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Biomedical subjects

F R Cobb

Publications and source records attributed to F R Cobb.

At least 91 records · Page 5Linked to original sources

Comparison of multigated radionuclide angiography with ultrasonic sonomicrometry over a wide range of ventricular function in the conscious dog.

This study compared the noninvasive assessment of left ventricular function with radionuclide angiography with that obtained with ultrasonic sonomicrometry. Left ventricular ejection fraction and rate of ventricular ejection (dV/dt) were measured with both techniques over a wide range of ventricular function. Six dogs were prepared with epicardial crystals across the major and minor axes of the left ventricle, paired transmural wall thickness crystals and a left ventricular catheter. The animals were studied while awake after they had recovered from operation. Left ventricular volume was calculated from the ultrasonic sonomicrometric dimension measurements and the equation for a prolate ellipsoid; dV/dt was calculated from the stroke volume and ejection time. Radionuclide angiograms were performed using technetium-99m--labeled red blood cells and an Anger camera with a converging collimator interfaced to a computer programmed for multigated acquisition. A wide range of ventricular function was produced with sequential infusion of isoproterenol, propranolol, phenylephrine and sodium thiamylal. Ejection fraction and dV/dt were measured simultaneously during each intervention using the time-activity curves of the multigated radionuclide angiogram and ultrasonic sonomicrometric dimensions. Regression analyses demonstrated a close correlation between the simultaneous measurements of ejection fraction (r values ranged from 0.95 to 0.99) and dV/dt (r values ranged from 0.87 to 0.99). These data indicate that noninvasive multigated radionuclide angiography accurately assesses changes in ejection fraction and dV/dt over a wide range of ventricular function.

Animals↗

Effect of age on the response of the left ventricular ejection fraction to exercise.

To assess the effects of age on the left ventricular ejection fraction (LVEF), we performed radionuclide angiocardiography at rest and during upright bicycle exercise in 77 healthy volunteers 20 to 95 years of age. Radionuclide measurements included left ventricular ejection fraction, end-diastolic volume, and regional wall motion. Age did not appear to influence any of these indexes at rest. However, during exercise the ejection fraction was less than 0.60 in 45 per cent of subjects over age 60 as compared with 2 per cent of younger subjects (P < 0.001). In addition, there was a decline in the change in LVEF (exercise LVEF minus rest LVEF) with increase in age (r = -0.71). Wall-motion abnormalities during exercise occurred with increasing frequency in patients who were 50 and older. In the older subjects these age-related changes in ejection fraction during exercise were not associated with differences in end-diastolic volume or blood pressure.

Adult↗

Effect of hyperoxia on regional blood flow after coronary occlusion in awake dogs.

The effect of 100% oxygen inhalation on regional transmural myocardial blood flow following 45 s of actue total left circumflex coronary artery occlusion was studied in six awake dogs chronically instrumented with a coronary occluder and catheters in the aorta and left atrium. After inhalation of either room air or 100% oxygen for at least 30 min and following the 45-s occlusion, transmural myocardial blood flow was determined with radioactive microspheres (7--10 micrometers). Each dog underwent two occlusions of the left circumflex coronary artery; one during inhalation of rrom air and the other during 100% oxygen. During room air inhalation, mean regional myocardial blood flow to nonischemic, intermediate, and ischemic regions was 0.92 +/- 0.05, 0.51 +/- 0.08, and 0.10 +/- 0.02 ml . min-1 . g-1, respectively. During 100% oxygen administration, flow was significantly diminished in each region to 0.75 +/- 0.04, 0.41 +/- 0.07, and 0.06 +/- 0.01 ml . min-1 . g-1, respectively. Transmural blood flow to each layer was uniformly reduced in all regions. These data indicate that 100% oxygen further reduces myocardial blood flow to ischemic regions.

Animals↗

Detecting abnormalities in left ventricular function during exercise before angina and ST-segment depression.

To determine if abnormalities in left ventricular function precede angina pectoris and electrocardiographic evidence of myocardial ischemia, we used radionuclide angiocardiography to measure left ventricular ejection fraction, volumes, cardiac output and wall motion in 10 normal subjects and 25 patients with coronary artery disease at rest and during two levels of upright bicylce exercise. In the patients with coronary artery disease, the first radionuclide study during exercise was performed before and the second after the onset of ST-segment depression. In all normal subjects, the ejection fraction increased more than 5%, the end-diastolic volume increased less than 25% and the end-systolic volume decreased from rest to both levels of exercise. Wall motion was normal at rest and increased with exercise. No patient with coronary artery disease had chest pain or ST-segment depression during the first level of exercise. The ejection fraction either decreased or increased less than 5% in 18 patients, the end-diastolic volume increased more than 25% in nine, the end-systolic volume increased in 19 and a segmental contraction abnormality developed in 14. Hemodynamic and wall motion abnormalities occurred in all patients during the second level of exercise when ST-segment depression was present. During exercise in patients with coronary artery disease, abnormalities in left ventricular function frequently develop before angina pectoris and electrocardiographic evidence of myocardial ischemia.

Adult↗

Effects of infarcted myocardium on regional blood flow measurements to ischemic regions in canine heart.

The present study assesses effects of acutely infarcted myocardium on apparent microsphere loss as a function of time, determines effects of apparent microsphere loss on blood flow measurements to ischemic regions, and determines to what extent apparent microsphere loss alters interpretation of serial measurements of collateral blood flow. Studies were performed in 35 awake mongrel dogs chronically instrumented with catheters in the aorta and left atrium and an occluder on the proximal circumflex coronary artery. Myocardial blood flow was measured before and 15 minutes after complete occlusion. Dogs were randomly divided into four groups to be killed at 6 and 24 hours, and 3 and 6 days. In the 3-day group, an additional blood flow measurement was made 24 hours postocclusion. The entire left ventricle was sectioned into 1- to 2-g samples and myocardial blood flow determined. The ratio of preocclusion blood flow in each ischemic sample to mean nonischemic flow was used to calculate apparent microsphere loss and to correct ischemic blood flow in each sample. Significant apparent microsphere loss occurred in epicardial layers at 24 hours and in epi- and endocardial layers at 3 and 6 days; maximum loss at each interval was 22.3, 19.4, and 22.2% respectively. Absolute blood flow corrections for ischemic myocardium were small, range -0.035 to 0.083 ml/min per g. Changes in flow to ischemic regions between 15 minutes and 24 hours were comparable before and after correction for apparent microsphere loss. Although infarction resulted in significant apparent microsphere loss, effects on ischemic blood flow measurements were very small and consequently did not prevent interpretation of serial blood flow measurements after infarction in animals killed at 3 days.

Analysis of Variance↗

Acute myocardial infarction and MB creatine phosphokinase. Relationship between onset of symptoms of infarction and appearance and disappearance of enzyme.

Sixty-six patients admitted to the coronary care unit within 12 hours of the onset of symptoms of acute myocardial infarction (AMI) were subjected to blood sampling at one- to two-hour intervals for analysis of creatine phosphokinase (CPK) and lactic dehydrogenase (LDH) enzymes and isoenzymes. Complete MB CPK curves were obtained in 27 patients, and these were analyzed for optimum times for sampling and minimum number of analyses for detection of AMI. The present study indicates that (1) optimum detection of AMI can be achieved by analysis for MB CPK in a minimum of two samples obtained at 12 and 24 hours after onset of symptoms of AMI; (2) negative results of analyses for MB CPK in samples obtained before 12 hours or after 24 hours should not be used to exclude the diagnosis of AMI; and (3) a total CPK value within the normal range is not a reliable screening test to exclude analysis of MB CPK.

Acute Disease↗

Effect of increases in afterload before and after coronary occlusion in awake dogs.

Ventricular function curves relating stroke work and left ventricular end-diastolic pressure were generated in awake dogs during increases in preload produced by infusion of fluid and during increases in afterload produced by administration of phenylephrine. The ventricular function curves produced by preloading were steeply upsloping whereas those produced by afterloading were essentially horizontal. Coronary occlusion produced downward displacement of these horizontal curves, but no change in slope. This increases in afterload did not help to demonstrate the functional impairment produced by coronary occlusion.

Animals↗

Effect of extension of infarction on serial CK activity.

The effects of extension of myocardial infarction by reduction of regional myocardial blood flow (RMBF) to an ischemic region on serum CK activity was examined in 14 awake dogs. Initial infarction was effected by occlusion of the distal left circumflex coronary artery (LCCA) and subsequent extension was produced by occlusion of the proximal LCCA 6, 12 or 18 hours after distal occlusion. Extension was verified by serial measurements of RMBF using radioisotope-labeled microspheres before and after proximal occlusion. Serum CK activity increased initially 2-4 hours after distal coronary occlusion and then increased rapidly and reached peak values 12 hours after occlusion. When the infarction was extended at 6, 12 or 18 hours after initial occlusion, CK appearance was immediately reduced in the 6- and 12-hour experiments, but not in the 18-hour experiments. Extension of infarction at each interval caused delayed increases in CK activity beginning 2-5 hours after proximal occlusion, with peak values occurring 12 hours later. The immediate effects of extension of infarction by reducing blood flow on CK activity are a function of whether the infarcted myocardium continued to release CK, e.g., at 6 and 12 hours after occlusion, or CK release was completed, e.g., 18 hours. The immediate effects of extension of infarction were the result of perfusion on myocardium that is infarcted and continues to release CK, and do not necessarily indicate alterations in the extent of myocardial injury. The delayed effects of proximal and distal occlusion on CK activity were comparable, suggesting that delayed and not immediate alterations in CK activity represent extension of infarction.

Acute Disease↗

Relation of creatine kinase isoenzyme MB to postoperative electrocardiographic diagnosis in patients undergoing coronary-artery bypass surgery.

We compared (a) the frequency of detection of isoenzyme MB of creatine kinase (CK; EC 2.7.3.2) in serum of patients undergoing coronary-artery bypass surgery, (b) the interval during uhich its activity was supranormal in serum, and (c) an index of the amount of CK released into blood ("CK-MB area") with postoperative electrocardiographic changes in 80 patients. The frequency of detection of CK-MB is a function of frequency of sampling during the early postoperative period. Because the duration of appearance and the calculated CK-MB area increased as the electrocardiogram became more specific for infarction (p less than 0.01), a twice-daily sampling schedule proved clinically relevant. Only 5.4% of patients had electrocardiographic evidence of infarction when CK-MB was absent by the second postoperative morning. When CK-MB was still detected at that time, 69.6% of patients had persistent new Q waves, consistent with infarction. In three patients who died postoperatively, significant myocardial necrosis was demonstrated. All three had had persistently increased values for CK-MB, related to electrocardiographic changes of infarction in one patient and ischemic changes in two. Evidently CK-MB is a more sensitive indicator of myocardial necrosis than the electrocardiogram and CK-MB area should be a useful criterion in evaluating methods of intra-operative myocardial protection.

Coronary Artery Bypass↗

Myocardial perfusion imaging using thallium-201: a new algorithm for calculation of background activity.

A method is presented for calculating a background image to be subtracted from TI-201 myocardial perfusion images. The method was derived from experimental measurements of background components in which hearts of animals injected with TI-201 were replaced with hearts from nonradioactive animals. The algorithm generates a background image that accounts for TI-201 activity in surrounding tissues and within the cardiac chamber. Comparison of the computer-generated background images with background images of the experimental models showed a mean difference of about 3% (range 1-6%). Clinical images using this method of background generation and subtraction are presented.

Animals↗

The relationship between enzymatic and histologic estimates of the extent of myocardial infarction in conscious dogs with permanent coronary occlusion.

Relationships between enzyme estimates (EE) and histologic measurements of infarct size (HIS) were analyzed in 14 conscious dogs with permanent occlusion of the circumflex coronary artery. EE were derived from serial CPK, CPK-MM, CPK-MB, and CPK-BB. Estimates were obtained using methods of Shell et al., Norris et al., and Roberts et al. HIS was determined from multiple histologic sections 5-6 days after infarction. In 14 animals, HIS ranged from 0.1-26.6 grams. Regression analysis demonstrated poor correlation (r2 less than 0.06) between EE by each method and HIS. Using the Shell method and restricting the analysis to HIS of less than 13 grams, improved the correlation (r2 = 0.42). Correlation in this subgroup could be further improved by using CPK-MM and MB data, elimination of animals with high background values, or limiting analysis to the portion of the curve where LDH isoenzymes indicated a cardiac zone. When the analysis was restricted to animals with HIS of less than 13 grams, Norris and Roberts modifications as compared to Shell's method improved correlation with CPK-MB but reduced correlation using CPK and CPK-MM data. In this subgroup, each method overestimated extent of HIS; Shell greater than Norris greater than Roberts. In this study it was not possible to distinguish small from large HIS by serum enzyme measurements.

Animals↗

Relationship between epicardial ST-segment elevation, regional myocardial blood flow, and extent of myocardial infarction in awake dogs.

This study was designed to examine the relationship between epicardial ST change (EpST) and regional myocardial blood flow (RMBF) following coronary occlusion and extent of myocardial infarction (MI) in awake dogs. Fifteen min and two hr after coronary occlusion simultaneous measurements of EpST and RMBF were made. Six days later histologic MI and RMBF were determined in transmural myocardial samples from each electrode site. Greatest ST elevation occurred at sites of greatest ischemia and MI. However, 15 min after occlusion 29% of sites with greater than 50% MI and 39% of sites with greater than 50% reduction in RMBF did not demonstrate ST elevation greater than 2 mV. There were poor correlations between EpST and MI (r = 0.59) and RMBF (r = 0.57). Comparable relationships were observed two hr after occlusion. In the present study, there were not close quantitative or qualitative relationships between EpST and MI or RMBF. A good correlation was observed between RMBF at two hr and MI (r = 0.89).

Animals↗