Licentiatavhandling (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 3 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2006. / Härtil 4 uppsatser.

This study examines the α-adrenergic constrictor tone varies with intensity of exercise, the effects of coronary α1-adrenergic blockade on left ventricular contractile function and regional myocardial perfusion, and compares the effects of increasing coronary blood flow by removing α1-constrictor tone.

Coronary artery disease has become a world wide medical problem. There is an overwhelming association between coronary atherosclerosis, angina pectoris, acute myocardial infarction and sudden death. The narrowing of coronary arteries is thought to damage the heart by limiting appropriate changes in coronary blood flow and by causing myocardial ischemia. This thesis attempts to examine the coronary circulation in patients who present with chest pain with and without coronary artery disease. One of the aims of this thesis is to validate the use of a short-lived radionuclide to study changes in regional myocardial perfusion. This technique has been applied in clinical medicine in an attempt to describe the disturbances of regional myocardial perfusion that occur in patients with coronary artery disease. These disturbances of perfusion have been related to the patients' symptoms, the electrocardiogram and the stenosed arteries seen in the arteriogram. Krypton-81m in solution is an inert freely diffusible gas (half-life 13 seconds) which emits a single 190 kev gamma ray. This tracer, a special catheter and a gamma camera have been developed in experiments to measure changes in regional myocardial perfusion. The systematic and rand-Om errors of the method have been defined in experiments. The results show that the mixing and delivered arterial concentration of krypton-81m are stable within a useful physiological range of changes in heart rate, blood pressure and coronary blood flow. Correlations with a reference technique have shown that the method can measure changes in regional myocardial perfusion between O and 3 ml/ml/min. The invasive method, the planar imaging and the need for calibration with washout at high levels of perfusion are investigated and described as limitations that must be considered. Eighty patients presenting with chest pain have been investigated by routine clinical methods, precordial mapping of the electrocardiogram during exercise and coronary arteriography. Changes in regional myocardial perfusion at rest and during atrial pacing has been measured using krypton-81m. The results have shown that stable mixing and delivered arterial concentration of krypton-81m can be achieved in the patients. Fifteen patients with negative exercise tests all demonstrated uniform increases in regional myocardial perfusion with pacing. The remaining 65 patients with positive exercise tests and significant coronary artery disease all showed both regional increases and decreases in myocardial perfusion during atrial pacing. In 16 of the 65 patients the jeopardized segment of ventricular myocardium showed significant increases in perfusion during the first 4 to 7 minutes of pacing. Th e increase stopped and regional perfusion in the affected segment then decreased progressively until the pacing was stopped. In 23 of the 65 patients the affected segment showed no changes in perfusion for 5 to 7 minutes of atrial pacing and then showed progressive decreases in regional myocardial perfusion until the pacing was stopped. Finally, in 26 of the 65 patients the affected segment showed immediate and progressive decreases of regional myocardial perfusion starting with the commencement of atrial pacing. In all the patients with disturbed perfusion ST segment depression in the electrocardiogram appeared after (140 ± 14 sec) the regional decrease of myocardial perfusion in the affected segment. Chest pain always appeared later at 220 ± 19 sec after the appearance of disturbed myocardial perfusion. Regional myocardial perfusion returned to normal in all the patients after the atrial pacing was stopped. There was a spatial relationship between the region of the ventricles affected by disturbed perfusion and the region of the precordium showing abnormal electrocardiographic signs during the exercise test. In conclusion, this clinical study has shown that patients with chest pain who have coronary artery disease suffer decreases of regional myocardial perfusion in affected segments of the ventricles during episodes of angina pectoris induced by atrial pacing. Regional perfusion may increase, remain stable or decrease in the affected segment following the onset of a stress test such as atrial pacing. This probably represents the amount of reserve function and adaptation left in the diseased coronary circulation and may be a useful physiological indicator of the severity of coronary disease and of patients at high risk. ST segment depression and pain have a close temporal relationship to the decreases of regional myocardial perfusion that occur in these patients. These studies suggest that there is a close relationship between myocardial perfusion and metabolism in health and disease. Both myocardial perfusion and metabolism will have to be affected by any rational therapy for angina pectoris and ischemic heart disease.

Indiana University-Purdue University Indianapolis (IUPUI) / Coronary microvascular function is markedly impaired by the onset of the metabolic syndrome and may be an important contributor to the increased cardiovascular events associated with this mutlifactorial disorder. Despite increasing appreciation for the role of coronary K+ channels in regulation of coronary microvascular function, the contribution of K+ channels to the deleterious influence of metabolic syndrome has not been determined. Accordingly, the overall goal of this investigation was to delineate the mechanistic contribution of K+ channels to coronary microvascular dysfunction in metabolic syndrome. Experiments were performed on Ossabaw miniature swine fed a normal maintenance diet or an excess calorie atherogenic diet that induces the classical clinical features of metabolic syndrome including obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, hyperleptinemia, and atherosclerosis. Experiments involved in vivo studies of coronary blood flow in open-chest anesthetized swine as well as conscious, chronically instrumented swine and in vitro studies in isolated coronary arteries, arterioles, and vascular smooth muscle cells. We found that coronary microvascular dysfunction in the metabolic syndrome significantly impairs coronary vasodilation in response to metabolic as well as ischemic stimuli. This impairment was directly related to decreased membrane trafficking and functional expression of BKCa channels in vascular smooth muscle cells that was accompanied by augmented L-type Ca2+ channel activity and increased intracellular Ca2+ concentration. In addition, we discovered that impairment of coronary vasodilation in the metabolic syndrome is mediated by reductions in the functional contribution of voltage-dependent K+ channels to the dilator response. Taken together, findings from this investigation demonstrate that the metabolic syndrome markedly attenuates coronary microvascular function via the diminished contribution of K+ channels to the overall control of coronary blood flow. Our data implicate impaired functional expression of coronary K+ channels as a critical mechanism underlying the increased incidence of cardiac arrhythmias, infarction and sudden cardiac death in obese patients with the metabolic syndrome.

Indiana University-Purdue University Indianapolis (IUPUI) / Regulation of coronary blood flow is a highly dynamic process that maintains the delicate balance between oxygen delivery and metabolism in order to preserve cardiac function. Evidence to date support the finding that Kv and Cav1.2 channels are critical end-effectors in modulating vasomotor tone and blood flow. Yet the role for these channels in the coronary circulation in addition to their interdependent relationship remains largely unknown. Importantly, there is a growing body of evidence that suggests obesity and its pathologic components, i.e. metabolic syndrome (MetS), may alter coronary ion channel function. Accordingly, the overall goal of this investigation was to examine the contribution coronary Kv and Cav1.2 channels to the control of coronary blood flow in response to various physiologic conditions. Findings from this study also evaluated the potential for interaction between these channels, i.e. electromechanical coupling, and the impact obesity/MetS has on this mechanism. Using a highly integrative experimental approach, results from this investigation indicate Kv and Cav1.2 channels significantly contribute to the control of coronary blood flow in response to alterations in coronary perfusion pressure, cardiac ischemia, and during increases in myocardial metabolism. In addition, we have identified that impaired functional expression and electromechanical coupling of Kv and Cav1.2 channels represents a critical mechanism underlying coronary dysfunction in the metabolic syndrome. Thus, findings from this investigation provide novel mechanistic insight into the patho-physiologic regulation of Kv and Cav1.2 channels and significantly improve our understanding of obesity-related cardiovascular disease.

Leung Hok Sum. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 128-147). / Abstracts in English and Chinese. / Declaration --- p.i / Acknowledgements --- p.ii / Abbreviation --- p.iii / Abstract in English --- p.iv / Abstract in Chinese --- p.vi / Contents --- p.viii / Chapter Chapter I - --- Introduction / Chapter 1.1. --- Steroid Hormone --- p.1 / Chapter 1.2. --- Estrogen Receptors --- p.2 / Chapter 1.3. --- Selective Estrogen Receptor Modulators --- p.5 / Chapter 1.3.1. --- Tamoxifen --- p.5 / Chapter 1.3.1.1. --- Cardiovascular Effects of Tamoxifen --- p.6 / Chapter 1.3.1.2. --- Acute Vascular Effects of Tamoxifen --- p.6 / Chapter 1.3.1.3. --- Chronic Vascular Effects of Tamoxifen --- p.7 / Chapter 1.3.1.4. --- Antioxidant Effects of Tamoxifen --- p.8 / Chapter 1.3.2. --- Raloxifene --- p.8 / Chapter 1.3.2.1. --- Cardiovascular Effects of Raloxifene --- p.8 / Chapter 1.3.2.2. --- Acute Vascular Effects of Raloxifene --- p.9 / Chapter 1.3.2.3. --- Chronic Vascular Effects of Raloxifene --- p.10 / Chapter 1.3.2.4. --- Ovariectomy and Raloxifene Treatment --- p.11 / Chapter 1.4. --- Mechanism of Action of SERMs --- p.15 / Chapter 1.5. --- Effects of Functional Endothelium and Nitric Oxide --- p.18 / Chapter 1.6. --- Dihydropyridine (DHP) Calcium Channel Antagonists --- p.19 / Chapter 1.6.1. --- Development of Newer Generation of Dihydropyridines --- p.19 / Chapter 1.6.2. --- Effects of Dihydropyridines on Vascular Endothelium (I) --- p.20 / Chapter 1.6.3. --- Effects of Dihydropyridines on Vascular Endothelium (II) --- p.21 / Chapter 1.6.4. --- Effects of Dihydropyridines on Nitric Oxide Synthase (NOS) --- p.21 / Chapter 1.6.5. --- Clinical Studies of Dihydropyridines --- p.22 / Chapter 1.7. --- Vascular Ion Channels --- p.25 / Chapter 1.8. --- Objectives of The Present Study --- p.26 / Chapter Chapter II - --- Materials and Methods / Chapter 2.1. --- Tissue Preparation --- p.27 / Chapter 2.1.1. --- Preparation of The Porcine Left Circumflex Coronary Arteries --- p.27 / Chapter 2.1.2. --- Removal of Functional Endothelium --- p.27 / Chapter 2.1.3. --- Organ Bath Setup --- p.27 / Chapter 2.1.4. --- Isometric Force Measurement --- p.29 / Chapter 2.2. --- In situ Endothelial [Ca2+]i Imaging --- p.29 / Chapter 2.2.1. --- Preparation of Porcine Left Circumflex Coronary Arteries --- p.29 / Chapter 2.2.2. --- Setup For In situ Endothelial [Ca2+]i Imaging --- p.30 / Chapter 2.3. --- Electrophysiological Measurement of BKCa Current --- p.31 / Chapter 2.3.1. --- Enzymatic Dissociation of Coronary Artery Smooth Muscle Cells --- p.31 / Chapter 2.3.2. --- Electrophysiological Measurement --- p.31 / Chapter 2.4. --- DPPH Free Radical Scavenging Assay --- p.31 / Chapter 2.5. --- Solutions and Drugs --- p.32 / Chapter 2.5.1. --- "Drugs, Chemicals and Enzymes" --- p.32 / Chapter 2.5.2. --- Solutions Used in Force Measurement --- p.34 / Chapter 2.6. --- Statistical Analysis --- p.34 / Chapter Chapter III - --- Tamoxifen-Induced Endothelial Nitric Oxide-Dependent Relaxation in Porcine Coronary Arteries via Ouabain- and BaCl2-Sensitive Mechanisms / Chapter 3.1. --- Abstract --- p.35 / Chapter 3.2. --- Introduction --- p.36 / Chapter 3.3. --- Methods and Materials --- p.37 / Chapter 3.3.1. --- Vessel Preparation --- p.37 / Chapter 3.3.2. --- Isometric Force Measurement --- p.38 / Chapter 3.3.3. --- In situ Endothelial [Ca2+]i Imaging --- p.39 / Chapter 3.3.4. --- Chemicals --- p.40 / Chapter 3.3.5. --- Data Analysis --- p.40 / Chapter 3.4. --- Results --- p.41 / Chapter 3.4.1. --- Relaxant Responses --- p.41 / Chapter 3.4.2. --- Effects of Inhibitors of NO-Dependent Relaxation --- p.41 / Chapter 3.4.3. --- Effects of Putative K+ Channel Blockers and Ouabain --- p.41 / Chapter 3.4.4. --- "Effects of Ouabain, Removal of Extracellular K+ Ions and BaCI2" --- p.42 / Chapter 3.4.5. --- SNP-Induced Relaxation --- p.42 / Chapter 3.4.6. --- Effects of Actinomycin D and Cycloheximide --- p.42 / Chapter 3.4.7. --- Relaxant Effect of 17β-Estradiol --- p.43 / Chapter 3.4.8. --- Effects on Endothelial [Ca2+]i in Isolated Coronary Arteries With Endothelium --- p.43 / Chapter 3.5. --- Discussion --- p.53 / Chapter Chapter IV - --- Endothelium-Independent Relaxation to Raloxifene in Porcine Coronary Arteries / Chapter 4.1. --- Abstract --- p.57 / Chapter 4.2. --- Introduction --- p.58 / Chapter 4.3. --- Methods and Materials --- p.59 / Chapter 4.3.1. --- Vessel Preparation --- p.59 / Chapter 4.3.2. --- Isometric Force Measurement --- p.60 / Chapter 4.3.3. --- Electrophysiological Measurement of BKCa Current --- p.61 / Chapter 4.3.3.1. --- Enzymatic Dissociation of Coronary Artery Smooth Muscle --- p.61 / Chapter 4.3.3.2. --- Electrophysiological Measurement --- p.62 / Chapter 4.3.4. --- Chemicals --- p.63 / Chapter 4.3.5. --- Data Analysis --- p.63 / Chapter 4.4. --- Results --- p.64 / Chapter 4.4.1. --- Effect of Raloxifene on Agonist-Induced Contractions --- p.64 / Chapter 4.4.2. --- Role of Endothelium --- p.64 / Chapter 4.4.3. --- Effect of ER Antagonist --- p.65 / Chapter 4.4.4. --- Effect of Putative K+ Channel Blockers --- p.65 / Chapter 4.4.5. --- Effect of Elevated Extracellular K+ Concentrations --- p.65 / Chapter 4.4.6. --- Effects of Raloxifene on BKCa Current --- p.65 / Chapter 4.5. --- Discussion --- p.75 / Chapter Chapter V - --- Therapeutic Concentrations of Raloxifene Augment Bradykinin Mediated Nitric Oxide-Dependent Relaxation in Porcine Coronary Arteries / Chapter 5.1. --- Abstract --- p.78 / Chapter 5.2. --- Introduction --- p.79 / Chapter 5.3. --- Methods and Materials --- p.80 / Chapter 5.3.1. --- Vessel Preparation --- p.80 / Chapter 5.3.2. --- Isometric Force Measurement --- p.80 / Chapter 5.3.3. --- In situ Endothelial [Ca2+]i Imaging --- p.81 / Chapter 5.3.4. --- Free Radical Scavenging Assay --- p.82 / Chapter 5.3.5. --- Chemicals --- p.83 / Chapter 5.3.6. --- Data Analysis --- p.83 / Chapter 5.4. --- Results --- p.84 / Chapter 5.4.1. --- Relaxation to Bradykinin --- p.84 / Chapter 5.4.2. --- Effect of Raloxifene on Bradykinin-Induced Relaxation --- p.84 / Chapter 5.4.3. --- Effect of Raloxifene on Relaxation Induced by Substance P and --- p.85 / Chapter 5.4.4. --- Effect of Estrogen on Bradykinin-Induced Relaxation --- p.85 / Chapter 5.4.5. --- Effect of Raloxifene on Sodium Nitroprusside-Induced Relaxation --- p.86 / Chapter 5.4.6. --- Free Radical Scavenging Effect --- p.86 / Chapter 5.4.7. --- Raloxifene Augmentation of Bradykinin-Stimulated Endothelial [Ca2+]i --- p.86 / Chapter 5.5. --- Discussion --- p.99 / Chapter Chapter VI - --- "Cilnidipine, a Slow-Acting Ca2+ Channel Blocker, Induces Relaxation in Porcine Coronary Arteries: Role of Endothelial Nitric Oxide and [Ca2+]i" / Chapter 6.1. --- Abstract --- p.102 / Chapter 6.2. --- Introduction --- p.103 / Chapter 6.3. --- Methods and Materials --- p.104 / Chapter 6.3.1. --- Vessel Preparation --- p.104 / Chapter 6.3.2. --- Isometric Force Measurement --- p.105 / Chapter 6.3.3. --- In situ Endothelial [Ca2+]i Imaging --- p.106 / Chapter 6.3.4. --- Free Radical Scavenging Assay --- p.107 / Chapter 6.3.5. --- Chemicals --- p.108 / Chapter 6.3.6 --- Data Analysis --- p.108 / Chapter 6.4. --- Results --- p.108 / Chapter 6.4.1. --- Relaxant Responses --- p.108 / Chapter 6.4.2. --- Role of the Endothelium --- p.109 / Chapter 6.4.3. --- Effect of Inhibitors of NO-Dependent Relaxation --- p.109 / Chapter 6.4.4. --- Effect of Indomethacin and w-conotoxin --- p.110 / Chapter 6.4.5. --- Effect of Cilnidipine on Sodium Nitroprusside-Induced Relaxation --- p.110 / Chapter 6.4.6. --- Effects on Endothelial [Ca2+]i in Isolated Endothelium-Intact Coronary Arteries --- p.110 / Chapter 6.4.7. --- Free Radical Scavenging Effect --- p.110 / Chapter 6.5. --- Discussion --- p.120 / Chapter Chapter VII - --- General Summary --- p.123 / References --- p.128

Indiana University-Purdue University Indianapolis (IUPUI) / The epidemic of obesity and associated cardiovascular complications continues to grow at an alarming rate. Currently, obesity is thought to initiate a state of chronic inflammation, which if unresolved potentially causes cardiovascular dysfunction and disease. Although poorly understood, release of inflammatory mediators and other cytokines from adipose tissue (adipocytokines) has been proposed to be the molecular link between obesity and coronary artery disease. Furthermore, the anatomic location of adipose has been increasingly recognized as a potential contributor to vascular disease. Importantly, the development of coronary atherosclerosis, a key component of heart disease, is typically found in segments of coronary arteries surrounded by perivascular adipose tissue. Accordingly, the goal of this project was to determine how perivascular adipose tissue affects coronary artery function and elucidate the critical mechanisms involved. Initial studies assessing arterial function were conducted with and without perivascular adipose tissue. Preliminary results demonstrated that factors released by perivascular adipose tissue effectively impaired coronary endothelial function both in vitro and in vivo. This observation was determined to be caused by direct inhibition of nitric oxide synthase (NOS), a critical enzyme for the production nitric oxide. Attenuation of endothelium-dependent vasodilation was independent of changes in superoxide production, smooth muscle response, or peroxide-mediated vasodilation. Additional studies revealed that perivascular adipose-induced impairment of NOS was due to increased inhibitory regulation by the β isoform of protein kinase C (PKC-β). Specifically, perivascular adipose-derived factors caused site specific phosphorylation of nitric oxide synthase at Thr-495. Additional experiments investigated how perivascular adipose-derived factors contributed to coronary artery disease in an animal model of obesity. Results from these studies indicated that perivascular adipose-derived leptin markedly exacerbated underlying endothelial dysfunction, and significantly contributed to coronary endothelial dysfunction through a PKC-β dependent mechanism. Findings from this project confirm epicardial perivascular adipose tissue as a local source of harmful adipocytokines. In addition, perivascular adipose-derived leptin was demonstrated to be a critical mediator of coronary vascular dysfunction in obesity. Together, the results strongly suggest that perivascular adipose tissue is a key contributor to coronary artery disease in obesity.

Pacientes sépticos com disfunção miocárdica apresentam mortalidade significativamente superior comparados aos sépticos sem alteração cardiovascular. Vários mecanismos contribuem para disfunção orgânica na sepse, como diminuição de perfusão tecidual. A sepse está relacionada a alterações na microcirculação e na permeabilidade capilar que apresentam papel fundamental na fisiopatologia das disfunções orgânicas. O objetivo do estudo foi analisar o papel da pressão de perfusão coronariana como fator determinante do fluxo sanguíneo na microcirculação miocárdica e sua correlação com a função cardíaca sistólica e diastólica em ratos endotoxêmicos. Ratos machos, Wistar, 300g, receberam LPS 10 mg/kg ip. Após uma hora e meia da injeção, um cateter de pressão-volume foi locado no VE e um cateter pressórico na artéria femoral para aquisição dos parâmetros hemodinâmicos cardíacos e sistêmicos respectivamente. Foram estudados os ratos que apresentaram choque endotoxêmico (PAM <= 65 mmHg). Um grupo foi tratado com norepinefrina iv e outro com araminol iv, para atingir PAM de 85 mmHg. Para o estudo do fluxo sanguíneo, microesferas amarelas (15 ?m) foram injetadas no VE para analisar a microcirculação cardíaca. O coração foi analisado em três partes: VD, região epicárdica e região subendocárdica do VE. O estudo demonstrou uma redução de 58% na PPC e de 50% no fluxo miocárdico nos ratos com choque endotoxêmico. Houve queda de 34% na dP/dt max e 15% na dP/dt min comparados ao controle. Os parâmetros de função cardíaca sistólica volume-independentes, Ees e dP/dtmax / EDV, também apresentaram redução. Nos ratos tratados com norepinefrina, observou-se aumento da PPC (38 ± 2 vs. 59 ± 3 mmHg, LPS vs. LPS+NOR) e do fluxo sanguíneo miocárdico (2,0 ± 0,6 vs. 6,2 ± 0,8 mL/min.g tecido, LPS vs. LPS+NOR) e os índices de função cardíaca sistólica e diastólica mostraram recuperação. A PPC apresentou correlação significativa com o fluxo sanguíneo subendocárdico do VE.Os dados demonstraram que os animais em choque endotoxêmico e, portanto com PPC baixa, apresentaram redução no fluxo sanguíneo na microcirculação miocárdica, sobretudo no ventrículo direito e na região subendocárdica de VE. Isto se correlacionou com a disfunção cardíaca sistólica e diastólica. Ao elevar-se a PPC com a utilização de norepinefrina, houve aumento do fluxo sanguíneo miocárdico acompanhado de recuperação dos índices de função cardíaca / Septic patients with myocardial dysfunction have higher mortality compared to patients with no cardiovascular alteration. The aim of the present study was to investigate the role of coronary driving pressure as determinant factor of myocardial microcirculation blood flow and its correlation with the cardiac function in endotoxemic heart. Wistar rats, male, 300g were used. Endotoxemia was induced by the injection of 10 mg / kg ip LPS. After 1.5 h of injection, hemodynamic evaluation was performed. It was studied rats with MAP <= 65 mmHg. Norepinephrine and araminol were used to handle MAP to 85 mmHg. Millar catheter was placed in the left ventricle to the acquisition of cardiac parameters. Microspheres were infused into the left ventricle with a pump and it was collected blood from femoral artery and tissue samples, to measure blood flow in the myocardium (RV, subendocardium LV e epicardium LV) and other organs. Left ventricle parameters demonstrated a reduction (34%) in dP/dt max and (15%) in dP/dt min. Load independent indexes, Ees and dP/dtmax/ EDV showed a reduction after LPS. The coronary driving pressure was (58%) reduced in the endotoxemic rats. We found a reduction in myocardial blood flow (80%) in animals with mean arterial blood pressure below 65 mmHg. Norepinephrine increased coronary driving pressure (38 ± 2 vs. 59 ± 3 mmHg LPS vs. LPS+NOR), and microcirculation perfusion (2.0 ± 0.6 vs. 6.2 ± 0.8 mL/min.g tissue, LPS vs. LPS+NOR). Coronary driving pressure presented a significant correlation with sub endocardium blood flow. These data indicated that myocardial blood flow of left ventricle subendocardial region and right ventricle was decreased in endotoxemic rats in a coronary driving pressure dependent way. The reduced myocardial blood flow was determinant of cardiac dysfunction. Increasing systemic arterial blood pressures and consequently the coronary driving pressure, it succeeded to improve myocardial blood flow and cardiac function

Pacientes sépticos com disfunção miocárdica apresentam mortalidade significativamente superior comparados aos sépticos sem alteração cardiovascular. Vários mecanismos contribuem para disfunção orgânica na sepse, como diminuição de perfusão tecidual. A sepse está relacionada a alterações na microcirculação e na permeabilidade capilar que apresentam papel fundamental na fisiopatologia das disfunções orgânicas. O objetivo do estudo foi analisar o papel da pressão de perfusão coronariana como fator determinante do fluxo sanguíneo na microcirculação miocárdica e sua correlação com a função cardíaca sistólica e diastólica em ratos endotoxêmicos. Ratos machos, Wistar, 300g, receberam LPS 10 mg/kg ip. Após uma hora e meia da injeção, um cateter de pressão-volume foi locado no VE e um cateter pressórico na artéria femoral para aquisição dos parâmetros hemodinâmicos cardíacos e sistêmicos respectivamente. Foram estudados os ratos que apresentaram choque endotoxêmico (PAM <= 65 mmHg). Um grupo foi tratado com norepinefrina iv e outro com araminol iv, para atingir PAM de 85 mmHg. Para o estudo do fluxo sanguíneo, microesferas amarelas (15 ?m) foram injetadas no VE para analisar a microcirculação cardíaca. O coração foi analisado em três partes: VD, região epicárdica e região subendocárdica do VE. O estudo demonstrou uma redução de 58% na PPC e de 50% no fluxo miocárdico nos ratos com choque endotoxêmico. Houve queda de 34% na dP/dt max e 15% na dP/dt min comparados ao controle. Os parâmetros de função cardíaca sistólica volume-independentes, Ees e dP/dtmax / EDV, também apresentaram redução. Nos ratos tratados com norepinefrina, observou-se aumento da PPC (38 ± 2 vs. 59 ± 3 mmHg, LPS vs. LPS+NOR) e do fluxo sanguíneo miocárdico (2,0 ± 0,6 vs. 6,2 ± 0,8 mL/min.g tecido, LPS vs. LPS+NOR) e os índices de função cardíaca sistólica e diastólica mostraram recuperação. A PPC apresentou correlação significativa com o fluxo sanguíneo subendocárdico do VE.Os dados demonstraram que os animais em choque endotoxêmico e, portanto com PPC baixa, apresentaram redução no fluxo sanguíneo na microcirculação miocárdica, sobretudo no ventrículo direito e na região subendocárdica de VE. Isto se correlacionou com a disfunção cardíaca sistólica e diastólica. Ao elevar-se a PPC com a utilização de norepinefrina, houve aumento do fluxo sanguíneo miocárdico acompanhado de recuperação dos índices de função cardíaca / Septic patients with myocardial dysfunction have higher mortality compared to patients with no cardiovascular alteration. The aim of the present study was to investigate the role of coronary driving pressure as determinant factor of myocardial microcirculation blood flow and its correlation with the cardiac function in endotoxemic heart. Wistar rats, male, 300g were used. Endotoxemia was induced by the injection of 10 mg / kg ip LPS. After 1.5 h of injection, hemodynamic evaluation was performed. It was studied rats with MAP <= 65 mmHg. Norepinephrine and araminol were used to handle MAP to 85 mmHg. Millar catheter was placed in the left ventricle to the acquisition of cardiac parameters. Microspheres were infused into the left ventricle with a pump and it was collected blood from femoral artery and tissue samples, to measure blood flow in the myocardium (RV, subendocardium LV e epicardium LV) and other organs. Left ventricle parameters demonstrated a reduction (34%) in dP/dt max and (15%) in dP/dt min. Load independent indexes, Ees and dP/dtmax/ EDV showed a reduction after LPS. The coronary driving pressure was (58%) reduced in the endotoxemic rats. We found a reduction in myocardial blood flow (80%) in animals with mean arterial blood pressure below 65 mmHg. Norepinephrine increased coronary driving pressure (38 ± 2 vs. 59 ± 3 mmHg LPS vs. LPS+NOR), and microcirculation perfusion (2.0 ± 0.6 vs. 6.2 ± 0.8 mL/min.g tissue, LPS vs. LPS+NOR). Coronary driving pressure presented a significant correlation with sub endocardium blood flow. These data indicated that myocardial blood flow of left ventricle subendocardial region and right ventricle was decreased in endotoxemic rats in a coronary driving pressure dependent way. The reduced myocardial blood flow was determinant of cardiac dysfunction. Increasing systemic arterial blood pressures and consequently the coronary driving pressure, it succeeded to improve myocardial blood flow and cardiac function