Significant alterations of biodistribution and immune responses in Balb/c mice administered with adenovirus targeted to CD40(+) cells.

CD40 ligation has been shown to promote antigen-presenting functions of dendritic cells, which express CD40 receptor. Here we reported significantly altered biodistribution and immune responses with the use of CD40-targeted adenovirus. Compared with unmodified adenovirus 5, the CD40-targeted adenovirus following intravenous administration (i.v.) resulted in increased transgene expressions in the lung and thymus, which normally do not take up significant amounts of adenovirus. Intradermal injection saw modified adenovirus being mainly processed in local draining lymph nodes and skin. Following intranasal administration (i.n.), neither unmodified nor targeted viruses were found to be in the liver or spleen, which predominantly took up the virus following i.v. administration. However, inadvertent infection of the brain was found with unmodified adenoviruses, with the second highest gene expression among 14 tissues examined. Importantly, such undesirable effects were largely ablated with the use of targeted vector. Moreover, the targeted adenovirus elicited more sustained antigen-specific cellular immune responses (up to 17-fold) at later time points (30 days post boosting), but also significantly hampered humoral responses irrespective of administration routes. Additional data suggest the skewed immune responses induced by the targeted adenoviruses were not due to the identity of the transgene but more likely a combination of overall transgene load and CD40 stimulation.

Circumferential radiofrequency ablation of pulmonary vein ostia: A new anatomic approach for curing atrial fibrillation.

BACKGROUND: The pulmonary veins (PVs) and surrounding ostial areas frequently house focal triggers or reentrant circuits critical to the genesis of atrial fibrillation (AF). We developed an anatomic approach aimed at isolating each PV from the left atrium (LA) by circumferential radiofrequency (RF) lesions around their ostia. METHODS AND RESULTS: We selected 26 patients with resistant AF, either paroxysmal (n=14) or permanent (n=12). A nonfluoroscopic mapping system was used to generate 3D electroanatomic LA maps and deliver RF energy. Two maps were acquired during coronary sinus and right atrial pacing to validate the lateral and septal PV lesions, respectively. Patients were followed up closely for >/=6 months. Procedures lasted 290+/-58 minutes, including 80+/-22 minutes for acquisition of all maps, and 118+/-16 RF pulses were deployed. Among 14 patients in AF at the beginning of the procedure, 64% had sinus rhythm restoration during ablation. PV isolation was demonstrated in 76% of 104 PVs treated by low peak-to-peak electrogram amplitude (0. 08+/-0.02 mV) inside the circular line and by disparity in activation times (58+/-11 ms) across the lesion. After 9+/-3 months, 22 patients (85%) were AF-free, including 62% not taking and 23% taking antiarrhythmic drugs, with no difference (P:=NS) between paroxysmal and permanent AF. No thromboembolic events or PV stenoses were observed by transesophageal echocardiography. CONCLUSIONS: Radiofrequency PV isolation with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF.

Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation.

BACKGROUND: Circumferential radiofrequency ablation around pulmonary vein (PV) ostia has recently been described as a new anatomic approach for atrial fibrillation (AF). METHODS AND RESULTS: We treated 251 consecutive patients with paroxysmal (n=179) or permanent (n=72) AF. Circular PV lesions were deployed transseptally during sinus rhythm (n=124) or AF (n=127) using 3D electroanatomic guidance. Procedures lasted 148+/-26 minutes. Among 980 lesions surrounding individual PVs (n=956) or 2 ipsilateral veins with close openings or common ostium (n=24), 75% were defined as complete by a bipolar electrogram amplitude <0.1 mV inside the lesion and a delay >30 ms across the line. The amount of low-voltage encircled area was 3594+/-449 mm(2), which accounted for 23+/-9% of the total left atrial (LA) map surface. Major complications (cardiac tamponade) occurred in 2 patients (0.8%). No PV stenoses were detected by transesophageal echocardiography. After 10.4+/-4.5 months, 152 patients with paroxysmal AF (85%) and 49 with permanent AF (68%) were AF-free. Patients with and without AF recurrence did not differ in age, AF duration, prevalence of heart disease, or ejection fraction, but the LA diameter was significantly higher (P<0.001) in permanent AF patients with recurrence. The proportion of PVs with complete lesions was similar between patients with and without recurrence, but the latter had larger low-voltage encircled areas after radiofrequency (expressed as percent of LA surface area; P<0.001). CONCLUSIONS: Circumferential PV ablation is a safe and effective treatment for AF. Its success is likely due to both PV trigger isolation and electroanatomic remodeling of the area encompassing the PV ostia.

Cardiac troponin T in chest pain unit patients without ischemic electrocardiographic changes: angiographic correlates and long-term clinical outcomes.

OBJECTIVES: We prospectively evaluated the relation between cardiac troponin T (cTnT) level, the presence and severity of coronary artery disease (CAD) and long-term prognosis in patients with chest pain but no ischemic electrocardiographic (ECG) changes who had short-term observation. BACKGROUND: Cardiac TnT is a powerful predictor of future myocardial infarction (MI) and death in patients with ECG evidence of an acute coronary syndrome. However, for patients with chest pain with normal ECGs, it has not been determined whether cTnT elevation is predictive of CAD and a poor long-term prognosis. METHODS: In 414 consecutive patients with no ischemic ECG changes who were triaged to a chest pain unit, cTnT and creatine kinase, MB fraction (CK-MB) were evaluated > or = 10 h after symptom onset. Patients with adverse cardiac events, including death, MI, unstable angina and heart failure were followed for as long as one year. RESULTS: A positive (>0.1 ng/ml) cTnT test was detected in 37 patients (8.9%). Coronary artery disease was found in 90% of 30 cTnT-positive patients versus 23% of 144 cTnT-negative patients who underwent angiography (p < 0.001), with multivessel disease in 63% versus 13% (p < 0.001). The cTnT-positive patients had a significantly (p < 0.05) higher percent diameter stenosis and a greater frequency of calcified, complex and occlusive lesions. Follow-up was available in 405 patients (98%). By one year, 59 patients (14.6%) had adverse cardiac events. The cumulative adverse event rate was 32.4% in cTnT-positive patients versus 12.8% in cTnT-negative patients (p = 0.001). After adjustment for baseline clinical characteristics, positive cTnT was a stronger predictor of events (chi-square = 23.56, p = 0.0003) than positive CK-MB (>5 ng/ml) (chi-square = 21.08, p = 0.0008). In a model including both biochemical markers, CK-MB added no predictive information as compared with cTnT alone (chi-square = 23.57, p = 0.0006). CONCLUSIONS: In a group of patients with chest pain anticipated to have a low prevalence of CAD and a good prognosis, cTnT identifies a subgroup with a high prevalence of extensive and complex CAD and increased risk for long-term adverse outcomes.

Wiktor stent for treatment of chronic total coronary artery occlusions: short- and long-term clinical and angiographic results from a large multicenter experience.

OBJECTIVES: This study reports the first multicenter experience with the Wiktor coil stent for treatment of chronic total coronary artery occlusions (CTOs). BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) of CTO is associated with very high restenosis and reocclusion rates. Coronary stenting has been proposed as a means of improving outcome. However, the Wiktor device for CTOs has never been tested in a large patient sample. METHODS: From January 1993 to December 1996, 89 patients with 91 CTOs underwent Wiktor stent implantation after successful PTCA. The post-stenting regimen consisted of warfarin (Coumadin) plus aspirin in the initial 49 patients (55%) and aspirin plus ticlopidine in 40 patients (45%). RESULTS: Stenting was successful in 87 patients (98%). At 1 month, 6% of patients had subacute stent thrombosis, 3% had a major bleeding event, and 1% had access-site complications. Subacute stent thrombosis showed univariate association with warfarin therapy (p = 0.009). Angiographic follow-up was obtained in 76 (93%) of 82 eligible patients. The restenosis rate was 32%, including 4% reocclusions. By multiple logistic regression analysis, restenosis was independently associated with multiple stents (adjusted odds ratio [OR] 27.67, 95% confidence interval [CI] 4.25 to 79.95, p = 0.0008) and increasing values of occlusion length (adjusted OR 1.23, 95% CI 1.09 to 1.39, p = 0.001). Freedom from death, myocardial infarction or stented vessel revascularization was 87% and 72% at 1 and 3 years, respectively. CONCLUSIONS: Short- and long-term clinical and angiographic outcomes are favorable in patients undergoing Wiktor stent implantation in CTO. Further technical improvement is needed to reduce the restenosis rate in patients with long lesions and multiple stents.

Randomized comparison of a strategy of predischarge coronary angiography versus exercise testing in low-risk patients in a chest pain unit: in-hospital and long-term outcomes.

OBJECTIVES: This randomized trial compared a strategy of predischarge coronary angiography (CA) with exercise treadmill testing (ETT) in low-risk patients in the chest pain unit (CPU) to reduce repeat emergency department (ED) visits and to identify additional coronary artery disease (CAD). BACKGROUND: Patients with chest pain and normal electrocardiograms (ECGs) have a low likelihood of CAD and a favorable prognosis, but they often seek repeat evaluations in EDs. Remaining uncertainty regarding their symptoms and diagnosis may cause much of this recidivism. METHODS: A total of 248 patients with no ischemic ECG changes triaged to a CPU were randomized to CA (n = 123) or ETT (n = 125). All patients had a probability of myocardial infarction < or =7% according to the Goldman algorithm, no biochemical evidence of infarction, the ability to exercise and no previous documented CAD. Patients were followed up for > or =1 year and surveyed regarding their chest pain self-perception and utility of the index evaluation. RESULTS: Coronary angiography showed disease (> or =50% stenosis) in 19% and ETT was positive in 7% of the patients (p = 0.01). During follow-up (374+/-61 days), patients with a negative CA had fewer returns to the ED (10% vs. 30%, p = 0.0008) and hospital admissions (3% vs. 16%, p = 0.003), compared with patients with a negative/nondiagnostic ETT. The latter group was more likely to consider their pain as cardiac-related (15% vs. 7%), to be unsure about its etiology (38% vs. 26%) and to judge their evaluation as not useful (39% vs. 15%) (p < 0.01 for all comparisons). CONCLUSIONS: In low-risk patients in the CPU, a strategy of CA detects more CAD than ETT, reduces long-term ED and hospital utilization and yields better patient satisfaction and understanding of their condition.

Prevention of restenosis after percutaneous coronary interventions: the medical approach.

Restenosis following successful percutaneous coronary revascularization continues to represent a major problem limiting the clinical efficacy of this procedure. The underlying mechanisms of restenosis are comprised of a combination of effects from vessel recoil, negative vascular remodeling, thrombus formation and neointimal hyperplasia. Indeed, there are important interactions among all of these mechanisms. For example, neointimal hyperplasia is stimulated by growth factors, which are released by local thrombi and the injured arterial segment itself, and act to enhance the expression of other growth-regulating proteins, in particular "second messengers", proto-oncogenes and other cell cycle controlling proteins. This results in an inflammatory and myofibroproliferative response, which may worsen vessel narrowing caused by recoil and result in the formation of a clinically significant restenotic lesion. A multitude of pharmacologic trials have been conducted in an attempt to prevent restenosis, but most have demonstrated little benefit. Studies in smaller numbers of patients have suggested a potential benefit for several classes of agents, including: 1) the antiproliferatives, angiopeptin, trapidil and tranilast; 2) selective elimination or alteration of proliferating cells; 3) enhancement of natural growth inhibitors; and 4) signal transduction blockade or inhibition of the gene expression for various growth-stimulating proteins. Finally, there have been advances in related areas, including development of antithrombotic catheters, novel polymers, and more efficient methods for transferring genes into the vessel wall. All of these offer the possibility of delivering agents (drugs, genes, or antisense oligonucleotides) locally at the site of intervention in a way that may optimize antiproliferative effects while minimizing systemic effects--ultimately leading to a more specific inhibition of the restenosis process.

Immediate and long-term clinical and angiographic results from Wiktor stent treatment for true bifurcation narrowings.

From January 1996 to December 1998, 90 consecutive patients with true bifurcation lesions underwent percutaneous coronary angioplasty with Wiktor stent implantation in our centers. In 1 group (group I, n = 45), a simple approach (main vessel stenting and balloon angioplasty of the side branch) was pursued. In the other group (group II, n = 45), both the main vessel and the side branch were stented ("T" technique). There was no significant difference in clinical and angiographic characteristics between the 2 groups. Angiographic and procedural successes were 100% and 95.6%, respectively, in both groups. Angiographic results for the side branch were better in group II than in group I. In-hospital and long-term (12 month) major cardiac events were similar in the 2 groups. Target lesion revascularization was 15.5% in group I and 35.5% in group II (p = 0.12). In the main vessel, restenosis rate was 12.5% in group I and 25% in group II (p = 0.15). In the side branch, restenosis rate was 37.5% in group II and 12.5% in group I (p = <0.05; odds ratio 2.42; 95% confidence interval 1.05 to 6.26). Event-free probability at 12 months was 61% in group II and 80% in group I (p = 0.10). When dealing with true bifurcation lesions, a simple strategy is associated with a lower risk of restenosis in the side branch. In contrast, a complex approach does not appear to give any benefit in terms of early or long-term outcome or restenosis rate.

Distribution of di(2-ethylhexyl) phthalate and products in blood and blood components.

In order to impart flexibility, plastic medical devices incorporate liquid plasticizers into their structure. Data from several laboratories, including ours, have shown that these compounds leach from blood bags and tubing during collection of blood, storage of various blood components and during kidney dialysis and cell and plasma apheresis procedures. After the plasticizer di(2-ethylhexyl) phthalate leaches from poly(vinyl chloride) blood packs, it is converted by a plasma enzyme to a more toxic metabolite, mono(2-ethylhexyl) phthalate. Blood fractionation products from outdated plasma contain mono(2-ethylhexyl) phthalate, the highest level being found in normal serum albumin. Recently, we have reported that di(2-ethylhexyl) phthalate actually binds to the red blood cell membrane and reduces its osmotic fragility. Current methods of red cells storage, which permit utilization up to 35 days after collection, are not possible without this membrane stabilization. Platelets are now stored for 5 days in the Fenwal PL 732 polyolefin bag. Although stated to be essentially free of liquid plasticizers, a significant level of leaching from this bag into the extracts of stored platelet concentrates was observed.

The effect of mono(2-ethylhexyl)phthalate on an isolated perfused rat heart-lung preparation.

Di(2-ethylhexyl)phthalate (DEHP), the plasticizer used in the biomedical production of blood storage bags, hemodialysis systems, cardiopulmonary bypass (CPB) circuitry, and intubation tubes, is extracted from the plastic material when it comes into contact with biological fluids and is converted to its principal metabolite, mono(2-ethylhexyl)phthalate (MEHP). We have shown that MEHP causes cardiac and respiratory arrest, as well as hypotension, when infused into anesthetized rats. Using a well-ventilated in vitro rat heart-lung preparation, we investigated the effect of MEHP on pulmonary artery pressure (PAP) and found that MEHP had a hypertensive effect on the pulmonary vasculature ending in constriction and edema. There was a significant increase of 0.58 mm Hg/min in the PAP of isolated rat lungs when perfused with MEHP dissolved in Krebs-Henseleit (K-H) buffer (p = 0.0003). The rat lungs that were perfused with K-H buffer only increased 0.094 mm Hg/min during the same perfusion time of 20 min. The water gained during this time was 0.22 g/min with MEHP in the buffer compared to 0.04 g/min with buffer alone. The pO2 in the effluent did not decrease during the perfusion time. The concentration of MEHP in the rat lungs after perfusion varied from 20 to 40 micrograms/g. Although the mechanism of action of MEHP on PAP is too complex to be fully elucidated by this model, the increase in PAP which we have demonstrated is significant and adds yet another toxic effect of this major metabolite of the ubiquitous plasticizer, DEHP.

Perioperative exposure to plasticizers in patients undergoing cardiopulmonary bypass.

Di(2-ethylhexyl)phthalate and its principal metabolite, mono(2-ethylhexyl)phthalate, are contaminants of blood that are extracted on contact with polyvinylchloride surfaces, such as blood collection bags and tubing used in cardiopulmonary bypass. In this study, levels of the two plasticizers were measured in patients who underwent coronary artery bypass grafting, orthotopic transplantation, implantation of the Jarvik 7-70 total artificial heart during bridge-to-transplant procedures, and in infants who underwent corrective operations for congenital defects. In all adult patients the levels of di(2-ethylhexyl)phthalate increased tenfold by the end of cardiopulmonary bypass, whereas the levels of mono(2-ethylhexyl)phthalate increased ninefold. In infants, levels of di(2-ethylhexyl)phthalate rose seven times by the end of bypass and mono(2-ethylhexyl)phthalate rose significantly as well. In most of the patients having coronary bypass, the two plasticizers declined to preoperative levels within 24 hours. However, in some of the patients having orthotopic transplantation and in those in whom the Jarvik 7-70 total artificial heart was used as a bridge to transplant, the levels were still detectable 120 hours postoperatively. Circulating levels of mono(2-ethylhexyl)phthalate are only 20- to 35-fold lower in patients undergoing cardiac operations than the level of mono(2-ethylhexyl)phthalate causing a 50% reduction in developed contractile force and arrhythmias in an in vitro human atrial trabecular preparation. This study shows that patients with multisystem failure and infants may be at risk for this acute exposure to mono(2-ethylhexyl)phthalate.

Use of stress testing to evaluate patients with recurrent chest pain after percutaneous coronary revascularization.

Controversy exists regarding the diagnostic accuracy, optimal technique, and timing of noninvasive stress testing after percutaneous transluminal coronary angioplasty (PTCA). Many patients return with chest pain after PTCA, and because the incidence of restenosis has been reported to be as high as 50%, a noninvasive test with a high predictive value is needed to reduce the need for unnecessary coronary angiography. Studies have shown that the sensitivity and specificity of stress testing varies depending on the amount of time elapsed since the procedure. Soon after a successful PTCA, perfusion defects on nuclear imaging following exercise or pharmacologic stress may be detected in asymptomatic patients without angiographic restenosis. In many patients, abnormal stress myocardial perfusion scans will normalize spontaneously, and thus stress testing with nuclear imaging within 4 to 6 weeks of PTCA lacks specificity for detecting restenosis. In contrast, stress echocardiography which detects wall motion abnormalities rather than perfusion mismatch has been reported to offer more specific information on myocardial ischemia and restenosis early after PTCA. In patients who develop chest pain more than 6 weeks after PTCA, the ability to accurately identify restenosis is shared by both echocardiographic and nuclear imaging methods. The purpose of this review is to clarify the strengths, pitfalls, and prognostic value of different stress modalities and cardiac imaging techniques in patients who develop chest pain within 6 months of undergoing PTCA.

Cardiac pacing in heart failure patients with left bundle branch block: impact of pacing site for optimizing left ventricular resynchronization.

BACKGROUND: Acute left ventricular pacing has been associated with hemodynamic improvement in patients with congestive heart failure and wide QRS complex. We hypothesized that pacing two left ventricular sites simultaneously would produce faster activation and better systolic function than single-site pacing. METHODS: We selected 14 heart failure patients (NYHA functional class III or IV) in normal sinus rhythm with left bundle branch block and QRS > 150 ms. An 8F dual micromanometer catheter was placed in the aorta for measuring +dP/dt (mmHg/s), aortic pulse pressure (mmHg), and end-diastolic pressure (mmHg). Pacing leads were positioned via coronary veins at the posterior base and lateral wall. Patients were acutely paced VDD at the posterior base, lateral wall, and both sites (dual-site) with 5 atrioventricular delays (from 8 ms to PR -30 ms). Pacing sequences were executed in randomized order using a custom external computer (FlexStim, Guidant CRM). RESULTS: Dual-site pacing increased peak +dP/dt significantly more than posterior base and lateral wall pacing. Dual-site and posterior base pacing raised aortic pulse pressure significantly more than lateral wall pacing. Dual-site pacing shortened QRS duration by 22 %, whereas posterior base and lateral wall pacing increased it by 2 and 12%, respectively (p = 0.006). CONCLUSIONS: In heart failure patients with left bundle branch block, dual-site pacing improves systolic function more than single-site stimulation. Improved ventricular activation synchrony, expressed by paced QRS narrowing, may account for the additional benefit of dual- vs single-site pacing in enhancing contractility. This novel approach deserves consideration for future heart failure pacing studies.

[Prospects of the treatment of atrial fibrillation. Circumferential radiofrequency ablation of pulmonary vein ostia]. / Prospettive nel trattamento della fibrillazione atriale. L'ablazione circonferenziale in radiofrequenza degli osti delle vene polmonari.

The dominance of the left atrium (LA) in the pulmonary vein (PV) regions for triggering and maintaining atrial fibrillation (AF) is now widely recognized. Radiofrequency (RF) PV isolation with electroanatomical guidance has recently emerged as a promising approach for AF treatment. We report the clinical outcome of the procedure in 251 consecutive patients with paroxysmal (n = 179) or permanent (n = 72) AF. Circular RF lesions were deployed transseptally during sinus rhythm or AF at 5 mm from PV ostia. Procedural and mapping times were 112 +/- 32 min and 75 +/- 27 min, respectively, with 29 +/- 11 min of fluoroscopy. Complete lesions (peak-to-peak bipolar electrogram amplitude < 0.1 mV inside the line and no double potentials) were achieved in 85% of the veins treated. Sinus rhythm was restored during RF delivery in 52% and by DC shock in the remaining. Major complications (cardiac tamponade) occurred in 3%. Extent of ablated area was 4.9 +/- 0.5 cm2, accounting for 28 +/- 9% of the total LA map surface. After 11 +/- 5 months, procedure success rates (freedom from AF without antiarrhythmic drugs) were 85% for paroxysmal and 68% for permanent AF. No PV stenoses were detected. By univariate analysis, an increased risk of recurrence was predicted by LA dilation (diameter > 50 mm), AF duration, and a low ablated area (< 15% of total LA surface). After adjustment, only the latter variable continued to be significant (odds ratio 3.5, 95% confidence interval, 1.6-5.8). In conclusion, RF PV isolation is safe and effective in either paroxysmal or permanent AF. Patients with enlarged left atrium may require wider lesions to achieve AF suppression.

Contamination of platelet storage bags by phthalate esters.

Phthalate esters are the most extensively used plasticizers in the manufacture of polyvinylchloride (PVC) plastic. Many medical devices used in the collection and storage of blood components are made of PVC plastic containing di(2-ethylhexyl) phthalate (DEHP). DEHP leaches at a rate of 100 micrograms/ml X d into platelet concentrate (PC) supernatant when PCs are stored in PVC containers. It is only possible to store PCs for 72 h in this DEHP plastic, after which time the platelet function has deteriorated and they cannot be used for transfusion therapy. Since it was desirable to find a container that permitted longer storage times and because of the concern for the toxicity of DEHP, new bags, manufactured with different plastic formulations without this plasticizer, were tested for PC storage. Using these new containers, such as the PL732 [polyolefin (PO) plastic], and the CLX300 and PL1240 [tri(2-ethylhexyl) trimellitate (TEHTM) PVC plastic], it was possible to store PCs for 5 d while preserving platelet function. In spite of these new plastic bags being manufactured without DEHP, we found DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) as contaminants of the supernatant of the PCs stored in these containers. After analyzing the plastic material of each of these containers, we were able to identify the source of the contamination as coming from the plastic materials that were used in the manufacture of the bags. The sterilization process of the PL732 bag was investigated, since it was found that when the plastic of the PL732 bag was analyzed prior to sterilization, no contamination by DEHP was detected; however, whether the PL732 bag was sterilized together with the primary PVC bag or separately, using ethylene oxide, contamination by DEHP was found, suggesting contamination of the sterilization unit by DEHP.

Platelet storage. Effects of leachable materials on morphology and function.

A polyolefin plastic (PL 732) bag formulated without liquid plasticizer allows storage of platelets for 5 and, now, up to 7 days. In order to assess the leaching of compounds from this new plastic, extracts of the supernatant from platelet concentrates stored in these bags were analyzed by high-performance liquid chromatography, mass spectrometry, and gas-liquid chromatography. A leachable material was detected and identified as di(2-ethylhexyl) phthalate (DEHP). During the sterilization process, migration of the DEHP occurs from the polyvinylchloride (PVC) bags into the PL 732 plastic bag. The level of DEHP was 12-fold less in the extracts of PC supernatant stored in the PL 732 bag than those in the polyvinyl chloride (PL 146) plastic bags which were used previously for platelet storage. Platelets stored in low DEHP concentrations in the PL 732 bags were composed of 10 to 35 percent of unclassifiable shapes. These shape changes were not observed in higher concentrations of plasticizer, although the morphology scores decreased during storage in PL 146 as well. This effect on morphology was not related directly to the dose of DEHP. When platelet membranes were isolated from platelets stored in the presence of radiolabeled DEHP, the amount of bound 14C-DEHP was found to be directly proportional to the concentration of DEHP in the plasma supernatant. However, while there was a linear relationship between the protein concentration in the membrane fraction and the amount of bound DEHP, no specific DEHP binding site could be identified by electrophoresis of the solubilized platelet membranes.

Incorporation of plasticizer into red cells during storage.

The development of flexible plastic blood bags has permitted effective blood component production and therapy. However, the plasticizer di(2-ethylhexyl)phthalate (DEHP), whose toxicity in humans is still undefined, is known to leach from the plastic into stored blood. Despite the availability of bags made of plastics not using DEHP, the collection and storage of red cells is still done in DEHP plasticized packs, and in fact the storage life for red cells has recently been increased up to 49 days using new anticoagulant-preservative solutions. We examined the relationship between DEHP and stored red cells. We found that 28 percent of available 14C-DEHP binds immediately to sites in both the membrane and cytosol fractions of the red cells, and that the total amount and distribution of 14C-DEHP does not change significantly over 7 days. When red cell concentrates were stored with or without DEHP, using either plastic (polyolefin) bags not containing DEHP or glass, definite reduction in the osmotic stability of the red cells was found in the absence of DEHP. Plasma-free hemoglobin levels were 90.3 mg per dl after 35 days of storage in plastic packs containing DEHP and 181.7 mg per dl in the polyolefin bags. The advantages of improved in vitro stability of red cells stored in plastics containing DEHP must be weighed against the potential hazards of patient exposure to DEHP.

[Usefulness of stress echocardiography in the evaluation of clinical and functional success of coronary angioplasty and prognostic stratification]. / Utilità dell'ecocardiografia da sforzo per la valutazione del successo clinico e funzionale dell'angioplastica coronarica e per la stratificazione prognostica.

The present study, selecting 39 patients undergoing elective coronary angioplasty (PTCA) with signs of myocardial ischemia during supine bicycle exercise stress test (EST) before PTCA and on medical therapy, was designed: to evaluate the efficacy of angiographically successful PTCA on functional capacity, in terms of work load, time of exercise and rate-pressure product (RPP), by comparing pre- and post-PTCA-EST performed in patients with post-PTCA disappearance (Group I, 44%) or persistence (Group II, 56%) of myocardial ischemia, and in the latter, to evaluate the effects of medical therapy, by repeating EST after its addition; to investigate the influence of PTCA on regional function, assessed by a 11 segment model and graded as usual, in the 25 patients group with pre-PTCA exercise-induced wall motion abnormalities, disappearing (Group A, 64%) or persisting (Group B, 36%) after the interventional procedure; to examine by a 12-month follow-up the eventuality of recurrent anginal symptoms, in the presence of myocardial ischemic signs in the territory supplied by the dilated vessel and/or of angiographic restenosis, in relation to the result of post-PTCA-EST. The results of our study showed a significant improvement in functional capacity after PTCA only in Group I patients, whereas in Group II patients effort tolerance significantly increased only after medical therapy, which was associated with the disappearance of myocardial ischemia. With regard to follow-up, exercise echocardiography showed a positive and negative predictive value for angina recurrence with angiographic restenosis of 78 and 92%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)