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Biomedical subjects

L I Deckelbaum

Publications and source records attributed to L I Deckelbaum.

At least 19 recordsLinked to original sources
PubMed2001

Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization.

BACKGROUND: Previous investigators have shown that systemic markers of inflammation may be increased in patients with acute ischemic syndromes or after percutaneous coronary revascularization and that persistent elevation in these markers is predictive of excess risk of subsequent adverse cardiac events. By virtue of its cross-reactivity with the glycoprotein IIb/IIIa, avbeta3, and alphaMbeta2 receptors, abciximab may reduce inflammatory processes. Methods and Results-- Assays for the inflammatory markers C-reactive protein, interleukin-6, and tumor necrosis factor-alpha were performed on serum samples obtained from 160 patients in a placebo-controlled, randomized trial of abciximab during angioplasty. Eighty patients each had received a placebo or abciximab bolus plus a 12-hour infusion. Serum samples were drawn at baseline (before revascularization), 24 to 48 hours after study drug administration, and 4 weeks after study drug administration. Between baseline and 24 to 48 hours, the increase in C-reactive protein was 32% less in patients receiving abciximab than placebo (P=0.025); the rise in interleukin-6 levels was 76% less in the abciximab group (P<0.001); and the rise in tumor necrosis factor-alpha levels was 100% less with abciximab therapy (P=0.112). By 4 weeks, most marker levels had returned to baseline, with no significant differences between placebo and abciximab groups. CONCLUSIONS: Systemic markers of inflammation increase in the first 24 to 48 hours after angioplasty, but the magnitude of that rise is diminished by periprocedural abciximab. Some of the long-term clinical benefit derived from this agent may be related to an anti-inflammatory effect.

Abciximab↗
PubMed2000

Global impairment of coronary blood flow in the setting of acute coronary syndromes (a RESTORE substudy). Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis.

Acute coronary syndromes result in a global impairment of coronary blood flow with nonculprit artery blood flow being associated with culprit artery flow and vice versa. Improvements in nonculprit artery flow are related to improvements in culprit artery flow after percutaneous intervention; nonculprit arteries with abnormal flow sustain greater improvements in their flow after culprit artery intervention.

Angina, Unstable↗
PubMed2000

Effect of plasma insulin level on myocardial blood flow and its mechanism of action.

Considerable evidence suggests that coronary endothelium regulates myocardial blood flow and metabolism by elaborating vasoactive substances. The physiologic signals mediating this process are uncertain. To test the hypothesis that the process is influenced by physiologic variation in local insulin concentration, we examined the effect of direct intracoronary insulin infusion on myocardial blood flow and oxidative substrate metabolism in 10 patients with coronary heart disease. Ten men (aged 51 to 68 years) who were fasting received a 60-minute intracoronary infusion of insulin at a rate (10 mU/min) sufficient to raise coronary venous plasma insulin from 12+/-4 to 133+/-17 mU/ml without increasing the systemic insulin level. Local coronary hyperinsulinemia increased coronary sinus blood flow in every subject, from 50+/-4 to 61+/-6 ml/min (p<0.01). Insulin also increased myocardial uptake of glucose (from 6+/-1 to 17+/-6 mmol/min) and lactate (from 8+/-2 to 12+/-5 mmol/min), resulting in approximately 30% increase in total oxidative substrate uptake, but without increasing myocardial oxygen consumption (7.0+/-0.7 vs. 7.1+/-0.8 ml/min). Thus, physiologic elevation in the local plasma insulin concentration increases coronary blood flow in the absence of any increase in myocardial oxygen demand or consumption, suggesting a primary reduction in coronary tone, while simultaneously restraining the oxidation of imported substrates. These observations are consistent with insulin-mediated elaboration of vasoactive and/or paracrine factors within the coronary circulation.

Aged↗
PubMed2000

Effect of hyperinsulinemia on myocardial amino acid uptake in patients with coronary artery disease.

Branched-chain amino acids (BCAAs) are oxidative energy substrates for the heart and may exert anabolic effects on myocardial protein. The factors regulating their myocardial uptake in patients with ischemic heart disease are therefore of interest. To examine whether myocardial BCAA utilization is influenced by the circulating insulin concentration, in 10 patients with chronic ischemic heart disease, we measured transmyocardial amino acid balance during fasting and again during a 90-minute euglycemic insulin infusion (plasma insulin, 218+/-25 microU x mL(-1)) with plasma BCAA concentrations held constant by coinfusion. In the fasting state, the myocardial fractional extraction of leucine (8%), isoleucine (9%), and valine (5%) from arterial plasma was slightly greater than that of glucose (3%), while net myocardial BCAA uptake (leucine, 409+/-207 nmol x min(-1); isoleucine, 220+/-144 nmol x min(-1); valine, 407+/-326 nmol x min(-1); and total BCAA uptake, 1.0+/-0.3 micromol x min(-1)) was about 13% that of glucose (8+/-2 micromol x min(-1)). During euglycemic hyperinsulinemia, myocardial glucose uptake increased 3-fold, but there was no change in the arterial-coronary sinus balance or net myocardial uptake of any BCAA under conditions where their plasma concentrations were held constant. Instead, the myocardial uptake of each BCAA correlated positively with its concentration in arterial plasma. These results demonstrate that in patients with cardiovascular disease, myocardial utilization of BCAAs is insensitive to the circulating insulin level and is regulated instead by their availability in arterial plasma. Hyperinsulinemia reduced the magnitude of both net glutamate uptake and alanine release, suggesting a possible salutary effect on myocardial oxidative efficiency.

Aged↗
PubMed1999

Combination therapy with tirofiban and enoxaparin in acute coronary syndromes.

BACKGROUND: Tirofiban, an intravenous glycoprotein IIb/IIIa antagonist, and enoxaparin, a low molecular weight heparin, have each been shown to be effective at reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q-wave myocardial infarction. The combination of these agents may offer further therapeutic benefit. MATERIALS AND METHODS: Fifty-five patients with non-Q-wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.1 microgram/kg/min i.v.) for 48-108 h coadministered with either enoxaparin (1 mg/kg sc q 12 h) (n=26) or unfractionated heparin (i.v. adjusted to activated partial-thromboplastin time) (n=27) to evaluate pharmacokinetics, pharmacodynamics, and safety. The primary objective of the study was to investigate the effect of unfractionated heparin versus enoxaparin on the plasma clearance of tirofiban. RESULTS: Coadministration of tirofiban and enoxaparin was generally well tolerated. Plasma clearance of tirofiban was 176.7+/-59.8 and 187.5+/-81.8 ml/min, respectively, for enoxaparin and unfractionated heparin-treated patients (P=NS). The mean difference was well within the prespecified criterion for comparability. Administration of tirofiban with enoxaparin vs. unfractionated heparin resulted in lesser variability and a trend towards greater inhibition of platelet aggregation using 5 microM adenosine phosphate agonist. More patients achieved target inhibition of platelet aggregation >70% in the tirofiban and enoxaparin group (84% vs. 65%, P=0.19). Median bleeding time was 21 min for tirofiban and enoxaparin vs. > or =30 min for tirofiban and unfractionated heparin (P=NS). For a given level of inhibition of platelet aggregation, bleeding time was less prolonged with tirofiban and enoxaparin than tirofiban and unfractionated heparin (adjusted mean bleeding time 19.6 vs. 24.9 min, P=0.02). Tirofiban plasma concentration and clearance were comparable whether coadministered with enoxaparin or unfractionated heparin. There were no major or minor bleeding events in either group by the TIMI criteria. INTERPRETATION: The more consistent inhibition of platelet aggregation and lower adjusted bleeding time of tirofiban and enoxaparin vs. tirofiban and unfractionated heparin support the therapeutic potential of combining these two agents. These data from the first clinical report of coadministration of a glycoprotein IIb/IIIa receptor antagonist and a low molecular weight heparin are consistent with prior data which show differential pharmacodynamic effects of enoxaparin and unfractionated heparin on platelet aggregation.

Angina, Unstable↗
PubMed1998

Six-month angiographic and clinical follow-up of patients prospectively randomized to receive either tirofiban or placebo during angioplasty in the RESTORE trial. Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis.

OBJECTIVES: This study sought to investigate the effects of tirofiban versus placebo on the incidence of adverse cardiac outcomes and coronary artery restenosis at 6 months. BACKGROUND: Tirofiban is a highly selective, short-acting inhibitor of fibrinogen binding to platelet glycoprotein IIb/IIIa. In a recent clinical study, tirofiban reduced the incidence of adverse cardiovascular events at both 2 and 7 days after coronary angioplasty or directional coronary atherectomy. This reduction persisted but was no longer statistically significant at 30 days. METHODS: The Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis (RESTORE) trial was a randomized, double-blind, placebo-controlled trial of tirofiban in patients undergoing balloon angioplasty or directional atherectomy within 72 h of presentation with either unstable angina pectoris or acute myocardial infarction. All patients received an initial bolus (10 microg/kg body weight over 3 min), followed by a 36-h infusion (0.15 microg/kg per min) of either tirofiban or placebo. RESULTS: At 6 months the composite end point (either death from any cause, new myocardial infarction, bypass surgery for angioplasty failure or recurrent ischemia, repeat target vessel angioplasty or stent insertion for actual or threatened abrupt closure) occurred in 1,070 placebo group patients (27.1%) and 1,071 tirofiban group patients (24.1%, p = 0.11). Analysis of 6-month coronary arteriograms by means of quantitative coronary arteriography showed no significant difference between placebo- and tirofiban-treated patients in either the incidence of a > or =50% diameter stenosis (57% vs. 51%, p = NS), a loss of > or =50% of lumen diameter gained (50% vs. 50%, p = NS) or a loss of > or =0.72 mm of lumen diameter (44% vs. 42%, p = NS). CONCLUSIONS: The 3% absolute reduction in the incidence of the composite end point at 6 months (27.1% placebo vs. 24.1% tirofiban) was similar to that previously reported at 2 days (8.7% vs. 5.4%, p < 0.005), and there does not appear to be any late effect of tirofiban on clinical end points between day 2 and 6 months. Tirofiban did not reduce the incidence of restenosis at 6 months when defined in a number of ways.

Adult↗
PubMed1997

Intracoronary Doppler assessment of moderate coronary artery disease: comparison with 201Tl imaging and coronary angiography. FACTS Study Group.

BACKGROUND: Coronary angiography may not reliably predict whether a stenosis causes exercise-induced ischemia. Intracoronary Doppler ultrasound may enhance diagnostic accuracy by providing a physiological assessment of stenosis severity. The goal of this study was to compare intracoronary Doppler ultrasound with both 201Tl imaging and coronary angiography. METHODS AND RESULTS: Fifty-five patients with 67 stenotic coronary arteries underwent coronary angiography with intracoronary Doppler ultrasound and had exercise 201Tl testing within a 1-week period. Coronary flow reserve was measured, and analyses were performed by independent core laboratories. The mean stenosis was 59+/-12%; 51 of 67 stenoses were intermediate in severity (40% to 70%). A coronary flow reserve < 1.7 predicted the presence of a stress 201Tl defect in 56 of 67 stenoses (agreement=84%; kappa=0.67; 95% CI=0.48 to 0.86). In the patients who achieved 75% of their predicted maximum heart rate, the Doppler and 201Tl imaging data agreed in 46 of 52 stenoses (agreement=88%; kappa=0.77; 95%CI=0.57 to 0.97). Scatter was evident when angiography was compared with coronary flow reserve (r=.43), and the angiogram did not reliably predict the results of the 201Tl stress test (kappa=0.21; agreement=57% to 63%). CONCLUSIONS: Doppler-derived coronary flow reserve accurately predicts the presence of exercise-induced ischemia on stress 201Tl imaging, and coronary angiography does not reliably assess the physiological significance of an intermediate coronary stenosis.

Aged↗
PubMed1995

Effect of intracoronary saline infusion on dissection during excimer laser coronary angioplasty: a randomized trial. The Percutaneous Excimer Laser Coronary Angioplasty (PELCA) Investigators.

OBJECTIVES: We sought to evaluate whether intracoronary saline infusion during excimer laser coronary angioplasty decreases the incidence of significant laser-induced coronary artery dissections. BACKGROUND: Despite procedural success rates > 90%, coronary artery dissections occur in 17% to 27% of excimer laser coronary angioplasty procedures. Excimer laser irradiation of blood results in vapor bubble formation and acoustomechanical trauma to the vessel wall. Saline infusion into a coronary artery may minimize blood irradiation and consequent arterial wall damage. METHODS: In this prospective, randomized, controlled study, consecutive patients undergoing excimer laser coronary angioplasty were randomly assigned to conventional laser irradiation in a blood medium or to laser irradiation with blood displacement by intracoronary saline infusion. In the patients randomized to intracoronary saline infusion, prewarmed normal saline was injected through the coronary artery guide catheter at a rate of 1 to 2 ml/s using a power injector. The incidence and severity of dissection after excimer laser ablation were evaluated in a core laboratory by angiographers with no knowledge of treatment assignment. The severity of coronary artery dissection was rated on an ordinal scale of 1 to 5. Dissections of grade 2 or higher were considered significant. RESULTS: The mean (+/- SE) dissection grade after laser angioplasty in patients treated with intracoronary saline infusion was 0.43 +/- 0.13 compared with 0.91 +/- 0.26 in patients undergoing laser angioplasty in a blood medium. The incidence of significant dissection was 7% in saline-treated patients compared with 24% in conventionally treated patients (p < 0.05). No significant complications were associated with saline infusion. CONCLUSIONS: Intracoronary saline infusion should be incorporated into all excimer laser coronary angioplasty procedures.

Aged↗
PubMed1995

Hyperinsulinemia inhibits myocardial protein degradation in patients with cardiovascular disease and insulin resistance.

BACKGROUND: Insulin resistance, hyperinsulinemia, and myocardial hypertrophy frequently coexist in patients. Whether hyperinsulinemia directly affects myocardial protein metabolism in humans has not been examined, however. To test the hypothesis that hyperinsulinemia is anabolic for human heart protein, we examined the effects of insulin infusion on myocardial protein synthesis, degradation, and net balance in patients with ischemic heart disease. METHODS AND RESULTS: Eleven men (aged 57 +/- 3 years) with coronary artery disease who had fasted for 12 to 16 hours received a constant infusion of insulin (50 mU.m-2.min-1) while plasma concentrations of glucose and amino acids were kept constant. Rates of myocardial protein synthesis, degradation, and net balance were estimated from steady state extraction and isotopic dilution of L-[ring-2,6-3H]phenylalanine across the heart basally and 90 minutes into infusion. Subjects had elevated fasting plasma insulin concentrations (173 +/- 21 pmol/L) and used little exogenous glucose during insulin infusion, suggesting resistance to the effects of insulin on whole-body carbohydrate metabolism. Basally, myocardial protein degradation, as estimated by phenylalanine release (133 +/- 28 nmol/min), exceeded protein synthesis, estimated by phenylalanine uptake (31 +/- 15 nmol/min), resulting in net negative phenylalanine balance (-102 +/- 17 nmol/min). Insulin infusion reduced myocardial protein degradation by 80% but did not affect protein synthesis, returning net phenylalanine balance to neutral. CONCLUSIONS: Acute hyperinsulinemia markedly suppresses myocardial protein degradation in patients with cardiovascular disease who are resistant to its effects on whole-body glucose metabolism. This antiproteolytic action represents a potential mechanism by which hyperinsulinemia could contribute to the development of myocardial hypertrophy in patients with cardiovascular disease.

Amino Acids↗
PubMed1995

Development of a new technique for reducing pressure pulse generation during 308-nm excimer laser coronary angioplasty.

Despite expectations that excimer laser ablation would result in a low incidence of coronary dissection, studies have documented a 15-20% incidence of dissection (including a 4-6% incidence of clinically significant dissection) during excimer interventions. This investigation sought to determine if pressure pulses produced by the exposure of fluid phase media (blood and contrast) to 308-nm excimer radiation might contribute to untoward outcomes. Pressure pulses generated in these media were quantitated to be > 100 atm. In vitro ablation of porcine aorta in the presence of blood or contrast resulted in tissue dissection, while ablation in pure crystalloid did not. Next, a "flush and bathe" technique designed to replace all blood and contrast with crystalloid was applied to a pilot population of 57 consecutive patients. There were no rhythm disturbances or laser-related clinically significant dissections in this group, and the clinical success rate was 95%. In summary, this report quantitates a potential etiology for excimer dissection and suggests that replacement of blood and contrast with crystalloid might improve procedural and clinical success rates.

Angioplasty, Laser↗
PubMed1995

Evaluation of a fluorescence feedback system for guidance of laser angioplasty.

BACKGROUND AND OBJECTIVE: Laser-induced fluorescence spectroscopy (LIFS) may be capable of guiding laser angioplasty by discriminating normal and atherosclerotic artery and by determining catheter-tissue environment. Previous optical multichannel analyzer based LIFS systems have been expensive and cumbersome. To simplify LIFS, a system based on photomultiplier tubes was developed and evaluated. STUDY DESIGN/MATERIALS AND METHODS: Tissue fluorescence was induced by a helium cadmium laser (wavelength = 325 nm, power = 0.2-0.5 mW), collected by clinical multifiber laser angioplasty catheters and directed through one of two filters (10 nm bandpass, 380 nm or 440 nm peak transmission) to a photomultiplier tube. An LIFS ratio was defined as the relative intensity at 380:440 nm after calibration with an elastin fluorescence spectrum; 157 coronary artery cadaveric specimens were evaluated spectroscopically and histologically. To evaluate the utility of LIFS to optimize catheter position by determining catheter-tissue contact, by determining saline dilution of blood, and by orienting eccentric multifiber catheters a new variable, the total fluorescence intensity (TFI) was defined as the sum of arterial fluorescence intensities at 380 nm and 440 nm. TFI was recorded in vitro through multifiber catheters from 20 arterial specimens in vitro in blood and evaluated as a function of the catheter-to-tissue distance (d) over a range from 0 to 400 mu. RESULTS: Defining normal specimens as those with an intimal thickness < or = 200 mu, and atherosclerotic as those with an intimal thickness > 200 mu, 47/50 (94%) normal and 85/107 (79%) atherosclerotic specimens were correctly classified using a threshold LIFS ratio of 2.0. Mean (+/- SE) normal ratio was 1.76 +/- 0.02 and mean atherosclerotic ratio was 2.78 +/- 0.08 (P < or = 0.01). The classification accuracy of atherosclerotic specimens increased with intimal thickness so that 95% of atherosclerotic specimens (69/73) with intimal thickness > or = 400 mu were correctly classified. TFI was capable of determining catheter-tissue contact as maximal TFI was recorded with the catheter in contact with the tissue (d = 0 mu) and decreased markedly with distance (to 52 +/- 6% at d = 100 mu, 19 +/- 4% at d = 200 mu, and 3 +/- 1% at d = 300 mu). TFI was recorded from ten arterial specimens in blood/saline mixtures ranging in hematocrit from 0% (saline) to 50% (whole blood). TFI was capable of detecting saline hemodilution of blood as TFI decreased markedly at higher hematocrits such that TFI could only by recorded at hematocrits < 10% for catheter-to-tissue distances > or = 300 mu. TFI was recorded through ecentric multifiber catheters from 25 arterial specimens and eval-uated as a function of the degree of catheter-tissue overlap. TFI was capable of detecting maximal catheter-tissue overlap as TFI correlated linearly with the area (A) of overlap (TFI = 1.12 A + .07, r = 0.92). CONCLUSIONS: By discriminating atherosclerotic from normal tissue and by confirming catheter-tissue contact and saline hemodilution, fluorescence feedback should minimize irradiation of normal tissue and/or blood and enhance the safety and efficacy of laser angioplasty.

Angioplasty, Laser↗
PubMed1995

Effect of midinfrared holmium: YAG laser angioplasty with and without balloon angioplasty on acute outcome and restenosis in atherosclerotic femoral arteries in rabbits.

BACKGROUND AND OBJECTIVE: Pulsed laser may lessen vascular damage and reduce restenosis. This study examined the acute and chronic effects of midinfrared laser angioplasty with and without balloon angioplasty in atherosclerotic femoral arteries in rabbits. STUDY DESIGN/MATERIALS AND METHODS: Atherosclerosis was induced in arteries by air desiccation and cholesterol feeding. Arteries were assigned to one of four groups: (1) laser angioplasty with a Thullium/Holmium/Chromium:YAG infrared laser (Eclipse), (2) balloon angioplasty, (3) laser followed by balloon angioplasty, and (4) no intervention. Arteries were examined angiographically and histologically at 2 hours and 28 days. RESULTS: Intervention groups had significant initial gain, but this gain was less with laser alone than after balloon or after laser plus balloon. At 2 hours, laser alone caused greater arterial damage and thrombosis compared to controls. At 28 days, arteries treated with laser plus balloon had greater narrowing compared with arteries treated with balloon angioplasty. By multivariate regression analysis, the severity of the pre-intervention stenosis (P = 0.001) and intervention with laser plus balloon (P = 0.01) correlated independently with the severity of luminal narrowing at 28 days. CONCLUSION: Midinfrared Ho:YAG laser angioplasty resulted in substantial acute damage with increased frequency of thrombus formation in this rabbit model. arteries treated with laser alone had suboptimal initial gain and more obstruction by plaque at 28 days compared to nonintervened arteries. The adjunctive use of balloon angioplasty improved initial gain, but correlated with smaller luminal diameters and more severe narrowing by plaque at 28 days.

Angioplasty, Balloon↗
PubMed1995

Differences in laser-induced autofluorescence between adenomatous and hyperplastic polyps and normal colonic mucosa by confocal microscopy.

Laser-induced autofluorescence has been used to discriminate normal from adenomatous colonic mucosa. However, few studies to date have studied the origin of colonic autofluorescence. Using confocal microscopy (excitation wavelength 488 nm), we have shown that autofluorescence at this wavelength is present predominantly in the lamina propria of normal mucosa but in the epithelium in adenomatous and hyperplastic polyps. The intensity ratio of epithelial cell to lamina propria fluorescence was significantly lower (P < 0.0001) in normal mucosa (0.52 +/- 0.01) compared with either adenomatous (1.6 +/- 0.2) or hyperplastic polyps (1.7 +/- 0.15). However, the ratios were not significantly different between hyperplastic and adenomatous polyps. Thus, confocal microscopy enables the detection of the sites of autofluorescence within colonic mucosa and the quantitation of differences in fluorescence between different tissue types.

Adenomatous Polyps↗
PubMed1994

Coronary laser angioplasty.

With the widespread growth of percutaneous transluminal coronary angioplasty (PTCA), the realization of limitations of balloon angioplasty stimulated the development of alternative revascularization approaches such as laser angioplasty. PTCA is best suited for the treatment of discrete atherosclerotic stenoses, with lower success rates and more difficult application in patients with diffuse atherosclerotic disease or total occlusions [1-3]. Moreover, despite an initially high primary success rate, coronary angioplasty is still plagued by a restenosis rate as high as 57% [4]. The potential advantages of laser angioplasty address the limitations of PTCA. In contrast to balloon angioplasty where the plaque material is compressed or displaced, laser angioplasty ablates the plaque material [5]. This bulk removal of plaque material could improve acute procedural success rates, decrease complication rates, treat "untreatable" lesions, and decrease restenosis rates. Because laser energy can vaporize atherosclerotic plaque, there may be no requirement for a preexisting channel, and therefore laser angioplasty may have a high success rate for the treatment of coronary occlusions. In its best embodiment, laser angioplasty offers the potential for passing a fiberoptic catheter through the entire length of the coronary circulation to vaporize all atherosclerotic plaque along the arterial wall. This applicability for the treatment of diffuse atherosclerotic disease would offer treatment opportunities currently unavailable with conventional bypass surgery or angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1994

Cardiovascular applications of laser technology.

Laser technology has been evaluated for the treatment of coronary artery disease, ventricular and supraventricular arrythmias, hypertrophic cardiomyopathy, and congenital heart disease. Developments in laser angioplasty, laser thrombolysis, transmyocardial laser revascularization, photochemotherapy, laser treatment of arrhythmias and/or laser diagnostics are directed at improving upon conventional non-laser approaches, and providing new therapeutic and diagnostic options. This review will summarize the current status of the multiple applications of laser technology for cardiovascular diagnosis and therapy.

Angioplasty, Laser↗
PubMed1994

Inhibition of smooth muscle cell proliferation by visible light-activated psoralen.

The present study was designed to evaluate the effect of 8-methoxypsoralen (8-MOP) activated with visible light (419 nm) on the suppression of smooth muscle cell (SMC) proliferation in vitro. We hypothesize that if visible light (VL) instead of UVA is used to photoactivate 8-MOP, cytotoxic 8-MOP-DNA cross-link formation can be minimized. Bovine aorta SMCs (2 x 10(4)/cm2) were incubated with 8-MOP (1 micrograms/mL) for 30 minutes (in the dark) and exposed to a range of VL (2 to 69 J/cm2) to determine the dose of VL that inhibits SMC proliferation with minimal toxicity. The results show that 8-MOP in combination with 2 to 12 J/cm2 VL reversibly inhibited SMC proliferation for up to 5 days after treatment. SMC viability was confirmed by trypan blue exclusion. 8-MOP in combination with 23- or 69-J/cm2 VL irreversibly inhibited SMC proliferation. In cell cycle studies, 12-J/cm2 VL was used to activate 8-MOP. A phase-specific G2 blockade that correlated temporally with recovery of SMC replication was observed. Photoadduct repair studies showed that cell proliferation rates recovered when 60% of the adducts had been removed. These results demonstrate for the first time the possibility of using VL to activate 8-MOP to inhibit cell proliferation and suggest that 8-MOP/VL photochemotherapy can be used to control SMC growth.

Animals↗