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Biomedical subjects

R M Norris

Publications and source records attributed to R M Norris.

At least 91 records · Page 5Linked to original sources

Propranolol disposition after acute myocardial infarction.

Serum propranolol concentration, elimination t 1/2, and protein binding were studied after a combined intravenous/oral regimen in 20 subjects with myocardial infarction (MI) and 15 with chest pain (CP). There was 1000% interindividual variation in propranolol concentrations in each group. In the MI group, mean total serum propranolol concentrations were greater than 100 nmol/l, except at 7 hr, when there was a trough not present in subjects with CP. Mean elimination t 1/2 s in subjects with MI (7.2) and CP (7.4 hr) did not differ. There were significantly higher alpha 1-acid glycoprotein concentrations and reduced percent unbound propranolol 27 hr after infarction. Free propranolol concentrations were lower 7 and 11 hr after dosing in the MI group, but concentrations thereafter were of the same order as those in subjects with CP. The only significant difference in any of the hemodynamic measurements was at 7 hr, when blood pressure was higher in the MI group. We conclude that propranolol kinetics were altered in subjects with MI and suggest that the regimen could be improved by increased propranolol dosage at commencement of therapy.

Administration, Oral↗

Subacute cardiac rupture: a surgical emergency.

Three cases of subacute cardiac rupture following acute myocardial infarction are described. All three patients experienced sudden collapse during convalescence and following cardiopulmonary resuscitation were in cardiogenic shock, the shock being due to haemopericardium causing cardiac tamponade. Two of the patients who had electrocardiographic monitoring at the time of their collapse showed nodal bradycardia and were apnoeic and unconscious with no recordable blood pressure (electromechanical dissociation). The diagnosis was confirmed in all three patients by echocardiography which showed pericardial fluid. The patients were referred for urgent cardiac surgery (infarctectomy and Teflon patching) without further investigation. All three patients survived the emergency operation, but two died soon after surgery. The third patient is alive and well five months after the operation.

Cardiac Tamponade↗

Severity of canine myocardial infarcts in relation to indices of oxygen demand: preservation of myocardial creatine kinase activity by vagal stimulation and propranolol.

The left anterior descending coronary artery was ligated in 58 open-chest anaesthetised dogs; 23 were controls, 15 were given intravenous propranolol 1 mg . kg-1 before and at 6 h intervals after coronary ligation, nine had bilateral cervical vagal nerve stimulation (VS) before and for 4 to 6 h after coronary ligation, and 11 had both VS and propranolol. None of the 20 dogs undergoing VS developed ventricular fibrillation within the first hour after coronary ligation compared to nine of the remaining 38 (P less than 0.05). Compared to controls, myocardial creatine kinase (CK) depletion in the epicardial layer of the infarct centre measured 24 h after coronary ligation was significantly less in the groups treated separately with vagal nerve stimulation and propranolol. Myocardial blood flow (MBF) measured at 15 min after coronary ligation was reduced to the normal myocardium by the interventions, but was unchanged at the infarct centre. Severely ischaemic myocardium (MBF less than or equal to 20% of normal) was better protected by the interventions than was moderately ischaemic myocardium. At 15 min after coronary ligation, the heart rate--blood pressure product (RPP) was reduced compared with controls by propranolol (18% reduction, P less than 0.05), reduced more by vagal stimulation (by 37%, P less than 0.001) and still more by vagal stimulation with propranolol (by 43%, P less than 0.001). Preservation of CK in myocardium with MBF less than or equal to 20% of normal was improved by VS and propranolol given separately roughly in proportion to reduction in RPP, but further reduction in RPP by VS and propranolol together did not improve CK levels further. We conclude that there may be an optimum level of indices of oxygen demand for preservation of very ischaemic myocardium in experimental infarction.

Animals↗

Serum myoglobin, creatine kinase and creatine kinase-MB as mutually supportive indices of myocardial infarction and infarct size.

A comparison was made between the appearance of serum myoglobin and creatine kinase in 22 patients with acute myocardial infarction who were admitted to a coronary-care unit within four hours of onset of chest pain. The MB isoenzyme of creatine kinase was measured in 12 patients. The more rapid appearance and disappearance of myoglobin relative to creatine kinase and creatine kinase-MB was confirmed, as was the correspondence between their respective peak values. A significant correlation was also obtained between the area under the myoglobin time-course and the respective peak levels. Whereas creatine kinase activity declined exponentially from a single peak, myoglobin appeared in multiple episodes inadequately represented by a single peak value and having no clear clinical correlation. The role of myoglobin as a diagnostic aid in myocardial infarction is probably limited to its ability to support creatine kinase and creatine kinase-MB as indices of infarct size.

Creatine Kinase↗

Vitamin A palmitate decreases intravenous glucose tolerance in man.

We tested retinyl palmitate for in vivo effects in man and in vitro effects on the IM-9 lymphocyte insulin receptor. Intravenous glucose tolerance tests (IVGTT) with 25 g glucose were performed on 10 healthy subjects before and after two intramuscular injections of retinyl palmitate (25,000 IU) 18 hours apart. In 9 of 10 subjects, glucose disposition was impaired after treatment with retinyl palmitate. In vitro, retinyl palmitate 10(-4) - 10(-6) M did not affect the binding or displacement of insulin 125I from lymphocyte receptors. We conclude that retinyl palmitate decreases glucose tolerance without demonstrable effects on insulin release or insulin binding to receptors.

Adult↗

Randomized controlled trial of intraaortic balloon counterpulsation in early myocardial infarction with acute heart failure.

The value of intraaortic balloon counterpulsation in limiting infarct size and improving survival was studied in patients with early transmural myocardial infarction complicated by acute heart failure. Thirty such patients, previously well, were randomly assigned to counterpulsation (14 patients) or standard therapy (16 patients). Counterpulsation was begun 4.8 to 13.7 hours (mean 7.1) after the onset of pain and continued for less than 1 to 11 days (mean 4.5). Peak creatine kinase was 1,794 +/- 846 IU/liter (mean +/- standard deviation) in patients receiving counterpulsation compared with 1,688 +/- 908 for those receiving standard therapy; cumulative creatine kinase was 3,590 +/- 1,936 IU/liter for patients receiving counterpulsation and 2,945 +/- 1,803 for those receiving standard therapy. Hospital mortality was similar (counterpulsation, 7 of 14; standard therapy, 7 of 16 [p = 0.05 for 25 percent mortality reduction]) as was mortality at follow-up (counterpulsation, 8 of 14; standard therapy, 10 of 16 [p = 0.09 for 25 percent mortality reduction]). Functional class at follow-up examination 1 to 36 months (mean 15) after infarction was also similar in the two groups. Counterpulsation did not appear to modify infarct size or to alter morbidity or mortality when initiated as primary therapy 4.8 to 13.7 hours after the onset of symptoms of myocardial infarction.

Acute Disease↗

Depletion of myocardial creatine kinase, lactate dehydrogenase, myoglobin and K+ after coronary artery ligation in dogs.

In order to compare the time-course of disappearance of macromolecules and electrolytes from ischaemic myocardium, measurements of creatine kinase and lactate dehydrogenase activity and myoglobin, K+ and Na+ concentration were made on myocardial extracts from dogs which had left anterior descending coronary artery ligation for 3, 6, 12 and 24 h (4 groups of 6 dogs each). Intensity of ischaemia was assessed by myocardial blood flow measured with 15+/- 5 micrometers microspheres at 15 min after ligation. Creatine kinase and lactate dehydrogenase activities and K+/Na+ concentration ratios were at all times correlated with the magnitude of collateral blood flow in the ischaemic myocardium, while myoglobin concentration was correlated with blood flow only at 12 and 24h. Comparisons of the intensity of depletion at the various times after ligation showed that K+, K+/Na+ and creatine kinase had all reached a steady state at 12 h after ligation while lactate dehydrogenase and myoglobin had still to reach a steady state at 24 h. We conclude that these indices are mutually supportive markers of the intensity of ischaemia of 24 h duration, but K+ or K+/Na+ may be the most reliable indices for shorter periods of ischaemia of 3 to 6 h duration.

Animals↗

Coronary surgery after recurrent myocardial infarction: progress of a trial comparing surgical with nonsurgical management for asymptomatic patients with advanced coronary disease.

A randomized trial of surgical vs nonsurgical management was carried out in men 60 years of age or younger who had recovered from a recurrent myocardial infarction. Of 205 patients considered, 100 had few or no symptoms and had coronary vessels favorable for bypass grafting; these patients fulfilled the trial conditions and were randomized (50 surgical and 50 nonsurgical). In 41 patients (elective nonsurgical group), randomization was not considered justifiable because of relatively unfavorable coronary anatomy or severe left ventricular dysfunction. Nineteen patients had elective surgery because of disabling angina despite full medical treatment or because of significant left main coronary stenosis. In 45 patients, coronary angiography was not undertaken because of medical contraindications or reluctance of the patient to enter the study. Actuarial survival curves (mean follow-up 4.5 years) show an annual mortality rate of 3-4% per year for all investigated patients, and no advantage for the randomized surgical over the randomized nonsurgical group. The results suggest that in the absence of disabling angina or left main coronary artery stenosis, coronary artery surgery need not be advised for survivors of recurrent infarctions who have severe coronary artery disease. Moreover, the prognosis for the group of patients not treated surgically appears to be better than has been previously described.

Adult↗

Rest and the acutely ischaemic heart.

Although rest has largely been abandoned for the treatment of acute myocardial infarction, there are strong theoretical arguments for using rest for restriction of myocardial ischaemic injury during the few hours after the onset when infarct size can be influenced by treatment. Rest (reduction of myocardial oxygen uptake) can be achieved (1) by reducing heart rate, (2) by reduction of contractility, (3) by reducing myocardial wall tension. All of these objectives are achieved by beta adrenoceptor blockade. Beta blockers have been shown to restrict infarct size experimentally and clinically. Their efficacy in reducing mortality and morbidity now needs to be assessed by large-scale clinical trial using intravenous beta blockers given within an hour or two of the onset of threatened or developing myocardial infarction.

Adrenergic beta-Antagonists↗

Angiocardiography and exercise testing at one month after a first myocardial infarction.

The results of exercise testing (77 patients), left ventriculography and coronary arteriography (78 patients) are presented for men under the age of 60, one month after a first myocardial infarct. Cineangiocardiography revealed that patients with anterior infarction (n = 25) had both poorer left ventricular function and more totally occluded vessels than those with either inferior (n = 33) or subendocardial infarction (n = 20). In contrast, patients with inferior and subendocardial infarction had a greater proportion of myocardium supplied by sub-total lesions likely to be haemodynamically significant (75%-99% cross sectional area loss). Subendocardial infarction was also characterised by the best left ventricular function and the fewest number of total coronary occlusions. Stress testing showed that the combination of ischaemic ST segment changes and angina during exercise was 91% predictive of severe coronary disease (equivalent to triple vessel disease) while no angina in the presence of a negative test was 81% predictive of mild or moderate disease. Stenoses of 75%-99% cross sectional area loss were more common when angina occurred during exercise testing, and both angina and ischaemic ST segment changes occurred within ten minutes in all four patients with haemodynamically significant left main coronary artery lesions. Our data supports the usefulness of exercise testing after a first myocardial infarct and may provide valuable baseline information in the analysis of long term prognosis.

Angiocardiography↗

Comparison of enzymic with cineangiocardiographic estimations of myocardial infarct size.

Comparisons were made between enzymic indices of myocardial infarct size (total creatine kinase appearance and peak enzyme activity) measured during the acute state of a first myocardial infarct in 32 male patients, and analysis of contraction abnormalities in biplane left ventricular cineangiocardiograms performed one month later. The cineangiocardiograms were analysed independently by two radiologists, each using two different methods for quantification of subjectively classified abnormalities of left ventricular wall motion. A very strong correlation was found between the two enzymic indices of infarct size and somewhat weaker correlations between assessment of contractility abnormalities made by the two radiologists using the same method, or by the same radiologist using the two different methods. Comparisons between enzymic and angiocardiographic indices for all infarcts showed correlation coefficients (r) within the range of 0.53 to 0.72. With all comparisons of enzymic with radiological indices r values were higher for anterior infarcts than for inferior infarcts, and there was a tendency for higher enzyme levels for a given degree of left ventricular damage in inferior than in anterior infarction. This may be the result of variable degrees of right ventricular damage in inferior infarction.

Angiocardiography↗

Regional 99m technetium diphosphonate uptake in experimental dog heart infarct: relation to duration and severity of ischaemia.

Regional uptake of 99mTechnetium diphosphonate was compared with regional myocardial blood flow 6, 12 and 24 h after the onset of myocardial infarction in dogs, and with regional creatine kinase depletion 24 h after the onset. Uptake of the imaging agent increased from 6 to 24 h, but no consistent relationship could be demonstrated between regional myocardial blood flow and regional uptake of the diphosphonate nor between uptake and regional creatine kinase depletion at the centre or border of the infarct. In addition, inappropriately high levels of 99m Technetium uptake could be demonstrated in the epicardial layer of the normal tissue surrounding the infarct. We conclude that diphosphonate uptake is not quantitatively related to the severity of ischaemia, and that use of this substance for imaging may over-estimate myocardial infarct size.

Animals↗