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Biomedical subjects

A D Timmis

Publications and source records attributed to A D Timmis.

At least 127 records · Page 7Linked to original sources

Contrast perfusion echocardiography: identification of area at risk of dyskinesis during percutaneous transluminal coronary angioplasty.

Two-dimensional contrast perfusion echocardiography was performed in 14 patients who underwent percutaneous transluminal coronary angioplasty to test the efficacy of this new technique for defining the area at risk of dyskinesis during acute coronary occlusion. In nine patients (group A) selective coronary injection of echocontrast medium through the central lumen of the angioplasty catheter was performed immediately before balloon inflation. This produced regional myocardial enhancement that defined the area of dyskinesis after balloon inflation. In five patients (group B) who underwent left coronary angioplasty, echocontrast medium was injected through the introducer catheter positioned in the left main coronary artery during balloon inflation. In each case this produced regional myocardial enhancement remote from the area of dyskinesis. There were no complications related to the intracoronary echocontrast injections, which produced no discernible exacerbation of chest pain or left ventricular contractile dysfunction. These data indicate that selective coronary injection of echocontrast medium defines the perfusion territory of the artery injected and also provides a means of identifying the area at risk of dyskinesis after balloon occlusion of the artery.

Adult↗

Early percutaneous transluminal coronary angioplasty in the management of unstable angina.

This report describes the results of percutaneous transluminal coronary angioplasty in 56 patients with unstable angina. In each case diagnostic coronary angiography had demonstrated a critical proximal stenosis in a major vessel. The stenosis was successfully dilated without complication in 70% of cases. Angiographic success was reflected by the abolition of symptoms and a nonischaemic predischarge stress test in 82 and 72% of cases, respectively. Importantly, at six months follow-up 69% of these patients remained symptom free though repeat angioplasty had been necessary in 21% of cases. The in-hospital incidence of myocardial infarction and death was 7.1 and 5.4%, respectively, but during the six month follow-up period only one additional complicating event occurred. Results were particularly favourable in patients with single vessel disease, 83% of whom had successful procedures. There was one uncomplicated myocardial infarct in this subgroup but no deaths. These data indicate that percutaneous transluminal coronary angioplasty may be undertaken with relative safety in patients with unstable angina and leads to a substantial improvement in symptoms that is sustained during early follow up. The benefits of this therapeutic approach may be particularly marked in patients with single vessel disease.

Adult↗

Reversible occlusion of a side branch and the left anterior descending coronary artery following angioplasty.

A 61-year-old man with unstable angina underwent emergency angioplasty of a proximal left anterior descending coronary stenosis. This was successful but a major first septal branch involved in the stenosis was occluded following the procedure. Recovery was uncomplicated, however, without chest pain or other evidence of myocardial infarction. Predischarge treadmill stress testing was negative for ischaemia but two hours afterwards abrupt coronary occlusion required a second emergency angioplasty procedure. Recanalization of the left anterior descending artery was achieved and the first septal branch was shown to be fully patent. Spasm probably accounted for the side branch occlusion which complicated the first procedure but the mechanism of the abrupt coronary occlusion following stress-testing is unclear.

Angina, Unstable↗

Anisoylated plasminogen streptokinase activator complex in acute myocardial infarction: a placebo-controlled arteriographic coronary recanalization study.

Anisoylated plasminogen streptokinase activator complex (APSAC) is a new thrombolytic agent that is of interest because of its ease of administration as an intravenous bolus injection. This report describes the first double-blind, placebo-controlled evaluation of intravenous APSAC for coronary recanalization in acute myocardial infarction. Unequivocal documentation of recanalization was provided by coronary arteriography before and after the drug intervention. Forty patients with acute myocardial infarction underwent coronary arteriography 3.1 +/- 1.2 hours after the onset of symptoms. This demonstrated occlusion of the infarct-related coronary artery in 29 patients who were then randomized to treatment with intravenous APSAC, 30 mg (n = 16), and placebo (n = 13) 3.3 +/- 1.3 hours after the onset of symptoms. Repeat arteriography 90 minutes later demonstrated recanalization of the infarct-related coronary artery in nine patients who had received APSAC compared with only one patient who had received placebo (56 versus 8%, p less than 0.05). The 95% confidence limits for this 48% difference between the groups are 20 to 76%. Arteriography at 3 days showed persistent patency of all recanalized coronary arteries except one (APSAC group) and also showed late recanalization in another four patients, three of whom had received APSAC. In the patients who had a patent infarct-related coronary artery at the initial arteriographic study, patency was maintained throughout the study period regardless of whether the patient was randomized to APSAC (n = 4) or placebo (n = 7). Complications related to APSAC therapy were excessive bruising at the catheterization site in seven patients and minor sensitivity reactions in three.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pulsed Doppler ultrasound compared with thermodilution for monitoring cardiac output responses to changing left ventricular function.

To determine the responsiveness of the pulsed Doppler technique to pacing and drug induced changes in left ventricular function 125 simultaneous cardiac output measurements by pulsed Doppler ultrasound and thermodilution were compared in 12 patients. The Doppler velocity frequencies were analysed using a signal averaging process and the validity of this method first tested in vitro. This showed almost perfect linearity of pulsed Doppler and electromagnetic flow determinations in a test rig. Although data points showed greater scatter in the clinical study, a highly significant linear relation between cardiac output measurements by pulsed Doppler and thermodilution was confirmed by regression analysis (r = 0.88, p less than 0.001). Certain mean values for cardiac output by the two techniques differed, however, by up to 0.9 litre.min-1. Despite this, changes in cardiac output in response to pacing, inotropic stimulation with dobutamine, and vasodilatation with nitrates were directionally similar, indicating a useful role for the pulsed Doppler technique in monitoring responses to treatment in the intensive care unit. Pulsed Doppler also provided a simple measure of left ventricular contractile function. Thus the inotropic response to dobutamine produced a significant rise in peak aortic flow velocity, and this variable was unaffected by either pacing or nitrate induced vasodilatation.

Cardiac Output↗

Coronary dilator effects of intracoronary nifedipine and isosorbide dinitrate.

Although both nitrates and calcium antagonists may be administered by the intracoronary route, the relative efficacy of these agents and of their combination is unknown. In this study, we investigated the coronary vasodilatory potential of intracoronary nifedipine, isosorbide dinitrate and their combination in patients undergoing routine coronary arteriography. Both normal and diseased segments of coronary arteries were studied. Coronary artery diameters were measured from 35 mm cine film before and after the administration of each drug. Two groups of 10 patients were studied: group I received nifedipine, 0.2 mg, followed by isosorbide dinitrate, 1 mg, group II received isosorbide dinitrate, 1 mg, followed by nifedipine, 0.2 mg. Both agents resulted in significant dilatation of normal and diseased segments of the coronary arteries when injected as the first drug, but neither nifedipine nor isosorbide dinitrate produced significant additional vasodilation when injected as the second drug. The degree of dilatation of both diseased and normal segments produced by either nifedipine or isosorbide dinitrate was similar, suggesting that the dose used, of either drug, produced near maximal coronary vasodilatation. Importantly, drug induced dilatation of stenotic segments was similar to that of normal segments.

Adult↗

Captopril versus placebo in congestive heart failure: effects on oxygen delivery to exercising skeletal muscle.

The effects of captopril versus placebo on oxygen consumption in the exercising leg have been examined using Doppler measurements of femoral flow and arteriovenous oxygen difference. Twenty patients with heart failure were randomized to captopril 25 mg (N = 10) or placebo (N = 10). Maximal supine exercise of one leg was performed before treatment and again 1 h and 4 h afterwards. Systemic haemodynamic variables were unaffected by placebo, but captopril increased stroke index at peak exercise from 26 +/- 3 to 34 +/- 3 ml beat-1 m-2 and reduced pulmonary artery wedge pressure from 26 +/- 3 to 16 +/- 3 mmHg (P less than 0.05). Despite the captopril-induced improvement in left ventricular function, exercise duration did not increase significantly and peak values for femoral flow (1059 +/- 178 to 938 +/- 134 ml min-1, P = NS), and oxygen consumption (134 +/- 26 to 111 +/- 18 ml min-1, P = NS) in the exercising leg were unaffected. Cutaneous flow, as reflected by skin temperature (27.5 +/- 0.4 to 27.6 +/- 0.4 degrees C, P = NS), was also unaffected. In the patients randomized to captopril, the acute improvement in left ventricular function was abbreviated and, after 4 h, all variables had returned towards baseline. Moreover, when the invasive studies were repeated after four weeks chronic treatment responsiveness to converting enzyme inhibition had attenuated and there were no detectable differences between the captopril and placebo groups. These data have demonstrated an acute captopril-induced improvement in left ventricular function in patients with congestive heart failure. Nevertheless the beneficial acute response was abbreviated predicting the development of early tolerance. Oxygen delivery to the exercising leg showed no tendency to increase either acutely when left ventricular function was significantly improved, or chronically when systemic responsiveness had attenuated. Thus irrespective of its effects on left ventricular function, captopril does not increase nutritive flow to exercising skeletal muscle in congestive heart failure.

Captopril↗

Arterial blood infusion for myocardial protection during percutaneous transluminal coronary angioplasty.

Much of the potential risk of percutaneous transluminal coronary angioplasty relates to regional myocardial ischaemia during balloon inflation. We have investigated the protective effect of infusing arterial blood through the angioplasty catheter into the distal coronary artery during 60 second balloon inflations. Symptomatic, electrocardiographic and echocardiographic indices of regional ischaemia were monitored during inflations with and without blood infusion. The effect of infusing Hartmann's solution was also evaluated to control for washout effects. Twelve patients were studied. Inflation without blood produced chest pain in eight patients, ST-segment elevation in ten patients and regional wall motion abnormalities in every case. During blood infusion manifestations of ischaemia were either delayed or prevented altogether. Chest pain occurred in only one patient while ST segment elevation and regional wall motion abnormalities occurred in three and four patients, respectively. Infusion of Hartmann's solution, on the other hand, had no significant effect on the development of regional myocardial ischaemia during balloon inflation indicating that delivery of arterial oxygen and not washout of metabolites was responsible for the beneficial effects of blood infusion. These data indicate that distal coronary perfusion with arterial blood during angioplasty reduces regional myocardial ischaemia and has the potential to improve the safety of the technique and to permit more prolonged periods of balloon inflation.

Angina Pectoris↗

The evolution of myocardial ischaemia during percutaneous transluminal coronary angioplasty.

Balloon inflation during percutaneous transluminal coronary angioplasty is a useful human model of acute coronary occlusion and regional myocardial ischaemia. We assessed the prevalence and duration of ischaemia during successive sixty-second balloon inflations in sixteen patients undergoing routine single vessel angioplasty by continuous six lead electrocardiography and cross-sectional echocardiography. The influence of rate-pressure product on the evolution of ischaemia was also evaluated. ST segment elevation developed in fourteen of the patients within 19 +/- 12 seconds and returned to baseline within 20 +/- 9 seconds of deflation. Reciprocal ST segment depression occurred in four patients, only one of whom had multivessel disease. Wall motion abnormalities on echocardiography occurred in all sixteen patients and were seen significantly earlier than electrocardiographic changes. Thus, dyskinesis developed 15 +/- 5 seconds after balloon inflation and disappeared 13 +/- 3 seconds following balloon deflation. Time to onset of ischaemia by both methods remained constant during successive balloon inflations. Rate pressure product prior to balloon inflation correlated inversely with time to onset of ischaemia detected by either technique: r = -0.73, P less than 0.05 (ECG), r = -0.65, P less than 0.05 (echocardiography). Nevertheless, evidence of ischaemia developed within 30 seconds in all patients regardless of rate-pressure product. This investigation indicates that electrocardiography and cross-sectional echocardiography have similar sensitivity for the detection of acute ischaemia during coronary angioplasty although echocardiographic change is seen significantly earlier. Resting myocardial oxygen consumption, as reflected by rate-pressure product, is an important determinant of time to onset of ischaemia following balloon inflation.

Angioplasty, Balloon↗

The effects of early coronary patency on the evolution of myocardial infarction: a prospective arteriographic study.

The effects of early spontaneous coronary patency on the evolution of myocardial infarction were evaluated in 41 patients. They had coronary arteriography (mean (SEM)) 3.1 (0.2) hours after the onset of chest pain with repeat studies 90 minutes and three days later. In 12 (29%) patients the infarct related coronary artery was patent at the first arteriogram (group 1). A further 10 patients, nine of whom received thrombolytic treatment, showed early recanalisation of the infarct related coronary artery within 90 minutes of treatment (group 2). In the remainder the infarct related coronary artery was persistently occluded (group 3). Baseline values for infarct location, the sum of ST elevation in all leads, QRS scores, and serum creatine kinase activity did not permit discrimination between the groups. Nevertheless, patterns of ST segment change and enzyme release in group 1 were closely similar to those that occurred in response to thrombolysis in group 2. Thus compared with group 3, groups 1 and 2 showed earlier 50% reduction in the sum of peak ST elevation in all leads and earlier peaking of serum creatine kinase activity. Importantly, creatine kinase release was significantly attenuated in group 1, rising to a peak serum activity (mean (SEM)) of only 1242 (415) IU/1. Analysis of angiographic left ventricular ejection fractions at three days indicated limitation of infarct size in groups 1 and 2 compared with group 3. Mean (SEM) ejection fraction, however, was best preserved in group 1 (62(6)%) and in this group the frequency of non-Q wave infarction was higher than in groups 2 and 3. Thus in patients who present with a patent infarct related coronary artery early during infarction: (a) there is a reduction in the pattern of infarct size as reflected by attenuation of release of creatine kinase, preservation of left ventricular ejection fraction, and a relatively high frequency of non-Q wave infarction; (b) patterns of ST segment change and creatine kinase release resemble those that occur after successful thrombolytic treatment, suggesting that early coronary patency is the result of spontaneous recanalisation of a previously occluded artery.

Adult↗

An interim report of a double-blind placebo-controlled recanalisation study of anisoylated plasminogen streptokinase activator complex in acute myocardial infarction.

This is an interim report of the initial 36 patients entered into the first double-blind, placebo-controlled invasive arteriographic study of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) for coronary recanalisation in acute myocardial infarction. Coronary arteriography was performed before and 90 minutes after a single intravenous bolus injection of APSAC or placebo given over 2 to 5 minutes. Pretreatment coronary arteriography was performed in 36 patients at a mean time of 189 +/- 75 minutes after the onset of symptoms. 28 patients had occluded infarct-related coronary arteries and were randomised to receive APSAC 30U (n = 15) or placebo (n = 13) by intravenous injection 195 +/- 72 minutes after the onset of symptoms. Coronary arteriography 90 minutes after treatment demonstrated recanalisation of the infarct-related coronary artery in 8 APSAC-treated patients compared with only 1 placebo-treated patient (p less than 0.02). Repeat coronary arteriography 3 days after treatment showed reocclusion in 1 of the 8 APSAC-treated patients and persistent perfusion in the single patient who reperfused on placebo. All patients with patent vessels at pretreatment coronary arteriography (3 APSAC, 5 placebo) remained patent throughout the study period. There were no haemorrhagic complications related to APSAC therapy. These data confirm that APSAC is a safe, effective thrombolytic agent which, when administered by the intravenous route, resulted in a 53% recanalisation rate.

Adult↗

Detection of early necrosis in a canine model of low flow myocardial ischemia using 125I-antimyosin (Fab')2.

Low flow myocardial ischemia in the distribution of the left anterior descending coronary artery was established in 32 anesthetized dogs. The early development of irreversible myocardial injury was identified using 125I-antimyosin (Fab')2--a specific immunological marker of myocardial necrosis. The simultaneous injection of 131I-nonspecific (Fab')2 controlled for variables unrelated to specific antimyosin activity. It was also possible to calculate the relative uptake of 125I-antimyosin (Fab')2 in the ischemic area. In order to prevent recirculation of the (Fab')2, and to limit the time of exposure to the myocardium, the fragments were injected directly into the coronary circulation during diversion of the coronary sinus effluent. The antibody fragments were given either two, three or five hours after the onset of low flow in different groups of dogs and the animals were sacrificed 60 minutes later. Selective accumulation of 125I-antimyosin (Fab')2 in the ischemic area occurred between two and three hours after the onset of low flow ischemia indicating that necrosis was already established at this time. Macroautoradiographs of cross sections of the left ventricle and autoradiographs of microscopic sections of the ischemic myocardium independently confirmed selective accumulation of 125I-antimyosin (Fab')2 and hence necrosis, at three hours after the onset of low flow. In this study the use of 125I-antimyosin (Fab')2, in contrast to the use of histology, as a marker of necrosis avoided error due to sampling and also permitted the detection of cell death early during the ischemic process. The demonstration, within a narrow time frame, of early necrosis in this low flow preparation provides a potential model with which to evaluate agents for myocardial preservation in obstructive coronary disease.

Animals↗

Factors predictive of early angiographic and functional success following percutaneous transluminal coronary angioplasty.

Baseline variables in 300 coronary angioplasty procedures were analysed to identify factors predictive of a successful outcome. Separate multivariate analyses distinguished between predictors of primary angiographic success and functional success as determined by the results of predischarge treadmill stress electrocardiography. Three independent predictors of primary angiographic success were identified: number of balloon inflations per procedure, initial stenosis, and operator experience. Of these, the number of balloon inflations per procedure and operator experience were also predictive of functional success, reflecting the dependence of a good functional result on a successful procedure. Other independent predictors of functional success were the severity of the residual stenosis and single vessel coronary artery disease suggesting that adequacy of revascularization is an important determinant of the functional result. These data illustrate the interaction between clinical, angiographic and functional variables in determining the success of PTCA. A good angiographic result may not translate into a good functional result if revascularization is incomplete.

Adult↗

Early results after percutaneous transluminal coronary angioplasty in 400 patients.

In a consecutive series of 400 patients treated by percutaneous transluminal coronary angioplasty 212 had single vessel disease, 142 had multivessel disease with only one vessel dilated, and 46 had multivessel dilatation. In addition sequential stenoses were dilated in the same vessel in all groups. There was no mortality among patients with single vessel disease. Success rates varied from 83% to 90% according to the artery in which angioplasty was attempted. Urgent surgery was required by 3.8%. Primary success was lower (74%) in the presence of multivessel disease and complications were more frequent, with four deaths (2.8%). In 46 patients with multivessel disease in whom all important lesions were dilated during the same procedure the overall primary success rate was 76% and within the last year of the study it was 91%. One (2%) patient died and three (7%) required urgent surgery. Twelve (86%) out of 14 stenosed vein grafts were successfully dilated and eight (53%) chronically occluded vessels were re-opened; in both groups there were no deaths, no infarctions, and no need for urgent surgery. In all groups symptoms improved greatly and predischarge exercise tests showed that there was no reversible ischaemia in 94% of patients with single vessel disease or in 65% of patients with incomplete revascularisation. Six months after the procedure 95% of the patients had improved symptomatically and 80% had normal exercise tests after one year. Percutaneous transluminal coronary angioplasty is the method of choice in single vessel disease and its use also results in a high proportion of other patients becoming symptom free. Complication rates are low and for selected patients results that are equivalent to those of cardiac surgery are obtained.

Adult↗

Milrinone in heart failure. Acute effects on left ventricular systolic function and myocardial metabolism.

Milrinone, a new bipyridine compound related to amrinone, is a potent non-adrenergic inotrope in experimental preparations and also shows vasodilator activity. In the present study the haemodynamic and metabolic effects of milrinone were evaluated in 12 patients with congestive heart failure. Milrinone 5 mg given orally produced a sharp reduction in left ventricular end diastolic pressure without significantly affecting stroke volume. The improvement in left ventricular function was due to a combination of vasodilation and positive inotropism. Thus small reductions in blood pressure and systemic vascular resistance were associated with increments in the isovolumic indices of left ventricular function. The relation between left ventricular end systolic pressure and dimension was displaced leftwards and downwards. Only reductions in left ventricular cavity dimension were statistically significant, however. Though myocardial oxygen consumption did not change significantly, it tended to increase whereas lactate consumption tended to decrease. This trend towards oxygen imbalance suggests the need for caution in the use of milrinone in patients with severe coronary artery disease.

Adult↗

Milrinone in heart failure. Effects on exercise haemodynamics during short term treatment.

The effects of milrinone, a new bipyridine inotropic agent, on the haemodynamic responses to treadmill exercise were studied in 12 patients with congestive heart failure. Four weeks' treatment with milrinone 20 mg daily produced an improvement in left ventricular function during exercise as reflected by significant increments in cardiac index and stroke volume index without change in pulmonary capillary wedge pressure. Systemic oxygen consumption, measured at submaximal exercise, also increased suggesting that the drug induced rise in stroke output was associated with improved skeletal muscle perfusion. Maximum exercise capacity increased. Importantly, the beneficial effects of milrinone on exercise haemodynamics and exercise tolerance were sustained throughout the four week treatment period. No drug related side effects occurred. After treatment with milrinone was stopped left ventricular function deteriorated to a level slightly, but significantly, worse than that before treatment. These observations indicate a potentially useful role for milrinone in treating heart failure.

Adult↗