Biomedical subjects

C M Kramer

Publications and source records attributed to C M Kramer.

At least 37 records · Page 2Linked to original sources

PubMed1998

Integrated approach to ischemic heart disease. The one-stop shop.

Magnetic resonance imaging is unique in its variety of applications for imaging the cardiovascular system. A thorough assessment of myocardial structure, function, and perfusion; assessment of coronary artery anatomy and flow; and spectroscopic evaluation of cardiac energetics can be readily performed by magnetic resonance imaging. One key to the advancement of cardiac magnetic resonance imaging as a clinical tool in the evaluation, the so called one stop shop. Improvements in magnetic resonance hardware, software, and imaging speed now permit this integrated examination. Cardiac magnetic resonance is a powerful technique with the potential to replace or complement other commonly used techniques in the diagnostic armamentarium of physicians caring for patients with ischemic heart disease.

Coronary Circulation↗

PubMed1998

Transient ischemia does not limit subsequent ischemic regional dysfunction in humans: a transesophageal echocardiographic study during minimally invasive coronary artery bypass surgery.

OBJECTIVES: This study sought to assess the effects of sequential coronary artery occlusion during minimally invasive coronary artery bypass graft surgery (CABG) on hemodynamic variables and left ventricular systolic function by means of transesophageal echocardiography (TEE). BACKGROUND: Clinical and experimental studies suggest a protective effect of ischemic preconditioning in patients with acute coronary syndromes. However, the effect of repetitive myocardial ischemia on myocardial mechanical function in humans is not completely understood. METHODS: Seventeen patients with left anterior descending coronary artery (LAD) stenosis > or =70% and normal rest left ventricular systolic function referred for minimally invasive CABG underwent intraoperative TEE for assessment of regional left ventricular wall motion and measurement of hemodynamic variables at baseline (baseline 1), during a 5-min coronary occlusion (occlusion 1), after a 5-min reperfusion period (baseline 2) and a during a second coronary occlusion during bypass anastomosis (occlusion 2). RESULTS: Left ventricular wall motion score (LVWMS) increased significantly from baseline (16.0) to occlusion 1 (21.4+/-3.1 [mean +/- SD], p < 0.05) and occlusion 2 (21.8+/-3.1, p < 0.05). No difference in LVWMS was noted between occlusions 1 and 2. Pulmonary artery systolic pressure increased significantly from baseline (25+/-6 mm Hg) to occlusion 1 (32+/-7 mm Hg, p < 0.05) and occlusion 2 (33+/-6 mm Hg, p < 0.05). Pulmonary artery diastolic pressure also increased significantly from baseline (12+/-4 mm Hg) to occlusion 1 (16+/-4 mm Hg, p < 0.05) and occlusion 2 (16+/-4 mm Hg, p < 0.05). No significant differences in pulmonary artery pressures were noted between occlusions 1 and 2. CONCLUSIONS: Ischemic dysfunction was precipitated by the 5-min LAD occlusion, as shown by the increase in LVWMS and pulmonary artery pressure. However, a 5-min coronary occlusion and the resulting ischemia do not alter regional left ventricular systolic function during subsequent ischemia in humans.

Aged↗

PubMed1998

Multiplane transesophageal echocardiographic identification of the involved scallop in patients with flail mitral valve leaflet: intraoperative correlation.

Although the role of multiplane transesophageal echocardiography in the diagnosis of flail mitral valve leaflet is well described, the accuracy of this modality in localizing the involved posterior leaflet scallop (medial, middle, or lateral) has never been validated. For 54 patients undergoing intraoperative transesophageal echocardiography for severe mitral regurgitation due to flail mitral valve leaflet, we assessed the accuracy of a systematic approach to localization of the flail mitral valve leaflet. Surgical confirmation was performed for all patients. At blinded review, a sensitivity of 78%, specificity of 92%, and overall diagnostic accuracy of 88% were achieved for correct localization of the flail posterior leaflet scallop. The middle scallop was most commonly affected in this series. The medial scallop was affected least often, and diagnosis of lesions in that area was least accurate. This diagnostic approach appears to be accurate and feasible and may assist in planning specific surgical therapy for this disorder.

Adult↗

PubMed1998

Geographic distribution of ticks (Acari: Ixodidae) in Michigan, with emphasis on Ixodes scapularis and Borrelia burgdorferi.

A 12-yr (1985-1996) passive survey in Michigan based upon tick submissions from citizens yielded 4,755 ticks of 21 species, 16 of which were probably indigenous in the state. Three species of Dermacentor [most common, D. variabilis Say and D. albipictus (Packard)]; 2 species of Amblyomma [most common, A. americanum (L.)]; and 12 species of Ixodes (most common, I. cookei Packard and I. scapularis Say), as well as Haemaphysalis leporispalustris (Packard), Rhipicephalus sanguineus Latreille, and the soft ticks Ornithodoros kelleyi Cooley & Kohls, and Otobius megnini (Duges) were submitted. New state records were I. kingi Bishopp, I. texanus Banks, I. sculptus Neumann, and I. baergi Cooley & Kohls. Examination of gut smears from dissections of 1,037 ticks of 13 species by indirect immunofluorescent assay, using murine monoclonal H9724 as the primary antibody, revealed that 11 of 175 I. scapularis were infected with Borrelia spp. All positive I. scapularis were from Menominee County in the upper peninsula of the state, which also provided 79.8% of all submitted I. scapularis. Surveys for ticks on 5,449 hunter-killed white-tailed deer were conducted from 1988 to 1990, encompassed deer taken from 65 of the state's 83 counties, and showed that although D. albipictus was distributed widely in the northern part of the state, I. scapularis occurred only on deer taken from southern townships of Menominee County. Of 1,218 canine sera tested for antibodies to B. burgdorferi in 1992 and 1993, 25 of 299 (8.0%) from Menominee County were positive but only 1 of 919 sera submitted from 5 counties in the lower peninsula was positive.

Animals↗

PubMed1997

Breath-hold dobutamine magnetic resonance myocardial tagging: normal left ventricular response.

Analysis of the changes in myocardial deformation produced by adrenergic stress has been limited by the imaging techniques used. We used rapid magnetic resonance imaging (MRI) myocardial tagging to map the dose-dependent response to incremental dobutamine in the normal human left ventricle. Thirteen volunteers underwent breath-hold tagged cine MRI during dobutamine infusion. Images were acquired throughout systole to a peak dose of 20 microg/kg/min. End-systolic percent circumferential shortening (%S) was measured at 3 transmural locations and 4 circumferential locations at 3 long-axis positions. Mean circumferential shortening velocity (CSV) was also calculated at each location and dose. Mean %S reached a maximum of 26 +/- 3% at 10 microg/kg/min compared with 21 +/- 4% at baseline (p <0.003). Peak %S was reached by 10 microg/kg/min before a significant increase in heart rate or blood pressure and was unchanged at higher doses. In contrast, CSV increased linearly with dobutamine dose from 4.4 +/- 0.9 mm/s at baseline to 9.8 +/- 1.4 mm/s at 20 microg/kg/min (p <0.0001). Breath-hold tagged dobutamine MRI is safe and effective in detecting regional and transmural changes in function during incremental dobutamine. CSV increased continuously across the dobutamine dose range. At low dose (< or =10 microg/kg/min) %S increased without any change in blood pressure or heart rate. Maintenance of peak %S beyond 10 microg/kg/min in the presence of decreasing systolic intervals resulted from a continued increase in CSV. Thus, CSV may be the preferred measure of contractile function during dobutamine stimulation in human myocardium.

Adrenergic beta-Agonists↗

PubMed1997

Usefulness of magnetic resonance imaging early after acute myocardial infarction.

In patients, early after acute myocardial infarction (AMI), rapid magnetic resonance imaging (MRI) techniques have been used to assess left ventricular (LV) structure, global and regional function, infarct artery patency, or contrast uptake individually. We hypothesized that MRI could be used as a comprehensive evaluation of the post-AMI patient, studying all of these parameters in < 1 hour. Twenty-seven patients were studied after first AMI. Complete examinations were performed in 23 patients, 16 with anterior and 7 with inferior wall myocardial infarction, on day 5 +/- 2 after the event. For measurement of LV structure and regional function, a breath-hold segmented k-space gradient echo tagging sequence was used. A fat-suppressed segmented k-space breath-hold sequence was used for coronary artery imaging. MRI contrast-enhanced images during bolus gadoteridol transit through the myocardium were obtained to assess first-pass contrast uptake. No adverse events were noted during the MRI scanning, which was completed in 46 +/- 5 minutes. The LV mass index, end-diastolic and end-systolic volume indexes, and ejection fraction were (mean +/- SD) 107 +/- 13 g/m2, 87 +/- 23 ml/m2, 54 +/- 20 ml/m2, and 39 +/- 12%, respectively. Intramyocardial percent circumferential shortening was 11 +/- 6% at the apex, 14 +/- 4% in the midventricle, and 15 +/- 4% at the base. Flow within all infarct arteries was visualized. Seventeen of 23 patients had regions of reduced contrast uptake on first-pass imaging with mean signal intensity of 47 +/- 24% that of remote regions. In patients with recent AMI, comprehensive assessment of LV structure and function, infarct artery patency, and regional myocardial contrast uptake was safe and feasible with MRI of < 1 hour.

Adult↗

PubMed1997

Survey of veterinary professionals and other veterinary conference attendees for antibodies to Bartonella henselae and B quintana.

OBJECTIVE: To determine serologic and epidemiologic characteristics of an occupational group potentially at risk for Bartonella sp infection. DESIGN: Epidemiologic survey. SAMPLE POPULATION: 351 veterinarians, veterinary technicians, and other individuals attending a veterinary conference in Ohio. PROCEDURE: A serum sample was obtained from each individual and tested for antibodies to Bartonella henselae or B quintana. A 24-question survey also was administered regarding demographic, occupational, and exposure information. RESULTS: 25 (7.1%) individuals were seropositive for B henselae or B quintana. Forty-seven, of whom 5 were seropositive, reported a history of illness consistent with cat-scratch disease and 18, of whom 3 were seropositive, reported a previous diagnosis of cat-scratch disease. Of the variables analyzed, only years of experience with cats was correlated with seropositivity. CLINICAL IMPLICATIONS: The overall seroprevalence for 2 species of Bartonella in this occupational group was only slightly higher than that reported from other surveys. Seroprevalences among veterinarians, veterinary technicians, hospital staff, and others were essentially identical. Small sample groups, high percentage of cat ownership among participants, unknown duration of seropositivity, and unknown prevalence of infection among cats were potential confounders.

Adult↗

PubMed1997

Reduced sympathetic innervation underlies adjacent noninfarcted region dysfunction during left ventricular remodeling.

OBJECTIVES: We examined the association of sympathetic denervation and reduced blood flow with mechanical dysfunction in adjacent noninfarcted regions late after myocardial infarction (MI). BACKGROUND: Using a well characterized ovine model of left ventricular (LV) remodeling after transmural anteroapical MI, we previously showed that histologically normal adjacent noninfarcted regions demonstrate mechanical dysfunction. METHODS: Ten sheep underwent coronary ligation. Magnetic resonance imaging was performed before and 8 weeks after infarction for measurement of LV mass, volumes, ejection fraction and regional intramyocardial circumferential shortening (%S). Iodine-123 metaiodobenzylguanidine (I-123 MIBG) and fluorescent microspheres before and after administration of adenosine were infused before death for measurement of sympathetic innervation, blood flow and blood flow reserve from matched postmortem regions. RESULTS: From baseline to 8 weeks after infarction, LV end-diastolic volume increased from (mean +/- SD) 1.5 +/- 0.3 to 2.6 +/- 0.5 ml/kg (p < 0.001), and LV mass increased from 2.0 +/- 0.3 to 2.6 +/- 0.5 g/kg (p = 0.001). Regionally, the decline in subendocardial %S was greater in adjacent (19 +/- 5% to 8 +/- 5%) than in remote noninfarcted regions (20 +/- 6% to 19 +/- 6%, p < 0.002). No difference in regional blood flow or blood flow reserve was found between adjacent and remote regions, whereas I-123 MIBG uptake was lower in adjacent than in remote myocardium (1.09 +/- 0.30 vs. 1.31 +/- 0.40 nmol/g, p < 0.003). Topographically, from apex to base at 8 weeks after infarction, %S correlated closely with I-123 MIBG uptake (r = 0.93, p = 0.003). CONCLUSIONS: In mechanically dysfunctional noninfarcted regions adjacent to chronic transmural myocardial infarction in the remodeled left ventricle, blood flow and blood flow reserve are preserved, yet sympathetic innervation is reduced. Chronic sympathetic denervation in adjacent noninfarcted regions, in association with regional mechanical dysfunction, may contribute to LV remodeling after infarction.

3-Iodobenzylguanidine↗

PubMed1997

Dissociation between changes in intramyocardial function and left ventricular volumes in the eight weeks after first anterior myocardial infarction.

OBJECTIVES: We sought to examine the relation between regional changes in intramyocardial function and global left ventricular (LV) remodeling in the first 8 weeks after reperfused first anterior myocardial infarction (MI). BACKGROUND: Because of limitations in imaging methods used to date, this relation has not been thoroughly evaluated. METHODS: We studied 26 patients (21 men, 5 women; mean age 51 years) by magnetic resonance imaging (MRI) on day 5 +/- 2 (mean +/- SD) and week 8 +/- 1 after their first anterior MI. All patients had single-vessel left anterior descending coronary artery disease and although they had received reperfusion therapy, all had regional LV dysfunction and an initial ejection fraction (EF) < or = 50%. Short-axis magnetic resonance tagging was performed spanning the LV. Percent intramyocardial circumferential shortening (%S) on a topographic basis, LV mass index, LV end-diastolic volume index (LVEDVI), LV end-systolic volume index and LV ejection fraction (LVEF) were measured. RESULTS: Left ventricular mass index tended to decrease, whereas the LVEDVI increased from 82 +/- 24 to 96 +/- 27 ml/m2 (p = 0.002). Left ventricular end-systolic volume index remained unchanged, whereas LVEF increased from 39 +/- 12% to 45 +/- 14% (p = 0.002). Apical %S improved from 9 +/- 6% to 13 +/- 5% (p < 0.0001), as it did in the midanterior (6 +/- 6% to 10 +/- 7%, p < 0.02) and midseptal regions (8 +/- 7% to 12 +/- 6%, p < 0.02). Early dysfunction in remote midinferior and basal lateral regions resolved by 8 weeks. By multivariate analysis, the only significant predictor of an increase in LVEDVI over the study period was peak creatine kinase (p = 0.04). CONCLUSIONS: In the first 8 weeks after a large, reperfused anterior MI, %S improved in the apex, midanterior and midseptal regions and normalized in remote noninfarct-related regions, but LV end-diastolic volumes also increased. This increased LVEDVI correlated with infarct size by peak creatine kinase and was not related to changes in global and regional LV function.

Adult↗

PubMed1996

Remote noninfarcted region dysfunction soon after first anterior myocardial infarction. A magnetic resonance tagging study.

BACKGROUND: Previous studies have demonstrated hyperkinetic endocardial motion of noninfarcted myocardium early after myocardial infarction (MI). We wished to substantiate the findings of increased function of remote noninfarcted regions using magnetic resonance (MR) myocardial tagging in patients soon after anterior MI. METHODS AND RESULTS: Twenty-eight patients (25 male; mean age, 52 years) were studied on day 5 +/- 2 after first anterior MI. All had single-vessel left anterior descending coronary artery (LAD) disease and had received reperfusion therapy but had evidence of regional left ventricular (LV) dysfunction and an ejection fraction (EF) < or = 50%. Breath-hold, segmented k-space, gradient-echo MR tagging was performed with short-axis imaging spanning the LV. Percent circumferential shortening (%S) on a topographic basis, LV mass, and EF were measured. Regional %S was compared with that in 10 normal subjects (7 male; mean age, 43 years). We found reduced intramyocardial %S throughout the LV in the patient group. Percent shortening was lower in patients compared with control subjects at all sites along the long axis of the ventricle (9 +/- 5% versus 23 +/- 3% at the apex, P < .0001; 11 +/- 5% versus 21 +/- 3% at the midventricle, P < .0001; 14 +/- 3% versus 17 +/- 5% at the base, P < .02). The basal lateral and midinferior regions, remote from LAD territory, demonstrated reduced %S and a strong trend toward reduced %S, respectively. CONCLUSIONS: Patients on day 5 after first anterior MI with single-vessel disease demonstrate reduced intramyocardial circumferential shortening throughout the LV, including remote noninfarcted regions. Potential mechanisms include altered coronary vasodilatory properties, changes in regional mechanical load, or mechanical tethering to infarcted regions.

Adult↗

PubMed1996

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elevates basal B-cell intracellular calcium concentration and suppresses surface Ig- but not CD40-induced antibody secretion.

Humoral immune responses to either T-independent or T-dependent antigens have previously been shown to be suppressed by the halogenated aromatic hydrocarbon environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through direct action on B-lymphocytes. To better understand the molecular nature of the TCDD-induced suppression of B-cell differentiation, we studied the effects of TCDD using in vitro models of T-independent (antibody directed against surface IgM) and T-dependent [activated T-helper (TH) cells bearing CD40 ligand] B-cell maturation. We report here that TCDD suppresses murine B-cell IgM secretion induced by either soluble or insolubilized anti-IgM plus lymphokines but does not affect IgM secretion stimulated by activated T(H)-cells and lymphokines. Because soluble or insolubilized anti-IgM but not fixed, activated TH-cells was found to trigger increases in intracellular ionized calcium in isolated B-cells, the effect of TCDD exposure on B-cell intracellular calcium concentration and mobilization was examined. In comparison to the endoplasmic reticulum calcium ATPase inhibitor thapsigargin, which induces an immediate rise in resting [Ca2+]i of up to four- to fivefold, TCDD treatment did not produce a rapid increase in [Ca2+]i but did result in an elevation of basal levels of nearly the same magnitude 18 hr postexposure. However, anti-IgM-induced calcium transients were similar in the presence or absence of TCDD. TCDD exposure also produced instability of the calcium concentration curve, with the observed elevation of basal intracellular calcium occurring after both in vitro and in vivo treatment paradigms. The immunomodulatory profiles of activity of TCDD and thapsigargin on the B-cell proliferative response to PMA plus ionomycin differ, suggesting that the kinetics of calcium release by these compounds dictates the overall effect on the responding B-cell. Taken together, the data indicate that TCDD elevates resting intracellular calcium levels in murine B-cells and may selectively inhibit calcium-dependent signaling pathways linked to surface Ig.

Animals↗

PubMed1996

Angiotensin-converting enzyme inhibition limits dysfunction in adjacent noninfarcted regions during left ventricular remodeling.

OBJECTIVES: We hypothesized that angiotensin-converting enzyme inhibitors would limit dysfunction in the first 8 weeks after transmural infarction in adjacent noninfarcted regions, as well as attenuate left ventricular remodeling. BACKGROUND: Angiotensin-converting enzyme inhibition limits ventricular dilation and hypertrophy and improves survival after anterior infarction, but its effect on regional function during remodeling is not well characterized. METHODS: Thirteen sheep underwent coronary ligation to create an anteroapical infarction. At postinfarction day 2, eight sheep were randomized to therapy with the angiotensin-converting enzyme inhibitor ramipril, and five sheep received no therapy. Animals were studied with magnetic resonance myocardial tagging before and 8 weeks after infarction. Left ventricular volume, mass and ejection fraction were measured, as were changes in percent circumferential shortening within the subendocardium and subepicardium of infarcted and noninfarcted myocardium, both adjacent to and remote from the infarction. RESULTS: Angiotensin-converting enzyme inhibition limited the increase in end-diastolic volume from a mean (+/- SD) of +1.5 +/- 0.7 ml/kg in control animals to +0.5 +/- 0.8 ml/kg in the treated group (p < 0.04). Segmental function within infarcted and remote noninfarcted tissue did not differ between groups. However, angiotensin-converting enzyme inhibition limited the decline in function in the adjacent noninfarcted region 8 weeks after infarction. Percent circumferential shortening in the subendocardium decreased by -13 +/- 5% in the control group compared with -5 +/- 5% in the treated group (p < 0.03). CONCLUSIONS: In concert with a reduction in left ventricular remodeling after anterior infarction, angiotensin-converting enzyme inhibition limits the decline in function in the adjacent noninfarcted region. Dysfunction in adjacent noninfarcted regions may be an important determinant of left ventricular remodeling after infarction.

Analysis of Variance↗

PubMed1995

Segmental motion and deformation of transmurally infarcted myocardium in acute postinfarct period.

Mechanical behavior of infarcted myocardium in the first week following coronary occlusion has not been well characterized. Prior unidimensional studies failed to account for perpendicular deformation or shearing. This study characterizes three-dimensional motion and deformation of transmural infarcts 1 wk after coronary ligation in seven sheep. Principal strains and systolic in-plane translation and rotation were calculated for triangular elements defined by tissue tagging in short- and long-axis magnetic resonance images. The magnitudes of the first and second principal strains were reduced in both the short- and long-axis planes 1 wk after infarction. In addition, the absolute angular difference between the direction of the first principal strain and the radial direction increased from 14.7 +/- 1.9 to 43.5 +/- 2.7 degrees in the short-axis plane and from 19.6 +/- 7.3 to 43.9 +/- 10.0 degrees (P < 0.05) in the long-axis plane. In-plane rigid-body translation and rotation were also reduced in both planes. In conclusion, marked reduction and reorientation of principal strains and reduction in segmental rigid-body motion characterize nonreperfused transmural myocardial infarctions 1 wk after coronary occlusion.

Animals↗

PubMed1994

Growth factors alter neonatal type II alveolar epithelial cell proliferation.

The type II alveolar epithelial cell plays a critical role in the repair of lung injury by repopulating the entire damaged alveolar epithelium. We report our studies of the effects of known growth factors on the in vitro proliferation of isolated neonatal rabbit type II cells. Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) increased [3H]thymidine incorporation, cell number, and labeling index above control. Transforming growth factor-beta (TGF-beta) decreased [3H]thymidine incorporation, cell number, and labeling index compared with control. When added simultaneously, TGF-beta blocked the stimulatory effect of TGF-alpha or EGF. If TGF-alpha is added before TGF-beta, the ability of TGF-beta to block the mitogenic effect of TGF-alpha was diminished the later in time TGF-beta was added. If TGF-beta was added first, later addition of TGF-alpha had no effect. The current work demonstrates that specific growth factors, including some known to be produced by other lung cells, alter the proliferation in vitro of isolated neonatal rabbit type II alveolar epithelial cells.

Animals↗

PubMed1994

Regional heterogeneity of function in hypertrophic cardiomyopathy.

BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), left ventricular ejection performance may be normal while segmental myocardial function is distinctly abnormal. The advent of magnetic resonance tissue tagging has allowed the noninvasive evaluation of intramyocardial segmental shortening in vivo in a topographic and temporal manner. METHODS AND RESULTS: Ten patients with HCM documented by echocardiography and 10 healthy volunteers were studied with magnetic resonance tissue tagging by spatial modulation of magnetization. Percent circumferential myocardial shortening (%S) was compared at endocardium, midwall, and epicardial levels at four regions around the left ventricular short axis and from four short axis slices from apex to base at four or five time intervals during systole. In 8 patients and 8 control subjects, longitudinal shortening was evaluated within the septum and the lateral free wall at three levels from apex to base. Circumferential %S was less in HCM patients than in control subjects in the septal (13 +/- 5% versus 24 +/- 6%, P = .0002), inferior (13 +/- 5% versus 21 +/- 4%, P = .001), and anterior (17 +/- 5% versus 21 +/- 3%, P < .03) regions but not in the lateral region. Circumferential end-systolic %S was reduced in patients with HCM compared with control subjects at all levels from apex to base. The normal transmural gradient in circumferential end-systolic shortening was preserved with greatest %S at the endocardium. Most of the total cumulative circumferential shortening occurred earlier in systole in patients compared with control subjects, especially within the septum. Longitudinal end-systolic %S was depressed throughout the septum in patients compared with control subjects, most markedly at the base, but was normal in the lateral free wall. CONCLUSIONS: Circumferential myocardial segment shortening is depressed in HCM in the septum, inferior, and anterior regions and at all levels from apex to base, and much of the total cumulative shortening occurs early in systole. Longitudinal shortening is reduced in the basal septum in HCM. The heterogeneity of regional function in these patients may reflect the regional variation in the myocardial disarray and fibrosis that is characteristic of this disorder.

Adolescent↗

PubMed1994

Three-dimensional left ventricular deformation in hypertrophic cardiomyopathy.

BACKGROUND: In hypertrophic cardiomyopathy, ejection fraction is normal or increased, and force-length relations are reduced. However, three-dimensional (3D) motion and deformation in vivo have not been assessed in this condition. We have reconstructed the 3D motion of the left ventricle (LV) during systole in 7 patients with hypertrophic cardiomyopathy (HCM) and 12 normal volunteers by use of magnetic resonance tagging. METHODS AND RESULTS: Transmural tagging stripes were automatically tracked to subpixel resolution with an active contour model. A 3D finite-element model was used to interpolate displacement information between short- and long-axis slices and register data on a regional basis. Displacement and strain data were averaged into septal, posterior, lateral, and anterior regions at basal, midventricular, and apical levels. Radial motion (toward the central long axis) decreased slightly in patients with HCM, whereas longitudinal displacement (parallel to the long axis) of the base toward the apex was markedly reduced: 7.5 +/- 2.5mm (SD) versus 12.5 +/- 2.0 mm, P < .001. Circumferential and longitudinal shortening were both reduced in the septum (P < .01 at all levels). The principal strain associated with 3D maximal contraction was slightly depressed in many regions, significantly in the basal septum (-0.18 +/- 0.05 versus -0.22 +/- 0.02, P < .05) and anterior (-0.20 +/- 0.05 versus -0.23 +/- 0.02, P < .05) walls. In contrast, LV torsion (twist of the apex about the long axis relative to the base) was greater in HCM patients (19.9 +/- 2.4 degrees versus 14.6 +/- 2.7 degrees, P < .01). CONCLUSIONS: HCM patients had reduced 3D myocardial shortening on a regional basis; however, LV torsion was increased.

Adolescent↗

PubMed1993

Regional differences in function within noninfarcted myocardium during left ventricular remodeling.

BACKGROUND: The mechanisms of ventricular enlargement and dysfunction during postinfarct remodeling remain largely unknown. Although global left ventricular architectural changes after myocardial infarction are well documented, differences in function between adjacent and remote noninfarcted myocardium during left ventricular remodeling have not been investigated. These functional differences may relate to regional differences in wall stress during contraction and may contribute to chamber enlargement and global dysfunction after infarction. METHODS AND RESULTS: Anteroapical infarcts were produced in seven sheep by ligation of the mid left anterior descending coronary artery and second diagonal branch at thoracotomy. Magnetic resonance short-axis and long-axis images tagged by spatial modulation of magnetization were obtained before and 1 week, 8 weeks, and 6 months after infarction. Left ventricular volumes, mass, ejection fraction, and lengths of infarcted and noninfarcted segments were measured. Circumferential and longitudinal shortening in the subendocardium and subepicardium, wall thickness, and histopathology were assessed in infarcted segments and regions adjacent to and remote from the infarct border. We found that a difference in circumferential and longitudinal segmental shortening between adjacent and remote noninfarcted myocardium present at 1 week persisted up to 6 months after myocardial infarction. However, partial improvement of function in adjacent regions occurred during infarct healing between 1 and 8 weeks after infarction. Left ventricular volume increased up to 6 months after infarction, out of proportion to the concomitant eccentric hypertrophy, whereas the ejection fraction fell. Left ventricular dilatation late in the remodeling process was secondary to lengthening of noninfarcted segments, which were free of significant fibrosis. CONCLUSIONS: Left ventricular dilatation and eccentric hypertrophy during remodeling are associated with persistent differences in segmental function between adjacent and remote noninfarcted regions. These functional differences may reflect increased wall stress in adjacent noninfarcted regions and contribute to the global dilatation and dysfunction characteristic of left ventricular remodeling after infarction.

Animals↗

PubMed1993

Characterization of protein phosphorylation by 2,3,7,8-tetrachlorodibenzo-p-dioxin in murine lymphocytes: indirect evidence for a role in the suppression of humoral immunity.

Studies were undertaken to more thoroughly characterize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced stimulation of kinase activity in murine lymphocytes. In female B6C3F1 mice, TCDD-induced phosphorylation of 29, 45, 52 and 63 KDa proteins was selective for B cells, with little or no enhancement observed in T cells. When B cells were purified and separated by density on a percoll gradient, phosphorylation was only observed in the band composed of activated B cells, and was not enhanced in the band composed of resting B cells. TCDD-stimulated phosphorylation was associated with both the cytosol (45 and 52 KDa species) and membrane (52 KDa species) fractions. Purified B cells from both DBA/2 (Ahdd) and C57B16 (Ahbb) mice demonstrated equivalent enhancement of phosphorylation in response to TCDD. Administration of human gamma interferon (Hu-IFNg) at concentrations from 0.5 to 500 Units/ml produced a dose-related reversal of TCDD-induced suppression of in vitro antibody responses to both the polyclonal B cell activator, LPS, and the T-dependent antigen, sRBC in whole splenocytes isolated from female B6C3F1 mice. These concentrations of Hu-IFNg did not affect the magnitude of either response in the absence of TCDD, and did not reverse dexamethasone-induced suppression of either in vitro antibody response. TCDD-induced suppression of the T-dependent response was reversed only when Hu-IFNg was added to culture within the first 18 hours after treatment with TCDD and sRBC. These studies demonstrate that Hu-IFNg can reverse TCDD-induced in vitro Ab response suppression if it is administered during the period of susceptibility to TCDD. TCDD-induced phosphorylation in isolated B cells was also antagonized following co-incubation with Hu-IFNg. The profile of TCDD-induced increases in protein phosphorylation, including the selective effect on activated B cells, the general involvement of both cytosolic and membrane proteins, the lack of segregation with the Ah-dependent processes, and the ability of Hu-IFNg to reverse both the suppression of the Ab response and the increase in phosphorylation, supports the interpretation that such phosphorylation is involved in TCDD-induced suppression of the Ab response.

Animals↗