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Biomedical subjects

M Hollenberg

Publications and source records attributed to M Hollenberg.

At least 55 records · Page 3Linked to original sources
PubMed1984

Quantitative analysis of seven-pinhole tomographic thallium-201 scintigrams: improved sensitivity and estimation of the extent of coronary involvement by evaluation of radiotracer uptake and clearance.

Recent studies have shown that the sensitivity of conventional thallium-201 scintigraphy can be increased by the quantitative assessment of myocardial radiotracer clearance rates in conjunction with the evaluation of radionuclide uptake. In this study, a similar analysis of tomographic scintigrams was performed to determine the feasibility and value of this approach, particularly in estimating the extent of disease and detecting three vessel coronary involvement. Seventy patients undergoing cardiac catheterization for chest pain were studied by exercise and 3 hour delayed thallium-201 scintigrams using the seven-pinhole tomographic technique. Each study was evaluated by visual inspection of the tomographic sections and quantitative analysis. The latter approach consisted of comparing circumferential profiles of the initial post-exercise radionuclide uptake and the 3 hour clearance rates generated from each of three left ventricular slices with similar profiles representing the lower 95% confidence limits derived from 15 middle-aged volunteers. An abnormality was considered present when a patient's profile fell below these limits for a 30 degrees arc, and was ascribed to disease in a particular artery when it involved that vessel's usual distribution. Among the 61 patients without apparent primary myocardial or valvular disease, the diagnostic sensitivity of thallium scintigraphy was increased from 86% (43 of 50) to 96% (48 of 50) without a change in specificity (both 9 of 11 or 82%). More importantly, the quantitative approach permitted detection of 85% (107 of 126) of significantly obstructed coronary vessels compared with 47% (59 of 126) by visual analysis (p less than 0.001), again without sacrificing specificity (85 versus 87%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Computer-derived treadmill exercise score quantifies the degree of revascularization and improved exercise performance after coronary artery bypass surgery.

A computer-derived treadmill exercise score (TES) that quantifies the severity of the ischemic ST response to exercise was used to detect noninvasively graft occlusion or the progression of new lesions after coronary artery bypass surgery. Three months after surgery TES completely normalized in 68% of patients and improved by more than 70% in another 18% of patients, thus reflecting excellent improvement in exercise-induced ischemia in 87% of patients. Surgical results correlated well with completeness of revascularization as shown by repeat coronary angiography. When TES, done serially up to 4 years after surgery, remained unchanged, grafts were patent and no new critical lesions had occurred. Deterioration in TES always predicted either late graft occlusion or appearance of new, high-grade lesions in the native vessels. Thus TES provides a new, accurate method that quantifies the ischemic response to exercise and detects graft occlusion or new obstructive lesions in the native coronary arteries.

Arterial Occlusive Diseases↗
PubMed1982

Comparison of myocardial thallium-201 clearance after maximal and submaximal exercise: implications for diagnosis of coronary disease: concise communication.

Recently the quantitation of regional thallium-201 clearance has been shown to increase the sensitivity of the scintigraphic detection of coronary disease. Although TI-201 clearance rates might be expected to vary with the degree of exercise, this relationship has not been explored. We therefore evaluated the rate of decrease in myocardial TI-201 activity following maximal and submaximal stress in seven normal subjects and 21 patients with chest pain, using the seven-pinhole tomographic reconstruction technique. In normals, the mean TI-201 clearance rate declined from 41% +/- 7 over a 3-hr period with maximal exercise to 25% +/- 5 after 3 hr at a submaximal level (p less than 0.001). Similar differences in clearance rates were found in the normally perfused regions of the left ventricle in patients with chest pain, depending on whether or not a maximal end point (defined as either the appearance of ischemia or reaching 85% of age-predicted heart rate) was achieved. In five patients who did not reach these end points, 3-hr clearance rates in uninvolved regions averaged 25% +/- 2, in contrast to a mean of 38% +/- 5 for such regions in 15 patients who exercised to ischemia or an adequate heart rate. These findings indicate that clearance criteria derived from normals can be applied to patients who are stressed maximally, even if the duration of exercise is limited, but that caution must be used in interpreting clearance rates in those who do not exercise to an accepted end point.

Adult↗
PubMed1981

Oxygen enhances fusion of cultured chick embryo myoblasts.

Fusion of mononucleate myoblasts to form multinucleated myotubes increases when skeletal muscle cells are grown in progressively higher oxygen concentrations (5%, 20%, and 40% oxygen). At four days of growth fusion of myoblasts (as expressed by the percent of all muscle nuclei that are located in myotubes) is 57 +/- 2% in 5% oxygen, 68 +/- 1% in 20% oxygen, and 78 +/- 2% in 40% oxygen (P less than 0.001). However, at a concentration of 40%, oxygen depresses the rate of cell division and thereby affects the number of myoblasts available for fusion. Thus, oxygen concentration significantly modifies growth of skeletal muscle in vitro. Its net effect on myotube formation results from the interaction of its separate effects to enhance cell fusion and to depress cell proliferation.

Animals↗
PubMed1978

Poly(adenosine dephosphate ribose) metabolism and regulation of myocardial cell growth by oxygen.

Control of the rate of cardiac cell division by oxygen occurs most probably by altering the redox state of a control substance, e.g. NAD(+)right harpoon over left harpoonNADH. NAD(+) (and not NADH) forms poly(ADP-ribose), an inhibitor of DNA synthesis, in a reaction catalysed by poly(ADP-ribose) polymerase. Lower partial pressure of oxygen, which increases the rate of division, would shift NAD(+)-->NADH, decrease poly(ADP-ribose) synthesis, and increase DNA synthesis. Chick-embryo heart cells grown in culture in 20% O(2) (in which they divide more slowly than in 5% O(2)) did exhibit greater poly(ADP-ribose) polymerase activity (+83%, P<0.001) than when grown in 5% O(2). Reaction product was identified as poly(ADP-ribose) by its insensitivity to deoxyribonuclease, ribonuclease, NAD glycohydrolase, Pronase, trypsin and micrococcal nuclease, and by its complete digestion with snake-venom phosphodiesterase to phosphoribosyl-AMP and AMP. Isolation of these digestion products by Dowex 1 (formate form) column chromatography and paper chromatography allowed calculation of average poly(ADP-ribose) chain length, which was 15-26% greater in 20% than in 5% O(2). Thus in 20% O(2) the increase in poly(ADP-ribose) formation results from chain elongation. Formation of new chains also occurs, probably to an even greater degree than chain elongation. Additionally, poly(ADP-ribose) polymerase has very different K(m) and V(max.) values and pH optima in 20% and 5% O(2). These data suggest that poly(ADP-ribose) metabolism participates in the regulation of heart-cell division by O(2), probably by several different mechanisms.

Animals↗
PubMed1977

Cardiac cellular responses to altered nutrition in the neonatal rat.

Rats reared in litters of 18, 12, and 6 to determine whether preweanling nutritional state would alter rates of cardiac cell division, weighed 31.7, 39.1, 48.2 g, respectively, at 21 days of age. Weights of left ventricles also increased (93.2, 123.5, and 167.2 mg) as did those of right ventricles (29.9, 43.2, and 54.3 mg). Total DNA content rose in both ventricles in the pups reared 6 per litter vs. those reared 18 per litter (6/litter vs. 18/litter), but more so in the left ventricle (79%) than in the right (24%). Autoradiography confirmed that this increase in ventricular DNA resulted from increased proliferation of cardiac muscle cells, fibroblasts, and vascular endothelial cells. When 3H-labeled thymidine was injected on day 1, autoradiographs prepared on day 21 reflected an increased dilution of label in the 6/litter rats, consistent with enhanced proliferation. The labeling index and grains per nucleus of left ventricular muscle cells of the 6/litter rats were 29% (P less than 0.005) and 20% (P less than 0.001) less than those of the 18/litter rats. Less vigorous but definite hyperplasia occurred in the right ventricle, which appeared to respond with an increase more in cell size than in cell number.

Animals↗
PubMed1976

Impaired parasympathetic responses in patients after myocardial infarction.

To assess whether vagal and sympathetic responses are impaired 3 months after myocardial infarction, 27 patients, 15 age-matched control subjects and 13 young normal subjects underwent physiologic stress tests. In patients, facial immersion in water at 25 degrees and 0 degrees C provoked less slowing of heart rate than in age-matched control subjects. Young normal persons responded with the greatest reduction in heart rate. Response to facial immersion decreased linearly with age in normal subjects (Y = -0.97X+86). Isometric handgrip or cold pressor test elicited brisk increases in blood pressure in almost all patients, but the vagal response to facial immersion correlated poorly with such pressor responses. Thus, in the patients studied 3 months after myocardial infarction, the parasympathetic response to facial immersion was significantly impaired whereas sympathetic pressor responses remained intact.

Adult↗
PubMed1976

Effects of hypoxia on cardiac growth in neonatal rat.

To determine whether low oxygen environments enhance cardiac cell division in the neonatal period, newborn rat pups were reared for 21 days in 12-15% oxygen. Left ventricle and right ventricle weights were 30 and 180% greater than controls matched for body weight (P less than 0.001) as were left ventricle/body weight ratios (3.68+/-0.26 vs. 2.99+/-0.05 mg LV/g body wt,P less than 0.001). Left ventricular total DNA and DNA concentration was 95 and 48% greater than controls (P less than 0.001). Autoradiography confirmed that this increase in ventricular DNA resulted from an increased rate of division of cardiac muscle cells, fibroblast, and vascular endothelial cells. When [3H]thymidine was injected on day ), autoradiographs prepared on day 21 reflected an increased dilution of label in hypoxic rats consistent with enhanced proliferation. The labeling index and grains per nucleus of ventricular muscle cells was 25% (P less than 0.01) and 20% (P less than 0.02) less than controls, Thus, hypoxic stress applied early in the neonatal period augments the rate of division and ultimate number of cardiac muscle cells. Whether this enhancement results from a primary effect of oxygen or from secondary hemodynamic factors remains unknown.

Animals↗
PubMed1976

Ankylosing spondylitis with complete heart block.

A patient with complete heart block due to ankylosing spondylitis exhibited an unusually brisk increase in ventricular rate with exercise. Despite broad ventricular (QRS) complexes, His bundle electrograms demonstrated a His deflection before each QRS complex and thus established the level of atrioventricular (A-V) block to be proximal to or localized to the His bundle. A junctional pacemaker accounted for the brisk response to exercise, atropine, or isoproteronol. Left bundle branch block pattern and prolongation of infranodal conduction time (H-Q) suggested additional disease involving the His bundle and/or right fascicle. Wide-spread disease affecting A-V nodal and infranodal conduction was compatible with pathologic changes seen in this disease. Because the pacemaker was able to respond to stress promptly and with appropriate increase in heart rate, the patient appeared not to warrant pacemaker implantation in his present state.

Atropine↗