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Biomedical subjects

G T Wilkins

Publications and source records attributed to G T Wilkins.

At least 19 recordsLinked to original sources

Elevated plasma active matrix metalloproteinase-9 level is associated with coronary artery in-stent restenosis.

OBJECTIVE: This study aimed to determine whether the plasma levels of matrix metalloproteinase-9 (MMP-9) or tissue inhibitor of metalloproteinases-1 (TIMP-1) were altered in patients with a history of symptomatic in-stent restenosis (ISR). METHODS AND RESULTS: A group of 158 patients with a history of ISR were compared with 128 symptom-free patients. Plasma samples and a detailed risk factor history were collected. Plasma samples were analyzed for pro-MMP-9 and latent MMP-9 and active MMP-9, latent MMP-3, and TIMP-1. Several variables were associated with ISR, including index coronary disease extent and severity (number of diseased vessels and American College of Cardiology/American Heart Association lesion classification), number, diameter, and total length of stent(s) inserted, and plasma high-density lipoprotein cholesterol. Plasma active MMP-9 (odds ratio, 1.96; 95% CI, 1.43 to 2.69) showed independent risk association with ISR. Patients with multiple sites of ISR had significantly higher levels of active MMP-9 compared with patients with only a single ISR lesion or no ISR. CONCLUSIONS: Plasma active MMP-9 levels may be a useful independent predictor of bare metal stent ISR.

Aged↗

Randomised comparison of the effects of nicardipine and esmolol on coronary artery wall stress: implications for the risk of plaque rupture.

OBJECTIVE: To determine whether the beta blocker esmolol reduces coronary artery wall stress more than the short acting dihydropyridine calcium antagonist nicardipine. DESIGN: Randomised double blind placebo controlled trial. SETTING: Tertiary cardiology centre. PATIENTS: Patients with coronary artery disease. INTERVENTIONS: 20 patients were randomised double blind to an infusion of nicardipine (n = 10) or esmolol (n = 10) titrated to reduce systolic blood pressure by 20 mm Hg. MAIN OUTCOME MEASURES: Peak systolic wall circumferential stress. RESULTS: Esmolol reduced peak coronary stress by a mean of 0.17 x 10(6) dyn/cm(2) (95% confidence interval (CI) 0.14 to 0.21 x 10(6) dyn/cm(2)) compared with a reduction of 0.07 x 10(6) dyn/cm(2) (95% CI 0.05 to 0.10 x 10(6) dyn/cm(2)) after nicardipine. Peak systolic radius was reduced by 0.04 mm (95% CI 0.03 to 0.06 mm) after esmolol compared with an increase of 0.08 mm (95% CI 0.05 to 0.10 mm) after nicardipine. Heart rate increased by 11.5 beats/min (95% CI 6.9 to 16.2 beats/min) after nicardipine and decreased by 5.3 beats/min (95% CI 1.9 to 8.6 beats/min) after esmolol. CONCLUSIONS: Intravenous esmolol is more effective than nicardipine at reducing circumferential coronary artery wall stress.

Adrenergic beta-Antagonists↗

Impaired endothelial function following a meal rich in used cooking fat.

OBJECTIVES: The purpose of this study was to test the hypothesis that intake of used cooking fat is associated with impaired endothelial function. BACKGROUND: Diets containing high levels of lipid oxidation products may accelerate atherogenesis, but the effect on endothelial function is unknown. METHODS: Flow-mediated endothelium-dependent dilation and glyceryl trinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 10 men. Subjects had arterial studies before and 4 h after three test meals: 1) a meal (fat 64.4 g) rich in cooking fat that had been used for deep frying in a fast food restaurant; 2) the same meal (fat 64.4 g) rich in unused cooking fat, and 3) a corresponding low fat meal (fat 18.4 g) without added fat. RESULTS: Endothelium-dependent dilation decreased between fasting and postprandial studies after the used fat meal (5.9 +/- 2.3% vs. 0.8 +/- 2.2%, p = 0.0003), but there was no significant change after the unused fat meal (5.3 +/- 2.1% vs. 6.0 +/- 2.5%) or low fat meal (5.3 +/- 2.3% vs. 5.4 +/- 3.3%). There was no significant difference in endothelium-independent dilation after any of the meals. Plasma free fatty acid concentration did not change significantly during any of the meals. The level of postprandial hypertriglyceridemia was not associated with change in endothelial function. CONCLUSIONS: Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.

Adult↗

Assessment of the mechanical properties of coronary arteries using intravascular ultrasound: an in vivo study.

The pressure-area relation of coronary arteries provides important information about the mechanical properties of these vessels. In human subjects methodological limitations have precluded measurement of instantaneous compliance and coronary stress in vivo. The purpose of this study was to assess a new method for measuring instantaneous values of coronary artery compliance and wall stress utilizing simultaneously acquired pressure and intravascular ultrasound measurements of vessel area. Ten subjects with coronary artery disease had intravascular ultrasound studies of the proximal left anterior descending or circumflex coronary arteries. Coronary luminal area was measured with a 30-MHz (3F or 3.5F) intravascular ultrasound catheter and simultaneous coronary pressure measured with a 2F micromanometer-tipped catheter. Using this technique the nonlinear pressure-area relation and mean circumferential wall stress were determined over the physiological pressure range. Coronary artery compliance at 100 mmHg ranged from 0.010 to 0.052 mm2/mmHg (mean +/- SD, 0.020+/-0.012 mm2/mmHg). Peak systolic circumferential stress ranged from 0.52 to 2.03 x 10(6) dyn/cm2 (1.09+/-0.42 x 10(6) dyn/cm2). This study describes a new method of determining coronary artery mechanical properties over the physiological pressure range. This technique may be useful in further studies of coronary artery mechanics.

Compliance↗

Long stenting in native coronary arteries: relation between vessel size and outcome.

Procedural and 6-mo clinical outcomes were evaluated in 34 consecutive patients who had stenting (<40 mm) of a long segment of coronary artery. Procedural success was achieved in 32 (96%) patients. Before stenting, 32 (96%) patients had Canadian Cardiovascular Society Class 3 or 4 angina compared to 7 (21%) at 6-mo follow-up (P<0.001). Eleven patients (32%) suffered either acute/subacute stent thrombosis (n=4) or restenosis (n=7). On logistic regression distal reference diameter <2.5 mm (odds ratio 26, P<0.01) and previous cardiac intervention (odds ratio 9.0, P<0.01) were independent predictors of a major adverse event during follow-up. There was no significant association between outcome and indication for stenting, type of stent, or use of ticlopidine and aspirin. These results indicate that distal vessel diameter <2.5 mm is a powerful predictor of subacute thrombosis or restenosis after long coronary artery stenting.

Adult↗

Association between activity at onset of symptoms and outcome of acute myocardial infarction.

OBJECTIVES: This study sought to compare the clinical features and outcome of a first myocardial infarction with onset of symptoms during or within 30 min of exercise, at rest and in bed. BACKGROUND: It is not known whether activity at onset influences outcome of acute myocardial infarction. METHODS: Information collected using a standard questionnaire was used to relate activity at the onset of symptoms to in-hospital outcome in 2,468 consecutive patients admitted to a coronary care unit with a first myocardial infarction between 1975 and 1993. RESULTS: Patients with exercise-related onset were more likely to be younger and male. Those with onset in bed were more likely to be older and have a history of stable or unstable angina. Compared with patients whose symptoms began at rest, those with exercise-related onset had a lower in-hospital mortality rate after adjusting for age, gender and year of admission (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.40 to 0.89), and patients with onset in bed had a higher mortality rate (OR 1.38, 95% CI 1.03 to 1.85). The incidence of cardiac failure requiring diuretic therapy was also lower for exercise-related onset (OR 0.83, 95% CI 0.67 to 1.04) and higher when onset was in bed (OR 1.36, 95% CI 1.11 to 1.66). CONCLUSIONS: There is an association between activity at onset and outcome of acute myocardial infarction. Differences in pathophysiology or in the population at risk could explain this observation.

Aged↗

Plasma natriuretic peptides and cardiac volume during acute changes in intravascular volume in haemodialysis patients.

1. Plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptides (BNP) were measured, along with left and right atrial and left ventricular volumes, in eight patients with chronic renal failure before and after the removal of 2.1 +/- 0.61 of fluid by ultrafiltration and again during volume repletion with intravenous sodium chloride solution (150 mmol/l saline) to restore body weight plus 0.5 kg. 2. Baseline levels of ANP (46.0 +/- 7.5 pmol/l) and BNP (22.0 +/- 4.4 pmol/l) were elevated above normal. There was a significant reduction in plasma ANP (26.5 +/- 4.7 pmol/l, P < 0.05) and BNP (19.1 +/- 4.9 pmol/l, P < 0.05)) following ultrafiltration. Changes in plasma ANP during ultrafiltration correlated significantly with changes in left atrial volume (r = 0.643, P < 0.05). 3. During volume repletion there was an exaggerated release of ANP (mean level post repletion 71.3 +/- 20.8 pmol/l) which was not paralleled by changes in BNP. Changes in BNP were small, showing no correlation with atrial or ventricular volumes during either ultrafiltration or volume repletion. 4. These findings indicate that in chronic renal failure without left ventricular dysfunction, moderate acute changes in volume status elict only small immediate responses in plasma BNP. Changes in plasma ANP are greater than BNP and more responsive to changes in left atrial volume.

Adolescent↗

Long-term effects of acute thrombolytic therapy on ventricular size and function.

To investigate the influence of thrombolytic therapy on the natural history of left ventricular size and regional function after myocardial infarction, 32 patients treated with acute thrombolytic therapy (treatment group) were studied by echocardiography on admission to the hospital and at 1 week, 3 months, and 1 year after myocardial infarction; they were compared with 40 patients who did not receive acute intervention (control group). The endocardial surface area index (cm2/m2) and the area of abnormal wall motion (cm2) were calculated from left ventricular dimensions and measurements of abnormal wall motion. Although no differences in the endocardial surface area index were noted over the year for the groups as a whole, a significant difference was noted in treated anterior infarctions with early functional infarct expansion compared with untreated infarct expansion (treatment group: 85.8 +/- 2.0 cm2/m2 [entry] to 77.4 +/- 2.7 cm2/m2 [1 week] to 69.9 +/- 4.2 cm2/m2 [3 months] to 67.2 +/- 6.4 cm2/m2 [1 year] versus control group: 84.0 +/- 6.4 cm2/m2 [entry] to 83.7 +/- 8.5 cm2/m2 [1 week] to 96.3 +/- 8.6 cm2/m2 [3 months] to 81.5 +/- 4.2 cm2/m2 [1 year]; p < 0.01). When early expansion was present, those receiving thrombolysis exhibited a consistent decrease in the initially enlarged endocardial surface area in contrast to control subjects, who demonstrated continued increases in endocardial surface area during the first 3 months. In all groups a decrease in the area of abnormal wall motion was observed during the year of follow-up. However, the magnitude and timing of the improvement was accelerated in the treatment group. Thus acute thrombolytic therapy alters the natural history of left ventricular size and function with a more rapid recovery of abnormal endocardial segments and reversal of functional infarct expansion.

Case-Control Studies↗

Progressive changes in ventricular structure and function during the year after acute myocardial infarction.

To investigate the long-term changes in left ventricular structure and function after myocardial infarction, 51 patients with a first myocardial infarction (17 anterior, 23 inferior, and 11 non-Q wave) were studied by two-dimensional echocardiography at the time of entry into the hospital, at 3 months, and 1 year after infarction. The left ventricular endocardial surface was reconstructed from these echocardiograms, and the endocardial surface area (ESA) index (in cm2/m2) and area of abnormal wall motion (AWM in cm2) were quantitated. Despite different trends in the ESA index between entry and 3-month values in those with and without early infarct expansion, a decrease in the ESA index from 3 months to 1 year was noted in anterior and non-Q wave infarctions (anterior with early expansion: 96.3 +/- 8.6 to 81.5 +/- 4.2 cm2/m2, p less than 0.05; anterior without early expansion: 59.7 +/- 2.0 to 54.7 +/- 2.0 cm2/m2, p less than 0.01; non-Q wave: 64.1 +/- 3.5 to 57.9 +/- 4.4 cm2/m2, p less than 0.01). The mean decline in ESA from 3 months to 1 year of 8.9 +/- 2.5 cm2 was independent of initial infarct size. Regional function, as represented by the area of AWM, was also improved but the timing of the improvement was related to the location and size of the infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomegaly↗

Unusual sequelae after percutaneous mitral valvuloplasty: a Doppler echocardiographic study.

Percutaneous mitral valvuloplasty is a promising new technique for the treatment of mitral stenosis, with a relatively low complication rate reported to date. To assess the sequelae of this procedure, Doppler echocardiographic studies were prospectively performed before and after percutaneous mitral valvuloplasty in a series of 172 patients (mean age 53 +/- 17 years). After balloon dilation, mitral valve area increased from 0.9 +/- 0.3 to 2 +/- 0.8 cm2 (p less than 0.0001), mean gradient decreased from 16 +/- 6 to 6 +/- 3 mm Hg (p less than 0.0001) and mean left atrial pressure decreased from 24 +/- 7 to 14 +/- 6 mm Hg (p less than 0.0001). Although most patients were symptomatically improved, six (4%) were identified who had unusual sequelae evident on Doppler echocardiographic examination immediately after percutaneous mitral valvuloplasty. These included rupture of a posterior mitral valve leaflet, producing a flail distal leaflet portion with severe mitral regurgitation detected on Doppler color flow mapping (n = 1); asymptomatic rupture of the chordae tendineae attached to the anterior mitral valve leaflet with systolic anterior motion of the ruptured chordae into the left ventricular outflow tract (n = 1); a double-orifice mitral valve (n = 1); and evidence of a tear in the anterior mitral valve leaflet (n = 3), producing on both pulsed Doppler ultrasound and color flow mapping a second discrete jet of mitral regurgitation in addition to regurgitation through the main mitral valve orifice. All six patients made a satisfactory recovery and none has required mitral valve replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Interaction between corticosteroid and beta-agonist drugs. Biochemical and cardiovascular effects in normal subjects.

The aim of this study was to investigate whether the administration of prednisone potentiates any of the acute biochemical and cardiovascular effects of high-dose inhaled beta-agonist drugs. These agents are known to cause dose-related changes in plasma potassium and glucose, as well as ECG changes in heart rate, corrected QT interval (QTc), T wave, and U wave. On theoretical grounds, the concomitant use of systemic corticosteroids might enhance these actions. Twenty-four healthy subjects were randomized to receive one of three treatments: salbutamol 5 mg or fenoterol 5 mg or normal saline solution. Each drug was administered twice, 30 min apart by nebulizer, and the procedure was repeated after each subject had received prednisone 30 mg daily for one week. Plasma potassium and glucose levels were measured, and ECGs were obtained after each treatment, together with 12-h Holter monitoring for arrhythmias. Changes in plasma potassium and glucose following nebulized beta-agonist were significantly greater after treatment with prednisone. Baseline potassium level fell from 3.75 mmol/L (95 percent CI 3.61, 3.89) to 3.50 mmol/L (95 percent CI 3.36, 3.64), and thereafter all values were significantly lower at each time point (p = 0.003). The lowest mean plasma potassium was obtained 90 min after fenoterol administration with prednisone pretreatment: 2.78 mmol/L (95 percent CI 2.44, 3.13). Increases in heart rate and QTc interval following both beta-agonist drugs were significant, but T-wave amplitude reductions did not reach significance. Prednisone treatment did not significantly alter the cardiovascular responses. Supraventricular and ventricular ectopic activity was related to beta-agonist use, but no potentiating effect was noted following steroid treatment. We conclude that the acute biochemical effects of beta-agonist administration are augmented by prior treatment with prednisone, but this is not the case for ECG effects. However, the degree of hypokalemia noted as a result of this drug interaction may be of clinical significance in the hypoxic conditions of acute airways obstruction.

Administration, Inhalation↗

Immediate regional endocardial surface expansion following coronary occlusion in the canine left ventricle: disproportionate effects of anterior versus inferior ischemia.

The exact time of onset of functional expansion after acute myocardial infarction/ischemia remains unclear in spite of its potential link to chronic pathologic infarct expansion and its potential implications for therapy. To examine this early change in ventricular morphology, 14 open-chest dogs were studied with two-dimensional echocardiography before and after occlusion (10 minutes) of the left anterior descending coronary artery (LAD, n = 7) or circumflex artery (CIRC, n = 7). The endocardial surface area (ESA) and the area of abnormal wall motion (AWM) were reconstructed from the echocardiographic data using a previously reported technique for quantitatively mapping the ESA and extent of AWM. For the total group (N = 14), the mean ESA before occlusion was 48.9 +/- 9.8 cm2, increasing to 65.7 +/- 18.9 cm2 at 10 minutes occlusion (p less than 0.001). For the LAD subgroup, the mean ESA before occlusion was 50.7 +/- 9.3 cm2, increasing to 79.1 +/- 14.1 cm2 at 10 minutes following occlusion (p less than 0.001). For the CIRC subgroup, the mean ESA before occlusion was 47.1 +/- 10.8 cm2, increasing to 52.3 +/- 12.6 cm2 at 10 minutes after occlusion (p less than 0.001). The ESA increase for the LAD subgroup was significantly larger than that of the CIRC subgroup (LAD range 14.5 to 49.9 cm2 versus CIRC range 1.5 to 9 cm2, p less than 0.0001). Coronary occlusion resulted in similarly sized regions of AWM for both subgroups (LAD, 31.3 +/- 12.2 cm2 versus CIRC, 25.9 +/- 10.3 cm2, p = n.s.). For the LAD group, the largest increase in endocardial circumference occurred within the zone of AWM at the apex (39.9 +/- 12%). The endocardial surface area therefore expands immediately after coronary occlusion and the magnitude of this process is primarily related to the site (anteroapical) rather than to the extent of AWM.

Animals↗

Prediction of successful outcome in 130 patients undergoing percutaneous balloon mitral valvotomy.

We studied 130 patients undergoing percutaneous balloon mitral valvotomy. The relation between valvular morphology according to a previously described echocardiographic scoring system and hemodynamic outcome expressed as qualitative ("good" and suboptimal) and as absolute change in valve area was analyzed. The relative importance of the individual components of this echocardiographic score (valvular thickening, mobility, calcification, and subvalvular disease) to the change in valve area after valvotomy was also examined. Mean transmitral pressure gradient decreased from 16 +/- 6 to 6 +/- 3 mm Hg (p less than 0.0001), and mitral valve area increased from 0.9 +/- 0.3 to 1.8 +/- 0.7 cm2 (p less than 0.0001). Results in individual patients were variable. Eighty-four percent (61 of 73) of patients with an echocardiographic score of 8 or less had a "good" outcome (final valve area greater than or equal to 1.5 cm2 and an increase in valve area of greater than or equal to 25%), whereas 58% (33 of 57) of patients with an echocardiographic score of 8 or more had a suboptimal result (p less than 0.001). The sensitivity of an echocardiographic score of 8 or less for predicting a "good" outcome was 72%, and the specificity was 73%. The echocardiographic score correlated negatively (r = -0.40, p less than 0.0001) with the absolute increase in mitral valve area after valvotomy, but there was substantial scatter in the data. Of the four components of the total echocardiographic score, valvular thickening correlated best with the absolute change in value area (r = -0.47, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Natural history of left ventricular size and function after acute myocardial infarction. Assessment and prediction by echocardiographic endocardial surface mapping.

To investigate the natural history of regional dyssynergy and left ventricular size after myocardial infarction, 57 patients with a first Q wave myocardial infarction (18 anterior, 35 inferior, and four apical by echocardiography) were studied by two-dimensional echocardiography and compared with 30 control patients. Measurements from the echocardiograms were used to construct maps of the left ventricular endocardial surface from which the endocardial surface area index (ESAi) and the percent of the endocardial surface area involved by abnormal wall motion (%AWM) were calculated. The maps from entry and 3-month echocardiograms were used to classify patients based on changes in ESAi and abnormal wall motion. Two subgroups of patients were identified at entry--those with a normal ESAi (group 1, n = 50) and those with an increased ESAi (group 2, n = 7). Group 1 patients was subdivided at 3 months by changes occurring in ESAi (1A, 5% increase [n = 19]; 1B, no change [n = 23]; 1C, 5% decrease [n = 8]). The increase in ESAi (64.9 +/- 5.2 to 75.4 +/- 7.5 cm2/m2, p less than 0.0001) in group 1A was associated with global ventricular dilatation (n = 11) and clinically silent infarct extension (n = 8). Groups 1B and 1C were composed predominantly of patients with inferior infarctions, and all exhibited either no change or a significant decrease in infarct size (infarct regression). Group 2 patients demonstrated a continued increase in ESAi by 3 months (88.2 +/- 10.0 to 101.4 +/- 15.5 cm2/m2, p less than 0.007). This group comprised only patients with anterior infarctions, and all exhibited infarct expansion at the left ventricular apex. The changes in left ventricular size and functional infarct size are heterogeneous after acute myocardial infarction and relate to the initial endocardial surface area, infarct location, and functional infarct size.

Acute Disease↗

Follow-up of patients undergoing percutaneous mitral balloon valvotomy. Analysis of factors determining restenosis.

This study reports the clinical follow-up (13 +/- 1 months) of 100 consecutive patients who underwent percutaneous mitral balloon valvotomy (PMV). Echocardiographic (n = 32) and cardiac catheterization (n = 37) data from this group are also included. Patients were divided into two groups by an echocardiographic score. PMV resulted in a good hemodynamic result (post-PMV mitral valve area, greater than or equal to 1.5 cm2) in 88% of patients with a score of 8 or less and 44% of patients with a score of more than 8. Eighty-eight percent of patients with a score of 8 or less (n = 57) were New York Heart Association (NYHA) functional Classes III and IV before PMV; at follow-up, 81% were NYHA Class I and 12% were NYHA Class II. There were no deaths; three patients underwent mitral valve replacement (MVR). Ninety-eight percent of patients with a score of more than 8 (n = 43) were NYHA Classes III and IV before PMV; at follow-up, 58% were NYHA Classes I and II. Seven patients who did not improve and were not surgical candidates died 3.8 +/- 1.2 months after PMV. Nine patients who were surgical candidates underwent elective MVR at 4 +/- 0.9 months after PMV. Repeat cardiac catheterization demonstrated restenosis in only one of 27 patients (4%) with a score of 8 or less. Mitral valve area after PMV was 1.9 +/- 0.1 cm2 and at follow-up was 2 +/- 0.1 cm2 (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗