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The lusitropic response of rat heart to beta-adrenergic stimulation is decreased in senescence
J Mol Cell Cardiol23
(Supplement
III) (1991)
P-3-1 1 THE LUSITROPIC RESPONSE OF RAT HEART TO BETA-ADRENERGIC
STIMULATION IS DECREASED IN SENESCENCE. George E.Taffet, Lloyd H. Michael, Charlotte A. Tate. Sections of Cardiovascular Sciences and Geriatrics, Dept. of Medicine, Baylor College of Medicine and Dept. of Pharmacology, Univ. of Houston, Houston, TX 77030. The decreased chronotropic and inotropic responsiveness of the senescent heart have been well documented, however the lusitropic responsiveness is uncertain. Left ventricular papillary muscles were isolated from 6, 12-, and 30-month virgin male Fischer 344 rats. Isometric contractile performance with half-relaxation time (RT1/2) and normalized -dT/dt (-dT/dt/T) as the measures of relaxation was studied at varying stimulation rates, Isoproterenol (Iso) concentrations with 0.75 mM and 2.5 mM bath Calcium(Ca). Response at RT l/2 (% decrease) -dT/dt/T (96 increase) Iso IO-7M 6m(n=lO) 12m(n=6) 30m(n=lO) 6m 12m 30m Ca-.75mM,0.2 Hz 20+2.4 20.1+4 10.2+3.2 15+3.9 17.8+.5 6.4+3.4 Ca-2.5mM,0.6 Hz 12.4+2 11.1+2 0.6+1.9 9.8+2 7.1+1.8 2.5+1.6 The 30m response to Iso was different from 6m and 12m at higher calcium and stimulation rate (p=O.O014) using repeated measures techniques. The blunted lusitropic response of the old heart appears to be exaggerated by higher calcium flux. Supported by NIH K08 AG00428, AHA TX Affiliate, Methodist Hospital Foundation.
lslmclsai
2 7 R&wto Femari, Jan Willem ld" Jong, F&do Di Lisa md 3Alessandm tQ.elli. czh3i.r of card$ology, tiversiQof&escia, Italy, &rdic&emic$. L&m&my, T-kr, Rotterdsm, 'Ihe Netherland, Center afMitcchm&ial Physiolo~,Padwa, Italy, Institute ofpharmacology, Fwmra, Italy. kk pr&reati intrsperitoneally 253 rsbbits up tc ten days with daily doses of 1 ml/& of propianyl-lcamtine (P-L&), or of Gcsmitine (J&Z) using saline-treated minx& as contml. 24 tmxs after thelastinjectim, misolated the papillary muscles for electmphysiology, and used the hearts in perfusionexperimnts for bicchmicsl and hcmodynmic rreaswemts. Papillary mles from, P-IX treated cinimls, stmwialengtheningofthe acticnpotmtial duration at-l&v Em 6% to lQ$ NE (P
P-3-13 THE HEART CRBATINE KINASE SYSTEM IN CARDIOMYOPATHY.
Valdur A.Saks. Laboratory Zaza A Khuchua, Andrey V Kuznetsov, Renee Ventura-Clapier, 3rd Cherepkovskaya 15A, Moscow, of Bioenergetics, USSR Cardiology Research Center, USSR. The alterations in creatine kinase (CK) system in experimental hereditary cardiomyopathy in Syrian hamster hearts (CHF 146 line) and in human hearts with dilated It was shown that in both cases total CK third stage cardiomyopathy were studied. Relative amount of mitochondrial creatine kinase (CKmit) activity was 50% of control. in hamster heart decreased from 33% of total CK in control to 17% in myopathy. At the same time the contents of the BB form increased from 5% to 20%. In human heart level of CKmit decreased from 21% in normal heart to 13% in myopathic heart. Decrease Contents of CK-MB increased from 20% in normal to 27% in myopathic heart. of CKmit was due to reduction of the number of mitochondria in tissue and to the Decrease of CKmit decrease of the amount of enzyme par mg mitochondrial protein. and increase of CK-B subunt in cardiomyopathic heart result in diminished energy supply for contraction. s.70
(Supplement
III) (1991)
P-3-1 1 THE LUSITROPIC RESPONSE OF RAT HEART TO BETA-ADRENERGIC
STIMULATION IS DECREASED IN SENESCENCE. George E.Taffet, Lloyd H. Michael, Charlotte A. Tate. Sections of Cardiovascular Sciences and Geriatrics, Dept. of Medicine, Baylor College of Medicine and Dept. of Pharmacology, Univ. of Houston, Houston, TX 77030. The decreased chronotropic and inotropic responsiveness of the senescent heart have been well documented, however the lusitropic responsiveness is uncertain. Left ventricular papillary muscles were isolated from 6, 12-, and 30-month virgin male Fischer 344 rats. Isometric contractile performance with half-relaxation time (RT1/2) and normalized -dT/dt (-dT/dt/T) as the measures of relaxation was studied at varying stimulation rates, Isoproterenol (Iso) concentrations with 0.75 mM and 2.5 mM bath Calcium(Ca). Response at RT l/2 (% decrease) -dT/dt/T (96 increase) Iso IO-7M 6m(n=lO) 12m(n=6) 30m(n=lO) 6m 12m 30m Ca-.75mM,0.2 Hz 20+2.4 20.1+4 10.2+3.2 15+3.9 17.8+.5 6.4+3.4 Ca-2.5mM,0.6 Hz 12.4+2 11.1+2 0.6+1.9 9.8+2 7.1+1.8 2.5+1.6 The 30m response to Iso was different from 6m and 12m at higher calcium and stimulation rate (p=O.O014) using repeated measures techniques. The blunted lusitropic response of the old heart appears to be exaggerated by higher calcium flux. Supported by NIH K08 AG00428, AHA TX Affiliate, Methodist Hospital Foundation.
lslmclsai
2 7 R&wto Femari, Jan Willem ld" Jong, F&do Di Lisa md 3Alessandm tQ.elli. czh3i.r of card$ology, tiversiQof&escia, Italy, &rdic&emic$. L&m&my, T-kr, Rotterdsm, 'Ihe Netherland, Center afMitcchm&ial Physiolo~,Padwa, Italy, Institute ofpharmacology, Fwmra, Italy. kk pr&reati intrsperitoneally 253 rsbbits up tc ten days with daily doses of 1 ml/& of propianyl-lcamtine (P-L&), or of Gcsmitine (J&Z) using saline-treated minx& as contml. 24 tmxs after thelastinjectim, misolated the papillary muscles for electmphysiology, and used the hearts in perfusionexperimnts for bicchmicsl and hcmodynmic rreaswemts. Papillary mles from, P-IX treated cinimls, stmwialengtheningofthe acticnpotmtial duration at-l&v Em 6% to lQ$ NE (P
P-3-13 THE HEART CRBATINE KINASE SYSTEM IN CARDIOMYOPATHY.
Valdur A.Saks. Laboratory Zaza A Khuchua, Andrey V Kuznetsov, Renee Ventura-Clapier, 3rd Cherepkovskaya 15A, Moscow, of Bioenergetics, USSR Cardiology Research Center, USSR. The alterations in creatine kinase (CK) system in experimental hereditary cardiomyopathy in Syrian hamster hearts (CHF 146 line) and in human hearts with dilated It was shown that in both cases total CK third stage cardiomyopathy were studied. Relative amount of mitochondrial creatine kinase (CKmit) activity was 50% of control. in hamster heart decreased from 33% of total CK in control to 17% in myopathy. At the same time the contents of the BB form increased from 5% to 20%. In human heart level of CKmit decreased from 21% in normal heart to 13% in myopathic heart. Decrease Contents of CK-MB increased from 20% in normal to 27% in myopathic heart. of CKmit was due to reduction of the number of mitochondria in tissue and to the Decrease of CKmit decrease of the amount of enzyme par mg mitochondrial protein. and increase of CK-B subunt in cardiomyopathic heart result in diminished energy supply for contraction. s.70