Biomedical subjects

W Marston

Publications and source records attributed to W Marston.

14 recordsLinked to original sources

PubMed1995

Physiologic variations in lower extremity venous valvular function.

We conducted this study to investigate the physiologic variations in venous valvular function and calf muscle pump function that occur in normal limbs after prolonged stationary standing. Twenty-two limbs from 11 healthy volunteers were studied after a brief period of activity and after 4 to 6 hours of stationary standing. Vein diameter, peak reflux flow velocity (PRFV), and valve closure time (VCT) were measured with duplex scanning in the standing position in the common femoral vein (CFV), superficial femoral vein (SFV), popliteal vein (POP), proximal greater saphenous vein (GSV), and greater saphenous vein at the knee (kGSV). Pneumatic rapid inflation-deflation cuffs were used to elicit reflux. Vein cross-sectional area (VA) and peak reflux volume (PRVol) were calculated. Venous volume (VV), venous filling index (VFI), ejection fraction (EF), residual volume fraction (RVF), and outflow fraction (OF) were measured with air plethysmography in all limbs. After stationary standing, there was no significant change or trend toward an increase in diameter or VA in any of the deep veins and there was no change in the PRFV or VCT. In the proximal GSV there was a significant increase in diameter (p = 0.0001) and VCT (p = 0.048) without a change in PRFV. No significant changes were noted in the kGSV. In the GSV the PRFV was significantly lower (p < 0.05) and the VCT significantly shorter (p < 0.05) compared with the SFV and POP but values were no different from those in the CFV. The PRFV was significantly higher in the SFV (p < 0.0001) and the POP (p < 0.002) compared with that in the CFV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

[Occurrence of CD44 and its isoforms under orthological and pathological conditions].

Variant isoforms of CD44 have been strongly implicated in malignant transformation and cancer metastasis. To ascertain the pattern of expression of these isoforms in human normal, fetal and tumor tissues (breast carcinomas, renal cell carcinomas, malignant melanomas, colon carcinomas, non-Hodgkin-lymphomas, neuroblastomas and brain tumors), we generated monoclonal antibodies against CD44 variant regions. Monoclonal antibodies were produced against variant regions encoded by exons 4v, 6v and 9v. CD44 variant isoforms are expressed on normal epithelial cells in a different pattern. Regions of epithelia that expressed the highest levels of the variant isoforms were those with a high rate of cell division. CD44 variant isoforms were not expressed by all investigated tumors (not by malignant melanomas, brain tumors and neuroblastomas). It is interesting that the expression of CD44 isoforms in non-Hodgkins lymphomas and colon carcinomas shows possibly a correlation with malignancy.

Antibodies, Monoclonal↗

PubMed1992

Altered patterns of T cell migration through lymph nodes and skin following antigen challenge.

Antigen challenge has profound effects on a regional lymph node (LN); it leads to an increase in blood flow to the node, and a marked increase in lymphocyte output through the efferent lymphatics. We used the isolated LN model developed in the sheep to see if antigen challenge in a LN resembled inflammation in peripheral tissues. Following stimulation with an antigen (purified protein derivative of tuberculin), lymphocyte output from the LN showed the typical periods of "lymphocyte shutdown" and "recruitment". The shutdown phase, when cell numbers in efferent lymph dropped by approximately 80%, affected almost exclusively the naive-type (adhesionlo, L-selectin+) T cell population. The large increase in T cell traffic through the node during the recruitment phase was mostly due to CD4+ memory-type T cells and, moreover, the majority of these T cells were L-selectin-, indicating that these cells were crossing from the blood by a molecular mechanism other than L-selectin interaction with its ligand, the "lymph node vascular addressin" (MECA-79). Examination of LN high endothelial venules revealed the presence of vascular cell adhesion molecule-1 (VCAM-1), an endothelial adhesion molecule which has been reported to bind preferentially memory-type T cells in inflammatory lesions. Within the skin, antigen challenge also induced the rapid expression of VCAM-1 on vascular endothelium. It was purely memory-type T cells (beta 1+, L-selectin+/-) that collected in lymph draining from this tissue. However within chronically inflamed skin, the MECA-79 determinant appeared on vascular endothelium, and a small proportion of T cells draining from chronically inflamed skin were of naive-type. The present results illustrate that there are similarities in the cellular and molecular events that characterize antigen stimulation of a LN and inflammation in a peripheral tissue.

Animals↗

PubMed1989

Thymic stroma is required for the development of human T cell lineages in vitro.

Development of the T cell lineage is characterized by the homing of hematopoietic precursors to thymus, followed by their acquisition of receptors for antigen. T cell receptors are alpha beta or gamma delta heterodimers associated with CD3 (TCR-CD3). Very early T cell precursors in humans have been characterized as CD7+ 45+ cells which lack the T cell differentiation antigens CD1, CD2, CD3, CD4, and CD8. A phenotypically equivalent early thymocyte population also occurs in postnatal life, and we have previously shown that interleukin 2 (IL2) promotes the development in vitro of both the alpha beta and the gamma delta T cells from these early thymocytes. Here we have analyzed the requirements of the induction of the IL2 pathway in early thymocytes, and their developmental potential. We show that: (i) thymic stromal cells, which are present in thymocyte suspensions, are necessary to induce the IL2 pathway and the development of alpha beta or gamma delta T cell lineages from early thymocytes in vitro; and (ii) when removed from the in vivo environment, early thymocytes can develop in vitro into TCR-CD3- cells of the natural killer (NK) lineage. We conclude that CD7+ 45+, CD1-2-3-4-8- early thymocytes are multipotential progenitors that, at least, have the capacity to develop into alpha beta or gamma delta T cell and NK lineages. The analysis of the mechanisms of generation and selection of human T and NK cell diversity, not feasible in bone marrow cultures, is now possible.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1989

Function of CD44(Pgp-1) homing receptor in human T cell precursors.

T cell precursors migrate from extrathymic hematopoietic tissues and differentiate after encountering the thymic microenvironment. We asked whether human T cell precursors express the CD44(Pgp-1/gp90HR) class of homing receptors that have been implicated in the traffic of hematopoietic cells, such as lymphocyte entry to peripheral lymphoid organs. Flow cytometry and immunoprecipitation studies demonstrate that CD7+34+, CD1-2-3-4-8-14-16-20- cells in bone marrow and thymus, which have been shown to exhibit features of T cell precursors, bear CD44. Immunohistological studies show that clusters of thymocytes in the subcapsular and the inner cortex and most medullary thymocytes are clearly CD44+, whereas the expression of CD44 is selectively downregulated in CD3- and CD3low functionally incompetent cortical thymocytes. The expression of CD44 is not restricted to T cell precursors but also occurs in thymic stroma, which bear a different molecular species of CD44. CD44-specific antibodies exert stimulatory effects on T cell precursors, a process that is dependent on stromal cells. We postulate that CD44 might be an adhesion molecule for precursor homing to thymus and that it participates in cell-to-cell interactions within the thymic environment.

Cell Movement↗

PubMed1989

Significance of the transmural diminution in regional hydrogen ion production after repeated coronary artery occlusions.

Previous studies have revealed that the regional accumulation of ischemic metabolites including hydrogen ion (H+) and PCO2 diminish after repeated occlusions. We postulated that this diminution reflects a blunted metabolic response that is related to the severity of ischemic injury and, hence, may be most pronounced in subendocardial (ENDO) regions. To investigate this hypothesis, the left anterior descending coronary artery was serially occluded three times in 51 dogs for a period of either 3 minutes (n = 15), 5 minutes (n = 18), or 15 minutes (n = 18). Each occlusion was separated by 45 minutes of reperfusion. Myocardial [H+] was measured in the endomyocardium and in the epimyocardium of the ischemic anterior wall by use of miniature pH glass electrodes. Accumulation of H+ during occlusion (delta [H+]) in the ENDO region was significantly less during the second occlusion when compared with the first occlusion (3-minute occlusions: 28.2 +/- 3.7 nM/l vs. 39.4 +/- 5.4 nM/l, p less than 0.002; 5-minute occlusions: 49.8 +/- 5.0 nM/l vs. 72.1 +/- 6.5 nM/l, p less than 0.0002; 15-minute occlusions: 132.3 +/- 14.6 nM/l vs. 225.6 +/- 27.7 nM/l, p less than 0.0003). A similar trend was noted for delta [H+] in the subepicardial (EPI) regions. During occlusion, the rise in [H+] occurred sooner, and delta [H+] was consistently greater in the ENDO when compared with the EPI regions (p less than 0.05). Regional myocardial blood flow did not change during the three occlusions, indicating that the diminution in H+ accumulation stemmed from a decrease in H+ production and not from an increase in collateral flow. The decrement in H+ accumulation between the first and second occlusions (delta [H+]1-delta [H+]2) 1) was greater in the ENDO than in the EPI regions (p less than 0.05); 2) correlated with the duration of occlusion (ENDO: r = 0.66, p less than 0.001; EPI: r = 0.82, p less than 0.0001); and 3) was related to the impairment of anterior wall systolic shortening after the first reperfusion period. These findings suggest that the diminution in H+ production that follows serial coronary occlusions reflects a blunted metabolic response that is related to both the duration of ischemia and the degree of systolic dysfunction. Moreover, though attenuation of ischemic metabolite production occurs transmurally, it is most pronounced in the deep ENDO regions.

Animals↗

PubMed1987

Reduction in myocardial acidosis using blood cardioplegia.

The composition of the ideal cardioplegic solution is controversial. Blood cardioplegia is an attractive alternative to standard crystalloid solutions, though its superiority in preserving myocardial metabolism has not been demonstrated. Using a new pH electrode system, this study contrasts the effects of blood and crystalloid solutions upon the generation of myocardial acidosis during global ischemia. Thirty-eight mongrel dogs underwent a 120-min period of aortic cross clamping using systemic hypothermia. To maintain myocardial temperature below 15 degrees C, 19 dogs received multiple doses of a bicarbonate containing crystalloid cardioplegic solution (Group I), while 19 dogs received multiple doses of blood cardioplegia (Group II). Myocardial pH and temperature were continuously monitored in the subendocardial region of the left ventricle. There was no difference in baseline pH between Group I (7.13 +/- 0.05) and Group II (7.17 +/- 0.05, P:NS). With systemic cooling and the initial bolus of cardioplegia, myocardial pH rose to 7.42 +/- 0.04 in Group I and 7.42 +/- 0.06 in Group II (P:NS). After 120 min of global ischemia, myocardial pH decreased to 6.61 +/- 0.05 in Group I and 7.07 +/- 0.05 in Group II (P less than 0.001). Blood cardioplegia was most effective during the first hour of aortic cross clamp when myocardial pH rose by 0.13 +/- 0.04 pH units. In contrast, myocardial pH in Group I during the first hour of global ischemia fell -0.35 +/- 0.08 pH units (P less than 0.001 compared to Group II). During the second hour of cross clamp, myocardial pH declined both in Group I (0.26 +/- 0.03 pH units) and in Group II (0.24 +/- 0.05 pH units, P:NS). However, the accumulation of hydrogen ion during the second hour was significantly greater in Group I (+128.0 +/- 21.4 nm/liter) than in Group II (+36.6 +/- 9.0 nm/liter, P less than 0.001). Thus, myocardial acidosis was reduced during the administration of blood cardioplegia when compared to a bicarbonate-buffered crystalloid solution. The salutary effects of blood cardioplegia on myocardial metabolism stem from blood's significant buffering capacity and its ability to deliver oxygen.

Acidosis↗

PubMed1986

Effects of bepridil on regional myocardial ischemia and comparison with verapamil.

This study was designed to assess the efficacy of bepridil in reducing regional myocardial ischemia and to compare its efficacy with that of verapamil. Forty-five anesthetized, open-chest dogs were subjected to three 5-minute occlusions of the left anterior descending coronary artery (LAD), each followed by 45 minutes of reperfusion. Eleven dogs (group 1) served as controls. In 10 dogs, bepridil, 5 mg/kg, was administered before the third occlusion (group 2). In 11 dogs, verapamil was administered before the third occlusion (group 3). In each dog, on-line intramyocardial hydrogen ion concentration and carbon dioxide tension were measured in the myocardial segment supplied by the LAD. Regional myocardial contractility was assessed in this area with 2 pairs of ultrasonic crystals inserted to determine percent segmental shortening. Regional myocardial blood flow was determined during each occlusion by washout of xenon-127. The increase in hydrogen ion concentration and carbon dioxide tension did not change from occlusion 2 to occlusion 3 in the control group. Both bepridil and verapamil elicited a significant reduction in the extent of regional ischemia, evidenced by a reduction in the accumulation of hydrogen ions, in occlusion 3 vs occlusion 2. Systolic bulging occurred during all occlusions and the periods of reperfusion were not sufficient to allow complete recovery of regional function. Bepridil and verapamil each caused a significant increase in percent segmental shortening (both p less than 0.025), and verapamil effected a significant improvement of function during occlusion 3 compared with occlusion 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Intraoperative assessment of the physiologic significance of coronary stenosis in humans.

Coronary angiography is generally considered the gold standard in assessing the significance of coronary stenosis. The inadequacy of coronary angiography has frequently been demonstrated by intraoperative findings that differ from those projected by the catheterization report. To better assess the physiologic significance of coronary stenosis, we measured intramyocardial pH intraoperatively in 50 myocardial segments supplied by stenotic coronary arteries before and after revascularization in 42 patients undergoing coronary artery bypass grafting. The hemodynamic, electrocardiographic, and pH responses to atrial pacing were recorded intraoperatively before and after revascularization. The coronary angiograms, performed within 3 months before bypass grafting, were reviewed by a single independent observer. Preoperative and postoperative radionuclide ventriculograms were performed and also reviewed by an independent observer. In response to atrial pacing, a fall exceeding 0.02 pH units was considered to represent ischemia and was observed in 28 segments. Patients exhibiting this response comprised Group I. Twenty-two segments demonstrated a fall of less than 0.02 pH units or a rise in pH in response to atrial pacing. Patients having this response comprised Group II. Segments in Group I responded dramatically to revascularization, with the pH during atrial pacing rising from -0.09 +/- 0.01 to -0.02 +/- 0.01 (p less than 0.001). Nine patients demonstrated ischemic S-T changes during atrial pacing, all in Group I. Pre-pacing hemodynamic parameters were similar in both groups. Group I patients, however, demonstrated a significant fall in mean arterial pressure during atrial pacing, from 92.0 +/- 3.0 to 78.4 +/- 3.3 mm Hg (p less than 0.001) whereas Group II patients did not. Twelve segments that angiograms indicated were supplied by critically stenotic vessels (greater than 75%) failed to demonstrate a significant fall in their pH during atrial pacing. In these segments, intraoperative findings and postoperative results corroborated the metabolic findings. Coronary angiography, therefore, was only 45% specific in assessing physiologically significant obstructions. The degree of segmental wall motion abnormalities likewise correlated poorly with the pH changes. Unlike coronary angiography, the response of intramyocardial pH to pacing is an accurate metabolic tool to assess myocardial ischemia in humans.

Angina, Unstable↗

PubMed1985

The significance of the late fall in myocardial PCO2 and its relationship to myocardial pH after regional coronary occlusion in the dog.

After acute regional coronary occlusion, myocardial tissue PCO2, as measured by mass spectrometry, rises, reaches a peak, and then gradually falls. This late fall in myocardial tissue PCO2 could be due to (1) a gradual increase in tissue blood flow (and hence improved carbon dioxide washout), (2) a gradual consumption of tissue bicarbonate, (3) a gradual reduction in the production of carbon dioxide due to progressive cellular damage, or (4) an artifact caused by the continued presence of the mass spectrometer probe in the ischemic tissue. To determine which of these four mechanisms is responsible for the late fall in myocardial tissue PCO2, we subjected 27 anesthetized open-chest dogs to 3-hour occlusion of the left anterior descending coronary artery. Both myocardial tissue PCO2 and intramyocardial hydrogen ion concentration were measured in the myocardial segment supplied by the left anterior descending coronary artery. Ten dogs (group 1) were killed after the occlusion (occlusion I), and 11 dogs (group 2) underwent reocclusion (occlusion II) at the same site after a 45-minute period of reflow. Regional myocardial blood flow was measured periodically by the intramural injection of 127Xe. Changes in myocardial tissue PCO2 and hydrogen ion concentration were related to ultrastructural changes in the tissues adjacent to the myocardial tissue PCO2 probe. Regional myocardial blood flow remained unchanged throughout the 3-hour occlusion, ruling out increased carbon dioxide washout as a cause for its late fall. Tissue hydrogen ion concentration, as measured by a new lead glass electrode, correlated well with myocardial tissue PCO2, with the reduction in regional myocardial blood flow, and with ischemic damage assessed histologically. Myocardial hydrogen ion concentration also exhibited a late fall after the occlusion, from a peak of 199.8 +/- 27.8 nmol/liter to 91.9 +/- 12.1 nmol/liter (mean +/- SEM). This ruled out consumption of tissue bicarbonate as the cause for the late fall in myocardial tissue PCO2. Peak rise in myocardial tissue PCO2 after occlusion II (71.2 +/- 7.9 mm Hg) was significantly lower than peak myocardial tissue PCO2 after occlusion I (116.7 +/- 13.9 mm Hg, P less than 0.001). The difference between these latter two values, as well as the magnitude of fall in myocardial tissue PCO2 during occlusion I, related directly to the degree of histological damage observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1984

The relative importance of alkalinity, temperature, and the washout effect of bicarbonate-buffered, multidose cardioplegic solution.

Recent experimental and clinical studies from our institution have shown that the administration of cold, bicarbonate-buffered, hyperkalemic crystalloid cardioplegic solution resulted in a significant rise in intramyocardial pH. This rise could theoretically be caused by (1) the alkalinity of the solution administered (pH 8.2 at 25 degrees C), (2) the washout of acid metabolites with each administration, and (3) hypothermia per se. To investigate the relative effects of each of these three factors on intramyocardial pH, dogs on cardiopulmonary bypass received crystalloid cardioplegic solution either at 10 degrees C (n = 9) or at 37 degrees C (n = 8) every 30 min during 2 hr of aortic cross-clamping. Myocardial temperature, intramyocardial pH, and CO2 tension (Pmco2) were measured continuously. Needle biopsy specimens were taken every 30 min for biochemical and ultrastructural analysis. Before aortic cross-clamping, intramyocardial pH was 7.07 +/- 0.06 in both groups (+/- SEM). Upon each administration of cardioplegic solution, hearts in the 10 degrees C group cooled to 10 degrees to 15 degrees C and intramyocardial pH increased on the average by 0.31 +/- 0.03 units (p less than .001). In the 37 degrees C group intramyocardial pH was unaffected by cardioplegic solution. At the end of the cross-clamping period, intramyocardial pH had declined to 6.49 +/- 0.13 in the 10 degrees C group and to 5.60 +/- 0.08 in the 37 degrees C group, the fall in pH being significantly greater in the 37 degrees C group than in the 10 degrees C group (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1983

Lack of effect of nitroglycerin on the transmural variation of tissue pH during fixed coronary stenosis.

A new MpH-measuring system was used to investigate the mechanism of action of intravenous NTG on pacing-induced myocardial ischemia during critical stenosis. In ten anesthetized open-chest dogs, two MpH electrodes were placed in a segment supplied by the CCA, one superficial and one deep. Atrial pacing at a rate 50 beats/min higher than baseline was instituted for a period of 10 min (Pacing I). Critical stenosis was then applied to the CCA. Three more similar periods of atrial pacing were instituted during critical stenosis. Pacing II was without any intervention, Pacing III was after the intravenous administration of a bolus of NTG, and Pacing IV was after the intravenous administration of NTG + A. NTG (metamarinol) during critical stenosis and atrial pacing did not alter preload and did not reduce afterload more than critical stenosis and atrial pacing alone. It did not significantly alter flow in the CCA measured by an electromagnetic flow meter. Consequently, the magnitude of fall in both endo- and epicardial MpH during critical stenosis and atrial pacing was no different with or without the administration of NTG. That under these conditions NTG failed to reduce the degree of myocardial ischemia suggests that the beneficial effects of NTG during fixed critical stenosis are determined primarily by its ability to reduce the determinants of myocardial oxygen demand, and not by a direct effect on the ischemic myocardium per se. The study also demonstrates for the first time a significant transmural gradient in MpH in the canine heart, even in the normal resting state.

Animals↗

PubMed1983

First report of intramyocardial pH in man. II. Assessment of adequacy of myocardial preservation.

Intramyocardial pH and temperature were continuously measured in the anteroseptal region in 40 patients undergoing aortic cross-clamping during cardiac operations. Myocardial protection was achieved with systemic cooling (25 degrees C) and multidose potassium cardioplegia (4 degrees C). A clinical myocardial preservation score was devised based on intraoperative and postoperative need for inotropic support, postoperative creatine kinase isoenzyme (CK-MB) and electrocardiographic changes, and radionuclide ventriculography. The patients were divided into three groups according to their preservation scores. Group I (n = 17) with good preservation (scores 0 to 2), Group II (n = 15) with fair preservation (scores 3 to 8), and Group III (n = 8) with poor preservation (scores 9 to 15). Baseline intramyocardial pH was similar in all groups (mean +/- SEM = 6.77 +/- 0.03). With the administration of cold potassium cardioplegia, intramyocardial pH rose above baseline in all three groups. The magnitude of this rise related directly to the adequacy of preservation and to the duration of the cross-clamp period. Patients with lowest preservation scores and shortest cross-clamp periods had the highest intramyocardial pH. In contrast, there was no relationship between myocardial temperature during cross-clamp and either intramyocardial pH or the preservation score. The integrated mean intramyocardial pH during cross-clamp was found to be the parameter that correlated most with the adequacy of preservation. The correlation between intramyocardial pH and myocardial temperature during the period of cross-clamping related to the length of this period; it was good (r = 0.76, p less than 0.01) in periods of 40 minutes or less and very poor in periods exceeding 60 minutes (r = 0.27, p greater than 0.10). It is concluded that (1) the magnitude of rise in intramyocardial pH during the period of aortic cross-clamping is a good indicator of the adequacy of myocardial preservation; (2) during periods of aortic cross-clamping exceeding 40 minutes, myocardial temperature is a poor indicator of adequacy of preservation, since progressive tissue acidosis may occur despite low myocardial temperatures; and (3) techniques and solutions that can effectively reduce the progression of tissue acidosis will, in most likelihood, enhance our ability to protect the ischemic myocardium during cardioplegic arrest.

Adult↗

PubMedDate not supplied

First report of intramyocardial pH in man: I. Methodology and initial results.

Continuous in vivo measurements of intramyocardial pH (MpH) have not been previously obtained in man. To achieve this goal, we developed in our laboratory a new, steel-jacketed, glass electrode, and circumvented temperature-related problems by recording the output in millivolts along with the adjacent myocardial temperature. A computer program was devised to calculate MpH in accordance with the Nernst equation. The need in this system for a remote, subcutaneous, reference electrode prompted two sets of experiments. The first set of experiments demonstrated in vitro that the adverse effect of varying the temperature of the reference electrode on the calibration of the pH electrode could be avoided if the reference electrode was placed in a potassium chloride (KCl) solution outside the body and connected to the subcutaneous tissues with a salt bridge. The second set of experiments, which were conducted in vivo in dogs, demonstrated that MpH measurements made with the reference electrode in the limb were not affected by ischemic electrocardiographic changes. This system was then used successfully in 10 patients undergoing coronary artery bypass surgery. Reliable, reproducible, and uniform changes were observed. Baseline MpH prior to revascularization was 6.81 +/- 0.07. Myocardial protection with cold K+ cardioplegia resulted in a significant rise in MpH to 7.45 +/- 0.06. Throughout the period of cross-clamping, MpH remained high. After revascularization and discontinuation of cardiopulmonary bypass, MpH stabilized at 6.93 +/- 0.04.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗