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Biomedical subjects

A M Tonkin

Publications and source records attributed to A M Tonkin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Pattern and significance of cerebral microemboli during coronary artery bypass grafting.

BACKGROUND: Strokes that occur during coronary artery bypass grafting are often caused by embolism. Intraoperative transcranial Doppler monitoring can detect cerebral microemboli. The aims of this study were to identify the pattern of microembolic phenomena during various stages of coronary artery bypass grafting, to verify whether numbers of high-intensity transient signals correlated with early neuropsychologic deficits, and to identify, using magnetic resonance imaging scans, whether radiologic evidence of cerebral infarction correlated with microembolic numbers during the bypass period. METHODS: Forty-one consecutive patients undergoing coronary bypass grafting with transcranial Doppler monitoring were enrolled in this study. All had preoperative and postoperative magnetic resonance imaging brain scans. A subgroup of 32 patients were studied by comparing microembolic load and early neuropsychological outcomes. RESULTS: Transcranial Doppler monitoring confirmed that most microemboli occurred during cardiopulmonary bypass. A significant early neuropsychological deficit after coronary artery bypass grafting did correspond to the total microembolic load during bypass (p = 0.008). However, patients with cerebral infarction on magnetic resonance imaging had significantly more microembolic signal during the preincision phases and not during the bypass period. CONCLUSIONS: Microembolic load during bypass is associated with early neuropsychologic deficits. In contrast, patients who show evidence of strokes during coronary artery bypass grafting have a higher microembolic load during the preincision phase than those without cerebral infarction. Differing mechanisms may be responsible for these different outcomes.

Aged↗
PubMed1998

Issues in extrapolating from clinical trials to clinical practice and outcomes.

Extrapolation of clinical trial results to clinical practice requires consideration of whether the trial patients were representative of clinical practice, whether the trial therapy studied was optimal, whether the sample size was adequate, and the impact of adjunctive treatments. In thrombolytic trials in particular, regional variations in attitudes to coronary angiography may have affected outcomes. Clinical trial results need to be interpreted in the light of the cost effectiveness of the application. The assessment of clinical outcomes depends on interplay between the structure and process of care, patient factors and chance. Large standardised databases are necessary to assess clinical practice and outcomes.

Clinical Trials as Topic↗
PubMed1998

Effects of left atrial dilatation on the endocardial atrial defibrillation threshold: a study in an ovine model of pacing induced dilated cardiomyopathy.

Left atrial (LA) dilation is a common finding in patients with chronic atrial fibrillation (AF). Progressive dilatation may alter the atrial defibrillation threshold (ADFT). In our study, epicardial electrodes were implanted on the LA free wall and right ventricular apex of eight adult sheep. Large surface area, coiled endocardial electrodes were positioned in the coronary sinus and right atrium (RA). LA dilatation was induced by rapid ventricular pacing (190 beats/min) for 6 weeks and echocardiographically assessed weekly along with the ADFT (under propofol anesthesia). LA effective refractory period (ERP) was measured every 2-3 days using a standard extra stimulus technique and 400 ms drive. The AF cycle length (AFCL) was assessed from LA electrograms. During the 6 weeks of pacing the mean LA area increased from 6.1 +/- 1.5 to 21.3 +/- 2.4 cm2. There were no significant changes in the mean ADFT (122 +/- 15 V), circuit impedance (46 +/- 5 omega), or LA AFCL (136 +/- 23 ms). There was a significant increase in the mean LA ERP (106 +/- 10 ms at day 0, and 120 +/- 13 ms at day 42 of pacing). In this study, using chronically implanted defibrillation leads, the minimal energy requirements for successful AF were not significantly altered by ongoing left atrial dilatation. This finding is a further endorsement of the efficiency of the coronary sinus/RA shock vector. Furthermore, the apparent stability of the AF present may be a further indication of a link between the type of AF and the ADFT.

Animals↗
PubMed1998

Susceptibility to atrial fibrillation: a study in an ovine model of pacing-induced early heart failure.

INTRODUCTION: The development of susceptibility to atrial fibrillation (AF) is a common consequence of many forms of cardiovascular disease, especially heart failure. In this study we used a sheep model of pacing-induced stable early heart failure to describe, quantify, and relate the level of susceptibility to AF to changes in structural and electrophysiologic parameters. METHODS AND RESULTS: Epicardial electrodes were implanted on the atria and right ventricles of nine sheep. The AF threshold, atrial vulnerability period, atrial effective refractory period (ERP), and interatrial conduction time were examined during control and over a 6-week period of ventricular pacing at 190 beats/min. Left atrial (LA) area and left ventricular (LV) fractional shortening were monitored using echocardiography. There were significant increases in LA susceptibility to AF (P < 0.0003), LA area (P < 0.0002), and LA ERP400 (P < 0.0002). Rate of increase in LA area was related positively to AF susceptibility (P = 0.02) and inversely to LA ERP400 (P = 0.002). LV fractional shortening decreased to approximately 50% of control value (P < 0.00001). No changes were observed in right atrial electrophysiology. CONCLUSION: In this study, susceptibility (the ability of an extrastimulus to induce AF) was rigorously measured within a predetermined format. Significant relationships were found to exist between susceptibility, certain of the observed changes in atrial electrophysiology and structure.

Animals↗
PubMed1997

The intraoperative assessment of ascending aortic atheroma: epiaortic imaging is superior to both transesophageal echocardiography and direct palpation.

OBJECTIVES: To determine the optimal method for detecting ascending aortic atheroma intraoperatively by comparing manual palpation by the operating surgeon, intraoperative transesophageal echocardiography, and epiaortic ultrasound (linear and phased-array imaging); and to assess risk factors for severe aortic atheroma. DESIGN: A longitudinal prospective study. Assessment of the atheroma by manual palpation was blinded to the results of the ultrasound images. SETTING: The study was performed in a single university tertiary referral hospital. PARTICIPANTS: One hundred consecutive patients undergoing coronary bypass or valve surgery were studied after their written, informed consent. INTERVENTIONS: Potential risk factors were evaluated by both a patient questionnaire and examination of prior hospital records. The ascending aorta was assessed by the following methods: manual palpation by the operating surgeon, intraoperative transesophageal echocardiography, and epiaortic ultrasound (linear and phased-array imaging) performed by an echocardiologist. For analysis, the ascending aorta was divided into three equal segments: proximal, mid, and distal, corresponding to regions of different operative manipulations. MEASUREMENTS AND MAIN RESULTS: Age older than 70 years and hypertension were significant risk factors for severe ascending aortic atheroma with adjusted odds ratios of 3.3 (95% CI, 1.2 to 9.3) and 3.9 (95% CI, 1.3 to 12.0), respectively. There was no significant difference in atheroma detection between the two ultrasonic epiaortic probes in any segment; however, epiaortic probes were superior to manual palpation in all segments and also superior to transesophageal echocardiography in the mid and distal segments of the ascending aorta. CONCLUSIONS: Age older than 70 years and hypertension are significant risk factors for severe ascending aortic atheroma. Intraoperative detection of ascending aortic atheroma is best achieved by epiaortic ultrasound with either a linear or phased array transducer. Transesophageal echocardiography is an insensitive technique for evaluation of mid and distal ascending aortic atheroma and, therefore, of little value in guiding surgical manipulations such as cross-clamping.

Age Factors↗
PubMed1997

A placebo-controlled trial verifying the efficacy of milrinone in weaning high-risk patients from cardiopulmonary bypass.

OBJECTIVE: To establish the efficacy of the phosphodiesterase inhibitor milrinone in facilitating weaning from cardiopulmonary bypass of high-risk patients with left ventricular dysfunction and/or pulmonary hypertension. DESIGN: A double-blinded, placebo-controlled longitudinal study. SETTING: A university teaching hospital. PARTICIPANTS: Thirty-two patients with preoperative left ventricular ejection fraction < or = 35% and/or mean pulmonary artery pressure > or = 20 mmHg were studied after their written informed consent. INTERVENTION: Patients were randomized to commence either intravenous milrinone, 50 micrograms/kg loading dose over 20 minutes followed by 0.5 microgram/kg/min infusion, or matching placebo 15 minutes before withdrawal of cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Two patients were withdrawn from the study and their results not analyzed: one because of early failure of hemodynamic monitoring and the other because of gross surgical bleeding. In the remaining 30 patients, who were well matched for clinical and baseline hemodynamic variables, bypass support was successfully withdrawn in all 15 patients randomized to receive milrinone but in only 5 of the 15 patients randomized to receive placebo. In the 10 patients who initially failed to wean from bypass while on placebo, bypass was reinstituted and open-label milrinone was administered in the dose outlined. After treatment with open-label milrinone, these patients could also be withdrawn from bypass support. During the period of hemodynamic monitoring, cardiac index increased in both milrinone- and placebo-treated patients, although this change was greater in those treated with milrinone. Perhaps related to routine clinical treatment, there were no significant differences between the two groups with mean pulmonary artery or pulmonary capillary wedge pressures, the other major hemodynamic endpoints. There were no significant adverse effects related to milrinone. CONCLUSIONS: This placebo-controlled, double-blind study has conclusively demonstrated the benefits of milrinone in facilitating weaning of high-risk patients from cardiopulmonary bypass.

Aged↗
PubMed1997

Low-dose but not high-dose captopril increases parasympathetic activity in patients with heart failure.

Parasympathetic nervous activity (PSNA) is an important determinant of the risk of sudden death and outcome in patients with cardiovascular disease, so the effects of drug therapy on PSNA may be of prognostic importance in patients with chronic heart failure (CHF). The angiotensin-converting enzyme (ACE) inhibitors are the only drugs that are reasonably accepted to improve prognosis in such patients. Accordingly we determined PSNA by heart-rate variability (HRV) analysis in nine patients (four women and five men, aged 73.6 +/- 6 yrs) with heart failure (NYHA Classes II-III) and in sinus rhythm. HRV was determined during 20-40 min supine rest at baseline and then at 2-weekly intervals during incremental dosing of oral captopril, 12.5 mg b.i.d., 25 mg b.i.d., and 50 mg b.i.d. Poincaré plot and conventional time- and frequency-domain measures were used to analyze the data. Low-dose captopril (12.5 mg b.i.d.) resulted in an increase in SD delta RR (16.0 +/- 6.6 to 22.0 +/- 9.1 ms; p < 0.05). We previously validated this as a measure of PSNA. Higher dose captopril (25 mg b.i.d.) also produced an increase in PSNA activity (16.0 +/- 6.6 to 18.7 +/- 7.8 ms), although this failed to reach statistical significance. However, the highest dose of captopril (50 mg b.i.d.) reduced PSNA activity to near-baseline values, as shown by measures of HRV in both the time and frequency domains. These data suggest that only a low dose of captopril augments PSNA in patients with heart failure. Dosing of ACE inhibitors may be important in optimizing their benefit in CHF.

Aged↗
PubMed1996

Atrial fibrillation with left atrial spontaneous contrast detected by transesophageal echocardiography is a potent risk factor for stroke.

Nonrheumatic atrial fibrillation (AF) frequently coexists with other risk factors for cerebral ischemia. This study was originally designed to determine which combinations of clinical and echocardiographic abnormalities were most closely associated with the risk of cerebral ischemic events. Patients with cerebral ischemic events (n = 214) and community-based control subjects (n = 201) underwent transesophageal echocardiography and carotid artery imaging. Adjusted odds ratios (ORs) were determined using multiple logistic regression analysis. Independent risk factors for cerebral ischemia included diabetes, carotid stenosis, aortic sclerosis, left ventricular dysfunction, left ventricular hypertrophy, left atrial (LA) spontaneous contrast, and proximal aortic atheroma. Nonrheumatic AF in combination with LA spontaneous contrast and LA enlargement showed a strong association with cerebral ischemic events (OR 33.7 [95% confidence interval 4.53 to 251]). In subjects with sinus rhythm or nonrheumatic AF, LA enlargement was not associated with an increased risk of cerebral ischemic events in the absence of LA spontaneous contrast. However, only 2 patients and 1 control subject had nonrheumatic AF without LA spontaneous contrast or LA enlargement. Therefore, study of a larger number of subjects is required to address the issue of whether nonrheumatic AF itself carries increased risk. The combination of nonrheumatic AF with LA spontaneous contrast is a potent risk factor for cerebral ischemia. Ascertaining the risk factor in nonrheumatic AF requires adequate examination for underlying cardiac, aortic, and carotid vascular disease. Transesophageal echocardiography may contribute to this assessment.

Aortic Diseases↗
PubMed1996

Prediction of outcome after revascularization in patients with poor left ventricular function.

BACKGROUND: In patients with poor left ventricular function, the determinants of outcome after revascularization are unknown. METHODS: We studied prospectively 57 patients with stable coronary artery disease and poor left ventricular function (left ventricular ejection fraction, 0.28 +/- 0.04) who underwent coronary artery bypass grafting. Clinical variables were assessed as predictors of outcome in all patients, and preoperative stress thallium-201 scintigraphic data were analysed in 37 patients. RESULTS: The operative mortality was 1.7%. At 12 months after operation, 46 of the 49 survivors were angina-free and 35 had fewer heart failure symptoms, but postoperative left ventricular ejection fraction (0.30 +/- 0.09) did not change significantly. Eighteen survivors had left ventricular ejection fraction improved by 0.05 or more (0.30 +/- 0.03 preoperatively, 0.40 +/- 0.05 postoperatively; p = 0.0001). The adjusted odds ratio of large reversible thallium-201 defects in predicting such outcome was 15 (95% confidence interval, 1.6 to 140), whereas other clinical variables had no predictive value. The transplantation-free 5-year survival was 73%. CONCLUSIONS: In patients with poor left ventricular function, surgical revascularization can be performed safely, with good symptomatic relief and long-term survival. One-year survival and improvement in left ventricular function is better in patients with large reversible defects on preoperative stress thallium-201 scintigraphy.

Aged↗
PubMed1996

Comparison of dobutamine echocardiography and positron emission tomography in patients with chronic ischemic left ventricular dysfunction.

OBJECTIVES: The aim of this study was to correlate dobutamine-induced contractile reserve as detected by echocardiography with findings on positron emission tomography in patients with chronic ischemic left ventricular dysfunction. BACKGROUND: Contractile reserve induced by low dose dobutamine infusion has been proposed as a marker of myocardial viability. METHODS: Sixty patients with stable coronary artery disease and left ventricular dysfunction (mean ejection fraction [+/- SD] 29 +/- 10%) underwent transthoracic echocardiography with dobutamine infusion (up to 10 micrograms/kg body weight per min) and positron emission tomography with nitrogen-13 ammonia and fluorine-18 (F-18) fluorodeoxyglucose as a perfusion and a metabolic tracer, respectively. Regional wall motion, perfusion and metabolism were analyzed semiquantitatively by using a 16-segment model. Segments with F-18 fluorodeoxyglucose uptake > 50% were considered viable on positron emission tomography. RESULTS: After dobutamine infusion, hemodynamic variables changed significantly, and myocardial ischemia was evident in 17 patients. All 60 patients had dysfunctional myocardium considered viable on positron emission tomography (8 +/- 4 segments/patient), whereas 52 patients had dysfunctional myocardium with contractile enhancement by dobutamine echocardiography (4 +/- 2 segments/patient, p = 0.01). The extent of dysfunctional myocardium with contractile reserve appeared to correlate less closely with the total extent of viable dysfunctional myocardium identified by positron emission tomography than with the number of such segments associated with a pattern of perfusion-metabolism mismatch. CONCLUSIONS: In patients with chronic ischemic left ventricular dysfunction, echocardiography can be used to identify enhancement in the contractile function of viable dysfunctional myocardium after infusion of low dose dobutamine. In this study, the presence and extent of such enhancement were relatively less than the values obtained from positron emission tomography.

Coronary Disease↗
PubMed1996

Poincaré plot of heart rate variability allows quantitative display of parasympathetic nervous activity in humans.

1. Time domain summary statistics and frequency domain parameters can be used to measure heart rate variability. More recently, qualitative methods including the Poincaré plot have been used to evaluate heart rate variability. The aim of this study was to validate a novel method of quantitative analysis of the Poincaré plot using conventional statistical techniques. 2. Beat-to-beat heart rate variability was measured over a relatively short period of time (10-20 min) in 12 healthy subjects aged between 20 and 40 years (mean 30 +/- 7 years) during (i) supine rest, (ii) head-up tilt (sympathetic activation, parasympathetic nervous system activity withdrawal), (iii) intravenous infusion of atropine (parasympathetic nervous system activity withdrawal), and (iv) after overnight administration of low-dose transdermal scopolamine (parasympathetic nervous system augmentation). 3. The "width' of the Poincaré plot, as quantified by SD delta R-R (the difference between successive R-R intervals), was determined at rest (median 48.9, quartile range 20 ms) and found to be significantly reduced during tilt (median 19.1, quartile range 13.7 ms, P < 0.01) and atropine administration (median 7.1, quartile range 5.7 ms, P < 0.01) and increased by scopolamine (median 79.3, quartile range 33 ms, P < 0.01). Furthermore, log variance of delta R-R intervals correlated almost perfectly with log high-frequency (0.15-0.4 Hz) power (r = 0.99, P < 0.01). 4. These findings strongly suggest that the "width' of the Poincaré plot is a measure of parasympathetic nervous system activity. The Poincaré plot is therefore a quantitative visual tool which can be applied to the analysis of R-R interval data gathered over relatively short time periods.

Adult↗
PubMed1995

Management of the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study after the Scandinavian Simvastatin Survival Study (4S).

The Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study was designed when considerable disagreement existed as to relative benefits and risks of cholesterol reduction. Between June 1990 and December 1992, 9,014 patients aged 31-75 years were randomized to receive either pravastatin 40 mg once daily or placebo. These patients had experienced either acute myocardial infarction or unstable angina within the preceding 3 months to 3 years and had total cholesterol levels of 155-271 mg/dl (4.0-7.0 mmol/liter). All patients received dietary advice. The LIPID study is projected for conclusion in 1997, after a follow-up period of at least 5 years. The primary study endpoint is mortality due to coronary artery disease (CAD). The Scandinavian Simvastatin Survival Study (4S) is the first secondary prevention trial to show a reduction in total mortality with lipid-lowering therapy. However, the LIPID study should continue for the following reasons: (1) important differences exist between the LIPID study and 4S cohorts. Overall, > 80% of the LIPID patients could not have been included in 4S on the basis of their cholesterol level, age, or history of CAD; (2) the LIPID study will also provide important information on noncoronary mortality and on other groups, such as women and diabetic patients, who have been underrepresented in previous trials; (3) the LIPID study design allows for clinical management, including lipid-lowering therapy, to be at the discretion of the physician managing a trial patient. The 4S results have been brought to the attention of all LIPID investigators, Institutional Ethics Committees, the physicians of the individual patients, and the patients themselves.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Atrial fibrillation after coronary artery bypass grafting is associated with sympathetic activation.

BACKGROUND: We prospectively investigated the role of sympathetic activation in the etiology of atrial fibrillation following coronary artery bypass grafting. METHODS: Continuous ambulatory monitoring was performed for 80 hours in 131 patients after coronary artery bypass grafting. Right atrial plasma norepinephrine levels were assessed preoperatively and every 4 hours for 48 hours postoperatively. RESULTS: Of the 131 patients, 50% (65) had development of atrial fibrillation and 36% (47) required treatment. Onset of atrial fibrillation was preceded by a significant increase in sinus rate and atrial ectopic activity. On multivariate logistic regression, elevated mean postoperative norepinephrine levels (5.78 +/- 2.83 versus 3.57 +/- 1.31 nmol/L; p < 0.0001), increased age (68.9 +/- 5.7 versus 63.8 +/- 8.7 years; p = 0.02), and decreased postoperative magnesium levels (0.79 +/- 0.09 versus 0.83 +/- 0.10 mmol/L; p = 0.02) were independently associated with the occurrence of atrial fibrillation. CONCLUSIONS: Elevated norepinephrine levels suggest that sympathetic activation may be important in the pathogenesis of atrial fibrillation after coronary artery bypass grafting, and this underlines the importance of beta-adrenoceptor blockade as prophylaxis.

Aged↗
PubMed1995

Application of the Poincaré plot to heart rate variability: a new measure of functional status in heart failure.

BACKGROUND: Conventional methods of quantifying heart rate variability using summary statistics have shown that decreased variability is associated with increased mortality in heart failure. However, many patients with heart failure have arrhythmias which make the 'raw' heart rate variability data less suitable for the use of summary statistical measures. AIMS: To examine the clinical potential of a new measure of heart rate variability data, presented by the Poincaré plot pattern, as an adjunct to the summary statistical measures of R-R interval variability. METHODS: We used the Poincaré plot pattern to display beat-to-beat heart rate variability data from a group of 23 patients with heart failure and compared them with data collected from 20 healthy age-matched control subjects. The data, which consists of 2000 consecutive R-R intervals, were gathered over 20-40 minutes while the subjects rested supine in a quiet darkened room. RESULTS: The morphological classification scheme proposed reflected the functional status of patients in heart failure. There was a significant difference (chi-square = 27.5, p < 0.0001) in the different pattern types between patients with NYHA Class I and II compared to patients with NYHA Class II and IV. All healthy subjects displayed a 'cluster' type of pattern characterised by normally distributed data. Sixteen of the 23 patients in heart failure also produced data which were normally distributed but the remaining seven produced data which required careful filtering to make them suitable for analysis using summary statistics, but which could be analysed by the Poincaré plot. CONCLUSIONS: The Poincaré plot pattern is a semi-quantitative tool which can be applied to the analysis of R-R interval data. It has potential advantages in that it allows assessment of data which are grossly non-Gaussian in distribution, and is a simple and easily implemented method which can be used in a clinical setting to augment the standard electrocardiogram to provide 'real time' visualisation of data.

Aged↗