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Biomedical subjects

R M Norris

Publications and source records attributed to R M Norris.

At least 19 recordsLinked to original sources
PubMed1992

Effects of progressive myocardial ischaemia on systolic function, diastolic dysfunction, and load dependent relaxation.

OBJECTIVE: The aims were to determine (1) the relationship between changes in contractile function (systolic shortening) and the appearance of diastolic dysfunction (postsystolic shortening) during progressive regional left ventricular ischaemia; (2) the effects of increased afterload (acute constriction of the descending thoracic aorta) on ischaemic contractile dysfunction; and (3) the effects of loading during ischaemia on load dependent relaxation. METHODS: Regional myocardial function, using sonomicrometry, was measured in the short and long axes of the apex of the left ventricle of eight open chest anaesthetised dogs (16-20 kg). Progressive apical ischaemia was induced by graded reductions in left anterior descending coronary artery flow (critical constriction, ischaemia 1, ischaemia 2, total coronary occlusion, and postocclusive maximum reactive hyperaemia). Acute afterloading was induced by a snare placed around the descending aorta. RESULTS: Consistent decreases in systolic shortening and increases in postsystolic shortening relative to the total segmental shortening in the short axis of the apical region were seen with worsening ischaemia. Aortic constriction increased the magnitude of apical postsystolic shortening and decreased apical systolic shortening in the short axis during critical constriction, ischaemia 1, and ischaemia 2. Long axis function changed in a qualitatively similar but quantitatively different manner. There was a significant decrease in the load dependency of relaxation with total coronary occlusion. CONCLUSIONS: (1) Changes in systolic and diastolic function occurred concomitantly as mild regional myocardial ischaemia developed and intensified; (2) afterloading significantly worsened regional systolic and diastolic dysfunction during mild ischaemia; and (3) progression of regional ischaemia resulted in loss of load dependent relaxation.

Animals↗
PubMed1992

Prognosis after recovery from myocardial infarction: the relative importance of cardiac dilatation and coronary stenoses.

In order to further define clinical and angiocardiographic predictors of long-term survival after myocardial infarction we followed 616 consecutive male patients under 60 years of age, survivors of a first (N = 455) or recurrent (N = 161) myocardial infarction, for 8.8 +/- 2.9 years. Patients had angiocardiography at 4-8 weeks after infarction; none had thrombolysis, but 33% had cardiac surgery, 14% on a clinical trial basis. Left ventricular end-systolic volume was the most powerful predictor of cardiac mortality; ejection fraction and end-diastolic volume added no further information. Myocardial score, a measure of the severity of coronary stenoses in relation to the amount of myocardium supplied, was of only borderline predictive value on multivariate analysis, possibly because any effect had been negated by coronary surgery. Administration of beta-blocker drugs had an independent effect of improving prognosis, while continued cigarette smoking worsened it. Age, status of index infarction (first or recurrent) and serum cholesterol did not affect survival. A trial of surgery, carried out in a subset of 200 of these patients who were relatively asymptomatic but had severe coronary disease, showed no survival advantage for intended surgical over non-surgical management. We conclude that a high left ventricular end-systolic volume remains the most important adverse prognostic factor after recovery from myocardial infarction.

Actuarial Analysis↗
PubMed1992

Reduced synthesis of tissue plasminogen activator by vascular endothelium during acute myocardial infarction.

We measured levels of tissue plasminogen activator (t-PA) antigen in 100 patients within six hours of the onset of acute myocardial infarction, in 34 patients with chronic angina but no recent infarction, and in 36 normal subjects. We also assayed von Willebrand factor in the acute patients and in the normal subjects. Measurements were repeated in 40 acute patients at three weeks after myocardial infarction. Although resting levels of t-PA antigen were not significantly different from normal during myocardial infarction, the capacity of the vascular endothelium to release t-PA after five minutes of venous occlusion was impaired (p less than 0.01). The acute phase vessel wall release of von Willebrand factor was increased during acute infarction (p less than 0.01). We conclude that impairment of t-PA production is associated with acute coronary thrombosis, although it is not possible to differentiate between a causative role or a secondary response due to exhaustion of the t-PA producing mechanism.

Adult↗
PubMed1991

Pressure-length loop area: its components analyzed during graded myocardial ischemia.

The changes in total pressure-length loop area were compared with changes in effective shortening area, systolic lengthening area and postsystolic shortening area (defined with respect to end-diastolic and end-systolic lengths) of the pressure-length loop during myocardial ischemia in seven anesthetized dogs instrumented for measurement of left ventricular pressure and regional segmental wall motion (sonomicrometry) in the minor axis of the apical region of the left ventricle. Ischemia was induced by gradual tightening of a micrometer-controlled snare around the left anterior descending coronary artery, which supplied the apical myocardium. Data were obtained at normal flow, after critical constriction (loss of pulsatile coronary flow), mild ischemia (ischemia 1: onset of regional dysfunction, i.e., postsystolic shortening and mild hypokinesia) and moderate ischemia (ischemia 2: marked hypokinesia). At each stage, acute afterloading was performed by partially occluding the descending thoracic aorta. The pressure-length loops were analyzed in terms of four areas: total loop area, effective shortening area, postsystolic shortening area and systolic lengthening area. Total loop area decreased only when marked hypokinesia was present (176 +/- 18.3 mm Hg x mm at ischemia 2 versus 245.1 +/- 26.9 mm Hg x mm at ischemia 1, p less than 0.05). However, effective shortening area (98.2 +/- 0.8% of total loop area at baseline; 93.8 +/- 2.4% at critical constriction; 76.3 +/- 7.2% at ischemia 1; 51.9 +/- 12.2% at ischemia 2) and postsystolic shortening area (1.8 +/- 0.8% of total loop area at baseline; 5.2 +/- 1.9% at critical constriction; 14.3 +/- 3/4% at ischemia 1; 23.8 +/- 5.1% at ischemia 2) changed significantly with each progressive stage of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Comparison of the effects of streptokinase and tissue plasminogen activator on regional wall motion after first myocardial infarction: analysis by the centerline method with correction for area at risk.

In a trial of streptokinase versus recombinant tissue-type plasminogen activator (rt-PA) for a first myocardial infarction, 270 patients were randomized. Regional left ventricular function was assessed in 214 patients at 3 weeks. The infarct-related artery was the left anterior descending artery in 78 patients, the right coronary artery in 122 and a dominant left circumflex artery in 14. Analysis was by the centerline method with a novel correction for the area of myocardium at risk, whereby the search region was determined by the anatomic distribution of the infarct-related artery. Infarct-artery patency at 3 weeks was 73% in the streptokinase group and 71% in the rt-PA group. Global left ventricular function did not differ between the two groups. Mean chord motion (+/- SD) in the most hypokinetic half of the defined search region was similar in the streptokinase and rt-PA groups (-2.4 +/- 1.5 versus -2.3 +/- 1.3, p = 0.63). There were no differences in hyperkinesia of the noninfarct zone. Compared with conventional centerline analysis, regional wall motion in the defined area at risk was significantly more abnormal. The two methods correlated strongly, however (r = 0.99, p less than 0.0001), and both methods produced similar overall results. Patients with a patent infarct-related artery and those with an occluded artery at the time of catheterization had similar levels of global function (ejection fraction 58 +/- 12% versus 57 +/- 12%, p = 0.58).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗
PubMed1991

Decision support systems and the healthcare strategic planning process: a case study.

The repertoire of applications that comprises health-care decision support systems (DSS) includes analyses of clinical, financial, and operational activities. As a whole, these applications facilitate developing comprehensive and interrelated business and medical models that support the complex decisions required to successfully manage today's health-care organizations. Kennestone Regional Health Care System's use of DSS to facilitate strategic planning has precipitated marked changes in the organization's method of determining capital allocations. This case study discusses Kennestone's use of DSS in the strategic planning process, including profiles of key DSS modeling components.

Capital Expenditures↗
PubMed1990

Reinfarction after thrombolytic therapy for acute myocardial infarction followed by conservative management: incidence and effect of smoking.

A group of 456 consecutive patients seen less than or equal to 6 h after the onset of acute myocardial infarction associated with ST segment elevation received thrombolytic therapy and were followed up for 12 months. Intravenous streptokinase was given to 315 patients and recombinant tissue-type plasminogen activator (rt-PA) to 141 patients. Reinfarction rate and risk factors for reinfarction were assessed. Management after thrombolysis was conservative; revascularization procedures were reserved for patients with symptoms refractory to medical therapy or for those with left main coronary artery stenosis. Coronary artery surgery or angioplasty was performed in only 3.7% of patients during the first 30 days after thrombolysis and in only 8.6% by 1 year. Most patients (79%) underwent coronary arteriography. Twenty-six patients (5.7%) exhibited signs of threatened reinfarction at 1 month after thrombolytic therapy as did 43 patients (9.4%) by 1 year. Reinfarction was prevented in four of these patients by early readministration of thrombolytic therapy. Multivariate analysis of possible risk factors for reinfarction identified at the time of initial infarction showed current cigarette smoking to be the only predictive factor (reinfarction occurred in 12.5% of smokers versus 6.3% of nonsmokers, p = 0.04). A second analysis of risk factors identified 3 weeks after initial infarction, including the severity of residual stenosis at coronary arteriography and exercise test variables, again showed continued cigarette smoking to be the only factor predictive of reinfarction. Twenty percent of patients who continued to smoke developed reinfarction compared with 5.1% of those who stopped (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Left ventricular function as an end-point of thrombolytic therapy.

For clinical prognosis, LV function is best described in terms of ejection fraction (EF) or end-systolic volume (ESV). Because deterioration of LV function is the most important adverse prognostic factor for patients after recovery from myocardial infarction, any agent which improves function should improve long-term survival. Clinical trials in which LV function has been measured have shown that early administration of all the presently available thrombolytic drugs improves LV function. There is, however, no evidence that one drug is better than another for preservation of LV function. Indeed in our double-blind comparison of streptokinase (SK) with tissue plasminogen activator (tPA) in which intervention was made at 2.5 +/- 0.6 h after onset, EF at 3 weeks after infarction was 58 +/- 12% for SK (n = 116) vs 58 +/- 12% for tPA (n = 124). The 95% confidence limit for the difference was 0 +/- 3%. Patency rates on the infarct-related artery at 3 weeks were similar in the two groups (75% SK, 76% tPA). Besides reflecting infarct size, LV function is also influenced by healing of the infarct, infarct expansion and LV remodelling. Two clinical trials have shown that captopril treatment started at 1-4 weeks after infarction and continuing for 1 year can prevent progressive LV dilatation in patients who have not received thrombolysis. One possible explanation for our own finding of similar effects of SK and tPA on LV function at three weeks after infarction, despite presumably more rapid reperfusion in patients given tPA, is that later reperfusion with SK prevented infarct expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗
PubMed1990

Safety and efficacy of repeat thrombolytic treatment after acute myocardial infarction.

Thrombolytic treatment for acute myocardial infarction increases the risk of subsequent reocclusion of the infarct related artery. The efficacy and safety of repeat thrombolytic treatment was assessed in 31 patients treated with streptokinase (n = 13) or tissue plasminogen activator (n = 18) a median of five days (1-716) after the first infusion. The indication for readministration was prolonged chest pain with new ST segment elevation. Efficacy was assessed by infarct artery patency at angiography at a median of eight days after readministration in 22 patients and by non-invasive criteria in 23 patients (reperfusion was deemed to be likely if serum creatine kinase was not increased or reached a peak less than 12 hours after infarction). Angiography showed patency of 70% of the infarct arteries after readministration of streptokinase and of 75% after tissue plasminogen activator. The corresponding patency rates assessed noninvasively were 73% and 75%. Reinfarction was prevented in nine (29%) patients. Allergic reactions occurred in four of eight patients who received streptokinase twice (plasmacytosis and acute reversible renal failure developed in one patient). Two patients had major bleeding and two minor bleeding, all after tissue plasminogen activator, and one of them died of cerebral haemorrhage. Repeat thrombolytic treatment results in late patency rates similar to the rates after the initial administration. Allergic reactions were common in those treated twice with streptokinase.

Acute Disease↗
PubMed1989

Effect of intravenous streptokinase as compared with that of tissue plasminogen activator on left ventricular function after first myocardial infarction.

In a double-blind trial comparing two thrombolytic agents as treatment for acute myocardial infarction, we randomized 270 consecutive patients an average (+/- SD) of 2.5 +/- 0.6 hours after the onset of chest pain from a first myocardial infarction--135 to receive intravenous streptokinase (1.5 million units over 30 minutes) and 135 to receive intravenous recombinant tissue plasminogen activator (rt-PA) (100 mg over three hours). The primary end point was left ventricular function as assessed by cineangiography performed three weeks after infarction. The effects of the two agents on left ventricular function were similar. The ejection fraction was identical (58 +/- 12 percent) in both groups. The end-systolic volume was 61 +/- 29 ml in the streptokinase group and 66 +/- 31 ml in the rt-PA group (P not significant). Patency rates at three weeks for the infarct-related artery were also similar (75 percent in the streptokinase group and 76 percent in the rt-PA group). Reinfarction rates at 30 days were the same (5 percent) in both groups. One patient had a fatal intracerebral hemorrhage 13 hours after receiving rt-PA, and another had a fatal cerebellar hemorrhage 21 hours after receiving rt-PA for reinfarction nine days after treatment with streptokinase. An intention-to-treat analysis revealed that mortality at 30 days was 3.7 percent in the rt-PA group as compared with 7.4 percent in the streptokinase group (P greater than 0.2). Follow-up for a mean of 9.0 months revealed no significant difference in survival; we observed 12 deaths (8.9 percent) in the streptokinase group and 8 deaths (5.9 percent) in the rt-PA group (P = 0.34). We conclude that rt-PA and streptokinase, in the doses given, have similar effects on left ventricular function after a first myocardial infarction. Because of the small number of deaths, it is not possible to determine whether their effects on mortality are similar.

Double-Blind Method↗
PubMed1988

Therapeutic trials in coronary thrombosis should measure left ventricular function as primary end-point of treatment.

Clinical trials in coronary thrombosis can record as end-points either death or an index of left ventricular function (ejection fraction or end-systolic volume) which can be used as a surrogate for long-term mortality. Hospital mortality for patients under 70 years of age in whom effective thrombolysis is achieved should now be no more than about 5%. To show a 20% reduction (to 4%) in mortality with an alpha error (two-sided) of 0.05 and a beta error of 0.2 requires 15,000 patients. By contrast, a 25% improvement towards normal in ejection fraction (from about 59% to about 62%) requires only 384 patients. Since it is likely that one of several thrombolytic agents will be effective in conjunction with one or more myocardial protective agents, many trials will be required, and it may be more appropriate in future studies to measure left ventricular function rather than mortality as the principal end-point.

Clinical Trials as Topic↗
PubMed1988

Propranolol and vagal nerve stimulation do not affect postsystolic shortening during acute myocardial ischaemia in the dog.

Changes in myocardial segment length (ultrasonic crystals) and myocardial blood flow (15(3) microns microspheres) were studied during 5 min occlusions of the left anterior descending coronary artery in open chest anaesthetised dogs, and the effects of occlusion without intervention were compared with those of occlusion during bilateral vagal nerve stimulation (n = 11) and occlusion after administration of 1 mg.kg-1 propranolol (n = 9) in the same dogs. Delineation of the perfusion beds of occluded and non-occluded arteries at necropsy verified placement of the crystals at the centres and immediately within the borders of the ischaemic areas. In untreated animals (n = 6) systolic shortening during occlusion decreased by 160(2)% (dyskinesis) in the centre zone and by 61(1)% (hypokinesis) in the border zone of ischaemia, myocardial blood flow decreased by 96(2)% in the centre and 81(2)% at the border, and the changes were reproducible over three successive occlusions. Postsystolic shortening (after peak decline of left ventricular pressure) was reproducible in control animals over three occlusions, was similar in magnitude to the magnitude of dyskinesis (centre zone) or to the degree of hypokinesis (border zone), and persisted after the release of occlusion. Vagal stimulation and propranolol decreased dyskinesis during occlusion but did not affect postsystolic shortening or collateral blood flow within the ischaemic zones. If postsystolic shortening of dyskinetic centre zone segments represents residual active shortening of these segments, as is suggested by other evidence, these results suggest that the oxygen sparing effects for very ischaemic myocardium of vagal stimulation and propranolol do not include a significant reduction in residual active shortening.

Animals↗
PubMed1988

Postsystolic shortening of acutely ischemic canine myocardium predicts early and late recovery of function after coronary artery reperfusion.

Postsystolic shortening and thickening of ischemic and postischemic myocardium are well-recognized phenomena, but their significance is controversial. To discover whether postsystolic shortening and thickening might represent an active process and to establish their place as possible predictors of functional recovery during and after recovery from ischemia, we examined correlations in severely ischemic dyskinetic myocardial segments in 14 open-chest anesthetized dogs (90 minutes' ischemia, n = 9; 180 minutes' ischemia, n = 5) between the magnitudes of postsystolic shortening and thickening during ischemia and either the magnitudes of systolic shortening and thickening in the same segments before coronary occlusion or the magnitudes of shortening and thickening at 30-60 minutes and at 2-3 weeks after reperfusion. We found positive correlations between preocclusion shortening and postsystolic shortening (r = 0.44, n = 33 myocardial segments; p less than 0.02) and between preocclusion thickening and postsystolic thickening (r = 0.73, n = 13 segments; p less than 0.01), both measured at 5 minutes after onset of ischemia. Strong correlations were found also between postsystolic shortening and thickening measured immediately before reperfusion and systolic shortening and thickening measured after recovery at 2-3 weeks (r = 0.73, n = 28; p less than 0.001 for shortening; r = 0.79, n = 12; p less than 0.01 for thickening). Significant but less-exact correlations were found between postsystolic shortening and thickening measured immediately before reperfusion and early recovery of shortening and thickening at 30-60 minutes after reperfusion (during the "stunned myocardium" period). Postsystolic shortening and thickening persisted early after reperfusion in dogs that had had 90 minutes of ischemia, and this predicted further significant return of function at 2-3 weeks. However, dogs that had had 180 minutes of ischemia did not have postsystolic shortening or thickening during early recovery and showed no further return of function at 2-3 weeks. The magnitudes of postsystolic shortening and thickening immediately before reperfusion were better predictors of late return of function than the histological appearance of the ischemic segments at 2-3 weeks or the magnitude of their blood flow during ischemia (15 +/- 3 micron microspheres). From correlations made immediately before reperfusion with those at functional recovery after reperfusion, we conclude that postsystolic shortening and thickening of dyskinetic myocardial segments are markers of their potential for recovery.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗