Advances in Pharmacological Research and Practice (eBook)

Front Cover 1
Pharmacological Protection of the Myocardium 4
Copyright Page 5
Table of Contents 8
PREFACE 6
Section 1: PHARMACOLOGICAL PROTECTION OF THE MYOCARDIUM 16
INTRODUCTION 18
Chapter 1. THE CYCLIC AMP—PROTEIN KINASE SYSTEM IN ACUTE MYOCARDIAL ISCHAEMIA 20
CYCLIC AMP AND CYCLIC AMP-DEPENDENT PROTEIN KINASE AS INTERMEDIATES IN THE CATECHOLAMINE-PHOSPHORYLASE CASCADE 20
ASSAYING CYCLIC AMP-DEPENDENT PROTEIN KINASE ACTIVITY IN DOG MYOCARDIUM 21
EFFECT OF PROPRANOLOL 24
CLINICAL IMPLICATIONS 25
References 25
Chapter 2. CELLULAR ELECTROPHYSIOLOGICAL DISORDERS IN ACUTE MYOCARDIAL ISCHAEMIA AND THEIR MODIFICATION BY DRUGS 28
Basic electrical phenom^ena 28
Ischaemic milieu 30
Drug modification 33
Resuperfusion - an ' in vitro' model of reperfusion 35
References 36
Chapter 3. ANTIARRHYTHMIC EFFECTS OF POSSIBLE ANTI-ISCHEMIC DRUGS 40
INTRODUCTION 40
METHODS 41
RESULTS 41
DISCUSSION 44
REFERENCES 45
Chapter 4. PROTECTION OF THE ISCHAEMIC HEART. PREVENTION OF PRIMARY VENTRICULAR FIBRILLATION 48
Table 1. Possible mode of action of cardioprotective drugs 49
Table 2. Influence of Iinoleic acid rich /LAR/1 diet on changesd due to coronary occlusion in the conscious rat infarction mode 49
Table 3. Antiischaemic drugs 50
Table 4. Indicators of cardiac antiischaemic action 51
Table 5. Non-steroid antiinflammatory drugs given 60 mln bcforo occlusion or. survival rate, incidence of VF and size of infarctod area after coronary occlusion In the conscious rat 51
Table 6. Effect of chloroquine on survival rate, latency from occlusion to first arrhythmia, duration of arrhythmias of ventricular fibrillation / VF/ and ventricular tachycardia / VT/ in the conscious rat infarction model 53
Table 7.Cytoprotective drugs 54
Table 8.Indicators ot cytoprotective action 55
References 56
Chapter 5. REFLECTIONS ON THE MODE OF ACTION OF BETA-ADRENOCEPTOR ANTAGONISTS IN PROLONGING LIFE AFTER ACUTE MYOCARDIAL INFARCTION 60
TRIGGER EVENTS 62
EFFECTS OF BETA BLOCKADE ON FACTORS PREDISPOSING TO SUDDEN DEATH 62
CONCLUSIONS 64
REFERENCES 65
Chapter 6. CARDIOPROTECTIVE AND CEREBROPROTECTIVE EFFECT OF LIPOCORTIN-LIKE SUBSTANCES 68
Abstract 68
Introduction 68
Methods 69
Results and discussion 70
References 72
Chapter 7. ANTIISCHAEMIC ACTIONS OF CALCIUM ANTAGONISTS 76
DETERMINANTS OF CARDIAC ISCHAEMIA 76
ACTIVITY OF HUMAN CORONARY ARTERIES 78
PROTECTION OF ISCHAEMIC MYOCARDIUM 79
References 80
Chapter 8. CARDIO-PROTECTIVE AND -NONPROTECTIVE EFFECTS 
82 
A/ Precursors of NAD- and Adenine Nucleotide /AN/-Synthesis 82
B/ The energy State during K+-Depolarization /13, 14/ 83
C/ Cardiotonic Drugs and Anoxic Contractile Work/Beat 13,4,15/ 84
D/ Reoxygenation and Auxotonic Contractile Work/Beat Influenced by Eicosanoids /16/ 84
Acknowledgements 85
References 85
Chapter 9. CARDIAC GLYCOSIDES AND MYOCARDIAL ISCHAEMIA 88
A/ THE ACTIONS OF CARDIAC GLYCOSIDES WHICH ARE HARMFUL IN ISCHAEMIA OR INFARCTION 88
./ FACTORS IN ISCHAEMIA OR INFARCTION THAT INCREASE SENSITIVITYOF THE HEART TO CARDIAC GLYCOSIDES AND LOWER TOLERANCE TO TOXIC EFFECTS 90
C/ BENEFICIAL ACTION OF CARDIAC GLYCOSIDES IN ISCHAEMIA AND 
92 
References 92
Chapter 10. PHARMACOLOGICAL CONTROL OF THROMBOTIC PROCESSES FOR PREVENTION OF MYOCARDIAL ISCHAEMIA 96
Introduction 96
PHARMACOLOGICAL CONTROL 97
REFERENCES 101
Chapter 11. THE PHARMACOLOGICAL PROTECTION OF THE ISCHAEMIC MYOCARDIUM PROBLEMS AND POSSIBILITIES 104
PROBLEMS CONCERNING THE ASSESSMENT OF THE EFFICACY OF PHARMACOLOGICAL AGENTS IN REDUCING MYOCARDIAL ISCHAEMIC DAMAGE 104
POSSIBLE PHARMACOLOGICAL APPROACHES TO MYOCARDIAL SALVAGE 108
Conclusions 111
References 112
Chapter 12. ETHACIZINE: ANTIARRHYTHMIC AND ANTIISCHAEMIC PROPERTIES 114
References 117
Chapter 13. EFFECTS OF DILTIAZEM AND VERAPAMIL IN A NEW CANINE MODEL OF MYOCARDIAL INFARCTION 118
Introduction 118
Methods 118
Results 119
Discussion 121
References 122
Chapter 14. POSSIBLE DIFFERENCES AMONG THE DRUG-INDUCED RESPONSES OF THE DESCENDING AND CIRCUMFLEX CORONARY ARTERIES IN THE ANAESTHETIZED DOG 124
Reference 127
Chapter 15. BETA-ADRENOLYTIC WITHDRAWAL REBOUND PHENOMENON: AN INTRODUCTION 128
References 130
Chapter 16. A CONTRIBUTION TO THE MECHANISM OF BETA-ADRENOLYTIC WITHDRAWAL SYNDROME 132
References 135
Chapter 17. ALTERATIONS IN THE EFFICACYOF BETA-ADRENOTROPIC DRUGS DUE TO CHANGES IN THE TONE OF THE AUTONOMIC NERVOUS SYSTEM 136
References 138
Chapter 18. ARTERIOVENOUS DIFFERENCE IN THE INHIBITION OF PLATELET AGGREGATION BY THE ANTIANGINAL DRUG: CH-102 140
Introduction 140
Methods 140
Results and discussion 141
References 143
Chapter 19. INHIBITION OF ADENYLATE CYCLASE BY Ca2+ IN THE ISCHAEMIC MYOCARDIUM A CONCEPT OF PROTECTION BY Ca2+ CHANNEL AND ß-BL0CKADE 144
EFFECT OF ISCHAEMIA AND REPERFUSION ON ISO PROTERENOL STIMULATED ADENYLATE CYCLASE 145
References 147
Chapter 20. PROTECTIVE EFFECT OF CALCIUM ANTAGONISTS ON ISCHAEMIC MYOCARDIAL METABOLISM DUE TO VASOPRESSIN INDUCED CORONARY SPASM 150
References 153
Chapter 21. INHIBITION OF cAMP-PHOSPHODIESTERASE FROM HEART AND CORONARY ARTERIES BY A NEW TRAPIDIL DERIVATIVE 154
References 156
Chapter 22. COMPARISON OF THREE CALCIUM ANTAGONISTS, 
158 
Introduction 158
Methods 158
Results 159
Discussion and conclusions 161
References 161
Chapter 23. EFFECT OF IS, A WATER SOLUBLE DERIVATIVE OF INDOMETHACIN, ON THE OUTCOME OF THE VERY EARLY PHASE OF EXPERIMENTAL MYOCARDIAL INFARCTION IN CONSCIOUS RATS 162
Introduction 162
Methods 162
Results 163
Discussion 164
References 165
Chapter 24. THE USE OF VOLTAGE CLAMP IN THE TESTING OF ANTIARRHYTHMIC DRUGS 166
References 171
Chapter 25. INTRACELLULAR ELECTROPHYSIOLOGICAL EFFECTS OF AMIODARONE AFTER ACUTE AND CHRONIC APPLICATION IN GUINEA PIG VENTRICULAR AND DOG PURKINJE FIBERS 174
Methods 174
Results 175
Conclusions 177
References 177
Chapter 26. ELECTRICAL AND MECHANICAL ACTIVITY OF THE MYOCARDIUM AS AFFECTED BY CH-101, AN ANTIARRHYTHMIC AGENT WITH PREFERENTIAL SUPRAVENTRICULAR ACTION 178
Introduction 178
Methods 178
Results 179
Conclusions 181
References 181
Chapter 27. INVOLVEMENT OF THE CENTRAL NICOTINIC RECEPTORS IN THE GENESIS OF THE CENTROGENIC CARDIAC ARRHYTHMIAS IN RATS 184
Introduction 184
Methods 184
Results 185
Discussion 185
References 187
Chapter 28. MORPHINE AND TIFLUADOM-INDUCED CENTROGENIC ARRHYTHMIAS IN ANAESTHETIZED RATS 188
Introduction 188
Methods 188
Results 189
Discussion 189
References 190
Chapter 29. STRUCTURE—ANTIARRHYTHMIC ACTIVITY RELATIONSHIP 
192 
References 195
Chapter 30. LONG TERM-TREATMENT 
198 
Material and Methods 198
Results 199
Discussion 200
Conclusions 200
References 200
Chapter 31 
202 
References 205
Chapter 32.MICROELECTROPHYSIOLOGICAL PROCEDURE 
206 
Introduction 206
Material and Methods 206
Results and Discussion 208
References 209
Chapter 33. SERUM LEVELS OF DIGOXIN DURING COMBINED TREATMENT WITH DIGOXIN AND AMIODARONE 212
Material and methods 212
Results 212
Discussion 213
Conclusion 214
Chapter 34.THE INOTROPIC EFFECT OF ISOPROTERENOL AND DOPAMINE UNDER DIFFERENT LEVELS OF OXYGENATION 216
Introduction 216
Methods 216
Results 216
Discussion 217
References 219
Chapter 35. THE INFLUENCE OF DOXORUBICIN COMBINED WITH OTHER DRUGS ON HAEMODYNAMIC PARAMETERS IN RABBITS 220
Material and methods 220
Results 221
Discussion 223
References 224
Chapter 36. NEW ANTIARRHYTHMIC AGENT WITH POSITIVE CARDIAC ACTIONS (GYKI-38 233) 226
METHODS 226
RESULTS 227
CONCLUSION 230
REFERENCES 230
Chapter 37. CARDIAC ELECTROPHYSIOLOGICAL EFFECTS OF LYSOLECITHIN, AN ISCHAEMIC METABOLITE, ON RABBIT ATRIAL AND VENTRICULAR MYOCARDIUM 232
Introduction 232
Materials and Methods 232
Results and Conclusion 233
References 237
Chapter 38. ACUTE AND CHRONIC EFFECTSOF IPRATROPIUM BROMIDE(ITROP) IN PATIENTS WITH BRADYCARDIA 238
Methods 238
Results 239
Discussion 240
Summary 241
References 241
Chapter 39. MYOCARDIAL PROTECTION BY COMPUTERISED LONG-TIME CONTROLLING OF THE MYOCARDIAL GLUCOSE-, INSULIN-, FATTY ACID-SUPPLY IN MAN 242
References: 245
LIST OF CONTRIBUTORS 248
SUBJECT INDEX 252
Section 2: PHARMACOLOGY OF THE VASCULAR SYSTEM 258
Chapter 40. CHEMICAL AND BIOCHEMICAL PARAMETERS ASSOCIATED WITH NEW CARDIOVASCULAR DRUGS 260
REFERENCES 264
Part 1: 
266 
Chapter 41. INTERACTIONS BETWEEN EFFECTS OF ADENOSINE AND INOSINE IN THE CORONARY CIRCULATION: A NEW HYPOTHESIS OF METABOLIC AUTO REGULATION 268
METHODS 269
RESULTS 270
DISCUSSION 274
SUMMARY 275
REFERENCES 276
Chapter 42. A PHARMACOLOGICAL APPROACH TO ADENOSINE RECEPTORS IN MYOCARDIUM, SINOATRIAL NODE AND VASCULAR SMOOTH MUSCLE 278
METHODS AND MATERIALS 278
RESULTS 279
DISCUSSION 282
REFERENCES 283
Part 2: CENTRAL MECHANISMS AND ACTIONS IN HYPERTENSION 286
Chapter 43. ADRENERGIC-OPIOID INTERACTIONS IN CENTRAL CARDIOVASCULAR AND PAIN CONTROL 288
CENTRAL SITE OF THE CLONIDINE-BETA-ENDORPHIN INTERACTION 288
ADRENERGIC-OPIOID INTERACTION IN NOCICEPTION 290
REFERENCES 291
Chapter 44. BETA-ENDORPHIN AND ANTIHYPERTENSIVE DRUGS 294
Prazosin-clonidine and prazosin-guanfacine interaction 295
Non adrenergic antihypertensive agents and plasma beta-endorphin 296
Conclusion 298
References 299
Chapter 45. THE RESPONSIVENESS OF ALPHA2-ADRENOCEPTORS IN SOME BRAIN REGIONS OF SPONTANEOUS AND VASOPRESSIN HYPERTENSIVE RATS 302
METHOD 302
RESULTS 303
Discussion 304
REFERENCES 306
Chapter 46. INTERFERENCE OF BLOOD PRESSURE VARIATION WITH THE EFFECT OF ANTIHYPERTENSIVE DRUGS IN NORMOTENSIVE MONKEYS MACACA MULATTA 308
Origin of animals 308
Housing 308
Blood pressure measurement 308
Blood pressure of untreated animals 309
Fluctuations of BP in untreated animals 309
Criteria for estimation of hypotensive effect 312
Effect of clinically active antihypertensive drugs 312
Chapter 47. THE INFLUENCE OF GABA-ERGIC SYSTEM —A NEW WAY IN PROPHYLAXIS AND TREATMENT OF HYPERTENSION IN EXPERIMENT 314
Chapter 48. HAEMODYNAMIC INTERACTIONS BETWEEN GUANFACINE AND ENDRALLAZINE IN HYPERTENSIVE PATIENTS 318
INTRODUCTION 318
MATERIALS AND METHODS 318
EXPERLMENTAL DESIGN 318
METHODS 318
STATISTICAL A 
319 
RESULTS 319
DISCUSSION 320
References 321
Part 3: ROLE OF CALCIUM ANTAGONISTS AND IN FLUENCE OF CALCIUM FLUXES 322
Chapter 49. ROLE OF CALCIUM ANTAGONISTS IN THE TREATMENT OF HYPERTENSION 324
Summary 324
Intracellular calcium correlates with blood pressure 325
Enhanced adrenoceptor-mediated and calcium influx dependent 
326 
Counterregulation codetermines antihypertensive response 327
Antihypertensive efficacy of calcium antagonists 328
References 331
Chaptar 50. THE EFFECT OF CALCIUM CHANNEL BLOCKERS ON THE RELEASE OF TRITIATED NORADRENALINE FROM THE PULMONARY ARTERY OF RABBIT 334
Introduction 334
Material and methods 334
Results 335
Discussion 336
References 337
Chapter 51. BLOOD PRESSURE LOWERING EFFECT OF NIFEDIPINE: ITS RELATIONSHIP WITH EXCHANGEABLE BODY SODIUM 338
Materials and methods 338
Results 339
Discussion 340
Conclusion 341
References 341
Chapter 52. ANALYSIS OF THE CALCIUM CHANNEL BLOCKERS 342
Chapter 53. COMPARATIVE CARDIOVASCULAR EFFECTS OF PRAZOSIN AND VERAPAMIL 344
METHODS 344
RESULTS 345
DISCUSSION 349
REFERNCES 349
Chapter 54. DRUG INTERACTIONS ON THE SMOOTH MUSCLES OF THE ISOLATED SPIRALLY CUT STRIP OF RAT AORTA 350
chapter 55. EFFECTS OF ISOQUINOLINE DERIVATIVES ON CYCLIC NUCLEOTIDES AND CALCIUM FLUXESIN RAT BLOOD VESSELS 354
REFERENCES: 357
Part 4: 
358 
Chapter 56. REPORT ON THE PHARMACOLOGICAL EFFECTS OF THREE NEW PERIPHERAL VASODILATOR COMPOUNDS RGH-0537, RGH-2981 AND RGH-2970 360
INTRODUCTION 360
METHODS 360
RESULTS 362
LITERATURE 363
Chapter 57. HEMODYNAMIC EFFECTS OF VASODILATORS ON PERIPHERAL CIRCULATION 364
Chapter 58. THE INFLUENCE OF AMEZINIUM ON REGULATION 
368 
Material and methods 368
Results 369
Discussion 370
Conclusions 370
References 370
Chapter 59. CIRCULATORY EFFECTS OF FUSARIC ACID DERIVATIVES 372
1./ Effects on the Normotonic Narcotised Rat 372
2./ Effects on the Spontaneously Hypertensive Rat 372
3./ Examinations on the Isolated Papillary Muscle of the Rabbit 373
4./ Examinations on the Cat 373
5./ Further effects and Summary 373
REFERENCES 373
Chapter60. PHARMACOLOGICAL INVESTIGATÓIONS OF THE CH-141, A NEW ISOQUINOLYL-OXADIAZINE DERIVATIVE 374
References 376
Part 5: ROLE OF ALPHA- AND BETA-ADRENERGIC AND 5-HT RECEPTORS 378
Chapter 61. REGULATION OF ALPHA-ADRENERGIC RECEPTORS IN DOGS' 
380 
INTRODUCTION 380
METHODS 380
DISCUSSION AND CONCLUSION 382
REFERENCES 383
Chapter 62.THE EFFECTS OF PENTACAINE AND RELATED LOCALANAESTHETICS ON BETA-ADRENERGIC RECEPTORS AND ADENYLATE CYCLASE ACTIVITY IN TURKEY ERYTHROCYTE AND RAT LIVER MEMBRANES 384
Introduction 384
Materials and methods 384
Results and Discussion 385
Summary 386
References 387
Chapter 63. A CONTRIBUTION TO THE MECHANISM OF BETA-ADRENOLYTIC WITHDRAWAL SYNDROME 388
REFERENCES 390
Chapter 64. THE EFFECT OF BETA–ADRENOCEPTOR BLOCKING DRUGS ON PLATELET AGGREGATION, CALCIUM DISPLACEMENT AND FLUIDIZATION OF THE MEMBRANE 392
ABSTRACT 392
INTRODUCTION 392
METHODS AND MATERIALS 392
RESULTS AND DISCUSSION 393
REFERENCES 395
Chapter 65. EFFECTS OF TOBANUM AND PROPRANOLOL 
396 
Patients and methods 396
Results and discussion 397
References 397
Chapter 66. INTERACTION OF DIHYDROERGOTAMINE WITH 5-HT RECEPTORS ON HUMAN BLOOD PLATELETS AND FEMORAL VEINS 398
Chapter 67. EFFECTS OF FORSKOLIN, TREQUINSINE AND ISOPROTERENOL ON NOREPINEPHRINE-INDUCED CONTRACTIONS, cAMP AND cGMP LEVELS OF ISOLATED VASCULAR TISSUE 402
SUMMARY 402
METHODS 402
RESULTS 403
DISCUSSION 404
REFERENCES 405
Part 6: 
406 
Chapter 68. OUABAIN EVOKED 3[H]-NORADRENALINE RELEASE FROM THE MAIN PULMONARY ARTERY OF THE RABBIT 408
INTRODUCTION 408
METHODS 408
RESULTS AND CONCLUSIONS 409
REFERENCES 411
Chapter 69. PHARMACOLOGICAL ACTIONS AND THE PULMONARY CIRCULATION 414
Method 414
Results and Discussion 414
Conclusion 416
References : 417
Part 7: 
418 
Chapter 70. EFFECT OF A NEW BENZHYDROLE DERIVATIVE (RGH-2801)ON THE LIPOPROTEIN AND LCAT LEVEL 420
MATERIALS AND METHODS 420
RESULTS 420
DISCUSSION 422
REFERENCES 423
ACKNOWLEDGMENTS 423
SUBJECT INDEX 430