assessed by inactivation of myocardial catalase activities following aminotriazole pretreatment) and increased myocardial ventricular developed pressures (DP), contractility (+dP/dt) but not relaxation rate (-dP/dt) in isolated crystalloid perfused rat hearts subjected to normothermic global ischemia (20 min) and then reperfusion (40 min). Albumin also decreased H2O2 concentrations in vitro. The findings support the possibility that albumin may act as a protective O2 metabolite scavenger in vivo.

Animals↗
PubMed1989

Xanthine oxidase-derived oxygen radicals induce pulmonary edema via direct endothelial cell injury.

Pulmonary hypoperfusion/ischemia-reperfusion (I/R) may initiate ARDS (nonhydrostatic pulmonary edema). Endothelial damage via xanthine oxidase (XO)-derived oxygen radicals (O2*) may mediate I/R injury. We previously documented Factor VIII antigen (F8) as a marker for endothelial injury. The purpose of this study was to (1) document I/R-induced nonhydrostatic pulmonary edema, (2) identify whether XO or O2* mediates nonhydrostatic edema, and (3) identify the site of injury (? endothelium). Rat lungs were isolated, ventilated, and perfused (100 min, control, or 40 min at 37 degrees C, I (static vent.), + 60 min, R). Effluent was analyzed for F8 release (ELISA: data relative to control). Tungsten-fed rats had negligible lung XO vs rats fed standard diet (3.6 vs 34.5 mU/g, (P less than 0.05). Catalase (CAT) 50 micrograms/ml) was added to perfusate prior to R. Sectioned lungs were fluorescein anti-F8 photographed (IF) and qualitatively assessed. (Table: see text). We conclude that (1) pulmonary hypoperfusion (I/R) leads to nonhydrostatic pulmonary edema, and (2) the edema results in part from XO-generated O2* directed at the capillary endothelium.

Animals↗
PubMed1989

Endotoxin pretreatment increases endogenous myocardial catalase activity and decreases ischemia-reperfusion injury of isolated rat hearts.

Hearts isolated from rats pretreated 24 hr before with endotoxin had increased myocardial catalase activity, but the same superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities, as hearts from untreated rats. Hearts isolated from rats pretreated with endotoxin 24 hr before also had increased myocardial function (decreased injury) after ischemia and reperfusion (Langendorff apparatus, 37 degrees C), as assessed by measurement of ventricular developed pressure, contractility (+dP/dt), and relaxation rate (-dP/dt), compared to control hearts. In contrast, hearts isolated from rats pretreated with endotoxin 1 hr before isolation or hearts perfused with endotoxin did not have increased catalase activity or decreased injury following ischemia and reperfusion. Aminotriazole pretreatment prevented increases in myocardial catalase activity and myocardial function after ischemia-reperfusion in hearts from endotoxin-pretreated rats. The results suggest that endotoxin pretreatment decreases cardiac ischemia-reperfusion injury and that increases in endogenous myocardial catalase activity contribute to protection.

Amitrole↗
PubMed1989

Erythrocytes decrease myocardial hydrogen peroxide levels and reperfusion injury.

Reperfusion with untreated, carbon monoxide-treated, or glutaraldehyde-fixed human erythrocytes (RBC) increased ventricular function and decreased myocardial hydrogen peroxide (H2O2) levels [assessed by H2O2-dependent aminotriazole (AMT) inactivation of myocardial catalase activities] of ischemic, isolated rat hearts. In contrast, reperfusion with RBC that lacked catalase (AMT treated) and/or glutathione (N-ethylmaleimide treated) did not increase ventricular function or decrease myocardial H2O2 levels as much as reperfusion with untreated RBC. By comparison, reperfusion with superoxide dismutase-depleted (diethyldithiocarbamate-treated) or anion channel-inhibited (diisothiocyanodisulfonic acid stilbene-treated) RBC increased ventricular function and decreased myocardial H2O2 levels the same as untreated RBC. The results suggest that catalase and/or glutathione in intact RBC can decrease endogenously generated H2O2 and related reperfusion injury in ischemic, isolated perfused hearts.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1989

Cytokines, sepsis and the surgeon.

Trauma and infection cause complex neuroendocrine responses. Afferent nervous stimuli, stimuli from the central nervous system, local wound factors and endocrine changes characterized by increases in stress hormones are some of these responses. Molecular biology has launched us into an age in which the categorization of these neuroendocrine changes will be broadened to include the profound effects of previously unidentified molecules. TNF and IL-1 are two protein hormones of the cytokine family. TNF causes hemorrhagic necrosis of solid tumors, mediates the lethal effects of endotoxemia and induces immune metabolic and intercellular changes. IL-1 is a mediator of inflammation and the acute phase response. The diversity of actions of TNF and IL-1 appear to be results of their multiple forms (alpha and beta) and their abilities to act both as membrane-associated and free proteins, to act locally (paracrine) as well as systemically, to act synergistically and to be involved in complex webs of self-promotion and amplification. On the basis of these diverse capabilities, they are prime candidates to be mediators of common surgical disease.

Animals↗
PubMed1989

Optimal hypothermic preservation of arrested myocardium in isolated perfused rabbit hearts: a 31P NMR study.

The purpose of this study was to (1) relate myocardial high-energy phosphate stores to functional recovery after ischemia and reperfusion, (2) assess the bioenergetics and functional influence of clinically relevant myocardial hypothermia, and (3) examine tissue pH as an independent indicator of postischemic recovery of function. Rabbit hearts were perfused via a modified Langendorff technique, monitored for developed pressure (DP) and left ventricular end-diastolic pressure (LVEDP) via an isovolumic left ventricular balloon catheter, and placed in a Brucker NMR magnet (4.7 tesla) to measure phosphocreatine (PCr), adenosine triphosphate (ATP), and pH. Hearts underwent 1 hour of global ischemia at 7 degrees, 17 degrees, 27 degrees and 37 degrees C initiated by one dose of K+ cardioplegia followed by 30 minutes of reperfusion. After reperfusion, DP (expressed as a percentage of preischemic control) and LVEDP (mm Hg) in 7 degrees and 17 degrees C hearts were no different (96 + 5% vs 97 +/- 3%; 5 +/- 2 mm Hg vs 6 +/- 2 mm Hg; p = NS), but were better (p less than 0.01) than 27 degree hearts (72 +/- 6%, 17 +/- 6 mm Hg) and 37 degree hearts (31 +/- 7%, 60 +/- 6 mm Hg). PCr was severely depleted in all groups. ATP was 90 +/- 7% and 87 +/- 5% of preischemic control in the 7 degree and 17 degree hearts, which was significantly better than the 68 +/- 3% and 21 +/- 3% in the 27 degree and 37 degree groups (p less than 0.01). The pH at end ischemia was 6.83, 6.89, 6.54, and 5.86 for the 7 degree, 17 degree, 27 degree, and 37 degree hearts, respectively (7 degrees vs 27 degrees or 37 degrees, p less than 0.01; 17 degrees vs 27 degrees or 37 degrees, p less than 0.01). Linear regression of DP on end-ischemic ATP (EIATP) and end-ischemic pH revealed: DP = 0.96 (EIATP) + 20 (r = 0.92) and DP = 60 (pH) -317 (r = 0.86). We conclude that (1) end-ischemic ATP predicts recovery of ventricular function, and, furthermore, there appears a threshold ATP concentration (80% of control) below which full recovery of function will not occur; (2) end-ischemic pH predicts recovery of ventricular function; (3) 7 degrees C hypothermic ischemia does not cause a clinically significant cold injury; and (4) in a single-dose crystalloid cardioplegia model, end-ischemic pH is linearly related to recovery of function (r = 0.86).

Adenosine Triphosphate↗
PubMed1989

The coincidence of myocardial reperfusion injury and hydrogen peroxide production in the isolated rat heart.

To investigate the specific nature and timing of oxygen (O2) metabolite reperfusion injury, we used a rat-heart model (Langendorff's solution, 37 degrees C) and hydrogen peroxide (H2O2)-dependent aminotriazole inactivation of catalase as a measure of myocardial H2O2 before, during, and after ischemia. We found that after ischemia (20 minutes, global, 37 degrees C), ventricular functional loss--as assessed by measurement of developed pressure (DP), +dp/dt, and -dp/dt with a ventricular balloon--occurred at 10 minutes of reperfusion and that myocardial H2O2 production was maximal by this time. Furthermore, H2O2 production did not occur during ischemia, and inhibition of xanthine oxidase by tungsten feeding or infusing a permeable O2 metabolite scavenger during reperfusion (dimethylthiourea) prevented ventricular functional loss. We conclude that (1) reperfusion injury is in part mediated by toxic oxygen metabolites, (2) H2O2 is the central O2 metabolite responsible for reperfusion injury, and (3) the timing of H2O2 production coincides with the timing of ventricular functional loss.

Amitrole↗
PubMed1988

Hydrogen peroxide mediates reperfusion injury in the isolated rat heart.

In an isolated, normothermic rat heart model (Langendorff, 37 degrees C), dimethylthiourea (DMTU) infusion only during reperfusion reduced both injury and measurable hydrogen peroxide (H2O2) concentrations after global ischemia. Cardiac function was assessed by measurement of ventricular developed pressure (DP). H2O2 was assessed using H2O2 dependent aminotriazole inactivation of myocardial catalase. Depletion of xanthine oxidase by two methods (tungsten or allopurinol inhibition) also improved recovery of function and H2O2 production. The results indicate that XO derived H2O2 contributes to myocardial reperfusion injury.

Amitrole↗