Wall Ischemia Research Articles

Abstract 2070: Transmural Strain Gradient of Normal, Hyperemic and Ischemic LV Walls Evaluated by New 2D Speckle Tracking System

PURPOSE: Currently available 2D echo speckle tracking system can track the endocardial and epicardial echo, but cannot reliably track the speckles from the myocardium. We assessed feasibility of newly developed prototype speckle tracking system in humans with normal, hyperemic and ischemic LV. METHODS: LV short-axis images were obtained by 2D echo (Aplio, TOSHIBA) at rest in 46 normal subjects and 52 patients with clinically diagnosed myocardial infarction (28 with non-Q wave and 24 with Q wave infarction), and during ATP infusion (0.14mg/min/kg) in 21 normals. Using the new system which could track the “myocardial” speckle (Figure ), we measured circumferential strain of the LV endocardium (Endo), mid-wall (Mid) and epicardium (Epi). RESULTS: In normal subjects, circumferential strain showed distinct transmural gradient (p<0.001, ANOVA) (Table ). ATP infusion increased Endo strain (p<0.001) and steepened the gradient. Strain of ischemic region was extremely reduced (p<0.001) in both non-Q and Q wave infarction group and the gradient was hardly recognized in the latter. CONCLUSION: “Myocardial” speckle tracking was feasible and can be used to evaluate the effects of coronary flow on transmural strain gradient. Figure. Speckle tracking of Mid as well as Endo and Epi

Mitochondrial respiration and membrane potential after low-flow ischemia are not affected by ischemic preconditioning

Mitochondrial function following prolonged ischemia and subsequent reperfusion is better preserved by ischemic preconditioning (IP). In the present study, we analyzed whether or not IP has an impact on mitochondrial function at the end of a sustained ischemic period. Göttinger minipigs were subjected to 90-min low-flow ischemia without ( n = 5) and with ( n = 5) a preconditioning cycle of 10-min ischemia and 15-min reperfusion. Mitochondria were isolated from the ischemic or preconditioned anterior wall (AW) and the control posterior wall (PW) at the end of ischemia. Basal mitochondrial respiration was not different between AW and PW. The ADP-stimulated (state 3) respiration in AW mitochondria compared to PW mitochondria was equally decreased in non-preconditioned and preconditioned pigs. The uncoupled respiration as well as the membrane potential (rhodamine 123 fluorescence) were not significantly different between groups. However, the recovery of the membrane potential (Δ rhodamine 123 fluorescence/s) after the addition of ADP was delayed in mitochondria obtained from AW compared to PW, both in non-preconditioned and in preconditioned pig hearts. Neither the amount of marker proteins for complexes of the electron transport chain nor the level of reactive oxygen species were affected by ischemia without or with IP. State 3 respiration and recovery of membrane potential were impaired in pig mitochondria after 90 min of low-flow ischemia. IP did not improve mitochondrial function during ischemia. Therefore, the preservation of mitochondrial function by IP may occur during reperfusion rather than during the sustained ischemic period.

Risk Stratification and Prognosis in Octogenarians Undergoing Stress Echocardiographic Study

The prognostic value of stress echocardiography (SE) for the diagnosis and risk stratification of coronary artery disease in octogenarians is not well defined. Follow-up of 5 years (mean 2.9 +/- 1.0 years) for confirmed nonfatal myocardial infarction (n = 17) and cardiac death (n = 37) was obtained in 335 patients, age > or =80 years (mean age 84 +/- 3 years, 44% male), undergoing SE (33% treadmill, 67% dobutamine). Left ventricular (LV) regional wall motion was assessed by a consensus of two echocardiographers and scored as per standard five-point scale, 16-segment model of wall motion analysis. Ischemic LV wall segment was defined as deterioration in the thickening and excursion during stress (increase in wall-motion score index (WMSI) > or =1). By univariate analysis, inducible ischemia (chi-square = 38.4, P < 0.001), left ventricular ejection fraction (chi-square = 41.2, P < 0.001), a history of previous myocardial infarction (chi-square = 22.3, P < 0.01), hypertension (chi-square = 33, P < 0.01), and age (chi-square = 27.7, P < 0.01) were significant predictors of future cardiac events. WMSI, an index of inducible ischemia, provided incremental prognostic information when forced into a multivariable model where clinical and rest echocardiography variables were entered first. WMSI effectively stratified octogenarians into low- and high-risk groups (annualized event rates of 1.2 versus 5.8%/year, P < 0.001). Stress echocardiography yields incremental prognostic information in octogenarians and effectively stratifies them into low- and high-risk groups. Precise therapeutic decision making in very elderly patients should incorporate combined clinical and stress echocardiography data.

Successful percutaneous treatment of anomalous left coronary artery from pulmonary artery

Anomalous origin of the left main coronary artery from the pulmonary artery (ALCAPA) is an uncommon congenital condition seen in the adult population, with most patients developing symptoms in infancy. We describe successful closure of an ALCAPA in an adult using a percutaneous transcatheter approach in a patient with evidence of anterior wall ischemia believed to be the consequence of myocardial steal. A 30-year-old female was noted to have continuous flow in the right ventricular septum on transthoracic echocardiography, with subsequent imaging confirming the presence of an ALCAPA. Myocardial perfusion imaging confirmed anterior wall ischemia, and as a strategy to optimize coronary perfusion pressure, the patient underwent percutaneous ALCAPA closure using an Amplatzer™ vascular plug. The procedure was well tolerated, with no evidence of anterior ischemia or myocardial dysfunction. Follow up perfusion imaging demonstrated no residual anterior wall ischemia. Transcatheter closure of an ALCAPA is a potentially safe and effective alternative treatment strategy in this patient population.

223 Heart frequency at which cardiac index starts its descending limb can identify ischemic wall motion abnormalities

223 Heart frequency at which cardiac index starts its descending limb can identify ischemic wall motion abnormalities

Effects of Right, Left, and Biventricular Pacing on Myocardial Perfusion in Ischemic Conditions

In normal hearts, the distribution of regional myocardial perfusion is altered by ventricular pacing. Little is known about the impact of ventricular pacing on regional myocardial perfusion in ischemic conditions. In this acute echocardiographic study, we compared the respective effects of right ventricular pacing (RVP), left ventricular pacing (LVP), and biventricular pacing (BVP) on regional perfusion in a swine model of graded ischemia. Ventricular pacing leads were placed at the apex of the right ventricle and on the lateral wall of the left ventricle in nine open-chest pigs. Myocardial contrast echocardiography was successively performed during spontaneous rhythm (SR), RVP, LVP, and BVP in random order at baseline and during three stages of incremental ischemia (left anterior descending + circumflex). At baseline, RVP decreased myocardial perfusion of the septal and inferior walls compared to SR (P < 0.05), whereas LVP decreased perfusion of the lateral wall (P < 0.05). No significant differences were observed in regional perfusion during BVP compared to SR. In ischemic conditions, RVP worsened myocardial perfusion in the ischemic anterior wall as well as in the septal and inferior walls (P < 0.05), whereas both LVP and BVP did not alter perfusion in the ischemic area compared to SR. Compared to baseline, in ischemic conditions, RVP has a more pronounced detrimental impact on perfusion abnormalities. In contrast, BVP induced a significant improvement in local myocardial perfusion. Therefore, BVP could be preferred to RVP in patients with ischemic cardiomyopathy.

A 7-year-old Boy with an Abdominal Wall Hernia and Ischemia of the Left Leg after a Bicycle Handle Bar Injury

Traumatic abdominal wall hernia is a rare event. We describe a 7-year-old boy in whom this rare injury was combined with a traumatic dissection of the external iliac artery. The hernia was corrected by primary repair, the dissection by resection of the injured part and endto-end anastomosis.

Inhibition of cyclooxygenase isoforms in late- but not midgestation decreases contractility of the ductus arteriosus and prevents postnatal closure in mice

Use of cyclooxygenase (COX) inhibitors to delay preterm birth is complicated by in utero constriction of the ductus arteriosus and delayed postnatal closure. Delayed postnatal closure has been attributed to loss of vasa vasorum flow and ductus wall ischemia resulting from constriction in utero. We used the murine ductus (which does not depend on vasa vasorum flow) to determine whether delayed postnatal closure may be because of mechanisms independent of in utero constriction. Acute inhibition of both COX isoforms constricted the fetal ductus on days 18 and 19 (term) but not earlier in gestation; COX-2 inhibition constricted the fetal ductus more than COX-1 inhibition. In contrast, mice exposed to prolonged inhibition of COX-1, COX-2, or both COX isoforms (starting on day 15, when the ductus does not respond to the inhibitors) had no contractile response to the inhibitors on days 18 or 19. Newborn mice closed their ductus within 4 h of birth. Prolonged COX inhibition on days 11-14 of gestation had no effect on newborn ductal closure; however, prolonged COX inhibition on days 15-19 resulted in delayed ductus closure despite exposure to 80% oxygen after birth. Similarly, targeted deletion of COX-2 alone, or COX-1/COX-2 together, impaired postnatal ductus closure. Nitric oxide inhibition did not prevent the delay in ductus closure. These data show that impaired postnatal ductus closure is not the result of in utero ductus constriction or upregulation of nitric oxide synthesis. They are consistent with a novel role for prostaglandins in ductus arteriosus contractile development.

Prevention of the ischemia-induced decrease in mitochondrial Tom20 content by ischemic preconditioning

Preserved mitochondrial function (respiration, calcium handling) and integrity (cytochrome c release) is central for cell survival following ischemia/reperfusion. Mitochondrial function also requires import of proteins from the cytosol via the translocase of the outer and inner membrane (TOM and TIM complexes). Since mitochondrial function following ischemia/reperfusion is better preserved by ischemic preconditioning (IP), we now investigated whether expression of parts of the import machinery is affected by ischemia/reperfusion without or with IP in vivo. We analyzed the mitochondrial content of the presequence receptor Tom20, the pore forming unit Tom40 and Tim23. Goettinger minipigs were subjected to 90 min of low-flow ischemia without or with preconditioning by 10 min ischemia and 15 min reperfusion. Mitochondria were isolated from the ischemic or preconditioned anterior wall of the left ventricle and from the control posterior wall. Infarct size was significantly reduced by IP (20.1 ± 1.6% of area at risk (non-preconditioned) vs. 6.5 ± 2.5% of area at risk (IP)). Using Western blot analysis, the ratio of Tom20 (normalized to Ponceau S) between mitochondria isolated from the anterior ischemic and posterior control wall was reduced (0.72 ± 0.11, a.u., n = 8), whereas the mitochondrial Tom20 content was preserved by IP (1.17 ± 0.16 a.u., n = 7, P < 0.05). The mitochondrial Tom40, Tim23 and adenine nucleotide transporter (ANT) contents were not significantly different between non-preconditioned and preconditioned myocardium. The preservation of the mitochondrial Tom20 protein level may contribute to the improved mitochondrial function after IP.

Dipyridamole/aspirin combination in secondary stroke prevention: effects on absolute myocardial blood flow and coronary vascular resistance

In the European Stroke Prevention Study (ESPS 2), oral administration of a fixed combination of 200 mg extended-release dipyridamole and 25 mg aspirin (twice daily) after ischemic stroke or transient ischemic attack, significantly reduced the risk of stroke compared to placebo as well as compared to aspirin or dipyridamole alone. However, the i.v. application of dipyridamole over 4 - 6 min is known to increase myocardial blood flow up to 6-fold, and thereby potentially provoke ischemic wall motion abnormalities in patients with coronary artery disease. We therefore assessed the cardiac side effects of the dipyridamole/aspirin combination on absolute myocardial blood flow (MBF) and coronary vascular resistance (CVR). MBF and CVR were measured using 150-water positron emission tomography in 24 patients after stroke or transient ischemic attack, before and 6.7 +/- 1.9 days after starting the dipyridamole/aspirin combination (Aggrenox) therapy. Resting MBF increased by 39% (max. 112%), from 0.92 +/- 0.13 (ml x g(-1) x min(-1)) at baseline to 1.28 +/- 0.27 (ml x g(-1) x min(-1)) under ongoing dipyridamole/aspirin combination therapy (p < 0.0005). CVR consecutively decreased from 105.3 +/- 16.9 to 74.1 +/- 16.5 (mmHg x ml(-1) x g x min) (p < 0.0005). The relative increase in MBF correlated negatively with the body surface area. No correlation was found between relative MBF increase and duration of dipyridamole/aspirin combination therapy (range 4 - 10 days). Orally administered dipyridamole/aspirin combination therapy in secondary stroke prevention increases MBF and decreases CVR significantly. These cardiac side effects of the dipyridamole/aspirin combination should be taken into account in stroke patients with proven or suspected coronary artery disease, particularly in combination with a small body surface area.

Adult intussusception due to cocaine-induced bowel wall hematoma: a case study

The authors present a patient in whom colocolic intussusception occurred as a result of bowel wall ischemia and hematoma. Imaging features and pathogenesis of bowel ischemia and intussusception will be briefly discussed, as well as its relationship to cocaine abuse. The importance of recognizing complications of cocaine abuse in today's emergency department patient population will be emphasized.

Comparison of various kinds of bone marrow stem cells for the repair of infarcted myocardium: Single clonally purified non-hematopoietic mesenchymal stem cells serve as a superior source

A variety of adult stem cells have been used to transplant into the infarcted (MI) heart, however, comparative studies are lacking to show more suitable source of cells for transplantation. We have identified a single non-hematopoietic mesenchymal stem cell subpopulation (snMSCs) isolated from human bone marrow and clonally purified, that over 99% of them expressed MSC marker proteins and cardiomyocyte marker proteins when induction in vitro. We also compared the effects of the snMSCs with unpurified MSC (uMSCs), mononuclear cells (BMMNCs), or peripheral blood mononuclear cells (PBMNCs) on myocardial repair after induction of MI in rats. Ninety days later, we observed a better cardiac function assessed by ejection fraction, fraction of shortening and lung wet/dry weight ratios, less remodeling of left ventricle (LV), lower collagen density in the LV, and more vessels in the ischemic wall in the snMSCs transplantation group than in other cell-transplanted groups. Furthermore, the transplanted cells expressing cardiomyocyte specific proteins or vascular endothelial cell marker proteins were more in the snMSCs group than in other ones. We conclude that transplantation with single clonally purified MSCs seems to be more beneficial to the cardiac repair than with other stem cells after MI.

Stroke and myocardial ischemia in a patient of pheochromocytoma: A rare clinical sequele

Pheochromocytoma classically presents with paroxysms of hypertension and adrenergic symptoms including headaches, palpitation, tremor and anxiety. However, these tumors can be clinically silent and occasionally manifest only when catecholamine release is upregulated by exogenous stimuli. In addition, the clinical presentation of pheochromocytoma can mimic a number of other medical conditions including migraine, cardiac arrhythmias, myocardial infarction and stroke, thus, making the diagnosis of pheochromocytoma difficult. We present a case of a 43-year old male patient who presented for evaluation of adrenal mass in the department of endocrine surgery. This patient had a previous history of right side hemiperasis and lateral wall ischemia, with no residual clinical deficit.<br>

Relation of End-Diastolic Wall Thickness and the Residual Rim of Viable Myocardium by Magnetic Resonance Imaging to Myocardial Viability Assessed by Fluorine-18 Deoxyglucose Positron Emission Tomography

End-diastolic wall thickness (EDWT) and thickness of the residual non-contrast-enhanced myocardial rim have been suggested as markers for the assessment of myocardial viability by cardiovascular magnetic resonance (CMR) imaging. This study compared these parameters as derived from contrast-enhanced CMR images for the prediction of myocardial viability as determined by fluorine-18 deoxyglucose positron emission tomography (FDG-PET). Twenty-two patients with ischemic cardiomyopathy (ejection fraction 31 +/- 11%) were investigated. For contrast-enhanced CMR imaging, a standard inversion-recovery sequence was used. FDG-PET was performed using a hyperinsulinemic-euglycemic clamp. Data were analyzed with a 17-segment model. Of 146 severely dysfunctional segments, 112 were assessed as viable and 34 as nonviable by nuclear imaging. Using receiver-operator characteristic analysis, areas under the curve were 0.95 for unenhanced myocardial rim (95% confidence interval 0.92 to 0.98) and 0.86 for EDWT (95% confidence interval 0.80 to 0.93, p <0.001 vs unenhanced myocardial rim) for the prediction of viability as assessed by FDG-PET. Cutoffs of 5.4 mm for EDWT and 3.0 mm for unenhanced myocardial rim were found to optimally differentiate viability by FDG-PET. In 25 segments with divergent results, 94% of segments with an EDWT < or =5.4 mm and an unenhanced myocardial rim >3.0 mm were scored as viable by FDG-PET, whereas 57% of segments with an EDWT >5.4 mm and an unenhanced myocardial rim < or =3.0 mm were scored nonviable with the reference technique. In conclusion, unenhanced myocardial rim is superior to EDWT for the prediction of myocardial viability as determined by FDG-PET and may be clinically useful for assessment of myocardial viability in patients with ischemic cardiomyopathy and regional wall thinning.

RNA interference targeting SHP‐1 attenuates myocardial infarction in rats

The Src homology domain 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1) plays a key role in apoptosis and decreases phosphorylation of Akt. Apoptosis of cardiomyocytes is thought to contribute to the increased area of acute myocardial infarction (AMI), and Akt activation exerts a powerful cardioprotective effect after ischemia. Thus, a therapeutic strategy designed to inhibit expression of SHP-1 would be beneficial in AMI. Here we report that siRNA targeting SHP-1 reduced infarct size in a rat model of AMI. Upon injection into the ischemic left ventricular wall, the vector-based siRNA significantly suppressed the increase in the SHP-1 mRNA and the SHP-1 protein levels. The siRNA vector also significantly reduced the SHP-1 that bound to Fas-R. The SHP-1 siRNA vector increased phospho-Akt and reduced DNA fragmentation and caspase activity compared with the scramble siRNA vector. Finally, the area of myocardial infarction was significantly smaller with the SHP-1 siRNA vector than with the scramble siRNA vector at 2 days after LCA ligation. In conclusion, SHP-1 in the heart increased from the early stage of AMI, and this increase was thought to contribute to the increased area of myocardial infarction. Suppression of SHP-1 with the SHP-1 siRNA vector markedly reduced the infarct size in AMI.

Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning

Connexin 43 (Cx43) is involved in infarct size reduction by ischemic preconditioning (IP); the underlying mechanism of protection, however, is unknown. Since mitochondria have been proposed to be involved in IP's protection, the present study analyzed whether Cx43 is localized at mitochondria of cardiomyocytes and whether such localization is affected by IP. Western blot analysis on mitochondrial preparations isolated from rat, mouse, pig, and human hearts showed the presence of Cx43. The preparations were not contaminated with markers for other cell compartments. The localization of Cx43 to mitochondria was also confirmed by FACS sorting (double staining with MitoTracker Red and Cx43) and immuno-electron and confocal microscopy. To study the role of Cx43 in IP, mitochondria were isolated from the ischemic anterior wall (AW) and the control posterior wall (PW) of pig myocardium at the end of 90 min low-flow ischemia without (n=13) or with (n=13) a preceding preconditioning cycle of 10 min ischemia and 15 min reperfusion. With IP, the mitochondrial Cx43/adenine nucleotide transporter ratio was 3.4+/-0.7 fold greater in AW than in PW, whereas the ratio remained unchanged in non-preconditioned myocardium (1.1+/-0.2, p<0.05). The enhancement of the mitochondrial Cx43 protein level occurred rapidly, since an increase of mitochondrial Cx43 was already detected with two cycles of 5 min ischemia/reperfusion in isolated rat hearts to 262+/-63% of baseline. These data demonstrate that Cx43 is localized at cardiomyocyte mitochondria and that IP enhances such mitochondrial localization.

T wave inversions following ablation of 125 posteroseptal accessory pathways

Background Cardiac memory, electrophysiological remodeling induced by periods of altered ventricular activation, has been observed after resumption of normal activation following ablation of overt accessory pathways. We studied the occurrence and temporal characteristics of cardiac memory (inferior T wave inversions) after ablation of overt posteroseptal accessory pathways. Methods T wave changes were assessed in the frontal plane (leads II, aVF, and III) up to one year after the ablation in 125 consecutive patients. T wave polarity immediately after ablation was compared with the pre ablation delta wave polarity and the dominant QRS force in each lead. The number of inferior leads (0–3) with post ablation T wave changes (estimate of degree of cardiac memory) was analyzed in relation to estimates of the degree of preexcitation (accessory pathway refractoriness and QRS duration) prior to ablation. Results Electrocardiogram (ECG) signs of cardiac memory were present in 123 (98%) of the patients within one day after ablation. The post ablation T wave vector had the same direction as the vector of the pre-excited QRS complex (and delta wave) creating inferior T wave inversions. There was no correlation between the degree of preexcitation pre ablation and the extent of cardiac memory post ablation. A majority (about 90%) of ECGs recorded 3–6 months after the procedure, showed complete or almost complete normalization. Conclusions T wave inversions were present in the vast majority of patients, persisted in some patients beyond 3 months, and might be misinterpreted as inferior wall ischemia.

Imbalanced chordal force distribution causes acute ischemic mitral regurgitation: Mechanistic insights from chordae tendineae force measurements in pigs

Ischemic mitral regurgitation is caused by an imbalance of the entire mitral-ventricular complex. This interaction is mediated through the chordae tendineae force distribution, which may perturb several elements of the mitral valve apparatus. Our objective was to investigate the association between the mitral valvular 3-dimensional geometric perturbations and chordae tendineae force redistribution in a porcine model of acute ischemic mitral regurgitation. In 9 pigs, acute ischemic mitral regurgitation was induced by repeated microembolization of the left circumflex coronary artery. Mitral leaflet coaptation geometry was determined by 2-dimensional echocardiography and reconstructed 3-dimensionally. Leading edge chordal forces were measured by dedicated miniature force transducers at control and during ischemic mitral regurgitation. During acute ischemic mitral regurgitation, there was a decreased tension of the primary chorda from the ischemic posterior left ventricular wall to the anterior leaflet (0.295 +/- 0.063 N vs 0.336 +/- 0.071 N [control]; P < .05). The tension of the chorda from the nonischemic anterior left ventricular wall to the anterior leaflet increased (0.375 +/- 0.066 N vs 0.333 +/- 0.071 N [control]; P < .05). In accordance, relative leaflet prolapse was observed at the ischemic commissural side, whereas there was an increase in the leaflet surface area at the nonischemic commissural side, indicating localized leaflet tethering. Acute ischemic mitral regurgitation due to posterior left ventricular wall ischemia was associated with focal chordal and leaflet tethering at the nonischemic commissural portion of the mitral valve and a paradoxical decrease of the chordal forces and relative prolapse at the ischemic site of the anterior mitral valve leaflet.

Impact of gender on risk stratification by exercise and dobutamine stress echocardiography: long-term mortality in 4234 women and 6898 men

Prior research is limited with regard to the diagnostic and prognostic accuracy of commonplace cardiac imaging modalities in women. The aim of this study was to examine 5-year mortality in 4234 women and 6898 men undergoing exercise or dobutamine stress echocardiography at three hospitals. Univariable and multivariable Cox proportional hazards models were used to estimate time to cardiac death in this multi-centre, observational registry. Of the 11 132 patients, women had a greater frequency of cardiac risk factors (P<0.0001). However, men more often had a history of coronary disease including a greater frequency of echocardiographic wall motion abnormalities (P<0.0001). During 5 years of follow-up, 103 women and 226 men died from ischaemic heart disease (P<0.0001). Echocardiographic estimates of left ventricular function (P<0.0001) and the extent of ischaemic wall motion abnormalities (P<0.0001) were highly predictive of cardiac death. Risk-adjusted 5-year survival was 99.4, 97.6, and 95% for exercising women with no, single, and multi-vessel ischaemia (P<0.0001). For women undergoing dobutamine stress, 5-year survival was 95, 89, and 86.6% for those with 0, 1, and 2-3 vessel ischaemia (P<0.0001). Exercising men had a 2.0-fold higher risk at every level of worsening ischaemia (P<0.0001). Significantly worsening cardiac survival was noted for the 1568 men undergoing dobutamine stress echocardiography (P<0.0001); no ischaemia was associated with 92% 5-year survival as compared with death rates of >/=16% for men with ischaemia on dobutamine stress echocardiography (P<0.0001). Echocardiographic measures of inducible wall motion abnormalities and global and regional left ventricular function are highly predictive of long-term outcome for women and men alike.

The radial artery as a coronary bypass conduit: dealing with hyperreactivity

The radial artery as a coronary bypass conduit: dealing with hyperreactivity