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J Ausma

Publications and source records attributed to J Ausma.

9 recordsLinked to original sources
PubMed1996

Only hibernating myocardium invariably shows early recovery after coronary revascularization.

BACKGROUND: The aims of this study were to identify hibernating myocardium (hypocontractile, hypoperfused viable myocardium that regains contractility after revascularization) in the clinical setting and to predict functional outcome in patients with coronary artery disease after coronary revascularization. METHODS AND RESULTS: Preoperative data related to the anterior free wall of the left ventricle were collected in 50 coronary bypass surgery candidates (positron emission tomography [PET], [13N]NH3 for flow, and [18F]FDG for metabolism [MET]; equilibrium-gated nuclear angiography [EGNA] for regional ejection fraction [REF]; and histological data from myocardial biopsies for percentage fibrosis and viable myocytes). Three months after surgery, the patients had follow-up PET and EGNA investigations. A principal-components analysis identified four patient clusters. Cluster 1 (n = 9) had normal viable myocardium. Cluster 2 (n = 18) had viable hypocontractile myocardium (REF, 39 +/- 12%) showing a PET mismatch pattern. Cluster 3 (n = 16) had viable hypocontractile myocardium associated with morphological myocyte injury showing a matched moderate decrease in flow (66 +/- 11%) and MET (70 +/- 11%). Cluster 4 (n = 7) had hypocontractile myocardium with mainly scar tissue (fibrosis, 74 +/- 12%). After surgery, only cluster 2, with hibernating myocardium, showed significant improvement in REF (from 39 +/- 12% to 50 +/- 13%, P < .05). Cluster 3, with sites of morphological myocyte injury, showed no recovery. The stepwise logistic regression showed a combination of low preoperative REF and high MET to be the best predictor of functional recovery (P < .008). CONCLUSIONS: Multivariate analysis identifies hibernating myocardium showing early postrevascularization recovery, as opposed to viable but myolytic myocardium with no early recovery. Postrevascularization recovery can be predicted (combination of low REF and high MET) by noninvasive techniques.

Adult↗
PubMed1996

Nuclear lamin expression in chronic hibernating myocardium in man.

Cardiomyocytes of chronic hibernating myocardium are known to undergo structural changes, indicative of dedifferentiation. Amongst these are changes in nuclear shape and chromatin distribution. Nuclear A-type lamins are known to be expressed in a differentiation-related fashion and to contribute to nuclear integrity and chromatin organization. Lamin expression was investigated with immunocytochemical staining procedures in biopsies from patients with chronic hibernating myocardium. The expression of A-type (lamin A and C) were shown to be downregulated during hibernation, while lamin B2 remained present in hibernating cardiomyocytes in a way similar to embryonic muscle cells. All heart muscle cells were shown to be negative for lamin B1. The absence of A-type lamins in chronic hibernating cardiomyocytes could be taken as an additional argument for the dedifferentiation state of these cells. The absence of A-type lamins was accompanied by dispersion of the nuclear heterochromatin, in a way similar to nuclei of embryonic cardiomyocytes.

Biopsy↗
PubMed1995

Regional myocardial blood flow, glucose utilization and contractile function before and after revascularization and ultrastructural findings in patients with chronic coronary artery disease.

In patients with chronic coronary artery disease, follow-up measurements of myocardial blood flow, metabolism and function were correlated with histology. In 41 patients with chronic coronary artery disease and a severely stenosed left anterior descending coronary artery, a positron emission tomographic (PET) flow/metabolism study and nuclear angiography were performed immediately before and 3 months after bypass surgery. Biopsies were taken from the left ventricular anterior wall at the time of surgery. Control biopsies were taken from donor hearts for cardiac transplantation and from hearts of patients with a defect of the atrial septum. A significant improvement of flow (P<0.01) and regional contractile function (P<0.01) was observed in the mismatch group. Glucose utilization was significantly lower (P<0.001) as compared to preoperative values. The group with preserved flow and the PET match group revealed no significant changes in flow, metabolism or function. Control biopsies revealed significantly less myolytic cells as compared to biopsies taken from both match and mismatch groups (P<0.01) and less fibrosis as compared to biopsies taken from the match group (P<0.01). Postoperatively, linear relationships were found between flow and both % fibrosis (r = 0.71, P<0.001) and regional anterior ejection fraction (r = 0.7, P<0.001). Only mismatch areas revealed significant recovery of both flow and function after revascularization with a disappearance of enhanced glucose uptake. The better linear correlation between flow and % fibrosis after surgery as compared to preoperatively was probably due to improvement of flow values in the mismatch group.

Coronary Artery Bypass↗
PubMed1995

Molecular changes of titin in left ventricular dysfunction as a result of chronic hibernation.

Cardiomyocytes of chronic hibernating myocardium are affected by partial to complete loss of sarcomeres, accumulation of glycogen, adaptations in size and shape of mitochondria, reorganisation of nuclear chromatin and depletion of sarcoplasmic reticulum. The nature of these changes, which from a purely morphologic viewpoint are akin to dedifferentiation, needed further clarification at the molecular level. For this purpose we have studied the expression and reorganization of titin, one of the earliest markers of cardiomyocytes differentiation. By use of monoclonal antibodies, recognizing different epitopes distributed over the whole length of the titin molecule, we were able to detect changes in its molecular organization as a result of chronic hibernation. The epitopes of the titin molecule attached to the Z-disc and those present close to the M-line remained detectable at all stages of hibernation, while epitopes at the A-I junction and parts of the myosin anchoring region of the molecule became masked or were lost. A fragmented or punctuated appearance of the titin staining pattern with antibodies to A-I junction related epitopes is found in cells which we consider to represent a more advanced stage of dedifferentiation. Changes in the distribution of the titin molecule or its molecular environment in hibernating myocardium resemble at least in part changes occurring during muscle cell differentiation, although in reversed order.

Animals↗
PubMed1995

Structural and metabolic correlates of the reversibility of chronic left ventricular ischemic dysfunction in humans.

Assessment of regional myocardial perfusion and glucose uptake with positron emission tomography (PET) identifies dysfunctional myocardium that shows improvement in function after revascularization. Yet little is known about the ultrastructural patterns of ischemic injury in myocardium with and without postoperative functional improvement in relation to residual perfusion and metabolism. Therefore dynamic PET with [13N]ammonia and 18F-labeled deoxyglucose was performed in 24 patients with coronary artery disease and anterior wall dysfunction undergoing bypass surgery. Transmural biopsies were obtained from the dysfunctional area during surgery and analyzed by optical and electron microscopy to quantify the presence of fibrosis and cardiomyocytes. As judged from the postoperative changes in contraction, left ventricular function improved in 16 patients. In myocardium that showed improved function after revascularization, preoperative flow and glucose uptake were higher by PET than in persistently dysfunctional myocardium. In tissue samples from myocardium that improved postoperatively, there were more cardiomyocytes, including a larger proportion of cells with excess glycogen stores (35 vs. 21%), and there was less fibrosis (24 vs. 49%) than in tissue samples from myocardium that did not improve functionally. Preoperative perfusion and postoperative wall motion were inversely correlated with the amount of tissue fibrosis, whereas preoperative 18F-labeled deoxyglucose uptake correlated positively with the amount of cardiomyocytes showing excess glycogen stores.

Adult↗
PubMed1994

Histological alterations in chronically hypoperfused myocardium. Correlation with PET findings.

BACKGROUND: In patients with chronic coronary artery disease (CAD) and left ventricular dysfunction, flow/metabolic studies of the myocardium with positron emission tomography (PET) are able to distinguish viable but dysfunctional myocardium from irreversible ischemic injury and scar tissue. In this study, PET findings of blood flow and metabolism in chronically hypoperfused myocardium were correlated with histology. METHODS AND RESULTS: We studied 33 patients suffering from CAD. In each patient, myocardial blood flow and metabolism were measured with PET 1 or 2 days before revascularization. During surgery, transmural biopsies were taken from the left ventricular anterior wall and planimetrically scored for the degree of myolysis (sarcomere loss). The amount of connective tissue was calculated using morphometric techniques. Contrast ventriculography demonstrated abnormal wall motion in 23 patients. Fourteen patients with a mismatch pattern (decreased flow with preserved metabolism) in the biopsy region after quantitative analysis of the PET data showed 11 +/- 6 vol% fibrosis and 25 +/- 13% cells with sarcomere loss. The space formerly occupied by sarcomeres was mainly replaced by glycogen and mitochondria. A significant wall motion improvement was noted 3 months after surgery. Nine patients showed a match pattern (concordant flow/metabolism defects). The biopsies revealed 35 +/- 25% fibrosis and 24 +/- 15% glycogen-storing cells. The biopsies of the 10 patients with normal anterior wall motion showed 8 +/- 4% fibrosis and 12 +/- 8% glycogen-accumulating cells. CONCLUSIONS: It can be concluded that areas with impaired wall motion and a PET match pattern show extensive fibrosis. Regions with reduced flow and preserved FDG metabolism, however, contain predominantly viable cells. In these regions, significant recovery of wall motion is found after revascularization. Regions with normal wall motion contain predominantly viable cells. Cells with reduced contractile material and increased glycogen content are mainly found in areas with wall motion impairment but are also present in areas with normal wall motion and a severe stenosis of the coronary vessel.

Biopsy↗
PubMed1991

Simultaneous purification of merozoites and schizonts of Eimeria tenella (Apicomplexa) by Percoll flotation and assessment of cell viability with a double fluorescent dye assay.

The asynchronous development of Eimeria tenella in orally infected chickens makes it possible to purify second generation merozoites (meros) and shizonts from a single mucosal homogenate. After centrifugation in 30% Percoll in phosphate-buffered saline (Percoll-PBS), debris, villi, and schizonts float, whereas meros and erythrocytes are pelleted. Erythrocytes are lysed by a mild hypotonic shock; meros are filtered through a cotton wool plug and collected by centrifugation. The 30% Percoll-PBS supernatant fraction is diluted to 25% Percoll-PBS and centrifuged to sediment mature schizonts. By repeated slow-speed centrifugation, schizonts are separated from nuclei and small-sized debris. In less than 3 hr, 8.8 +/- 2.3 x 10(8) meros and 7.2 +/- 3.9 x 10(6) schizonts are collected from 10 infected chickens. Contamination with host material is 2% for meros but variable for schizonts. For the assessment of cell viability, ethidium bromide (EB) and acridine orange (AO) have been used as markers for dead and living cells, respectively, in a single step method. More than 95% of the schizonts and meros accumulate AO and no EB, whereas lysed erythrocytes and all cells hosting a schizont are permeable to EB. After incubation of meros and schizonts in synthetic media with [5,6- 3H]uracil, label accumulates in the perchloric acid-soluble and -insoluble fractions, indicating transport, salvage, and incorporation of the pyrimidine precursor in nucleic acids. If stored on ice, meros and schizonts retain metabolic activity for at least 5 hr, but metabolism declines rapidly during incubation at 41 C.

Acridine Orange↗
PubMedDate not supplied

Chronic hibernating myocardium: interstitial changes.

Chronic left ventricular dysfunctional but viable myocardium of patients with chronic hibernation is characterized by structural changes, which consist of depletion of contractile elements, accumulation of glycogen, nuclear chromatin dispersion, depletion of sarcoplasmic reticulum and mitochondrial shape changes. These alterations are not reminiscent of degeneration but are interpreted as de-differentiation of the cardiomyocytes. The above mentioned changes are accompanied by a marked increase in the interstitial space. The present study describes qualitative and quantitative changes in the cellular and non-cellular compartments of the interstitial space. In chronic hibernating myocardial segments the increased extracellular matrix is filled with large amounts of type I collagen, type III collagen and fibronectin. An increase in the number of vimentin-positive cells (endothelial cells and fibroblasts) compared with normal myocardium is seen throughout the extracellular matrix. The increase in interstitial tissue is considered as one of the main determinants responsible for the lack of immediate recovery of contractile function after restoration of the blood flow to the affected myocardial segments of patients with chronic left ventricular dysfunction.

Actins↗