ischaemic preconditioning of the human heart. - Leicester Research ...

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JACC Vol. 37, No. 3,2001 Ghosh st aL 715 March 1,2001: 711-8 In Ohmood Nýmnbm 0 3.1 (D CID I 10 (D 3: cm E 25 0 7S 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 A. * * Aerobic Ischernia PC Diazoxide Glibenclamide Control Alone + B. Aerobic Ischemia Control Alone * PC PC Diazoxide Glibenclamide Nowe 3. Creatine kinase (CK) leakage (A) during the 120 min reoxygenation period (last 120 min in the aerobic control group) and Mrr reduction (B) at the end of the reox7genation period in StudY 1 (for protocol see Fig. 1). Data are expressed as mean ± standard error of mean of six oqmiments. *p < O. o5 versus corresponding group subjected to ischeraia alone. While bar = nondiabetics; black bar = diet-controlled diabeter, striped bar = nonumlin-4endent diabetes; hatched bar = insulin-dependent diabetes; PC = preconditioning on various intracellulu regulatory proteins and messenger systems (22). It is therefore conceivable that diabetes may affiect ischemic injury. Howem, our results show that the diabetic human myocardium is not more sensitive to lethal ischemic injury than the nondiabetic myocardium under the conditions of the present study. Because epidemiological studies have dearly shown that patients with either IDD or NIDD are more prone to develop myocardial infarction and (10,23), it postinfarction complications may be argued that the in diabetics is cause of cardiac complications not the tolerance of the heat to ischemia. The literature is inconsistent with respect to how susceptible the hearts of diabetic ar , Limals are to injury from ischemia/reperfusion, and whereas some studies have observed a greater susceptibility PC to ischemia/reperfusion injury (15), others have reported no significant effiect (24,25). The divergent results may be explained by experimental differences, but if our results in the human atrial. myocardium can be confirmed in ventricular mYocardium. then our attention to reduce cardiac complications in diabetes should be centered in the context of blood components and the vasculature rather than in the own myocardium. Our studies have demonstrated that PC afords protection of the myocardiurn from patients with DCD but that this is lost when patients are on long-term hypoglycemics or become insulin dependent. These results are in agreement with those reported by Cleveland et al. (16). These investigators showed that myocardium fiom patients with dia-
716 chmä et aL Pi unamOso äu In Ohm»d ffý kbwwdhm 0 0, (5 15 0 -j C) 0 6 0 ;ý0.6 .! 2 1.2 0.8 0.4 2 0.2 A. B. Aerobic Ischernia Control Alone Aerobic Ischernia Control Alone * * * JACC Vol. 37, No. 3,2001 March 1,2001: 711-8 * t : 1 P 1 T PC Diazoxide * * *t PC Diazoxide Figm 4. Creatine kinase (CK) leakage (A) during the 120 min reoxygenation period (last 120 min in the aerobic control group) and MI7 reduction (B) at the end of the reoxygenation period in study 2 (for protocol see Fig. 2). Data are expressed as mean t standard error of mean of six experiments. p 0.05 versus corresponding group subjected to ischemia alone; tp < 0.05 versus corresponding group subjected to preconditioning (PC). White bar. left ventricular ejection fiwfion (LVEF) >5096, striped bar LVEF = 30% to 50%, black bar LVEF
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ISCHAEMIC PRECONDITIONING OF THE HU
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ABSTRACT Ischaemic preconditioning
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andomised clinical study with the f
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CHAPTERI Introduction 35 Matefials
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Discussion 151 CHAPTER Vill Conclus
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44 CK leakage and MTT reduction on
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The Wellcome Trust and The British
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Presentations International "The Ef
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Abbreviations An attempt has been m
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1.1 Introduction Ischaernic heart d
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1.2 Myocardial Ischaemia Myocardial
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hours up to several days to complet
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phosphates and its influence on hyd
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1.4 Myocardial Protection This refe
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performed. This process is repeated
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1.6 Possible Mechanisms of Ischaemi
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kilodalton stress proteins. These p
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and these proteins have been sugges
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K vi-1, channels were initially fou
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tissues the K.. %,.,, channels are
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Subsequently, Jaburek et al 1145] i
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venous capacitance vessels. At ther
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preconditioning to be investigated
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In the angioplasty model, Tomai et
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patients were randomized into two g
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CHAPTER 11 THE HUMAN RIGHT ATRIAL T
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inexpensive. Briefly in this model,
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of each ischemic period, slices wer
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30 nini FO linlin L 60 min 120 inin
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In Study 3 (see Figure 2.4), slices
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D. Metabolite analysis Samples were
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leakage is calculated as the net LD
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B. Effect of the severity of ischae
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2.11 DISCUSSION: The present studie
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clearly insufficient to induce myoc
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The present model may facilitate th
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2.12 Conclusiow I have characterise
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3.5 3 V 2.5 3: m Je m Z0 z 2 1.5 0.
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(3 3 2.5 a 1.5 - -r T 0 2 0.5 0 I P
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Q oro . 21 . 0 'a IP 10 '. R -C3 A
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=3 0 h X CD 0 x CD :3 0 , 7, CD 0 0
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CHAPTER III PRECONDITIONING THE HUM
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3.2 MATERIALS AND METHODS-. 3.2.1 E
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A117'reduction- At the end of the e
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-4 ýi r. () .1 a 0 1 tli n F5* - C
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v M. %; n C) .0 ý U ý ý - - - -2
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leakage resulting from precondition
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3.5 DISCUSSION: The present studies
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during cardiac surgery totalling 10
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different. The cellular mechanisms
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cn Je 8 7 6 5 4 1 0 0.8 0.7 0.6 0.5
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8 6 C) 2 0.7 0.6 Q) 0.5 0) E 25 0.4
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6 5 CY) ,u3 CF) m -ýe m 2 1 0 -0.8
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CHAPTERIV THE ROLE OF THE KATPCHANN
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It has been reported that K.. %-I-p
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0 a- I a 3 I cr =r Cl. 2 qQ 0'-ý 0
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Figure 4.7 shows that ischaemia alo
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Figure 4.2 Dosc-responsc experiment
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Figure 4.4 Dose-response experiment
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Figure 4.6 Dosc-response experiment
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1 0.9 -ý 0.8 0.7 E 0.6 0.5 0.4 0.2
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activity, and showed that diazoxide
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Furthermore, Van den Hoek et al [3
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mechanism by which the opening of m
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5.1 INTRODUCTION: Within the enormo
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5.2 MATERIALS AND METHODS: 5.2.1 Ex
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M77'rechiction: At the end of the e
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oc 0 0 cr F; * 10 eb I ý; o I 5 0
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Pages missing original in the
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esulted in a decrease of CK leakage
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are on long-term hypoglycaernics or
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absence of uniformity of expeniment
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5.7 Conclusion Preconditioning is a
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0.9 0.8 07 m 0.6 E -0 0t 4 0.3 02 0
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-0 1.2 1 &8 0.6 04 0.2 o Aerobic Is
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6.1 INTRODUCIFION' Life expectancv
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(MI-T) to blue t'()rmazan product C
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The demonstration that ischaemic in
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Table 61 Patients' demographic and
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Nure 6,1: Creatine Kinase (CK) leak
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CHAPTER VII IN VIVO STUDIES ON T"E
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The apparent discrepancy bet,.,,, e
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In the off-pump group, coronary byp
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eduction as described in section 3.
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7.4.2 In vitro studies Figures 7.3A
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preconditioning stimulus in man is
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myocardium. Several investigators [
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Table 7.2 - Patients haemod-v-namic
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(0 -I 3 CD CD CD 1 3 0 :3 0 0 =r w
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0 co t X 3 co 0 0 Cumulative Releas
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-& a) c) UT 0 =r w CD 3 CD 0 1ý (a
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When ischaernic preconditioning was
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evidence tbr the involvement ot'PKC
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institution o fcardiopu Imo nary by
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Biblioqraphv 1. Abete P, Ferrara N,
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14. Auchampach J, Cavero, I and Gro
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27. Becker LB, Van den Hoek TLV, Sh
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41. Bums PG, Krunkenkamp IB, Calder
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55. Cohen G, Shirai T, Weisel RD, e
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69. Currie RW and White FP (1983).
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83. Downey JM, Liu GS and Thornton
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97. Ganote C, Armstrong S and Downe
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110. Grover GJ, D'Alonzo A, Hess T,
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122. Hamilton T and Weston A (1989)
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137. Hu H, Sato T, Seharaseyon J, L
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151. Jennings R, Steenbergen C, Kin
Page 213 and 214: 164. Kelpzig H, Kobert G, Mafter C,
Page 215 and 216: 178. Lamping K, Christensen C, Pelc
Page 217 and 218: 192. Liu GS, Thornton J, Van Winkle
Page 219 and 220: 206. Maulik N, Yoshida T, Das DK. (
Page 221 and 222: 219. Miyawaki H, Zhou X, Ashraf, M.
Page 223 and 224: 233. Okazaki Y, Kodama K, Sato H, K
Page 225 and 226: 248. Pryzlenk K, Li G, Whittaker P
Page 227 and 228: 260. Saito S, Tamura Y, Moriuchi M,
Page 229 and 230: 274. Schulz R, Post H, Valhaus C, e
Page 231 and 232: 288. Stewart JR, Blackwell WH, Crut
Page 233 and 234: 300. Tani M, Suganuma Y, Hasegawa H
Page 235 and 236: 312. Tosaki A, Engelman DT, Engelma
Page 237 and 238: 324. Walker D, Marber M, Walker J a
Page 239 and 240: 337. Yamashita N, Nishida M, Hoshid
Page 241 and 242: 351. Zhang JG, Lindup WE. (1993). R
Page 243 and 244: 444 J. -G. Zhang and others are dif
Page 245 and 246: 446 J. -G. Zhang and others Assessm
Page 247 and 248: 448 J. -G. Zhang and others 0.9 0.8
Page 249 and 250: 450 J. -G. Zhang and others C E 07
Page 251 and 252: 4S2 J. -G. Zhang and othen effects
Page 253 and 254: ELSEVIER Abstract Cardiovascular Re
Page 255 and 256: 936 S. Ghosh et al. / Cardiovascula
Page 257 and 258: 938 S. Ghosh et al. / Cardiovascula
Page 259 and 260: 940 S. Ghosh et al. [41 Goto M, Liu
Page 261 and 262: 712 0" et &L h wcomMe geg in Obwa»
Page 263: 714 Gbosb ot aL hmoo dmoWmbDbsnedH
Page 267: 718 ehe* et &L ditioning in the hum
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