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Alterations of catecholamines and adrenergic receptors in evolving myocardial infarction
9 MECHANICAL PERFORMANCEOF VENTRICULAR PAPILLARY MUSCLES IN CREATINE DEPLETED RATS. Brandejs, Y.A., Korecky, B., Department of Physiology, U n i v e r s i t y of Ottawa, Canada. To evaluate the r o l e of the c r e a t i n e - s h u t t l e i s o l a t e d p a p i l l a r y muscles with normal and reduced c r e a t i n e (C) l e v e l s were tested under isometric c o n d i t i o n s . Rats were fed a d i e t with e i t h e r I% B-guanadinopropionate (8-GPA), or with 2% B-guanadinobutyrate (8-GBA) which are poor substrates f o r C-kinase. A f t e r 7 weeks t o t a l C (C+PC) in the v e n t r i c l e s decreased from 14.5 umol/g to 4.7 ~mol/g for B-GPA, and to 2.6 umol/g f o r 8-GBA with accumulated concentrations of B-GPA and B-GBA 8.51 ~mol/g and 5.51 ~mol/g wet tissue r e s p e c t i v e l y . The maximum developed tension, i t s maximum rates of development and decay, i t s mean rate of development, time to maximum tension, h a l f r e l a x a t i o n time and frequency-force r e l a t i o n s h i p at Lmax were determined. No s i g n i f i c a n t differences in body weights, in length and cross-sectional area of p a p i l l a r y muscles were seen among the three groups. Only the preload to obtain Lmax was s i g n i f i c a n t l y lower in the B-GBA treated r a t s , (p
PHARMACOLOGY OF SODIUM CURRENTS IN SINGLE HEART CELLS. A.M. Brown, D.L. Kunze and A . Yatani. Dept. of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77550. We examined whole cell and single channel Na currents in single ventricular myocytes of neonatal and adult rat and adult guinea pig using gigaseal and blown-out patch clamp methods or the suction pipette method. Na currents were partially suppressed by using holding potentials of -80 mY and by reducing extracellular Na by three-fourths. Local anesthetics of the tertiary amine class such as lidocaine blocked rested channels and had use-dependent effects due to increased binding to inactivated channels, Neutral anesthetics (benzocaine) also bound to both channel states but were cleared from the membrane more quickly. The dihydropvridine Ca_~hannel modulator nitrendipine has an antagonist actio n with an IC of about 5 x i0 M for Ca channels. It also blocks Na channels with an IC50 that ~ 50-100 times greater. The binding was to both rested and inactivated channels with the latter preferred. Extracellular acidity also affected Na channels. Conductance-voltage relationships were shifted to depolarized potentials and current flow through open channels was reduced. We also examined whether Na channels once opened inactivate to an absorbing state. This was not found to be the case and considerable reopening of channels occurred at potentials where inactivation was prominent.
ALTERATIONS OF CATECHOLAMINES AND ADRENERGIC RECEPTORS IN EVOLVING MYOCARDIAL INFARCTION. L.M. Buja, K.H. Muntz, J.T. Willerson. Departments of Pathology and Internal Medicine, University of Texas Health Science Center, Dallas, Texas. These studies evaluated alterations in myocardial c~techolamines (CAT) and beta adrenergic receptors (BAR) early after ligation of the left anterior descending artery in the dog. Tissue CAT were measured radioenz~m~tically, and CAT-containing nerve terminals wer~ evaluated by quantitative histochemistry. BAR were measured by dihydroalprenolol ( H - D H A ) binding to membranes and by ~utoradiography of tissue sections. After 3 hours, values (percent control) for total tissue CAT were 83% in ischemic subepicardium and 76% in ischemic snbendocardi~m, whereas values for CAT-containing nerve terminals were 58% and 51%, respectively. Diffusion of CAT from the nerve terminals frequently was noted and degenerative changes in nerve terminals were demonstrated by electron microscopy. BAR numbers were increased significantly in cardiac myocytes but not in blood vessels in ischemic areas at I hour. Quantitative light microscopy showed significant myocyte damage only in the subendocardium after 1 hour, and in the subepicardium and subendocardium after 3 hours of ischemia. Thus, ischemic injury is associated with the redistribution and abnormal localization of CAT and an increase in BAR in cardiac myocytes in ischemic myocardium and these phenomena occur during the transmural spread of necrosis in evolving myocardial infarction.
PHARMACOLOGY OF SODIUM CURRENTS IN SINGLE HEART CELLS. A.M. Brown, D.L. Kunze and A . Yatani. Dept. of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77550. We examined whole cell and single channel Na currents in single ventricular myocytes of neonatal and adult rat and adult guinea pig using gigaseal and blown-out patch clamp methods or the suction pipette method. Na currents were partially suppressed by using holding potentials of -80 mY and by reducing extracellular Na by three-fourths. Local anesthetics of the tertiary amine class such as lidocaine blocked rested channels and had use-dependent effects due to increased binding to inactivated channels, Neutral anesthetics (benzocaine) also bound to both channel states but were cleared from the membrane more quickly. The dihydropvridine Ca_~hannel modulator nitrendipine has an antagonist actio n with an IC of about 5 x i0 M for Ca channels. It also blocks Na channels with an IC50 that ~ 50-100 times greater. The binding was to both rested and inactivated channels with the latter preferred. Extracellular acidity also affected Na channels. Conductance-voltage relationships were shifted to depolarized potentials and current flow through open channels was reduced. We also examined whether Na channels once opened inactivate to an absorbing state. This was not found to be the case and considerable reopening of channels occurred at potentials where inactivation was prominent.
ALTERATIONS OF CATECHOLAMINES AND ADRENERGIC RECEPTORS IN EVOLVING MYOCARDIAL INFARCTION. L.M. Buja, K.H. Muntz, J.T. Willerson. Departments of Pathology and Internal Medicine, University of Texas Health Science Center, Dallas, Texas. These studies evaluated alterations in myocardial c~techolamines (CAT) and beta adrenergic receptors (BAR) early after ligation of the left anterior descending artery in the dog. Tissue CAT were measured radioenz~m~tically, and CAT-containing nerve terminals wer~ evaluated by quantitative histochemistry. BAR were measured by dihydroalprenolol ( H - D H A ) binding to membranes and by ~utoradiography of tissue sections. After 3 hours, values (percent control) for total tissue CAT were 83% in ischemic subepicardium and 76% in ischemic snbendocardi~m, whereas values for CAT-containing nerve terminals were 58% and 51%, respectively. Diffusion of CAT from the nerve terminals frequently was noted and degenerative changes in nerve terminals were demonstrated by electron microscopy. BAR numbers were increased significantly in cardiac myocytes but not in blood vessels in ischemic areas at I hour. Quantitative light microscopy showed significant myocyte damage only in the subendocardium after 1 hour, and in the subepicardium and subendocardium after 3 hours of ischemia. Thus, ischemic injury is associated with the redistribution and abnormal localization of CAT and an increase in BAR in cardiac myocytes in ischemic myocardium and these phenomena occur during the transmural spread of necrosis in evolving myocardial infarction.