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

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human myocardium However, atria] and ventricular myocardiurn possess characteristics of their own that may influence the susceptibility to ischaemia/reperfusion injury and as a consequence results from one may not be applicable to the other. Thus, for example, the reported differences in the distribution of potassium channels [5,132], which contribute to the charactenstic differences between atrial and ventricular action potentials, may determine a different response to ischaemia/reperfusion. Undoubtedly, KATpchannels are present in both atnurn and ventricle [1321, although their density in both tissues is unknown. It must also be mentioned that the preparation is superfused ("simulated ischaemia") as opposed to being artenally perfused and simulated ischaernia is achieved by removal of oxygen and blocking glycolytic ATP production with 2-deoxyglucose. This results in metabolic conditions within the myocardium that may be different than that which occurs in the myocardium during clinical ischaernia. Another possible limitation might be that right atrial appendages were obtained from patients subjected to various medical treatments (e. g. nitrates, P-blockers, calcium antagonists) and that in principle may have influenced ischaemia/reperfusion injury and the protection induced by preconditioning. However, it should be emphasized, that all medication was stopped the day before surgery when specimens were taken for the study and that significant effect of the medication was unlikely since all preparations responded to ischaemia/reperfusion with a similar degree of injury. It should be mentioned that the preparation used in this study was not electrically stimulated (i. e. non-beating) and therefore one should be cautious when extrapolating to the in vivo situation. 127
5.7 Conclusion Preconditioning is a potent protective intervention which use has been advocated in clinical situations such as angioplasty and cardiac surgery. The results of my studies have obvious clinical implications in that preconditioning cannot be beneficial to patients with NIDD and IDD and those with cardiac failure. They also show that in the failing heart a similar degree of protection to that seen with preconditioning can be obtained by the administration of a selective opener of mito K,,, Tpehannels, an intervention that is not effective in diabetics 128
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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
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
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: absence of uniformity of expeniment
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 and 152: 6.1 INTRODUCIFION' Life expectancv
Page 153 and 154: (MI-T) to blue t'()rmazan product C
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
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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
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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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260. Saito S, Tamura Y, Moriuchi M,
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274. Schulz R, Post H, Valhaus C, e
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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
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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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