Alpha-adrenergic blockade improves recovery of myocardial perfusion and function after coronary stenting in patients with acute myocardial infarction

BACKGROUND: AMI reperfusion by thrombolysis does not improve TIMI flow and LV function. The role of infarct-related artery (IRA) stenosis and superimposed changes in coronary vasomotor tone in maintaining LV dysfunction must be elucidated. METHODS AND RESULTS: Forty patients underwent diagnostic angiography 24 hours after thrombolysis. Seventy-two hours after thrombolysis, the culprit lesion was dilated with coronary stenting. During angioplasty, LV function was monitored by transesophageal echocardiography. Percent regional systolic thickening was quantitatively assessed before PTCA, soon after stenting, 15 minutes after stenting, and after phentolamine 12 microg/kg IC (n=10), the alpha1-blocker urapidil 600 microg/kg IV (n=10), or saline (n=10). Ten patients pretreated with beta-blockers received urapidil 10 mg IC. Coronary stenting significantly improved thickening in IRA-dependent and in non-IRA-dependent myocardium (from 27+/-15% to 38+/-16% and from 40+/-15% to 45+/-15%, respectively). Simultaneously, TIMI frame count decreased from 39+/-11 and 40+/-11 in the IRA and non-IRA, respectively, to 23+/-10 and 25+/-7 (P<0.05). Fifteen minutes after stenting, thickening worsened in both IRA- and non-IRA-dependent myocardium (to 19+/-14% and 28+/-14%, P<0.05), and TIMI frame count returned, in both the IRA and non-IRA, to the values obtained before stenting. Phentolamine and urapidil increased thickening to 36+/-17% and 41+/-14% in IRA and to 48+/-11% and 49+/-17% in non-IRA myocardium respectively, and TIMI frame count decreased to 16+/-6 and to 17+/-5, respectively. Changes were attenuated with beta-blocker pretreatment. CONCLUSIONS: Our finding that alpha-adrenergic blockade attenuates vasoconstriction and postischemic LV dysfunction supports the hypothesis of an important role of neural mechanisms in this phenomenon.     

Effects of alpha-adrenergic blockade on regional myocardial function in canine ischemic myocardium during beta-adrenergic blockade

OBJECTIVE: The contribution of alpha-adrenergic receptor subtypes in mediation of coronary vasoconstriction during ischemia remains controversial. This study investigated the effects of alpha-adrenergic subtypes blockade on regional myocardial function in a canine ischemic model. DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental animal laboratory in a university medical center. PARTICIPANTS: Thirty-two adult dogs, weighing 13 to 22 kg. INTERVENTIONS: The animals were prepared with pentobarbital, oxygen, enflurane and pancuronium. Two selective alpha 1-adrenergic antagonists (bunazosin, 50 micrograms/kg/min, n = 8, and prazosin, 25 micrograms/kg/min, n = 8) and the alpha 2-adrenergic antagonist (yohimbine, 15 micrograms/kg/min, n = 8) were administered after the partial occlusion of the left circumflex coronary artery (LCX) during beta-adrenergic blockade (propranolol, 1 mg/kg). MEASUREMENTS AND MAIN RESULTS: Myocardial systolic segment shortening (%SS) and a myocardial lactate extraction ratio (LER) were used as indices of regional myocardial and metabolic function. Compared with poststenotic condition, coronary blood flow of the LCX was increased by 123% with bunazosin and 138% with prazosin (p < 0.05, respectively). Both %SS and LER in the ischemic myocardium were significantly improved after treatment with both alpha 1-adrenergic antagonists (in the bunazosin group, %SS, 8.3 +/- 1.9 to 10.4 +/- 2.2%, p < 0.05; LER, -12.8 +/- 12.3 to 6.2 +/- 15.9%, p < 0.01; in the prazosin group, %SS, 8.5 +/- 1.6 to 10.3 +/- 1.9%, p < 0.05; LER, -10.2 +/- 5.7 to 3.6 +/- 10.2%, p < 0.05). In contrast, coronary blood flow of the LCX, %SS and LER were not different from poststenotic condition during alpha 2-adrenergic receptor blockade with yohimbine. The salutary effect of bunazosin was also observed after mechanically controlling for the afterload reduction produced by alpha 1-adrenergic blockade (n = 8). Prazosin and yohimbine were found to produce a significant increase in plasma norepinephrine levels in contrast to bunazosin, which had no significant effect. CONCLUSIONS: These data indicate that alpha 1-adrenergic blockade increases coronary blood flow and improves regional myocardial function during myocardial ischemia.     

Exercise-induced T-wave normalization predicts recovery of regional contractile function after anterior myocardial infarction

AIMS: We investigated the ability of T-wave pseudonormalization and ST-segment elevation, which are demonstrated in infarct-related leads during submaximal exercise testing, to predict late recovery of contractile function. METHODS: We studied 88 consecutive patients (73 males, mean age 59 +/- 8 years) with anterior infarction, persistent T-wave inversion and a documented lesion of the proximal segment of the left anterior descending coronary artery. They all underwent 2D-echocardiography on admission, 4 weeks as well as 6 months after myocardial infarction to evaluate the dysfunction score and the ejection fraction. Submaximal (75% of maximal predicted heart rate) exercise testing was performed in 80 patients 2 weeks after myocardial infarction following discontinuation of treatment. RESULTS: During exercise testing, 59 of the 88 patients showing negative T-waves on the resting electrocardiogram exhibited pseudonormalization (group A) in at least three adjacent precordial leads, whilst 29 (group B) did not. Patients of group A more frequently exhibited an early creatine kinase peak (41% vs 24%, P < 0.05) and residual angiographic perfusion (97% vs 69%, P < 0.05). The dysfunction score did not change in group B (from 19 +/- 7 to 22 +/- 4), but decreased in group A (from 18 +/- 4 to 11 +/- 6 P < 0.05). The ejection fraction was similar in the two groups on admission (group A: 48 +/- 7%, group B: 45 +/- 10%), but was significantly different at 4-week (52 +/- 99 vs 42 +/- 11%, P < 0.05) and 6-month follow-up (58 +/- 9 vs 44 +/- 10%, P < 0.01). The concomitant presence of ST-segment elevation and T-wave normalization showed the highest positive predictive value for left ventricular function recovery (100%). CONCLUSIONS: T-wave normalization induced by submaximal exercise test is frequently associated with residual perfusion to the infarct area and predicts progressive improvement in regional wall motion, especially if associated with ST-segment elevation. Therefore, these electrocardiographic findings may be used as easily obtainable markers of residual viability that predict late recovery in contractile function.     

Correlates of unrecognized acute myocardial infarction detected via perfusion imaging

Research using the electrocardiogram (ECG) indicates that about 1/3 of acute myocardial infarctions (AMIs) are unrecognized. To date, no studies of unrecognized AMIs have employed perfusion imaging, although it is more sensitive than the ECG and provides more information about infarct characteristics, such as size and location. In this study, 82 of 258 consecutive patients (31.8%) undergoing exercise testing with technetium-99m sestamibi perfusion imaging had fixed, nonartifactual perfusion defects, suggesting AMI. These patients were interviewed regarding their recognition of AMI; 27 patients (32.9%) had unrecognized AMI. Unrecognized AMI was significantly associated with (1) smaller infarcts, (2) infarcts not in the apical or septal regions, (3) diabetes mellitus, (4) lack of angina, (5) a negative family history for cardiac disease, and (6) being African-American. Many of these variables were significantly intercorrelated, and in multivariate analysis, unrecognized AMI remained significantly predicted by a smaller infarct and lack of angina. This study suggests that the incidence of unrecognized AMI detected via perfusion imaging on a clinic population is similar to that detected via electrocardiographic studies on community samples. This study also replicates prior findings of the medical history and demographic correlates of unrecognized AMI, and indicates that infarct size and location are also associated with unrecognized AMI.     

ECG-gated dual-isotope myocardial SPECT with 201Tl and 99mTc-tetrofosmin: simultaneous assessment of stress/rest myocardial perfusion and left ventricular function

ECG-gated dual-isotope acquisition protocol involving rest imaging with 201Tl and stress 99mTc-tetrofosmin (TF) SPECT was designed for the simultaneous assessment of rest/stress myocardial perfusion and rest ventricular systolic function. This study assessed the feasibility and diagnostic accuracy of this protocol. Forty-five patients underwent the dual-isotope SPECT protocol. Twenty minutes after resting injection of 111 MBq of 201Tl, 370 MBq of 99mTc-TF was administered at a peak exercise. The dual-isotope gated SPECT acquisition was performed 1 hour later. Then, the regional count increase rate (%WT) of 99mTc-TF from end-diastole end-systole was calculated using an automated method which was developed for quantification of regional wall thickening based on circumferential profile analysis in our laboratory. Myocardial perfusion and contractility analysis was carried out using 8 segments of left ventricle with comparison of coronary angiographical findings. The sensitivity and specificity for the detection of diseased coronary vessels (> = or 75% stenosis) were 76% and 94%, respectively. Infarcted regions showing reversible defect had significantly greater %WT as compared with those with fixed defects (63 seg; 12.7 +/- 6.1% vs. 36 seg; 8.9 +/- 7.2%, p < 0.01). In conclusion, this dual-isotope protocol has some advantages; i.e., shortening an examination time, having the exact registration of stress/rest perfusion, and simultaneous evaluation of resting regional wall thickening.     

Induction of ST-segment elevation by regional myocardial stretch in normal canine hearts in vivo

The purpose of this study was to evaluate ST-segment elevation induced by regional myocardial stretch without myocardial ischemia in canine hearts. A strain gauge arch (TH-601T) was sutured to the left ventricular epicardium, parallel to the short axis, to shorten the end-diastolic length of the myocardium beneath the arch (stretch zone; SZ) and to produce regional myocardial stretch in each of 6 dogs. An increase in preload caused by altering the height of a saline-filled reservoir affected prolongation or shortening of the myocardium both in the SZ and outside the arch (normal zone; NZ) to increase myocardial stretch. An epicardial electrocardiogram was recorded in both the SZ and the NZ. After suture of the strain gauge arch, the ST segment was elevated in the SZ. An increase in preload augmented stretch during systole in the SZ, resulting in additional ST-segment elevation. These results suggest that regional myocardial stretch itself plays an important role in ST-segment elevation.     

Left ventricular function and coagulation activity in healed myocardial infarction

We investigated the plasma levels of molecular markers for the thrombotic and fibrinolytic status in patients with healed myocardial infarction to determine the relation between left ventricular (LV) function and coagulation activity. Our findings demonstrated that the coagulation activity was increased in patients with healed myocardial infarction along with LV dysfunction, suggesting that anticoagulant therapy is considered in patients with severe LV dysfunction to prevent systemic thromboembolism.     

Comparison of left and right ventricular function in acute myocardial infarction

Pulmonary arterial end-diastolic and mean right atrial pressures were compared in 25 patients with acute myocardial infarction and in one patient with unstable angina. No consistent relationship was observed between these pressures. Simultaneous ventricular function curves relating the stroke work of each ventricle to its respective filling pressure were constructed on 34 occasions, dextran infusion or diuresis being used to alter the filling pressure. The curves from each ventricle were described mathematically by a quadratic (parabolic) function as well as by a straight line function and then compared by canonical correlation analysis. Alterations in the left ventricular function curves occurred with and without depression or right ventricular function curves. These hemodynamic measurements demonstrate that acute myocardial infarction can alter the relationship between left and right ventricular function.     

Gated planar technetium 99m-labeled sestamibi myocardial perfusion image inversion for quantitative scintigraphic assessment of left ventricular function

BACKGROUND: Quantitative assessment of left ventricular systolic performance in conjunction with myocardial perfusion scintigraphy would significantly expand the clinical information obtained from these studies. METHODS AND RESULTS: Left ventricular function was evaluated in 264 patients in whom planar 99mTc-labeled sestamibi myocardial perfusion images were obtained in the best septal left anterior oblique projection. Digital inversion of these perfusion images allows semiautomated evaluation of the left ventricular cavity, with the commonly available edge-detection software designed for equilibrium blood pool imaging. In this study, ejection fractions derived from this technique were compared with those obtained from a myocardial perfusion phantom, first-pass radionuclide angiography, and contrast ventriculography. In vitro validation demonstrated that the myocardial perfusion image inversion ejection fractions correlated linearly with those obtained from a double-chamber phantom (r = 0.999). In vivo, there was good linear correlation between image inversion and first-pass (r = 0.88; image inversion = 0.98 first-pass +0.11), with 95% agreement on the presence or absence of significant left ventricular systolic dysfunction. There was also very good correlation between image inversion and contrast ventriculographic ejection fractions (n = 35; r = 0.85; image inversion = 0.8 contrast +0.05). Intraobserver and interobserver variability of the image inversion ejection fractions was very small (mean difference of 0.4 +/- 0.8 and 2.8 +/- 4.7 units, respectively). CONCLUSION: Gated 99mTc-labeled sestamibi myocardial perfusion image inversion allows evaluation of the dynamics of the left ventricular chamber changes during the cardiac cycle, providing a method for evaluation of systolic function during myocardial perfusion imaging, with highly reproducible results that correlate well with established techniques.     

Normovolaemic haemodilution and hyperoxia have no effect on fractal dimension of regional myocardial perfusion in dogs

The neurotoxicity of dibucaine was compared with that of commercially available local anesthetics in studies using rabbit desheathed cervical vagus nerve preparation. Dibucaine dose-dependently suppressed the evoked action potential of myelinated A beta nerve component and nonmyelinated C nerve component. The potential of A beta nerve component was more strongly suppressed, compared with that of C nerve component. At low concentrations of 0.0001-0.001%, the suppression was reversible and recovery with C nerve component was faster and more complete. At higher concentrations, the suppression was irreversible. The minimum concentrations of irreversible blockade were 0.003% for A beta nerve component and 0.03% for C nerve component. Electron microscopically, marked damages in the myelin layer and intraaxonal structure were observed in nerves treated with 0.03% dibucaine. When the neurotoxic effect of dibucaine was compared, in terms of safety margins (minimum concentration of irreversible blockade/clinically used concentrations), with those of commercially available local anesthetics, the rank order was dibucaine, tetracaine and bupivacaine; dibucaine showing the lowest safety margin.     

Wall thickening at rest and contractile reserve early after myocardial infarction: correlation with myocardial perfusion and metabolism

BACKGROUND: Abnormalities in wall thickening and their reaction to stimulation can be studied by magnetic resonance imaging. OBJECTIVE: To analyse the relationship between these abnormalities and changes in myocardial perfusion and fatty acid metabolism. METHODS: Fifteen patients with a myocardial infarction underwent low-dose dobutamine magnetic resonance imaging to assess their wall thickening and contractile reserve, and technetium-99m sestamibi (MIBI) and beta-methyl-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission tomography to assess their myocardial perfusion and fatty acid uptake. For nine segments per patient, the wall thickening was scored as normal, hypokinetic or akinetic, and the myocardial perfusion as normal (> 65%), mildly to moderately reduced (35-65%) or severely reduced (< 35%). Abnormalities in fatty acid uptake were compared with the myocardial perfusion and defined as matched (difference < or = 10%) or mismatched (difference > 10%) reduction. RESULTS: Thirty-four segments had abnormal wall thickening (13 hypokinetic and 21 akinetic). The wall thickening at rest was significantly related to the uptake of MIBI (P < 0.001), but not to abnormalities in the uptake of BMIPP. All of the akinetic segments had an abnormal uptake of MIBI (15 severely and six mildly to moderately reduced), whereas 7 of 13 hypokinetic segments had a normal and five a midly to moderately reduced uptake. A significant relationship between abnormalities of fatty acid metabolism and the contractile reserve was also found (P < 0.002): 14 of 16 segments with and only six of 18 without contractile reserve had a mismatched reduction in uptakes of MIBI and BMIPP. CONCLUSION: This study confirms the relationship between the wall thickening at rest and the residual perfusion after infarction. On the other hand, the contractile reserve, which is an accepted indicator of the viability of the infarct region, is associated strongly with abnormalities of fatty acid metabolism.     

Long-term recovery of regional wall motion in patients with medically treated anterior myocardial infarction: quantitative assessment of the post-infarction left ventriculograms

Contrast sensitivity has been shown to be affected in Alzheimer's disease (Ad). We investigated low contrast acuity and contrast sensitivity using clinical test charts in this patient population. Additionally, we tested patients with vascular dementia (vd) and mixed dementia (md), (Alzheimer' with vascular dementia). Contrast sensitivity was assessed using the Vistech VCTS 6500 test chart. Low contrast acuity was measured using the Regan charts at four contrast levels (96%, 50%, 25% and 11%). The patient population consisted of 19 Ad patients, 9 vd patients and 10 md patients. Reduction in acuity was found with contrast level in all cases. Regression lines were fit to the data and statistical analysis was performed. We did not find a statistically significant difference between the Ad and vd or md groups. We did, however, find a difference between the vd and md groups. We did find reduction in contrast sensitivity at all spatial frequencies when compared to the elderly normal. Correspondingly, we found a significant difference in acuity when compared with normal data at the four contrast levels tested. Acuity is reduced with contrast in all patient groups. Our contrast sensitivity results are similar to those reported in the literature. This study points out the importance of using simple clinical test charts and further underscores the idea that there is a primary visual deficit in Ad.     

Relation between ST-segment changes and myocardial perfusion evaluated by myocardial contrast echocardiography in patients with acute myocardial infarction treated with direct angioplasty

The aim of this study was to evaluate the relation between myocardial perfusion and ST-segment changes in patients with acute myocardial infarction treated with successful direct angioplasty. Thirty-seven patients, successfully treated with direct angioplasty, underwent myocardial contrast echocardiography before and after angioplasty. The sum of ST-segment elevation divided by the number of the leads involved (ST-segment elevation index) was calculated at 1, 5, 10, 20, and 30 minutes after restoration of a Thrombolysis In Myocardial Infarction trial grade 3 flow. After recanalization, myocardial reperfusion within the risk area was observed in 26 patients, whereas a no-reflow phenomenon occurred in 11. In patients with myocardial reperfusion, the ST-segment elevation index progressively declined, whereas in patients with no reflow, no significant change was observed. Reduction of > or = 50% in the ST-segment elevation index occurred in 20 of the 26 patients with reflow and in 1 of the 11 with no reflow (p = 0.0002). An additional increase of > or = 30% in the ST-segment elevation index occurred in 3 patients with reflow and in 7 with no reflow (p = 0.003). Sensitivity, specificity, positive and negative predictive values, and accuracy of the reduction in the ST-segment elevation index for predicting microvascular reflow were 77%, 91%, 95%, 62%, and 81%, respectively. The corresponding values of the increase in ST-segment elevation index for predicting no reflow were 64%, 88%, 70%, 85%, and 81%, respectively. In conclusion, after successful angioplasty, different patterns of myocardial perfusion are associated with different ST-segment changes. Analysis of ST-segment changes predicts the degree of myocardial reperfusion.     

Myocardial tactile stiffness: a variable of regional myocardial function

OBJECTIVES: We developed a new sensor system for in situ measurement of myocardial tactile stiffness-stiffness in a direction perpendicular to the wall-and validated its use for providing a reasonable estimation of regional myocardial function. BACKGROUND: Numerous attempts have been made to directly assess regional myocardial function. The complexity and highly invasive nature of the measuring devices have hampered their in situ application. METHODS: In open chest mongrel dogs, myocardial tactile stiffness, ventricular pressure and ventricular volume were monitored. Under the preload reduction, these variables were measured to determine the relation between the end-systolic pressure-volume relation (ESPVR) and the end-systolic tactile stiffness-volume relation (ESSVR). The changes in myocardial tactile stiffness were monitored in the regional ischemic myocardial model and infarcted model to evaluate their usefulness as indexes of regional myocardial function. RESULTS: Myocardial tactile stiffness changed cyclically and followed a time course similar to left ventricular pressure. When preload was altered, the ESSVR was as linear as the ESPVR. The slope of the ESSVR and that of the ESPVR showed a strong correlation over a wide range of contractility. These results suggest that myocardial tactile stiffness can be a good index of regional wall stress or fiber stress. End-systolic myocardial tactile stiffness of ischemic and infarcted regions decreased significantly, with a concomitant increase in end-diastolic stiffness compared with that of intact myocardium. CONCLUSIONS: Using our tactile sensor system, regional myocardial tactile stiffness of a beating heart was measured with reasonable temporal resolution. We consider myocardial tactile stiffness to be a useful index of regional myocardial function.     

Early contrast-enhanced MRI predicts late functional recovery after reperfused myocardial infarction

BACKGROUND: We have observed 3 abnormal patterns on contrast-enhanced MRI early after reperfused myocardial infarction (MI): (1) absence of normal first-pass signal enhancement (HYPO), (2) normal first pass signal followed by hyperenhanced signal on delayed images (HYPER), or (3) both absence of normal first-pass enhancement and delayed hyperenhancement (COMB). This study examines the association between these patterns in the first week after MI and late recovery of myocardial contractile function by use of magnetic resonance myocardial tissue tagging. METHODS AND RESULTS: Seventeen patients (14 men) with a mean age of 53+/-12 years were studied after a reperfused first MI. Contrast-enhanced images were acquired immediately after bolus administration of gadolinium and 7+/-2 minutes later. Tagged images were acquired at weeks 1 and 7. Circumferential segment shortening (%S) was measured in regions displaying HYPER, COMB, or HYPO contrast patterns and in remote regions (REMOTE) at weeks 1 and 7. At week 1, %S was depressed in HYPER, COMB, and HYPO (9+/-8%, 7+/-6%, and 5+/-4%, respectively) and were less than REMOTE (18+/-6%, P<0.003). However, in HYPER, %S improved at week 7 from 9+/-8% to 18+/-5% (P<0.001 versus week 1). In contrast, HYPO did not improve significantly (5+/-4% to 6+/-3%, P=NS) and COMB tended to improve 7+/-6% to 11+/-6% (P=0.06). CONCLUSIONS: HYPER has partially reversible dysfunction and represents predominantly viable myocardium. COMB shows borderline improvement and likely contains an admixture of viable and necrotic myocardium. HYPO shows little functional improvement at 7 weeks, presumably because of irreversible myocardial damage.     

Rest or redistribution thallium myocardial imaging for resting myocardial perfusion: a detailed comparison with regional wall motion

Redistribution thallium-201 (201T1) imaging is the most common method of assessing resting myocardial perfusion. However, the equivalence of a redistribution image and a separate rest injection is unclear. Although the presence of a defect on rest imaging has normally been equated with the presence of a myocardial infarction, it has recently been shown that a significant proportion of fixed defects on exercise-redistribution 201T1 actually represent areas of viable myocardium. This study was a detailed comparison of rest and redistribution imaging in 30 patients undergoing routine exercise 201T1 scanning for the assessment of coronary artery disease. A small dose (15 MBq) of 201T1 was administered at rest following the imaging in three standard planar views. Similar stress images were acquired using a further 50-55 MBq of 201T1 administered at peak effort. Redistribution images were acquired 3-4 h later and equilibrium blood pool ventriculography performed using in vivo labelling with 600 MBq 99Tcm-pertechnetate. Of 150 abnormal segments on the exercise scans, 74 (49%) were identified as being reversible on the redistribution scans and 58 (39%) on the rest images. Only 39 (53%) of these reversible defects were identified on both the redistribution and rest scans. Only 41% of the fixed defects on the redistribution images (32% of fixed defects on the rest images) had abnormal wall motion. Therefore, rest and redistribution images are not equivalent. Both rest and redistribution images significantly overestimate myocardial infarction. This may have significant effects on patient selection for revascularization procedures and therefore all patients having perfusion scintigraphy should also have additional assessment of regional wall motion to allow accurate classification of the functional status of myocardial segments.