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Biomedical subjects

A P Rae

Publications and source records attributed to A P Rae.

At least 37 records · Page 2Linked to original sources

Coronary venous lipid peroxide concentrations after coronary angioplasty: correlation with biochemical and electrocardiographic evidence of myocardial ischaemia.

BACKGROUND: Raised lipid peroxide concentrations in coronary venous plasma have been reported after coronary angioplasty in humans. This may reflect increased free radical activity after myocardial ischaemia and reperfusion. If so, it may be possible to correlate lipid peroxide concentrations with the degree of myocardial ischaemia produced during angioplasty. METHODS: 15 patients (age range 42-70; 12 men) with stable angina pectoris undergoing angioplasty of a proximal left anterior descending coronary artery stenosis were studied. Plasma lipid peroxide and lactate concentrations were measured in sequential blood samples taken from the great cardiac vein before and immediately after one to five serial 60 second balloon inflations. The maximum ST segment shift during each balloon inflation was also measured. RESULTS: Lipid peroxide concentrations in coronary venous plasma were raised from pre-angioplasty values by more than 2 SDs of the relevant measurement error after 27 out of 46 (59%) balloon inflations. Lactate concentrations were raised after 43 out of 46 (93%) balloon inflations. No significant difference was found between the peak percentage change of either lipid peroxide or lactate concentrations after any of the first three serial inflations. The maximum ST segment shift after each of the first three serial inflations was also similar. Coronary venous lactate concentrations after balloon inflation correlated positively with the maximum ST segment shift, but did not correlate with lipid peroxide concentrations. CONCLUSIONS: Raised lipid peroxide concentrations in coronary venous plasma can be detected in humans after balloon angioplasty. There is no positive correlation between lipid peroxide concentrations in coronary venous plasma after angioplasty and the degree of preceding myocardial ischaemia as assessed by either ST segment shift or lactate production. These indices showed that one to three serial 60 second balloon inflations each produce a similar degree of myocardial ischaemia. The origin of the raised lipid peroxide concentrations in coronary venous plasma after angioplasty remains unknown.

Adult↗

Monitoring of streptokinase resistance titre in acute myocardial infarction patients up to 30 months after giving streptokinase or anistreplase and related studies to measure specific antistreptokinase IgG.

OBJECTIVE: To examine the induction of antistreptokinase antibodies after giving streptokinase or anistreplase to patients with acute myocardial infarction. DESIGN: Patients were randomly allocated to receive either 1.5 x 10(6) IU, streptokinase or 30U anistreplase in a double blind study. Blood samples were collected immediately before treatment and subsequently at intervals up to 30 months; plasma samples were assayed for streptokinase resistance titre (functional assay) and streptokinase binding by IgG (microradioimmunoassay). SETTING: Cardiology department in a general hospital. PATIENTS: 128 consecutive eligible patients. Samples were collected for up to one year according to a prospective design: a subsection of 47 patients was selected for intensive study over the first 14 days. After one year, all available patients (67) were sampled on one further occasion. RESULTS: Antibody responses to streptokinase and anistreplase were similar. Streptokinase resistance titres exceeded pretreatment concentrations five days after dosing, and values peaked at 14 days. By 12 months after dosing, 92% of resistance titres (n = 84) had returned to within the pretreatment range. Antistreptokinase IgG concentrations also exceeded baseline concentrations within five days and peaked at 14 days. Half of the individual values had returned to within the pretreatment range by 12 months (n = 84) and 89% by 30 months (n = 18). CONCLUSION: Although we cannot be sure of the clinical significance, because of the increased likelihood of resistance due to antistreptokinase antibody, streptokinase and anistreplase may not be effective if administered more than five days after an earlier dose of streptokinase or anistreplase, particularly between five days and 12 months, and increased antistreptokinase antibody may increase the risk of allergic-type reactions.

Adult↗

A comparison of the pharmacokinetic properties of streptokinase and anistreplase in acute myocardial infarction.

1. The pharmacokinetics of streptokinase (SK) and anistreplase in conventional dosage regimens of 1.5 x 10(6) i.u. of SK infused over 60 min and 30 units of anistreplase over 5 min were studied in 24 consecutive patients presenting with acute myocardial infarction, using a functional bioassay to assess concentrations. 2. The two agents were found to have similar volumes of distribution (5.68 and 5.90 l), but SK was cleared significantly more rapidly than anistreplase, resulting in a shorter terminal phase half-life (0.61 vs 1.16 h) and a shorter mean residence time (0.76 vs 1.55 h).

Aged↗

Double blind crossover comparison of the effects of dual chamber pacing (DDD) and ventricular rate adaptive (VVIR) pacing on neuroendocrine variables, exercise performance, and symptoms in complete heart block.

OBJECTIVE: To compare the effects of dual chamber pacing (DDD) and ventricular rate adaptive pacing (activity sensing) (VVIR) in patients with complete heart block. DESIGN: Double blind crossover comparison with one month in each pacing mode. PATIENTS: 10 consecutive patients aged 23-74 presenting with complete anterograde atrioventricular block at rest and on exercise and with an intact atrial rate response received Synergyst I (Medtronic) pacemakers. MAIN OUTCOME MEASURES: Symptom scores, maximal exercise performance on a treadmill, and the plasma concentrations of atrial natriuretic peptide, adrenaline, and noradrenaline. RESULTS: No significant differences were identified between pacing modes in symptom scores for dyspnoea, fatigue, and mood disturbance; exercise time; and maximal oxygen consumption. One patient with intact ventriculoatrial conduction developed pacemaker syndrome during VVIR pacing. Resting plasma concentrations of atrial natriuretic peptide were raised in complete heart block and were restored to normal by DDD pacing but not by VVIR pacing. Resting plasma catecholamine concentrations were normal in complete heart block and in both pacing modes. During exercise the increase in the concentrations of all three hormones was similar in both pacing modes. CONCLUSIONS: In patients with complete anterograde and retrograde atrioventricular block, symptoms and maximal exercise performance were no better during DDD than during VVIR pacing.

Adult↗

A pilot study of the efficacy and safety of bolus administration of alteplase in acute myocardial infarction.

OBJECTIVE: To examine the efficacy, safety, and the pharmacokinetic profile of a bolus dose administration regimen of alteplase in the treatment of acute myocardial infarction. DESIGN: An open pilot study. SETTING: District general hospital. PATIENTS: 33 suitable consecutive patients presenting within six hours of the onset of symptoms who satisfied the electrocardiographic criteria for acute myocardial infarction. INTERVENTIONS: Two intravenous boluses of 35 mg alteplase, 30 minutes apart. MAIN OUTCOME MEASURES: Angiographic coronary patency at 90 minutes and 24 hours. Plasma alteplase concentration-time profile and pharmacokinetic analysis. RESULTS: Coronary patency at 90 minutes: 26 of 30 arteries (87%, 95% confidence interval (CI) 74-99%). Coronary patency at 24 hours: 24 of 29 arteries (83%, CI 69-97%). Mean (SD) plasma tissue plasminogen activator (t-PA) concentration reached 4434.8 (2117.8) and 4233.3 (2217.5) ng/ml within 10 minutes of each bolus and fell to 425.8 (288.3) ng/ml between boluses. The estimated peak concentrations at two minutes after boluses were 12,389 (8580) ng/ml and 10,811 (6802) ng/ml. The derived pharmacokinetic variables were volume of distribution 3.11 (1.89) 1, clearance 21.3 (9.3) 1/h, half life 5.9 (1.7) minutes. CONCLUSIONS: This simple administration regimen achieved brief, high concentrations of plasma t-PA that were well tolerated. The regimen was associated with a high coronary patency rate at 90 minutes that was well maintained at 24 hours.

Adult↗

Angiographic patency study of anistreplase versus streptokinase in acute myocardial infarction.

128 patients with acute myocardial infarction of duration 6 h or less were randomised in double-blind fashion to receive 30 U anistreplase over 5 min or 1.5 MU streptokinase over 1 h, both intravenously. Angiographic patency was assessed 90 min and 24 h from the start of therapy. 55% of patients who received anistreplase and 53% of patients who received streptokinase had patent infarct-related arteries (TIMI grade 2-3) at 90 min (95% CI 42-68% and 40-66%, respectively). At 24 h 81% and 87.5% of arteries were patent respectively (95% CI, 71-91% and 83.5-91.5%). Time to therapy had no significant effect on patency rates. There was one early reocclusion within 24 h in each treatment group and clinical evidence of reocclusion was recorded between 24 h and hospital discharge in a further 5 patients (streptokinase 3, anistreplase 2). With these regimens, therefore, anistreplase and streptokinase gave the same patency rates.

Adult↗

Quantification of aortic regurgitation using continuous and pulsed wave Doppler echocardiography.

In a prospective blind study, continuous and pulsed wave Doppler echocardiography were used to predict the severity of angiographically assessed aortic regurgitation in 36 patients. High quality continuous wave spectral recordings of the regurgitant jet were obtained in 32 patients but four patients with mild aortic regurgitation had dropout of high velocity signals precluding accurate assessment. The deceleration slope of the peak to end-diastolic velocity measured by continuous wave Doppler, and pulsed wave Doppler mapping of the regurgitant jet in the left ventricle were compared with angiographic severity. The deceleration slope was significantly steeper in patients with severe rather than mild or moderate aortic regurgitation (3.65 +/- 1.04 vs. 1.89 +/- 0.42 vs. 1.52 +/- 0.59 m sec-2). A decay slope of greater than 3 m sec-2 was observed only in patients with 3+ or 4+ aortic regurgitation and a decay slope less than 1.2 m sec-2 was seen only in mild 1+ aortic regurgitation but there was considerable overlap between groups, making it difficult in individual cases to assess severity on the basis of the continuous wave deceleration slope. The pulsed wave Doppler technique was more time consuming, added little to the continuous wave Doppler assessment and underestimated severe regurgitation in almost 50% of cases. Hence, there are significant problems using either Doppler technique in quantitatively assessing aortic regurgitation.

Adolescent↗

Adenosine or adenosine triphosphate for supraventricular tachycardias? Comparative double-blind randomized study in patients with spontaneous or inducible arrhythmias.

The effects of intravenous adenosine and adenosine triphosphate (ATP) were studied in a double-blind randomized study during 68 episodes of supraventricular tachycardia in 39 patients. Adenosine restored sinus rhythm in 20 patients (25 of 27 episodes) and produced atrioventricular block to reveal atrial arrhythmias in nine. ATP restored sinus rhythm in 17 patients (22 of 25 episodes) and revealed atrial tachyarrhythmias in six. In patients receiving both compounds, the effective dosage of adenosine was 3.8 mg and of ATP it was 6.6 mg (p less than 0.05), suggesting molar equipotency. Transient side effects were common, occurring in 81% of episodes with adenosine and in 94% with ATP. Symptom scores (0 to 10) were not significantly different (median score for adenosine was 5, for ATP it was 6). Adenosine and ATP were equally effective for the diagnosis and treatment of supraventricular tachycardias and the incidence and severity of side effects were similar. Adenosine has the advantage of being more stable.

Adenosine↗

Study of serum C-reactive protein concentration in cardiac failure.

The serum concentration of C-reactive protein was prospectively assessed in 37 patients with various degrees of heart failure. The serum concentration of C-reactive protein was higher than normal in 26 (70%) patients. The concentration was directly related to the severity of heart failure and the stage of decompensation. Hepatic cell damage is the most likely stimulus to cytokine production and hence release of C-reactive protein in heart failure. Heart failure is an additional cause of raised serum concentration of C-reactive protein but the pathological importance of this feature is not yet known.

Aged↗

Verapamil or adenosine for the immediate treatment of supraventricular tachycardia.

A comparison of verapamil with adenosine for the immediate treatment of supraventricular tachycardia was made from a retrospective review of 164 spontaneous episodes of paroxysmal tachycardia in 43 patients. Verapamil administered to 33 patients restored sinus rhythm in 91 of 112 episodes (81 per cent). Hypotension occurred in 9 per cent of episodes. Adenosine terminated 94 per cent of episodes of supraventricular tachycardia in 25 patients. The arrhythmia recurred shortly after adenosine restored sinus rhythm in 20 episodes. Transient side effects were common. Fifteen patients were treated with both agents. Adenosine was successful in all, but verapamil failed to restore sinus rhythm at least once in seven of the 15 patients. Early recurrence of tachycardia occurred in five of these after adenosine, but in only one after verapamil. Verapamil and adenosine are both effective in the treatment of supraventricular tachycardia; adenosine has the higher success rate and is safer, but transient symptoms are common and arrhythmias may recur.

Adenosine↗

Impact of a policy of direct admission to a coronary care unit on use of thrombolytic treatment.

Because thrombolytic treatment is effective only if it is given within six hours of acute myocardial infarction it is vital to admit patients to the coronary care unit as soon as possible after the acute event. A policy of admitting patients to the coronary care unit at the request of the patient's general practitioner by a telephone line that is independent of the hospital switchboard significantly reduced the delay. Those admitted via the accident and emergency department at the same hospital reached the coronary care unit 1 h 32 min after being seen by the general practitioner whereas the patients admitted directly took only 43 minutes [corrected]. The policy of direct admission also significantly increased both the percentage of patients who received thrombolytic treatment and the percentage of patients admitted within three hours from the onset of symptoms.

Coronary Care Units↗

Value and limitations of adenosine in the diagnosis and treatment of narrow and broad complex tachycardias.

The diagnostic and therapeutic potential of intravenous adenosine was studied in 64 patients during 92 episodes of regular sustained tachycardia. In 40 patients who had narrow complex tachycardias (QRS less than 0.12 s) adenosine (2.5-25 mg) restored sinus rhythm in 25 with junctional tachycardias (46 of 48 episodes) and produced atrioventricular block to reveal atrial or sinus tachycardia in 15. In 24 patients with broad complex tachycardias (QRS greater than or equal to 0.12 s) adenosine terminated the tachycardias in six patients and revealed atrial or sinus arrhythmias in four. The tachycardias persisted in 14 patients despite doses up to 20 mg, but adenosine allowed the diagnosis of ventricular tachycardia with retrograde atrial activation in two patients by producing transient ventriculoatrial dissociation. Diagnosis based on adenosine induced atrioventricular nodal block was correct in all patients with narrow complex tachycardias and in 92% of those with broad complex tachycardias, compared with correct electrocardiographic diagnoses in 90% and 75% respectively. Adenosine gave diagnostic information additional to the electrocardiogram in 25%. The response to adenosine in broad complex tachycardias identified those of supraventricular origin with 90% sensitivity, 93% specificity, and 92% predictive accuracy. Adenosine restored sinus rhythm in all patients with junctional reentrant tachycardias, but in 10 (35%) the arrhythmias recurred within two minutes. Symptomatic side effects (dyspnoea, chest pain, flushing, headache) were reported by 40 (63%) patients and, although transient, were severe in 23 (36%). There were ventricular pauses of over 2 s in 16% of patients, the longest pause being 6.1 s. Adenosine is of value in the diagnosis and treatment of narrow and broad complex tachycardias, but its use is limited by symptomatic side effects, a tenfold range in minimal effective dosage, occasional action at sites other than the atrioventricular node, and early recurrence or arrhythmia.

Adenosine↗

Proarrhythmic effects of antiarrhythmic drugs in patients with malignant ventricular arrhythmias evaluated by electrophysiologic testing.

The provocation or worsening of arrhythmias by antiarrhythmic regimens was evaluated in patients with malignant ventricular arrhythmias undergoing electrophysiologic studies. In 314 patients with sustained or nonsustained ventricular tachycardia or ventricular fibrillation, 801 drug studies were performed using a standard protocol of programmed electrical stimulation. The criteria for proarrhythmia were: 1) initiation of sustained ventricular tachyarrhythmia in a patient in whom only nonsustained tachycardia was induced at baseline; 2) conversion of a sustained tachycardia that could be terminated by programmed electrical stimulation at baseline to one that required cardioversion for termination during drug therapy; 3) initiation of a sustained tachyarrhythmia by a less aggressive mode of stimulation than was required at baseline; and 4) development of spontaneous or incessant ventricular tachycardia. Proarrhythmia criterion 1 occurred during 20 (18%) of 118 studies and at least once in 15 (28%) of 54 patients. Criterion 2 was met during 39 (7%) of 578 studies and at least once in 29 (13%) of 220 patients. Criterion 3 was achieved during 135 (20%) of 687 studies in patients with sustained ventricular tachyarrhythmias at baseline. Criterion 4 occurred during 9 (1%) of 801 drug studies. In 40 patients in whom well tolerated ventricular tachycardia was initiated with fewer extrastimuli during drug study than at baseline, the drug was continued and the patients were followed up. The recurrence rate of tachycardia was the same in these patients as in 73 patients followed up on regimens on which the number of extrastimuli required for initiation was not reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Misuse of intravenous verapamil in patients with ventricular tachycardia.

Intravenous verapamil is effective in the acute termination of supraventricular tachycardia but is also used for broad-complex tachycardia when the diagnosis is uncertain. This study analysed the responses to verapamil in 57 episodes of ventricular tachycardia, incorrectly diagnosed as supraventricular tachycardia, in 32 patients. Diagnostic electrocardiographic features of ventricular tachycardia were present in 81% of episodes. Intravenous verapamil (mean dose 9.8 mg) failed to terminate the tachycardia in 45 episodes (79%). 2 patients sustained cardiac arrest after verapamil (1 ventricular fibrillation, 1 asystole), and in 22 episodes severe hypotension occurred. At least one serious adverse effect occurred in 19 patients (59%). Sinus rhythm was restored after verapamil on 10 occasions in 6 patients. Verapamil is ineffective and potentially hazardous in most patients with ventricular tachycardia. It should not be used to treat broad-complex tachycardia unless a supraventricular origin has been established.

Adult↗

Proarrhythmic responses during electrophysiologic testing.

Antiarrhythmic drugs may worsen ventricular arrhythmias in certain patients. This effect, termed proarrhythmia, aggravation or provocation of arrhythmia, can be investigated with either noninvasive or invasive techniques. Using electrophysiologic study, 160 patients with ventricular tachycardia or ventricular fibrillation were evaluated during treatment with 432 different antiarrhythmic regimens. Proarrhythmic responses were noted in 68 drug trials (16%), and at least 1 event was observed in 51 patients (32%). Nonsustained ventricular tachycardia was converted to sustained ventricular tachycardia in 17% of these studies. Hemodynamically stable ventricular tachycardia was converted to an arrhythmia that required cardioversion for termination in 5% of the studies. Ventricular tachyrhythmia was more easily induced in 12% of trials. These proarrhythmic responses were not related to changes in QRS duration, QT interval or JT interval measured at baseline or to changes produced by antiarrhythmic drugs.

Anti-Arrhythmia Agents↗

Electrophysiologic assessment of antiarrhythmic drug efficacy for ventricular tachyarrhythmias associated with dilated cardiomyopathy.

To determine the benefit of serial electrophysiologic drug testing in patients with ventricular tachyarrhythmias related to dilated cardiomyopathy, programmed ventricular stimulation was performed in 38 patients. In the baseline study, sustained ventricular tachycardia (VT) was induced in 18 patients, ventricular fibrillation in 7 and nonsustained VT in 13. The patients underwent a total of 84 trials of drug therapy (mean 2.3 +/- 1.4 trials/patient). Complete success (induction of fewer than 6 repetitive responses) was recorded in 19 trials and partial success (induction of at least 6 but no more than 15 repetitive responses) in 7. Potential proarrhythmic effects were observed in 9 trials. Overall, at least 1 successful regimen was identified for 20 patients (53%). During a mean follow-up of 21 +/- 13 months, there were no arrhythmia recurrences or episodes of sudden death among patients discharged with a drug regimen determined to be effective by serial drug testing. In comparison, among patients taking regimens that failed to prevent arrhythmia induction, there were 3 arrhythmia recurrences and 2 sudden deaths (p less than 0.05). Serial electrophysiologic drug testing provides an effective method of identifying successful medical therapy for patients with ventricular arrhythmia related to dilated cardiomyopathy.

Adult↗