Search PubMed⌕ Search

Biomedical subjects

C M Oakley

Publications and source records attributed to C M Oakley.

At least 73 records · Page 4Linked to original sources
PubMed1994

Co-expression of renin-angiotensin system component genes in human atrial tissue.

OBJECTIVES: To detect co-expression of genes coding for components of the renin-angiotensin system and investigate the potential for variation in the level of angiotensin converting enzyme (ACE) gene expression in the right atrial appendage of patients undergoing heart surgery. DESIGN: The right atrial appendage was collected at the time of surgery from 30 randomly chosen patients and was rapidly frozen in liquid nitrogen prior to extraction of messenger (m)RNA. Surgical samples of heart valve (n = 6) and papillary muscle (n = 3) were also examined. METHODS: Aliquots of purified mRNA were reverse-transcribed for analysis of gene expression by a polymerase chain reaction amplification assay. Primers specific for angiotensinogen, renin, ACE, cardiac chymase, atrial natriuretic peptide, glyceraldehyde-3-phosphate dehydrogenase, adenosine deaminase and the transferrin receptor were used for a qualitative analysis of co-expression of these genes within the same sample. In a subgroup of eight patients, a quantitative comparison of the relative levels of ACE gene expression was performed using a competitive polymerase chain reaction. RESULTS: Angiotensinogen and ACE expression were detected in all atrial, valve and ventricular samples examined, at levels similar to those of 'housekeeping' genes such as the transferrin receptor. Atrial renin and chymase expression were more difficult to detect, being demonstrable in only 70 and 63% of the samples, respectively. Higher levels of chymase were detected in ventricular samples than in atrial tissues. A quantitative analysis of ACE expression in eight atrial samples provided evidence of interindividual variation in the relative level of atrial ACE expression. CONCLUSIONS: The essential components of the renin-angiotensin system are co-expressed at a low level in the right atrial appendage and are detectable in other regions of the human heart. Renin and chymase genes are expressed at a lower level than the angiotensinogen and ACE genes and exhibit regional differences in expression. Interindividual variation in the relative level of ACE expression can be detected by a competitive polymerase chain reaction.

Angiotensinogen↗
PubMed1993

Detection of atherosclerotic lesions in the aorta by transesophageal echocardiography.

Transesophageal echocardiographic studies were prospectively performed in 152 consecutive patients older than age 40 years referred to the echocardiography laboratory to assess the prevalence of atherosclerosis in the thoracic aorta and relate this to a history of systemic embolization. Forty-four patients (29%) had at least 1 atherosclerotic lesion in the thoracic aorta. This was associated with a higher prevalence of coronary artery disease (78% of all patients with coronary artery disease), carotid artery disease (88% of all patients with carotid artery disease) and peripheral vascular disease (all symptomatic patients). Forty-two of all patients (28%) had systemic emboli, 20 (48%) of whom had at least 1 atheromatous lesion in the thoracic aorta. Conversely, only 24 of 110 patients (22%) without previous systemic emboli had atheromatous lesions (p < 0.001). It is concluded that atherosclerotic lesions in the thoracic aorta can readily be identified with transesophageal echocardiography. The detection of atherosclerotic plaques of the aorta represents a marker of diffuse atherosclerotic disease, often associated with carotid, coronary and peripheral vascular disease and with the occurrence of systemic emboli. Transesophageal echocardiography may be used serially to investigate whether dietary or pharmacologic maneuvers, or both, can shrink established atherosclerotic plaques in the thoracic aorta.

Adult↗
PubMed1993

Prognostic value of dobutamine echocardiography in patients with high pretest likelihood of coronary artery disease.

To examine the value of transient regional asynergy on dobutamine stress echocardiography as a noninvasive predictor of future cardiac events, 51 symptomatic patients (aged 54 +/- 9 years) with suspected coronary artery disease (CAD) were studied using an incremental regimen of 5, 10, 15 and 20 micrograms/kg/min. Pretest likelihood of CAD was (mean +/- standard error of the percentage) 79.7 +/- 5.6% before and 83.4 +/- 5.2% after exercise electrocardiography using probability analysis based on age, sex and symptoms. Two-dimensional images were analyzed with reference to an 11-segment model and gave good interrater agreement. During 24 +/- 4 months (range 19 to 32) of follow-up, 23 patients had events (1 myocardial infarction, 9 unstable angina, 10 coronary bypass surgery, 3 coronary angioplasty) and 28 were event free. Age, proportion with baseline asynergy and both pretest echocardiographic ejection fraction and its response to dobutamine were similar in these 2 groups (all p = not significant). Transient asynergy was seen in 17 of 23 patients (74%) with and 8 of 28 patients (29%) without events (p < 0.01); 5 of 6 patients (83%) with involvement of 3 segments had events. Myocardial infarction or unstable angina occurred in 8 of 25 (32%) with a positive and 2 of 26 (8%) with a negative stress echocardiogram (p < 0.05). Both exercise duration (389 +/- 195 vs 517 +/- 237 seconds, p < 0.05) and time to diagnostic ST-segment shift (291 +/- 192 vs 447 +/- 212 seconds, p = 0.05) were shorter in those with inducible asynergy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Cardiocytolytic antimyolemmal antibodies in dilated cardiomyopathy following presentation: observations in 7 patients.

The prevalence of lytic activity of circulating antimyolemmal antibodies in dilated cardiomyopathy of recent onset is unclear. To obtain preliminary data we studied 7 consecutive patients with dilated cardiomyopathy (age 44 +/- 14 years) and symptoms for fewer than 6 months. The presence of antimyolemmal antibodies was determined in vitro using intact rat and human cardiocytes and indirect immunofluorescence. Serum cytolytic index for antimyolemmal antibodies was measured by microcytotoxicity assay and the data were compared with that from 70 controls (normal range 0.92 +/- 0.07, effective cytolysis < 0.75). Autoantibody screening was uniformly negative and only 1 patient had positive viral serology. Light microscopy of cardiac biopsies revealed non-specific histology in 2, focal myocarditis in 1 and healing or healed myocarditis in 4. Significant binding of IgG, IgM or polyvalent antibodies to antimyolemmal antibodies bound to rat or human cardiocytes was present in every patient and 5 of them were positive with all 3 markers. Cytolytic index for the group ranged from 0.47 to 0.60 indicating effective lysis in all patients (P < 0.01 versus controls). Cardiocytolytic antimyolemmal antibodies are commonly present in dilated cardiomyopathy following presentation. Their detection might reflect ongoing disease activity and help identify patients likely to benefit from immunomodulative therapy.

Adolescent↗
PubMed1993

A double-blind, placebo-controlled crossover trial of nadolol and verapamil in mild and moderately symptomatic hypertrophic cardiomyopathy.

OBJECTIVES: The aim of this study was to determine whether therapy with a beta-adrenergic or calcium channel blocking agent can improve the functional capacity and quality of life of patients with mild or moderately symptomatic hypertrophic cardiomyopathy. BACKGROUND: Both beta-blockers and calcium channel blockers may alleviate symptoms in hypertrophic cardiomyopathy, but previous studies have been performed in hospitalized patients or have been open studies without control subjects. METHODS: A randomized, double-blind crossover trial of nadolol, verapamil and placebo, administered for periods of 4 weeks each, was performed in 18 patients with mild or moderately symptomatic hypertrophic cardiomyopathy (10 men, 8 women; mean age +/- SD 39 +/- 17 years). A detailed symptom assessment, bicycle exercise testing, echocardiography and Holter monitoring were performed in each period. RESULTS: Two patients withdrew from the study owing to symptomatic sinus bradycardia during nadolol therapy. Neither drug improved maximal oxygen consumption (placebo 26 +/- 8, verapamil 23 +/- 6, nadolol 21 +/- 7 ml/kg per min; p = 0.1). Peak exercise work load was reduced by > or = 10 W in 13 patients (81%) during nadolol therapy and in 4 patients (25%) during verapamil therapy (p = 0.005, nadolol vs. verapamil). Despite the effects on exercise capacity, 13 patients (81%) preferred drug treatment (8 verapamil, 5 nadolol) over placebo (p = 0.001). Verapamil improved reported performance at work compared with nadolol (p = 0.01) and tended to improve other measures of health-related behavior and symptoms compared with nadolol and placebo. CONCLUSIONS: In patients with mild or moderately symptomatic hypertrophic cardiomyopathy, exercise capacity was not improved by nadolol or verapamil, and individuals were more often impaired by nadolol than with verapamil. Nevertheless, many patients derived symptomatic benefit from drug therapy, especially with verapamil.

Adolescent↗
PubMed1993

An additional marker for familial hypertrophic cardiomyopathy?

BACKGROUND: Family screening for hypertrophic cardiomyopathy using conventional techniques yields some equivocal cases. Although mutations in the beta-cardiac myosin heavy-chain gene (MYH7) have been demonstrated in some patients, additional diagnostic methods are desirable to clarify the equivocal cases until the full genetic spectrum is characterized. Because coronary flow reserve is reduced in patients with typical hypertrophic cardiomyopathy independent of the severity of left ventricular hypertrophy, this measurement may help to identify patients with equivocal features of the disease. METHODS: Coronary flow reserve was measured in two subjects: one with a MYH7 mutation but without typical diagnostic features of hypertrophic cardiomyopathy, and one with borderline left ventricular hypertrophy but no mutation in the MYH7 gene. Both subjects underwent screening for hypertrophic cardiomyopathy because of a family history of the disease. Positron-emission tomography was performed to measure myocardial blood flow (MBF) with oxygen-15 labeled water. MBF was measured at baseline and during coronary vasodilatation obtained by intravenous dipyridamole (0.56 mg/kg body weight infused over 4 minutes). Coronary flow reserve was expressed as the ratio MBF-dipyridamole/MBF-baseline. RESULTS: Coronary flow reserve was 1.69 and 1.12 in the two subjects. Both of these values are 2 SD below that (3.87 +/- 1.08) measured in 17 normal subjects using the same method. CONCLUSIONS: Noninvasive quantification of coronary flow reserve by positron-emission tomography may have a role in identifying patients with equivocal hypertrophic cardiomyopathy and should be further explored.

Adolescent↗
PubMed1993

Beat-to-beat variability in stroke volume during VVI pacing as predictor of hemodynamic benefit from DDD pacing.

To determine whether the magnitude of Beat-to-Beat variability in stroke volume (SV) during VVI pacing can predict hemodynamic benefit from DDD pacing, we undertook Doppler recordings of systolic and diastolic LV flow during VVI and DDD pacing in 20 patients (age 54 +/- 9 years) with DDD pacemakers implanted due to AV block. SV increased by 19% +/- 10% from VVI to DDD (P < 0.01). This increase was greater (29% +/- 9%) in patients with a ratio of early (E)/late (A) filling < 1 compared to those with E/A > 1 (10% +/- 9%) (P < 0.001). Beat-to-Beat variability in SV was greater in VVI (13% +/- 8%) compared to DDD (4% +/- 1%) (P < 0.001). Patients with E/A < 1 showed greater Beat-to-Beat variability in SV during VVI pacing (19 +/- 6%) compared to those with E/A > 1 (8% +/- 4%) (P < 0.001). Beat-to-Beat variability in SV during VVI pacing correlated with both percent change in SV from VVI to DDD (r = 0.89, P < 0.001) and E/A (r = -0.71, P < 0.001). In conclusion, patients with E/A < 1 derive greater hemodynamic benefit at rest from DDD pacing compared with E/A > 1. In addition, patients with complete AV block who show large variations in SV during VVI pacing may obtain greater hemodynamic benefit at rest from DDD pacing than patients with small variations.

Adolescent↗
PubMed1993

Effects of lisinopril on cardiorespiratory, neuroendocrine, and renal function in patients with asymptomatic left ventricular dysfunction.

OBJECTIVE: To determine the cardiac, renal, and neuroendocrine effects of lisinopril in men with untreated, symptom free left ventricular systolic dysfunction. DESIGN: A randomised, double blind cross over trial with six week treatment periods to compare lisinopril (10 mg/day) and matching placebo. SETTING: Hospital outpatient department. PATIENTS: Patients with pronounced systolic dysfunction on cross sectional echocardiography due to myocardial infarction at least six months previously, without angina and with no or minimal breathlessness. Eighteen men were identified of whom 15 completed the study. INTERVENTIONS: Lisinopril (10 mg) or placebo given once daily by mouth. MAIN OUTCOME MEASURES: Primary: oxygen consumption at peak exercise. Secondary: resting cardiac function as measured by radionuclide ventriculography and echocardiography, renal function estimated radioisotopically, and plasma indices of neuroendocrine activity. RESULTS: Compared with placebo, lisinopril increased (mean (SD)) peak oxygen consumption during exercise (19.8(3.1) ml/kg/min v 21.4(3.2) ml/kg/min; p < 0.003). Lisinopril did not improve indices of cardiac function at rest. It reduced plasma concentrations of angiotensin II (median values 7 pg/ml to 5 pg/ml; p < 0.02), aldosterone (median values 113 pg/ml to 66 pg/ml; p < 0.05) and atrial natriuretic peptide (median values 69 pg/ml to 40 pg/ml; p < 0.04), but noradrenaline and antidiuretic hormone concentrations did not change. Renal blood flow increased and glomerular filtration rate declined. CONCLUSIONS: Even before the onset of heart failure lisinopril improves the cardiopulmonary response to exercise in patients with systolic ventricular dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Autonomic function in hypertrophic cardiomyopathy.

BACKGROUND: Autonomic dysfunction has been found to be a powerful predictor of arrhythmic events and sudden death after myocardial infarction. Hypertrophic cardiomyopathy carries a risk of sudden death and this risk is increased by the occurrence of syncope. OBJECTIVES: To determine if autonomic dysfunction occurs in patients with hypertrophic cardiomyopathy and if it is associated with the occurrence of syncope. PATIENTS AND METHODS: Autonomic function was measured in 30 patients with hypertrophic cardiomyopathy, 15 with and 15 without a history of syncope, and in 28 healthy volunteers. RESULTS: Tests of parasympathetic activity showed that the mean (SD) variation in heart rate during deep breathing was reduced in patients compared with controls, 17 (9) v 22 (9) beats/min, p = 0.03, the Valsalva ratio was also reduced in patients, 1.52 (0.33) v 1.70 (0.36), p = 0.05 but the immediate heart rate response to standing, the 30:15 ratio, was similar in both groups. Tests of sympathetic activity--namely the diastolic blood pressure response to sustained handgrip and the change in systolic blood pressure on standing--did not differ between patients and controls. There was no significant difference in autonomic function between patients with and without a history of syncope. A secondary predetermined analysis showed that the degree of impairment in variation of heart rate with breathing was correlated with the severity of left ventricular hypertrophy, r = 0.39, p = 0.03. CONCLUSIONS: Patients with hypertrophic cardiomyopathy have a selective impairment of variability of heart rate with deep breathing and the Valsalva manoeuvre indicating decreased cardiac parasympathetic activity. The data suggest that the afferent limb of these reflexes is impaired and that the severity of impairment is related to the degree of left ventricular hypertrophy.

Adolescent↗
PubMed1993

Optimal timing of surgery for chronic mitral or aortic regurgitation.

Symptoms tend to develop late in the course of both chronic mitral and chronic aortic regurgitation, and when the regurgitation is stable patients may enjoy many years of full activity free from disability. In the absence of complicating atrial fibrillation or coronary artery disease the onset of dyspnoe and fatigue usually indicate myocardial failure and possibly a lost opportunity for a low risk operation and long term benefit. Valve replacement for aortic regurgitation is a good operation which reduces left ventricular work. However, mitral valve replacement is unphysiologic and not surprisingly, the operative mortality and long term results are worse with an excess of deaths caused by left ventricular failure. While the need for operation is obvious when patients already have symptoms or when valvar regurgitation is increasing, timing is far more difficult for patients with severe, chronic, stable regurgitation who still enjoy a high quality of life. It is even more difficult in mitral regurgitation because the stakes are higher with a higher operative risk, but suitability for mitral valve reconstruction justifies earlier operation and therefore makes it mandatory for cardiologists to identify such patients.

Aortic Valve Insufficiency↗
PubMed1992

Angiotensin-converting enzyme inhibitors, left ventricular dysfunction, and early heart failure.

A study was undertaken to examine the effects of the angiotensin-converting enzyme inhibitor lisinopril on exercise performance in 18 patients with major impairment of left ventricular systolic function. The study was a randomized, double-blind, crossover design, and patients received treatment with either once-daily lisinopril (2.5-10 mg) or placebo for a period of 6 weeks. A total of 15 patients completed the study. Compared with placebo, lisinopril had no significant effect on supine or standing blood pressure or heart rate. Although lisinopril had no effect on exercise duration during a low-intensity exercise protocol, in patients undergoing a high-intensity exercise protocol, there was a trend toward improved exercise time and peak oxygen consumption improved significantly. In addition, treatment with lisinopril resulted in an increase in renal blood flow and a reduction in glomerular filtration rate. Moreover, administration of once-daily lisinopril 10 mg resulted in a decrease in plasma concentrations of angiotensin II, aldosterone, and atrial natriuretic peptide, and an increase in plasma concentrations of active renin.

Aldosterone↗
PubMed1992

Influence of left ventricular hypertrophy and function on the occurrence of ventricular tachycardia in hypertrophic cardiomyopathy.

Sixty-nine patients with hypertrophic cardiomyopathy were studied by 2-dimensional and Doppler echocardiography and 72-hour Holter monitoring to examine the relation between the degree of left ventricular (LV) hypertrophy and dysfunction and the occurrence of ventricular tachycardia (VT). Episodes of nonsustained VT were detected in 20 patients (29%). Maximal wall thickness was not different between patients with (22 +/- 5 mm) and without (21 +/- 5 mm) VT. Total hypertrophy score, calculated as the sum of 10 segmental wall thicknesses, was also similar in both groups (157 +/- 22 and 153 +/- 32 mm, respectively; p = not significant). Furthermore, no significant differences were found between the 2 groups in LV end-diastolic dimension (41 +/- 7 vs 40 +/- 6 mm), fractional shortening (33 +/- 7 vs 34 +/- 10%) and left atrial size (40 +/- 10 vs 41 +/- 11 mm). An LV outflow tract gradient was detected in 25% of patients with and 35% without VT (p = not significant). One or more Doppler indexes of diastolic function were abnormal in 70% of patients, but no difference in any of these indexes was found between those with and without VT. In summary, the occurrence of VT in hypertrophic cardiomyopathy is not related to the degree of LV hypertrophy, outflow tract gradient or dysfunction. This finding suggests a dissociation between the arrhythmogenic substrate and echocardiographic features of the disease.

Adolescent↗