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Biomedical subjects

D W Myears

Publications and source records attributed to D W Myears.

8 recordsLinked to original sources
PubMed1989

Optimal criteria for rapid detection of myocardial reperfusion by creatine kinase MM isoforms in the presence of residual high grade coronary stenosis.

Analysis of isoforms of MM creatine kinase (CK) in plasma is being developed as a means for rapid detection of coronary recanalization in patients given thrombolytic agents. To determine whether flow-limiting residual stenosis typical of that seen in patients affects plasma isoform profiles, stenosis sufficient to preclude reactive hyperemia was induced in dogs before coronary occlusion, followed by recanalization in 2 h. Plasma activities of the MM CK isoform released from myocardium (MM3) and its two conversion products elaborated sequentially (MM2 and MM1) were assayed in serial samples with a rapid quantitative chromatofocusing procedure. Reperfusion in 10 dogs shortened the mean intervals (+/-SD) to the occurrence of peak MM3 activity (3.7 +/- 0.9 h), peak MM3 expressed as a percent of total CK activity (MM3%, 2.5 +/- 0.3 h) and the maximal ratio of MM3 to MM1 (2.7 +/- 0.3 h) compared with results in 10 control dogs without reperfusion. Nevertheless, the appearance of these peaks was delayed by 8% to 57% when residual stenosis was present. In contrast, the rate of increase of MM3% was delineated before the peak, was fivefold greater with recanalization (1.19 +/- 0.46 versus 0.26 +/- 0.11% min-1 in control dogs) and was not attenuated by residual stenosis. Thus, this criterion appears capable of delineating recanalization early after thrombolysis whether or not high grade residual stenosis is present.

Animals↗
PubMed1989

Validity of estimates of myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography despite altered patterns of substrate utilization.

We recently demonstrated that the myocardial turnover rate constant (k) measured noninvasively with positron emission tomography (PET) after intravenous administration of [11C]acetate provides a reliable index of myocardial oxidative metabolism (MVO2) theoretically independent of the pattern of myocardial substrate use. However, because estimates of metabolism with other metabolic tracers are sensitive to substrate use, we measured k in 12 dogs during baseline conditions and again after infusion of either glucose (n = 8) or Intralipid (n = 4), interventions that raised arterial glucose or fatty acids by more than fivefold with concomitant changes in myocardial substrate use. Following glucose administration k increased, but no difference was detected after compensation for changes in hemodynamics and myocardial work induced by the infusion (0.18 +/- 0.03 min-1 (t1/2 = 3.9 min) at baseline compared with 0.22 +/- 0.06 min-1 (t1/2 = 3.2 min, p = N.S.). k was not affected by Intralipid infusion (k = 0.15 +/- 0.06 min-1 at baseline and 0.14 +/- 0.04 min-1 during infusion), and correlated closely with MVO2 measured directly (n = 19 comparisons, r = 0.89). The results indicate that estimates of MVO2 using [11C]acetate and PET are valid despite changes in the pattern of myocardial substrate utilization.

Acetates↗
PubMed1988

Noninvasive assessment of canine myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography.

Noninvasive quantification of regional myocardial metabolism would be highly desirable to evaluate pathogenetic mechanisms of heart disease and their response to therapy. It was previously demonstrated that the metabolism of radiolabeled acetate, a readily utilized myocardial substrate predominantly metabolized to carbon dioxide (CO2) by way of the tricarboxylic acid cycle, provides a good index of oxidative metabolism in isolated perfused rabbit hearts because of tight coupling between the tricarboxylic acid cycle and oxidative phosphorylation. In the present study, in a prelude to human studies, the relation between myocardial clearance of carbon-11 (11C)-labeled acetate and myocardial oxygen consumption was characterized in eight intact dogs using positron emission tomography. Anesthetized dogs were studied during baseline conditions and again during either high or low work states induced pharmacologically. High myocardial extraction and rapid blood clearance of tracer yielded myocardial images of excellent quality. The turnover (clearance) of 11C radioactivity from the myocardium was biexponential with the mean half-time of the dominant rapid phase averaging 5.4 +/- 2.2, 2.8 +/- 1.3 and 11.1 +/- 1.3 min in control, high and low work load studies, respectively. No significant difference was found between the rate of clearance of 11C radioactivity from the myocardium measured noninvasively with positron emission tomography and the myocardial efflux of 11CO2 measured directly from the coronary sinus. The rate of clearance of the 11C radioactivity from the heart correlated closely with myocardial oxygen consumption (r = 0.90, p less than 0.001) as well as with the rate-pressure product (r = 0.95, p less than 0.001). Hence, the rate of oxidation of 11C-acetate can be determined noninvasively with positron emission tomography, providing a quantitative index of oxidative metabolism under diverse conditions.

Acetates↗
PubMed1988

Compromise of beneficial effects of reperfusion on myocardium supplied by vessels with critical residual stenosis.

Coronary thrombolysis in patients frequently unmasks high grade residual stenosis. To determine whether beneficial effects of reperfusion are compromised by critical residual coronary stenosis, 14 dogs were instrumented with an external left anterior descending coronary artery balloon occluder, Doppler flow probe and adjustable screw clamp. In eight of the dogs, critical stenosis (abolition of reactive hyperemia after a 20 s occlusion; 95.7 +/- 1.0% cross-sectional area reduction) was induced before occlusion and maintained. In the control group (n = 6), no stenosis was induced. Each dog was subjected to 2 h of myocardial ischemia followed by balloon deflation and 24 h of reperfusion. Myocardial blood flow assessed with microspheres was similar during balloon inflation in both groups and indicative of profound ischemia. Transmural blood flow to the reperfused zone assessed 1 min after balloon deflation was significantly greater in control dogs without residual stenosis (383% of normal compared with 120% of normal in dogs with stenosis) (p less than 0.01). Compromise of transmural flow persisted in dogs with stenosis (85% compared with 121% of normal in control dogs after 1 h, p less than 0.05; and 49% compared with 68% after 24 h of reperfusion, p less than 0.05). Diminution of subendocardial blood flow after reperfusion was particularly marked. The extent of infarction was greater in the heart of dogs with residual stenosis. Thus, residual critical coronary stenosis compromises nutritional perfusion and salvage of reperfused myocardium after recanalization. These observations underscore the need for prompt identification of patients with high grade residual stenosis early after coronary thrombolysis and the potential value of angioplasty or coronary surgery in selected patients soon after initial recanalization.

Angioplasty, Balloon↗
PubMed1987

Substrate use in ischemic and reperfused canine myocardium: quantitative considerations.

The patterns of use of substrate in reperfused myocardium are not yet well elucidated, and their delineation is essential for adequate interpretation of results of analyses performed after positron emission tomography with labeled substrates to differentiate normal from abnormal heart muscle. Accordingly, in open-chest, anesthetized dogs we measured glucose and fatty acid utilization in normal, ischemic, and reperfused myocardium and assessed the contributions of metabolism of each substrate to overall oxidative metabolism. Intracoronary [3H]glucose and [14C]palmitate were administered in five control dogs, eight dogs subjected to 1 h of coronary occlusion, and nine dogs subjected to reperfusion after 1 h of ischemia. Regional coronary venous blood samples were assayed sequentially. In reperfused myocardium, utilization of glucose (463 +/- 88 nmol X g-1 X min-1) was 103% greater than that in ischemic and 273% greater than in normal myocardium (P less than 0.05 for each). Utilization of fatty acid during reperfusion (55 +/- 10 nmol X g-1 X min-1), although greater than that in ischemic myocardium, was significantly less than that in normal myocardium (48% of control, P less than 0.05) despite restoration of flow to 80% of control values. Although glucose constituted 70% of the substrate oxidized in ischemic myocardium, its contribution to overall oxidative metabolism in reperfused myocardium was only 25%. In contrast, despite diminished net uptake of fatty acid, oxidation of fatty acid accounted for 63% of total oxygen consumption in reperfused myocardium. These studies indicate that canine myocardium reperfused after 1 h of ischemia exhibits enhanced uptake of glucose and impaired utilization of palmitate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Intramuscular administration of human tissue-type plasminogen activator in rabbits and dogs and its implications for coronary thrombolysis.

To determine whether sustained plasma concentration of human tissue-type plasminogen activator (t-PA) can be induced promptly after intramuscular injection with enhancers of absorption devoid of deleterious local and systemic effects, we studied 250 rabbits and 13 dogs. In rabbits with t-PA injected directly into exposed muscle followed by local electrical stimulation at the site, early absorption was increased markedly by addition of 0.63M methylamine plus 0.079M hydroxylamine to the excipient. Elevations peaked within 5 min and increased with dose of t-PA, concentration of methylamine, and volume of injection medium. The enhancers were effective with percutaneous injections in the absence of local electrical stimulation as well. They did not elicit any obviously deleterious local or systemic effects. In separate experiments in rats, intramuscular injections of 0.63M methylamine plus 0.079M hydroxylamine induced local egress of intravascular radiolabeled albumin within the injection site and endothelial gaps in venules detected with colloidal carbon--changes consistent with direct effects on vascular permeability. In dogs, percutaneous intramuscular injection of t-PA in excipient without enhancers did not lead to early elevations of human t-PA in plasma, although late elevations were seen. When the enhancers were used, early elevations occurred as well, with functional activity documented by fibrin plate assays of serially obtained plasma samples and by sequential coronary angiography delineating thrombolysis after experimentally induced coronary thrombosis. The results indicate that intramuscular administration of t-PA with selected enhancers of absorption is a feasible approach for rapid induction of fibrinolysis.

Absorption↗
PubMed1985

Functional versus organic vocal cord paralysis: rapid diagnosis and decannulation.

Functional versus organic vocal cord paralysis can be difficult to differentiate at times. If a tracheostomy has already been performed, the distinction can be made by the use of intratracheal pressure monitoring while the patient is being sedated. If the problem is functional then rapid decannulation can be accomplished as described in this report.

Adult↗