Inadequate Myocardial Perfusion Research Articles

The Use of Intracoronary Sodium Nitroprusside to Treat No-Reflow after Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction

The no-reflow phenomenon is characterized by an inadequate myocardial tissue perfusion in the presence of a patent epicardial coronary artery. The incidence of no-reflow appears to be highest in patients undergoing primary percutaneous coronary intervention (PCI) in acute myocardial infarction or during PCI of saphenous vein grafts (SVGs). Treatment of no-reflow phenomenon is based on the intracoronary administration of medications that induce vasodilatation in small distal coronary vasculature. Sodium nitroprusside (NTP) is a direct nitric oxide donor and does not require intracellular metabolism to induce vasodilatation in microcirculation. Two patients are reported, in whom no-reflow following primary PCI of SVG and native coronary artery was successfully treated with intracoronary NTP. Repeated injections of 50 microg NTP were given selectively distal to the occlusion site utilizing coronary microcatheter (a total NTP dose of 200 microg was given in both cases). Because of the extremely short half-life, the use of intracoronary NTP was easily tolerated by both patients, without causing prolonged or profound hypotension. The authors therefore propose the use of NTP for treatment of no-reflow phenomenon in both vein grafts and native coronary arteries in the setting of acute myocardial infarction.

Ischemic myocardial injuries after cardiac malformation repair in infants may be associated with oxidative stress mechanisms

Despite advances in pediatric cardiac surgery, perioperative myocardial injury can be the major determinant of postoperative dysfunction after cardiac surgery. This study investigated the pathology-related differences in 29 infants with congenital heart disease that led to death. The infants were treated at the University Hospital of Ribeirão Preto, Brazil. The patients were divided into four groups: Group 1, 16 infants who underwent operations for congenital heart disease on cardiopulmonary bypass; Group 2, four infants who underwent off-cardiopulmonary bypass operations for congenital heart disease; Group 3, nine infants who died from congenital heart disease prior to surgical treatment; and Group 4 (control group), five infants with no congenital heart disease and who died from other causes. The myocardial injuries and oxidative stress mechanisms were assessed by histopathology and immunohistochemistry and were quantified by morphometrical analyses. Contraction band necrosis and dystrophic calcification were found primarily in infants of Group 1. Coagulation necrosis and healing were prominent in Group 2, while infants without repair (Group 3) showed mainly colliquative myocytolysis. Apoptotic cells were more prominent in the operative groups. The control group showed no significant myocardial lesions. Lipid peroxidation was the principal mechanism of oxidative stress accounting for the myocardial lesions. The diversity of the lesions observed in these hearts seemed to indicate a large spectrum of cell damage due to inadequate myocardial perfusion, especially when these infants underwent surgery. Oxidative mechanisms could be a common mediator in the pathogenesis of myocardial injuries, mediated by peroxidation of the membrane phospholipids and resulting in changes in the permeability of the cell membrane, cell death, and intracellular calcium overload. Furthermore, an immature and often hypertrophied myocardium may promote unfavorable conditions, leading to heart failure and a lethal outcome.

Percutaneous Cardiopulmonary Support in Refractory No-Reflow with Cardiogenic Shock after Coronary Stenting in Acute Myocardial Infarction

Coronary no-reflow is defined as inadequate myocardial perfusion of a given coronary segment without angiographic evidence of mechanical vessel obstruction. No-reflow is visualized angiographically as a reduction in thrombolysis in myocardial infarction (TIMI) flow grade and is typically accompanied by chest pain, electrocardiographic changes with ST-segment shift and possible hemodynamic compromise. No-reflow during primary percutaneous coronary intervention (PCI) results in increasing mortality and morbidity. Therefore, treatment of noreflow is associated with improved clinical outcomes. Generally, the treatment of no-reflow is based on pharmacotherapy. In this case, despite maximal pharmacotherapy and intraaortic balloon pump (IABP), refractory no-reflow accompanied with cardiogenic shock was successfully treated with percutaneous cardiopulmonary support (PCPS).

Thrombectomy in Acute Myocardial Infarction

Percutaneous coronary intervention (PCI) is the preferred management strategy for ST-segment-elevation myocardial infarction (STEMI) patients. However, a significant number of revascularisations result insuboptimal restoration of epicardial antegrade flow and inadequate myocardial tissue perfusion. This is mainly attributed to the underlying thrombus burden within the infarct-related vessel. Interventions for thrombotic lesions are clearly associated with an increased risk of acute and long-term complications. Thrombus remains a predictor of ischaemic complications, immediate and late stent thrombosis, increased in-hospital complications, death at six months and recurrent MI. Two types of thrombus removal device are available for utilisation in the setting of acute MI (AMI): aspiration-based catheters and mechanical thrombectomy. Administration of either systemic or selective adjunct pharmacotherapy can be useful in conjunction with application of all thrombus removal devices. Recent studies have demonstrated that thrombus aspiration is applicable and safe in a large majority of patients with STEMI, resulting in better reperfusion and clinical outcomes than standard PCI. However, it is unclear whether these findings are a direct result of a reduction in thrombus burden, facilitation of direct stenting or a combination of the two. The heavier the underlying thrombus burden, the higher the yield of mechanical thrombectomy over aspiration catheter. The role of thrombectomy as a useful adjunct therapy aimed specifically at direct contact and clearance of AMI-related thrombus continues to evolve.

Pharmacological Approach of No-Reflow Phenomenon Related with Percutaneous Coronary Interventions

The no-reflow phenomenon (NRP) is characterized by an inadequate myocardial tissue perfusion in the presence of a patent epicardial coronary artery. It generally occurs after temporary occlusion of the artery causing myocardial ischemia and necrosis that persist after relief of the vessel occlusion, without evidence of epicardial mechanical obstruction. Currently, the main scenario of NRP is the setting of percutaneous coronary interventions (PCI), especially in patients with acute myocardial infarction or saphenous vein graft disease, and its occurrence is associated with adverse clinical outcomes. Pathophysiology of NRP is not fully understood but it seems to be related with microvascular damage. Several mechanisms have been involved, such as distal microembolization, interstitial and intracellular edema, coronary spasm and capillary plugging. Diagnosis of NRP is generally based on clinical and angiographic data. Several methods have been proposed for the assessment of NRP, such as electrocardiography, myocardial contrast echocardiography, contrast-enhanced magnetic resonance imaging, nuclear imaging or positron emission tomography, that have demonstrated additional prognostic value over angiography. There are different pharmacological and mechanical approaches for the prevention of NRP but none of them have demonstrated a clear efficacy. The treatment of established NRP is mainly based on the administration of coronary vasodilators, like adenosine, verapamil or nitroprusside, but clinical results are frequently disappointing. The objective of this review is to describe the state of the art of the pathophysiology, diagnosis and pharmacological management of NRP.

Management of ‘no‐reflow’ complicating reperfusion therapy

No-reflow phenomenon, defined as inadequate myocardial perfusion of the adequately dilated target vessel without evidence of angiographic mechanical obstruction. It is a multifactorial, well-recognised, secondary phenomenon following reperfusion therapy such as thrombolysis or percutaneous coronary interventions (PCI). The pathophysiological mechanisms leading to the no-reflow state are incompletely understood. Embolization of the atheromatous material to the distal vasculature and intense arteriole vasospasm caused by microembolization of platelet-rich thrombi that release vasoactive agents resulting in microvascular obstructions are likely mechanisms. Current prophylaxis and management strategies are derived from limited clinical data. Intracoronary verapamil, adenosine and nitroprusside have been most frequently studied and administered for angiographic no-reflow during PCI for acute myocardial infarction or saphenous vein graft (SVG) lesions and have been shown to improve epicardial flow and microvascular perfusion. The use of distal embolic protection devices in SVG interventions also provide microvascular protection and improve clinical outcomes. However, by far the most important measures are prevention and anticipation during PCI as once no-reflow established, complete reversal of the situation may not be possible.

Evaluation of No-Reflow Phenomenon Using 201TlCl/123I-BMIPP Dual-isotope Myocardial SPECT

We assessed the usefulness of (201)thallous chloride (TlCl)/(123)I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) dual-isotope single-photon emission computed tomography (SPECT) to identify the "no-reflow phenomenon," defined as inadequate myocardial perfusion through a given segment of the coronary circulation without angiographic evidence of mechanical vessel obstruction. (201)TlCl/(123)I-BMIPP SPECT was performed in 73 patients within approximately 1 week of initial acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). We divided the left ventricular myocardium into 17 segments on each SPECT image and scored tracer accumulation in each segment with a five-point scoring system according to the American Heart Association criteria. Total severity scores were calculated by summing the scores for all 17 segments. The mismatch ratio between myocardial perfusion and metabolism was derived from the (201)TlCl and (123)I-BMIPP total severity scores: mismatch ratio=((123)I-BMIPP total severity score -(201)TlCl total severity score)/(123)I-BMIPP total severity score. Patients were classified according to Thrombolysis in Myocardial Infarction (TIMI) flow grade as having TIMI reflow grade 0-I (TIMI 0-I reflow group; n=11), II (TIMI II reflow group; n=17) and III (TIMI III reflow group; n=45). The TIMI III reflow group was subdivided into two groups with (201)TlCl total severity scores of < or =13 (TIMI III (A) reflow group; n=36) and > or =14 (TIMI III (B) reflow group; n=9), respectively. The mismatch ratios in the TIMI II (0.4 +/- 0.3) and TIMI III (0.4 +/- 0.2) reflow groups were significantly higher than that in the TIMI 0-1 reflow group (0.1 +/- 0.1, p<0.05). Although coronary angiography revealed TIMI III flow after reperfusion, the mismatch ratios in the TIMI III (B) reflow group (0.2 +/- 0.1) and in the TIMI 0-I reflow group (0.1 +/- 0.1) were significantly lower than that in the TIMI III (A) reflow group (0.4 +/- 0.2, p<0.01), reflecting noneffective recanalization (so called no-reflow phenomenon). (201)TlCl/(123)I-BMIPP dual-isotope myocardial SPECT reveals the biochemical degree of the no-reflow phenomenon, whereas coronary angiography shows recanalized vascular flow only. Dual-isotope myocardial SPECT might be useful for evaluating reperfusion therapy.

Incidence and Management of "No-Reflow" Following Percutaneous Coronary Interventions

No-reflow is a complex condition associated with inadequate myocardial perfusion of the coronary artery in the absence of epicardial obstruction. It can occur in several settings, including percutaneous coronary intervention, especially in complex thrombotic lesions of native arteries and vein grafts and in primary angioplasty. The causes of no-reflow are not completely understood, and current treatments consist of intracoronary vasodilators, antithrombotic therapies, and mechanical devices (including aspiration thrombectomy catheters and embolic protection devices).

Volumetric intravascular ultrasound evidence that distal embolization during acute infarct intervention contributes to inadequate myocardial perfusion grade

We studied 35 consecutive patients with myocardial infarction (MI) who were treated with direct infarct percutaneous coronary intervention (PCI) using standard angiographic (complete assessment of flow grade and blush grade) and pre- and post-PCI volumetric intravascular ultrasound analysis. Plaque reduction, which is evidence of distal embolization, contributes to inadequate tissue reperfusion in this lesion setting and supports the use of distal protection in the setting of an acute MI.

Sustained ventricular tachycardia as a marker of inadequate myocardial perfusion during the acute phase of myocardial infarction.

Sustained ventricular tachycardia (VT) complicating the acute phase of myocardial infarction (AMI) is a quite rare event but with short-term unfavorable prognosis. The clinical characteristics as well as the therapeutic implications have not yet been well defined. This paper attempts to prove that VT may be considered a marker of inadequate myocardial perfusion after thrombolysis. To assess the clinic-electroangiographic characteristics and prognosis of patients with VT occurring within the first 4 days of an AMI, a case-control study was carried out in 23 patients from a total of 1,100 patients (1.9%) hospitalized with AMI between March 1993 and July 1997. These patients were compared with a control group of 131 patients hospitalized consecutively. A statistical analysis was made using the chi-square test, t-test, and logistic regression. There were no differences among groups with regard to age, gender, and area of necrosis. Average time for the onset of VT was 26 h (range 0-92 h). Sixteen patients underwent coronary angiography: 4 patients had left main coronary artery disease, 2 had single-vessel disease, 8 had lesions in two vessels, and 2 had triple-vessel disease. Univariate analysis showed that patients with VT had a higher incidence of creatine phosphokinase (CPK)-MB peak > 300 UI/l (61 vs. 30%; p<0.001), more frequent occurrence of previous AMI (48 vs. 17%; p<0.001), and acute intraventricular conduction disorders (26 vs. 4%; p<0.001). Furthermore, these patients suffered ischemia previous to VT more frequently (65 vs. 11%; p<0.0001), and had a greater mortality rate than that in the control group (35 vs. 4%; p<0.0001). In the multivariant analysis, the variables related to the occurrence of VT were CPK-MB peak > 300 IU/l (OR 5.9; 95% CI 1.6-21), acute intraventricular conduction disorders (OR 9.02; 95% CI 1.7-48), and ischemia immediately prior to VT (odds ratio [OR] 19.64; 95% confidence interval [CI] 5.3-73). Ventricular tachycardia may be considered a marker of inadequate myocardial perfusion after thrombolysis; therefore, a more aggressive revascularization treatment in these patients would be advisable. The profile of patients with AMI, hospitalized in the coronary care unit, who will likely suffer from VT is previous AMI, CPK-MB peak > 300, acute intraventricular conduction disorders, Killip > I, and ischemia previous to VT.

Pulmonary atresia and intact ventricular septum: an overview

Pulmonary atresia and intact ventricular septum is a complex malformation with a virtually complete obstruction to right ventricular outflow and a marked variation in the size and structure of the right ventricle and tricuspid valve. Coronary artery abnormalities are frequently present, may result in inadequate myocardial perfusion, and contribute to poor outcome. Risk factors for a poor prognosis include a small diameter tricuspid valve ( Z score <2), right ventricular dependent coronary circulation, low birth weight and neonates who require cardio-pulmonary bypass during surgery. Beyond the neonatal period, prognosis was best after biventricular repair.

Prevalence of coronary artery disease in patients with aortic stenosis with and without angina pectoris

Patients with aortic stenosis often seek medical attention because of angina pectoris. Previously published studies1 have reported that about half the subjects with aortic stenosis and angina pectoris have coronary artery disease; in the other half, angina is believed to be due to markedly increased myocardial oxygen demands in the setting of inadequate myocardial perfusion. At the same time, there is disagreement about the incidence of coronary artery disease in patients with aortic stenosis who do not have angina pectoris. On the one extreme, several investigators2–5 have reported that the incidence of coronary artery disease in these subjects is <10%, leading some of them6,7 to suggest that coronary angiography (in preparation for valve replacement) is unnecessary in these subjects. In contrast, a few investigators8–10 have shown that 25% to almost 50% of subjects with aortic stenosis but without angina pectoris have coronary artery disease. Apart from this wide disparity in results, many of these reports are limited by: (1) small numbers of patients, and (2) the inclusion of subjects with substantial aortic regurgitation. Accordingly, this study was performed to assess the incidence of coronary artery disease in a large number of subjects (> 100) with isolated aortic stenosis who did not have angina pectoris.

Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion

Successful reperfusion after acute myocardial infarction (MI) has traditionally been considered to be restoration of epicardial patency, but increasing evidence suggests that disordered microvascular function and inadequate myocardial tissue perfusion are often present despite infarct vessel patency. Thus, optimal reperfusion is being redefined to include intact microvascular flow and restored myocardial perfusion, as well as sustained epicardial patency. Coronary angiography has been used as the gold standard to define failed reperfusion, according to the Thrombolysis In Myocardial Infarction (TIMI) flow grades. However, new angiographic techniques, including the corrected TIMI frame count and myocardial blush grade, have been used to show that epicardial TIMI flow grade 3 may be an incomplete measure of reperfusion success. Furthermore, evolving noninvasive diagnostic techniques, including measurement of infarct size with cardiac marker release patterns or technetium-99m–sestamibi single-photon emission computed tomographic imaging and analysis of ST segment resolution appear to be useful complements to angiography for the assessment of myocardial tissue reperfusion. Promising adjunctive therapies that target microvascular dysfunction, including platelet glycoprotein IIb/IIIa inhibitors, and agents designed to improve tissue perfusion and attenuate reperfusion injury are being evaluated to further improve clinical outcomes after acute MI. To accelerate development of these new reperfusion regimens, an integrated approach to phase II clinical trials that incorporates multiple efficacy variables, including angiography and noninvasive biomarkers of microvascular dysfunction, should be considered. Thus, as the reperfusion era moves into the next millennium, the open-artery hypothesis is expected to shift downstream and guide efforts to further improve myocardial salvage and clinical outcomes after acute MI.

Treatment strategies for microvascular dysfunction following acute myocardial infarction.

Successful reperfusion following acute myocardial infarction is considered to be restoration of epicardial infarct vessel patency, but recent studies suggest that disrupted microvascular function and inadequate myocardial tissue perfusion are often present despite epicardial patency. New angiographic techniques, including the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count and myocardial blush grade, have been used to demonstrate that restoration of downstream coronary flow and tissue perfusion may be the key links to improved clinical outcomes. Additionally, other diagnostic techniques, including infarct size measurement with cardiac marker release patterns, or (99m) Tc-sestamibi single photon emission computed tomography imaging, and analysis of ST-segment resolution have also been used to assess microvascular function and tissue perfusion. Promising adjunctive therapies that target microvascular dysfunction, including platelet glycoprotein IIb/IIIa inhibitors, anti-inflammatory agents, vasodilators, glucose-insulin-potassium, and embolization protection devices, may ameliorate microvascular dysfunction following epicardial reperfusion. However, these therapies have not yet been shown to improve clinical outcomes and are thus currently being studied together with fibrinolytics and primary angioplasty in clinical trials. Therefore, shifting the focus of reperfusion therapy to the microcirculation offers the potential to further improve myocardial salvage and clinical outcomes following acute myocardial infarction.

Scarring of the left ventricular papillary muscles in sickle-cell disease

A number of publications have described various findings in the heart in patients with sickle-cell disease. 1,2 In general, both ventricular cavities are dilated, cardiac mass is increased, and the epicardial coronary arteries are dilated. Although the cardiac valve leaflets are usually normal anatomically, precordial systolic murmurs are common in these patients. 2,3 Although infarcts are common at necropsy in the lungs, spleen, liver, kidneys and even brain in sickle-cell disease, grossly visible myocardial infarcts are rare in these patients. 4,5 Because patients with sickle-cell disease usually have severe and chronic anemia, and because the papillary muscles are believed to be the last portion of the heart to be perfused by blood through the coronary system, we systematically examined the left ventricular papillary muscles at necropsy in a group of patients with sickle-cell anemia for foci of necrosis or fibrosis, findings indicative of inadequate myocardial perfusion.

Vascular effects of systemic hypertension

Hypertension is a major risk factor for cardiovascular diseases, including coronary artery disease (CAD), stroke, left ventricular hypertrophy (LVH), congestive heart failure, peripheral vascular disease, renal failure, and aortic aneurysms. It is also a potent promoter of atherosclerosis. Observational studies have shown a linear relationship between a wide range of blood pressures and the risk for CAD and stroke. Clinical trials have indicated that hypertension reduction leads to the predicted reduction in stroke incidence, but that CAD incidence is affected to a lesser extent than predicted. The modest effect of traditional antihypertensive drugs on CAD may be due to several factors, including failure to reverse well-established coronary atherosclerosis, particularly if multiple risk factors are not reduced as well. Metabolic side effects of antihypertensive drugs or excessive lowering of blood pressure leading to inadequate myocardial perfusion, especially in patients with increased left ventricular (LV) mass, also may play important roles. Hypertension is a major cause of renal failure, particularly in black males, but control of the hypertension does not necessarily prevent deterioration of renal function. Increased glomerular pressure is thought to play a causative role in the development of renal failure in hypertensive and diabetic patients. Antihypertensive drugs may have a direct effect on the arterial wall, which may be independent of their antihypertensive action. Beta-adrenergic blockers, calcium antagonists, and angiotensin-converting enzyme (ACE) inhibitors inhibit the development of vascular lesions in response to hypercholesterolemia or to iatrogenic balloon injury, but the clinical importance of these observations remains to be determined.

Quantification of absolute myocardial perfusion at rest and during exercise with positron emission tomography after human cardiac transplantation

The maximal exercise capacity of cardiac transplant recipients is reduced compared with that of normal subjects. To determine if this reduced exercise capacity is related to inadequate myocardial perfusion during exercise, myocardial perfusion was measured noninvasively with use of positron emission tomography and nitrogen (N)-13 ammonia. Twelve transplant recipients with no angiographic evidence of accelerated coronary atherosclerosis were studied. Serial N-13 ammonia imaging was performed at rest and during supine bicycle exercise. The results were compared with those from 10 normal volunteers with a low probability of having cardiac disease. A two-compartment kinetic model for estimating myocardial perfusion was applied to the data.Transplant recipients achieved a significantly lower exercise work load than did the volunteers (42 ± 16 vs. 128 ± 22 W), but a higher venous lactate concentration (31.3 ± 14.9 vs. 13.7 ±4.1 mg/100 ml). Despite the difference in exercise work load, there was no significant difference in the cardiac work achieved by transplant recipients and normal subjects as evidenced by similar rate-pressure products of 24,000 ± 3,400 versus 21,300 ±2,800 beats/min per mm Hg, respectively. In addition, myocardial blood flow during exercise was not significantly different between the two groups (1.70 ± 0.60 vs. 1.56 ± 0.71 ml/min per g, respectively).This study demonstrates that the myocardial flow response to the physiologic stress of exercise is appropriate in transplant recipients and does not appear to explain the decreased exercise capacity in these patients.

Circadian Influence in Cardiovascular Disease (Part 1)

This department will offer stylized clinical presentations of current cardiovascular issues. Questions raised as a case history evolves highlight key elements that are elaborated upon in the discussions which follow.

Myocardial Infarction with Normal Coronary Arteries After Acute Exposure to Carbon Monoxide

This report describes a 46-year-old white man who suffered an acute myocardial infarction after carbon monoxide exposure. The electrocardiogram and serum enzymes showed myocardial infarction. The coronary angiogram performed one week after admission failed to reveal evidence of coronary obstructive lesions. The case presented is of interest because the clinical presentation suggestive of myocardial infarction was absent, the patient was found unconscious and his medical profile was negative for coronary heart disease risk factors. It is assumed that COHb causes myocardial infarction by severe generalized tissue hypoxia and a direct toxic effect on the myocardial mitochondria. Contributing factors that might also decrease myocardial oxygenation are an inadequate myocardial perfusion and an increased thrombotic tendency.

Reduced subendocardial myocardial perfusion as one mechanism for congestive heart failure

One mechanism for the eventual decompensation of the hypertrophied to the failing heart may involve inadequate myocardial perfusion. In support of this concept are studies in experimental models of both right and left ventricular hypertrophy and failure. These studies demonstrate blunted reactive hyperemic responses to brief periods of coronary artery occlusion, and reduced vasodilation in response to adenosine, when the most severe impairment in coronary reserve occurs in the subendocardium. During exercise, in the hypertrophied and failing heart, the normal coronary vasodilator response is also blunted. Although endocardial/epicardial blood flow ratios are depressed in congestive heart failure under baseline conditions, the endocardial/epicardial ratio decreases further with stress, e.g., during either adenosine or reactive hyperemia. These data suggest that one mechanism of failure of the severely hypertrophied heart may involve inadequate coronary perfusion to the subendocardium.