Advances in Pharmacology: Anesthesia and Cardiovascular Disease By Zeljko J. Bosnjak
Publisher: Academic Pr
Number Of Pages: 688
Publication Date: 1995-04
ISBN-10 / ASIN: 0121188604
ISBN-13 / EAN: 9780121188603
Product Description:
Each volume of Advances in Pharmacology provides a collection of reviews on various topics. Volume 31 deals with the mechanisms of anaesthetic actions under normal conditions as well pathophysiologic states.
Preface
The purpose of this book is to emphasize the close relationship and
interdependence between anesthesiology and physiology, especially in
the area of cardiovascular function. This book represents some of the
most recent experimental observations and hypotheses with emphasis on
the cardiovascular effects of anesthetics and the mechanisms that may be
involved in normal and pathophysiological states.
Many patients anesthetized for surgical procedures under general anesthesia
have some degree of cardiovascular disease. Sadly, knowledge of
how anesthetics and drugs used during anesthesia contribute and/or interact
with altered physiological states that are responsible for cardiovascular
instability is far from complete. Although there are a number of likely
causes for perioperative cardiovascular morbidity, noteworthy among
these are the involvement of altered physiological states, autonomic imbalance,
altered stress responses, concurrent disease, and factors that directly
relate to the quality or type of care provided in the perioperative setting.
Many of the drugs commonly used during general anesthesia, including
the inhalational anesthetics, alter cardiovascular regulation as a side effect
of their primary purposes to produce surgical anesthesia.
The cardiovascular depressant properties of potent volatile anesthetics
are due not only to their direct effects on the heart and peripheral circulation
but also to their depressant effects on reflex regulation of the cardiovascular
system. There is a considerable body of evidence that the inhibitory
effects of potent volatile anesthetics occur at multiple sites. These
include central nervous system (CNS) regulatory sites, sympathetic preganglionic
and postganglionic sites, sympathetic and parasympathetic ganglionic
transmission sites, and the nerve endings, as well as direct end
organ effects. Although the depression of the cardiovascular system at
anesthetic levels required for surgical anesthesia is usually moderate and
reversible in healthy patients, it may be much more extensive in patients
with either chronic or acute disorders of the cardiovascular system, as
well as associated diseases which may impair cardiovascular function.
Many of the topics in this book deal with effects of anesthetics in the
presence of altered physiological states including myocardial ischemia,
diastolic dysfunction, hypertension, respiratory distress syndrome, acidosis,
cerebral injury, and isovolemic hemodilution. It is not surprising that
the anesthesiologist is faced with increased challenges to provide safe
anesthesia for complex surgical procedures especially in these groups of
patients. It is imperative, therefore, that we gain a better understanding
xxix
xxx Preface
of not only normal cardiovascular function but also the mechanisms by
which the volatile anesthetics interfere with disorders of the cardiovascular
system and associated diseases.
It is hoped that this book will in part contribute to a better understanding
of the ways in which the potent anesthetics alter cardiac function in order
to provide a more rational basis for therapeutic interventions and as a
guide in choosing anesthetic approaches which are more likely to provide
the level of anesthesia required for surgery with the least disturbance in
the cardiovascular regulation. The 42 chapters in this book are organized
into six parts covering ( 1 ) cardiac muscle, (2) coronary circulation,
(3) cellular targets, (4) reflex regulation, ( 5 ) peripheral circulation, and
(6) cerebral circulation.
The book begins with a section that deals primarily with the basic
cardiac effects of anesthetics and provides information on the normal
and ischemic processes controlling or affecting cardiac function. Part I1
focuses on the effects of volatile anesthetics on coronary circulation and
presents data obtained from in situ experiments, isolated coronary rings,
and isolated single smooth muscle cells including single-channel recordings.
Part I11 addresses the various effects of anesthetics on specific
cellular targets. Part IV examines the effects of anesthesia on reflex regulation
along with the major circulatory effects of chronic hypertension.
Part V focuses on the effects of anesthetics on the peripheral circulation
including pulmonary vascular regulation. The effects of nitric oxide in
the adult respiratory distress syndrome and other lung diseases are also
reviewed. Part VI deals with anesthetic effects on cerebral circulation
along with cerebral reperfusion injury.
It is our hope that future work will lead to further understanding of basic
mechanisms of the interaction between anesthetics and cardiovascular
disorders and a greater appreciation of the therapeutic and pathophysiological
implications of these mechanisms.
The editors thank all the contributors for providing their own original
presentation and interpretation of the data. We gratefully acknowledge
the excellent secretarial support of Anita Tredeau and her superb care in
coordinating the editorial phases of publication. We also thank Criticare
Systems, Inc., for generous support. The editors also express profound
gratitude to Jasna Markovac, the Biomedical Sciences Editor of Academic
Press, for help in overseeing production of this book.
Zeljko J . Bosnjak
John P . Kampine
Contents
Contributors xxi
Preface xxix
Part I
Cardiac Muscle
Regulation of the Calcium Slow Channels of Heart by Cyclic
Nucleotides and Effects of Ischemia
Nicholas Sperelakis
I. introduction 1
11. Types of Calcium Channels 2
111. Cyclic AMP Stimulation of Slow Calcium Channels
1V. Phosphorylation Hypothesis 7
V. Protein Kinase A Stimulation 9
VI. Cyclic GMP Inhibition of Slow Calcium Current
VII. Protein Kinase G Inhibition 14
VIII. Inhibition by Muscarinic Agonists 16
6
9
IX. Protein Kinase C and Calmodulin Protein Kinase 18
XI. Direct Stimulation of Slow Calcium Channels by G, Proteins and
/?-Receptors 20
References 2 1
X. Comparison with Vascular Smooth Muscle and Skeletal Muscle 18
XII. Summary 20
Functional Adaptation to Myocardial Ischemia: Interaction
with Volatile Anesthetics in Chronically Instrumented Dogs
Patrick F. Wouters, Hugo Van Aken, Marc Van de Velde,
Marco A. E. Marcus, and Willem Flameng
1. Introduction 25
11. Chronic Instrumentation and Monitoring 26
111. Effects of Ischemic Preconditioning on Functional Recovery from
Stunning in Conscious Dogs 29
IV. Discussion 31
References 36
V
vi Contents
Excitation-Contraction Uncoupling and Vasodilators for
Long-Term Cold Preservation of Isolated Hearts
David F. Stowe
I. Introduction 39
11. Long-Term Cardiac Perfusion 42
111. Preservation of Isolated Hearts 46
A. Atrial Rate, Atrial-Ventricular Conduction, and
B. Left Ventricular Pressure and Cardiac Efficiency
C. Coronary Flow and Oxygen Extraction
D. Responses to Vasodilators 51
IV. Discussion 54
References 59
Cardiac Rhythm 46
47
49
Troponin T as a Marker of Perioperative Myocardial
Cell Damage
H. Machler, H. Gombotz, K. Sabin, and H. Metzler
I. Introduction 63
11. Cardiac Troponin 64
111. Troponin T in Coronary Artery Bypass Patients with
IV. Troponin T versus Conventional Markers of Myocardial Cell Damage in
Unstable Angina 65
Perioperative Settings 70
References 72
V. Summary 71
Silent Myocardial Ischemia: Pathophysiology and
Perioperative Management
Anders G. Hedman
I. Introduction 75
A. Type I Silent Myocardial Ischemia
B. Type I1 Silent Myocardial Ischemia
C. Type 111 Silent Myocardial Ishemia
A. Global Deficiency in Pain Perception
B. Anatomic Changes in Pain Receptors and Nerves
C. Quantitative Theory of Silent Myocardial Ischemia
75
76
76
11. Pathophysiology of Silent Myocardial Ischemia
76
76
77
77
111. Detection of Silent Myocardial Ischemia 79
Contents vii
1V. Which Laboratory Methods Should Be Used for
Screening Purposes? 80
A. Exercise Stress Test 80
B. Thallium-201 Dipyridamole Myocardial Imaging
C. Ambulatory Long-Term Electrocardiographic Monitoring of
V. Perioperative Medical Management of Silent Myocardial Ischemia
8 1
ST Segment 81
82
A. Nitrates 84
B. a-Adrenergic Blockers 84
C. p-Adrenergic Blockers 84
D. Calcium Antagonists 84
E. Surgery and Angioplasty 85
References 85
VI. Summary 85
Effect of Halothane on Sarcolemmal Calcium Channels
during Myocardial Ischemia and Reperfusion
Benjamin Drenger, Yehuda Ginosar, and Yaacov Gozal
11. Canine Model for Myocardial Ischemia and Reperfusion
I . Introduction 89
90
111. Isolation of Sarcolemma-Enriched Preparation
IV. Binding Capacity of Isradipine 92
92
V. Summary 95
References 95
Myocardial Ischemic Preconditioning
Donna M. Van Winkle, Grace L. Chien, and Richard F. Davis
1. Introduction 99
11. Myocardial Ischemia 100
Ill. Effects on Infarct Size 103
IV. Discussion 106
References 107
Effects of Hypoxia/Reoxygenation on lntracellular Calcium
Ion Homeostasis in Ventricular Myocytes during
Halothane Exposure
Paul R. Knight, Mitchell D. Smith, and Bruce A. Davidson
I. Introduction 109
11. Intracellular Calcium Measurements I 1 1
A. Preparation of Ventricular Myocytes
B. Measurement of Intracellular Calcium-Ion Concentration 1 12
1 1 1
viii Contents
111. Effects of Hypoxia, with or without Halothane, on
IV. Effects of Hypoxia, with or without Halothane, on
Myocyte Morphology 113
Intracellular Calcium 114
Calcium Transients 116
Calcium Transients 117
VII. Discussion 117
References 122
V . Effects of Hypoxia, with or without Halothane, on Electrically Induced
VI. Effects of Hypoxia, with or without Halothane, on Caffeine-Induced
Mechanical Consequences of Calcium Channel Modulation
during Volatile Anesthetic-Induced Left Ventricular Systolic
and Diastolic Dysfunction
Paul S. Pagel and David C. Warltier
11. Materials and Methods 127
I . Introduction 125
A. Nifedipine 127
B. Bay k 8644 128
C. Calculation of Indices of Systolic and Diastolic Left
D. Statistics 130
Ventricular Function 129
111. Effects of Anesthetics and Calcium Channel Modulation 130
IV. Discussion 135
References 139
Anesthetic Actions on Calcium Uptake and Calcium-
Dependent Adenosine Triphosphatase Activity of Cardiac
Sarcoplasmic Reticulum
Ning Miao, Martha J. Frazer, and Carl lynch 111
I . Introduction 145
11. Sarcoplasmic Reticulum 147
A. Preparation of Cardiac Sarcoplasmic Reticulum
B. Calcium Uptake Measurement 148
C. Phosphate Production Measurement 149
D. Reagents and Anesthetic Administration
147
149
Ill. Calcium Uptake and ATPase Activity
IV. Discussion 156
150
A. Control Behavior 157
B. Anesthetic Effects 159
References 162
Contents ix
Interaction of Anesthetics and Catecholamines on Conduction
in the Canine His-Purkinje System
Lawrence A. Turner, Sanja Vodanovic, and Zeljko J. Bosnjak
1. Introduction 167
11. Catecholamine-Anesthetic Interaction 168
111. Summary 180
References 18 1
Anesthetics, Catecholamines, and Ouabain on Automaticity
of Primary and Secondary Pacemakers
John L. Atlee 111, Martin N. Vicenzi, Harvey J. Woehlck,
and Zeljko J. Bosnjak
1. Introduction 185
11. Isolated and Chronic Atrial Preparations 186
A. Canine Right Atrial Preparation 187
B. Chronically Instrumented Dogs 188
A. Canine Right Atrial Preparation 190
B. Chronically Instrumented Dogs 193
A. Experiments in Isolated Hearts 198
B. Experiments in Intact Hearts
111. Anesthetic Interactions with Ouabain and Catecholamines 190
IV. Discussion 197
200
V. Conclusions 203
V1. Future Directions 203
References 203
The Role of L-Type Voltage-Dependent Calcium Channels in
Anesthetic Depression of Contractility
Thomas J, J. Blanck, D. L. lee, S. Yasukochi, C. Hollmann,
and J. Zhang
I. Introduction 207
11. Isolated Heart Preparation 210
Ill. Effects of Anesthetics on Isradipine Binding 21 1
IV. Discussion 213
References 2 14
X Contents
Effects of Inhibition of Transsarcolemmal Calcium Influx on
Content and Releasability of Calcium Stored in Sarcoplasmic
Reticulum of Intact Myocardium
Hirochika Komai and Ben F. Rusy
I. Introduction 215
11. Isolated Papillary Muscle Preparation 216
Ill. Calcium Influx and Release 216
IV. Discussion 220
References 220
Arrhythmogenic Effect of Inhalation Anesthetics: Biochemical
Heterogeneity between Conduction and Contractile Systems
and Protein Unfolding
lssaku Ueda and Jang-Shing Chiou
1. Introduction 223
11. Cyclic AMP and the Conduction System 224
111. Myocardial Sensitizing Agents and Phosphodiesterase
IV. Mode of Anesthetic-Protein Interaction 226
VI. Specific Binding: Lack of Definition
225
V. Unfolding of Proteins 228
231
References 232
Part II
Corona ry Ci rcu la tio n
Potassium Channel Current and Coronary Vasodilatation by
Volatile Anesthetics
Nediljka Buljubasic, Jure Marijic, and Zeljko J. Bosnjak
I. Introduction 235
11. Isolated Vessel Ring Experiments 236
111. Patch Clamp Experiments 238
IV. Effects of Anesthetics on Isolated Coronary Vessels 239
V. Effects of Anesthetics on Whole-Cell Potassium Current 241
V1. Effects of Anesthetics on Single Potassium Channel Current 243
VII. Discussion 248
References 25 1
Contents xi
Potassium Channel Opening and Coronary Vasodilation
by Halothane
D. R. Larach, H. G. Schuler, K. A. Zangari, and R. L. McCann
1. Introduction 253
11. Isolated Coronary Vessel Preparation 254
111. Effects of Endothelin 258
IV. Effects of Methacholine 260
A. Endothelium-Denuded Rings 260
B. Endothelium-Intact Rings 261
V. Effects of Potassium 263
VI. Discussion 263
References 266
Volatile Anesthetics and Coronary Collateral Circulation
Judy R. Kersten, J. Craig Hartman, Paul S. Pagel,
and David C. Warltier
I . Introduction 269
11. Chronic Animal Instrumentation 270
111. Regional Myocardial Function and Perfusion
IV. Coronary Steal Prone Anatomy Model
V. Hemodynamic Effects of’ Isoflurane, Sevoflurane, and Adenosine
VI. Regional Myocardial Perfusion: lsoflurane, Sevoflurane,
271
273
275
and Adenosine 278
VII. Discussion 280
References 283
Myocardial Oxygen Supply-Demand Relations during
lsovolemic H emod ilution
George J. Crystal
1. Introduction 285
11. Experimental Studies 286
A. Limit to Cardiac Compensation during lsovolemic Hemodilution:
Influence of Coronary Stenosis 286
B. Comparison of Effects of lsovolemic Hemodilution in Right and
Left Ventricles 300
C. Cardiac Effects of Combined Isovolemic Hemodilution and
Controlled Hypotension 308
111. Summary 311
References 3 1 I
xii Contents
Part I I I
Cellular Targets
Plasma Membrane Ca2 -ATPase as a Target for
Volatile Anesthetics
Danuta Kosk-Kosicka
1. Introduction 313
11. Isolation and Activity Assay of CaZt-ATPase 315
111. Effects of Anesthetics 316
IV. Discussion 320
References 32 1
Enhancement of Halothane Action at the Ryanodine
Receptor by Unsaturated Fatty Acids
Jeffrey E. Fletcher and Vincent E. Welter
I. Introduction 323
11. Calcium Efflux 324
111. Calcium Release from Heavy Sarcoplasmic Reticulum Fraction
A. Effects of Fatty Acids in Absence of Halothane in Rat
B. Interaction between Fatty Acids and Halothane in Rat
C. Displacement of Fatty Acids from Binding Sites
325
Cardiac Muscle 325
Cardiac Muscle 325
by Halothane 326
IV. Discussion 328
References 330
Adrenergic Receptors: Unique Localization in Human Tissues
Debra A. Schwinn
I. Introduction 333
11. Methods Used to Study Receptor Distribution 337
111. Localization of Receptors in Human Tissue
IV. Summary 340
338
References 341
Volatile Anesthetic Effects on lnositol Triphosphate-Gated
lntracellular Calcium Stores in GH3 Cells
Alex S. Evers and M. Delawar Hossain
I. Introduction 343
11. Intracellular Calcium Measurements 344
Contents xiii
111. Effects of Anesthetics 345
A. TRH-Stimulated Inositol Phosphate Accumulation
B. Effects of Halothane on Resting Intracellular Calcium
C. Effects of Halothane on TRH-Stimulated Increases in
Intracellular Calcium 346
D. Mechanism of Halothane Inhibition of Peak Intracellular Calcium
Responses to TRH 347
E. Effects of Isoflurane and Octanol on Peak Intracellular Calcium
Response to TRH 349
345
345
1V. Summary 349
References 350
Part IV
Ref1 ex Regulation
Differential Control of Blood Pressure by Two Subtypes of
Carotid Baroreceptors
Jeanne 1. Seagard
I. Introduction 351
11. Carotid Baroreceptors 353
A. Anodal Block 354
B. Anesthetic Block 355
C. Baroreceptor Activation 355
A. Blocking of Normal Activity by Anodal Current
B. Block of Nerve Activity by Anesthetic
111. Carotid Sinus Nerve Activity 357
357
359
IV. Discussion 361
References 366
V. Anesthetic Implications 364
Sympathetic Activation with Desflurane in Humans
Thomas J. Ebert and Michael Muzi
1. Introduction 369
11. Sympathetic Microneurography 370
III. Anesthetics and Sympathetic Activation
IV. Discussion 375
371
A. Induction Responses 375
B. Steady-State Responses 376
C. Transition Responses 376
xiv Confents
V. Summary 377
References 378
Randomized, Prospective Comparison of Halothane,
Isoflurane, and Enflurane on Baroreflex Control of Heart
Rate in Humans
Michael Muzi and Thomas J. Ebert
I . Introduction 379
11. Baroreflex Function in Humans 380
111. Effects of Anesthetics 381
IV. Discussion 383
References 386
Baroreflex Modulation by lsoflurane Anesthesia in
Normotensive and Chronically Hypertensive Rabbits
Leonard B. Bell
I. Introduction 389
11. Chronically Hypertensive Rabbit Model and
111. Effect of Isoflurane on Arterial Pressure-Renal Sympathetic Nerve
Experimental Protocol 390
Activity and Arterial Pressure-Heart Rate Barocurves
A. Mean Arterial Pressure-Renal Sympathetic Nerve
B. Mean Arterial Pressure-Heart Rate Baroreflexes 398
A. Effect of Isoflurane Anesthesia on Arterial Pressure-Heart
Rate Baroreflex 401
B. Effect of lsoflurane Anesthesia on Arterial Pressure-Renal
Sympathetic Nerve Activity Baroreflex 402
C. Effect of Isoflurane on Steady-State Resting Levels of Renal
Sympathetic Nerve Activity and Heart Rate
D. Effect of Chronic Hypertension on Mean Arterial Pressure-Heart
Rate Baroreflex 402
E. Effect of Chronic Hypertension on Mean Arterial Pressure-Renal
Sympathetic Nerve Activity Baroreflex 403
F. Effect of Chronic Hypertension on Steady-State Resting Levels of
Renal Sympathetic Nerve Activity and Heart Rate
G. Interaction of Isoflurane Anesthesia and Chronic Hypertension on
Baroreflex Function 405
References 406
394
Activity Baroreflexes 396
IV. Discussion 401
402
404
Contents xv
Part V
Peripheral Circulation
Effects of lsoflurane on Regulation of Capacitance
Vessels under Normotensive and Chronically
Hypertensive Conditions
Thomas A. Stekiel, Leonard 6. Bell, Zeljko J. Bosnjak,
and John P. Kampine
I. Introduction 409
11. Hypertensive Rabbit Preparation 41 I
Ill. Mesenteric Reflex Measurements 41 1
IV. Circulatory Responses to Baroreflex and Chemoreflex Responses in
Normotensive and Hypertensive Animals 413
V. Effects of Isoflurane on Hypoxia and Baroreflex-
Mediated Responses 4 19
V1. Effects of lsoflurane on Prestimulation Baseline Measurements 421
VII. Discussion 421
References 428
Effect of Volatile Anesthetics on Baroreflex Control of
Mesenteric Venous Capacitance
J. Bruce McCallum, Thomas A. Stekiel, Anna Stadnicka,
Zeljko J. Bosnjak, and John P. Kampine
I. Introduction 431
11. Measurement of Venous Capacitance 432
111. Response to Baroreceptor Stimulaton 434
1V. Response to Electric Stimulation 440
V. Discussion 440
References 446
Effect of General Anesthesia on Modulation of Sympathetic
Nervous System Function
Margaret Wood
I . Introduction 449
11. Effect of Intravenous and lnhalational Anesthetics on
Norepinephrine Kinetics 450
111. P-Adrenergic Receptor-Mediated Release of Norepinephrine 454
xvi Contents
IV. Effect of Inhalational Anesthesia on Prejunctional Norepinephrine
Release in Viuo 456
References 457
V. Conclusions 457
Inhibition of Nitric Oxide-Dependent Vasodilaton by
Halogenated Anesthetics
Ming Jing, Jayne L. Hart, Saiid Bina, and Sheila M. Muldoon
I. Introduction 459
11. Methods 460
111. Effects of Anesthetics on Endotheliurn-Dependent Relaxations of
IV. Effects of Halothane and lsoflurane on Nitric Oxide-, Nitroglycerin-, and
Isolated Blood Vessels 462
Carbon Monoxide-Induced Relaxations of Rat Aorta
V. Effects of Halothane on Nitric Oxide-Stimulated
Cyclic GMP 464
V1. Interactions of Halothane and Nitric Oxide in Absence
of Tissues 465
VII. Discussion 467
References 469
463
Effects of Epidural Anesthesia on Splanchnic Capacitance
Quinn H. Hogan, Anna Stadnicka, and John P. Kampine
I. Introduction 471
11. Epidural Anesthesia 472
111. Splanchnic Capacitance 473
IV. Summary 482
References 482
Anesthetic Modulation of Pulmonary Vascular Regulation
Paul A. Murray
I. Introduction 485
11. Measurement of Pulmonary Vasoregulation
A. Surgical Preparation for Chronic Instrumentation
B. Physiological Measurements 486
C. Generation of Pulmonary Vascular Pressure-Flow Plots
D. General Protocols 487
A. Effects of Anesthesia on Baseline
Pressure-Flow Relationship 488
B. Anesthesia and Autonomic Nervous System Regulation of
Pressure-Flow Relationship 490
486
486
487
111. Anesthesia and Pulmonary Vasoregulation 488
Contents xvii
C. Anesthesia and Humoral Regulation of
Pressure-Flow Relationship 493
D. Anesthesia and Regulation of the Pressure-Flow Relationship by
Cyclooxygenase Metabolites 494
E. Anesthesia and Pulmonary Vascular Response
to Hypoperfusion 495
F. Anesthesia and Endothelium-Dependent and -Independent
Pulmonary Vasodilation 498
1V. Summary 502
References 503
Pulmonary Mechanics Changes Associated with
Cardiac Surgery
Ron Dueck
I. Introduction 505
11. Dynamic Lung Compliance 506
111. Effects of Sternotomy 506
IV. Discussion 509
References 5 12
Inhaled Nitric Oxide in Adult Respiratory Distress Syndrome
and Other Lung Diseases
Warren M. Zapol and William E. Hurford
I. Introduction 513
II. Pulmonary Hypertension in Adult Respiratory
Distress Syndrome 514
111. Nitric Oxide 514
IV. Rationale for Use of Inhaled Nitric Oxide in Patients with Adult
Respiratory Distress Syndrome 5 15
A. Acute Pulmonary Hypertension 515
B. Bronchodilation 518
VI. Clinical Studies of Nitric Oxide Inhalation in Adult Respiratory
Distress Syndrome 5 19
VII. Inhaled Nitric Oxide in Other Lung Diseases Associated with
Pulmonary Hypertension 522
A. Neonatal Respiratory Failure 522
B. Chronic Pulmonary Hypertension 523
C. Congenital and Acquired Heart Disease
V . Laboratory Studies of Inhaled Nitric Oxide 515
523
VIII. Toxicity of Nitric Oxide
References 527
524
IX. Guidelines for Nitric Oxide Inhalation 525
xviii
First Pass Uptake in the Human Lung of Drugs Used
during Anesthesia
David L. Roerig, Susan B. Ahlf, Christopher A. Dawson,
John H. Linehan, and John P. Kampine
I. Introduction 531
11. First Pass Drug Uptake in Human Lung 532
111. Factors Affecting Pulmonary Drug Uptake 538
A. Saturability 538
B. Plasma Protein Binding 542
C. Effect of Cardiac Output
References 547
545
IV. Conclusions 547
Contents
Lactic Acidosis and pH on the Cardiovascular System
Yuguang Huang, James B. Yee, Wang-Hin Yip, and K. C. Wong
1. Introduction 551
11. Induction of Lactic Acidosis 552
111. Cardiovascular Effects of Acute Acidosis 554
1V. Discussion 562
References 564
Part VI
Cerebra I Circulation
Role of Oxygen Free Radicals and Lipid Peroxidation in
Cerebral Reperfusion Injury
Laurel E. Moore and Richard J. Traystman
1. Introduction 565
11. Free Radicals 566
111. Mechanisms of Brain Injury 567
IV. Potential Therapeutic Agents 568
V. Conclusion 571
References 572
Contents xix
Effects of Volatile Anesthetics on Cerebrocortical Laser
Doppler Flow: Hyperemia, Autoregulation, Carbon Dioxide
Response, Flow Oscillations, and Role of Nitric Oxide
Antal G. Hudetz, Joseph G. Lee, Jeremy J. Smith, Zeljko J. Bosnjak,
and John P. Kampine
I . Introduction 577
111. Resting Flow 581
IV. Autoregulation 582
V. Hypocapnia and Hypercapnid 584
VI. Role of Nitric Oxide 586
VII. Spontaneous Flow Oscillations 588
VIII. Conclusions 59 1
11. Measurement of Laser Doppler Flow 579
References 591
Cerebral Blood Flow during lsovolemic Hernodilution:
Mechanistic Observations
Michael M. Todd
I. Introduction 595
11. Influence of Hernodiluton on Cerebral Blood Volume 596
111. Influence of Focal Cortical Brain Lesion on Regional Cerebral Blood
Flow Response to Hemodilution 597
1V. Comparison of Cerebrovascular and Metabolic Changes Produced by
Hypoxia and Hemodilution 599
V. Role of Nitric Oxide in the Cerebral Blood Flow Response
to Hemodilution 602
VI. Discussion 603
References 603
Cerebral Physiology during Cardiopulmonary Bypass:
Pulsatile versus Nonpulsatile Flow
Brad Hindman
I. Introduction 607
11. Pulsatile versus Nonpulsatile Bypass
Ill. Influence of Arterial Pressure Waveform 61 1
IV. Summary 614
610
References 6 14
xx Confents
Anesthetic Actions of Cardiovascular Control Mechanisms in
the Central Nervous System
William T. Schmeling and Neil E. Farber
I. Introduction 617
11. Studies Performed in Cats 619
A, Preparation for Acute Studies
B. Preparation for Studies of Intermediolateral Cell Column
Evoked Potentials 620
619
111. Studies in Mongrel Dogs 621
IV. Central Nervous System Pressor Site Responses in Cats and
Intermediolateral Cell Column Evoked Potential
VI. Histological Documentation of Electrode Sites 634
623
V. Anesthetic Responses in Dogs 625
VII. Discussion 634
References 639
Index 643
Contents of Previous Volumes 655
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