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Development of resistance of cardiac sarcoplasmic reticulum Ca-pump during adaptation to physical load and stress
CARDlAC MEMBRANE-PROTECTNE EFFECT OF CYTOSOLIC FACTORS IN STRESS AND ADAPTATlON Tatyana 0. Saaontova, Aleksey A. Matskevich & Yuuj V. Arkhlpenko. lnstltute of General Pathology and Pathophysiology, Moscow, Russia. We have shown eartier that stress-induced inhibition of iontransport enzymes, e.g., the sarcoplasmic reticulum (SR) Capump, reaches 30-504/o, which may strongly affect the muscle cell function. However, despite the significant drop of enzyme activity responsible for the maintenance of Ca2’ homeostasis and contractton-relaxation, stress has no effect on heart contractility, blood pressure or heart rate. These findings point to the existence in stress-induced heart of a system responsible for the decline of enzyme activity which maintains its normal function. Since in this case we deal with short-term stress, such compensation cannot be attributed to the de nova synthesis of protein molecules. It was thus assumed that the observed reconstitution of enzyme activity is rather due to the involvement of low-molecular-weight cytosolic molecules. indeed, the thermal resistance of the Ca-pump markedly increase after combination of the cytosolic fraction from stress-exposed animals with stress-damaged SR membranes. As a result, the enzyme activity returns to the control level, which makes it possible to maintain the physiological function of the heart. Adaptation of rats to immobilization stress (1 h, 12 sessions) significantly enhanced the resistance of the enzyme to free radical, autoiytic and other damages and the conformational stability and thermal resistance of the protein complex. An addition of the cytosolic fraction from adapted animals to adapted membranes had little effect on the activity and resistance of SR membranes, however, the cross effect of the cytosolic components from stress-adapted rats was well-pronounced and was manifested in complete recovery of the myocardial SR Capump from stress-induced injuries and significant enhancement of the enzyme activity.
Hoepilal,
Jcmawkm
myocardium
was
Israel.
studied
in
&iv.
Trabeculae hm the right atrial appendage obtained during cardiac surgery were sqerli~sed with Krebs-Henseleit. Following 30 mio stabibaticq.’ “iscbemia”
tmbeculse and 90 min
OF COLLATERAL PREVENTS ANGIO-
Dimitri Scholz, Tlbor Ziegelhoeffer, Armin Helisch, Shawn Wagner, Christian Fried&h, Hanno Eisaesser, Swen Wolfram & Wolfgang Sc;;w; Max-Planck-Institute, Bad Nauhelm,
Cydosporin A (CSA) was foynd to pnxondition (PC) animal katts. Efficacy of CSA to PC human
Damage of the myocardial sarcoplasmic reticulum (SR) Capump is accompanied by an increase in the level of free Ca” in cardiomyocytes, resulting in the development of cardiovascular diseases. Recent studies have been concerned with non-medicamentous, adaptive methods of prophylaxis against these disorders. We examined the formation of the protective effect on the rat cardiac SR Capump (Caseksctive electrode, ionometer Orion EA 940) in the dynamics of adaptation to stress (immobilization, 1 h every other day, 23 days) and physical load (swimming, 1 h, every day, 30 days). It was found that at early stages of aotation to stress (days 9-11) there was no protective effect: the resistance of the Ca-pump to thermal inactivation and to high levels of Ca*’ decreased. On day 15, the resistance of the Ca-pump increased I .4-l .6-fold. Long-term adaptation produced the maximum protective effect: the activity and resistance of the Ca-pump to the damaging factors increased. Adaotation to ohvsical load. The resistance of Ca-pump increased after 4-11 sessions. The maximum initial rate of the Ca-pump (155% of control) and maximum resistance to damaging factors were observed after 30 days. Thus, in the initial steps of adaptation to stress the enzyme resistance to damaging factors decreased. In contrast, adaptation to physical load induced protective effects already in earlier steps, Long-term adaptation of both model had similar beneficial effect on the activity and resistance of the cardiac SR Ca-pump.
AUGMENTATION ;z;/;k GROWTH
IN VIRTO PRECONDITIONING OF THE HUMAN MYOCARBHJM BY cYcLosPoRIN A. Aviva Schneider, Uzi Izhar, Gideon Merin, Joespb B. Barman, Herd Scbwdb. Joseph LlmenfeMCardiBcsn~Resareb, Hadassab
DEVELOPMENT OF RESISTANCE OF CARDIAC SARCOPUWW RETlCULUM Ca-PUMP DURING ADAPTATION TO PHYSICAL LOAD AND STRESS Tatyana G. Sazontova B Yurij V. Arkhipsnko. Institute of General Pathology and Pathophysiology, Moscow, Russia.
were exposed ‘Leperfusion”
to 90 min (control). In
the PC group 0.2 ph4 CSA was added during the stabilization period. In another group 0.1 mM of 5-hydroxydeuW& (S-ID) WBS ridded with the CSA during ?he stabiition period. Viiity was assessed by reduction of MTT (Sigma). Trabeculae subjected to ischemii-repehsion exhibited recovery of 55.5rt17?4. CSA e&an& remwry to 85.1*15.9% (M+SD, p
We studied the recovery of hindlimb et-fusion after femoral artery occlusion in Balb/ 8 and SV129 mice. Collateral vessels grow by cell proliferation from the pre-existing arteriolar connections in the proximal limb (arteriogenesis) whereas capillary sprouting occurs in the ischemic distal limb (angiogenesis). Morphometry of collateral vessels three weeks after occlusion suggested that arteriogenesis increased blood flow in SV129 mice 15fold and in BalbK mice 45fold. Capilla sprouting increased blood flow 1.7-fold in Balbl7s mice but not significantly in SV129 mice. Postocclusive monitoring of the pedal blood flow by laser Doppler, of the tissue oxygen saturation by light absorption and of the exercise capacity on the treadmill showed an accelerated recovery in the SVi29 strain. Intra-arterial infusion of 5 pg of fibroblast growth factor 2 (FGF-2) by osmotic minipump in seven days accelerated arteriogenesis but inhibited angiogenesis. Conclusion: Collateral vessel growth but not the sprouting of capillaries can effectively prevent ischemia. Augmentation of collateral vessel growth may result in decreased angiogenesis by reducing the severity of ischemia in the distal hindlimb. A107
Hoepilal,
Jcmawkm
myocardium
was
Israel.
studied
in
&iv.
Trabeculae hm the right atrial appendage obtained during cardiac surgery were sqerli~sed with Krebs-Henseleit. Following 30 mio stabibaticq.’ “iscbemia”
tmbeculse and 90 min
OF COLLATERAL PREVENTS ANGIO-
Dimitri Scholz, Tlbor Ziegelhoeffer, Armin Helisch, Shawn Wagner, Christian Fried&h, Hanno Eisaesser, Swen Wolfram & Wolfgang Sc;;w; Max-Planck-Institute, Bad Nauhelm,
Cydosporin A (CSA) was foynd to pnxondition (PC) animal katts. Efficacy of CSA to PC human
Damage of the myocardial sarcoplasmic reticulum (SR) Capump is accompanied by an increase in the level of free Ca” in cardiomyocytes, resulting in the development of cardiovascular diseases. Recent studies have been concerned with non-medicamentous, adaptive methods of prophylaxis against these disorders. We examined the formation of the protective effect on the rat cardiac SR Capump (Caseksctive electrode, ionometer Orion EA 940) in the dynamics of adaptation to stress (immobilization, 1 h every other day, 23 days) and physical load (swimming, 1 h, every day, 30 days). It was found that at early stages of aotation to stress (days 9-11) there was no protective effect: the resistance of the Ca-pump to thermal inactivation and to high levels of Ca*’ decreased. On day 15, the resistance of the Ca-pump increased I .4-l .6-fold. Long-term adaptation produced the maximum protective effect: the activity and resistance of the Ca-pump to the damaging factors increased. Adaotation to ohvsical load. The resistance of Ca-pump increased after 4-11 sessions. The maximum initial rate of the Ca-pump (155% of control) and maximum resistance to damaging factors were observed after 30 days. Thus, in the initial steps of adaptation to stress the enzyme resistance to damaging factors decreased. In contrast, adaptation to physical load induced protective effects already in earlier steps, Long-term adaptation of both model had similar beneficial effect on the activity and resistance of the cardiac SR Ca-pump.
AUGMENTATION ;z;/;k GROWTH
IN VIRTO PRECONDITIONING OF THE HUMAN MYOCARBHJM BY cYcLosPoRIN A. Aviva Schneider, Uzi Izhar, Gideon Merin, Joespb B. Barman, Herd Scbwdb. Joseph LlmenfeMCardiBcsn~Resareb, Hadassab
DEVELOPMENT OF RESISTANCE OF CARDIAC SARCOPUWW RETlCULUM Ca-PUMP DURING ADAPTATION TO PHYSICAL LOAD AND STRESS Tatyana G. Sazontova B Yurij V. Arkhipsnko. Institute of General Pathology and Pathophysiology, Moscow, Russia.
were exposed ‘Leperfusion”
to 90 min (control). In
the PC group 0.2 ph4 CSA was added during the stabilization period. In another group 0.1 mM of 5-hydroxydeuW& (S-ID) WBS ridded with the CSA during ?he stabiition period. Viiity was assessed by reduction of MTT (Sigma). Trabeculae subjected to ischemii-repehsion exhibited recovery of 55.5rt17?4. CSA e&an& remwry to 85.1*15.9% (M+SD, p
We studied the recovery of hindlimb et-fusion after femoral artery occlusion in Balb/ 8 and SV129 mice. Collateral vessels grow by cell proliferation from the pre-existing arteriolar connections in the proximal limb (arteriogenesis) whereas capillary sprouting occurs in the ischemic distal limb (angiogenesis). Morphometry of collateral vessels three weeks after occlusion suggested that arteriogenesis increased blood flow in SV129 mice 15fold and in BalbK mice 45fold. Capilla sprouting increased blood flow 1.7-fold in Balbl7s mice but not significantly in SV129 mice. Postocclusive monitoring of the pedal blood flow by laser Doppler, of the tissue oxygen saturation by light absorption and of the exercise capacity on the treadmill showed an accelerated recovery in the SVi29 strain. Intra-arterial infusion of 5 pg of fibroblast growth factor 2 (FGF-2) by osmotic minipump in seven days accelerated arteriogenesis but inhibited angiogenesis. Conclusion: Collateral vessel growth but not the sprouting of capillaries can effectively prevent ischemia. Augmentation of collateral vessel growth may result in decreased angiogenesis by reducing the severity of ischemia in the distal hindlimb. A107