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Biomedical subjects

R A Schatz

Publications and source records attributed to R A Schatz.

At least 19 recordsLinked to original sources

Emergent use of balloon-expandable coronary artery stenting for failed percutaneous transluminal coronary angioplasty.

BACKGROUND: The balloon-expandable intracoronary stent developed by Palmaz and Schatz is undergoing clinical evaluation for use in unfavorable anatomic situations and in the prevention of restenosis. Because the stent's mechanism of action would suggest effectiveness in salvaging certain percutaneous transluminal coronary angioplasty (PTCA) failures, we retrospectively examined the results of emergency unplanned coronary artery stenting for failed PTCA procedures, including acute occlusion. METHODS AND RESULTS: The study population consisted of all US patients receiving emergency unplanned stent implantation in a nonrandomized fashion at seven centers over a 2 1/2-year period (n = 56). All available medical records and angiograms were reviewed to determine retrospectively the reason for stenting: Group 1 consisted of 23 patients with a suboptimal angioplasty result; group 2 included patients with evidence of impending vessel closure after PTCA (n = 15); and group 3 were patients with frank acute occlusion after PTCA (n = 18). The immediate and final (30-day) results of stenting were examined with respect to major complications, which included death, need for coronary artery bypass graft surgery, and occurrence of myocardial infarction. Finally, restenosis rates (greater than or equal to 50% stenosis) based on follow-up angiography were calculated. Baseline characteristics of the study population included a mean +/- SD age of 58 +/- 11 years and a large prevalence of angiographic characteristics generally considered unfavorable for PTCA, which include lesion eccentricity (49%), intimal dissection (9%), or angiographically visible thrombus (6%). After conventional balloon angioplasty, there was an increased incidence of intimal dissection (74%) and thrombus formation (38%), and overall stenosis severity was unchanged (75 +/- 12% versus 70 +/- 27%, p = NS). Successful stent deployment was achieved in 55 (98%) of 56 patients with initial success (freedom from death, surgery, and infarction) in 52 (93%) of 56 patients. The success rate at 1 month fell to 71% primarily because of the occurrence of subacute stent thrombosis (16%) and its associated complications. Overall, major complications occurred in 16 (29%) of 56 patients within 30 days. The only predictor of subacute stent thrombosis in multiple stepwise logistic regression analysis was the presence of angiographically visible thrombus after stenting (p = 0.03). Angiographic restenosis was documented in eight (23%) of 35 eligible patients. CONCLUSIONS: Emergency stenting may be a useful and effective treatment for failed angioplasty. High initial success rates (greater than 90%) can be achieved, but subsequent complications, often related to subacute thrombosis, occur in a substantial portion of patients. Patients who receive stents on an emergency basis, particularly those with previous acute occlusion, should be considered to be at greater than usual risk for complications and receive more careful anticoagulation and follow-up.

Aged

Effect of intracoronary stenting on intimal dissection after balloon angioplasty: results of quantitative and qualitative coronary analysis.

The effect of the Palmaz-Schatz stent on the angiographic appearance and residual luminal stenosis in patients with intimal dissection after balloon angioplasty was evaluated in 84 consecutive patients (90 lesions). Coronary angiography was performed before angioplasty, after conventional angioplasty and after stent implantation. The degree of intimal disruption was assessed as follows: grade 0, no dissection; grade 1, simple dissection (intraluminal linear defect or extraluminal cap extravasation); or grade 2, complex dissection (nonlinear spiral defect or luminal defect with multiple irregular borders). Quantitative coronary analysis of digitized cineangiograms was performed with use of a computerized automatic edge detection algorithm. After balloon angioplasty, 31 (34%) of 90 lesions demonstrated intimal dissection (18 simple, 13 complex). After stent implantation, intimal dissection improved by greater than or equal to 1 grade in 29 (94%) of the 31 lesions with 27 (87%) reduced to grade 0 (that is, no dissection). Dissection grade improved after stenting in 16 (89%) of 18 simple dissections and in all 13 complex dissections. Mean diameter stenosis was 77 +/- 17% before angioplasty, 47 +/- 17% after angioplasty and 14 +/- 10% after stenting (before angioplasty vs. after angioplasty and after angioplasty vs. after stenting, p less than 0.0001). In conclusion, intracoronary stenting is effective in reducing the residual luminal stenosis and in improving the angiographic appearance of intimal dissections after conventional balloon angioplasty.

Adult

The effect of toluene on rat lung benzo[a]pyrene metabolism and microsomal membrane lipids.

Toluene (1 g/kg, i.p., 1 and 4 h) was shown to decrease total cytochrome P-450 (P450) content in rat lung. At both timepoints, reduction in pulmonary P450 content was associated with a decrease in aryl hydrocarbon hydroxylase (AHH) activity, a detoxication pathway for benzo[a]pyrene (BaP). At 4 h, toluene increased the toxication/detoxication ratios of BaP metabolites in pulmonary microsomes, primarily via inhibition of hydroxy metabolite formation. The structurally analogous solvents p- and m-xylene have been previously shown to produce a similar pattern of MFO changes in rat lung; the inhibition of BaP metabolism was found to be related to alterations in pulmonary microsomal lipids following administration of p- but not m-xylene. In the present study, toluene-induced alterations in MFO parameters were not found to be associated with changes in microsomal lipids. Toluene did not affect either total phospholipid or cholesterol content at either timepoint. Similarly, no changes in speciated phospholipids were observed. Membrane integrity, expressed as conjugated diene formation, also remained unchanged following toluene administration. Toluene did, however, decrease microsomal inner-core membrane fluidity at 4 h but had no effect on membrane leaflet fluidity at either timepoint. These data suggest that the fatty acid composition of microsomal lipids may play a role in the metabolic alterations observed in pulmonary microsomes following toluene administration.

Animals

Pulmonary microsomal alterations following short-term low level inhalation of p-xylene in rats.

Rats exposed to 300 ppm para-xylene vapor for 1, 3 or 5 days, 6 h/day, exhibited alterations in pulmonary microsomal membrane structural and metabolic parameters. Following 1 day of exposure, conjugated diene levels were elevated while total phospholipid levels, P-450 content, benzyloxyresorufin O-dealkylase activity and 2-aminofluorene N-hydroxylase activity were decreased. Core and leaflet membrane fluidity, ethoxyresorufin O-deethylase activity and aryl hydrocarbon hydroxylase (AHH) activity were unchanged at this time. Altered parameters began to return to control values by day 3 of exposure except for 2-aminofluorene N-hydroxylase activity, which remained decreased throughout the time course, and core membrane fluidity which was increased following 3 days of exposure. After 5 days of exposure, all parameters returned to control levels with the exception of AHH activity which was increased 41% at this time. Extracellular surfactant levels were also decreased by 1 and 3 days of exposure but returned to control values after 5 days. Initial pulmonary alterations produced by low level p-xylene exposure may be mediated by a peroxidative process. The initial damage triggers an adaptive response in lung tissue which possibly involves enzyme induction and/or cell proliferation. The increase in AHH activity after 5 days of exposure could have important consequences on the metabolism of co-administered xenobiotics.

Administration, Inhalation

Clinical experience with the Palmaz-Schatz coronary stent.

Complications that occurred in 247 patients who underwent successful elective stenting to native coronary arteries with the Palmaz-Schatz balloon expandable stent included subacute thrombosis in 7 patients (2.8%), myocardial infarction in 3 (1.2%), death 3 (1.2%), urgent bypass surgery in 4 (1.6%) and major bleeding events in 24 (9.7%). Angiographic restenosis occurred in 21 (20%) of 103 patients who received a single stent. Subgroup analysis, however, revealed that restenosis of a single stent occurred in 3 (7%) of 45 patients without prior angioplasty compared with 25 (27%) of 91 patients with prior angioplasty. Patients with "suboptimal" angioplasty results (dis-section) who received a single stent seemed to have a higher thrombosis rate perioperatively (4 [4%] of 98), but no higher incidence of restenosis (7 [15%] of 46) than that of the total group of patients who received a single stent. Coronary stenting may be a valuable adjunct to coronary angioplasty in carefully selected patients. Complication rates are similar to those of routine angioplasty; however, angiographic restenosis may be reduced in certain subsets of patients.

Adult

Aortic bifurcation stenosis: treatment with intravascular stents.

Balloon-expandable intravascular stents were employed to correct atherosclerotic stenosis of the aortic bifurcation. The devices were placed in the proximal iliac arteries with the cephalic end of the stents contacting in the midline. This arrangement provided an adequate lumen for the distal portion of the aortic wall and the proximal iliac arteries. Six of seven patients who received this form of treatment had hemodynamic and clinical improvement of their vascular insufficiency at an average follow-up of 1 year.

Angioplasty, Balloon

Phenytoin treatment and folate supplementation affect folate concentrations and methylation capacity in rats.

Phenytoin (PHT) has long been known to cause folate depletion with chronic use. In animal models PHT has been shown to interfere with folate-dependent one-carbon metabolism. Folic acid supplementation in humans has been shown to restore blood levels of folates to normal, but the effects of folic acid supplementation on the PHT-induced effects on one-carbon metabolism have not been addressed. In the present study rats were treated for 8 wk with 1) PHT, 2) folic acid, 3) PHT plus folic acid or 4) vehicle (propylene glycol). Phenytoin treatment caused a decrease in weight gain over the 8 wk of treatment. This effect on weight gain was reversed by folic acid supplementation, but the decrease in brain folate concentration caused by PHT was not reversed by folic acid supplementation, which by itself apparently caused a decrease in brain folate concentration. Phenytoin treatment tended to increase methylation capacity (S-adenosylmethionine:S-adenosylhomocysteine ratio) in the brain and decrease methylation capacity in the liver. Folate supplementation by itself increased methylation capacity in the liver but had no effect in the brain. Folic acid and PHT apparently had independent but opposite effects in the liver, leading to a normalization of methylation capacity. These data suggest that folic acid supplementation in PHT therapy may be effective in reversing the peripheral effects of chronic PHT treatment on one-carbon metabolism but not the central effects.

Animals

Clinical experience with the Palmaz-Schatz coronary stent. Initial results of a multicenter study.

Stenting of native coronary arteries with a balloon-expandable stent was attempted in 226 patients after elective angioplasty. Delivery of the device was successful in 213 (94%) of the patients. Of these, 39 received aspirin and dipyridamole only (group 1) and 174 received aspirin, dipyridamole, and warfarin for 1-3 months (group 2). There was no abrupt closure (less than or equal to 1 day) or perioperative death in either group. In-hospital or perioperative complications in group 1 compared with group 2 were as follows: subacute closure (1-14 days), seven (18%) patients versus one (0.6%) patient, respectively, p less than 0.0001; myocardial infarction, five (13%) patients versus one (0.6%) patient, respectively; condition requiring urgent bypass surgery, one (2.5%) patient versus no patients, respectively. Thus, the incidence of major complications such as death, myocardial infarction, or a condition requiring urgent bypass surgery was 15% in group 1 and 0.6% in group 2. Clinical follow-up revealed that 92% of the patients were asymptomatic at 3 months after stenting compared with 6% before stenting (p less than 0.0001). Of the 13 patients who were symptomatic, nine underwent cardiac catheterization and, ultimately, successful elective coronary angioplasty or bypass surgery. We conclude that a high delivery success rate can be expected with this device and that clinical thrombosis is less frequent in anticoagulated patients than in nonanticoagulated patients. Furthermore, in this selected patient population, coronary stenting results in a low incidence of in-hospital and perioperative complications. Clinical success, defined by absence of symptoms, appears to be sustained at 3 months.

Angioplasty, Balloon, Coronary

Role of isozyme-specific inhibition of cytochrome P450IIB1 activity in m-xylene-induced alterations in rat pulmonary benzo(a)pyrene metabolism.

1. m-Xylene (1 g/kg, i.p., 1 h) increased formation of benzo(a)pyrene (BP) mutagenic bay region diols, BP-7,8-diol (66%) and BP-9,10-diol (56%) by rat pulmonary microsomal preparations, while formation of individual BP phenols and quinones was unaltered. 2. m-Xylene administration produced a decrease in cytochrome P450IIB1 activity as measured by pentoxy- and benzyloxy-resorufin O-dealkylation (PROD, BROD), while cytochrome P450IA1 activity, expressed as ethoxyresorufin O-dealkylation (EROD), was unaltered. 3. Pulmonary microsomal epoxide hydrolase activity was also unaltered by m-xylene. 4. In summary, m-xylene alters the relative contribution of P-450 isozymes to BP metabolism resulting in inhibition of BP detoxication and increased production of toxic metabolites.

Animals

[Coronary angioplasty with the implantation of a vascular support (stent)].

Coronary angiography in a 55-year-old man with coronary heart disease and typical physical activity-induced angina revealed a subtotal stenosis in the middle third of the right coronary artery while left ventricular function was normal. Percutaneous transluminal coronary angioplasty (PTCA) was performed in January 1989, achieving a residual stenosis of less than 50%. However, restenosis of more than 90% developed within six months, necessitating another PTCA, followed immediately by implantation of a metal (Palmaz-Schatz) stent in the stenotic area. No stenosis was demonstrable afterwards. Maintenance medication with anticoagulants (phenprocoumon) and platelet-function inhibitors (aspirin and dipyridamole) was instituted and repeat angiography three months later demonstrated good dilatation results without any restenosis.

Angioplasty, Balloon, Coronary

Placement of balloon-expandable intraluminal stents in iliac arteries: first 171 procedures.

Balloon-expandable intraluminal stents were used to treat iliac artery stenoses or occlusions that failed to respond to conventional balloon angioplasty. One hundred seventy-one procedures were performed in 154 patients, of whom 48 had a limb at risk for amputation. Thirty-six had severe and 70 had moderate intermittent claudication. At the latest follow-up examination (average, 6 months; range, 1-24 months), 137 patients demonstrated clinical benefit, 113 of whom had become asymptomatic. Eleven patients showed no initial benefit, and six improved initially but later developed new vascular symptoms. Complications occurred in 18 patients. In three patients, complications were directly related to the device. Two occlusions were successfully recanalized, and an intramural collection of contrast material secondary to balloon perforation evolved favorably. The remaining patients had groin hematoma (n = 6), distal embolization (n = 4), extravasation (n = 2), transient renal failure (n = 1), pseudoaneurysm at the puncture site (n = 1), or subintimal dissection (n = 1). All stents have remained patent to the latest follow-up examination without evidence of migration or aneurysm formation.

Adult

Altered synaptosomal phospholipid metabolism after toluene: possible relationship with membrane fluidity, Na+,K(+)-adenosine triphosphatase and phospholipid methylation.

The mechanism by which toluene decreased synaptosomal phosphatidylethanolamine (PE) was investigated by studying degradative and synthetic phospholipid pathways. Toluene stimulated a PE-specific phospholipase (PLase) C both in vivo (44-75%) and in vitro (20-30%) whereas PLase A, PLase D and base exchange enzymes were unchanged. Toluene, in vivo, also increased the synthesis of PE (27%) when expressed as [3H]ethanolamine incorporation into [3H]PE, but had no effect on PE synthesis when administered in vitro. Perhaps this reflects a compensatory mechanism in synaptosomes to replace PE via increasing de novo synthesis. Phospholipid methylation, an event proposed to be related to the transduction of singals across membranes, as well as a measure of membrane function, was studied. Toluene was found to rapidly increase phospholipid methylation (43%, 15 min), followed by a significant decrease (35%, 1 hr). Another measure of membrane, as well as cell function used in these studies was ATPase activity. Toluene, both in vivo and in vitro, stimulated Na+, K(+)-adenosine triphosphatase (ATPase) activity (20-30%, 15-30 min), whereas Mg(++)-ATPase and Ca(++)-ATPase were unaffected, an indication that toluene alters neuronal cell function. Membrane fluidity studies using fluorescence polarization reported that toluene, both in vivo and in vitro, increased the outer synaptosomal membrane fluidity using the probe trimethylammonium-diphenylhexatriene, whereas no effect was observed on the central core fluidity using diphenylhexatriene. These are the first studies to demonstrate that an organic solvent effects only specific membrane region fluidities. One possibility is that early synaptic alterations resulting from toluene exposure may be preceded by increases in outer membrane fluidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of toluene on rat synaptosomal phospholipid methylation and membrane fluidity.

This study investigated the effects of toluene (1 g/kg, 1 hr, i.p.) on rat synaptosomal phospholipid methylation (PLM), phospholipid composition, and membrane fluidity. Toluene significantly decreased basal PLM (35%) in studies using [3H]methionine [( 3H]Met) as the methyl donor; this was reflected by similar decreases in phosphatidylmonomethylethanolamine (PME) (30%). No effects were observed in either PLM reactions that used [3H]adenosylmethionine [( 3H]AdoMet) as methyl donor, or AdoMet synthetase, suggesting that toluene preferentially affects PLM reactions that derive methyl groups from [3H]Met. Also, toluene decreased synaptosomal phosphatidylethanolamine (PE) (24%), the initial substrate for PLM, and the addition of PE back to PE-depleted synaptosomes restored methyltransferase activity. Agonist-stimulated PLM using norepinephrine (NE) demonstrated that agonist-receptor coupling returned PLM to control values in synaptosomes from toluene-treated rats. NE-stimulated PLM was also blocked by propranolol (PRO), suggesting a role for toluene in receptor-mediated events. Membrane fluidity studies demonstrated that in vivo administration of toluene increased the outer synaptosomal membrane fluidity, whereas in vitro administration of toluene had no effect. Our observations support a positive relationship between increased PLM activity and increased outer, not core, membrane fluidity. These data demonstrate that specific toluene-phospholipid interactions occur in synaptosomes, resulting in altered membrane composition, function and fluidity.

Animals

The effect of m-xylene on rat lung benzo[a]pyrene metabolism and microsomal membrane lipids: comparison with p-xylene.

m-Xylene (1 g/kg, i.p., 1 h) was shown to decrease aryl hydrocarbon hydroxylase (AHH) activity, a detoxification pathway for benzo[a]pyrene (BaP), in the rat lung. Inhibition was maximal at 1 g/kg, 1 h after treatment and was sustained for at least 24 h. Reduction in cytochrome P-450 activity in rat lung was also observed, while liver activity was unchanged. p-Xylene has been previously shown to produce a similar pattern of MFO changes in rat lung. The lipid composition of the microsomal membrane is important to mixed function oxidase (MFO) regulation and function. Since the xylenes are lipophilic, these compounds were studied to determine whether they alter pulmonary microsomal lipids. p-Xylene produced an organ specific increase in lipid peroxidation in the rat lung. This was accompanied by decreases in lung microsomal total phospholipid (PL) and phosphatidylcholine (PC) content. Pulmonary microsomal membrane fluidity was also reduced by p-xylene administration. In comparison, m-xylene administration did not change any of the lipid membrane parameters tested. These divergent results leave unresolved the role of altered PL metabolism in solvent-induced inhibition of MFO activity.

Animals

Angioplasty and stenting of completely occluded iliac arteries.

Percutaneous angioplasty and placement of balloon-expandable intraluminal stents were performed in 12 iliac occlusions in 12 patients. Indications were limb salvage in seven and claudication in five. After successful stenting, ankle-brachial indexes improved by 0.15 or more in 11 of 12 patients (mean increase, 0.40), transstenotic pressure gradients decreased to less than 5 mm Hg (mean, 0.58 mm Hg) in all patients, and improvement in clinical grade was seen in all patients. At follow-up at 1-14 months (median, 6 months), ankle-brachial indexes were stable (mean, 0.95), and clinical grades were unchanged in all patients. Complications occurred in two patients; both experienced distal embolization, and one, who was receiving corticosteroid therapy, also suffered stent thrombosis. Local surgical embolectomy was successful in both patients, and the thrombosed stent was recanalized with urokinase. This early experience suggests that stenting may play an important role in the management of iliac occlusions, especially in poor surgical candidates.

Adult

Toluene-induced alterations in rat synaptosomal membrane composition and function.

Toluene is a widely used organic solvent that can produce acute central nervous system (CNS) effects. Since toluene reaches relatively high concentrations in the CNS and is extremely lipophilic, we investigated its effects on rat brain membrane composition and function. Toluene (1 g/kg, lh) did not alter total brain microsomal phospholipid (PL) or cholesterol (CL) content. However, synaptosomal PL was decreased (24%), while synaptosomal CL was unaltered. The PL/CL ratio, an indirect index of membrane fluidity, did not change, suggesting that toluene did not affect membrane fluidity. Fluorescence polarization studies employing 1,6-diphenyl-1,3,5-hexatriene (DPH) showed that toluene did not alter synaptosomal membrane fluidity after administration in vivo (1 g/kg) or in vitro (0.5 to 5.0 mM). Dose-response and time-course studies showed that toluene maximally decreased synaptosomal PL after 1 g/kg, 1 h. The dose-response and time-course studies also showed that the toluene-induced decreases in PL were a result of specific decreases in phosphatidylethanolamine (PE). Since PE was decreased, we assessed whether toluene altered synaptosomal membrane function by investigating phospholipid methylation, a reaction which uses PE as its initial substrate. Toluene decreased the incorporation of methyl groups into lipid when [3H]-methionine was used as the methyl donor, but did not affect methylation when [3H]-adenosylmethionine was the methyl donor. These data suggest that toluene-induced specific decreases in synaptosomal PE and inhibition of phospholipid methylation may alter normal synaptic function and play a critical role in the mechanism(s) of action of toluene's CNS effects.

Animals

Changes in rat lung microsomal lipids after p-xylene: relationship to inhibition of benzo[a]pyrene metabolism.

The relationship between p-xylene's effects on microsomal membranes, cytochrome P-450, and benzo[a]pyrene (BaP) metabolism was studied. p-Xylene (1 g/kg, ip, 1 h) inhibited 3-hydroxy BaP (3-OH) formation and decreased arylhydrocarbon hydroxylase (AHH) activity approximately 40% in rat lung microsomes. BaP dihydrodiol and quinone formation were unchanged by p-xylene administration. Cytochrome P-450 was below the limit of detection in lung microsomes from p-xylene-treated rats. Total phospholipid (PL) and phosphatidylcholine (PC) in microsomal membranes were decreased 28% and 17%, respectively. Cholesterol (CL), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and sphingomyelin (SM) were unchanged. The net activity of enzymes involved in the synthesis of PC, phosphatidylethanolamine-N-methyltransferase I and II (PMT I and PMT II), was slightly elevated by p-xylene. PL/CL and PC/PE ratios, indicators of membrane fluidity, were decreased 34% and 13%, respectively, in microsomes from p-xylene-treated rats. Analysis of fluidity by fluorescence polarization showed that the actual fluidity of treated microsomes was slightly decreased (5%) as compared to controls. The decrease in P-450, PL, and PC is considered to contribute to the inhibition of BaP metabolism.

Animals