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

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2.5 Study groups Three different studies were performed to investigateý (i) the stability of the preparation (Study I ), (11) the effect of the severity of ischaernia (Study 2), and (ifi) the effect of the duration of reoxygenation (Study 3). In Study I (Figure 2.2), atnal slices (n=6/group) were subjected to various periods of aerobic incubation after an initial 30 min equilibration period. At the end of the experimental time, samples from the incubation media were taken for the assessment of LDH leakage and the slices were removed for the determination of oxygen consumption, tissue viability, nucleotide metabolite analysis and morphological examination. Study 2 was divided into two parts. In study 2A (Figure 2.3A), slices (n=6/group) were initially equilibrated for 30 min and then they were randomized to be subjected to various periods of ischaemia (30,60 and 120 min) followed by 120 min of rcoxygenation. In Study 2B (see Figure 2.313), the slices were (n=6/group) randomly subjected to an identical protocol of ischaernia and reoxygenation as that in Study 2A with the only exception being that they were incubated aerobically for 24 hr before they were subjected to ischaemia and reoxygenation. At the end of the experimental time, samples from the incubation media were taken for the measurement of LDH leakage and the slices were taken for the determination of tissue viability in both Study 2A and Study 2B. In addition, oxygen consumption of the slices was assessed in study 2A only. 39
30 nini FO linlin L 60 min 120 inin Equilibration Aerobic Incubation 7 240 min 360 min 12 lir Figure 2.2. Experimental protocols in Study 1. All groups were equilibrated for '10 min in aerobic conditions ( 37C). Following this, the right atrial slices (n=6/group) were further incubated aerobically for various time periods. Group I (Aerobic Control) Group 20 (Iscliacniia for 30 irdn) Group 3 (Ischacinia for 60 min) Group 4 (Ischaemia for 120 inin) 24 hr 48 fir inin 120 min 120 min Equilibration Ischaemia Rcoxygcnation Figure 2.3A. Experimental protocols for Study 2A. In Group 1, the slices were then incubated aerobically for 240 min. After 120 min, the incubation medium was changed and the slices were incubated for further 120 min. In Group 2,3) and 4, after equilibration, the slices were subjected to 30,60 and 120 min of ischaernia respectively and then subjected to 120 min reoxygenation. 40 I
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ISCHAEMIC PRECONDITIONING OF THE HU
Page 3 and 4:
ABSTRACT Ischaemic preconditioning
Page 5 and 6: andomised clinical study with the f
Page 7 and 8: CHAPTERI Introduction 35 Matefials
Page 9 and 10: Discussion 151 CHAPTER Vill Conclus
Page 11 and 12: 44 CK leakage and MTT reduction on
Page 13 and 14: The Wellcome Trust and The British
Page 15 and 16: Presentations International "The Ef
Page 17 and 18: Abbreviations An attempt has been m
Page 19 and 20: 1.1 Introduction Ischaernic heart d
Page 21 and 22: 1.2 Myocardial Ischaemia Myocardial
Page 23 and 24: hours up to several days to complet
Page 25 and 26: phosphates and its influence on hyd
Page 27 and 28: 1.4 Myocardial Protection This refe
Page 29 and 30: performed. This process is repeated
Page 31 and 32: 1.6 Possible Mechanisms of Ischaemi
Page 33 and 34: kilodalton stress proteins. These p
Page 35 and 36: and these proteins have been sugges
Page 37 and 38: K vi-1, channels were initially fou
Page 39 and 40: tissues the K.. %,.,, channels are
Page 41 and 42: Subsequently, Jaburek et al 1145] i
Page 43 and 44: venous capacitance vessels. At ther
Page 45 and 46: preconditioning to be investigated
Page 47 and 48: In the angioplasty model, Tomai et
Page 49 and 50: patients were randomized into two g
Page 51 and 52: CHAPTER 11 THE HUMAN RIGHT ATRIAL T
Page 53 and 54: inexpensive. Briefly in this model,
Page 55: of each ischemic period, slices wer
Page 59 and 60: In Study 3 (see Figure 2.4), slices
Page 61 and 62: D. Metabolite analysis Samples were
Page 63 and 64: leakage is calculated as the net LD
Page 65 and 66: B. Effect of the severity of ischae
Page 67 and 68: 2.11 DISCUSSION: The present studie
Page 69 and 70: clearly insufficient to induce myoc
Page 71 and 72: The present model may facilitate th
Page 73 and 74: 2.12 Conclusiow I have characterise
Page 75 and 76: 3.5 3 V 2.5 3: m Je m Z0 z 2 1.5 0.
Page 77 and 78: (3 3 2.5 a 1.5 - -r T 0 2 0.5 0 I P
Page 79 and 80: Q oro . 21 . 0 'a IP 10 '. R -C3 A
Page 81 and 82: =3 0 h X CD 0 x CD :3 0 , 7, CD 0 0
Page 83 and 84: CHAPTER III PRECONDITIONING THE HUM
Page 85 and 86: 3.2 MATERIALS AND METHODS-. 3.2.1 E
Page 87 and 88: A117'reduction- At the end of the e
Page 89 and 90: -4 ýi r. () .1 a 0 1 tli n F5* - C
Page 91 and 92: v M. %; n C) .0 ý U ý ý - - - -2
Page 93 and 94: leakage resulting from precondition
Page 95 and 96: 3.5 DISCUSSION: The present studies
Page 97 and 98: during cardiac surgery totalling 10
Page 99 and 100: different. The cellular mechanisms
Page 101 and 102: cn Je 8 7 6 5 4 1 0 0.8 0.7 0.6 0.5
Page 103 and 104: 8 6 C) 2 0.7 0.6 Q) 0.5 0) E 25 0.4
Page 105 and 106: 6 5 CY) ,u3 CF) m -ýe m 2 1 0 -0.8
Page 107 and 108:
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).
Page 201 and 202:
83. Downey JM, Liu GS and Thornton
Page 203 and 204:
97. Ganote C, Armstrong S and Downe
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110. Grover GJ, D'Alonzo A, Hess T,
Page 207 and 208:
122. Hamilton T and Weston A (1989)
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137. Hu H, Sato T, Seharaseyon J, L
Page 211 and 212:
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
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206. Maulik N, Yoshida T, Das DK. (
Page 221 and 222:
219. Miyawaki H, Zhou X, Ashraf, M.
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233. Okazaki Y, Kodama K, Sato H, K
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248. Pryzlenk K, Li G, Whittaker P
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260. Saito S, Tamura Y, Moriuchi M,
Page 229 and 230:
274. Schulz R, Post H, Valhaus C, e
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288. Stewart JR, Blackwell WH, Crut
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300. Tani M, Suganuma Y, Hasegawa H
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312. Tosaki A, Engelman DT, Engelma
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324. Walker D, Marber M, Walker J a
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337. Yamashita N, Nishida M, Hoshid
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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
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448 J. -G. Zhang and others 0.9 0.8
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450 J. -G. Zhang and others C E 07
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4S2 J. -G. Zhang and othen effects
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ELSEVIER Abstract Cardiovascular Re
Page 255 and 256:
936 S. Ghosh et al. / Cardiovascula
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938 S. Ghosh et al. / Cardiovascula
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940 S. Ghosh et al. [41 Goto M, Liu
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712 0" et &L h wcomMe geg in Obwa»
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714 Gbosb ot aL hmoo dmoWmbDbsnedH
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716 chmä et aL Pi unamOso äu In O
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718 ehe* et &L ditioning in the hum
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