The effects of thermogenic agents on hindlimb oxygen consumption in the dog: ICI D7114 and noradrenaline

OBJECTIVES: The purpose of this study was to test the hypothesis that the diameter of the recipient coronary artery of the well developed collateral circulation in patients with acute myocardial infarction increases because of the augmented intravascular pressure caused by subsequent collateral development. BACKGROUND: It is well known that collateral circulation develops after acute myocardial infarction. However, some patients have a well developed collateral circulation at the onset of infarction, which may limit the angiographic evaluation of further development of collateral circulation. METHODS: We measured the diameter of the donor and recipient arteries of the collateral circulation by means of a computer-assisted analysis system in seven patients with acute myocardial infarction who had a totally occluded infarct-related coronary artery during the acute and chronic stages of infarction. All coronary angiograms were obtained after the administration of sublingual nitroglycerin. The measurement was repeated immediately after (within 6 h) and late after (42 +/- 11 days) the onset of acute myocardial infarction. RESULTS: The diameter of the donor artery remained unchanged (1.32 +/- 0.98 vs. 1.42 +/- 1.12 mm). In contrast, the diameter of the recipient artery increased from 1.25 +/- 0.63 to 1.55 +/- 0.61 mm (p < 0.01). These changes in coronary artery diameter were associated with an improvement in regional myocardial wall motion at rest in infarct areas (6.7 +/- 7.0% vs. 13.6 +/- 10.7%, p < 0.05). CONCLUSIONS: These findings indicate that serial measurement of coronary artery diameter is useful for the evaluation of collateral development after acute myocardial infarction.     

Subendocardial myocardial ischemia as assessed with myocardial contrast echocardiography in patients with ischemic heart diseases

Myocardial contrast echocardiography was used to characterize changes in the regional and transmural myocardial blood flow distribution that were provoked by rapid atrial pacing stress in patients with coronary artery diseases. In patients with coronary organic stenosis, a decrease in the myocardial contrast-enhancement in the subendocardial half after rapid atrial pacing was associated with stress-induced chest pain and electrocardiographic ST-T changes. The decrease in the myocardial contrast-enhancement in the subendocardial half after rapid atrial pacing was not observed in patients without coronary stenosis or after coronary angioplasty. Thus, the finding was considered to reflect myocardial ischemia. Pacing-induced decreases in myocardial contrast-enhancement were observed in some patients with old myocardial infarction and significant resting coronary collaterals. In these patients, myocardial ischemia was considered to have developed at rapid pacing because collateral function was good enough to perfuse the infarct myocardium at rest, but was not good enough to prevent myocardial ischemia at stress. Thus, myocardial contrast echocardiography seems to be particularly useful in assessing myocardial ischemia at stress due to coronary stenosis in patients with angina pectoris and due to poor dynamic collateral function in patients with old myocardial infarction.     

Functional significance of coronary collateral vessels in patients with previous 'Q' wave infarction: relation to aneurysm, left ventricular end diastolic pressure and ejection fraction

The importance of coronary collateral circulation in relation to the left ventricular function, aneurysm formation and size was investigated in 100 patients with previous 'Q' wave myocardial infarction who underwent coronary angiography. Aneurysms were present in 20% of patients. The majority of these (80%) patients had severe or total occlusion of the left anterior descending artery. Thirty four percent of patients without aneurysm had significant collaterals whereas 25% of patients with aneurysms had collaterals (P > 0.05). However, the size of the aneurysm was smaller when adequate collateral circulation was present (Collateral Index 2 or above). The incidence of hypertension and diabetes was similar in both groups. Collateral circulation was more frequently seen in the anterior (60%) as compared to inferior myocardial infarction (40%), but Collateral Index was higher in right coronary artery disease. The number of patients with an elevated left ventricular end-diastolic pressure (> 12) or poor ejection fraction was similar in the two groups with and without collaterals. Thus, there was no beneficial effect of collateral circulation on left ventricular function. The incidence of aneurysm was not significantly lower, although the size of the aneurysm was significantly smaller in the presence of collateral circulation.     

Noninvasive prediction of residual blood flow within the risk area during acute myocardial infarction: a multicenter validation study of patients undergoing direct coronary angioplasty

BACKGROUND: In a previous study from a single center, radionuclide measures of collateral flow with technetium 99m sestamibi have been shown to be significantly associated with angiographic residual (antegrade and collateral) flow and independent predictors of final infarct size in acute myocardial infarction. This study examined whether the previously described radionuclide measures of blood flow to the infarct zone were reproducible with different laboratories and imaging systems. METHODS AND RESULTS: Residual flow to the infarct zone was assessed by both invasive and noninvasive methods in 77 patients with first-time myocardial infarction (32 anterior, 45 nonanterior). All patients underwent acute coronary angiography before any intervention within 8 hours of the onset of chest pain (4.0 +/- 1.5 hours; range 1.2 to 7.9 hours). 99mTc sestamibi was injected intravenously before reperfusion therapy, and tomographic imaging was performed 1 to 6 hours after injection. A central core laboratory processed the acquired images from three centers, each with a unique camera and computer system. Three previously published methods based on the severity of the acute perfusion defect were used to measure residual flow to the infarct zone (nadir, severity index, area). Antegrade (Thrombolysis in Myocardial Infarction flow) and collateral flow before direct angioplasty were blindly graded on a four-point scale (0 to 3) from the acute angiogram. The simple sum of the two grades was defined as the angiographic flow index, representing residual flow to the jeopardized zone. All three noninvasive measures of residual flow were highly associated with the angiographic flow index in a linear fashion: severity index (p = 0.0006), area (p = 0.003), and nadir (minimum/maximum counts; p = 0.004). This association was independent of the laboratory where the data were acquired. CONCLUSIONS: Despite different laboratories and camera systems, radionuclide measures of residual flow were highly associated with the angiographic flow index before reperfusion therapy. These results suggest that these measures are applicable on a broader scale for the noninvasive determination of collateral and antegrade flow in acute myocardial infarction.     

Improvement of exercise capacity by sarpogrelate as a result of augmented collateral circulation in patients with effort angina

OBJECTIVES: The purpose of this study was to evaluate whether a serotonin blocker, sarpogrelate, improves exercise capacity as a result of vasodilation of coronary collateral channels in patients with effort angina. BACKGROUND: Serotonin has been reported to decrease coronary collateral blood flow by collateral vasoconstriction in a canine model, suggesting that platelet activation in feeding coronary arteries of the collateral network has the potential to cause collateral vasoconstriction. METHODS: The subjects consisted of 22 patients with effort angina and reproducible ischemic threshold (group A, 11 patients with thrombolysis in myocardial infarction (TIMI) grade 2 or 3 flow of the ischemia-related coronary artery and Rentrop's collateral index 0 or 1; group B, 11 patients with TIMI grade 0 or 1 flow and Rentrop's collateral index 2 or 3). We repeated the symptom-limited treadmill exercise test using the Balke-Ware protocol and exercise tetrofosmin myocardial perfusion scintigraphy with and without pretreatment with 200 mg orally administered sarpogrelate. Each exercise test was performed at 9:00 a.m. on different days. The order of tests with and without sarpogrelate was randomized. RESULTS: In group A, sarpogrelate increased neither exercise time at 0.1 mV ST depression nor double product at 0.1 mV ST depression. In contrast, in group B sarpogrelate increased the exercise duration at 0.1 mV ST depression from 181+/-112 (SD) to 248+/-131 s (p < 0.05) and also increased the double product at 0.1 mV ST depression by 21% (p < 0.01). The severity score using myocardial perfusion scintigraphy at the same workload was significantly (p < 0.01) decreased by 37% in group B, but not in group A (11%), due to the sarpogrelate treatment. CONCLUSIONS: Sarpogrelate augments flow reserve of the collateral circulation and improves exercise capacity in anginal patients with well-developed collaterals. These findings indicate that a serotonin blocker, sarpogrelate, is useful not only as an antiplatelet drugs, but as an antianginal drug.     

Practical coronary physiology. Clinical application of the Doppler flow velocity guide wire

Coronary angiography incompletely delineates the physiologic consequences of many epicardial stenoses. Intracoronary translesional flow velocity measurements using the Doppler flow wire during cardiac catheterization provide immediate data discriminating the physiologic significance of coronary stenoses. The validity and accuracy of the flow wire for analyzing lesion hemodynamic significance have been confirmed in multiple studies. Flow velocity analysis provides objective criteria for refining the selection of cases for revascularization, and prospective clinical data have confirmed the safety of deferring intervention on lesions with normal physiologic assessment. Translesional and distal coronary flow velocity dynamics during procedures also provide immediate data assessing the physiologic adequacy of intervention. Impaired postintervention distal coronary flow velocity and vasodilator reserve can predict subsequent clinical events, and comparisons of flow velocity indices prestenting and poststenting suggest that physiologically inadequate results of angioplasty may be improved by additional intervention. Flow velocity assessment may also have utility in profiling the adequacy of infarct artery reperfusion following acute myocardial infarction. Evidence has been accumulated to support use of Doppler flow velocity analysis as a clinically relevant technique for improving both diagnostic and therapeutic aspects of cardiovascular medicine.     

Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1

The mechanisms regulating coronary collateral circulation are largely unknown owing to both the complex and variable nature of clinical models and the difficulty to obtain quantitative and differentiated flow measurements within the various coronary tree portions. With the aim of assessing collateral flow reserve, we studied 19 patients with effort angina, without myocardial infarction and with isolated occlusion of either the left anterior descending coronary artery (n = 14) or the circumflex coronary artery (n = 5). Flow values were measured basally, during atrial pacing induced tachycardia and following ev dipyridamole infusion (0.56 mg/kg of body weight in 4 min), by means of positron emission tomography and nitrogen-13 ammonia as flow tracer, within both regions depending on collateral circulation and the remote ones. Results have been compared with those obtained in 13 normal subjects. Basal flow values in regions depending on collateral circulation and in the remote regions (0.61 +/- 0.11 vs 0.63 +/- 0.17 ml/min/g) were found to be similar, but lower than in normal subjects (1.00 +/- 0.20 ml/min/g, p < 0.01). During atrial pacing, flow increased to 0.83 +/- 0.25 and to 1.11 +/- 0.39 ml/min/g, in the regions depending on collateral circulation and in the remote regions, respectively (p < 0.05 as compared to baseline); again, values were lower than in normal subjects (1.86 +/- 0.61 ml/min/g, p < 0.01). Dipyridamole infusion further increased flow in the remote regions (1.36 +/- 0.57 ml/min/g, p < 0.01 as compared to atrial pacing) but it did not in the regions depending on collateral circulation (0.94 +/- 0.37 ml/min/g, NS as compared to atrial pacing); both values were lower than in normal subjects (3.46 +/- 0.78 ml/min/g, p < 0.01). Flow reserve in the regions depending on collateral circulation was found to have a direct linear correlation with the one in the remote regions (r = 0.83; p < 0.01). In conclusion, in spite of basal hypoperfusion, collateral circulation maintains a flow reserve which, even if reduced, is able to cope with moderate increments in oxygen consumption. An analogous flow reduction can be observed in the remote regions, suggesting that the entire coronary tree is involved, beyond the obstructive lesions of the main arterial branches.     

Coronary collateral quantitation in patients with coronary artery disease using intravascular flow velocity or pressure measurements

OBJECTIVES: This study evaluated two methods for the quantitative measurement of collaterals using intracoronary (IC) blood flow velocity or pressure measurements. BACKGROUND: The extent of myocardial necrosis after coronary artery occlusion is substantially influenced by the collateral circulation. So far, qualitative methods have been available to assess the human coronary collateral circulation, thus restraining the conclusive investigation of, for example, therapies to promote collateral development. METHODS: Fifty-one patients with a coronary artery stenosis to be treated by percutaneous transluminal coronary angioplasty (PTCA) were investigated using IC PTCA guidewire-based Doppler and pressure sensors positioned distal to the stenosis. Simultaneous measurements of aortic pressure, IC velocity and pressure distal to the stenosis during and after PTCA provided the variables for calculating collateral flow indices (CFIv and CFIp) that express collateral flow as a fraction of flow via the patent vessel. Both CFIv and CFIp were compared with conventional methods for collateral assessment, among them ST-segment changes >1 mm on IC and surface electrocardiogram (ECG) at PTCA. Also, CFIv and CFIp were compared with each other. RESULTS: In 11 patients without ECG signs of ischemia during PTCA (sufficient collaterals), relative collateral flow amounted to 46% as determined by Doppler and pressure wire. Patients with insufficient collaterals (n=40) had relative collateral flow values of 18%. Using a threshold of CFI=30%, sufficient and insufficient collaterals could be diagnosed with 100% sensitivity and 93% specificity by IC Doppler, and 75% sensitivity and 92% specificity by IC pressure measurements. The agreement between Doppler and pressure measurements was good: CFIv=0.08 + 0.8 CFIp, r=0.80, p=0.0001. CONCLUSIONS: Intracoronary flow velocity or pressure measurements during routine PTCA represent an accurate and, at last, quantitative method for assessing the coronary collateral circulation in humans.     

Arrhythmias associated with acute myocardial infarction and thrombolysis

Ninety percent of patients with acute myocardial infarction have some cardiac rhythm abnormality, and approximately twenty-five percent have cardiac conduction disturbance within 24 hours following infarct onset. Almost any rhythm disturbance can be associated with acute myocardial infarction, including bradyarrhythmias, supraventricular tachyarrhythmias, ventricular arrhythmias, and atrioventricular block. With the advent of thrombolytic therapy, it was found that some rhythm disturbances in patients with acute myocardial infarction may be related to successful coronary artery reperfusion. This article addresses the role and treatment of arrhythmias and conduction disturbances that complicate the course of patients with acute infarction and thrombolysis.     

Complete occlusion of the left main coronary artery and the importance of coronary collateral circulation

Study of four patients who survived complete occlusion of the left main coronary artery forms the basis of conclusions concerning the functional significance of coronary collateral circulation. Each of these patients had prominent collateral circulation from the right coronary artery. Global left ventricular function was maintained to the extent that congestive heart failure did not occur; the biplane ejection fraction was normal in the two patients where measurement was possible. The peak rate of systolic wall thickening by roentgen videometry in anterior left ventricular segments was normal in one patient and mild to moderately depressed in another. Experience with the patients described herein indicates that coronary collateral flow can provide critically needed circulatory support for the patient with coronary artery disease.     

Physiologic and clinical significance of myocardial blood flow quantitation: what is expected from these measurements in the clinical ward and in the physiology laboratory?

In this essay we review data on absolute quantitation of myocardial blood flow (MBF) in humans. Earlier work established that coronary heart disease (CAD) can be detected by coronary angiography and that this disease has characteristic features at rest and during stress, which indicate the linkage between regional metabolic needs and myocardial perfusion. In the 1970s myocardial perfusion was mapped in patients with radioxenon, but this method had significant technical limitations. About the same time, radioactive microspheres were introduced for cardiovascular research and investigations; these particles provided insights on MBF in acute infarction and ischemia, myocardial reperfusion, collateral circulation, myocardial blood flow during exercise, coronary flow reserve (CFR), and layer-to-layer distribution of MBF. Studies with microspheres also permitted investigators to establish the presence in the heart of MBF heterogeneity. Currently, there are several techniques that aim at extending these concepts into clinical investigation. Two of these techniques, i.e. Doppler coronary flow velocity and fast magnetic resonance imaging assess epicardial flow dynamics and CFR. Contrast myocardial echocardiography is another novel technique which has been useful in mapping the area at risk, reperfusion, myocardial viability and collateral circulation. This essay also considers the emerging technique of intracoronary ultrasound which has shown evidence of disease underestimation by conventional contrast angiography. Positron emission tomography (PET) is a noninvasive technique that uniquely and quantitatively maps myocardial perfusion and CFR. The latter can be computed before and after angioplasty. PET studies have further demonstrated that chronic myocardial ischemia does not exist as a distinct state in patients with CAD. From the above investigations the concept has arisen that not only is CAD an entity involving epicardial vessels but also, in a significant portion of patients, an abnormal microcirculation plays an important role in the pathogenesis of ischemic syndromes. PET studies have relatively low spatial resolution since they cannot resolve layer-to-layer absolute MBF.     

Postinfarction left ventricular pseudoaneurysm

Left ventricular wall rupture after myocardial infarction is a mechanical complication that may result in a pseudoaneurysm. Between January 1994 and October 1996, false or pseudoaneurysms were detected in 6 (0.0026%) of 2,600 consecutive patients (4 women, 2 men; mean age 59.4 years) undergoing cardiac catheterization at University Medical School, Debrecen, Hungary. All patients had a history of cardiovascular disease, with diagnosis of pseudoaneurysm confirmed by echocardiography. The average time from the occurrence of acute infarction to diagnosis was 37.0 days (range 3-80 days). All patients were in New York Heart Association functional class IV congestive heart failure; in four patients cardiogenic shock was present. Five patients underwent coronary angiography, which demonstrated multivessel disease and occlusion of the infarct-related artery (TIMIO) without adequate collateral circulation (grade 0-1). Five patients had surgical repair of the false aneurysm, and, in three patients, concomitant coronary bypass grafting was performed. The 2-year mortality rate for all patients was 50%. Early diagnosis of false aneurysm is facilitated by echocardiography, and coronary angiography is required before surgery. Early surgical correction with coronary revascularization is advised.     

Aneurysm of the right colic artery

Primary PTCA as a means of reestablishing coronary blood flow in the infarct related artery is preferable in certain subgroups of patients with acute myocardial infarction. While the success rate of primary PTCA is very high, the procedure is not without risk. We report a case of hemodynamic collapse during PTCA due to an Amplatz guide catheter-induced, acute, and reversible aortic insufficiency. With the increasing use of the left Amplatz catheter for better guide support during PTCA, this unusual and previously unreported complication should be borne in mind.     

Effect of intracoronary estrogen on coronary collateral blood flow velocity

The effect of estrogen on collateral circulation has not been previously investigated. We assessed the acute effect of estradiol on collateral blood flow velocity with the Flowire during percutaneous transluminal coronary angioplasty and found that intracoronary estradiol decreased collateral blood flow velocity compared with controls.     

Detection of severity of coronary stenosis by quantitative myocardial tomography with Tc-99m-MIBI at rest

To evaluate the role of myocardial tomography with Tc-99m-MIBI (MB) in detecting abnormal coronary arteries, 34 patients with myocardial infarction underwent resting quantitative SPEC with MB and coronary arteriography within one month. When segmental MB uptake was < 560% of the left ventricular peak activity, there was 88% probability that a totally occluded or severely stenosed coronary artery (stenosis > 90%) was involved. There was 82% probability of finding no significant stenosis of coronary arteries in the normal myocardial segments. In the myocardial segments supplied by occluded coronary arteries, there was significantly higher MB uptake in the segments with good collateral circulation as compared with those subtended by a vessel totally occluded with poor collateral circulation (P < 0.05). The sensitivity and specificity of detecting abnormal coronary artery by quantitative analysis of myocardial tomography was 87% and 90% respectively. It is suggested that quantitative analysis of myocardial tomography with MB can differentiate between myocardial segments supplied by severely stenosed and normal coronary artery and evaluate the existence of collateral circulation.     

Influence of bypass grafting to the infarct artery on late potentials in coronary operations

BACKGROUND: Late potentials (LPs) after myocardial infarction identify the risk of arrhythmic events and sudden death, and the absence of anterograde flow in the infarct-causing occluded coronary artery frequently is associated with LPs on signal-averaged electrocardiography. The present study was designed to clarify the influence of revascularization of the infarct artery on the LPs in the late course after myocardial infarction. METHODS: We studied 21 patients after myocardial infarction with positive LPs who had at least one occluded infarct coronary artery. We investigated the LPs on signal-averaged electrocardiograms on the day of elective coronary artery bypass grafting (CABG) and 1 week after CABG. RESULTS: There were 25 infarct arteries in the study patients, 13 of which were grafted. The positive LPs disappeared soon after CABG in 13 patients, 10 of whom had grafts to all of the infarct arteries. The LPs persisted in 8, who received no graft to the infarct artery. One week after CABG, the LPs were still present in 4, all of whom had no graft to the infarct right coronary artery. CONCLUSIONS: In patients with positive LPs late after myocardial infarction, grafting to the infarct artery eliminated the LPs soon after CABG.     

Molecular basis of fibrinolysis, as relevant for thrombolytic therapy

The fibrinolytic system comprises an inactive proenzyme, plasminogen, that is converted by plasminogen activators to the active enzyme, plasmin, that degrades fibrin. Two physiological plasminogen activators have been identified: tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Plasminogen activation for clot lysis is regulated by specific molecular interactions between tissue-type plasminogen activator (t-PA), plasminogen and fibrin, whereby the lysine-binding sites of the plasminogen molecule play a crucial role by mediating its binding to fibrin, and by controlling the inhibition rate of plasmin by alpha 2-antiplasmin. The recognition that thrombosis within the infarct related coronary artery plays a major role in the pathogenesis of acute myocardial infarction and the observation that early administration of thrombolytic agents results in recanalization of occluded coronary arteries, have provided the basis for the development of thrombolytic therapy in acute myocardial infarction. The elucidation of the biochemical mechanism of fibrin-specific plasminogen activation has fueled the hope that specific and efficacious thrombolytic agents might become available. Comparative studies between the non-fibrin-selective streptokinase and fibrin-selective recombinant t-PA (rt-PA) have shown a difference in efficacy for early coronary artery recanalization, whereas the GUSTO trial has established that clinical benefit in patients with acute myocardial infarction is indeed correlated with the rapidity and frequency of sustained recanalization and that effective thrombolysis requires adequate anticoagulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical and angiographic features of patients with an occluded versus a patent infarct vessel after intravenous streptokinase for acute myocardial infarction

Despite early treatment with thrombolytic agents for acute myocardial infarction, a significant portion of patients fail to achieve a patent infarct artery. To study the various factors related to achieving patency in the infarct vessel, 201 patients who received streptokinase within six hours of symptoms were studied. All patients underwent cardiac catheterization during the same hospitalization at 5.40 +/- 3.26 days after admission. Forty-five (22.4%) patients were found to have an occluded infarct artery (group 1) and 156 (77.6%) had a patent infarct vessel (group 2). There was no difference in the time from onset of symptoms to receiving streptokinase between the two groups. The two groups were similar to each other with regard to age, gender, history of myocardial infarction or angina, and major risk factors for coronary disease. Coagulation parameters before and after streptokinase therapy, reflecting the lytic state, were similar in both groups. The left ventricular end diastolic pressure was significantly higher and the left ventricular ejection fraction was significantly lower in group 1 than in group 2. These observations suggest that despite early initiation of thrombolytic therapy in patients with acute myocardial infarction, a significant portion of patients fail to achieve a patent infarct artery. This failure cannot be explained by the observed clinical parameters or the lytic state after streptokinase.     

Myocardial contrast echocardiography in acute myocardial infarction. Pathophysiological background and clinical applications

Myocardial contrast echocardiography is a technique used in experimental and clinical settings in order to visualize the pattern of intramyocardial perfusion. In the acute phase of myocardial infarction, regional absence of flow during myocardial contrast echocardiography delineates the area at risk of necrosis, while the definitive non-perfused area expresses infarct size. Reopening the infarct-related artery, which may be achieved spontaneously by thrombolysis or percutaneous transluminal coronary angioplasty, is not a reliable indicator of intramyocardial reperfusion. If myocardial ischaemia due to coronary occlusion has been sufficiently prolonged and severe, not only myocyte viability, but also microvascular integrity is lost. Myocardial contrast echocardiography, using intracoronary injection of sonicated contrast medium, gives information about microvascular integrity and the effective presence of intramyocardial reflow. Anatomical integrity of microvasculature does not necessarily imply preserved function, and thus the microvessel vasodilating reserve may also be impaired. Myocardial contrast echocardiography has the potential to assess alterations in microvascular function, showing, in the myocardial area with reduced coronary reserve, a relatively reduced increase in echocontrast signal intensity when an intravenous vasodilator agent is administered.     

Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty

BACKGROUND: Severity of coronary artery stenosis has been defined in terms of geometric dimensions, pressure gradient-flow relations, resistance to flow and coronary flow reserve, or maximum flow capacity after maximum arteriolar vasodilation. A direct relation between coronary pressure and flow, however, may only be presumed if the resistances in the coronary circulation are constant (and minimal) as theoretically is the case during maximum arteriolar vasodilation. In that case, pressure measurements theoretically can be used to predict maximum flow and assess functional stenosis severity. METHODS AND RESULTS: A theoretical model was developed for the different components of the coronary circulation, and a set of equations was derived by which the relative maximum flow or fractional flow reserve in both the stenotic epicardial artery and the myocardial vascular bed and the proportional contribution of coronary arterial and collateral flow to myocardial blood flow are calculated from measurements of arterial, distal coronary, and central venous pressures during maximum arteriolar vasodilation. To test this model, five dogs were acutely instrumented with an epicardial, coronary Doppler flow velocity transducer. Distal coronary pressures were measured by an ultrathin pressure-monitoring guide wire (0.015 in.) with minimal influence on transstenotic pressure gradient. Fractional flow reserve was calculated from the pressure measurements and compared with relative maximum coronary artery flow measured directly by the Doppler flowmeter at three different levels of arterial pressure for each of 12 different severities of stenosis at each pressure level. Relative maximum blood flow through the stenotic artery (Qs) measured directly by the Doppler flowmeter showed an excellent correlation with the pressure-derived values of Qs (r = 0.98 +/- 0.01, intercept = 0.02 +/- 0.03, slope = 0.98 +/- 0.04), of the relative maximum myocardial flow (r = 0.98 +/- 0.02, intercept = 0.26 +/- 0.07, slope = 0.73 +/- 0.08), and of the collateral blood flow (r = 0.96 +/- 0.04, intercept = 0.24 +/- 0.07, slope = -0.24 +/- 0.06). Moreover, the theoretically predicted constant relation between mean arterial pressure and coronary wedge pressure, both corrected for venous pressure, was confirmed experimentally (r = 0.97 +/- 0.03, intercept = 9.5 +/- 13.3, slope = 4.4 +/- 1.2). CONCLUSIONS: These results provide the experimental basis for determining relative maximum flow or fractional flow reserve of both the epicardial coronary artery and the myocardium, including collateral flow, from pressure measurements during maximum arteriolar vasodilation. With a suitable guide wire for reliably measuring distal coronary pressure clinically, this method may have potential applications during percutaneous transluminal coronary angioplasty for assessing changes in the functional severity of coronary artery stenoses and for estimating collateral flow achievable during occlusion of the coronary artery.