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

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grafted for the same period and then reperfused for another 5-minutes betlore proceeding with bypass grafting. Patients with low ejection fractions (EF - 30`0, unstable angina, recent myocardial infarctions (-: I month), additional cardiac discascs, severc non-cardiac discascs, diabetcs, and (in mcdication that includcd ATP- dependent potassium channel (K,., i-p) openers were excluded The study %vas approved by the local ethics committee and all patients gave written informed consent to the study. Pre-operative characteristics of the patients are highlighted in Table 71 7 2.2 Operative Procedure Anaesthetic technique was standardized for all patients Anaesthesia vvas induced bN, fentanyl and maintained with enflurane in all patients All operations were perflormed through a median sternotomy and full heparinisation (3 mL,, Ik-_g Iv) CIIB was conducted with non-pul. %atile perfusion flow (2 2-2 4 I! mlmlm2) with ascending aomic cannulation and 2-staged venous cannulation and moderate systemic hypothermia (32'C). When cardiac arrest was achieved with cold blood (0 10-C) caudiople, 'j. 1, 1000 mL of the solution (composition in mmoUl. 16 61-1.0,2 CaCl_ 20 KCI, 147 NaCl. 1.0 procaine HCI, ph 7.40) was mixed with blood from the pump in a ratio of II and injected into the aortic root immediately afler aortic cross-claniping to obtain a myocardial temperature of 12'C to 15'C An additional dose of 500 nil. (it' cardioplegla . vas injected after 30min of ischaemia. In the group in which intermittent aortic cross-clamp fibrillation was used, reperfusion was carried out flor ., nunwe,; between each period One single distal coronai), ariM, anastomosis was performed Cý during each ischaernic period Proximal anastomosis were completed on the heatill- heart with aortic partial occlusion clamp in all groups 146
In the off-pump group, coronary bypass grafting was performed on the beating heart using the Octopus myocardial stabilisation device (Medtronic Inc) The suction cups were placed on the epicardial surface on either side of the artery to be grafted, with a suction pressure of no more than 600 mm Hg. Small coronary clamps %yere applied to proximal and distal to the site of the anastomosis with just enough pressure to occlude coronary flow and therefore allow grafting in a bloodless field They were released when the anastomosis was complete. The proximal anastomosis was performed using a partial occlusion aortic clamp. Ischaernic preconditioning was applied prior to the first dose of cardloplegia or immediately before the aortic cross application or the coronary artery Occlusion The use of a Khuri Tissue pli Analyser (Vascular Tech., Mass USA) showed that the pi I of the myocardium decreased from >7.3 to
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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
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 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: The apparent discrepancy bet,.,,, e
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
Page 203 and 204: 97. Ganote C, Armstrong S and Downe
Page 205 and 206: 110. Grover GJ, D'Alonzo A, Hess T,
Page 207 and 208: 122. Hamilton T and Weston A (1989)
Page 209 and 210: 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,
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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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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
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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
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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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