Differences In Coronary Blood Flow Research Articles

Effect of side branch flow upon physiological indices in coronary artery disease

Recent efforts have demonstrated the ability of computational models to predict fractional flow reserve from coronary artery imaging without the need for invasive instrumentation. However, these models include only larger coronary arteries as smaller side branches cannot be resolved and are therefore neglected. The goal of this study was to evaluate the impact of neglecting the flow to these side branches when computing angiography-derived fractional flow reserve (vFFR) and indices of volumetric coronary artery blood flow. To compensate for the flow to side branches, a leakage function based upon vessel taper (Murray’s Law) was added to a previously developed computational model of coronary blood flow. The augmented model with a leakage function (1Dleaky) and the original model (1D) were then applied to predict FFR as well as inlet and outlet flow in 146 arteries from 80 patients who underwent invasive coronary angiography and FFR measurement. The results show that the leakage function did not significantly change the vFFR but did significantly impact the estimated volumetric flow rate and predicted coronary flow reserve. As both procedures achieved similar predictive accuracy of vFFR despite large differences in coronary blood flow, these results suggest careful consideration of the application of this index for quantitatively assessing flow.

Sex-specific differences in coronary blood flow and flow velocity reserve in symptomatic patients with non-obstructive disease.

Reduced coronary flow velocity reserve (CFVR) is associated with adverse cardiovascular outcomes. Whether CFVR and coronary blood flow (CBF) are similar in men and women with chest pain and non-obstructive CAD remains unknown. We hypothesised sex differences in CFVR and CBF. A total of 1,683 patients with signs/symptoms of ischaemia and angiographically unobstructed coronary arteries (<40% angiographic stenosis) underwent coronary vasomotion evaluation. CFVR was measured as hyperaemic/resting average velocity in the LAD. Mid-LAD diameter was measured with quantitative angiography and CBF calculated at rest (rCBF) and hyperaemia (hCBF). Resting microvascular resistance (rMR) was calculated as mean arterial pressure/rCBF. Of the total number of patients, 1,096 (65%) were women, median age 51 [42, 59] years. Compared to men, women had lower median CFVR (2.7 [2.4, 3.2] vs 3.1 [2.7, 3.6], p<0.001), higher rCBF (49.7 [34.0, 71.1] vs 45.9 [31.8, 68.7] ml/min, p=0.04), lower hCBF (139.5 [93.0, 195.2] vs 147.1 [95.7, 218.6] ml/min, p=0.02), but similar rMR (p=0.82). Female sex was an independent predictor of lower CFVR, higher rCBF, and lower hCBF. Compared to men, women with signs/symptoms of ischaemia and non-obstructive CAD have lower CFVR, higher rCBF, and lower hCBF. Female sex is a predictor of these sex-specific differences. The clinical diagnostic and prognostic implications of sex differences in coronary physiology need further evaluation.

Differences in Coronary Blood Flow in Aortic Regurgitation and Systemic Arterial Hypertension Have Implications for Diastolic Blood Pressure Targets: A Systematic Review and Meta‐Analysis

The objective was to evaluate coronary blood flow (CBF) in patients with systemic arterial hypertension (HTN) and to compare it with CBF in patients with aortic regurgitation (AR). A systematic literature search was conducted using the reference terms "coronary blood flow" and either "aortic regurgitation" or "hypertension." The selection criteria included CBF measurement in a concomitant control group, except studies evaluating CBF with aortic-valve replacement surgery. Twenty-two studies met the inclusion criteria. There were 318 persons with HTN, with 185 controls; and 102 persons with AR, with 144 controls. Despite an overall increase in CBF in HTN, CBF per gram of left ventricular mass was significantly (P < 0.0001) reduced. In contrast, CBF per gram of left ventricular mass was significantly (P = 0.004) increased in AR. Aortic regurgitation was associated with a significant (P < 0.0001) increase in CBF during systole and away from diastole, in contrast to persons with HTN. Aortic-valve replacement reversed the increase in systolic CBF. These data suggest that patients with HTN are more vulnerable than patients with AR to lower diastolic blood pressure (DBP), because resting CBF is compromised in HTN. Furthermore, patients with HTN may not compensate for DBP reductions by shifting CBF to systole, such as can occur with the low DBP in AR. Lower DBP in patients with AR cannot be used to justify treating patients with HTN to similar DBP because of the dramatic differences in CBF between the 2 conditions.

E0650 The effects of biventricular synchronous pacing on CBF, MVO2 and CWE in dogs

ObjectiveTo compare the effects of biventricular synchronous pacing with different pacing site on coronary Blood flow (CBF), myocardial oxygen consumption (MVO2) and cardiac work efficiency (CWE).MethodsRA-cHisB and RA-RVA sequential pacing,...

Effects of ischemia on myocardial function during rapid left ventricular pacing

Introduction Coronary artery disease is often accompanied with deterioration in left ventricular function. Left ventricular pacing has been shown to improve cardiac function in chronic heart failure. However, data are limited about left ventricular pacing during acute ischemia. Therefore, we studied the effects of acute myocardial ischemia on myocardial function during left ventricular pacing. Methods In 8 anesthetized dogs, the left ventricle was rapidly paced (180 bpm) from a basolateral and apicoseptal site during normal perfusion and mild and severe ischemia of the left anterior descending coronary artery. Effects on myocardial function were measured at each level of ischemia before and during pacing. Results Significant differences ( p < 0.05) between basolateral and apicoseptal pacing were found for segmental shortening (12.1 ± 1.6 vs. 10.8 ± 1.6%), and QRS duration (77.3 ± 4.1 vs. 85.7 ± 3.8 ms) at normal coronary perfusion. During mild ischemia, significant differences ( p < 0.05) were seen for myocardial contractility d P/d t max (1277 ± 197 vs. 1158 ± 156 mm Hg/s), segmental shortening (10.3 ± 1.9 vs. 8.1 ± 1.7%), left ventricular end-systolic pressure (76.9 ± 7.5 vs. 69.6 ± 7.9 mm Hg), and QRS duration, and for myocardial contractility d P/d t max (1033 ± 209 vs. 917 ± 207 mm Hg/s) and left ventricular end-systolic pressure (69.2 ± 13.5 vs. 62.2 ± 15.0 mm Hg) during severe ischemia. There were no significant differences in coronary blood flow during pacing from both sites. Conclusions During acute myocardial ischemia, depression of left ventricular function was lowest, when pacing from a left ventricular basolateral site. The effects of rapid left ventricular pacing were amplified by reduced coronary perfusion pressures. The choice of pacing site did not relevantly influence coronary blood flow.

Acetaminophen and myocardial infarction in dogs.

The hypothesis that acetaminophen can reduce necrosis during myocardial infarction was tested in male dogs. Two groups were studied: vehicle- (n=10) and acetaminophen-treated (n=10) dogs. All dogs were obtained from the same vendor, and there were no significant differences in their ages (18 +/- 2 mo), weights (24 +/- 1 kg), or housing conditions. Selected physiological data, e.g., coronary blood flow, nonspecific collateral flow, epicardial temperature, heart rate, systemic mean arterial pressure, left ventricular developed pressure, the maximal first derivative of left ventricular developed pressure, blood gases, and pH, were collected at baseline and during regional myocardial ischemia and reperfusion. There were no significant differences in coronary blood flow, nonspecific collateral flow, epicardial temperature, heart rate, systemic mean arterial pressure, or blood gases and pH between the two groups at any of the three time intervals, even though there was a trend toward improved function in the presence of acetaminophen. Infarct size, the main objective of the investigation, was markedly and significantly reduced by acetaminophen. For example, when expressed as a percentage of ventricular wet weight, infarct size was 8 +/- 1 versus 3 +/- 1%(P <0.05) in vehicle- and acetaminophen-treated hearts, respectively. When infarct size was expressed as percentage of the area at risk, it was 35 +/- 3 versus 13 +/- 2% (P <0.05) in vehicle- and acetaminophen-treated groups, respectively. When area at risk was expressed as percentage of total ventricular mass, there were no differences in the two groups. Results reveal that the recently reported cardioprotective properties of acetaminophen in vitro can now be extended to the in vivo arena. They suggest that it is necessary to add acetaminophen to the growing list of pharmaceuticals that possess cardioprotective efficacy in mammals.

Cardioesophageal reflex: A mechanism for “linked angina” in patients with angiographically proven coronary artery disease

Objectives. The purpose of this study was to investigate the presence of a cardioesophageal reflex in patients with coronary artery disease that may explain the mechanism of “linked angina”.Background. It has been previously shown that esophageal acid stimulation can reduce coronary blood flow in patients with syndrome X, suggesting the presence of a cardioesophageal reflex in humans.Methods. We studied the effect of esophageal acid stimulation on coronary blood flow in 14 patients with angiographically documented significant coronary artery disease and in 18 heart transplant recipients. Hydrochloric acid (0.1 mol/liter) and 0.9% saline solution were infused in random, double-blind manner (60 ml over 5 min) through a fine-bore tube positioned in the patient's distal esophagus, and coronary blood flow measurements were obtained after each infusion by use of a 3.6F intracoronary Doppler catheter positioned in the proximal left anterior descending coronary artery.Results. Coronary blood flow was reduced significantly by esophageal acid stimulation in the coronary artery disease group (before acid 70.4 ± 14.3 ml/min, after acid stimulation 46.4 ± 19.1 ml/min [mean ± SD], p < 0.01). However, there was no significant difference in coronary blood flow during saline infusion (73.5 ± 15.3 vs. 72.5 ± 14 ml/min). Coronary blood flow in the heart transplant group was not affected by acid or saline infusion.Conclusions. Esophageal acid stimulation can cause angimal attacks and significantly reduce coronary blood flow in patients with coronary artery disease. The lack of any significant effect in heart transplant recipients with heart denervation suggests a neural reflex.

Variations in the size of the ischemic myocardium due to differences in the normal file

The myocardial thallium concentration is different during pharmacologic than exercise stress testing due to differences in coronary blood flow and cardiac output. These differences may affect the quantitative measurement of the size of ischemic myocardium if a stress-specific normal file is not used. This study examined this concept in 34 patients with isolated left anterior descending coronary artery disease. All patients underwent tomographic thallium imaging during adenosine infusion (140 micrograms/kg/min for 6 minutes). The size of the ischemic myocardium was measured from the polar map using two different normal files; one derived from normal subjects undergoing treadmill exercise testing, and the second from normal subjects undergoing adenosine stress testing. The extent perfusion abnormality was 19 +/- 13% using the exercise file, and 11 +/- 10% using adenosine file (difference; 8.1 +/- 1.6%, P = 0.0001), the severity score was 580 +/- 480 using exercise file, and 310 +/- 310 using the adenosine file (P < 0.001). The differences were present in the 20 patients with moderate stenosis (50 to 70% diameter stenosis); 17 +/- 10% versus 7 +/- 7% (P = 0.001), and in the 14 patients with severe stenosis (> 70% diameter stenosis); 24 +/- 16% versus 18 +/- 10% (P = 0.03). Thus, stress-specific normal file should be used for sizing the perfusion abnormality. The use of exercise file overestimates defect size in patients undergoing pharmacologic stress testing.

Coronary haemo-dynamics and myocardial metabolism during weaning from mechanical ventilation in cardiac surgical patients

The present clinical study was undertaken to assess the alterations in myocardial metabolism and coronary haemodynamics during weaning from mechanical ventilation in postoperative cardiac surgical patients. Global and regional myocardial blood flow and metabolism were assessed using a dual port coronary sinus-great cardiac vein thermodilution catheter in 17 patients who had undergone coronary revascularization and who were being weaned from mechanical ventilation. Anaerobic myocardial metabolism, as demonstrated by the production of myocardial lactate, manifested in 8 of 17 patients during at least one of the weaning phases. There were no differences in coronary blood flow between patients who produced myocardial lactate and those who maintained aerobic cardiac metabolism. However, lactate producers exhibited larger changes in systemic vascular resistance and mean arterial pressure than the non-lactate producers. This metabolic manifestation of myocardial ischaemia was not accompanied by electrocardiographic changes of ischaemia, nor presence of chest pain, and may represent another form of silent ischaemia. We conclude that despite coronary revascularization, the myocardium may remain vulnerable to ischaemic anaerobic metabolism in the immediate postoperative period.

Tolerance of the hypertrophic heart to ischemia. Studies in compensated and failing dog hearts with pressure overload hypertrophy.

Tolerance of the canine heart to prolonged ischemic arrest was studied in 10 hearts from normal control dogs and 15 hearts from dogs with left ventricular hypertrophy (LVH); experiments were performed 1 year after banding the aorta in 8-week-old puppies. At 1 year, hemodynamic studies revealed decreased left ventricular (LV) fiber shortening and elevated end-diastolic pressure (EDP) in five dogs (group with LVH failure); 10 dogs exhibited normal shortening and normal EDP (group with LVH compensation). The left ventricle-to-body weight ratio (g/kg) was 4.4 +/- 0.8 in the control group of dogs, 7.7 +/- 1.0 in the group with LVH compensation, and 10 +/- 2.5 in the group with LVH failure. The tolerance to 60 minutes of global ischemia (37 degrees C) followed by 90 minutes of reperfusion was studied in an isolated blood-perfused heart apparatus (isovolumic left ventricle, coronary perfusion pressure of 100 mm Hg). In the baseline (preischemic) state, coronary blood flow, myocardial oxygen consumption, lactate extraction, and myocardial high-energy phosphate content were essentially equal in the three groups; with LV volume adjusted to produce a systolic pressure of 100 mm Hg, there were no significant differences in LVEDP among the three groups. During ischemia, the diastolic (asystolic) pressure increased from 11 +/- 3 to 28 +/- 16 mm Hg (p less than 0.05) in the group with LVH failure; however, it did not increase in the control or the LVH compensation groups. Myocardial ATP levels declined equally in all three groups. During early reperfusion, lactate washout was lowest in the group with LVH failure. By 90 minutes of reperfusion, there were no significant differences in coronary blood flow, myocardial oxygen consumption, lactate extraction, or high-energy phosphate levels. High diastolic pressure persisted at 90 minutes of reperfusion in the LVH failure group (EDP was 34 +/- 19 mm Hg); however, there was no significant change in EDP during reperfusion in the control or with LVH compensation groups. After 90 minutes of reperfusion, developed pressures in the control (54 +/- 9 mm Hg), the LVH compensation (49 +/- 18 mm Hg), and the LVH failure (67 +/- 17 mm Hg) groups were not significantly different. These data indicate that hearts with compensated LVH do not exhibit an impaired tolerance to ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Exercise training increases coronary transport reserve in miniature swine

Female yucatan miniature swine were trained on a treadmill (ET) or were cage confined (C) for 16-22 wk. The ET pigs had increased exercise tolerance, heart weight-to-body weight ratio, and skeletal muscle oxidative capacity. After anesthesia the left anterior descending coronary artery was cannulated and pump perfused with blood while aortic, central venous, and coronary perfusion pressures, electrocardiogram, heart rate, and coronary blood flow were monitored. Capillary permeability-surface area product (PS) for EDTA was determined with the single-injection indicator-diffusion method by use of an organ model based on the Sangren-Sheppard equations for capillary transport. Coronary blood flow (CBF) and PS were compared before and during maximal adenosine vasodilation with coronary perfusion pressures at 120 mmHg. Results indicate that there were no differences in base-line CBF or PS between C and ET groups. alpha-Receptor blockade with phentolamine and/or prazosin, before adenosine vasodilation, produced increases in PS in C pigs but had little effect in ET pigs. During maximal vasodilation with adenosine, ET pigs had greater CBF (447 +/- 24 vs. 366 +/- 27 ml.min-1.100 g-1) and greater PS (83 +/- 9 vs. 55 +/- 7 ml.min-1.100 g-1) than the C group. It is concluded that ET induces an increased coronary transport capacity in miniature swine that includes a 22% increase in blood flow capacity and a 51% increase in capillary exchange capacity.

Preoperative Cardiovascular Monitoring

Summary Clinicians have available to them a variety of preoperative screening and monitoring techniques allowing detection of CAD, infarction, and evaluation of ventricular function, factors that have been shown to correlate with postoperative cardiac morbidity. Electrocardiography has been the traditional mainstay for detecting CAD. The increasing use of ambulatory ST-segment monitoring should ensure its importance for the foreseeable future. The use of techniques that unmask CAD by increasing myocardial oxygen demand, or by use of pharmacologic vasodilation to induce regional differences in coronary blood flow, have greater sensitivity than tests performed in the resting state. Dipyridamole-thallium imaging, attractive due to its application to patients unable to exercise, has grown in popularity. Although it may be a sensitive predictor of adverse outcome or intraoperative ischemia, evidence suggests that it has little value as a routine screening tool. Evaluation of left ventricular function is possible using many different techniques, although radionuclide angiography is the most sensitive. Low ejection fraction, especially below 0.40, identifies a subgroup of patients at high risk. Aggressive therapy of myocardial ischemia or congestive heart failure, identified by these techniques, may enhance perioperative survival in these patients. Preoperative assessment remains the cornerstone of perioperative care.

The Influence of Heart Rate on Coronary Artery Atherosclerosis

Elevated “casual” heart rate (HR) has been found to be an independent predictor of coronary heart disease (CHD) in human beings. The current study provides data on the association between coronary artery atherosclerosis (CAA) and naturally occurring individual differences in the casual HRs of cynomolgus macaques (Macaca fascicularis). The data demonstrate that naturally occurring differences in casual HR are related to CAA (plaque area in mm) with high HR monkeys having lesions more than twice as extensive as those of low HR monkeys (high HR; n=7, 159 beats/min: 0.76 mm2 ± 0.21 SD; low HR; n = 8, 133 beats/min: 0.31 mm2 ± 0.30; t = 3.01, p<0.01). The data show further that the distribution of individual differences in casual HR is consistent and stable over periods of at least 12 months. Importantly, the relationship between elevated casual HR and CAA was independent of the association between an index of HR "responsivity" to stress and CAA, found in the same monkeys. Similar to a recent finding in human beings, high casual HR also was associated with significantly lowered serum concentrations of high-density lipo-protein cholesterol; differences in CAA were, however, independent of the lipid difference. The CAA differences may depend instead on HR-induced differences in coronary blood flow between high and low HR monkeys. Subsequent work with β-adrenergic blockade suggested that elevated casual HRs in monkeys are associated with sympathetic arousal.

Morphometry of the coronary microvasculature of the canine left ventricle.

The objective of this study was to test for the presence of transmural gradients of various components of the coronary microvasculature of the canine left ventricle. In order to achieve study objectives, the heart and coronary circulation were fixed in a reproducible state of myocardial and vascular tone (diastolic cardiac arrest and maximal coronary vasodilation). Morphometric methods which treat the coronary microvasculature as anisotropically arranged structures were applied for quantitative structural analysis. Eight dog hearts were fixed with a glutaraldehyde-cacodylate-buffered fixative by retrograde perfusion of the aorta with the heart in diastolic arrest and with maximal coronary vasodilation. Tissue samples were taken from areas near to the anterior and posterior papillary muscles from the subendocardium, subepicardium, and intermediate transmural locations. Morphometric results showed a homogeneously arranged array of microvascular and myocardial components with no significant differences in any of the primary morphometric measurements, down to the ultrastructural level, in myocytes relative to transmural location. The results suggest that transmural differences in coronary blood flow are not due to transmural structural differences but rather are due to physiological regulatory mechanisms of coronary blood flow. Further, the results indicate that failure to correct for anisotropy of myocardial structures can lead to erroneous conclusions concerning the structural basis of function in the heart.

Alpha-receptor restriction of coronary blood flow during atrial fibrillation

The effects of atrial fibrillation (AF) on coronary circulation before and after alpha-receptor blockade were studied in 14 anesthetized, open-chest dogs. AF was induced by electrical stimulation of the left atrial appendage; identical rhythmic heart rates were adjusted by left atrial pacing. During atrial pacing, coronary vascular resistance (CVR) was 0.97 ± 0.10 mm Hg × min × 100 g/ml (resistance units [RU]), coronary blood flow (CBF) 125 ± 14 ml/min × 100 g, and oxygen saturation 30 ± 2%; plasma epinephrine was 193 ± 42 pg/ml and norepinephrine 584 ± 111 pg/ml. During AF, CVR was higher (1.16 ± 0.11 RU, p < 0.0005), whereas CBF (92 ± 9 ml/min × 100 g, p < 0.001) and coronary sinus oxygen saturation (24 ± 2%, p < 0.0025) were lower than during atrial pacing. When AF was induced, epinephrine increased to 333 ± 98 pg/ml (p < 0.05) and norepinephrine to 1,005 ± 214 pg/ml (p < 0.005). The large increase in plasma catecholamines suggested an activation of the sympathoadrenal system during AF. In addition, the alphareceptor blocker phenoxybenzamine (10 mg/kg, intravenously) abolished the differences in CVR, CBF and oxygen saturation between AF and atrial pacing. The data suggest that the decrease in CBF and increase in CVR during experimentally induced AF are caused by coronary vasoconstriction, mediated by sympathetic activation of alpha receptors in the coronary vascular bed.

Myocardial protection by coronary washout during global ischemic cardiac arrest

The effect of intermittent coronary washout (WO) during global ischemic cardiac arrest (ICA) was evaluated in isolated blood perfused dog hearts undergoing 90 min normothermic ICA and 90 min reperfusion. WO consisted of infusion of 100 ml normothermic dog plasma at 100 mm Hg every 10 min during ICA. Systolic and diastolic pressures were measured at constant volume with a left ventricular balloon. Coronary blood flow (CBF) was measured, and transmyocardial oxygen, lactate, and glucose differences were calculated. Adenosine triphosphate (ATP), creatine phosphate (CP), calcium (Ca 2+), glycogen, and water content were measured from left ventricular biopsies. During 90 min of WO, hearts extracted glucose (15 ± 4 mg/g dry wt LV) and lost lactate (90 ± 5 μmole/g dry wt LV). ATP and CP were significantly depressed at arrest in both groups although WO resulted in significantly higher levels of ATP and CP. CP returned to control levels at 90 min reperfusion in the WO group but remained depressed in the ICA group. Calcium accumulation was greater in hearts with ICA. With reperfusion, both ICA and WO groups demonstrated early hyperemia and rapid lactate washout. There were no differences in total CBF, AVO 2, MOV 2, and myocardial glycogen or water content. Systolic performance was equally depressed in both groups at 90 min of reperfusion. Diastolic compliance, while still impaired, was better preserved in WO when measured in the arrested heart at 90 min ICA ( P < 0.01) and in the contracting heart after 90 min reperfusion ( P < 0.02). Normothermic coronary washout during 90 min of normothermic ischemic arrest without cardioplegic agents produces improved ventricular compliance and energy metabolism, and reduces myocardial calcium accumulation.

Effects of Myocardial Strains on Coronary Blood Flow

Systole causes a redistribution of coronary blood flow away from the subendocardium. In the present study the relative contribution of shortening of the myocardial fibers (wall strains) and of pressure development in the ventricular lumen to redistribution were determined. The distribution of coronary blood flow during systole in hearts ejecting into a severed aorta (large wall strains and near-zero afterload) was compared with that in isovolumetrically contracting hearts (reduced wall strains and significant afterload). A quantitative index of the distribution of coronary blood flow during systole was provided by the myocardial uptake of a bolus of 86 Rb or 42 K injected when constant-pressure perfusion of the left coronary artery was restricted with a solenoid-controlled pump to the period of systole. The coronary blood flow during systole in the subendocardium of the ejecting heart was 62% of that in the subepicardium. A similar gradient in the systolic flow with the endocardium receiving 37% of the blood flow to the epicardium was observed in the hearts contracting isovolumetrically. Removing the afterload by severing the aorta abolished the transmural differences in coronary blood flow. In the present experiment cardiac strains per se did not redistribute coronary blood flow through shear or traction forces on the coronary vasculature, but rather, coronary blood flow was affected only by compressive stresses in the myocardium. Contraction in the absence of afterload influenced overall coronary resistance, however; 18% of the resting coronary resistance was associated with shortening alone. An additional 11% of the resting coronary resistance appeared when pressure development accompanied shortening. Coronary blood flow patterns indicated two separate compressive stresses in the left ventricle. The first stress was associated with pressure development and increased with myocardial depth. The second stress was smaller; it was associated with shortening and uniformly distributed.