Reduced toxicological activity of cigarette smoke by the addition of ammonium magnesium phosphate to the paper of an electrically heated cigarette: smoke chemistry and in vitro cytotoxicity and genotoxicity.

The effects of the addition of ammonium magnesium phosphate (AMP) to the paper of an electrically heated cigarette (EHC) prototype on smoke composition and toxicity were quantified and the underlying mechanisms investigated. Smoke from EHC prototypes with and without AMP and from conventional cigarettes, i.e. the University of Kentucky Standard Reference Cigarette 1R4F and eight American-blend market cigarettes, was compared. Endpoints for comparison were smoke chemistry, where toxic constituents were measured, cytotoxic activity, as measured in murine fibroblasts embryo cells by the Neutral Red Uptake Assay, and genotoxic activity, as measured in bacteria by the Salmonella Reverse Mutation Assay and in murine lymphoma cells by the TK Assay. The addition of AMP to the EHC led to a reduction of toxic substances and toxicological activity of approximately 30% compared to the EHC without AMP. Compared to the conventional cigarettes, the EHC with AMP showed reductions of 75-90%. Smoke from the EHCs generated in nitrogen atmospheres supplemented with different concentrations of ammonia and oxygen was assayed for its in vitro cytotoxicity and genotoxicity. The results indicate that the ammonia released by AMP at the heating site of the EHC is responsible for the reductions in cytotoxicity and mutagenicity for the EHC with AMP compared with the EHC without AMP. Thus, while the EHC approach distinctly reduces toxic smoke constituents compared to conventional cigarettes, the use of AMP in the paper of an EHC leads to further distinct reductions. In the study presented here, in vitro assays were used as quantitative tools to investigate toxicity-related mechanisms.

Prediction of infarction-related artery occlusion and multivessel disease in postinfarction angina.

CONDENSED ABSTRACT: To investigate the predictive value of clinical data for infarction-related artery (IRA) occlusion and multivessel coronary disease in postinfarction angina (PIA), we studied 181 consecutive patients presenting PIA following a first uncomplicated ST elevation AMI. Multivariate analysis showed ECG changes during PIA and the absence of thrombolytic therapy as independent predictors of IRA occlusion. Independent clinical predictors of multivessel coronary disease were age, previous history of angina and the number of cardiovascular risk factors. We conclude that reversible ECG changes during PIA correlated to IRA occlusion but failed to predict a multivessel coronary disease. AIM: To identify clinical variables predictive of infarction-related artery (IRA) occlusion and multivessel coronary disease in patients with postinfarction angina pectoris (PIA) after a first uncomplicated acute myocardial infarction (AMI). METHODS: We studied 181 consecutive patients with PIA following a first uncomplicated AMI. Clinical variables included cardiovascular risk factors, clinical history of angina before the event of inclusion, use of thrombolytic therapy in the previous AMI, ST-T changes during PIA, time to onset, number of episodes and delay to angiography after PIA. Angiographic variables were IRA TIMI flow, number of diseased vessels and ventricular function. RESULTS: The IRA was occluded in 67 patients with PIA (37.0%). Reversible ECG changes during PIA were detected in 121 patients (67.0%): 79 cases (43.6%) with ST/T elevation and 42 cases (23.2%) with ST/T depression. Multivariate logistic regression analysis showed ECG changes during PIA (OR 3.12 CI 95% 1.48-6.54, p<0.01) and the absence of thrombolytic therapy (OR 2.21 95% CI 1.11-4.43, p<0.05) as independent predictors of IRA occlusion. We found multivessel coronary disease in 89 patients (49.2%) without any correlation to ECG changes during PIA. Independent clinical predictors of multivessel coronary disease were age (OR 1.03 95% CI 1.01-1.06, p<0.05), previous history of angina (OR 2.37 95% CI 1.06-5.28, p<0.05) and the number of cardiovascular risk factors (OR 1.37 95% CI 0.97-1.92, p=0.07). CONCLUSIONS: ECG changes during PIA was correlated to IRA occlusion in spite of previous thrombolytic therapy but failed to predict a multivessel coronary disease in our patients.

[Initial results and 6 month clinical follow-up after implantation of a silicon carbide coated coronary stent]. / Resultados iniciales y seguimiento clínico a 6 meses tras el implante de un stent coronario recubierto de carburo de silicio.

INTRODUCTION AND OBJECTIVES: To present the initial Spanish experience with the Tenax coronary stent, a laser sculpted from high-precision 316L stainless steel coated with hydrogen rich amorphous silicon carbide that reduces thrombogenecity and improves biocompatibility. PATIENTS AND METHODS: From July 1998 to July 1999, 206 patients (62 +/- 5 years) underwent implantation of 231 Tenax stents in 9 centers as the only revascularization procedure. The most frequent clinical indication was unstable angina (66%), and most of the lesions were complex (class B2 and C). The target vessels were the left anterior descending (51%) and right coronary arteries (36%). The ejection fraction was < 0.5 in 19% cases. RESULTS: Revascularization was complete in 70%, elective in 80%, and the implantation was direct in 25% of the cases. The procedure was successful in all the lesions, reducing stenosis from 62 +/- 16 to 16 +/- 10% and increasing the minimal luminal diameter from 0.81 +/- 0.40 to 2.61 +/- 0.59 mm. The TIMI flow was reduced in 30%, but normalized after the stent in all but one case. The incidence of cardiac events was minimal: 1 acute thrombosis (0.5%) resolved by a new angioplasty and 1 non-Q myocardial infarction (0.5%). At the 6-month clinical follow-up 10% of the patients presented complaints of angina greater than class II, and a new angioplasty was carried out in 1.9% of these cases. CONCLUSION: Clinical and angiographic data suggest that the hydrogenated silicon carbide coating of the Tenax coronary stent may indeed play a beneficial role in patient outcome, and should therefore be evaluated by prospective clinical trials.

The form of nicotine in tobacco. Thermal transfer of nicotine and nicotine acid salts to nicotine in the gas phase.

Thermal transfer to nicotine in the gas phase from neat nicotine, from various nicotine carboxylic acid salts, and from endogenous nicotine in Burley, Bright, and Oriental tobacco samples has been examined by thermogravimetric/differential thermal analysis/mass spectroscopy and evolved gas analysis. Under the conditions used in these studies, the peak transfer temperatures of these substances to nicotine in the gas phase are nicotine and nicotine acetate, both ca. 110-125 degrees C; nicotine malates, ca. 110-210 degrees C for nicotine to malic acid ratios of 1:0.56 and 1:1 and ca. 160-210 degrees C for a nicotine to malic acid ratio of 1:2; (S)-nicotine bis[(2R,3R)-hydrogen tartrate] dihydrate, ca. 195-210 degrees C; and tobacco samples, a range of ca. 160-220 degrees C. These results suggest that nicotine is mostly protonated in tobacco leaf. In all cases, the temperature of the transfer of nicotine to the gas phase was found to be many hundreds of degrees below the temperatures observed around the coal of a burning cigarette (smolder, ca. 500-775 degrees C; dynamic smoking, 600 to over 950 degrees C). Within the narrow zone of a puffing cigarette that encompasses an intermediate temperature range (125-250 degrees C), kinetic data suggest that these temperatures are not sufficient to volatilize significant amounts of nonprotonated nicotine, assuming any exists at all, during the short puff duration (2 s). It is concluded that nonprotonated nicotine and protonated nicotine (salts of nicotine with natural tobacco carboxylic acids) will transfer nicotine to smoke with comparable yields and efficiencies during the smoking process.

Normal angiogram after myocardial infarction in young patients: a prospective clinical-angiographic and long-term follow-up study.

This is an observational study in which we compared the clinical characteristics and the long-term course of young patients having acute myocardial infarction and angiographically normal coronary arteries and young patients showing significant coronary artery disease. In 87 patients aged < or = 40 years who suffered an acute myocardial infarction, enrolled in a prospective study over a period of 6.5 years, coronary anatomy was determined by angiography within a month of admission. The risk factors, clinical data, ventricular function and the long-term outcome were compared between patients with normal angiograms (Group 1, n = 12) and patients with coronary artery disease (Group 2, n = 75). Patients in Group 1 had a lower number of risk factors associated with them (17% vs. 64% with > 1 risk factor, P < 0.005), were younger (32 +/- 5 vs. 36 +/- 4, P < 0.01), lighter smokers (25% vs. 55% for > or = 2 packs per day, P < 0.05), had less frequent hypertension (0 vs. 25%, P < 0.05), hypercholesterolemia (17% vs. 52%, P = 0.02) and had a lower mean total cholesterol level (201 +/- 42 vs. 245 +/- 60 mg/100 ml, P < 0.05) than patients in Group 2. They also had a more common onset of their infarction during heavy physical exertion (67% vs. 17%, P < 0.001). A history of previous myocardial infarction, infarct location, global left ventricular function and regional wall motion were similar in both groups. After a mean follow-up period of 41 +/- 23 months, no patient died or had a second myocardial infarction in Group 1, and 4 patients had died in Group 2. The appearance of angina, less frequent in Group 1 than Group 2, tended to correlate with the extension of the coronary artery disease. We concluded that young patients with myocardial infarction have good prognosis irrespective of the coronary anatomy, although patients with normal coronary angiograms had less risk factors and less frequent new ischaemic events.

Myocardial infarction in men aged 40 years or less: a prospective clinical-angiographic study.

HYPOTHESIS: The study was undertaken to characterize acute myocardial infarction (AMI) in young patients. METHODS: In all 108 consecutive Mediterranean patients with AMI (102 men and 6 women), aged < or = 40 years, were prospectively included in this study over a period of 6.5 years. Coronary angiography was carried out within the first month and data from these patients with normal or diseased coronary arteries were compared. Clinical features, risk factors, and in-hospital and late morbidity and mortality were evaluated. RESULTS: Young patients with AMI represent 4.1% of the 2,644 patients admitted because of definite AMI during this period. The most common risk factors were cigarette smoking (94.5%) and hypercholesterolemia (48%). Location of the AMI was anterior in 37%, inferior in 57.5%, and non-Q in 5.5%. A history of previous angina was present in 42.5% of the patients, including all seven patients with previous myocardial infarction (6.5%). However, in 52% of the patients the anginal episodes started in the week prior to the AMI. In-hospital mortality and mortality during a mean follow-up of 41 +/- 23 months were 3.7 and 3.8%, respectively. The Kaplan-Meier actuarial curve assessed on 97 of 104 survivors was 100 and 94% at 1 and 5 years, respectively. Coronary arteries were angiographically normal in 17 (20%) of 87 survivors. Compared with young patients who had obstructive lesions, this subset had a lower age and fewer risk factors, reinfarction (p < 0.05), and late angina (p < 0.01), but development of congestive heart failure and survival were similar in both groups. CONCLUSION: These data suggest that young patients with AMI are very frequently heavy smokers, have a high incidence of angiographically normal coronary arteries, and that the short- and long-term prognosis is excellent.

Spontaneous coronary artery dissection in mitral stenosis.

Spontaneous coronary artery dissection is a rare disease that occurs most commonly in young people, especially in peripartum or postpartum women. It has rarely been diagnosed during life and has never before been observed associated with any other non-ischaemic heart disease. We report a case associated with mitral stenosis, in which successful valvular and coronary surgery were carried out. We speculate whether rheumatic coronary arteritis was a cause of the dissection.

Coronary angioplasty of anomalous right coronary artery originating from the left sinus of Valsalva.

Coronary angioplasty of an anomalous coronary artery can be technically challenging because of difficulty in cannulating the aberrant vessel and in obtaining a stable guiding catheter position. Only three cases with the right coronary artery originating from the left sinus of Valsalva were previously reported. We present a new case in which a successful angioplasty was obtained using a Williams LR guiding catheter.

Selective ergonovine-induced coronary artery spasm and ST-segment alternans after blunt thoracic trauma.

A 24-year-old man was found to have angiographically normal coronary arteries shortly after suffering blunt thoracic trauma. Selective ergonovine administration into the left coronary artery induced total occlusion of the left anterior descending branch and electrical alternans of the ST-segment. This case demonstrates coronary artery spasm as a possible mechanism of coronary occlusion after blunt thoracic trauma.

[Chest pain of esophageal origin in patients with a normal coronary angiogram and ergonovine-induced coronary spasm]. / Dolor torácico de origen esofágico en pacientes con arteriograma coronario normal y espasmo coronario inducido por ergonovina.

In order to differentiate the cardiac or oesophageal origin of chest pain, 55 patients with chest pain, normal coronary arteriogram and normal left ventricular function, were studied. Patients were evaluated with ergonovine test to induce coronary artery spasm and oesophageal function study (including basal manometry in all cases, ClH acid instillation in 53, manometry during ClH instillation in 32 and edrophonium test in 9). There was coronary artery spasm following ergonovine test in 8 patients (group 1) and negative results in 47 (group 2). There was oesophageal disfunction in 50% patients in group 1 and in 62% patients in group 2 (p = NS). The incidence of motor disorders or chest pain following acid instillation was not significatively different in both groups. Nevertheless, in group 1 a tendency to a greater incidence of oesophageal spasm was observed while in group 2 unspecified disorders were more frequent. Thus, in patients with chest pain and normal coronary arteriogram, we always must discard coronary artery spasm and oesophageal disfunction, because, due to a probably common cause, association between both disorders is frequent.

[Acute myocardial infarct and coronary artery aneurysm during pregnancy]. / Infarto agudo de miocardio y aneurisma arterial coronario durante el embarazo.

We present the first published case in Spain on a gestant woman with acute myocardial infarction. She was angiographically studied showing a coronary artery aneurysm with inner thrombus. This is also the first time that such a lesion is described in vivo in a gestant woman.

[The selective induction of a spasm with ergonovine in a normal coronary artery in the presence of contralateral stenosis]. / Inducción selectiva de espasmo con ergonovina en una arteria coronaria normal en presencia de estenosis contralateral.

We present a patient with circumflex artery stenosis and recent unstable angina. Selective ergonovine administration on angiographically normal right coronary artery evidenced that at least some of the anginal crisis could be due to spasms of it. We comment the usefulness of the ergonovine intracoronary test in the presence of fixed obstructive lesions.

[The local and systemic effects of intracoronary ergonovine in patients with normal and nonspastic coronary arteries. A comparison with the intravenous ergonovine test]. / Efectos local y sistémico de la ergonovina intracoronaria en pacientes con arterias coronarias normales y no espásticas. Comparación con el test de ergonovina intravenoso.

Local and systemic effects of intracoronary (two bolus injections of 25 micrograms at 3-min intervals) ergonovine were determined in 60 patients with angiographic non-spastic normal coronary arteries and were compared with the most usual intravenous ergonovine dose to induce coronary artery spasm (incremental doses of 50, 100 and 200 micrograms at 3-min intervals). The mean diameter of the vessels was reduced by 15% after selective injections (baseline 2.38 +/- 0.7; after intracoronary ergonovine 2.02 +/- 0.6 mm; p less than 0.001) and no significant changes were induced in the heart rate (before 80 +/- 15; after 79 +/- 15 beats/min) and systolic aortic pressure (before 147 +/- 27; after 149 +/- 28 mmHg). Following intravenous administration, the mean coronary diameter decreased by 20% (1.90 +/- 0.6 mm; p less than 0.01 vs intracoronary dose) and the heart rate diminished slightly (76 +/- 12 beats/min; p less than 0.01). Nevertheless, the systolic aortic pressure did increase by 16% (171 +/- 28 mmHg; p less than 0.001). No major complications were observed and the appearance of side effects was minimal. Thus, the intracoronary delivery route, at the applied dosage, induces lesser vasoconstriction than usual intravenous administration, and systemic effects, such as hypertension, are avoided.

Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole. Grupo Español para el Seguimiento del Injerto Coronario (GESIC)

To analyze the efficacy of low-dose aspirin in preventing early aortocoronary vein graft occlusion, 1,112 consecutive patients were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial comparing 50 mg t.i.d. aspirin, 50 mg aspirin plus 75 mg t.i.d. dipyridamole, and placebo. All patients received 100 mg q.i.d. dipyridamole for 48 hours before surgery, and assigned treatment was started 7 hours after surgery. Vein graft angiography was performed in 927 patients (83%) within 28 days of surgery (mean, 10 days). Aspirin plus dipyridamole significantly (p = 0.017) reduced the occlusion rate of distal anastomoses from 18% (placebo) to 12.9%. Occlusion rate in the aspirin group was 14%, which approached statistical significance (p = 0.058). Furthermore, only aspirin plus dipyridamole reduced (p = 0.01) the number of patients with occluded grafts (placebo, 33%; aspirin, 27.1%; aspirin plus dipyridamole, 24.3%). Mediastinal drainage was slightly higher (p = 0.04) in the aspirin plus dipyridamole group (713 +/- 456 ml) than in the other two groups (placebo, 670 +/- 437 ml; aspirin, 629 +/- 337 ml), but hospital mortality (average, 4.6%) and early reoperation (average, 3.9%) rates were similar among the three groups. Thus, low-dose aspirin plus dipyridamole safely improves early saphenous vein aortocoronary graft patency; this effect is an added benefit to a preoperative regimen of dipyridamole.

Effects of intracoronary injection of ergonovine on angiographic normal coronary arteries: study of 108 consecutive patients.

To assess the local and systemic intracoronary (IC) ergonovine maleate (EM), single or repeated 25 micrograms bolus injections were administered to 108 consecutive patients with chest pain and normal coronary arteriograms. Coronary artery spasm (CAS) was induced in 17 (15.7%) patients. None of these patients developed ST-segment depression, and ST-segment elevation appeared in only 6 (35.3%). In 59 of the 91 patients without CAS, both the IC and the intravenous (IV) EM arteriographic and hemodynamic effects were compared. The mean diameter of the vessels was reduced by 15% (p less than 0.001) after two single 25 micrograms ICEM injections. Only insignificant changes were induced in the heart rate (baseline 80 +/- 15; after ICEM 79 +/- 15 beats/min; p = NS) and systolic aortic pressure (baseline 147 +/- 27; after ICEM 149 +/- 28 mmHG; p = NS). Following 350 micrograms of cumulative IVEM, the mean coronary diameter decreased by 20% (p less than 0.01 vs. ICEM dose) and the heart rate diminished slightly (76 +/- 12 beats/min, p less than 0.01). However, the systolic aortic pressures did increase by 16% (171 +/- 28 mmHg; p less than 0.001). No major complications were observed. Thus, to induce CAS the IC delivery route appears to be safe, allows for more accurate titration, and adverse systemic effects, such as hypertension, are avoided.

The use of a biocompatible orthopaedic polymer in the treatment of loose total hip prostheses.

Seventeen cases of loose total hip prostheses were treated with biocompatible orthopaedic polymer, an osteoconductive co-polymer. Biocompatible orthopaedic polymer permits improved stability and secondary bone repair and may also act as a vehicle for adjunctive antibiotic therapy. The available forms of biocompatible orthopaedic polymer and their methods of application are described and the results obtained with their use are compared with the pre-operative clinical observations. Of the 17 patients studied, pain disappeared in 14, unlimited walking became possible in seven, while another eight patients were subsequently able to walk for over 300 m. Mobility became normal in 13 cases; full weight bearing on one leg became possible in 12 cases and became normal in another four. Radiological examination showed the development of a bony interface between the cortex and the prosthesis as the radiolucent biocompatible orthopaedic polymer material was converted into bone. It may, therefore, be concluded that, in this indication, biocompatible orthopaedic polymer appears to be an active interface for stabilizing loose total hip prostheses.