Assessing the coronary circulation in hypertension

Systemic arterial hypertension is one of the major risk factors for coronary artery disease, coronary microangiopathy, and left ventricular hypertrophy, all of which can potentially lead to cardiac failure and sudden cardiac death. Coronary flow reserve is defined as the maximal increase in coronary flow above its resting, autoregulated level for a given perfusion pressure. In arterial hypertension functional and structural alterations are observed at the level of epicardial vessels as well as in resistive vessels requiring sophisticated approaches to assess coronary flow reserve and thus myocardial perfusion. Electrocardiographic tests and echocardiography can be regarded as monitoring and screening methods. Myocardial scintography is useful to semiquantitatively estimate hypertension-associated perfusion abnormalities, whereas positron emission tomography provides the only quantitative approach of a non-invasive technique for myocardial blood flow measurement. Invasive methods for the assessment of coronary blood flow need cardiac catheterization procedures, such as techniques requiring catheterization of the coronary sinus, angiographic methods, and guidewire based methods. Thermodilution and venous oxymetry in the coronary sinus systematically underestimate coronary flow reserve and are thus considered as only semiquantitative approaches. In contrast, the gas chromatographic argon method allows a quantitative measurement of coronary blood flow at baseline and during maximum vasodilation; thus it is possible to distinguish between an altered autoregulated and maximal flow as the major cause of a reduced coronary flow reserve and to evaluate long-term therapeutic interventions in hypertensive hearts. Videodensitometric and angiographic methods should be restricted only to patients with coronary microangiopathy or with coronary single-vessel disease. Guidewire-based Doppler techniques are suitable to semiquantitatively assess coronary flow reserve with a considerable spatial and time resolution. Myocardial biopsies may gain insight into hypertension-associated structural alterations in small arterioles. Long-term treatment of hypertensive heart disease aims to normalize blood pressure, to reduce left ventricular hypertrophy and to achieve cardioreparation including reversal of the abnormal structure and function of coronary circulation. Based on the different methods for assessment of coronary circulation the therapeutic value of different classes of antihypertensive therapeutics will be evaluated in this overview.     

Effects of various degrees of compression and active decompression on haemodynamics, end-tidal CO2, and ventilation during cardiopulmonary resuscitation of pigs

The effects of various degrees of compression and active decompression during cardiopulmonary resuscitation were tested in a randomized cross-over-design during ventricular fibrillation in eight pigs using an automatic hydraulic chest compression device. Compared with 4/0 (compression/decompression in cm), mean carotid arterial blood flow rose by 60% with 5/0, by 90% with 4/2 and 4/3, and 105% with 5/2. Two cm active decompression increased mean brain and myocardial blood flow by 53% and 37%, respectively, as compared with 4/0. Increasing standard compression from 4 to 5 cm caused no further increase in brain or heart tissue blood flow whether or not combined with active decompression. Tissue blood flow remained unchanged or decreased when active decompression (4/3) caused that 50% of the pigs were lifted from the table due to the force required. Myocardial blood flow was reduced with 5/0 vs. 4/0 despite no reduction in end decompression coronary perfusion pressure ((aortic-right atrial pressure) (CPP), (7 +/- 8 mmHg with 4/0, 14 +/- 11 mmHg with 5/0)(NS)). End decompression CPP increased by 186% with 4/2 vs. 4/0, by 200% with 4/3, and by 300% with 5/2. Endo-tracheal partial pressure of CO2 was significantly increased during the compression phase of active decompression CPR compared with standard CPR. Active decompression CPR generated an significantly increased ventilation compared with standard CPR. Conclusion: Carotid and tissue blood flow, ventilation, and CPP increase with 2 cm of active decompression. An attempt to further increase the level of active decompression or increasing the compression depth from 4 to 5 cm did not improve organ blood flow.     

Heart rate affects the dependency of myocardial oxygen consumption on flow in goats

The effect of flow steps in coronary arterial flow (Qa) on myocardial oxygen consumption (MVo2) was investigated at different heart rates (HR) to further elucidate the dependency of myocardial oxygen consumption on perfusion. In six anesthetized goats the left main coronary artery and the great cardiac vein were cannulated. The hearts were paced alternately at 60 and 130 beats per min. Flow steps were applied at both HR during control and maximal vasodilation by adenosine. MVo2, in steady state before and after the flow step, was calculated by multiplication of Qa and arterio-venous oxygen content difference (Fick's law). Heart rate affected the MVo2 dependency on flow during control as well as during maximal vasodilation. With vascular tone present, the MVo2 dependency on flow (DeltaMVo2/DeltaQa), in mu l O2/ml, was 16.0 +/- 3.6 at HR 60 and 21.7 +/- 3.9 at HR 130. During maximal vasodilation, these values were 9.5 +/- 2.9 and 17.0 +/- 5.3 at HR 60 and 130, respectively. The higher MVo2 dependency on flow at high HR may be explained via a dependency of MVo2 on microvascular pressure. The pressure change in the microvessels induced by a flow step is probably larger at high HR than at low HR because of increased venous resistance at high HR, due to increased compression by the heart contraction.     

Myocardial dysfunction after successful resuscitation from cardiac arrest

OBJECTIVE: To investigate the functional and metabolic changes in the myocardium after successful resuscitation from cardiac arrest. DESIGN: Prospective, randomized, sham-controlled study. SETTING: Animal laboratory at a university center. SUBJECTS: Domestic pigs. INTERVENTIONS: Electric induction of ventricular fibrillation by alternating current delivered to the right ventricular endocardium through a pacing electrode. Electric defibrillation was attempted after an interval of 12 mins of ventricular fibrillation, which included 4 mins of untreated ventricular fibrillation and 8 mins of precordial compression in 13 animals, seven of which were successfully resuscitated. Seven additional animals were randomized to serve as "sham" controls, in which cardiac arrest was not induced. MEASUREMENTS AND MAIN RESULTS: Left ventricular pressure-volume relationships utilizing the conductance method were obtained in conjunction with conventional hemodynamic and metabolic measurements at baseline and during a 6-hr interval after successful cardiac resuscitation. Progressive and striking increases in left ventricular volumes were observed after successful cardiac resuscitation. The end-diastolic volume increased from a prearrest level of 89 +/- 21 mL to a maximum of 154 +/- 53 mL (p<.05) at 360 mins after successful resuscitation. The time-coincident end-systolic volume increased from 54 +/- 21 to 126 +/- 54 mL (p<.05), such that the ejection fraction was reduced from 0.41 +/- 0.10 to 0.20 +/- 0.07 ( p<.05). Ventricular dilation was associated with marked reductions in stroke volume and ventricular work. However, compensatory increases in heart rate maintained cardiac output at levels that sustained adequate systemic oxygen delivery. The slope of the end-systolic pressure-volume relationships progressively decreased from 5.04 +/- 1.88 to 2.00 +/- 0.57 mm Hg/mL (p<.05) at 360 mins after successful resuscitation. The volume intercept at left ventricular pressure of 100 mm Hg increased from 43 +/- 19 to 94 +/- 51 mL (p=.03). Both the decrease in the slope and the increase in the volume intercept were characteristic of progressive impairment in contractile function. The rate of left ventricular pressure decrease was unchanged. Accordingly, no substantial changes in lusitropic properties were identified. Despite large increases in end-diastolic volume, the end-diastolic pressure remained unchanged. CONCLUSION: Postresuscitation myocardial dysfunction in this animal model was characterized by impaired contractile function, decreased work capability, and ventricular dilation.     

Effects of magnesium sulphate on the cardiovascular system, coronary circulation and myocardial metabolism in anaesthetized dogs

We have studied the effects of i.v. bolus doses of magnesium sulphate (MgSO4) 60, 90 and 120 mg kg-1 on haemodynamic state, the coronary circulation and myocardial metabolism in nine dogs anaesthetized with pentobarbitone and fentanyl. MgSO4 produced dose-dependent decreases in arterial pressure, heart rate, left ventricular dP/dtmax and left ventricular minute work index (LVMWI) and an increase in the time constant of left ventricular isovolumic relaxation. Stroke volume increased, systemic vascular resistance decreased and cardiac output did not change significantly. MgSO4 produced decreases in coronary perfusion pressure, coronary vascular resistance and myocardial oxygen consumption (MVO2). Coronary sinus blood flow, lactate extraction ratio and the ratio of LVMWI to myocardial MVO2, that is an index of cardiac efficiency, did not change significantly. This study indicated that the depressant effect of MgSO4 on cardiac function was offset by lowering of peripheral vascular resistance, so that cardiac pump function remained effective, and the almost constant coronary sinus blood flow resulted from the decrease in coronary vascular resistance even at higher doses.     

Sex and crime: heterotrimeric G proteins in fungal mating and pathogenesis

The coronary circulation is the major determinant of myocardial oxygen balance which in turn is necessary for adequate cardiac function under a variety of conditions. Experiments in the fetal lamb suggest short-term functional coronary autoregulation in response to increase in afterload and acute hypoxemia. Long-term, acute-on-chronic hypoxemia is associated with a marked increase of maximal myocardial flow reserve suggesting coronary vascular angio-neogenesis during the period of chronic hypoxemia. In the human fetus, flow velocity waveforms from the coronary arteries may be obtained by color-coded and pulsed wave Doppler sonography in normally developed fetuses from 31 weeks of gestation onwards under favorable imaging conditions. Coronary blood flow may also be visualized in selected fetuses with intrauterine growth restriction, absent or reversed end-diastolic flow in the umbilical artery, cephalization of blood flow and abnormal flow patterns in the precordial veins and the umbilical vein. In these fetuses visualization of coronary blood flow may be possible as early as 26 weeks gestation and is consistently associated with a significant increase in the peak velocity index for veins in the ductus venosus. In this circulatory state, visualization of coronary blood flow is suddenly very easy. This "visualization threshold" may be a sign of maximal increase in coronary blood flow in an attempt to "spare" the fetal heart of hypoxemia. Although highly operator dependent, demonstration of coronary blood flow in intrauterine growth restriction identifies fetuses at high risk for intrauterine fetal death and postpartum circulatory failure.     

Effect of hypertonic saline solution and dextran on ventricular blood flow and heart-lung interaction after hemorrhagic shock

BACKGROUND: Hypertonic saline solutions may have beneficial hemodynamic effects in the resuscitation of hemorrhagic shock. The effects on cardiac function and potential interaction with lung function are controversial and served as the basis for this study. METHODS: Domestic swine were resuscitated from hemorrhagic shock with equivalent sodium loads of lactated Ringer's solution (LR) or 7.5% NaCl plus 10% dextran (HSD). Hemodynamic data were obtained at baseline, shock, and after resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time (dP/dt) were used to index contractility. Regional myocardial blood flow was determined with microspheres. Lung water was determined gravimetrically. RESULTS: There were no differences in the ability to restore hemodynamic parameters with equivalent sodium loads of LR and HSD resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time were only transiently affected by shock and resuscitation. Regional myocardial blood flow was increased above baseline values after HSD. The total resuscitation volumes were 1958 +/- 750 mL and 140 +/- 31 mL with LR and HSD, respectively. CONCLUSIONS: Although LR and HSD were equally effective in the early resuscitation of hemorrhagic shock, this occurred at the expense of significantly greater volume requirements for resuscitation with LR. This may contribute to cardiac dysfunction in this setting. Enhanced regional myocardial blood flow after HSD resuscitation may be beneficial against ongoing myocardial stress.     

Non-invasive continuous haemodynamic and PETCO2 monitoring during peroperative cardiac arrest

We describe a cardiac arrest which occurred during general anaesthesia in the prone position for surgical correction of lumbar kyphosis in a patient with Marfan's syndrome. Peroperative monitoring was routine with ECG, non-invasive arterial pressure, oximetry, PETCO2 and central venous pressure, plus aortic blood flow and and systolic time intervals via an oesophageal echo-Doppler device. Forty-five minutes after the start of surgery, a sudden decrease in aortic blood flow followed by a decrease in PETCO2 suggested acute cardiac failure despite continuation of the ECG signal. Initial CPR in the prone position produced a slight increase in PETCO2. When the patient was turned to the supine position and the legs elevated, chest compression was more efficient and spontaneous circulation was rapidly restored. Circulatory arrest could be explained by incompletely treated hypovolaemia, or by myocardial depression (decrease in aortic blood flow and lengthened pre-ejection period) combined with excessive hypotension in a patient with Marfan's syndrome, thus compromising coronary blood flow producing ST segment depression. Continuous non-invasive aortic blood flow and PETCO2 monitoring proved valuable in the early detection and treatment of circulatory arrest and in the evaluation of the efficiency of peroperative CPR.     

Measurement of coronary flow reserve and its role in patient care

Coronary anatomy and myocardial blood flow are major determinants of clinical symptomatology and survival in patients with coronary artery disease. While coronary anatomy has been successfully assessed by coronary angiography and intravascular ultrasound imaging, measurements of coronary blood flow are more difficult and their prognostic value has not been definitively evaluated. Measurements of coronary flow reserve (CFR), defined as maximal hyperemic flow divided by resting flow, have been used to assess the functional significance of coronary artery lesions. However, functional assessment of epicardial coronary lesions is limited by several factors, such as diffuse coronary artery disease, small-vessel disease, regional variations in myocardial flow, endothelial dysfunction, and left ventricular hypertrophy. CFR can be measured by several techniques, each one with distinct advantages and limitations, which are discussed in this review. An important distinction is between techniques that measure coronary blood flow (e.g., positron emission tomography) and those that measure blood flow velocity (e.g., Doppler catheters), from which coronary velocity reserve (CVR) is calculated. Although clinical CFR measurements have been possible for over fifteen years, their implementation in patient care has been slow due to several factors including the requirement for a sophisticated technology, the difficult interpretation of CFR results, and the limited knowledge of their prognostic value. While a normal CFR in patients with single vessel coronary disease is associated with a good prognosis, the converse has not been established, i.e., that there is a critical reduction in CFR that requires interventional treatment. A recent study (DEBATE) showed a decrease in the incidence of cardiac events at 6 months after coronary balloon angioplasty in patients with a post-procedural percent diameter stenosis < 35% and a CVR > 2.5. The complex relation between coronary anatomy, myocardial perfusion, and patient outcome have enormous implications for both patient care and health costs, which need to be addressed in future prospective trials.     

Substrate specificity of human prolyl-4-hydroxylase

BACKGROUND: The mechanism responsible for the forward blood flow associated with external chest compression is still controversial. Evidence for both blood flow caused by direct cardiac compression and blood flow generated by a general increase in intrathoracic pressure has been found in experimental as well as clinical studies. No data are available concerning the mechanism causing forward blood flow in hypothermic patients undergoing cardiopulmonary resuscitation. Therefore, echocardiographic findings during external chest compression in seven hypothermic arrest victims are reported. METHODS: All transesophageal echocardiographic studies performed at the Anaesthesia department between 1994 and 1997 were reviewed and seven hypothermic patients with transesophageal echocardiography performed during cardiopulmonary resuscitation were identified. RESULTS: An open mitral valve or a circumferential reduction in aortic diameter during the compression phase was found in four of seven patients, indicating that primarily an increase in intrathoracic pressure (thoracic pump mechanism) generated forward blood flow. In three patients, mitral valve closure during external chest compression indicated that direct cardiac compression (cardiac pump mechanism) contributed to forward blood flow. Two patients studied during active compression-decompression cardiopulmonary resuscitation demonstrated enhanced right ventricular filling and aortic valve opening during active decompression of the thorax. CONCLUSIONS: In contrast to normothermic arrest victims, an open mitral valve during external chest compression is a common finding during hypothermia, indicating that thoracic pump mechanism is important for forward blood flow during cardiopulmonary resuscitation in hypothermic arrest victims. Aortic valve opening in two hypothermic arrest victims suggests forward blood flow also during active decompression of the thorax with the Cardiopump.     

The isolated supported canine heart: a model for the evaluation of drug effects on regional myocardial blood flow

The present investigation was designed to determine the effect of propranolol on regional myocardial blood flow and oxygen consumption (MVO2) in the isolated supported dog heart preparation perfused at a constant coronary blood flow. The transmural distribution of blood flow, determined by the radioactive microsphere technique, was expressed as the epicardial/endocardial blood flow ratio (epi/endo). Propranolol (0.5 mg/kg i.v.) produced a significant decrease in heart rate and myocardial contractile force and an increase in coronary artery perfusion pressure due to an increase in coronary vascular resistance. These hemodynamic changes were accompanied by significant decreases in epi/endo (increased endocardial perfusion) and MVO2. Reduction of perfusion pressure to control by a decrease in total coronary blood flow produced no further change in epi/endo or MVO2. However, increasing heart rate to control increased epi/endo to predrug levels. Contractile force and MVO2 remained reduced below control. Norepinephrine infusion (1 mug/min intracoronary) produced a significant increase in heart rate and contractile force and decrease in perfusion pressure. These changes were accompanied by an increase in epi/endo and MVO2. Propranolol (0.5 mg/kg i.v.) abolished the response to norepinephrine. Propranolol may produce beneficial effects in angina pectoris by a decrease in epi/endo (via a reduction in heart rate) and MVO2 and by beta adrenergic blockade of the deleterious effects of catecholamines.     

Magnetic resonance imaging of perfusion in the isolated rat heart using spin inversion of arterial water

Measurement of regional myocardial perfusion is important for the diagnosis and treatment of coronary artery disease. Currently used methods for the measurement of myocardial tissue perfusion are either invasive or not quantitative. Here, we demonstrate a technique for the measurement of myocardial perfusion using magnetic resonance imaging (MRI) with spin tagging of arterial water. In addition, it is shown that changes in perfusion can be quantitated by measuring changes in tissue T1. Perfusion images are obtained in Langendorff-perfused, isolated rat hearts for perfusion rates ranging from 5 to 22 ml/g/min. The MRI-determined perfusion rates are in excellent agreement with perfusion rates determined from measurement of bulk perfusate flow (r = 0.98). The predicted linear dependence of the measured T1 (T1app) on perfusion is also demonstrated. The ability of perfusion imaging to measure regional variations in flow is demonstrated with hearts in which perfusion defects were created by ligation of a coronary artery. These results indicate that MRI of perfusion using spin inversion of arterial water gives quantitative maps of cardiac perfusion.     

Cardiovascular effects of amitriptyline in anaesthetized dogs

1. The effect of amitriptyline on cardiovascular variables has been studied in anaesthetized dogs. 2. In small doses (0.25 mg/dg) amitryptyline caused small increases in heart rates, contractility, blood pressure, coronary blood flow and aortic flow. 3. Large doses produced initial depressant effects on myocardial reflex rises in these and rate and blood pressure, which were followed by secondary reflex rises in these measurements. 4. The depressant effects were dose-related and were accompanied by marked increases in coronary flow and smaller increases in ortic flow. 5. The secondary reflex rises in cardiac parameters were abolished by propranolol and that of the blood pressure was much reduced.     

Methods for coronary functional assessment

Functional evaluation of coronary vasomotion encompasses the assessment of dynamic changes in coronary lumen, vessel wall, blood flow, intracoronary pressure and myocardial perfusion in response to specific pharmacologic stimuli. These parameters are obtained to characterize mechanisms of physiologic regulation and to evaluate pathophysiologic processes and potential therapeutic strategies, especially with regard to the development of coronary atherosclerosis. To this end, a variety of direct (invasive) and indirect (non-invasive) diagnostic tools are employed. Among the invasive methods are registration of intracoronary Doppler flow, coronary pressure measurements, quantitative coronary angiography and intravascular ultrasound. The non-invasive modalities consist of coronary Doppler echocardiography, positron emission tomography, myocardial scintigraphy and magnetic resonance imaging. Because of the different technical and physiological principles involved, these methods are complementary by providing independent access to different aspects. The combined invasive functional testing as employed in the cardiac catheterization laboratory allows for a simultaneous synopsis of high-resolution coronary imaging and direct measurement of physiologic parameters during local application of defined pharmacologically active substances. However, the demands in terms of equipment, time and operator skills are high and limit this combined invasive approach to specialized centers. Besides these research purposes, a number of functional methods has entered the clinical arena. They are employed to evaluate the hemodynamic significance of coronary lesions and to assess functional outcome of therapeutic interventions in the catheterization laboratory. The underlying principles and applications of the different methods are described and an overview of selected results is presented.     

Insights into the assessment of myocardial perfusion offered by different cardiac imaging modalities

Myocardial perfusion may be very broadly defined as the tightly regulated nutrient delivery to cardiac tissue. The different components of perfusion are myocardial blood flow, oxygen delivery, myocardial oxygen consumption, and myocardial blood volume. Historically, focus has been placed mostly on the assessment of blood flow. In many instances, knowledge of flow without information about these other aspects is inadequate. This review discusses the various cardiac imaging techniques used for the assessment of myocardial perfusion that represent diverse physiologic measures of "perfusion." Their strengths and limitations are discussed as is their relevance to specific clinicopathologic conditions. Significant work still needs to be performed before all the aspects of myocardial perfusion can be precisely measured in human beings.     

The effects of coronary vasodilatation on cardiac performance during endotoxin shock

Results of studies have suggested that endotoxin and lowered coronary arterial perfusion pressures are detrimental to cardiac performance and lead to failure. Prevention of cardiac failure in the isolated canine heart preparation confronted with endotoxin and decreased coronary perfusion pressure was possible by perfusing these hearts with sodium nitroprusside. Prevention of failure was manifested by a lowered left ventricular endiastolic pressure and was associated with increased coronary flow and decreased coronary resistance with increased oxygen delivery and decreased oxygen extraction. Possible explanations for improved performance by dilator perfusion include increased delivery of oxygen and nutrients to myocardial tissue as well as a reduction of ventricular wall tension by dilating the coronary vascular skeleton. Prevention of extravasation of interstitial fluid into myocardial tissue by reducing overperfusion of potentially damaged coronary vessels could serve to maintain myocardial integrity and ventricular compliance. The potential use of such therapy warrants further study, with emphasis on evaluating the hemodynamics of the intact animal.     

Effect of ortho-iodo sodium benzoate on hemoglobin-oxygen affinity in normal and ischemic myocardium

The effect of ortho-iodo sodium benzoate (OISB) on the oxyhemoglobin dissociation curve of coronary venous blood was studied in an isolated canine heart preparation perfused at a constant coronary blood flow. Changes in P-50 (millimeters of mercury) [the oxygen tension (pO2) at which hemoglobin is 50% saturated], were used to express hemoglobin-oxygen affinity. Intracoronary infusion of OISB (200, 400 and 800 mg/min) produced a dose-related increase in coronary venous P-50 and a concurrent increase in coronary venous pO2. In addition, OISB produced a significant decrease in heart rate and increase in coronary artery perfusion pressure. During cardiac pacing at 150, 190 and 230 beats/min, OISB (400 mg/min) significantly increased coronary venous P-50, myocardial oxygen exrraction (O2E) and oxygen consumption (MVO2) whereas coronary venous PO2 was not changed. Furthermore, a 5-minute intracoronary infusion of OISB (200 mg/min) during myocardial ischemia produced an increase in O2E, MVO2 and myocardial contractility with little change in coronary venous pO2. These results suggest that acute pharmacological manipulation of the oxyhemoglobin dissociation curve may enhance oxygen release to the myocardium while maintaining the effective driving pressure (as reflected in coronary venous pO2) for diffusion of oxygen to the myocardium.     

Perfusion of ischemic myocardium during anesthesia with sevoflurane

BACKGROUND: Sevoflurane produces direct vasodilation of coronary arteries in vitro and decreases coronary vascular resistance in vivo, pharmacologic properties that may contribute to the development of "coronary steal." This investigation examined the effects of sevoflurane on the distribution of regional myocardial perfusion in chronically instrumented dogs with steal-prone coronary artery anatomy. METHODS: Dogs were chronically instrumented for measurement of aortic and left ventricular pressure, diastolic coronary blood flow velocity and subendocardial segment length. After recovery from surgery, dogs underwent repetitive, brief, left anterior descending coronary artery (LAD) occlusions via an implanted hydraulic vascular occluder to enhance collateral development. A progressive left circumflex coronary artery (LCCA) stenosis was also obtained using an ameroid constrictor. After development of LCCA stenosis, the LAD was totally occluded to produce a model of multivessel coronary artery disease. Systemic hemodynamics, regional contractile function and myocardial perfusion measured with radioactive microspheres were assessed in the conscious state and during sevoflurane anesthesia at 1.0 and 1.5 MAC with and without restoration of arterial blood pressure and heart rate to conscious levels. RESULTS: Total LAD occlusion with simultaneous LCCA stenosis increased heart rate, mean arterial pressure, left ventricular systolic and end-diastolic pressures, end-diastolic segment length, and rate-pressure product in conscious dogs. Subsequent administration of sevoflurane caused dose-related decreases in arterial pressure, left ventricular systolic pressure, double product, and peak rate of increase of left ventricular pressure at 50 mmHg. Perfusion of normal myocardium was unchanged during sevoflurane anesthesia. In contrast, sevoflurane caused dose-dependent decreases in blood flow to myocardium supplied by the stenotic LCCA, which returned to control levels after restoration of heart rate and arterial pressure. No reduction in collaterally derived blood flow to the occluded region was produced by 1.0 or 1.5 MAC sevoflurane. No redistribution of blood flow away from the occluded LAD region to normal or stenotic myocardium occurred during sevoflurane anesthesia. In fact, increases in the ratio of blood flow between occluded and normal zones or occluded and stenotic zones were observed in the subepicardium during 1.5 MAC sevoflurane with maintenance of the heart rate and arterial pressure at conscious levels. CONCLUSIONS: The results demonstrate that sevoflurane does not reduce or abnormally redistribute myocardial blood flow derived from coronary collateral vessels in a chronically instrumented canine model of multivessel coronary artery obstruction.     

Disturbed intracoronary hemodynamics in myocardial bridging: early normalization by intracoronary stent placement

BACKGROUND: The purpose of this study was to evaluate the hemodynamic mechanisms leading to myocardial ischemia in patients with myocardial bridging. Myocardial bridging is known to induce angina and even severe myocardial ischemia. METHODS AND RESULTS: In 12 symptomatic patients with myocardial bridges, quantitative coronary angiography was performed to obtain systolic/diastolic vessel diameters within the bridged segments. Coronary flow velocities, flow reserve, and pressures were determined with a 0.014-in Doppler and a 0.014-in pressure microtransducer. In 3 symptomatic patients, coronary stents were implanted and hemodynamic measurements were repeated immediately and after 7 weeks. An in vitro validation of the pressure measurements was performed. Angiography revealed a systolic diameter reduction of 80.6+/-9.2% and a persistent diastolic reduction of 35.3+/-11% within the bridged segment. Diastolic flow velocities (cm/s) were increased (31.5+/-14.3 within versus 17.3+/-5.7 proximal and 15.2+/-6.3 distal, P<.001). Coronary flow reserve distal to the bridge was 2.5+/-0.5. There was an increased peak systolic pressure within the bridged segment (171+/-48 versus 113+/-10 mm Hg proximal, P<.001). Stent placement abolished the phasic lumen compression, the diastolic flow abnormalities, the intracoronary peak systolic pressure, and clinical symptoms. Coronary flow reserve improved to 3.8+/-0.3. CONCLUSIONS: Coronary hemodynamics in myocardial bridges are characterized by a phasic systolic vessel compression with a localized peak pressure, persistent diastolic diameter reduction, increased blood flow velocities, retrograde flow, and a reduced flow reserve. These alterations may explain the occurrence of symptoms and ischemia in these patients. Intracoronary stent placement abolished all hemodynamic abnormalities and may improve clinical symptoms in otherwise unsuccessfully treated patients with myocardial bridges.     

Inhibition of angiotensin-converting enzyme increases the nitric oxide levels in canine ischemic myocardium

Since angiotensin-converting enzyme (ACE) produces angiotensin II in the heart, ACE inhibitors may prevent coronary vasoconstriction and increase coronary blood flow. On the other hand, since ACE inhibitors also inhibit kininase II which results in reduced degradation of bradykinin, ACE inhibitors may increase cardiac nitric oxide (NO) levels via stimulation of bradykinin receptors. This study was undertaken to test whether ACE inhibitors increase the cardiac NO levels and coronary blood flow in the ischemic myocardium. In 34 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery. When either imidaprilat or cilazaprilat of 3 microg/kg/min was infused into the bypass tube for 10 min after reduction of coronary blood flow due to partial occlusion of the bypass tube, coronary blood flow increased from 31 +/- 1 to either 45 +/- 5 or 43 +/- 4 ml/100 g/min despite no changes in coronary perfusion pressure (43 +/- 2 mmHg). During an infusion of either imidaprilat or cilazaprilat, bradykinin and the end-products of NO (nitrate + nitrite) concentrations of coronary venous blood were markedly increased, which were attenuated by either HOE-140 (an inhibitor of bradykinin receptors) or by N(omega)-nitro-L-arginine methyl ester (an inhibitor of NO synthase). We also observed increases in cardiac bradykinin and NO levels due to either imidaprilat or cilazaprilat in the low constant coronary blood flow condition. It is concluded that ACE inhibitors can increase cardiac NO levels via the accumulation of bradykinin in the ischemic myocardium.