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Role of the lymphatics in aiding regression of hypokalemic lesions in rat cardiac muscle
J Mol
Cell
Cardiol
20 (Supplement
III)
(1988)
16 ROLE OF
THE LYMPHATICS IN AIDING REGRESSION OF HYPOKALEMIC LESIONS IN RAT CARDIAC MUSCLE. Steven Tepper and Wolfgang Mergner. Department of Pathology, School of Medicine, UMAB. (Supported by University of MD DRIF Fund #FY1988 and the APTA.) Prior studies have revealed hypokalemic cardiac lesions reduced significantly after 72 hours re-feeding of potassium into the diet of rats (~(0.01). This ultrastructural investigation was to establish the role of the lymphatics as a means of reducing the lesion area. Hypokalemic rats were sacrificed via perfusion fixation during the hypokalemic periods and during the potassium resupplementation periods. During the hypokalemic period macrophages were found engulfing necrotic myocytes. With re-feeding of potassium, lymphatic channels were dilated and full of mononuclear cells containing engulfed necrotic cardiac debris. These channels which were maintained during the hypokalemic period were differentiated from the vascular capillaries by standard morphological size may uptake of
criteria. be due proteinaceous
In in
conclusion,
part material
to the by
the rapid removal of the lymphatics.
reduction phagocytic
in lesion cells and
17 EXPRESSION OF THE CtGi GENE IN THE FAILING HEART. A.M. Feldman, A.E. Gates, M.R.
School of Medicine, Baltimore, MD: Bristow, C. Van Dop. The Johns Hopkins University The University of Utah School of Medicine, Salt Lake City, UT: and The Howard Hughes Institute at Children's Hospital, Boston, MA. We recently demonstrated that the concentration of a Mr 40,000 pertussis toxin This substrate ( aGi ) is increased approximately 35% in the failing human heart. rise correlated with an increased functional effect of Gi on adenylate cyclase in membranes from the failing hearts. To determine whether this increased Gi resulted from altered expression of an ClGi gene, we measured tissue levels of mRNA encoding aGi in hearts obtained at cardiac transplantation from six patients with idiopathic dilated cardiomyopathy and in hearts from six organ donors whose non-failing hearts could not be used for transplant. Specific mRNAs were quantified utilizing dot blots that were prepared from total RNA and hybridized using a cDNA encoding rat O1Gi. With this probe hybridized a single mRNA appropriate hybridization stringency conditions, on northern blot analysis. Hybridization intensity of the ClGi signal in different samples was normalized by comparison with hybridization intensity of a @-actin cDNA on the same blots. Compared to non-failing controls, the failing hearts contained 55% (f. 15%, p ~0.01) greater amounts of mRNAencoding aGi* These results indicate that in the failing human heart, the augmentation in functional Gi is associated with a proportionate rise in steady state levels of cellular mRNAencoding aGi.
18
MYOCARDIAL EDEMA COMPROMISES CARDIAC FUNCTION. Glen A. Laine. Center for Microvascular and Lymphatic Studies and Department of Anesthesiology, University of Texas Medical School, Houston, TX 77030. The accumulation of myocardial edema (ME) following disruption of myocardial microvascular permeability has been shown to compromise cardiac function (Laine, Circ. Res., August, 1987). Accumulation of myocardial edema in chronic arterial hypertension also reaches levels which have been shown to adversely affect cardiac function (Lsine, Circ. Res., May, 1988). We postulated that various combinations of reducing myocardial lymph flow and elevating coronary sinus pressure (CSP) would potentiate ME and compromise cardiac function (cardiac output vs left atrial pressure). We reduced myocardial lymph flow by direct constriction of the left CSP was elevated using a balloon tipped catheter. ventricular lymphatic trunk. Myocardial edema was quantitated using a standard wet to dry weight ratio (W/D) technique with control values of 2.9+0.2. W/D ratios were increased to a maximum of 4.5. Compromised cardiac fun&i& began at a W/D of approximately 3.7 and became progressively worse with further fluid accumulation. We conclude that accumulation of myocardial edema, following decrease in myocardial lymph flow and compromises cardiac function. Supported by increase in coronary sinus pressure, HL-36115.
S.6
Cell
Cardiol
20 (Supplement
III)
(1988)
16 ROLE OF
THE LYMPHATICS IN AIDING REGRESSION OF HYPOKALEMIC LESIONS IN RAT CARDIAC MUSCLE. Steven Tepper and Wolfgang Mergner. Department of Pathology, School of Medicine, UMAB. (Supported by University of MD DRIF Fund #FY1988 and the APTA.) Prior studies have revealed hypokalemic cardiac lesions reduced significantly after 72 hours re-feeding of potassium into the diet of rats (~(0.01). This ultrastructural investigation was to establish the role of the lymphatics as a means of reducing the lesion area. Hypokalemic rats were sacrificed via perfusion fixation during the hypokalemic periods and during the potassium resupplementation periods. During the hypokalemic period macrophages were found engulfing necrotic myocytes. With re-feeding of potassium, lymphatic channels were dilated and full of mononuclear cells containing engulfed necrotic cardiac debris. These channels which were maintained during the hypokalemic period were differentiated from the vascular capillaries by standard morphological size may uptake of
criteria. be due proteinaceous
In in
conclusion,
part material
to the by
the rapid removal of the lymphatics.
reduction phagocytic
in lesion cells and
17 EXPRESSION OF THE CtGi GENE IN THE FAILING HEART. A.M. Feldman, A.E. Gates, M.R.
School of Medicine, Baltimore, MD: Bristow, C. Van Dop. The Johns Hopkins University The University of Utah School of Medicine, Salt Lake City, UT: and The Howard Hughes Institute at Children's Hospital, Boston, MA. We recently demonstrated that the concentration of a Mr 40,000 pertussis toxin This substrate ( aGi ) is increased approximately 35% in the failing human heart. rise correlated with an increased functional effect of Gi on adenylate cyclase in membranes from the failing hearts. To determine whether this increased Gi resulted from altered expression of an ClGi gene, we measured tissue levels of mRNA encoding aGi in hearts obtained at cardiac transplantation from six patients with idiopathic dilated cardiomyopathy and in hearts from six organ donors whose non-failing hearts could not be used for transplant. Specific mRNAs were quantified utilizing dot blots that were prepared from total RNA and hybridized using a cDNA encoding rat O1Gi. With this probe hybridized a single mRNA appropriate hybridization stringency conditions, on northern blot analysis. Hybridization intensity of the ClGi signal in different samples was normalized by comparison with hybridization intensity of a @-actin cDNA on the same blots. Compared to non-failing controls, the failing hearts contained 55% (f. 15%, p ~0.01) greater amounts of mRNAencoding aGi* These results indicate that in the failing human heart, the augmentation in functional Gi is associated with a proportionate rise in steady state levels of cellular mRNAencoding aGi.
18
MYOCARDIAL EDEMA COMPROMISES CARDIAC FUNCTION. Glen A. Laine. Center for Microvascular and Lymphatic Studies and Department of Anesthesiology, University of Texas Medical School, Houston, TX 77030. The accumulation of myocardial edema (ME) following disruption of myocardial microvascular permeability has been shown to compromise cardiac function (Laine, Circ. Res., August, 1987). Accumulation of myocardial edema in chronic arterial hypertension also reaches levels which have been shown to adversely affect cardiac function (Lsine, Circ. Res., May, 1988). We postulated that various combinations of reducing myocardial lymph flow and elevating coronary sinus pressure (CSP) would potentiate ME and compromise cardiac function (cardiac output vs left atrial pressure). We reduced myocardial lymph flow by direct constriction of the left CSP was elevated using a balloon tipped catheter. ventricular lymphatic trunk. Myocardial edema was quantitated using a standard wet to dry weight ratio (W/D) technique with control values of 2.9+0.2. W/D ratios were increased to a maximum of 4.5. Compromised cardiac fun&i& began at a W/D of approximately 3.7 and became progressively worse with further fluid accumulation. We conclude that accumulation of myocardial edema, following decrease in myocardial lymph flow and compromises cardiac function. Supported by increase in coronary sinus pressure, HL-36115.
S.6