INVESTIGATIONS INTO HYPERLIPIDEMIA AND ITS POSSIBLE ...

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iii ABSTRACT Investigations into Hyperlipidemia and its Possible Associations with Pancreatitis in Dogs. (May 2011) Panagiotis Xenoulis, D.V.M., Aristotle University Chair of Advisory Committee: Dr. Jörg M. Steiner The relationship between hyperlipidemia and pancreatitis remains obscure in dogs. The aim of the present study was to investigate any possible association between hyperlipidemia and pancreatitis in dogs. In the first part of the study, Miniature Schnauzers with hypertriglyceridemia were found to have significantly higher serum cPLI concentrations than Miniature Schnauzers with normal serum triglyceride concentrations (P=0.0001). Also, Miniature Schnauzers with severe hypertriglyceridemia (>862 mg/dL) had 4.5 times higher odds (P=0.0343) for having a serum cPLI concentration consistent with pancreatitis. In the second part of the study, 17 Miniature Schnauzers prospectively enrolled with a history of pancreatitis were significantly more likely to have hypertriglyceridemia (71%) after resolution of pancreatitis than 34 age-matched Miniature Schnauzers without a history of pancreatitis (33%; odds ratio=5.02; P=0.0163). For the third part of the study, assessment of the feasibility and usefulness of a novel density gradient ultracentrifugation method using NaBiEDTA for lipoprotein profiling in dogs was attempted. Density gradient ultracentrifugation using NaBiEDTA
iv was found to be useful for the study of lipoprotein profiles in dogs. Significant differences were detected in the lipoprotein profiles (mainly involving TRL and specific LDL fractions) among healthy Miniature Schnauzers, dogs of various other breeds, and hypertriglyceridemic Miniature Schnauzers. In the fourth part of the study, the effect of a commercially available low-fat diet on serum lipid and pancreas-specific lipase (Spec cPL ® ) concentrations and lipoprotein profiles in Miniature Schnauzers with primary hypertriglyceridemia was evaluated. The study diet was found to be effective in significantly reducing serum triglyceride and cholesterol concentrations and changing the lipoprotein profiles of the dogs studied within 2 months. However, there was no significant effect of the study diet on serum Spec cPL concentrations. In the last part of the study, serum triglyceride and cholesterol concentrations and lipoprotein profiles were compared between dogs with naturally occurring pancreatitis and healthy dogs. The majority of dogs with naturally occurring pancreatitis had normal serum triglyceride and cholesterol concentrations. Important differences were identified in lipoprotein profiles between dogs with pancreatitis (higher LDL 2 , LDL 3 , and LDL 4 fractions and lower TRL, HDL 2a , and HDL 3c fractions) and healthy control dogs.
Page 1 and 2: INVESTIGATIONS INTO HYPERLIPIDEMIA
Page 3: INVESTIGATIONS INTO HYPERLIPIDEMIA
Page 7 and 8: vi ACKNOWLEDGEMENTS I would like to
Page 9 and 10: viii TABLE OF CONTENTS Page ABSTRAC
Page 11 and 12: x LIST OF FIGURES FIGURE Page 1 Cor
Page 13 and 14: xii FIGURE Page 20 1-dimensional sl
Page 15 and 16: 2 the results of these initial stud
Page 17 and 18: 4 and HDL 1 concentrations and a de
Page 19 and 20: 6 and, in smaller concentrations, L
Page 21 and 22: 8 HDL molecules can be further subd
Page 23 and 24: 10 reach the vasculature, they acqu
Page 25 and 26: 12 Endocrine disease Most commonly,
Page 27 and 28: 14 with varying frequencies in dogs
Page 29 and 30: 16 hypercholesterolemia was found o
Page 31 and 32: 18 Primary hyperlipidemia with hype
Page 33 and 34: 20 Atherosclerosis Although dogs ap
Page 35 and 36: 22 Dietary management Typically, th
Page 37 and 38: 24 therapy when the latter fails to
Page 39 and 40: 26 followed from the 1970s until to
Page 41 and 42: 28 this theory, zymogen granules th
Page 43 and 44: 30 be quite different, especially i
Page 45 and 46: 32 Drugs As in humans, drug-induced
Page 47 and 48: 34 Signalment Dogs of any age, bree
Page 49 and 50: 36 erroneously direct the clinician
Page 51 and 52: 38 of changes over time in serum Sp
Page 53 and 54: 40 they have been shown to have a l
Page 55 and 56:
42 revealed either a normal pancrea
Page 57 and 58:
44 At present, a definitive diagnos
Page 59 and 60:
46 factors should always be investi
Page 61 and 62:
48 associated pancreatitis is much
Page 63 and 64:
50 clear whether hyperlipidemia was
Page 65 and 66:
52 hepatobiliary disease in both Mi
Page 67 and 68:
54 the reference range, while Group
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56 ROC analysis and calculation of
Page 71 and 72:
58 Figure 3. Serum cPLI concentrati
Page 73 and 74:
60 There was no significant differe
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62 severe (typically ≥1,000 mg/dl
Page 77 and 78:
64 gastrointestinal signs or suspec
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66 CHAPTER III SERUM TRIGLYCERIDE C
Page 81 and 82:
68 logical assumption that a defect
Page 83 and 84:
70 pancreatitis. For the same reaso
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72 Spec cPL concentrations were mea
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74 were significantly more likely t
Page 89 and 90:
76 Figure 5. Comparison of serum tr
Page 91 and 92:
78 Figure 7. Comparison of serum tr
Page 93:
80 pancreatitis as it cannot be pre
Page 96 and 97:
83 Although serum cholesterol conce
Page 98 and 99:
85 Footnotes a Spec cPL ® , IDEXX
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87 several subfractions, with diffe
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89 Miniature Schnauzers (Group 2) T
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91 Assays Serum triglyceride (refer
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93 Figure 8. Custom-built fluoresce
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95 range HDL 1 has not been accurat
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97 mg/dL) were significantly higher
Page 112 and 113:
99 Figure 10: Serum cholesterol con
Page 114 and 115:
101 (Eigenvalues=0.5455; P=0.00017;
Page 116 and 117:
103 Figure 12: Representative lipop
Page 118 and 119:
105 Figures 14A and 14B: Representa
Page 120 and 121:
107 Specifically, 97% of non-hypert
Page 122 and 123:
109 The fraction of TRLs was a sign
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111 Schnauzers without hyperlipidem
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113 Footnotes a Roche/Hitachi MODUL
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115 The biochemical, metabolic, and
Page 130 and 131:
117 Study design Each one of the do
Page 132 and 133:
119 Questionnaires and consent form
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121 a target intensity of 30%, and
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123 might affect lipid metabolism (
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125 Figure 16. Serum triglyceride c
Page 140 and 141:
127 Figure 18. Serum Spec cPL conce
Page 142 and 143:
129 Figure 19. 1-dimensional sliced
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131 Dogs that did not respond to th
Page 146 and 147:
133 Hypertriglyceridemia has been l
Page 148 and 149:
135 degrees. One possible explanati
Page 150 and 151:
137 Footnotes a Royal Canin Gastroi
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139 concentrations and lipoprotein
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141 inclusion criteria for the stud
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143 light source j , located in a d
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146 Serum triglyceride and choleste
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148 Figure 22. Serum triglyceride c
Page 163 and 164:
150 Figure 24. 1-dimensional sliced
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152 Discussion The purpose of the p
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154 fraction of these dogs (about 3
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156 of lipoproteins might also have
Page 171 and 172:
158 Footnotes a Roche/Hitachi MODUL
Page 173 and 174:
160 the etiology of pancreatitis, b
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162 times (P=0.0343) for a serum cP
Page 177 and 178:
164 peaks than dogs of other breeds
Page 179 and 180:
166 19.3; 95% CI, 2.0-184.0; P=0.00
Page 181 and 182:
168 4) Specific lipoprotein classes
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170 REFERENCES 1949;8:96-97. 1. Lew
Page 185 and 186:
172 17. Whitney MS, Boon GD, Rebar
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174 33. Ford RB. Clinical managemen
Page 189 and 190:
176 50. Nelson RW, Turnwald GH, Wil
Page 191 and 192:
178 66. Williams DA, Steiner JM. Ca
Page 193 and 194:
180 82. Yilmaz Z, Senturk S. Charac
Page 195 and 196:
182 97. Fojo SS, Stalenhoef AF, Mar
Page 197 and 198:
184 111. Lam CW, Yuen YP, Cheng WF,
Page 199 and 200:
186 127. Crispin SM. Ocular manifes
Page 201 and 202:
188 144. Lindsay S, Entenmann C, Ch
Page 203 and 204:
190 161. Steiner JM. Canine pancrea
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192 176. Steiner JM, Teague SR, Wil
Page 207 and 208:
194 191. Steiner JM. Diagnosis of p
Page 209 and 210:
196 208. Talukdar R, Vege S. Recent
Page 211 and 212:
198 224. Koch K, Drewelow B, Liebe
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200 241. Petrov MS, van Santvoort H
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202 258. Ewald N, Hardt PD, Kloer H
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204 274. Otvos JD, Jeyarajah EJ, Be
Page 219 and 220:
206 289. Carpentier YA, Scruel O. C
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