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

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Table 7.2 - Patients haemod-v-namic data. Variable Grou V a, - PS 7 Pre-operative X-clamn RCP HR Mean MAP (mmHg) CVP (mmHg) Mean PAP (mmHg) PCWI' (mmHg) (A PVRI SVRI (L)m2permin) (dvn/%, --c/cm5, m2) -PC 68.412.7 71. R+5.7 10.3f-0.8 20.4+1.1 5.8+2.1 2.8+0.2 1(),; + 11 1Wt 102 ýPc 75.8+2.3 69.4+3.5 9.8±2.1 19.4 t 5.2 6.4 13.9 2.4 t 0.4 182 t 20 160203 -PC 59.40.4 65.7f6.9 7.8+5.7 22.616.4 5.1 t 2.6 2.9tO. 4 201 t 13 1497 t 11 , PC 65.1 t 6.8 70.2 12.1 9.1 t 2.4 2 5.1 f 9.3 7.4 t 1.1 1.05to. 19 215! 25 1629! 98 Off-purnp -PC 52.412.9 59.8t8.7 5.6f22 15.9fil. 4 9.3tl. 5 2.52tO. 54 156t12 1307-109 4 Pc 49.50.7 61.4ill. 2 6.7±4.1 21.7t4.8 5.7t2.8 2.74tO. 29 168t25 1567 t 63 I hr post-termination of Ischnemia X -cýp 10 1.3+ -PC 1.9 65.4t4.7 9.4+12 18.1 t2.7 10.4 t 1.3 2.50 t0 11 217t2O 2(X) I1 52 . -, - PC 95.6+2.4 59.4+7.2 1 l212.7 22.4 ý- 5.1 8.5-2,1 2. (16*0.28 271,16 1050*11; 7 BCP Ofl-pumv -PC 99.8+10.4 71,2+5.9 8.6-0.5 16A+6.9 11.3 t 1.4 2.76 t 0.22 301 t27 2100-554 + PC 92.7+4.9 64.8 t 6.8 10.2+2.9 21.9+2.4 9.4 t 3.9 2.98+0.15 . 15,7t 12 1 X)3 t 261 -PC 105.5 16.5 7 5.4 t 8.7 11.6 13.9 24.7 19.4 12.1 t 2.6 2.02 t 0.26 298 t 21 1506t23 + PC 112.2+9.2 77.6±6.2 13.5-0.7 19.7-0.1 10.5 1 1.1 2.43 t 0.18 312 t 12 1709t 141 3 hours post-termination of Ischaemin Vcbn RCP ()IT-Pqw -PC 92.4111.5 67.5 15.9 7.7 t 3.2 20.9 t 5.2 11.9 t 6.4 4 PC 84.2+12.7 71.8+11.8 9.2+2.7 19.8 13.4 9.7 t 2.9 -PC 953f 15.1 67.8+11.9 9.8 t 2.4 2 3.7 t 6.8 102 t 1.9 . PC 105.3 124.9 7 7.4 t 4.9 10.7 t 3.1 2 2.7 t 3.6 11.6 t 2.7 -PC 79.5 t 12.9 71.51 12.7 9.4 12.5 21.912.7 8.4 t 2.5 +PC 86.7il4.7 75. lt8.3 7.9t4.2 26.4-t 5.9 9.6 11.6 24 hours post-termination of Ischaemia X -c imp H(T ()tITYMP -PC 61.5 t 6.4 62.7 t 2.9 6.4 t: 2.9 19.2 t 2.7 5.8 t 2.3 + PC 72.9 f 5.8 58.4t9.1 7.6+6.1 16.7t4.9 10.4 f 1.7 -PC 77.9t9.6 61.9t4.6 5.4 t 3.8 21.6 t 5.8 92 t 1.5 +PC 75.4-t 113 71.3+6.1 7.8+1.6 24.9 i 1.1 4.6: 2.8 -PC 91.6-8.7 88.1 f 53 4.410.8 19.6 t 4.6 7.8 t 3.8 ý PC 84.3 t 10.4 90.1 Q. 8 6.8t 1.7 2 3.3 t 3.3 102 t 1.4 2.52 t 0.3 8 250t 17 1954,100 2.2 1t0.2 7 291 ! 67 2304! 328 2.64t0.12 333 t 29 1796 t 447 2.57 t 0.2 5 401 t 46 1667 t 169 2.11 10.15 412 t 29 1509t225 2.92 t 0.26 368t36 1882! 203 2.96 t0 26 208t22 1804t234 2.35 t 0.36 214t50 20N t 102 2.5 5t0.46 289t16 1620198 3. ) 9t0.53 295 t 26 1492. -207 2.46 t 0.34 312t28 1623t115 2.89t0,41 256 t 33 2 (KM t 204 IICP blood cardioplegia, CI cardiac index, CVP central venous pressure, IIR heart rate: MAP mean arterial pressure: PAP pulmonary artery pressure, PCWII pulmonary capillary wedge prc%sure, PVRI pulnionarN%ascularrt: %i%tiuiceiiide-k. WRI systemic vascular resistance index. Data are expressed as mean t standard deviation. 157
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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
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 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: myocardium. Several investigators [
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,
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
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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
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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
Page 239 and 240:
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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