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Tissue distribution of fibroblast growth factor (FGF) in ischemic, collateralized pig myocardium
J Mol Cell Cardiol 22 (Supplement f’T4
III) (1990)
KBDOGENOUS DIGOXIB-LIKE FACTOR (EDLF) IX? ACUTE MYQCARDIAL Il?FARCTIOIi (AMI) Alexey Ya.Bagrov, Olga V.Fedorova, Marina U.Maslova, Matalia I. Roukogatkina, Maria V.Ukhanova, and Eugenii P.Zhabko. I.I.Dzhanelidze
First Aid Research Institute, and I.H.Sechenov Institute of Evolutionary Physiology and Biochemistry Acad.Sci. USSR, Leningrad, USSR Activity of the whole erythrocytes (Er) ouabain-sensitive Na,K-ATPase is known to reflect plasma levels of EDLP. In AM1 in rats we observed a 46% inhibition
of
the
whole
Er la,K-ATPase,
which
correlated
with
the incidence of ventricular arrhythmia (r-0.86, p': 0.01). Pretreatment of the animals with antidigoxin antibodies (AA) prevented both In 25 patients in the first 24 hr arrhythmia and enzyme inhibition. of AK1 the whole Er Na,K-ATPaae was inhibited (1.26 pM Pi*ml-lsh-l, ps:O.Ol) as compared with 20 healthy controls (3.4) and 11 patients with unstable angina pectoris (3.11, whereas no difference was ob served in enzyme activity in Er ghosts. There was a correlation between the Er ATPase activity and plasma Na,K-ATPase-inhibitory potency (m-0.64, p< 0.001) in patients with ANI. Plasma inhibitory of activity was blocked by AA. The data presented sug eat an increase circulating EDLP in AW, that plays probably a cer f ain role in pathogenesis of ischemia-induced cardiac arrhythmia.
PT5
TISSUE DISTRIBUTION OF FIBROBLAST GROWTH FACTOR (FGF) IN ISCHRMIC, COLLATERALIZED PIG MYOCARDIUM Schott, Wolfgang Quinkler, Hari Sabine Bernotat-Danielowski, Robert J. S. Sharma, Peter Kremer, Wolfgang Schaper, Max-Planck-Institute and Kerckhoff-Clinic, Bad Nauheim, FRG We induced a progressive coronary artery stenosis in pig hearts by implanting an ameroid constrictor around the left coronary circumflex artery (CX). The subtotal occlusion results in the growth of new vessels and enlargement of existing ones in the ischemic area. We investigated the presence and tissue distribution of FGF in ischemic and con-
trol heart tissue using monoclonal antibodies raised against aFGF purified from bovine heart (Mr 16 kD) and against recombinant bFGF (Mr 18 kD). Only in the ischemic region, where collateralisation was
demonstrated angiographically and histologically, the cardiomvocytes. We found a focal distribution nantly near-fibrotic tissue. Interstitial tissue stained. bFGF was detected neither in ischemic nor heart. These results indicate that aFGF, but not ischemic myocytes and may play an important role duced angiogenesis.
PT6
aFGF was detected in of stainina Dredomiand vessels-w&e not in normallv perfused bFGF, is produced by in the ischemia in-
DIFFKRERYIbL PBGIORAL SBRSITIVIYY YO CALCIYOKIR G.EHBKI~IXJXD PEPTIDE (CGBP) IN PIG LEFT AIERRIOR DESCBHDIIIGCOPOMRY ARl%RIBS (LADCA) Roland Foulkes, Hina Shaw, Ian Marshall*, David Gray* & Bernadette Hughes. Department of Pharmacology, Celltech Ltd., Slough and Department of Pharmacology, UCL, London* CGRP is a potent coronary vasodilator, present in high concentration in the nerve endings around coronary vessels. In the present study, the vasorelaxant effects of human a-CGRP were studied in two distinct regions of the same porcine coronary artery. LADCA were removed from isolated pig hearts (n = 6) and pairs of l-2mm length dia)
(endothelium and one near
denuded) to the
rings apex ((
cut from lmm dia).
each
: one near the Rings were mounted
circumflex under
2~
(3-5mm restinn
tension in 1Oml organ bath containing Krebs.solution gassed with 95% 0, and 5X CO; and kept at 37OC. Rings were preconstricted with lo-‘M U46619 following which CGRP was added cumulatively. Five consecutive concentration response curves were constructed with a 30 min interval between induced tone elicited by CGBP was similar in 10%) rings. The EC,, was significantly less lo-‘OM) compared to large (2.4 f 0.6 x 10egM)
tolerance data
indicates
to repeated
CGRP administration
a difference
LAD and may reflect
differential
in
sensitivity
regional
each one. small (126 (P ( 0.05) rings and
whereas to
CGRP
distribution s.29
the
The maximum reversal in 12%) and large (116 2 in the small (6 t 2.5 x the large rings developed *
small
along
the
ones did
not.
length
the
of
of CGRP receptors.
These porcine
III) (1990)
KBDOGENOUS DIGOXIB-LIKE FACTOR (EDLF) IX? ACUTE MYQCARDIAL Il?FARCTIOIi (AMI) Alexey Ya.Bagrov, Olga V.Fedorova, Marina U.Maslova, Matalia I. Roukogatkina, Maria V.Ukhanova, and Eugenii P.Zhabko. I.I.Dzhanelidze
First Aid Research Institute, and I.H.Sechenov Institute of Evolutionary Physiology and Biochemistry Acad.Sci. USSR, Leningrad, USSR Activity of the whole erythrocytes (Er) ouabain-sensitive Na,K-ATPase is known to reflect plasma levels of EDLP. In AM1 in rats we observed a 46% inhibition
of
the
whole
Er la,K-ATPase,
which
correlated
with
the incidence of ventricular arrhythmia (r-0.86, p': 0.01). Pretreatment of the animals with antidigoxin antibodies (AA) prevented both In 25 patients in the first 24 hr arrhythmia and enzyme inhibition. of AK1 the whole Er Na,K-ATPaae was inhibited (1.26 pM Pi*ml-lsh-l, ps:O.Ol) as compared with 20 healthy controls (3.4) and 11 patients with unstable angina pectoris (3.11, whereas no difference was ob served in enzyme activity in Er ghosts. There was a correlation between the Er ATPase activity and plasma Na,K-ATPase-inhibitory potency (m-0.64, p< 0.001) in patients with ANI. Plasma inhibitory of activity was blocked by AA. The data presented sug eat an increase circulating EDLP in AW, that plays probably a cer f ain role in pathogenesis of ischemia-induced cardiac arrhythmia.
PT5
TISSUE DISTRIBUTION OF FIBROBLAST GROWTH FACTOR (FGF) IN ISCHRMIC, COLLATERALIZED PIG MYOCARDIUM Schott, Wolfgang Quinkler, Hari Sabine Bernotat-Danielowski, Robert J. S. Sharma, Peter Kremer, Wolfgang Schaper, Max-Planck-Institute and Kerckhoff-Clinic, Bad Nauheim, FRG We induced a progressive coronary artery stenosis in pig hearts by implanting an ameroid constrictor around the left coronary circumflex artery (CX). The subtotal occlusion results in the growth of new vessels and enlargement of existing ones in the ischemic area. We investigated the presence and tissue distribution of FGF in ischemic and con-
trol heart tissue using monoclonal antibodies raised against aFGF purified from bovine heart (Mr 16 kD) and against recombinant bFGF (Mr 18 kD). Only in the ischemic region, where collateralisation was
demonstrated angiographically and histologically, the cardiomvocytes. We found a focal distribution nantly near-fibrotic tissue. Interstitial tissue stained. bFGF was detected neither in ischemic nor heart. These results indicate that aFGF, but not ischemic myocytes and may play an important role duced angiogenesis.
PT6
aFGF was detected in of stainina Dredomiand vessels-w&e not in normallv perfused bFGF, is produced by in the ischemia in-
DIFFKRERYIbL PBGIORAL SBRSITIVIYY YO CALCIYOKIR G.EHBKI~IXJXD PEPTIDE (CGBP) IN PIG LEFT AIERRIOR DESCBHDIIIGCOPOMRY ARl%RIBS (LADCA) Roland Foulkes, Hina Shaw, Ian Marshall*, David Gray* & Bernadette Hughes. Department of Pharmacology, Celltech Ltd., Slough and Department of Pharmacology, UCL, London* CGRP is a potent coronary vasodilator, present in high concentration in the nerve endings around coronary vessels. In the present study, the vasorelaxant effects of human a-CGRP were studied in two distinct regions of the same porcine coronary artery. LADCA were removed from isolated pig hearts (n = 6) and pairs of l-2mm length dia)
(endothelium and one near
denuded) to the
rings apex ((
cut from lmm dia).
each
: one near the Rings were mounted
circumflex under
2~
(3-5mm restinn
tension in 1Oml organ bath containing Krebs.solution gassed with 95% 0, and 5X CO; and kept at 37OC. Rings were preconstricted with lo-‘M U46619 following which CGRP was added cumulatively. Five consecutive concentration response curves were constructed with a 30 min interval between induced tone elicited by CGBP was similar in 10%) rings. The EC,, was significantly less lo-‘OM) compared to large (2.4 f 0.6 x 10egM)
tolerance data
indicates
to repeated
CGRP administration
a difference
LAD and may reflect
differential
in
sensitivity
regional
each one. small (126 (P ( 0.05) rings and
whereas to
CGRP
distribution s.29
the
The maximum reversal in 12%) and large (116 2 in the small (6 t 2.5 x the large rings developed *
small
along
the
ones did
not.
length
the
of
of CGRP receptors.
These porcine