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A new concept for donor heart preservation: Nucleoside transport inhibition
J Mol Cell Cardiol 22 (Supplement III) (1990) PS31 DEMONSTRATION ~&IEAIt~
OF OXlD4TlW USING H
STRESS ACROSS CELL MEMBRANES SPIN ECHO NMR SPECl’ROSCOPY
IN CHRONIC OF INTACT
John Reglinski, Mridula Cho ra, John McMurray*, Henry J Dargie’, W Ewen Smith. Departments of Chemistry, LFmversity of Strathclyde, and Cardiology, Western Infirmary, GIaSgOW.
and intracelhdar
MEMBRANE-SH + GSH ----> MEMBRANE-SSG + 2H+ + 2e (1) In this way essentialmembrane protein function is protected by GSH during oxidative stress.
ps32
A NEW CONCEPT FOR W.FLAMENG, T.M&LHOFF,
DONOR
HEART
PRESERVATION:
NUCLEOSIDE
TRANSPORT
INHIBITION.
SSUKEHIRO, JMINTEN, H.VAN BELLE, P.JANSSEN K.U.LEUVEN, MBORATORY EXPERIMENTAL CARDIAC SURGERY, LEUVEN, BELGIUM Actually donor heart preservation is limited to 4 hours: longer preservation periods are accompanied by increasing operative mortality rates. In this experimental study the beneficial effects of nucleoside transport inhibition (N.T.I.) are assessed in dogs. Twelve dogs were at random allocated to two groups. In the first group (group I, n = 6) the hearts were arrested with co@ hyperkalemic cardioplegic solution (NIH-solution), excised and stored for 24 hours at 0.5%. After 24 hours the hearts were transplanted orthotoptcally. In group II (n = 6) the same procedure was followed but the N.T.I. (R753231) was added to the NIH cardiopfegic solution (1 mg/l) and administrated intravenously to the recipient dog before reperfusion of the transplanted heart (0.1 mg/kg). In spite of maxlmal positive inotropic support none of the control animals (group I) could be weaned from cardiopulmonary bypass: within 1 hour irreversible cardiienic shock occurred in all animals. In group II all hearts could be weaned from cardiobutmonarv bvoass and were hemodynamidally~ stable without positive inotropic support. Serial transmkral LV-biopsies revealed in group I moderate catabolism of ATP during cold storage which proceeded uoon reperfusion. In group II ATP breakdown was less during r!old storage but continued up to 1 hour after reperfusion. The nucleosides adenosine and inosine were not washed out. After 2 hours of reperfusion a complete restoration of ATP content was found.These results show that the N.T.I. is highly effective in long term preservation of donor hearts.
PS33 MORPHOLOGICAL AND BIOCHEMICAL
INFLUENCE OF AFTERLOAD DEPRESSION IN HYPERTENSIVE RATS BY USING THE HEART LUNG PREPARATION. H.A. Baba, A. Takeda, M. Nagano. Department of Internal Medicine Jikei University Aoto Hospital, Tokyo, 125 Japan. In our recent research we have studied the effects of rapid blood pressure depression in hypertensive rats, since there are only a few previous investigations reported on this theme. The aim of the experiment was to observe mainly the acute myocardial changes which take place in heart lung preparation by reducing the afterload in relation to the initial blood pressure. The blood pressure was depressed under various levels for 60 min. and subsequently the heart was investigated morphologically and biochemically. Light microscopic examinations was used to obtain the degree of cardiac hypertrophy and the content of interstitial fibrosis was determined by an computer added imaging system. The ultrastructural investigation showed ischemic damaged mitochondria in relation to the grade of blood pressure depression. The cardiac glucose metabolites and high-energy phosphate were studied and showed a shift from a normal control distribution, on markedly depression cases the results showed hypoxic metabolic pattern. s.99
OF OXlD4TlW USING H
STRESS ACROSS CELL MEMBRANES SPIN ECHO NMR SPECl’ROSCOPY
IN CHRONIC OF INTACT
John Reglinski, Mridula Cho ra, John McMurray*, Henry J Dargie’, W Ewen Smith. Departments of Chemistry, LFmversity of Strathclyde, and Cardiology, Western Infirmary, GIaSgOW.
and intracelhdar
MEMBRANE-SH + GSH ----> MEMBRANE-SSG + 2H+ + 2e (1) In this way essentialmembrane protein function is protected by GSH during oxidative stress.
ps32
A NEW CONCEPT FOR W.FLAMENG, T.M&LHOFF,
DONOR
HEART
PRESERVATION:
NUCLEOSIDE
TRANSPORT
INHIBITION.
SSUKEHIRO, JMINTEN, H.VAN BELLE, P.JANSSEN K.U.LEUVEN, MBORATORY EXPERIMENTAL CARDIAC SURGERY, LEUVEN, BELGIUM Actually donor heart preservation is limited to 4 hours: longer preservation periods are accompanied by increasing operative mortality rates. In this experimental study the beneficial effects of nucleoside transport inhibition (N.T.I.) are assessed in dogs. Twelve dogs were at random allocated to two groups. In the first group (group I, n = 6) the hearts were arrested with co@ hyperkalemic cardioplegic solution (NIH-solution), excised and stored for 24 hours at 0.5%. After 24 hours the hearts were transplanted orthotoptcally. In group II (n = 6) the same procedure was followed but the N.T.I. (R753231) was added to the NIH cardiopfegic solution (1 mg/l) and administrated intravenously to the recipient dog before reperfusion of the transplanted heart (0.1 mg/kg). In spite of maxlmal positive inotropic support none of the control animals (group I) could be weaned from cardiopulmonary bypass: within 1 hour irreversible cardiienic shock occurred in all animals. In group II all hearts could be weaned from cardiobutmonarv bvoass and were hemodynamidally~ stable without positive inotropic support. Serial transmkral LV-biopsies revealed in group I moderate catabolism of ATP during cold storage which proceeded uoon reperfusion. In group II ATP breakdown was less during r!old storage but continued up to 1 hour after reperfusion. The nucleosides adenosine and inosine were not washed out. After 2 hours of reperfusion a complete restoration of ATP content was found.These results show that the N.T.I. is highly effective in long term preservation of donor hearts.
PS33 MORPHOLOGICAL AND BIOCHEMICAL
INFLUENCE OF AFTERLOAD DEPRESSION IN HYPERTENSIVE RATS BY USING THE HEART LUNG PREPARATION. H.A. Baba, A. Takeda, M. Nagano. Department of Internal Medicine Jikei University Aoto Hospital, Tokyo, 125 Japan. In our recent research we have studied the effects of rapid blood pressure depression in hypertensive rats, since there are only a few previous investigations reported on this theme. The aim of the experiment was to observe mainly the acute myocardial changes which take place in heart lung preparation by reducing the afterload in relation to the initial blood pressure. The blood pressure was depressed under various levels for 60 min. and subsequently the heart was investigated morphologically and biochemically. Light microscopic examinations was used to obtain the degree of cardiac hypertrophy and the content of interstitial fibrosis was determined by an computer added imaging system. The ultrastructural investigation showed ischemic damaged mitochondria in relation to the grade of blood pressure depression. The cardiac glucose metabolites and high-energy phosphate were studied and showed a shift from a normal control distribution, on markedly depression cases the results showed hypoxic metabolic pattern. s.99