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Biomedical subjects

J L Ritchie

Publications and source records attributed to J L Ritchie.

At least 19 recordsLinked to original sources

Quantitative gated blood pool tomographic assessment of regional ejection fraction: definition of normal limits.

OBJECTIVE: Our aim was to select a method of analysis for gated blood pool tomography that reduced variability in a group of normal subjects, allowed comparison with normal limit files and displayed results in the bull's-eye format. BACKGROUND: Abnormalities in left ventricular function may not be accurately detected by measures of global function because hyperkinesia in normal regions may compensate for abnormal regional function. Gated blood pool tomography acquires three-dimensional data and offers advantages over other noninvasive modalities for quantitative assessment of global and regional function. METHODS: Alternative methods for selecting the ventricular axis, calculating regional ejection fraction and choosing the number of ventricular divisions were studied in 15 normal volunteers to select the combination of parameters that produced the lowest variability in quantitative regional ejection fraction. Methods for quantitative comparison of regional ejection fraction with normal limit files and for display in the bull's-eye format were also examined. RESULTS: A fixed axis (the geometric center of the ventricle defined for end-diastole and used for end-systole) gave ejection fractions that were significantly higher in the lateral wall versus in the septum, 82 +/- 8 (mean +/- 1 SD) versus 39 +/- 17 (p less than 0.001) at the midcavity and 66 +/- 11 versus 21 +/- 20 (p less than 0.001) at the base. A floating axis system (axis defined individually for end-diastole and end-systole and realigned at the center) gave more uniform regional ejection fraction: 63 +/- 6 versus 64 +/- 8 (p = NS) at the midcavity and 44 +/- 16 versus 45 +/- 15 (p = NS) at the base. The coefficient of variability for regional ejection fraction was consistently lower using a floating axis. Calculating regional ejection fraction by dividing the regional stroke volume by the end-diastolic volume of the region gave a lower coefficient of variability and a more easily understood value than dividing the regional stroke volume by the total end-diastolic volume of the ventricle. Although the variability was lower using five versus nine ventricular divisions, nine regions offer greater spatial resolution. Comparison of regional ejection fraction with normal data identified regions greater than 2.5 SD below the mean as abnormal. We described the two-dimensional bull's-eye format as a method for displaying the regional three-dimensional data and illustrated abnormalities in patients with prior myocardial infarction. CONCLUSIONS: Gated blood pool tomography performed using a floating axis system, regional stroke volume calculation of ejection fraction and nine regions uses all the three-dimensional blood pool data to calculate regional ejection fraction, allow quantitative comparison with normal limit files, display the functional data in the two-dimensional bull's-eye format and demonstrate abnormalities in patients with myocardial infarction.

Adult

Long-term survival in 618 patients from the Western Washington Streptokinase in Myocardial Infarction trials.

OBJECTIVES: The aim of this study was to determine whether streptokinase treatment improves long-term survival in patients with acute myocardial infarction. BACKGROUND: Thrombolytic treatment for acute myocardial infarction reduces early mortality and improves the 1-year survival rate, but the long-term (3 to 8 years) survival benefits of treatment and the relation between survival and baseline clinical characteristics, infarct size and ventricular function have not been established. METHODS: We assessed survival status at a minimum of 3 and a mean of 4.9 +/- 2.3 years in 618 patients randomized between 1981 and 1986 to receive conventional treatment (n = 293) or thrombolysis with streptokinase (n = 325) in the Western Washington Intracoronary (n = 250) and Intravenous (n = 368) Streptokinase in Myocardial Infarction trials. The relation between long-term survival and thrombolytic treatment, admission baseline clinical characteristics and late radionuclide tomographic thallium-201 infarct size and ejection fraction was assessed in a subset of patients. RESULTS: Survival at 6 weeks was 94% in patients who received streptokinase versus 88% in the control group (p = 0.01). However, survival at 3 years was 84% in the streptokinase group and 82% in the control group and for the total period of follow-up, there was no significant survival benefit (p = 0.16). Analysis by infarct location showed a higher survival rate at 3 years for patients treated with anterior infarction (76% vs. 67% for the control group), but no overall survival benefit (p = 0.14). Survival at 3 years for patients with an inferior infarction was 89% in the streptokinase group and 91% in the control group (p = 0.62). By stepwise Cox regression analysis, admission clinical variables associated with decreased long-term survival were anterior infarction, advanced age, history of prior infarction and the presence of pulmonary edema or hypotension. Although streptokinase therapy was associated with improved survival, it was not an independent determinant of survival (p = 0.069). Ejection fraction and thallium-201 infarct size measured approximately 8 weeks after enrollment had a strong association with long-term survival. Univariate analysis in a subgroup of 289 patients with complete data selected infarct size, ejection fraction, age and history of prior infarction as predictors of survival. In the multivariate model, only ejection fraction (p < 0.0001), age (p = 0.008) and prior myocardial infarction (p = 0.02) remained strong predictors. CONCLUSIONS: In these early trials of thrombolytic therapy for acute myocardial infarction, streptokinase improved early survival, but there was little long-term survival benefit. This failure to show an improvement in the 3- to 8-year survival rate may also reflect the need to study a larger group of patients or to initiate treatment earlier after symptom onset.

Aged

Noninvasive arterial thrombus imaging with 99mTc monoclonal antifibrin antibody.

BACKGROUND: The T2G1s monoclonal antifibrin antibody binds specifically to fibrin but not to fibrinogen. METHODS AND RESULTS: In a canine model of acute arterial thrombosis, we determined the feasibility of imaging thrombi using a 99mTc-labeled Fab' fragment. In 14 dogs, 10 carotid and 13 femoral artery thrombi were produced using 2-hour temporary occlusion, crush injury, and local thrombin injection methods. A sham-operated carotid artery served as control. Antifibrin antibody was injected intravenously at the end of temporary occlusion. Serial planar radionuclide images were obtained immediately and at 1 and 2 hours. Following killing the dogs at 2 hours, we measured antibody uptake ex vivo in 5-mm-long segments of thrombus, the adjacent injured artery, and a control artery. Antibody was cleared from the blood with a mean +/- SD t1/2 of 121 +/- 23 minutes. The thrombi weighed 218 +/- 140 mg. Antibody uptake in the thrombi was patchy, and the thrombi were closely adherent to the injured arterial wall. In the segment with maximal ex vivo antibody uptake, the ratio of control artery to blood counts/g/sec was 0.65 +/- 0.46, the injured artery-to-blood ratio was 2.35 +/- 1.01 (p less than 0.0001 versus control), and the thrombus-to-blood ratio was 4.24 +/- 2.58 (p less than 0.0001 versus control). In three dogs, an isotype-matched ovarian tumor antibody labeled with 111In was injected with T2G1s but was not taken up in the thrombus or the adjacent arterial wall. Visual analysis of the in vivo carotid radionuclide images showed uptake by 2 hours in all 10 carotid thrombi. Quantitative image analysis, measured as the thrombus-to-opposite carotid artery ratio, showed increasing uptake over time with ratios of 1.1 +/- 0.3, 1.6 +/- 2.0, and 2.2 +/- 1.3 on the immediate, 1-hour, and 2-hour images, respectively. All quantitative ratios of 1.3 or greater were visually identified. CONCLUSIONS: 99mTc-labeled Fab' fragments of the T2G1s antibody are taken up specifically by acute arterial thrombi after intravenous injection. Uptake is progressive over a 2-hour period, and all thrombi are detected by radionuclide imaging at 2 hours. These results show that it is feasible to noninvasively detect arterial thrombi within 2 hours of formation.

Animals

Rarity of preclinical alcoholic cardiomyopathy in chronic alcoholics less than 40 years of age.

Preclinical alcoholic cardiomyopathy, myocardial damage in the absence of overt congestive heart failure in chronic alcoholics, is well characterized at necropsy, but attempts to identify such a clinical entity before death have produced conflicting results. Studying subjects only at rest, the inclusion of older alcoholics and limitations of noninvasive techniques may explain some of the disagreement. To determine if preclinical alcoholic cardiomyopathy could be identified independent of the aforementioned limitations, 25 asymptomatic chronic alcoholics aged less than 40 years (mean 34), each of whom had consumed a minimum of 1 pint of whiskey or one 6-pack of beer greater than or equal to 5 days per week for greater than or equal to 5 years, underwent radionuclide ventriculography for measurements of systolic and diastolic function at rest, peak supine exercise and during recovery, and echocardiography for assessment of chamber size, wall thickness and left ventricular mass. Red blood cell levels of selenium and thiamine were measured to determine whether abnormalities were present in these 2 potential mediators of alcoholic cardiomyopathy. For comparison, an age-matched group of healthy control subjects was also studied. For alcoholics and control subjects at rest, mean ejection fraction (67 +/- 7% vs 71 +/- 6%) and diastolic peak filling rate (3.4 +/- 0.6 vs 3.3 +/- 0.6 end-diastolic volumes per second [EDV/s]) were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Thrombolysis by rotational thrombectomy followed by tissue plasminogen activator: evaluation by angioscopy.

Thrombus removal using percutaneous rotational thrombectomy (PRT), followed by tissue plasminogen activator (t-PA), was studied by contrast angiography and fiberoptic angioscopy in a canine femoral artery model of thrombosis. After thrombus induction and following each treatment, comparisons were made between angioscopy and angiography for the detection of thrombus and subintimal dissection. Angioscopic images were scored in a blinded fashion for lining, protruding, or occlusive thrombus (class 1,2, or 3) as well as estimated wall coverage by thrombus. Angiograms were studied for percent diameter stenosis and the presence of flaps. Following external forceps crush injury of 18 arteries, two hour occlusion, and injection of thrombin, mean angiographic stenosis was 66%, thrombus coverage by angioscopy was 81%, and mean angioscopy class was 2.5. Following PRT, stenosis decreased to 27% (p less than 0.008), thrombus coverage was reduced to 49% (p less than 0.02), and angioscopy class dropped to 2.0 (p less than 0.07). After t-PA treatment, these values were further reduced to 25% (p = NS), 26% (p less than 0.02), and 1.3 (p less than 0.008), respectively. In comparison to angiography, subintimal dissection (seen as flaps) and thrombus (lining, protruding, or occlusive) were present significantly more often by angioscopy (p less than 0.001). It is concluded that PRT results in significant thrombolysis, apparent by angiography and angioscopy. Follow-up t-PA can produce additional, incremental thrombolysis, apparent only by angioscopy. A beneficial role for t-PA following mechanical thrombolysis is suggested by this model. The superior sensitivity of angioscopy for detection of flaps and thrombus is underscored by this study.

Animals

Radionuclide assessment of infarct size and left ventricular function in clinical trials of thrombolysis.

Mortality, left ventricular ejection fraction, and infarct size are important end points in evaluating the efficiency of thrombolytic treatment in clinical trials. Radionuclide assessment of ejection fraction and infarct size is safe, accurate, reproducible, and readily available. Its use in clinical trials supplements mortality data and allows meaningful results in trials with smaller patient numbers. Single photon emission computed tomography improves the detection and quantification of infarct size, and its use with new radiopharmaceuticals will assume an important role in future trials. For an 8-year period, these radionuclide techniques have been used in the Western Washington Thrombolysis Trials and have generally shown smaller infarct size and higher ejection fractions in patients receiving streptokinase and tissue-type plasminogen activator. However, in the most recent trial there was no direct relation between these end points and the time between symptom onset and initiation of treatment. Future trials that direct efforts to treatment in the first hour after symptom onset should further clarify this observation.

Evaluation Studies as Topic

The Western Washington Myocardial Infarction Registry and Emergency Department Tissue Plasminogen Activator Treatment Trial.

This study comprised a registry and an emergency department treatment trial using recombinant tissue plasminogen activator. During 1 year, 1,028 patients with documented acute myocardial infarction (AMI) were evaluated for eligibility for thrombolytic therapy. Of these, 221 patients (22%) were eligible for thrombolytic therapy under currently accepted criteria, 175 (79%) of them were correctly identified by emergency department physicians for thrombolytic therapy, and 160 were enrolled in the trial. Only 3 patients (2%) enrolled by emergency department physicians did not subsequently evolve documented AMI. In all, 807 patients (78%) were ineligible for thrombolytic therapy: 335 (33%) because of greater than or equal to 1 contraindications, 364 (36%) because of nondiagnostic electrocardiograms on presentation, and 105 (10%) because of age greater than 75 years, or greater than 6 hours of chest pain at presentation, or both. Mortality in treated patients at 14 days was 5.6%, and survival at 1 year was 92%. The mean time from hospital arrival to thrombolytic treatment was 55 +/- 27 minutes. Initial management of AMI with recombinant tissue plasminogen activator in the emergency department provided rapid and safe treatment comparable to that reported in trials that started treatment in the coronary care unit. The proportions of eligible patients could be increased from 1 in 5 to 1 in 3, if patients currently excluded only because of age greater than 75 years or because of greater than 6 hours of chest pain were offered treatment.

Aged

Distal embolization during mechanical thrombolysis: rotational thrombectomy vs. balloon angioplasty.

To determine the incidence and extent of distal embolization during percutaneous transluminal balloon angioplasty (PTA) and rotational thrombectomy (PRT), we collected, filtered, and weighed the distal effluent of acute thrombotically occluded canine arteries following mechanical thrombolysis. PRT (n = 11) and PTA (n = 10) were equally effective in recanalizing occluded vessels (91% vs. 90%) and reduced percent diameter stenosis to a similar degree (97 +/- 6% to 8 +/- 11% and 100 +/- 0% to 17 +/- 23%, respectively). Distal embolization following mechanical intervention was observed in 10 of 10 and 8 of 9 arteries recanalized with PRT and PTA, respectively. The mean weights of collected emboli were similar between the two groups (18 +/- 24 mg vs. 37 +/- 79 mg, PRT vs. PTA, P = NS), although the range of size and weight of thromboemboli was larger in the PTA group (0-206 mg vs. 2-51 mg, PRT). Angiographically defined residual thrombus was significantly less frequent in arteries recanalized with PRT as compared with PTA (10% vs. 55%, P = 0.03). In summary, PRT and PTA are equally effective in recanalizing acutely occluded canine arteries and result in similar reductions in percent diameter stenosis. Each intervention results in distal embolization of thrombi. PRT is associated with a reduced incidence of angiographically evident residual thrombus at the site of arterial injury and may avoid embolization of large fragments occasionally produced by PTA. Thus PRT may serve as a useful alternative to coronary angioplasty during acute myocardial infarction.

Angioplasty, Balloon

Combined mechanical and chemical thrombolysis in an experimental animal model: evaluation by angiography and angioscopy.

In an experimental animal model of femoral artery thrombosis, contrast angiography was compared to intravascular angioscopy. Additionally, the effect of mechanical, rotational thrombectomy and the additive benefit of the administration of intravascular streptokinase were assessed by means of both procedures. After external forceps crush injury alone, contrast angiograms were generally normal (6 of 14) or showed minimal luminal irregularity (3 of 14), and 5 of 14 had 30% to 50% stenosis. With angioscopy, none appeared normal, and 14 of 14 showed thrombi layered along the wall, as well as intimal flaps, and 6 of 14 had partially occlusive thrombi (p less than 0.001 angiography vs angioscopy). After 2-hour occlusion and injection of thrombin into the injured segment, angiographic total (5 of 14), subtotal (3 of 14), or partial thrombotic occlusions (5 of 14) were created. Angioscopy showed similar results, except that total occlusions were classed as subtotal occlusions. After rotational thrombectomy, most arteries again appeared normal by contrast angiography (6 of 11) but none were angioscopically normal (p less than 0.006). Streptokinase, administered after rotational thrombectomy in seven arteries, normalized one 30% angiographic stenosis; there were no other angiographic changes. Findings with angioscopy were also unchanged. We conclude that in the diagnosis and treatment of intravascular thrombosis, angioscopy is generally more sensitive in the detection of intravascular thrombi, with the exception of total thrombotic occlusions. Angioscopy was uniquely effective in identifying subintimal flaps, which were never identified by angiography. In this model, streptokinase provided little or no additional thrombolytic benefit to mechanical thrombectomy alone.

Angiography

111In platelet imaging of left ventricular thrombi. Predictive value for systemic emboli.

To determine whether a positive indium 111 platelet image for a left ventricular thrombus, which indicates ongoing thrombogenic activity, predicts an increased risk of systemic embolization, we compared the embolic rate in 34 patients with positive 111In platelet images with that in 69 patients with negative images during a mean follow-up of 38 +/- 31 (+/- SD) months after platelet imaging. The positive and negative image groups were similar with respect to age (59 +/- 11 vs. 62 +/- 10 years), prevalence of previous infarction (94% vs. 78%, p less than 0.05), time from last infarction (28 +/- 51 vs. 33 +/- 47 months), ejection fraction (29 +/- 14 vs. 33 +/- 14), long-term or paroxysmal atrial fibrillation (15% vs. 26%), warfarin therapy during follow-up (26% vs. 20%), platelet-inhibitory therapy during follow-up (50% vs. 33%), injected 111In dose (330 +/- 92 vs. 344 +/- 118 microCi), and latest imaging time (greater than or equal to 48 hours in all patients). During follow-up, embolic events occurred in 21% (seven of 34) of patients with positive platelet images for left ventricular thrombi as compared with 3% (two of 69) of patients with negative images (p = 0.002). By actuarial methods, at 42 months after platelet imaging, only 86% of patients with positive images were embolus free as compared with 98% of patients with negative images (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets

Early versus late hospital arrival for acute myocardial infarction in the western Washington thrombolytic therapy trials.

In the 3 Western Washington thrombolytic therapy trials, 54.9% of patients with acute myocardial infarction arrived at the hospital within 2 hours of symptom onset. These early arrivers were younger and more likely to be hypotensive and in cardiogenic shock than were patients arriving later. There were decreases in the time from symptom onset to hospital arrival (p = 0.0002) and in the time from hospital arrival to institution of thrombolytic therapy (p less than 0.0001) in the 8 hospitals that participated in both the Western Washington intravenous streptokinase and tissue plasminogen activator trials from 1983 to 1988. For those patients receiving thrombolysis, early arrival was associated with increased survival (p = 0.031) after adjustment by Cox regression analysis for important clinical predictors of long-term survival. These covariates included pulmonary edema, anterior wall acute myocardial infarction, hypotension and absence of chest pain at hospital arrival. Reductions in barriers to timely administration of thrombolytic therapy can be achieved and can result in improved survival.

Aged

Rotational thrombectomy in acute canine coronary thrombosis.

We have developed a mechanical thrombolytic catheter which defibrinates a fresh intra-arterial thrombus by wrapping fibrin about its rotating shaft. Defibrination results in liquification of the thrombus and reperfusion of the thrombotically occluded vessel. In this study, we employed this catheter-based approach in dogs with coronary thrombosis to simulate possible clinical use in acute myocardial infarction. Total coronary thrombosis was generated in 11 dogs. Spontaneous reperfusion did not occur over a 30-minute control period. All vessels studied were initially totally thrombosed. After mechanical thrombolysis, there was a significant improvement in percent diameter stenosis from 100% to 28 +/- 26% (P less than 0.001). After thrombolysis, angiographically graded blood flow was normal in 9 of 11 arteries and was mildly delayed in 2 of 11. Complications included perforation of 2 vessels. We conclude that mechanical thrombolysis, with a rotating catheter, results in prompt reperfusion of the infarct vessel and significant improvement in distal blood flow. This approach, unlike angioplasty, removes the thrombus and might serve as an alternative to or supplemental form of mechanical thrombolysis.

Angioplasty, Balloon

Congestive cardiomyopathy with segmental wall motion abnormalities and a non-uniform pattern of fibrosis.

A case of congestive cardiomyopathy in a 46-year-old smoker with single-vessel right coronary artery disease is presented. Segmental contraction abnormalities were present in the anterior wall. Pathologic analysis showed diffuse fibrosis consistent with a cardiomyopathy in areas of abnormal contraction and normal muscle in areas of normal contractility. Segmental wall motion abnormalities have been reported but none with microscopic studies of areas of both abnormal and normal contractility.

Cardiomyopathies

R-wave synchronized blood-pool imaging.

Three methods for determining the left ventricular ejection fraction (EF) from R-wave synchronized blood-pool images were compared to contrast angiography; the reproducibility of these methods was established in 51 patients. The EF was systematically underestimated by the fixed region-of-interest (ROI) method compared to the two methods that used varying ROI's which track the left ventricular boundary. All methods correlated reasonably well with angiography and were highly reproducible. Use of varying ROI's resulted in EF values that were essentially identical to those determined by angiography. Resolution-recovery image processing appeared to improve reproducibility when varying ROI's were used.

Angiography

Platelet survival in patients previously resuscitated from out-of-hospital ventricular fibrillation.

Platelet survival times were measured in 11 ambulatory patients within 5 to 21 months of out-of-hospital ventricular fibrillation unassociated with acute myocardial infarction. The mean platelet survival time of 7.7 +/- 2.1 days was shortened when compared with 28 normal controls of similar age (9.0 +/- 1.0 days, p less than 0.03) but not different from 56 other patients with stable angina pectoris (6.85 +/- 1.81 days, p less than 0.2). One patient with a near normal survival time of 7.5 days experienced recurrent ventricular fibrillation without associated acute myocardial infarction 1 month following the platelet survival study. Although one platelet inhibitory agent, sulfinpyrazone, may lower the incidence of sudden cardiac death following acute myocardial infarction, the shortened platelet survival time in the group of patients experiencing out-of-hospital ventricular fibrillation did not distinguish them from others with coronary artery disease.

Aged