Determinants Of Coronary Blood Flow Research Articles

A patient-specific approach to assessing blood pressure management in patients with hypertension and coronary artery disease.

The objective was to improve the management of patients with hypertension (HTN) and coronary artery disease (CAD), utilizing a model which integrates 3 determinants of coronary blood flow (CBF)-CAD severity, diastolic blood pressure (DBP), and left ventricular (LV) mass. We validated non-parametric equations for CBF estimation in a consecutive patient sample (N=81) with HTN and CAD. There was a highly significant correlation (r=.565; P<.01) between clinical DBP and estimated CBF. Greater LV mass and more severe CAD shifted the relationship towards less CBF at the same DBP. LV mass was more critical when DBP >70mmHg. Estimated changes in CBF at different DBP considering the severity of CAD and LV mass can be calculated. In summary, the severity of CAD from coronary CT or coronary angiography combined with LV mass from echocardiography permits clinicians to guide the extent of, or target for, DBP to avoid seriously compromising CBF.

Determinants of coronary blood flow in sandbar sharks, Carcharhinus plumbeus.

The coronary circulation first appeared in the chordate lineage in cartilaginous fishes where, as in birds and mammals but unlike most teleost fishes, it supplies arterial blood to the entire myocardium. Despite the pivotal position of elasmobranch fishes in the evolution of the coronary circulation, the determinants of coronary blood flow have never been investigated in this group. Elasmobranch fishes are of special interest because of the morphological arrangement of their cardiomyocytes. Unlike teleosts, the majority of the ventricular myocardium in elasmobranch fishes is distant to the venous blood returning to the heart (i.e., the luminal blood). Also, the majority of the myocardium is in close association with the coronary circulation. To determine the relative contribution of the coronary and luminal blood supplies to cardiovascular function in sandbar sharks, Carcharhinus plumbeus, we measured coronary blood flow while manipulating cardiovascular status using acetylcholine and adrenaline. By exploring inter- and intra-individual variation in cardiovascular variables, we show that coronary blood flow is directly related to heart rate (R 2=0.6; P<0.001), as it is in mammalian hearts. Since coronary blood flow is inversely related to coronary resistance both in vivo and in vitro, we suggest that in elasmobranch fishes, changes in heart rate mediate changes in coronary vascular resistance, which adjust coronary blood flow appropriately.

The Impact of Left Ventricular Mass on Diastolic Blood Pressure Targets for Patients With Coronary Artery Disease.

Defining the optimal diastolic blood pressure (DBP) for patients with hypertension and coronary artery disease (CAD) is an ongoing challenge in part because of the concern that low DBP may have adverse cardiac effects (the J curve hypothesis). Left ventricular mass (LV mass) was measured on the echocardiogram of individuals (N = 92) with CAD who had coronary blood flow (CBF) in the left anterior descending (LAD) artery estimated from artery diameter and DBP distal to coronary stenosis. CBF approached 0 in a small but defined proportion of persons at DBP of 70mm Hg. CBF was significantly lower in persons with higher LV mass (above the median of 83g/m(2)) when DBP was ≥75mm Hg. Higher electrocardiogram QRS voltage (sum of S V1 and R in V6), in the absence of LV hypertrophy (LVH), identified persons with significantly lower CBF at DBP ≥ 80mm Hg. In multivariate analysis, LV mass was a significant CBF determinant after adjusting for DBP and CAD severity. LV mass has a major impact on CBF when DBP is >70mm Hg, while DBP is the primary determinant of CBF when DBP is ≤70mm Hg. Multivariate analysis confirmed a significant interaction between LV mass and DBP. DBP ≤ 70mm Hg is associated with a progressively greater proportion in whom CBF in the LAD approaches 0. For DBP > 70mm Hg, persons with higher LV mass, even in the absence of LVH, have lower CBF, suggesting LV mass is an important consideration when DBP is reduced in patients with CAD.

Myocardial perfusion pressure in patients with hypertension and coronary artery disease

The target blood pressure (BP) in patients with hypertension and coronary artery disease (CAD) has been controversial. Whether patients with both diabetes mellitus and CAD should follow targets for either diabetes mellitus or CAD is uncertain. Focusing only on one determinant of coronary blood flow (CBF) - myocardial perfusion pressure (MPP) - coronary BP in patients with hypertension was used to estimate the impact of setting BP targets. A consecutive series of 101 patients referred for coronary angiography for stable angina pectoris or possible CAD had BP measurements proximal and distal to coronary artery stenosis. Fractional flow reserve (FFR) was measured from adenosine-induced maximal hyperemia. DBP after the coronary stenosis was the MPP. The most severe coronary lesion for each person was selected. Of 101 patients, 65.0 ± 10.6 years (mean ± SD), there were 69 with hypertension and 33 with diabetes mellitus of whom 25 had diabetes mellitus along with hypertension. In hypertension, FFR was 0.83 ± 0.08, range from 0.49 to 0.97, with 40% having FFR less than 0.8. There was a significant linear relationship between systemic DBP and MPP. CBF approximates zero with MMP of 50 mmHg under resting conditions and 40 mmHg with coronary vasodilatation. On the basis of our findings in hypertension, if DBP were 80, 70, 65 and 60 mmHg, 1.4, 7.1, 15.7 and 54.3%, respectively, of patients would have an MPP of less than 50 mmHg. The values were similar for patients with diabetes mellitus. In our patient group with moderate coronary artery stenosis, a target DBP of 60 mmHg or less would be associated with unacceptably low MPPs. In patients with diabetes mellitus, the presence and severity of CAD stenosis may be more important factor in setting BP targets for treatment of hypertension. Because the degree of coronary stenosis is unknown in most patients with hypertension and CAD, guideline recommendations should consider cautioning clinicians about the potential for myocardial ischaemia at low DBP.

499 Myocardial Perfusion Pressure in Patients With Coronary Artery Disease and Hypertension With and Without Diabetes Mellitus: Implications for Diastolic Blood Pressure Targets in Hypertension Management

vasculopathy characterized by enhanced pulmonary artery smooth muscle cells (PASMC) proliferation and suppressed apoptosis. This results in both increase in pulmonary arterial pressure and pulmonary vascular remodeling. Recent studies have shown the implication of different transcription factors and proteins such as signal of transducer and activator of transcription 3 (STAT3), bone morphogenetic protein receptor 2 (BMPR2) and peroxisome proliferatoractivated receptor gamma (PPARa) in the etiology of PAH. Indeed, the activation of STAT3 induces BMPR2 downregulation contributing to the decrease in PPARa activity. In chondrocytes, the activation of this axis has been attributed to the advanced glycation endproducts receptor (RAGE). In a PAH proteomic study, RAGE has been demonstrated as one of the most upregulated protein in the PAH patients’ lungs. Thus, we hypothesized that by activating STAT3, RAGE induces BMPR2 and PPARa downregulation promoting PAH-PASMC proliferation and resistance to apoptosis in PAH. METHODS/RESULTS: We confirmed on human PAH lung biopsies that RAGE is overexpressed (n 5; qRT-PCR). In vitro, using PASMC isolated from PAH and healthy patients (n 3), we demonstrated that RAGE is overexpressed in PAH-PASMC compare to healthy PASMC. Its upregulation induces STAT3 activation and BMPR2 and PPARa decrease (qRT-PCR; western blot). The activation of the RAGE/STAT3/BMPR2/PPARa axis promotes PAHPASMC proliferation (Ki67) and suppresses apoptosis (TUNEL). This phenotype was totally reversed upon RAGE inhibition (by siRNA) or PPARa activation (by rosiglitazone). Furthermore, control cells treated with a RAGE agonist (S100A4 peptide) or with a PPARa antagonist (W9662) have a proliferative phenotype, mimicking the pathology. The S100A4 proliferative phenotype is reversed when PPARa is activated and we also demonstrated that PPARa is a downstream target of RAGE. In vivo, RAGE inhibition (siRNA nebulization i.t.) in rats with monocrotaline and sugen-induced PAH had decreased mean PA pressure (catheterization and Doppler echography) and right ventricular hypertrophy (M-mode ultrasound, n 8 per group). This decrease in PAH was associated with a significant improvement in lung perfusion measured by CT-angiogram and decreased PA wall thickness. Decrease in PA remodeling is associated with a decrease in both proliferation (Ki67) and resistance to apoptosis (TUNEL), associated with RAGE/STAT3/BMPR2/PPARa axis deregulation. Thus, we demonstrated for the first time that RAGE is an upstream regulator of PPARa and that Sugen-induced PAH could be reversed by protein inhibition. CONCLUSION: We demonstrated the implication of RAGE in the etiology of PAH. Moreover, we showed that RAGE constitutes a new and attractive therapeutic target for PAH. Featured Research

Anatomy and physiology of coronary blood flow

Regional myocardial blood flow can now be measured noninvasively in units of milliliters blood per minute per gram myocardium. These noninvasive measurements are not confined to a specific imaging modality but are available with MRI, CT, and PET, although, thus far, most investigations of the coronary circulation in humans have employed PET flow measurements. Flow estimates with these different imaging modalities were found in animal experiments to correlate well with invasive flow estimates by the arterial blood sampling-microsphere technique widely considered as the “gold standard” of flow measurements.1-11 In these comparison studies, noninvasively-derived estimates corresponded linearly with invasively-measured myocardial blood flows over a wide flow range, i.e., from as low as 0.3 mL/minute/g to as high as 5-6 mL/minute/g. When tested in the human heart, noninvasive flow estimates correlated well with those obtained through invasively-obtained indices of flow and its changes by well-established alternate measurement approaches.12-16 Development and commercial availability of user-friendly software programs have facilitated the use of these new measurement capabilities so that they are now readily available in the clinical environment for the study of patients with cardiovascular disease. As several investigations have indicated, measurements of myocardial blood flow at rest contain only limited diagnostic information. For example, even in patients with advanced cardiovascular disease such as nonischemic dilated or ischemic cardiomyopathy, hypertrophic cardiomyopathy, or coronary artery disease, resting myocardial blood flows frequently are similar to those in normal individuals.17-19 It is the response of myocardial blood flow to specifically-targeted pharmacological or physiological interventions that can uncover the presence of functional or structural disease-related alterations of the coronary circulation. This then underscores the need for closely examining these targets and how they relate to anatomical and functional determinants of coronary blood flow and, by inference, to myocardial blood flow and their alterations in cardiovascular disease. Local and systemic mechanisms regulate the complex interactions between flow and anatomy in order to meet the heart’s energy needs. A comprehensive description of the coronary circulatory function and its control exceeds the scope of this review so that the interested reader is referred to detailed reviews on this topic.20,21 This review then seeks to describe in broad strokes the major functional and anatomical determinants of coronary blood flow as they pertain to noninvasive measured myocardial blood flows.

Central Hemodynamics and Oxygen Transport during Alveolar Mobilization in Early Periods after Extracorporeal Circulation

Objective: to study central hemodynamics, the determinants of coronary blood flow and myocardial oxygen demand, and the parameters of blood oxygen-transport function during alveolar mobilization in early periods after extracorporeal circulation in patients operated on for coronary heart disease. Subjects and methods. Twenty-nine patients were examined after myocardial revascularization. The alveolae were mobilized 63±2 min after extracorporeal circulation. The peak airway pressure was 31±0.3 H2O. Invasive hemodynamic monitoring was provided with Swan-Ganz catheters. Results. After building up the peak airway pressure, there was a 7.5—15 mm Hg blood pressure reduction (p<0.05) and 3.7 mm Hg right atrial and pulmonary artery wedge pressure elevations (p<0.05). Total pulmonary vascular resistance increased by 44% (p<0.05). Cardiac index reduced by 15% (p<0.05) due to decreased stroke volume. Coronary perfusion gradients and myocardial oxygen demand proportionally changed: r=0.62—0.77 (p<0.001). Oxygen transport significantly unchanged due to alveolar mobilization. After the latter, there was a close correlation between oxygen delivery and uptake (r=0.74; p<0.001). After alveolar mobilization, the changes in oxygen utilization coefficient and cardiac index had a significant correlation (r=0.43; p=0.02). After switching to artificial ventilation in the fitted mode, all the study parameters did not differ from the baseline values. Conclusion. The production of the peak airway pressure required for alveolar mobilization is attended by cardiac depression due to the right and left ventricular function determinant changes resulting in reductions in stroke volume and blood pressure. At the same time, there is imbalance between the conditions for coronary blood flow and the myocardial oxygen demand values. After artificial ventilation with the fitted positive end-expiratory pressure is switched, the mean hemodynamic values return to the baseline levels; however, there are signs of tense blood transport function. Key words: alveolar mobilization in cardiosurgical patients, hemodynamic effects of alveolar mobilization, recruitment maneuver.

Central Hemodynamics and Oxygen Transport in Various Activation of Patients Operated On Under Extracorporeal Circulation

Objective: to study central hemodynamics, the determinants of myocardial oxygen balance, and the parameters of oxygen transport in various activation of patients after surgery under extracorporeal circulation. Subjects and methods. Thirty-four patients aged 57.8±2.5 years who had coronary heart disease were divided into 2 groups: 1) those with late activation (artificial ventilation time 157±9 min) and 2) those with immediate activation (artificial ventilation time 33±6 min). Group 2 patients were, if required, given fentanyl, midazolam, or myorelaxants. Results. During activation, there were no intergroup differences in the mean levels of the major parameters of cardiac pump function, in the determinants of coronary blood flow (coronary perfusion gradients) and myocardial oxygen demand (the product of heart rate by systolic blood pressure), and in the parameters of oxygen transport, including arterial lactatemia. After tracheal extubation, the left ventricular pump coefficient was increased considerably (up to 3.8±0.2 and 4.4±0.2 gm/mm Hg/m2 in Groups 1 and 2, respectively; p&lt;0.05) with minimum inotropic support (dopamine and/or dobutamine being used at 2.7±0.3 and 2.4±0.3 mg/kg/min, respectively). In both groups, there were no close correlations between the indices of oxygen delivery and consumption at all stages of the study, which was indicative of no transport-dependent oxygen uptake. Conclusion. When the early activation protocol was followed up, the maximum acceleration of early activation, including that using specific antagonists of anesthetics, has no negative impact on central hemodynamics, the determinants of myocardial oxygen balance and transport in patients operated on under extracorporeal circulation. Key words: early activation, surgery under extracorporeal circulation, tracheal extubation in the operating-room, central hemodynamics, oxygen transport.

Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents

Starting out from a brief description of the determinants of coronary blood flow (perfusion, pressure, extravascular compression, autoregulation, metabolic regulation, endothelium-mediated regulation and neurohumoral regulation) the present review highlights the overwhelming importance of metabolic regulation such that coronary blood flow is increased at increased heart rate under physiological circumstances and the overwhelming importance of extravascular compression such that coronary blood flow is decreased at increased heart rate through reduction of diastolic duration in the presence of severe coronary stenoses. The review goes on to characterize the role of heart rate in the redistribution of regional myocardial blood flow between a normal coronary vascular tree with preserved autoregulation and a poststenotic vasculature with exhausted coronary reserve. When flow is normalized by heart rate, there is a consistent close relationship of regional myocardial blood flow and contractile function for each single cardiac cycle no matter whether or not there is a coronary stenosis and what the actual blood flow is. beta-Blockade improves both flow and function along this relationship. When the heart rate reduction associated with beta-blockade is prevented by pacing, alpha-adrenergic coronary vasoconstriction is unmasked and both flow and function are deteriorated. Selective heart rate reduction, however, improves both flow and function without any residual negative effect such as unmasked alpha-adrenergic coronary vasoconstriction or negative inotropic action.

Automated Technique for Angiographic Determination of Coronary Blood Flow and Lumen Volume

Visual interpretation of angiographic images has been shown to be inadequate for assessing the severity of intermediate coronary stenoses. An approach for evaluating both the anatomic and functional impact of a stenosis is needed. An automated technique for determining both coronary blood flow and lumen volume based on a first-pass analysis (FPA) of coronary angiograms and a template matching algorithm was evaluated. Coronary angiograms of a swine animal model were obtained during power injections of contrast material into the left coronary ostium. Background anatomy was subtracted with an automated phase matching program. A template matching algorithm and first-pass analysis were then used to quantify coronary blood flow and lumen volume. Coronary blood flow and lumen volume measurements were validated with a transit-time ultrasound flow probe and a polymer cast of the coronary arteries, respectively. In 14 independent comparisons, the mean coronary blood flow measured with FPA showed strong correlation with the mean flow measured with the ultrasound flow probe (Q(FPA) = 0.88Q(probe) - 1.99; r = 0.977; standard error of estimate = 3.23 mL/minute). The lumen volumes determined with FPA and cast measurements demonstrated excellent correlation and can be related to each other by V(FPA) = 0.95V(C) - 0.01 (r = 0.997; standard error of estimate = 0.01 mL). The proposed automated method for accurate determination of coronary blood flow and lumen volume can supplement visual evaluation of coronary anatomy with quantitative physiologic data. This automated technique potentially offers a clinically feasible method of quantifying coronary blood flow and lumen volume in conjunction with routine cardiac catheterization.

Determinants of coronary blood flow in humans: quantification by intracoronary Doppler and ultrasound

The direct determinants of coronary flow are lumen area and blood flow velocity; however, the precise mechanisms that control these factors are not fully understood. The aim of the present study was to assess by which mechanisms lumen area and coronary flow velocity interact with hemodynamic and morphometric factors, thereby influencing coronary flow. Intracoronary Doppler and ultrasound measurements were performed in 28 patients without coronary lumen irregularities. Flow velocity and lumen cross-sectional area were measured in the proximal segments of all three coronary arteries. Global lumen cross-sectional area and global flow were obtained by adding up the values of all three coronary arteries. Left ventricular mass was assessed by echocardiography. Stress-mass-heart rate and pressure-rate products reflecting myocardial oxygen demand were calculated. Global coronary flow increased during adenosine-induced hyperemia from 197 +/- 72 to 637 +/- 204 ml/min (P < 0.001). Global coronary flow closely correlated with the stress-mass-heart rate product (r = 0.62; P < 0.001). Looking at the two constituents of flow separately, global coronary cross-sectional area was closely related to left ventricular muscle mass (r = 0.61; P < 0.001), whereas mean coronary flow velocity at rest showed a strong linear relation with the pressure-rate product (r = 0.64; P < 0.001). There was no interaction between cross-sectional area and blood flow velocity in any of the coronary vessels. Coronary lumen size and flow velocity, the two determinants of coronary flow, are principally determined by different physiological factors. Long-term flow adaptation is achieved by an increase in coronary lumen size, whereas short-term myocardial oxygen requirements are met by changes in resting flow velocity.

Coronary and myocardial angiography: angiographic assessment of both epicardial and myocardial perfusion.

Angiographic assessment of epicardial coronary artery blood flow has played a pivotal role in our understanding of the “time-dependent open artery hypothesis” and in the evaluation of reperfusion strategies over the past 2 decades.1–8 It has become increasingly apparent, however, that clinical outcomes are not only associated with angiographic flow in the epicardial artery, but also with angiographic flow in the myocardium.9–13 To this end, the goal of reperfusion therapies has shifted to include reperfusion downstream at the level of capillary bed, and it might be more appropriate that the hypothesis now be termed “the time dependent open artery and open microvascular hypothesis.” The goal of this article is to review angiographic methods used to evaluate myocardial ischemia and infarction and to discuss the insights into the pathophysiology of acute coronary syndromes provided by these angiographic indexes of coronary artery blood flow and myocardial perfusion. For nearly 2 decades now, the Thrombolysis In Myocardial Infarction (TIMI) flow grade classification scheme has been successfully used to assess coronary blood flow in acute coronary syndromes1 (Table). It has been a valuable tool to compare angiographic outcomes following reperfusion, and the association of the TFGs with clinical outcomes (including mortality) has been well documented.2–8 The relationship between TFG and mortality does satisfy what some consider to be 3 criteria required to validate a surrogate end point for mortality, as follows: (1) There is an association between TIMI grade 3 flow and mortality, (2) an agent such as recombinant tissue plasminogen activator improves TIMI grade 3 flow by 22% over another agent such as streptokinase, and (3) the agent tissue plasminogen activator improves mortality 1.1% over streptokinase. View this table: Definitions of the TFG and the TMPG Systems On the basis of this relationship between TIMI flow and mortality observed in the GUSTO …

Determinants of coronary blood flow following primary angioplasty for acute myocardial infarction

Determinants of coronary blood flow following primary angioplasty for acute myocardial infarction

Determinants of coronary blood flow following primary angioplasty for acute myocardial infarction.

The aim of this study was to evaluate determinants of coronary blood flow following primary angioplasty (PA) in acute myocardial infarction (AMI). The corrected TIMI (thrombolysis in myocardial infarction) frame count and the TIMI flow grade were used as indexes of coronary blood flow, and its determinants were examined in 115 consecutive AMI patients who underwent PA (pain onset </= 12 hr). The following were validated as univariate predictors of slower corrected TIMI frame count: a lower pressure-derived farctional collateral flow (PDCF) index (P < 0.01), poor angiographic collaterals (P < 0.01), TIMI flow 0, 1 before PA (P < 0.05), and the presence of heavy thrombi (P < 0.01). The PDCF index and the presence of heavy thrombi were independent predictors of the corrected TIMI frame count. Likewise, the PDCF index (chi(2) = 12.9; P < 0.01) and the presence of heavy thombi (chi(2) = 11.4; P < 0.01) were independent predictors of TIMI 3 flow. In conclusion, collateral flow and the presence of thrombi are major determinants of coronary blood flow after PA in AMI.

Organ Preservation, Vol. 37, No. 2 of International Anesthesiology Clinics.

Organ Preservation, Vol. 37, No. 2 of International Anesthesiology Clinics.Roysten D, ed. Philadelphia: Lippincott Williams & Wilkins, 1999. ISSN 0020-5907. 130 pages, $61.00. Although the title of the book may suggest the preservation of organs for transplantation, the authors’ objectives were to review molecular pathogenesis of organ dysfunction and scientific rationale for specific interventions and treatments of organ dysfunction associated with cardiac surgery. The book is composed of five chapters; the host defense system by cellular blood components, myocardial protection during cardiac surgery, pulmonary hypertension after cardiac surgery, the role of the intestines in postoperative morbidity, and renal preservation. The first chapter contains an in-depth description of the cellular host defense system and hemostasis contributed by neutrophils and platelets, respectively. The review of molecular interaction of inflammatory response and hemostasis is informative. It appears that the authors’ intention was to describe hemostasis as a part of inflammatory response or a host defense mechanism. However, a relatively weak description of the interaction of two systems gives an impression of one chapter with two isolated topics. The chapter on myocardial preservation describes mechanisms of myocardial stunning, determinants of coronary blood flow, and myocardial protection by chemical cardioplegia and ischemic preconditioning. Pulmonary hypertension observed during cardiac surgery and cardiac transplantation is described in the third chapter. Description of pathophysiology of pulmonary hypertension during and after cardiac surgery and cardiac transplantation is quite extensive. In addition, the rationale and mode of treatment including nitric oxide, prostacyclin, phosphodiesterase inhibitors, adenosine, adrenomedulin, and mechanical support are described. The effect of translocation of intestinal bacteria and endotoxin into the systemic circulation on the development of the systemic inflammatory response syndrome is described in the fourth chapter. In addition, the authors describe potential causes of mucosal hypoxia, various methodologies of monitoring mucosal perfusion status, and approaches to preventing postoperative gut-derived complications. The chapter on renal protection describes potential causes and interventions of postoperative renal dysfunction. The authors, however, do not comment on molecular mechanisms of renal dysfunction. Overall, this monograph describing organ dysfunctions associated with major surgery is easily readable for most clinical anesthesiologists. It is admirable that the authors tried to cover molecular mechanisms of specific organ dysfunction and relate to clinical complications and their interventions. There are two drawbacks in this book: 1) the other two major organ functions, namely central nervous system and pulmonary system, are not addressed and 2) the difficulty in combining molecular biology and clinical science results in superficial coverage of both areas. The authors, however, have achieved their objectives if they were able to deliver a scientific background of organ dysfunction to clinicians.

Determinants of coronary blood flow after thrombolytic administration

OBJECTIVESThis study evaluated the determinants of coronary blood flow following thrombolytic administration in a large cohort of patients.BACKGROUNDTighter residual stenoses following thrombolysis have been associated with slower coronary blood flow, but the independent contribution of other variables to delayed flow has not been fully explored.METHODSThe univariate and multivariate correlates of coronary blood flow at 90 min after thrombolytic administration were examined in a total of 2,195 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 10B and 14 trials. The cineframes needed for dye to first reach distal landmarks (corrected TIMI frame count, CTFC) were counted as an index of coronary blood flow.RESULTSThe following were validated as univariate predictors of delayed 90-min flow in two cohorts of patients: a greater percent diameter stenosis (p < 0.0001 for both cohorts), a decreased minimum lumen diameter (p = 0.0003, p = 0.0008), a greater percent of the culprit artery distal to the stenosis (p = 0.03, p = 0.02) and the presence of any of the following: delayed achievement of patency (i.e., between 60 and 90 min) (p < 0.0001 for both cohorts), a culprit location in the left coronary circulation (left anterior descending or circumflex) (p = 0.02, p < 0.0001), pulsatile flow (i.e., reversal of flow in systole, a marker of heightened microvascular resistance, p = 0.0003, p < 0.0001) and thrombus (p = 0.002, p = 0.03). Despite a minimal 16.4% residual stenosis following stent placement, the mean post-stent CTFC (25.8 ± 17.2, n = 181) remained significantly slower than normal (21.0 ± 3.1, n = 78, p = 0.02), and likewise 34% of patients did not achieve a CTFC within normal limits (i.e., <28 frames, the upper limit of the 95th percent confidence interval previously reported for normal flow). Those patients who failed to achieve normal CTFCs following stent placement had a higher mortality than did those patients who achieved normal flow (6/62 or 9.7% vs. 1/118 or 0.8%, p = 0.003).CONCLUSIONSLumen geometry is not the sole determinant of coronary blood flow at 90 min following thrombolytic administration. Other variables such as the location of the culprit artery, the duration of patency, a pulsatile flow pattern and thrombus are also related to slower flow. Despite a minimal 16% residual stenosis, one-third of the patients treated with adjunctive stenting still have a persistent flow delay following thrombolysis, which carries a poor prognosis.

Myocardial oxygen supply:demand ratio as reference for coronary vasodilatory drug effects in humans.

OBJECTIVE: Introduction and measurement of human myocardial oxygen supply:demand ratio as a reference for quantification of coronary microvascular vasodilating drug effects in clinical studies. Myocardial oxygen consumption is the major...

Effect of L-arginine on coronary endothelial function in cardiac transplant recipients. Relation to vessel wall morphology.

Coronary endothelial vasodilator dysfunction is a common finding in cardiac transplant recipients and may represent an early marker for the development of intimal thickening and graft atherosclerosis. The present study tested the hypothesis that endothelial dysfunction precedes intimal thickening and that administration of L-arginine, the precursor of endothelium-derived relaxing factor, improves endothelial vasodilator function of coronary conduit and resistance vessels if given at an early stage of graft atherosclerosis. Acetylcholine (10(-6), 10(-5), 10(-4) mol/L) was infused into the left anterior descending or circumflex artery and repeated after intravenous infusion of L-arginine (10 mg.kg-1.min-1 over 20 minutes) in 18 cardiac transplant recipients. Epicardial responses were evaluated by quantitative angiography, and the microcirculation was studied by determination of coronary blood flow with a Doppler flow velocity wire. Intimal thickening was assessed by intravascular ultrasound (n = 14). In epicardial coronary arteries, acetylcholine tended to elicit vasoconstriction. Epicardial coronary vasoconstriction elicited by acetylcholine was attenuated by infusion of L-arginine (10(-4) mol/L, -6.8% versus -2.8%; P < .01); this beneficial effect was observed predominantly in patients with normal intravascular ultrasound characteristics. In coronary resistance vessels, acetylcholine induced vasodilation, reflected by increases in coronary blood flow. The acetylcholine-induced increase in blood flow was significantly enhanced with L-arginine (at a dose of 10(-4) mol/L, + 121% versus 176%; before versus after L-arginine, P < .002). The coronary vasculature of cardiac transplant recipients exhibits a generalized endothelial dysfunction of conduit and resistance vessels. L-Arginine improves endothelial dysfunction of both coronary microvasculature and epicardial coronary arteries. The reversibility of epicardial endothelial dysfunction by L-arginine is more likely in vessels with normal wall morphology.

The role of the membrane potential of endothelial and smooth muscle cells in the regulation of coronary blood flow.

In the mammalian heart the supply of oxygen and energy-rich substrates through the coronary arterioles is continuously adapted to the variations of cardiac work. The coronary resistance arteries and the surrounding myocardium form a functional unit with multiple interactions between coronary endothelial cells, smooth muscle cells, perivascular nerves, and cardiac muscle cells. We describe the mechanisms underlying the electrical and chemical communication between the different cell types, the ionic channels contributing to the resting potential of endothelial and smooth muscle cells, and the mechanisms responsible for modulation of the resting potential. The main conclusion of our analysis is that the membrane potential of coronary endothelial and smooth muscle cells is one of the major determinants of coronary blood flow, and that modulation of the membrane potential provides a way to dilate or constrict coronary resistance arteries. It is proposed that the membrane potential of the myo-endothelial regulatory unit, i.e., of the endothelial cells and the underlying smooth muscle cells in the terminal arterioles, may function as an integrator of the numerous local and global vasodilator and constrictor signals that provide for the adaptation of coronary blood flow to the metabolic demands of the heart.

Mechanical determinants of coronary blood flow during dynamic alterations in myocardial contractility.

Recently it has been proposed that the decrease in coronary blood flow (CBF) resulting from cardiac contraction referred to as systolic flow impediment (SFI) is dependent on the level of left ventricular elastance (Ees). The average rate of LV relaxation (Ravg) has been shown to be major determinant of diastolic flow development (DFD). We tested these hypotheses using the unique hemodynamic condition of pulsus alternans (PA) where end-systolic LV pressure and instantaneous Ees vary on beat-to-beat basis. In six mongrel dogs instrumented with LV and aortic manometers, ultrasonic dimension crystals, and Doppler coronary flow probes we measured phasic CBF and Ees during PA and control conditions. Maximal pressure development over time (dP/dtmax) and SFI were significantly different between weak (WB) and strong beats (SB) as were Ravg and DFD. Minimum CBF (Qmin) was not different between SB and WB; however, Qmin and peak Ees occurred nearly simultaneously in the WB. Qmin occurred much earlier than peak Ees in the strong and control beats. Plots of instantaneous LV elastance and CBF showed that for control beats and for the strong beats of PA CBF was similar during systole and diastole, suggesting elastance is a unique determinant of CBF. This was quantified as CBF at the time in either systole or diastole when elastance was half-maximal for that beat (E50). During the WB of PA, however, CBF at E50 was significantly higher during systole than during diastole. We conclude that while SFI and DFD are highly dependent on the dP/dt and Ravg, Ees is not a unique determinant of CBF under all conditions.