Table of Contents
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LIST OF ABBREVIATIONS ... 6
GENERAL INTRODUCTION ... 9
1. Sepsis and septic shock ... 10
1.1. Definitions and epidemiology ... 10
1.2. Sepsis and organ dysfunction ... 10
2. Renal perfusion and metabolism in septic AKI ... 11
2.1. Definitions and epidemiology ... 11
2.2. Renal blood flow ... 11
2.3. Regional perfusion ... 12
2.4. Microcirculation ... 12
2.5. Renal metabolism ... 14
3. Renal autoregulation ... 15
3.1. Renal autoregulation in sepsis and septic shock ... 15
3.2. Renal autoregulation and vasopressor therapy ... 16
4. Summary and conclusions ... 17
HYPOTHESES ... 20
MATERIALS AND METHODS ... 22
1. General materials and methods ... 23
1.1. Anesthesia and ventilation ... 23
1.2. Surgical preparation ... 23
1.3. General experimental protocol ... 24
1.4. Systemic hemodynamics and general monitoring ... 24
1.5. Renal hemodynamics and kidney function ... 25
1.6. Assessment of renal cortex metabolism ... 25
1.7. Statistical analysis ... 27
2. Protocol-specific materials and methods ... 27
2.1. Kidney perfusion and renal cortex metabolism ... 27
2.2. Fenoldopam in experimental septic shock ... 28
2.3. Renal denervation in experimental septic shock ... 29
2.4. Renal autoregulation in experimental septic shock ... 29
KIDNEY PERFUSION AND RENAL CORTEX METABOLISM IN OVINE SEPTIC SHOCK ... 32
1. Introduction ... 33
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2.1. General hemodynamics and metabolism ... 34
2.2. Renal hemodynamics and metabolism ... 34
2.3. Renal function ... 37
3. Discussion ... 38
4. Conclusions ... 39
THE EFFECTS OF FENOLDOPAM ON RENAL FUNCTION AND CORTICAL METABOLISM IN OVINE SEPTIC SHOCK ... 41
1. Introduction ... 42
2. Results ... 43
2.1. General findings and systemic hemodynamics ... 43
2.2. Systemic metabolic variables ... 43
2.3. Sublingual microcirculation ... 44
2.4. Renal hemodynamics and metabolism ... 45
2.5. Renal function ... 47
3. Discussion ... 47
4. Conclusions ... 50
THE EFFECTS OF ACUTE RENAL DENERVATION ON KIDNEY PERFUSION AND METABOLISM IN OVINE SEPTIC SHOCK ... 51
1. Introduction ... 52
2. Results ... 53
2.1. General findings and systemic hemodynamics ... 53
2.2. Renal hemodynamics and metabolism ... 54
2.3. Renal function ... 57
3. Discussion ... 57
4. Conclusions ... 59
RENAL AUTOREGULATION IN EXPERIMENTAL SEPTIC SHOCK AND ITS RESPONSE TO VASOPRESSIN AND NOREPINEHRINE ADMINISTRATION . 60 1. Introduction ... 61
2. Results ... 62
2.1. General hemodynamics and kidney function ... 62
2.2. NE and AVP and general hemodynamics ... 62
2.3. Indices of renal autoregulation ... 64
3. Discussion ... 66
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GENERAL DISCUSSION ... 69
1. Renal perfusion in sepsis ... 70
1.1. Renal blood flow ... 70
1.2. Regional perfusion ... 71
1.3. Renal microcirculation ... 73
2. Renal metabolism in sepsis ... 75
3. Renal autoregulation in sepsis ... 76
4. Limitations ... 78
5. Summary and conclusions ... 80
ACKNOWLEDGEMENTS ... 82
PUBLICATIONS ... 84
6. Scientific publications ... 85
7. Scientific presentations ... 85
