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

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demonstrated in the aged sheep hearts 1208] but it has been questioned in the aged myocardiurn ofthe rat 1248, MII and rabbit 1411 heart The aims of this study %%ere 0) to determine the effect of age on the tolerance of the human myocardium to ischaemia and (11) to investigate whether age affects the protection afforded by Ischaernic preconditioning 6.2 METHODS 6.2. / 1-. ', clx, rimt, iiiiill)rt-lkzr(itioti Experiments were performed on myocardium obtained from the right atnal appendage , open heart surgery as described of 90 patients underv oing in previous chapters. , Experiments were performed as described in section 23 (Chapter 2). 6.2.2 Solun(om The incubation medium was prepared daily as described in section 2.3 (Chapter 2) 6.2.3 1-. '., cl), t, rimt, iiiiill)rotot-oI After sectioning the atnium, the preparations were allowed to Stabilise for 30min and then randomly allocated to one of the following group& (i) aerobically incubated for 210min to serve as aerobic time matched controls, (n) simulated ischaernia for a period of 90min followed by 120min of reoxygenation, and (iii) ischaernic preconditioning induced by Smin ischaemia/5min reoxygenation immediately before the 90min ischaernia Patients were divided by age into three different groupsý between 30-49 (n - 12), 50-69 (n-48) and 70-90 (n-30) years old. 6.2.4 Asse. v. vment (? f us-vue mlijrý, aml wahihýy: At the end of each experimental protocol, tissue injury was determined by measuring the leakage of creatinine kinase (CK) into the incubation medium and tissue viability by the reduction of 3-14,5-Dimethylthiazol-2-yll-2,5 diphenyltetrazolium bromide 135
(MI-T) to blue t'()rmazan product CK Letikage I he actP* ity ofCK leakage into the media during the reoxygenation perilod (I', g, wet w-t) was assaved as described in section 3.6B (Chapter 3). A117 rechiction At the end of the experimental time, MTT analysis was performed as described in section 2 OB (Chapter 2) and the results expressed as mmol/g wet wt 6.2.5 Stalivicalanahkvi All data are presented as mean +SD ANOVA was used for multiple comparisons with application of a post hoc Tukey's test Linear regression analysis was used where appropnate Statistical siv 'fi mi icance was taken as p--0.05. 6.3 RESULTS Table 61 shows that the demographic data and the nsk factors were similar in the three age groups Figures 6.1 A and 6.1 B show that simulated ischaemia/reoxygenal Ion resulted in significant Increases in CK leakage and decreases in MTT reduction that were similar in all three age groups. They also show that ischaemic preconditioning afforded similar protection in all age groups. The linear regression analysis shown in Figures 6.2A and 6.213 clearly demonstrates that the degree of' ischaemic injury and the protection obtained with ischaernic preconditioning does not change with increasing age. 136
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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
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
Page 109 and 110: It has been reported that K.. %-I-p
Page 111 and 112: 0 a- I a 3 I cr =r Cl. 2 qQ 0'-ý 0
Page 113 and 114: Figure 4.7 shows that ischaemia alo
Page 115 and 116: Figure 4.2 Dosc-responsc experiment
Page 117 and 118: Figure 4.4 Dose-response experiment
Page 119 and 120: Figure 4.6 Dosc-response experiment
Page 121 and 122: 1 0.9 -ý 0.8 0.7 E 0.6 0.5 0.4 0.2
Page 123 and 124: activity, and showed that diazoxide
Page 125 and 126: Furthermore, Van den Hoek et al [3
Page 127 and 128: mechanism by which the opening of m
Page 129 and 130: 5.1 INTRODUCTION: Within the enormo
Page 131 and 132: 5.2 MATERIALS AND METHODS: 5.2.1 Ex
Page 133 and 134: M77'rechiction: At the end of the e
Page 135 and 136: oc 0 0 cr F; * 10 eb I ý; o I 5 0
Page 137 and 138: Pages missing original in the
Page 139 and 140: esulted in a decrease of CK leakage
Page 141 and 142: are on long-term hypoglycaernics or
Page 143 and 144: absence of uniformity of expeniment
Page 145 and 146: 5.7 Conclusion Preconditioning is a
Page 147 and 148: 0.9 0.8 07 m 0.6 E -0 0t 4 0.3 02 0
Page 149 and 150: -0 1.2 1 &8 0.6 04 0.2 o Aerobic Is
Page 151: 6.1 INTRODUCIFION' Life expectancv
Page 155 and 156: The demonstration that ischaemic in
Page 157 and 158: Table 61 Patients' demographic and
Page 159 and 160: Nure 6,1: Creatine Kinase (CK) leak
Page 161 and 162: CHAPTER VII IN VIVO STUDIES ON T"E
Page 163 and 164: The apparent discrepancy bet,.,,, e
Page 165 and 166: In the off-pump group, coronary byp
Page 167 and 168: eduction as described in section 3.
Page 169 and 170: 7.4.2 In vitro studies Figures 7.3A
Page 171 and 172: preconditioning stimulus in man is
Page 173 and 174: myocardium. Several investigators [
Page 175 and 176: Table 7.2 - Patients haemod-v-namic
Page 177 and 178: (0 -I 3 CD CD CD 1 3 0 :3 0 0 =r w
Page 179 and 180: 0 co t X 3 co 0 0 Cumulative Releas
Page 181 and 182: -& a) c) UT 0 =r w CD 3 CD 0 1ý (a
Page 183 and 184: When ischaernic preconditioning was
Page 185 and 186: evidence tbr the involvement ot'PKC
Page 187 and 188: institution o fcardiopu Imo nary by
Page 189 and 190: Biblioqraphv 1. Abete P, Ferrara N,
Page 191 and 192: 14. Auchampach J, Cavero, I and Gro
Page 193 and 194: 27. Becker LB, Van den Hoek TLV, Sh
Page 195 and 196: 41. Bums PG, Krunkenkamp IB, Calder
Page 197 and 198: 55. Cohen G, Shirai T, Weisel RD, e
Page 199 and 200: 69. Currie RW and White FP (1983).
Page 201 and 202: 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
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164. Kelpzig H, Kobert G, Mafter C,
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178. Lamping K, Christensen C, Pelc
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192. Liu GS, Thornton J, Van Winkle
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206. Maulik N, Yoshida T, Das DK. (
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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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337. Yamashita N, Nishida M, Hoshid
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351. Zhang JG, Lindup WE. (1993). R
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444 J. -G. Zhang and others are dif
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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
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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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