Coronary Vascular Reserve Research Articles

Abstract 11882: Exploring Abnormalities in Coronary Vascular Resistance Reserve as a Distinct Feature of The Hfpef Syndrome in Women

Introduction: Heart failure with preserved ejection fraction (HFpEF) is more common in women than men, but mechanisms underlying this female predominance are incompletely understood. Impaired systemic vasodilatory reserve and coronary microvascular dysfunction have been separately described as key abnormalities of HFpEF. However, the coronary vascular resistance reserve (CVRR), defined as the drop in coronary vascular resistance (CVR) from rest to peak stress, and its sex-specific nuances have not been explored in HFpEF. We sought to: (1) determine whether stress CVR differs between HFpEF and controls, and (2) assess sex differences in CVRR in HFpEF. Methods: We performed a cross-sectional study of 32 HFpEF participants and 26 controls, all without obstructive epicardial coronary artery disease. HFpEF was defined according to ESC Guidelines. Dipyridamole stress 82 Rb positron emission tomography was performed, and rest and stress CVR was calculated by dividing mean arterial pressure by coronary flow at rest and stress. Multivariable linear regression assessed (1) the association of HFpEF with stress CVR; and (2) the association of female sex with CVRR in patients with and without HFpEF. Results: Mean age was 74±7 years, 67% were women and mean LVEF was 62±5%: no difference between HFpEF and controls (P>0.05 for each). Results of the multivariable models are summarized in the Image. HFpEF was independently associated with higher global left ventricular CVR at peak vasodilatory stress. In addition, women had lower global left ventricular CVRR as compared to men, and this was unique to women with HFpEF. Results were the same for coronary-specific CVR and CVRR (analyses not shown). Conclusions: To our knowledge, this is the first study to non-invasively explore CVR and CVRR in HFpEF. Our findings suggest increased stress CVR in HFpEF, with a distinct abnormality in CVRR in women with HFpEF. Abnormal CVRR in women may contribute to the female predominance of HFpEF.

Effect of Platelet GPIIb/IIIa Receptor Blockade With MK383 on Infarct Size and Myocardial Blood Flow in a Canine Reocclusion Model.

Platelet activation and aggregation during ischemia influence reperfusion-related myocyte necrosis, myocardial perfusion at the microvascular level, and thereby eventual recovery of cardiac performance. Inhibition of platelet activity therefore represents a worthwhile target to reduce cellular injury. The current study examined the effects of MK383 (tirofiban), a potent inhibitor of platelet aggregation, on infarct size and myocardial perfusion in canine subjects to either reocclusion (ie, 120-minute + 60-minute ischemia with intervening reperfusion) or prolonged occlusion (ie, 3 hours) followed by reperfusion (180 minutes). Platelet aggregation, infarct size (tetrazolium staining), coronary blood flow (flow probe), coronary vascular reserve, and myocardial perfusion (microspheres) were evaluated. MK383, administered at the time of reperfusion, produced a modest reduction of tissue necrosis (compared to saline-treated controls) in the reocclusion and prolonged occlusion studies. Blood flow in the infarct-related artery after coronary occlusion was comparable between treatment groups, as was myocardial perfusion in the deeper layers of the ischemic region; coronary vascular reserve decreased progressively during reperfusion. Of note, compensatory changes in blood flow within the adjacent nonischemic myocardium were not observed. In conclusion, we report that that limiting platelet aggregation during reperfusion impacted infarct development. Continued investigation into the mechanisms by which inhibition of platelet activity protects myocardium against ischemia-reperfusion injury and improves clinical outcomes is necessary.

Impact of Chronic Kidney Disease on Myocardial Blood Flow Regulation in Dogs

Background/Aims: Chronic kidney disease (CKD) increases cardiovascular risk possibly due to coronary microvessel dysfunction and impaired myocardial flow reserve. This study investigated the effects of CKD on the regulation and transmural distribution of myocardial blood flow along with oxygen demand during intravenous dobutamine-induced increases in cardiac work. Methods: CKD was produced in dogs by a two-stage subtotal nephrectomy (kidney ablation-infarction model). Serum creatinine and blood urea nitrogen were evaluated during the development of CKD along with systemic blood pressure (tail-cuff plethysmography). After 5 weeks, the CKD dogs were staged according to the International Renal Interest Society staging system; all dogs were anesthetized and surgically prepared for blood flow studies. Data analyses were performed between sham control (CTR) and stage 1 and 2 CKD dogs. Results: At baseline, myocardial blood flow and diastolic aortic pressure were similar for all groups. During intravenous dobutamine, myocardial blood flow was markedly higher than CTR even though hematocrit levels declined with the severity of CKD. In the CTR dogs, myocardial blood flow increased in direct relation to cardiac work. However, in the CKD dogs (stage 1 and 2), maximum blood flow was achieved with low-dose dobutamine, indicating that coronary autoregulation is more readily exhausted with minimal increases in cardiac work during CKD. Conclusion: We report that CKD markedly impairs coronary vascular reserve and myocardial blood flow regulation which could contribute to greater cardiovascular risk and poor clinical outcomes in CKD patients.

Influence of Cardiac Decentralization on Preconditioning-Mediated Cardioprotection in Anesthetized Dogs

The role of cardiac nerves on development of myocardial tissue injury after acute coronary occlusion remains controversial. We investigated whether acute cardiac decentralization (surgical) modulates myocardial protection and coronary vascular reserve in preconditioned dogs subject to ischemia-reperfusion (IR).

Alteration in systemic vascular resistance and cardiac output during acute cellular rejection and recovery in heart transplant recipients

Coronary vascular reserve is impaired during acute cellular rejection of the orthotopically transplanted heart, but changes in the peripheral vasculature during rejection have not been well described. To investigate whether peripheral vascular compensatory mechanisms are preserved after orthotopic heart transplantation (OHT), we longitudinally observed systemic vascular resistance (SVR) and cardiac output (CO) during acute cellular rejection. CO decreased during high-grade acute cellular rejection, and maintenance of mean arterial pressure was achieved by increases in SVR, and these changes did not return to baseline until several months after histologic resolution of rejection.

Left ventricular hypertrophy induced by aortic banding impairs relaxation of isolated coronary arteries

LVH (left ventricular hypertrophy) is associated with impaired coronary vascular reserve. In the present study, we examined the effect of pressure-overload hypertrophy on vasorelaxant responses of guinea-pig isolated coronary small arteries and compared them with mesenteric small arteries. Pressure-overload was induced by banding the ascending aorta of guinea-pigs. Haemodynamics, and ventricular, atrial and lung weights were measured 168 days after banding. Isolated coronary and mesenteric small arteries were contracted with a thromboxane mimetic (U46619) and relaxation to ACH (acetylcholine), ISO (isoprenaline), FSK (forskolin) and SNP (sodium nitroprusside) was examined. Arterial wall morphology was examined by light microscopy. Aortic banding reduced cardiac output and increased systemic vascular resistance; atrial, ventricular and lung weights were increased. Coronary artery adventitial and medial thickness were increased, but mesenteric arterial wall morphology was unaffected. Coronary artery relaxation to ACH, ISO, FSK and SNP were reduced in banded animals. In contrast, relaxation of mesenteric arteries to ACH, FSK and SNP were unaffected by banding, although ISO-induced relaxation was reduced. A COX (cyclo-oxygenase) inhibitor, indomethacin, had no effect on coronary artery responses to ACH in banded or sham animals, but the differences in relaxation of coronary arteries between banded and sham animals were no longer significant following pre-incubation with the NO inhibitors L-NMMA (N(G)-monomethyl-L-arginine) and oxyhaemoglobin. In conclusion, pressure-overload-induced LVH causes impaired relaxation of small coronary arteries to endothelium-dependent and -independent relaxants. These findings are indicative of alterations in vascular smooth muscle responsiveness to vasodilators. Impairment of coronary arterial vasodilation may contribute to the reduced coronary vascular reserve seen in LVH.

Influence of Acute Renal Failure on Coronary Vasoregulation in Dogs

Impaired renal function is associated with an increased risk for cardiovascular events and death, but the pathophysiology is poorly defined. The hypothesis that coronary blood flow regulation and distribution of ventricular blood flow could be compromised during acute renal failure (ARF) was tested. In two separate groups (n = 14 each) of dogs with ARF, (1) coronary autoregulation (pressure-flow relations), vascular reserve (reactive hyperemia), and myocardial blood flow distribution (microspheres) and (2) coronary vessel responses to intracoronary infusion of select endothelium-dependent and -independent vasodilators were evaluated. In addition, coronary pressure-flow relations and vascular reserve after inhibition of nitric oxide and prostaglandin release were evaluated. Under resting conditions, myocardial oxygen consumption increased in dogs with ARF compared with no renal failure (NRF; 11.8 +/- 9.2 versus 5.0 +/- 1.5 ml O(2)/min per 100 g; P = 0.01), and the autoregulatory break point of the coronary pressure-flow relation was shifted to higher diastolic coronary pressures (60 +/- 17 versus 52 +/- 8 mmHg in NRF; P = 0.003); the latter was shifted further rightward after inhibition of both nitric oxide and prostaglandin release. The endocardial/epicardial blood flow ratio was comparable for both groups, suggesting preserved ventricular distribution of blood flow. In dogs with ARF, coronary vascular conductance also was reduced (P = 0.001 versus NRF), but coronary zero-flow pressure was unchanged. Vessel reactivity to each endothelium-dependent/independent compound also was blunted significantly. In conclusion, under resting conditions, coronary vascular tone, reserve, and vessel reactivity are markedly diminished with ARF, suggesting impaired vascular function. Consequently, during ARF, small increases in myocardial oxygen demand would induce subendocardial ischemia as a result of a limited capacity to increase oxygen supply and thereby contribute to higher risk for adverse coronary events and mortality.

Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease

The aim of this study was to analyse non-invasively the regional effect of therapy with an HMG-CoA reductase inhibitor on myocardial blood flow in patients with coronary artery disease (CAD) with special reference to segments with initially substantially impaired vasodilation. The study included 26 patients with untreated hypercholesterolaemia. Coronary angiography revealed CAD in nine patients with stenosis >50% and wall irregularities or minimal stenosis <30% in 17 patients. Before and 4.6+/-1.8 months after atorvastatin therapy, ( 13)N-ammonia positron emission tomography (PET) studies were performed at rest and under pharmacological stress. Minimum coronary vascular resistance (MCR) and coronary flow reserve (CFR) were determined. Segments were divided into those with normal or near-normal (MBF during adenosine > or =2.0 ml/min/g) and those with abnormal (MBF<2.0 ml/min/g) vasodilator flow response. In CAD patients, 156 segments were analysed, 85 of which had abnormal MBF; in the non-obstructive group, 59 of 297 segments had abnormal MBF. LDL cholesterol decreased after atorvastatin therapy from 186+/-43 mg/dl to 101+/-26 mg/dl (p<0.001). In normal segments no significant changes in MBF, CFR and MCR were found. However, initially abnormal segments showed significant improvements in MCR (15%, p<0.0001) and MBF during adenosine (30%, p<0.0001) after therapy. The improvement in regional coronary vasodilator function after atorvastatin in patients with coronary atherosclerosis may be caused, at least in part, by increased flow-mediated (endothelium-dependent) dilation of the total arteriolar and arterial vascular system. These data further support the concept of non-invasive management of stable CAD by statin therapy and life-style modification guided by PET.

Coronary flow characteristics after a Bentall procedure with or without sinuses of Valsalva.

The sinuses of Valsalva are known to contribute to the normal function of the aortic valve. Little is known about their role in promoting coronary artery blood flow. The aim of this study was to compare coronary artery flow characteristics among patients undergoing a Bentall operation by means of a conventional cylindrical Dacron conduit or with a new conduit with pseudosinuses of Valsalva or in patients retaining their natural sinuses of Valsalva after aortic valve and supracoronary ascending aorta replacement. One year after a Bentall procedure with a standard cylindrical Dacron conduit (7 patients, group A) or with the new conduit (7 patients, group B), or after aortic valve and ascending aortic replacement (control group, 7 patients, group C) coronary flow velocity reserve and diastolic to systolic time integral ratio at baseline and after maximal hyperemia (with 40 microg of adenosine) were assessed by using a 0.014-in. Doppler guidewire positioned in the middle portion of the left anterior descending coronary artery. All patients were in NYHA class I, sinus rhythm and free of coronary disease. Arterial blood pressures and heart rate were comparable among groups. Intracoronary Doppler measurements did not show any significant difference in coronary vascular reserve between the three groups (3.6+/-0.4 vs 3.1+/-0.7 vs 3.7+/-0.5, P = 0.2). A greater diastolic component at baseline was present in group B patients (5.5+/-1.9 vs 3.5+/-0.9 in group A and 3.7+/-0.9 in group C, P = 0.024). After maximal hyperemia the diastolic component increased slightly in group A patients (8%) while both in groups B and C significantly decreased (-15 and -20%, respectively) (P = 0.017). The presence of pseudosinuses of Valsalva does not influence coronary flow reserve. After maximal coronary vasodilation the increase in the systolic component of coronary flow is more evident in the presence of sinuses or pseudosinuses of Valsalva, thus suggesting that coronary flow pattern may be affected by the presence of sinuses.

Diastolic coronary vascular reserve: a new index to detect changes in the coronary microcirculation in hypertrophic cardiomyopathy

ObjectivesThe present study introduces a modification of the diastolic coronary conductance concept that maintains its sensitive properties to detect changes in the coronary microcirculation in human hypertrophy. BackgroundDecrements of coronary flow in hypertrophy have been explained by changes in the coronary microcirculation. No measure is available to detect these changes. MethodsDoppler velocity catheters were introduced into the left anterior descending artery (LAD) and left circumflex coronary artery (LCx) of patients with obstructive hypertrophic cardiomyopathy (HCM) (n = 11) and into the LAD of cardiac transplant recipients (n = 9). The diastolic coronary conductance was measured at rest and after maximal hyperemia induced by a bolus injection of adenosine. Diastolic coronary vasodilator reserve (DCVR) was calculated as the hyperemic diastolic coronary conductance, divided by the coronary conductance during resting conditions. ResultsLeft ventricular outflow tract gradient in the HCM group (83 ± 31 mm Hg) was significantly higher (p < 0.05). Septal wall thickness was significantly increased (p < 0.05), while wall thickness was unchanged in the posterior wall of the HCM group. The coronary flow reserve was significantly decreased in the HCM-LCx region (to 64 ± 7% of control) and in the HCM-LAD regions (to 57 ± 7% of control). The DCVR was only decreased in the HCM-LAD (to 46 ± 3% of control) and not in the HCM-LCx group (86 ± 6%, p > 0.05). Esmolol did affect the pressure gradient and systolic shortening, but did not affect the maximal diastolic conductance. ConclusionsThe DCVR, in contrast with the coronary flow reserve, is decreased in those regions that display a disturbance in the microcirculation and may, therefore, offer a new way to study coronary adaptations in patients with hypertrophy.

Thoracic Epidural Anesthesia and the Patient with Heart Disease

Thoracic Epidural Anesthesia and the Patient with Heart Disease

Coronary vascular reserve is similarly reduced in hypertensive patients without any other coronary risk factors and in normotensive smokers and hypercholesterolemic patients with angiographically normal coronary arteries

Hypertensive patients (HTP) with left ventricular hypertrophy have reduced coronary vascular reserve (CVR), but in HTP without left ventricular hypertrophy, CVR is within the normal range according to values determined in subjects without taking into account coronary risk factors such as cigarette smoking or hypercholesterolemia. To examine the influence of hypertension, cigarette smoking, and hypercholesterolemia on coronary flow and resistance reserve, coronary flow velocity was measured using a Doppler catheter before and after a maximally vasodilating dose of papaverine in 15 normotensive subjects without any coronary risk factors (Group 1), in 12 nonsmoker HTP with normal lipid profiles who had never been treated (Group 2), in 8 normotensive smoker patients (Group 3), in 9 normotensive nonsmoker patients with hypercholesterolemia (Group 4), and in 13 normotensive smoker patients with hypercholesterolemia (Group 5). All patients had normal coronary arteriography and left ventricular mass and function. Peak-to-resting coronary flow velocity ratio and mean aortic pressure were used to determine coronary flow reserve (CFR) and a minimal coronary vascular resistance index (MCVRI). Results show that in groups 2, 3, 4, and 5 comparatively to Group 1, CFE was similarly reduced (4.60 ± 0.74 [ P < .001], 4.59 ± 0.35 [ P < .001], 5.01 ± 0.55 [ P < .05], 5.03 ± 0.78 [ P < .05], groups 2 to 5, respectively, compared to group 1 5.66 ± 0.68), and that MCVRI was similarly augmented (0.19 ± 0.03) [ P < .01], 0.20 ± 0.01 [ P < .001], 0.19 ± 0.02 [ P < .05], 0.19 ± 0.03 [ P < .05], groups 2 to 5, respectively, compared to group 1 0.16 ± 0.02). In conclusion, HTP without left ventricular hypertrophy have a similar reduction of their CVR as smokers and hypercholesterolemic patients when compared to a group of subjects without any coronary risk factors. This should be taken into account when determining a group of control subjects for coronary reserve.

Effects of hypercholesterolaemia on physiological recruitment of coronary vascular reserve in swine.

1. The endothelium participates in the regulation of coronary vascular tone. As evidence exists from studies performed on epicardial vessels that hypercholesterolaemia impairs endothelial function, we tested the hypothesis that hypercholesterolaemia impairs coronary vascular reserve in an intact animal. 2. Domestic swine, maintained on a regular (n = 9) or a 2% high-cholesterol (n = 9) diet for 3 months were instrumented with a catheter in the left atrium for microsphere injection, a catheter in the anterior interventricular vein for venous sampling and an 82% stenosis in the left anterior descending artery. Papaverine was used to determine coronary vascular reserve. Regional coronary flow as reflected by perfusion (microsphere measurement), lactate consumption, oxygen consumption and haemodynamics were obtained at baseline, after 10 mg of papaverine and after atrial pacing at a rate of 120 beats/min and 150 beats/min. 3. Cholesterol was elevated in animals on the high cholesterol diet (350 +/- 50 mg/dl versus 99 +/- 10 mg/dl, P < 0.001). Baseline haemodynamics were similar between groups. Baseline transmural flow and its augmentation with papaverine were comparable in the two groups in the control (circumflex) and stenosed (left anterior descending artery) zones. In both groups, perfusion increased in the control zone in response to increased oxygen demand, whereas in the stenosis zone no increase was observed in either group (P not significant for normal versus high cholesterol diet). Endocardial flow reserve in the stenosis zone was exhausted in both groups. Epicardial flow in the stenosis zone increased significantly in the normal (P < 0.02) but not in the hypercholesterolaemic animals (P not significant). 4. The endocardial/epicardial ratio in the control zone at baseline revealed greater endocardial dominance in the normal compared with the hypercholesterolaemic animals (1.35 versus 1.10, P < 0.01). With papaverine, similar ratios indicated a similar reserve potential in both groups. During increased oxygen demand, normal animals continued to demonstrate endocardial dominance whereas it diminished in the hypercholesterolaemic group. In the stenosis zone, endocardial blood flow dominated at baseline in the normal animals and to a lesser extent in the hypercholesterolaemic animals (1.30 versus 1.10, P = 0.10). During increased oxygen demand, endocardial dominance decreased significantly in both groups of animals; however, it remained greater than 1.0 only in the normal animals. 5. Exposure to elevated cholesterol levels did not impair an animal's ability to augment coronary blood flow in response to an increase in oxygen demand. In contrast to this lack of effect on recruitment of coronary reserve, regional coronary blood flow was altered in the hypercholesterolaemic animals.

Coronary vascular reserve in humans: a critical review of methods of evaluation and of interpretation of the results.

The concept of coronary vascular reserve stems from the description of coronary autoregulation by Mosher in 1964. Schematically, the coronary blood flow at rest depends on the determinants of myocardial oxygen demand (heart rate, contractility and ventricular load). If maximal coronary vasodilation is produced, it results in a linear and steep pressure-flow relationship. The increment of coronary flow above its basal value is called the coronary flow reserve, which indicates the flow added to the basal flow for a given coronary perfusion pressure when the coronary vascular bed is maximally dilated. Thus, in the absence of epicardial coronary artery stenosis, the maximal coronary flow is a function of the coronary perfusion pressure and of the maximal surface area of the coronary circulation at the resistance vessel level. Evaluation of the coronary reserve in humans raises three major concerns: (1) methods for measuring or evaluating coronary flow are imprecise and inconvenient (diffusible indicators), invasive (coronary sinus thermodilution, intracoronary Doppler), expensive and require sophisticated technology (ultrafast computed tomography, positron emission tomography), or in the process of being validated (contrast echocardiography, transoesophageal Doppler echocardiography, myocardial scintigraphy: (2) the compounds used to produce maximal coronary vasodilation are administered either by the intracoronary route (papaverine) or intravenously (dipyridamole, adenosine); (3) how to interpret the data: is the alteration of the coronary reserve due to a modification of the basal coronary flow or/and of the maximal coronary flow? Thus, each method has its own limitations and constraints that must be taken into account in order to avoid crude misinterpretations. In conclusion, the measurement of coronary reserve may be an important means of understanding coronary physiology and pathophysiology. Recently developed non-invasive methods (ultrafast computed tomography, positron emission tomography, echography) and the ability to produce maximal coronary vasodilation by the intravenous route are promising.

744-5 Ischemic Heart Failure is Associated with Reduced Blood Flow Reserve in Non-embolized Arteries in Awake Dogs

With coronary obstruction, as in myocardial infarction, there is increased reliance on collateral blood flow from remote arteries. However, it remains unknown whether, with the development of heart failure (HF) consequent to the infarction, there are changes in the physiology of the remote vessels which may modify their ability to provide collateral flow. The goal of this study was to determine vasodilator capacity in non-embolized coronary vasculature in ischemic HF. Dogs were chronically instrumented to measure systemic hemodynamics. A catheter was implanted into a dominant coronary artery for multiple embolizations and a Doppler flow probe was placed on a non-catheterized coronary artery for measurements of coronary blood flow (CBF). HF was produced by repeated coronary embolizations and characterized by elevated left ventricular (LV) end-diastolic pressure and reduction in maximum LVdp/dt as well as clinical signs of HF. CBF at rest was 24 ± 0.4 ml/min vs 17 ± 1 ml/min before and after HF. The peak CBF responses following release of a brief coronary artery occlusion (Occ), to acetylcholine (Ach) and to adenosine (ADO) were examined before and after HF. The % changes of CBF from baseline are: Before heart failure After heart failure Occ. (sec) 10 261.7 ± 10% 131.6 ± 69% 15 250.7 ± 6% 102.8 ± 63% 30 240.4 ± 8% 96.4 ± 68% Ach (μg/kg) 0.25 74.4 ± 7% 19.4 ± 14% 5 162.1 ± 29% 41.7 ± 22% 10 144.4 ± 6% 66.2 ± 31% ADO (μMol/kg) 0.25 114 ± 25% 36.7 ± 32% 2 202.3 ± 36% 47.2 ± 49% 5 206.9 ± 46% 41.8 ± 71% Thus, in ischemic HF, baseline flow is decreased and coronary vascular reserve is markedly decreased in remote, non-infarct vessels of the heart. This may contribute importantly to the progression of left ventricular dysfunction even at remote areas.

Mathematical Analysis of Coronary Autoregulation and Vascular Reserve in Closed-Loop Circulation

The autoregulatory capacity of the coronary circulation has traditionally been studied in open-loop animal models where the coronary circulation was decoupled from the systemic circulation. In the closed-loop circulation, changes in arterial pressure alter coronary flow. Pressure variations can be caused by changes in cardiac contractility, preload, afterload, and heart rate. These changes also affect myocardial oxygen consumption. To maintain equilibrium between oxygen supply and consumption, coronary flow is altered by the autoregulation mechanism. Coronary resistance must change to produce the required change in coronary flow. The direction of change in coronary resistance is not directly predictable. Increased arterial pressure may result in either increased or decreased coronary resistance. To study the changes in coronary resistance in response to changes in arterial pressure that are produced by circulatory parameters, we used mathematical models. Coronary resistance was calculated to obtain equilibrium between ventricular oxygen consumption and supply for different values of contractility, preload, afterload, and heart rate. Maximum coronary resistance, indicating largest coronary vascular reserve and highest efficiency of arterial pressure generation, was defined as an optimal condition. The model predicted that the optimal value of cardiac contractility is its resting value. Minimizing end-diastolic volume and heart rate and maximizing peripheral resistance were shown to improve ventricular coronary vascular reserve. These observations suggest that afterload reduction therapy may not be beneficial for improving myocardial oxygen balance while venous vasodilatation and heart rate reduction result in greater coronary reserve.

Characterization of spatial patterns of flow within the reperfused myocardium by myocardial contrast echocardiography. Implications in determining extent of myocardial salvage.

Since myocardial blood flow changes dynamically after reperfusion and since both hyperemia and impairment in microvascular function exist within the acutely reperfused bed, we sought to investigate the role of myocardial contrast echocardiography (MCE) in (1) defining the temporal variability in perfusion patterns after reflow and relating these to microsphere-derived blood flow; (2) differentiating viable from infarcted tissue during different periods of reflow; and (3) defining spatial perfusion patterns within the infarct bed in response to exogenously induced maximal vasodilation and relating these to infarct size and extent of myocardial salvage. Twenty-one dogs with 3 hours of left anterior descending coronary artery occlusion and 2 to 3 hours of reflow were studied. MCE was performed at 15 and 45 minutes and 2 and 3 hours after reflow. It was also performed at either 2 or 3 hours after reflow in the presence of 0.56 mg/kg of dipyridamole. Radiolabeled microsphere-derived blood flow was measured at 15 minutes and 2 and 3 hours after reflow and during dipyridamole effect. Infarct size was measured at the end of the experiment by use of triphenyl tetrazolium chloride. MCE data were processed with color-coding schemes that highlighted differences in myocardial videointensities in proportion to the concentration of microbubbles within the microvasculature. There was significant variability in MCE-defined perfusion patterns after reflow, with contrast defects noted mainly within the endocardium. There were fair and significant (P < .05) correlation (r = -.73 to r = -.55) between MCE defect size and normalized endocardial blood flow. Except at 15 minutes after reflow, there was poor correlation (r = .31 to r = .51) between MCE defect and infarct sizes. Even at 15 minutes after reflow, MCE defect size underestimated infarct size by 50%. In comparison, in the presence of dipyridamole, MCE defect size correlated strongly (r = .87, P < .001) with infarct size and reasonably well with normalized transmural blood flow (r = -.62, P = .04). Moreover, the topography of the MCE perfusion defect reflected the topography of the infarct. MCE revealed striking temporal heterogeneity in the spatial distribution of myocardial perfusion during postischemia reflow and either significantly underestimated or did not correlate with infarct size during reperfusion. Because of abnormalities in coronary vascular reserve specific to infarcted tissue, MCE in conjunction with intravenous dipyridamole depicted, in vivo, the actual topography of the infarct with remarkable accuracy.

Myocardial ischemia is not a prerequisite for the stimulation of coronary collateral development

To understand better the temporal sequence of coronary collateral development and the factors that may govern that development, dogs were chronically instrumented with left circumflex (LCf) Doppler flow probe, ameroid constrictor, balloon occluder, and left atrial and aortic catheters. Collateral blood flow was measured at least weekly or when the coronary artery occluded. The reactive hyperemic response (RH) to a 15-second LCf occlusion was recorded three times per week. Most LCf arteries occluded during the 4th week after surgery. Two patterns of coronary collateral development were observed. In 11 animals collateral flow did not change for 2 or 3 weeks; peak RH and flow debt repayment, indexes of coronary vascular reserve, changed little. The next week there was an abrupt increase in collateral flow from approximately 15% of normal to 100%. This increase was coincident with a sudden loss of coronary vascular reserve and therefore suggests myocardial ischemia was the principal stimulus. However, in 11 dogs collateral flow increased gradually over 3 to 4 weeks as indexes of RH slowly decreased. The greatest increase in collateral flow occurred while peak RH was still approximately twice baseline flow, representing 80% of peak flow measured 1 week after surgery. Therefore in these animals ischemia is less likely to have been the major stimulus of coronary collateral development.

Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function.

Evidence is increasing for small-vessel disease and disturbance of endothelium-dependent vasodilation in diabetic patients. The aim of this study was to compare coronary circulation in 11 diabetic patients (6 type I and 5 type II) and 7 control subjects. All patients had normal left ventricular systolic function and angiographically normal coronary arteries. To evaluate the maximal area of coronary microcirculation, coronary vascular reserve was determined by intracoronary Doppler and a maximally vasodilating dose of intracoronary papaverine (peak-to-resting coronary flow velocity ratio). To assess coronary endothelial function responses to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) M coronary estimated concentrations) were analyzed on four different segments in each patient by quantitative angiography. Peak-to-resting coronary flow velocity ratio was lower in diabetic patients than in control subjects (3.9 +/- 0.9 and 5.0 +/- 0.7, respectively, P < 0.02). Acetylcholine did not produce any diameter change at 10(-8) and 10(-7) M, but a progressive diameter reduction was observed at 10(-6) and 10(-5) M (-8.0 +/- 15.2%, P < 0.02 and -24.0 +/- 13.6%, P < 0.001, respectively). In control subjects, a progressive diameter dilation was produced from 10(-8) to 10(-6) M acetylcholine (5.1 +/- 3.4, 12.1 +/- 7.0, and 16.4 +/- 7.3%, respectively, all P < 0.001), and a moderate reduction was observed at 10(-5) M (-4.9 +/- 7.5%, P < 0.02). In the two groups, all segments dilated similarly after intracoronary isosorbide dinitrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function

Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function