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Biomedical subjects

M B Forman

Publications and source records attributed to M B Forman.

At least 19 recordsLinked to original sources
PubMed1992

Role of perfluorochemical emulsions in the treatment of myocardial reperfusion injury.

Perfluorochemicals are substances with small particle size, low viscosity, and high oxygen-carrying capacity. The role of one perfluorochemical preparation. Fluosol, an emulsion of two perfluorocarbons, a detergent Pluronic F-68 (poloxamer 188), and phospholipids on myocardial reperfusion injury was investigated in a closed-chest canine model of regional ischemia. Intracoronary and intravenous infusions of Fluosol in the perireperfusion period significantly reduced infarct size and improved ventricular function in animals that were examined for up to 2 weeks after reperfusion. Fluosol preserved endothelial structure and endothelium-dependent relaxation of large and small vessels. Fluosol reduced neutrophil plugging of capillaries and attenuated neutrophil infiltration into the reperfused bed. Ex vivo studies of neutrophil function demonstrated apparent suppression of chemotaxis and lysozyme degranulation in cells from animals that were treated with Fluosol. However, treatment of cells in vitro manifested enhanced superoxide anion production within 5 minutes of incubation even with low concentrations of Fluosol. This effect was found to be almost entirely attributable to the detergent, Pluronic F-68. The stimulation of neutrophils by Fluosol was found to result directly from phagocytosis and indirectly from activation of the complement cascade. These findings suggest that perfluorochemicals may provide a novel form of therapy to enhance myocardial salvage after successful reperfusion. The mechanism appears to be due to stimulation and subsequent "deactivation" of neutrophils peripherally, which thereby reduces their cytotoxic potential in the reperfused myocardium. The role of the oxygen-carrying ability of the perfluorocarbons in the reduction of reperfusion injury remains to be determined. In a pilot study in human beings, Fluosol that was used as adjunctive therapy with angioplasty has also been shown to improve regional ventricular function. Clinical trials with perfluorochemical emulsions appear warranted to determine the role of reperfusion injury in limiting myocardial salvage in patients who are undergoing pharmacologic or mechanical reperfusion.

Animals↗
PubMed1992

The effects of intravenous infusions of selective adenosine A1-receptor and A2-receptor agonists on myocardial reperfusion injury.

To determine the efficacy of very low doses of adenosine on myocardial reperfusion injury and whether its effect is receptor mediated, 78 rabbits underwent 30 minutes of left circumflex artery occlusion and 48 hours of reperfusion. Animals were randomly assigned to receive one of three doses of adenosine, cyclopentyladenosine (a selective A1-receptor agonist), or CGS 21680C (a selective A2-receptor agonist). The drugs were infused for 65 minutes beginning 5 minutes before reperfusion. A significant reduction in histologically determined infarct size was noted with all three doses of adenosine, intermediate and low doses of the A1-receptor agonist (cyclopentyladenosine), and high and intermediate doses of the A2-receptor agonist (CGS 21680C). Furthermore, all three adenosine receptor agonists afforded similar degrees of protection. Results of this study demonstrate that intravenous infusions of very low doses of adenosine significantly enhance myocardial salvage and this protection is receptor mediated. Furthermore, the administration of the A1-receptor agonist would be clinically appealing, since it would avoid the potential side effects associated with activation of A2 receptors.

Adenosine↗
PubMed1992

Pharmacologic perturbation of neutrophils by Fluosol results in a sustained reduction in infarct size in the canine model of reperfusion.

Previous studies have demonstrated that intravenous administration of large doses of Fluosol, a perfluorochemical preparation, reduced infarct size 24 h after reperfusion, an effect that was associated with reduced neutrophil infiltration. The effect of a clinically tolerable dose of Fluosol on infarct size after a prolonged period of reperfusion and its mechanism of action on neutrophils remain unknown. Twenty-one anesthesized closed chest dogs were subjected to 90 min of proximal left anterior descending coronary artery occlusion and 72 h of reperfusion. An additional five dogs that did not undergo regional myocardial ischemia were utilized to explore the mechanism of action of Fluosol on neutrophil function. In the infarct study, animals were randomized to receive either intravenous Fluosol (n = 10) or an equivalent volume of Ringer's lactate solution (control; n = 11) at 15 ml/kg body weight during the last 30 min of occlusion and for the 1st 30 min of reperfusion. Fluosol significantly reduced infarct size when expressed as percent area at risk 72 h after reperfusion (13.7 +/- 2.7% vs. 38.3 +/- 4.5%, respectively, p less than 0.001). This reduction was associated with significant improvement in regional wall motion (18.4 +/- 2.3% vs. 5.5 +/- 2%, p less than 0.001). Endocardial blood flow in the ischemic bed was significantly higher 3 h after reperfusion in Fluosol-treated dogs (0.63 +/- 0.08 vs. 0.34 +/- 0.07 ml/min per g, p = 0.01). Reduced capillary plugging by neutrophils with relative preservation of endothelial cell structure was observed in Fluosol-treated animals. Infusion of Fluosol produced a marked transient decrease in peripheral neutrophil and platelet counts in both ischemic and nonischemic dogs and was associated with a significant reduction in total hemolytic complement levels. Studies of neutrophil function ex vivo revealed a reduction in chemotaxis and lysozyme degranulation after infusion of Fluosol. In vitro experiments showed that Fluosol produced a rapid and sustained activation of neutrophils determined by superoxide anion production. These data demonstrate that low dose intravenous Fluosol produces a sustained reduction in infarct size in the canine model. The beneficial effect may be in part due to the suppression of various neutrophil functions in the reperfused myocardium subsequent to peripheral activation by Fluosol. Such interventions may offer a novel therapy to enhance myocardial salvage by sequestration of circulating neutrophils during the critical early reperfusion period.

Animals↗
PubMed1992

Phagocytic activation of human neutrophils by the detergent component of fluosol.

Fluosol (Alpha Therapeutic Corporation, Los Angeles, CA) an emulsion of perfluorocarbons with a high oxygen-carrying capacity, was approved as an adjunct to alleviate myocardial ischemia during coronary angioplasty. This drug also significantly enhances myocardial salvage presumably related to an action on the neutrophil. The mechanism by which fluosol and its individual components, including the detergent Pluronic F-68, affected neutrophil function was examined. During the incubation of neutrophils with fluosol, a rapid stimulation of superoxide anion production and degranulation which progressively increased over a 30-minute period was detected. Neutrophils incubated with only Pluronic F-68 produced similar amounts of superoxide anion. Cytochalasin B, an inhibitor of phagocytosis, significantly inhibited this superoxide anion generation. As shown previously, neutrophils incubated with fluosol for 30 minutes and then subsequently stimulated manifested a reduction in lysozyme release as compared with untreated cells. Results of an electron microscopic examination confirmed the cellular uptake of the fluosol within phagocytic vacuoles. Neutrophil viability determined by trypan blue was unaffected after fluosol treatment. These observations show that the fluosol emulsion, primarily through micelles formed by the detergent Pluronic F-68, activates human neutrophils by serving as a phagocytic stimulus, which produces a cell refractory to subsequent stimulation.

Blood Substitutes↗
PubMed1991

Role of adenosine in the treatment of myocardial stunning.

Adenosine is an endogenous nucleoside produced from the breakdown of adenosine triphosphate (ATP) that possesses a number of complex cellular and metabolic effects that could ameliorate postischemic contractile dysfunction (myocardial stunning). Potential mechanisms include the repletion of high-energy phosphate stores, reduced myocardial oxygen consumption, a decrease in oxygen-derived free radicals, restoration of calcium homeostasis, and an increase in regional myocardial blood flow. Experimental studies have shown that adenosine can reduce myocardial stunning with or without a concomitant increase in the total myocardial ATP stores. Adenosine may be a useful pharmacologic strategy in the prevention and treatment of ventricular dysfunction following episodes of regional or global ischemia, although further studies are needed to clarify the precise cellular mechanisms involved.

Adenosine↗
PubMed1991

Myocardial reperfusion injury in the canine model after 40 minutes of ischemia: effect of intracoronary adenosine.

To explore the contribution of reperfusion injury to final infarct size after a short duration of ischemia, closed-chest dogs underwent 40 minutes of proximal left anterior descending artery occlusion followed by 3 days of reperfusion. Animals randomly received intracoronary adenosine (n = 8) at 3.75 mg/min during the first hour of reperfusion or no therapy (control, n = 9). Infarct size was measured histologically. Regional ventricular function was determined with contrast ventriculography. The risk region was similar and collateral blood flow in the inner two thirds of the ischemic zone was markedly reduced in both groups (adenosine: 0.05 +/- 0.07 ml/min/gm; control: 0.02 +/- 0.07 ml/min/gm; p = NS). Infarct size as a percent of the area at risk was significantly reduced in the adenosine group (5.0 +/- 1.3% versus 13.5 +/- 3.2%; p = 0.03), associated with a trend for improved recovery of regional ventricular function. Relative endothelial preservation was seen in the adenosine group. These results suggest that reperfusion injury contributes to final myocardial cell necrosis in the closed-chest canine model subjected to 40 minutes of regional ischemia.

Adenosine↗
PubMed1991

Effect of intravenous adenosine on myocardial reperfusion injury in a model with low myocardial collateral blood flow.

The purpose of this study was to investigate the effects of various doses of adenosine administered intravenously on myocardial reperfusion injury in a model with poor collateral blood flow. New Zealand White rabbits were subjected to 30 minutes of occlusion of the obtuse marginal branch of the left circumflex artery and to 48 hours of reperfusion. Animals were randomized to receive intravenous adenosine in doses of 0.1 mg/min (low), 0.3 mg/min (intermediate), or 0.55 mg/min (high), or an equivalent volume of saline (control) commencing 5 minutes prior to reperfusion and continuing through the first 60 minutes of reperfusion. The area at risk was determined in vivo with Monastral blue dye and the area of necrosis was histologically examined with Masson's trichrome stain. Both the intermediate and high doses of adenosine, but not the low dose, significantly (p less than 0.05) decreased mean blood pressure. However, all three doses of adenosine produced a significant (p less than 0.05) and comparable decrease in infarct size expressed as a percent of area at risk (control, 52.0 +/- 4.6%; low, 35.3 +/- 4.1%; intermediate, 31.7 +/- 4.6%; high, 31.3 +/- 4.6%). Regional myocardial blood flow was significantly increased and coronary vascular resistance decreased by all three doses of adenosine in a subset of animals that did not undergo coronary occlusion (p less than 0.05). This study demonstrates that intravenous administration of nonhypotensive doses of adenosine given during the early reperfusion period attenuates reperfusion injury in a model with poor collateral blood flow.

Adenosine↗
PubMed1991

Demonstration of myocardial reperfusion injury in humans: results of a pilot study utilizing acute coronary angioplasty with perfluorochemical in anterior myocardial infarction.

Reperfusion may limit the amount of potentially salvageable myocardium through the introduction of cellular elements into previously ischemic but viable myocardium (reperfusion injury). It has been demonstrated that intracoronary infusion of a 20% intravascular perfluorochemical emulsion (Fluosol) significantly reduces infarct size and results in improved left ventricular function in the canine model. This pilot study was performed to explore the existence of myocardial reperfusion injury in humans. Utilizing Fluosol as a probe in conjunction with emergency coronary angioplasty, 26 patients presenting within 4 h with a first anterior myocardial infarction were randomized to emergency angioplasty or angioplasty followed by a 30-min intracoronary infusion of Fluosol at 40 ml/min. Global and regional ventricular function were assessed immediately and a mean of 12 days after successful angioplasty with contrast ventriculography. Infarct size was semiquantitated with thallium-201 single-photon emission computed tomography (SPECT) images before discharge. Twelve patients (six undergoing angioplasty alone, six treated with angioplasty and Fluosol) had an occluded infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] grade 0 to 1) at the time of emergency catheterization and were included in the final analysis. At 12 days after successful angioplasty, the improvement in regional ventricular function was greater in patients receiving adjunctive therapy with intracoronary Fluosol versus those undergoing angioplasty alone utilizing both the radial shortening and centerline method, respectively (23 +/- 3.1% vs. 8 +/- 2.3%, p less than 0.02; and -1.6 +/- 0.4 vs. -2.9 +/- 0.2 SD/chord, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1991

Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period.

Adenosine influences the function of several cell types thought to be involved in the pathogenesis of myocardial reperfusion injury. We have previously demonstrated that intracoronary administration of adenosine enhances myocardial salvage 24 hours after reperfusion. To determine if these beneficial effects could be obtained during a prolonged period of reperfusion using an intravenous route of administration, 22 closed-chest dogs were subjected to 90 minutes of proximal left anterior descending coronary artery occlusion and 72 hours of reperfusion. Animals randomly received either intravenous adenosine (0.15 mg/kg/min) or an equal volume of Ringer's lactate during the first 150 minutes of reperfusion. The area at risk was defined in vivo with Monastral blue, and infarct size was measured histologically with Mallory's trichrome stain. Serial global and regional ventricular function were determined with contrast ventriculography and analyzed using a computerized radial shortening method. Biopsies were obtained from the central ischemic zone to assess endothelial ultrastructure and capillary obstruction. No significant effects in heart rate or blood pressure were noted during adenosine infusion. Transmural collateral blood flow during ischemia was similar in the groups. Infarct size expressed as a percentage of the anatomical area at risk was significantly less in the adenosine-treated group (35.3 +/- 4.3% in controls versus 17.1 +/- 4.3% in treated animals, p less than 0.01). A progressive decrease in transmural blood flow was noted in control animals during reperfusion, resulting in a significant reduction at 3 hours compared with the preocclusion value (0.69 +/- 0.11 ml/min/g [at baseline versus 0.45 +/- 0.10 ml/min/g at 3 hours, p less than 0.05]). In contrast, flow in adenosine animals at 3 hours was similar to baseline values (0.91 +/- 0.15 ml/min/g at baseline versus 0.98 +/- 0.14 ml/min/g at 3 hours, p = NS) and was significantly higher (p less than 0.05) than the control group. Radial shortening in the ischemic zone was significantly improved at 3 (-2.6 +/- 2.8% in controls versus 11.6 +/- 3.3% in treated animals, p less than 0.01) and 72 hours (5.5 +/- 2.0% in controls versus 17.3 +/- 3.5% in treated animals, p less than 0.01) after reperfusion in treated animals. Electron microscopy showed reduced neutrophil and erythrocyte plugging of capillaries with relative preservation of endothelial cell structure in the adenosine group.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗
PubMed1990

Reduction of myocardial ischemia during percutaneous transluminal coronary angioplasty with oxygenated Fluosol.

The effects of perfusion of an oxygen-carrying perfluorochemical emulsion (Fluosol) in alleviating symptoms of myocardial ischemia during balloon occlusion were examined in a multicenter trial of 245 patients. Severe anginal pain occurred less frequently in patients receiving Fluosol perfusion (21%) than in those receiving routine angioplasty (34%) (p less than 0.05). ST-segment changes at balloon deflation in routine angioplasty patients were significantly greater than in patients who received oxygenated Fluosol perfusion (2.2 +/- 1.2 vs 1.7 +/- 0.9 mm; p less than 0.03). Profound regional wall dysfunction (-561 +/- 224 U) was observed in routine angioplasty patients by 2-dimensional echocardiography. Patients receiving oxygenated Fluosol perfusion, however, maintained near baseline levels of ventricular function (-61 +/- 335 U) during occlusion (p less than 0.0001). Mean global left ventricular ejection fraction was preserved at baseline levels during balloon inflation in patients perfused with oxygenated Fluosol but decreased significantly (p less than 0.001) during occlusion in routine angioplasty patients. A total of 26 complications (19 routine group; 7 perfusion group) was reported. Adverse responses to the perfusate were infrequent, occurring in 1.6 and 2.0% of patients after the test dose and during perfusion, respectively. Thus, transcatheter perfusion with an oxygen-carrying perfluorochemical emulsion is effective in alleviating myocardial ischemia during angioplasty and can be safely administered in this patient population.

Aged↗
PubMed1990

Long-term effects of excision of the mitral apparatus on global and regional ventricular function in humans.

To evaluate the long-term sequelae of mitral valve excision on global and regional wall motion, contrast left ventriculograms from 21 patients with suspected prosthetic mitral valve dysfunction performed 10.4 +/- 2.1 years after mitral valve replacement were analyzed by a computerized radial shortening method. Patients with significant coronary artery disease (greater than 30% stenosis in any vessel) were excluded. In 8 of the 21 patients in whom preoperative ventriculograms were available, regional wall motion was normal before valve replacement. Although average radial shortening (35.6 +/- 4.8% versus 35.3 +/- 3.8%, p = NS) and left ventricular ejection fraction (62.8 +/- 4.2% versus 57.9 +/- 2.8%, p = NS) were unchanged in the preoperative and postoperative studies of these eight patients, radial shortening in the vicinity of insertion of the posteromedial papillary muscle declined significantly (38.4 +/- 6.4% to 20.8 +/- 4.4%, p less than 0.04). Postoperative radial shortening for all 21 patients at the site of insertion of the papillary muscle was also reduced to a significant degree compared with the average radial shortening (32.9 +/- 10.3% versus 17.5 +/- 2.0%, p less than 0.001). The findings demonstrate significant long-term and possibly permanent regional ventricular dysfunction after severing the chordae tendineae during mitral valve replacement.

Female↗
PubMed1990

Intracoronary adenosine administration during reperfusion following 3 hours of ischemia: effects on infarct size, ventricular function, and regional myocardial blood flow.

Previous studies have demonstrated that adenosine significantly enhances myocardial salvage after 90 minutes of regional ischemia. To determine its effect after prolonged ischemia, closed-chest dogs underwent 3 hours of left anterior descending artery occlusion followed by 72 hours of reperfusion. Intracoronary adenosine (3.75 mg/min; at 1.5 ml/min:total volume = 90 ml; n = 10) or an equivalent volume of saline (1.5 ml/min: total volume = 90 ml; n = 9) was infused into the left main coronary artery during the first 60 minutes of reperfusion. Regional myocardial blood flow was assessed serially with microspheres and regional ventricular function was assessed by contrast ventriculography. Infarct size was determined histologically. Light and electron microscopy were utilized to assess neutrophil infiltration and microvascular injury. Adenosine failed to reduce infarct size expressed as a percentage of the area at risk (38.0 +/- 4.9% versus 34.8 +/- 4.6%; p = NS) or to improve regional ventricular function as measured by the radial shortening method (3.2 +/- 1.8% versus 2.2 +/- 3.1%; p = NS) at 72 hours after reperfusion. Vasodilatory effects were not observed in the endo- and midmyocardial regions of the ischemic zone during adenosine administration. This was associated with a similar extent of capillary endothelial changes and neutrophil infiltration in both adenosine-treated and saline control groups. These results suggest that severe functional abnormalities are present in the vasculature after 3 hours of ischemia and that adenosine therapy is ineffective in enhancing myocardial salvage.

Adenosine↗
PubMed1990

Effect of coronary angioplasty on electrocardiographic changes in patients with unstable angina secondary to left anterior descending coronary artery disease.

The effect of semiemergent percutaneous transluminal coronary angioplasty on clinical and electrocardiographic (ECG) variables was assessed in 76 patients with unstable angina secondary to an isolated severe proximal left anterior descending coronary artery stenosis. All patients manifested symmetric T wave inversion in two or more anterior ECG leads. Wall motion abnormalities were present in 37 patients on ventriculography before dilation. Angioplasty was successful in 70 patients (92%), resulting in a reduction in luminal diameter stenosis from 91 +/- 8% to 21 +/- 6%, with no major acute procedure-related complications observed. The other six patients underwent semiurgent (less than 48 h) coronary artery bypass surgery and three patients experienced a myocardial infarction (before bypass surgery in two). Serial ECGs revealed complete resolution of ST-T wave changes in 51% of patients at 14 weeks and in 90% at 28 weeks. In contrast, prolongation of the corrected QT interval, which was present in 16 patients (8%), normalized within 48 h of successful angioplasty. Twelve of these 16 patients with a prolonged QT interval had nonocclusive thrombus formation and poor collateral circulation on angiography. Patients were followed up for 6 to 43 months (mean 23 +/- 10). Angiographic evidence of restenosis was present in 34% of patients, all of whom underwent a successful second or third procedure. One death occurred at 8 months after successful angioplasty. Wall motion abnormalities had completely resolved in 13 of 15 patients who underwent repeat ventriculography, at which time 10 had a normal ECG. This study demonstrates that ECG changes may persist for up to 7 months in patients who undergo successful angioplasty for severe left anterior descending coronary artery disease and unstable angina. Semiemergent angioplasty was associated with a high initial success rate and excellent long-term outcome.

Adult↗
PubMed1990

Enhanced left ventricular contractility in autonomic failure: assessment using pressure-volume relations.

Severe autonomic failure is usually characterized by both supine hypertension and orthostatic hypotension. Inadequate preload reserve, insufficient arterial resistance and abnormal cardiac performance have been postulated to contribute to the hypotension. To clarify these mechanisms, left ventricular performance and contractility were assessed using radionuclide ventriculography and systolic pressure-volume relations when supine and with graded head-up tilt in 11 patients with autonomic failure. Results were compared with those of 12 normal subjects, using phenylephrine infusion for pharmacologic afterload augmentation after autonomic blockade with atropine and propranolol. In a subset of four patients with autonomic failure, systolic pressure-volume relations were similar by both the tilt and phenylephrine methods. In autonomic failure, end-diastolic volume, end-systolic volume and stroke volume decreased with progressive degrees of tilt (p less than or equal to 0.007 for each). The supine radionuclide ejection fraction and cardiac output were similar to those of normal subjects (69% versus 68% and 5.4 versus 4.9 liters/min, respectively, p = NS). However, the slopes of the pressure-volume relations and the supine pressure/volume ratio in autonomic failure were much greater than normal (8.8 versus 2.5, and 6.3 versus 3.6 mm Hg/ml, respectively, p less than or equal to 0.04 for both). The baseline total peripheral resistance was greater than normal (24.9 versus 17.4 mm Hg.min-1/liter, p = 0.01), but the resistance at maximal tilt failed to increase (20.8 +/- 6.1 units). Plasma norepinephrine concentrations were lower than normal. Thus, patients with autonomic failure had hypercontractile left ventricular performance when assessed by pressure-volume relations, and their hearts were well matched to the elevated peripheral resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The effect of perfluorochemical fluosol-DA (20%) on myocardial infarct healing in the rabbit.

Although the perfluorochemical Fluosol-DA 20% has been shown to reduce myocardial infarct size, its effect on the evolution of infarct healing has not been determined. Rabbits (n = 91) were randomized to ether-oxygenated Fluosol-DA (20 ml/kg) administered intravenously at the time of reperfusion after 30 min of coronary occlusion or no intervention. Animals were sacrificed at 1, 3, 7, and 14 days after infarction. Infarct size was significantly reduced in Fluosol-DA treated animals when compared with controls at one and three days. Infarct thinning was observed at one and three days in both groups. Left ventricular wall thickness in the infarcted area was greater with Fluosol-DA than control at 7 and 14 days. Increasing amounts of foamy macrophages containing perfluorochemical particles were noted in treated animals at 7 and 14 days. No differences were noted in hydroxyproline content between groups. These studies suggest that Fluosol-DA results in persistence of foamy macrophages without significantly altering infarct topography in the temporary occlusion rabbit model.

Analysis of Variance↗
PubMed1990

Prevention of neutrophil-mediated injury to endothelial cells by perfluorochemical.

Myocardial salvage after reperfusion may be limited by neutrophil-mediated microvascular damage. The effect of the perfluorochemical, Fluosol-DA, and its various components on neutrophil adherence, cytotoxicity, and proteolytic enzyme release was examined on sheep large and small vessel endothelial cells in vitro. Cells were studied under normoxic (N) and anoxic conditions (A). Various concentrations of Fluosol (10%, 25%, and 50%) significantly reduced neutrophil adherence under both experimental conditions [mean 22 +/- 3.25% versus 7 +/- 0.8% (N) and 20 +/- 3.2% versus 7.5 +/- 0.9% (A); P less than 0.01]. The perfluorocarbons, perfluorodecalin (PFD), and perfluoro-tripropylamine (PFTP) in a 50 volume/percent concentration exhibited profound effects on adherence, particularly on cells subjected to anoxia (51% and 69% reduction in adherence, respectively; P less than 0.01). No effect on adherence was observed with other components, including the detergent, pluronic F68. A 25% reduction (P less than 0.02) in endothelial cytotoxicity was noted when neutrophils were preincubated with Fluosol. However, pretreatment of endothelial cells with Fluosol did not inhibit neutrophil adherence. Neutrophils stimulated with cytochalasin B and FMLP showed a significant reduction in lysozyme release after incubation with Fluosol (28 +/- 5% versus 17 +/- 4%; P less than 0.01). This study demonstrates that Fluosol significantly attenuates neutrophil adherence, cytotoxicity, and enzyme release in an in vitro model of microvascular injury. It also suggests that prevention of neutrophil-mediated microvascular damage may be an important mechanism whereby Fluosol enhances myocardial salvage after ischemia and reperfusion.

Animals↗