An experimental model of chronic myocardial hibernation

BACKGROUND: Hibernating myocardium describes persistently impaired ventricular function at rest caused by reduced coronary blood flow. However, a realistic animal model reproducing this chronic ischemic state does not exist. The purpose of this study was to explore whether chronic low-flow hibernation could be produced in swine. METHODS: Miniswine underwent 90% stenosis of the left circumflex coronary artery. Positron emission tomography and dobutamine stress echocardiography were performed 3 and 30 days (n = 6) or 14 days (n = 4) after occlusion to evaluate myocardial blood flow and viability. Triphenyl tetrazolium chloride assessed percent infarction. Electron microscopy was used to identify cellular changes characteristic of hibernating myocardium. RESULTS: Positron emission tomography (13N-labeled-ammonia) 3 days after occlusion demonstrated a significant reduction in myocardial blood flow in the left circumflex distribution. This reduced flow was accompanied by increased glucose use (18F-fluorodeoxyglucose), which is consistent with hibernating myocardium. Thirty days after occlusion, positron emission tomography demonstrated persistent low flow with increased glucose use in the left circumflex distribution. Dobutamine stress echocardiography 3 days after occlusion demonstrated severe hypocontractility at rest in the left circumflex region. Regional wall motion improved with low-dose dobutamine followed by deterioration at higher doses (biphasic response), findings consistent with hibernating myocardium. The results of dobutamine stress echocardiography were unchanged 30 days after occlusion. Triphenyl tetrazolium chloride staining (n = 6) revealed a mean of 8% +/- 2% infarction of the area-at-risk localized to the endocardial surface. Electron microscopy (n = 4) 14 days after occlusion demonstrated loss of contractile elements and large areas of glycogen accumulation within viable cardiomyocytes, also characteristic of hibernating myocardium. CONCLUSIONS: Chronic low-flow myocardial hibernation can be reproduced in an animal model after partial coronary occlusion. This model may prove useful in the study of the mechanisms underlying hibernating myocardium and the use of therapies designed to improve blood flow to the heart.     

冠状动脉粥样硬化性心脏病外科治疗进展

对冠状动脉继样硬化心脏病外科治疗进行综述。目前,全动脉移植再血管化（ＣＡＭＲ０虽取得了可喜的近期临床效果,但远期效果尚有待观察,可选择性应用;动脉移植可选择性应用于左前降支和主要冠状动脉;对老年重症、糖尿病和急症手术患者,仍以应用动静脉混合移植为好。浙江心肌打孔再血管化远期疗效不肯定,人们的兴趣在下降;当前激光心肌打孔再血管化与缺血心肌局部注射血管内皮生长因子（基因治疗）联合使用,其前景还有等研究。非体外循环心脏不停跳下做冠状动脉旁路移植术（ＣＡＢＧ）在微创冠状动脉旁路移植术中开展较早,手术病例也较多;不开胸建立体外循环下手术,发展应用机器人完成冠状动脉旁路移植术,前景均很好。高龄重征患者存在更多的危险因素,手术结果显示可以改善生活质量。随着诊断和技术的发展,缺血性心肌病治疗策略已在发生变化,正电子断层显像能提     

Hibernating myocardium: clinical and functional response to revascularisation

Objective: We assessed the effects of coronary bypass grafting on left ventricular (LV) function, exercise capacity and symptom profile in patients with LV impairment and evaluated the role of identifying myocardial hibernation in a prospective non-randomised study. Methods: Of 120 patients screened, 47 patients with LV ejection fraction <35% and three vessel coronary artery disease were studied. All underwent stress/redistribution and separate day rest/redistribution Tl-201 imaging together with cine MRI at enrolment, and cine MRI at follow-up. Group 1, 30 patients undergoing bypass surgery, underwent symptom limited treadmill exercise testing with peak VO₂ measurement, and symptom profile evaluation less than 3 months before, and 3–6 months after operation. Revascularisation was assessed by post-operative Tl-201 imaging and repeat coronary angiography. Group 2, 17 patients treated on medical therapy alone underwent symptom profile assessment at enrolment and follow-up for those who survived. Segmental hibernation was defined as the equivalent of greater than 50% of maximal Tl-201 uptake where wall motion was severely impaired on resting imaging. Patients were considered to be hibernating where two of nine LV segments fulfilled these criteria. Results: In group 1, five patients died (17%), peri-or post-operatively, two defaulted and 23 attended follow-up studies. In group 2, three patients died prior to follow-up (18%). In the surgical group there was an increase in mean LVEF from 24.0±8% to 29.7±11% (P<0.05) while in the medical group there was a fall from 25.7±10% to 20.6±8% (P<0.05). In group 1, the mean NYHA dyspnoea grade improved from 2.7 to 1.4 while in the medical group it was unchanged, 2.6 to 2.5. In patients with myocardial hibernation identified pre-operatively, 18/19 (95%) improved LVEF after CABG compared with 2/4 (50%) of patients without hibernation. 17/19 (86%) patients with hibernation improved NYHA dyspnoea class compared with 2/4 (50%) of patients without. 60/93 (65%) of hibernating segments improved function after revascularisation while 47/53 (89%) hibernating segments showed no improvement on medical therapy alone. Conclusion: In patients with severe LV impairment with myocardial hibernation, coronary artery bypass grafting improves both global and regional systolic LV function, and symptom profile. Medical treatment of patients with LV impairment and myocardial hibernation does not improve LV contractile function or symptoms. Both surgical and medical therapy carry a high mortality rate.     

Coronary revascularization in ischemic cardiomyopathy

This article first discusses coronary artery disease, including left-ventricular dysfunction, hibernating myocardium, the relationship between stunning, hibernation, and heart failure, and molecular mechanisms underlying myocardial hibernation. Left ventricular function and the prognosis and pathophysiology of left-ventricular dysfunction are then examined. Selection of patients for revascularization is discussed, to include which coronary patients should be investigated for myocardial viability, and other surgical considerations are outlined. The outcome following revascularization in the heart failure patient, the results of revascularization, and the time course of functional recovery after coronary artery bypass graft are also covered.     

Heartmate II Implantation with Right Coronary Bypass Grafting in Ischemic Cardiomyopathy with "Fixed" Pulmonary Hypertension: Treatment Strategy to Protect Right Ventricular Function

Abstract   A 49-year-old male patient suffering from end-stage ischemic cardiomyopathy with a left ventricular ejection fraction below 15% was presented to redo coronary artery bypass grafting (CABG). Coronary angiogram demonstrated an occluded left anterior descending artery and occluded right coronary artery, perfused retrogradely from the circumflex artery. Since positron emission tomography did not demonstrate viable left ventricular myocardium except for the basis of the left ventricle, CABG was considered futile. Cardiac transplantation was contra-indicated due to pharmacologically unresponsive pulmonary artery hypertension. The patient successfully underwent left ventricular assist device implantation in combination with right coronary artery revascularization. The article reflects the regimen of right ventricular preservation in this patient. (J Card Surg 2010;25:116-119)     

Ischemically compromised myocardium displays different time-courses of functional recovery: correlation with morphological alterations?

OBJECTIVE: It has been demonstrated that positron emission tomography (PET) predicts the functional recovery of viable but ischemically compromised myocardium. Reversible contractile dysfunction after revascularization has been reported for 'hibernating myocardium' and stunned myocardium, however, there are little data concerning the time-course and the extent of improvement of the two different pathophysiological conditions. METHODS: Twenty-nine patients with advanced coronary artery disease and severely reduced left ventricular function (EF 18--35%) who were referred for isolated coronary artery bypass grafting underwent preoperative PET viability assessment and were functionally assessed by two-dimensional echocardiography preoperatively at 11 days, 14 weeks, and more than 12 months after surgical revascularization. Intraoperative biopsies were taken from dysfunctional areas defined by PET as segments of normal perfusion and normal metabolism (stunned myocardium) and from areas with a 'mismatch' between perfusion and metabolism (hibernating myocardium). The degree of morphological alterations was evaluated by electron microscopy. RESULTS: In 70% of the 240 dysfunctional segments, 'stunned myocardium' was present whereas 'hibernating myocardium' could be detected in only 24% (P < 0.01). Hibernating myocardium was associated with more severe preoperative wall motion abnormalities and incomplete postoperative recovery. After 1 year, 31% of 'stunned' segments vs. only 18% of 'hibernating' segments showed complete functional restoration (P < 0.05). This incomplete improvement was associated with more severe morphological alterations including depletion of sarcomeres, accumulation of glycogen, loss of sarcoplasmatic reticulum, and cellular sequestration. CONCLUSIONS: These data indicate that in patients with severe ischemic left ventricular dysfunction 'stunned myocardium' is more prevalent than 'hibernation'. Functional normalization is more frequent in 'stunned' segments, whereas areas of 'hibernation' showed more severe tissue injury and protracted recovery. Different degrees of myocardial injury coexist in most patients, which determines the time-course and the extent of improvement after revascularization.     

Intramyocardial and intracoronary basic fibroblast growth factor in porcine hibernating myocardium: a comparative study

OBJECTIVE: Therapeutic angiogenesis is an alternative method of revascularization for end-stage coronary artery disease. We determined the effects of intramyocardial and intracoronary basic fibroblast growth factor 2 on myocardial blood flow and function in a porcine model of hibernating myocardium. METHODS: Twenty-four mini-swine with 90% left circumflex artery stenosis and documented hibernating myocardium by positron emission tomography and dobutamine stress echocardiography were randomized to intramyocardial basic fibroblast growth factor 2 at 0.6 microg/kg (mid-dose, n = 6, 30 injections/animal), 6 microg/kg (high-dose, n = 6, 30 injections/animal), or intramyocardial vehicle control (n = 6). The intracoronary group received 6 microg/kg basic fibroblast growth factor 2 (n = 6) into the right and left circumflex artery coronary arteries. Positron emission tomography and dobutamine stress echocardiography were repeated at 1 and 3 months. RESULTS: In the vehicle group, normalized left circumflex artery myocardial blood flow was 0.74 +/- 0.04 at 1 month and 0.75 +/- 0.07 at 3 months compared with 0.68 +/- 0.03 at baseline. In the intracoronary group, myocardial blood flow was 0.71 +/- 0.03 at 1 month and 0.72 +/- 0.04 at 3 months compared with 0.67 +/- 0.04 at baseline. In the mid group, myocardial blood flow was 0.73 +/- 0.06 at 1 month and 0.85 +/- 0.05 at 3 months (P <.001) compared with 0.67 +/- 0.04 at baseline. In the high group, myocardial blood flow was 0.81 +/- 0.06 at 1 month and 0.83 +/-.04 at 3 months (P =.03) compared with 0.71 +/- 0.02 at baseline. No significant improvements in ischemia were demonstrated in any of the groups by dobutamine stress echocardiography at 1 or 3 months. CONCLUSIONS: In porcine hibernating myocardium, intramyocardial basic fibroblast growth factor 2 significantly improved regional myocardial blood flow 3 months after treatment. There was no significant change in function in any of the 4 groups. These data suggest that intramyocardial dosing of basic fibroblast growth factor 2 (0.6 microg/kg) may be an optimal dose for improving perfusion in the treatment of end-stage coronary artery disease.     

Staged coronary artery bypass grafting after percutaneous angioplasty for intracranial vascular stenosis

OBJECTIVE: Cerebrovascular disease is commonly associated with coronary artery disease and is a major risk factor for cardiac surgery. Concomitant coronary artery bypass grafting and carotid endarterectomy may reduce the risk of stroke; however, this staged operation is effective only for extracranial lesions. The strategy for on-pump coronary artery bypass grafting for patients with intracranial vascular stenosis is still controversial. METHODS: The subjects were 157 consecutive candidates for coronary artery bypass grafting who underwent computed tomography and digital subtraction cerebral angiography preoperatively to check for cerebrovascular disease. Additional single-photon emission computed tomography was performed to evaluate cerebral ischemia, according to the neurologist's request. Patients with diffuse intracranial vascular stenosis impossible to treat with percutaneous transluminal angioplasty underwent off-pump coronary artery bypass grafting. Patients with a circumflex coronary artery lesion first underwent percutaneous transluminal angioplasty for cerebral vascular stenosis followed by secondary on-pump coronary artery bypass grafting. RESULTS: Three patients were selected for staged operations. Percutaneous transluminal angioplasty was performed for 4 intracranial stenotic lesions. All lesions were dilated successfully, and no complications developed during or after the procedure. All patients tolerated staged coronary artery bypass grafting and were extubated within 1 day without any mental disturbance. No further neurologic complication occurred, and computed tomography performed postoperatively revealed no significant changes. CONCLUSION: Staged on-pump coronary bypass after percutaneous transluminal angioplasty for cerebrovascular disease may reduce the risk of stroke during cardiopulmonary bypass, and it is useful especially in patients with intracranial cerebrovascular disease.     

How to discriminate between hibernating and stunned myocardium

AIM: The aim of the present study was to examine if it is possible to discriminate between hibernating and stunned myocardium in vivo by determining the ratio between diastolic and systolic coronary arterial inflow and by measuring oxygen saturation in draining coronary venous blood. METHODS: Experiments were performed in 32 open chest pigs anesthetized with sodium pentobarbital. In 11 pigs hibernation was induced in a part of the left ventricular myocardium by reducing flow in the mid-left anterior descending coronary artery (LAD) to about 60% of baseline flow. In 12 pigs stunning was induced by occluding mid-LAD twice for 10 min with a 30 min interval. In 9 pigs (control group) coronary flow was not manipulated. RESULTS: We found, at comparable degrees of regional dysfunction, that the ratio between diastolic and systolic flow in stunned myocardium remained unaltered, but fell from about 2 to 1 in hibernating myocardium. Furthermore, coronary venous oxygen saturation decreased from about 30% to 17% in blood draining hibernating myocardium, but remained statistically unaltered in blood draining stunned myocardium. CONCLUSION: We conclude that it is possible to discriminate between hibernating and stunned myocardium by measuring phasic coronary arterial blood flow and oxygen saturation in blood draining the region in question. During hibernation only, the diastolic flow component of coronary arterial inflow is reduced and the coronary venous oxygen extraction increased.     

Assessment of CABG-related risk in patients with CAD and LVD. Contribution of PET with [18F]FDG to the assessment of myocardial viability.

BACKGROUND: Previous studies have demonstrated that hibernating myocardium can be assessed by [18F]fluorodeoxyglucose ([18F]FDG) and positron emission tomography (PET). This study evaluated the use of [18F]FDG-PET for CABG related risk assessment in patients with coronary artery disease (CAD) and left ventricle dysfunction (LVD). METHODS: We retrospectively evaluated 241 to patients candidate CABG presenting with signs and symptoms of congestive heart failure (CHF) prevailing over ischemic signs. Of the 241 patients, 153 had undergone [18F]FDG-PET as well as conventional assessment: 110 out of 153 (group A) were operated because of PET evidence of hibernation. Of the 241 patients, 88 had not undergone [18F]FDG-PET: 86 out of 88 (group B) were operated on. The outcome of surgical patients was evaluated by considering all major perioperative complications including the use of mechanical and pharmacological support and in-hospital mortality. After hospital discharge, each patient was examined at 1, 4 and every 6 months thereafter. RESULTS: Perioperative use of mechanical supports and inotropic drugs, was significantly lower for the PET selected group (A) than for the non PET selected group (B). Mortality within 30 days of surgery was 0.9% in group A and 19.8% in group B. The only predictors of perioperative outcome were the presence of hibernating tissue and the ejection fraction. CONCLUSIONS: [18F]FDG-PET prior to CABG can be crucial for the assessment of perioperative risk in patients with CAD.     

PET Scan Predicts Recovery of Left Ventricular Function After Coronary Artery Bypass Operation

Background. Viable but hypocontractile myocardium can show functional improvement after revascularization (hibernation). It is sometimes difficult, however, to predict viability and recovery in patients with severe left ventricular function. This study sought to identify possible predictive factors of recovery of cardiac function after revascularization in patients with three-vessel disease.

Methods. Positron emission tomography (fluoro-18-deoxyglucose uptake for metabolism; nitrogen 13–labeled ammonia for flow) and equilibrium-gated nuclear angiography (for the global ejection fraction) were performed in 59 patients with three-vessel disease before and after undergoing coronary artery bypass grafting. The positron emission tomographic data were expressed as match normal (flow and metabolism normal), mismatch (low flow, high metabolism), match viable (moderate decrease in flow and metabolism), and match necrosis (low flow and metabolism).

Results. Stepwise logistic regression analysis showed that only mismatch regions played a significant role in predicting postoperative improvement in function (p = 0.019). There were 1.7 ± 1.5 mismatch regions in 31 patients who showed an improvement in their ejection fraction (0.47 ± 0.14 versus 0.58 ± 0.11; mean ± standard deviation) versus 0.8 ± 1.0 mismatch regions (p = 0.017) in patients who did not show recovery. There was more pronounced functional improvement with increasing numbers of mismatch regions, and patients with at least one mismatch region had a high likelihood of recovery (p < 0.001). In patients with a very low preoperative ejection fraction and two or more mismatch regions, there was early significant recovery (0.27 ± 0.08 versus 0.46 ± 0.06; p = 0.009).

Conclusions. At least one mismatch region must be present for there to be a postoperative functional benefit. When a low left ventricular ejection fraction is associated with mismatch, early recovery is substantial.     

Ball thrombus induced by hibernating myocardium in the left ventricle; report of a case

An 80-year-old man was admitted to our hospital for examination of a ball thrombus incidentally found in the left ventricle (LV). Coronary angiogram revealed severe triple vessel disease and LV dysfunction. Although LV wall motion in the septum and the apex was akinetic, there were no signs of myocardial infarction. It was diagnosed as an acute LV ball thrombus with hibernating myocardium due to ischemia of the left anterior descending coronary artery. Emergency coronary artery bypass grafting (CABG) and excision of the thrombus were performed. Two weeks after surgery, LV function improved and the patient was discharged from the hospital without any complication. A LV ball thrombus without myocardial infarction is rare, and thought to be caused by hibernating myocardium.     

Revascularization of severe hibernating myocardium in the beating heart: early hemodynamic and metabolic features

BACKGROUND: We investigated the effects of coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) in selected patients with severe hibernating myocardium. METHODS: Twelve patients (EF = 25% +/- 0.7%) with reversible ventricular dysfunction (from 2.0 +/- 0.06 to 1.6 +/- 0.05 left ventricular score index by echodobutamine, p < 0.01) in the territory of the left anterior descending artery (LAD) have been studied. Revascularization was achieved by anastomosing the left internal mammary artery to the LAD. The ischemic time of LAD was 9.0 +/- 0.4 minutes. RESULTS: Left ventricular function increased 6 hours and 48 hours after revascularization (left ventricular stroke work index from 32 +/- 1.8 to 42 +/- 1.5 and 40 +/- 0.6 gxm/m2, respectively: p = 0.0001). During the surgical procedure, the heart did not release lactate or creatine phosphokinase. There were no perioperative deaths or severe complications. CONCLUSIONS: Early hemodynamic and metabolic features of CABG without CPB in patients with hibernating myocardium suggest that this procedure is safe and results in a significant improvement of cardiac function without affecting myocardial metabolism.     

Prolonged ischemic heart disease and coronary artery bypass - relation to contractile reserve.

OBJECTIVE: A major effect of coronary artery bypass grafting (CABG) in patients with ischemic heart disease and impaired left ventricular (LV) contractile function is believed to be an improvement in LV function due to recovery of dysfunctional, but viable myocardium. However, recent studies have indicated a time limit for such a recovery. We therefore investigated the extent of viable myocardium in patients with impaired LV function due to ischemic heart disease after a prolonged strategy of medical treatment and its relation to changes in clinical variables after CABG. METHODS: Forty-five consecutive patients with a mean duration of ischemic heart symptoms of 9 years and LV ejection fraction (EF) <45% referred for CABG were included and LV extent of viable myocardium was measured preoperatively by glucose metabolism--blood flow positron emission tomography imaging and dobutamine stress echocardiography. Symptoms, exercise-capacity and LV function were evaluated before and 7 months after surgery in event-free survivors. RESULTS: LV extent of myocardial viability was <30% in most patients. In event-free survivors, LVEF decreased from 31+/-7 to 26+/-8% 7 months after CABG. The decrease in LVEF was correlated to the LV extent of myocardial metabolism--blood flow reverse mismatch. Most of the patients experienced an improvement in their angina pectoris, heart failure symptoms and exercise capacity after CABG; the overall 3-year survival was 77%. CONCLUSIONS: Patients with chronic ischemic heart disease and impairment of LV function, in whom an initial long-standing conservative treatment has been practiced, benefit from CABG, despite a lack of LV functional reserve.     

Improved perfusion and contractile reserve after transmyocardial laser revascularization in a model of hibernating myocardium

Background. Transmyocardial laser revascularization (TMR) has been demonstrated effective for relieving angina, although prior studies have yielded inconsistent results regarding postoperative myocardial perfusion and function. This study evaluated long-term changes in myocardial perfusion and contractile reserve after TMR in a model of hibernating myocardium.

Methods. Miniswine had subtotal left circumflex coronary artery occlusion to reduce resting blood flow to 10% of baseline. After 2 weeks in the low-flow state, positron emission tomography and dobutamine stress echocardiography were performed to document ischemic, viable (hibernating) myocardium in the left circumflex distribution. Animals then had sham redo thoracotomy (n = 4) or TMR (n = 6). Six months later the positron emission tomography and dobutamine stress echocardiography studies were repeated.

Results. Myocardial blood flow in the left circumflex distribution as measured by positron emission tomography was significantly reduced in all animals after 2 weeks in the low-flow state. In animals that had TMR, there was significant improvement in myocardial blood flow to the lased regions 6 months postoperatively. No significant change in myocardial blood flow was seen in sham animals at 6 months. Dobutamine stress echocardiography after 2 weeks of low-flow demonstrated severe hypocontractility at rest in the left circumflex region of all animals, with a biphasic response to dobutamine consistent with hibernating myocardium. In animals that had TMR, there was a trend toward improved resting function and significantly improved regional stress function in the lased segments 6 months postoperatively, consistent with a reduction in ischemia. Global left ventricular wall motion at peak stress improved significantly as well. There was no change in wall motion 6 months postoperatively in sham-operated animals.

Conclusions. This study found improvements in myocardial perfusion and regional and global contractile reserve 6 months after TMR in a porcine model of hibernating myocardium. This improved perfusion and function likely accounts for the clinical benefits of the procedure.     

Improved cerebral perfusion and metabolism after stenting for basilar artery stenosis: technical case report

OBJECTIVE: Recent advances in stent technology have allowed the introduction of more flexible stents that may be tracked more easily in the intracranial vessels. We present a patient with improved cerebral blood flow and metabolism as assessed by positron emission tomography after stent-assisted angioplasty for symptomatic basilar artery stenosis. CLINICAL PRESENTATION: A 62-year-old man, who had undergone left superficial temporal artery to middle cerebral artery bypass surgery for left internal carotid artery occlusion 10 years previously, presented with dizziness, blurred vision, and memory disturbance. Angiography revealed severe stenosis of the proximal basilar artery. Positron emission tomographic scans revealed decreased cerebral blood flow associated with increased oxygen extraction fraction in the entire brain, particularly in the posterior circulation and the left middle cerebral artery territory. Despite medical treatment, the patient experienced worsening visual disturbance and right-sided motor weakness. INTERVENTION: Ticlopidine and aspirin were used as antiplatelet agents. In addition, we used argatroban, which is a direct thrombin inhibitor, as an anticoagulant during the procedure. Predilation with a coronary artery balloon was performed, followed by placement of a GFX 3- by 8-mm stent (Arterial Vascular Engineering, Santa Rosa, CA), with excellent angiographic results. The patient made a good neurological recovery, and the postoperative positron emission tomographic scan demonstrated increases in both cerebral blood flow and cerebral metabolic rate of oxygen with a normalization of oxygen extraction fraction. CONCLUSION: Stent-assisted angioplasty can provide a favorable clinical course as well as improved cerebral perfusion and metabolism for a patient with basilar artery stenosis. Long-term follow-up data and additional clinical experience are required to assess the durability of this approach.     

Factors excercising an influence on recovery of hibernating myocardium after coronary artery bypass grafting.

OBJECTIVE: Coronary artery bypass grafting (CABG) in patients with endstage coronary disease (CAD) significantly improves symptoms and prolongs life expectancy. Left ventricular function is also improved in some patients, but not in others. Factors which influence functional recovery of hibernating myocardium after revascularization are at present under investigation. METHODS: From 3/2000 to 8/2002, we analyzed 41 patients with an ejection fraction (EF) of < or =30%, who underwent CABG, prospectively. All patients received low-dose dobutamine echocardiography (DE), dobutamine myocardial scintigraphy with SPECT, dobutamine magnetic resonance tomography (MRI), contrast-enhanced MRI and, when necessary, positron emission tomography (PET). Hibernating myocardium (area of interest) was identified with these diagnostic tools preoperatively and biopsy samples were taken intraoperatively. RESULTS: All patients received complete coronary revascularization. Early mortality was 2.4%. Three patients died during follow-up. Six months after the operation DE, MRI and SPECT were repeated. EF increased in 23 patients (group I) by at least >or =5%, and in 14 patients (group II) it did not improve. The wall motion score in the area of interest had increased during preoperative DE in group I significantly. The score did not change in group II. In addition the diastolic-systolic wall thickness increase in the area of interest rose >15% during DE in group I preoperatively; the increase was < or =15% in group II. MRI hyperenhancement of the left ventricle was significantly lower in group I compared to group II preoperatively. SPECT showed myocardial viability in the area of interest in all 37 patients. There were no significant differences between group I and II seen in SPECT. When the area of interest was located in the anterior wall the patients more frequently showed ventricular improvement postoperatively than patients with an area of interest located in the inferior, lateral or posterior wall. Light microscopy showed more severe myocardial cell hypertrophy (>19 microm) and less severe destruction of myocardial cell architecture in biopsies of group I compared to group II (myocardial cell hypertrophy < or =17 microm). Electron microscopy showed mitochondrial abnormalities in size and shape, lack of contractile material and large areas containing nonspecified cytoplasm, lipid droplets, and large glycogen-filled regions, but no significant differences between the two groups. Gene expresssion of the pro-apoptotic genes BAK and BAX was lowered compared to expression in 'normal' myocardium. The anti-apoptotic gene BCL-XL was significantly more expressed in the 'area of interest' of group II patients than in group I patients. CONCLUSIONS: We conclude that in patients with endstage CAD myocardial recovery after coronary revascularization can be predicted using DE and MRI preoperatively. Myocardial regions without any potential of functional recovery show less adaptation (less pronounced myocardial cell hypertrophy), a more severe degree of myocardial architecture destruction and a higher degree of anti-apoptotic gene expression. We recommend a myocardial biopsy when DE and MRI are not favorable in a patient with end stage coronary artery disease referred to us with the option of heart transplantation or coronary bypass.     

Composite arterial Y graft has less coronary flow reserve than independent grafts

BACKGROUND: It is not known whether a composite Y graft of the left internal thoracic artery can provide sufficient blood flow to the whole left coronary system. The aim of this study was to compare regional myocardial blood flow (MBF) and coronary flow reserve after coronary artery bypass grafting using arterial composite Y graft or independent arterial grafts. METHODS: Positron emission tomography was performed at rest and after dipyridamole infusion using oxygen-15-labeled water 2 weeks after coronary artery bypass grafting. Regional MBF was calculated in seven segments of the left ventricle. Coronary flow reserve was defined as the ratio of MBF after dipyridamole infusion to MBF at rest. In the Y graft group (n = 22), a free arterial graft to obtuse marginal arteries was anastomosed to the proximal side of in situ left internal thoracic artery, which was anastomosed to the left anterior descending artery. In the independent graft group (n = 13), left anterior descending and obtuse marginal arteries were independently revascularized using in situ left internal thoracic artery and a free arterial graft. RESULTS: There was no difference between the groups in MBF at rest. Coronary flow reserve in the Y graft group was lower than that in the independent group in the anterobasal (1.43 +/- 0.07 versus 1.90 +/- 0.13, p = 0.038), apical (1.24 +/- 0.06 versus 1.64 +/- 0.12, p = 0.003), septal (1.34 +/- 0.05 versus 1.75 +/- 0.13, p = 0.023), and lateral regions (1.19 +/- 0.04 versus 1.66 +/- 0.09, p = 0.001). CONCLUSIONS: Although arterial composite Y graft improved MBF at rest, it was not as effective as independent grafts for improving coronary flow reserve soon after coronary artery bypass grafting.     

Autologous bone marrow cell transplantation combined with off-pump coronary artery bypass grafting in patients with ischemic cardiomyopathy

Background

Clinical studies have demonstrated that intracoronary or intramyocardial transplantation of bone marrow mononuclear cells (BMMNCs) into ischemic myocardium improves cardiac function. The objective of the present study was to evaluate the safety and feasibility of intramyocardial BMMNC transplantation into nongraftable areas in combination with off-pump coronary artery bypass grafting in patients with ischemic cardiomyopathy.

Methods

Five male patients with myocardial infarction lasting for more than 1 month and with nongraftable myocardium received autologous mononuclear cell transplantation during off-pump coronary artery bypass grafting. Autologous bone marrow was aspirated from the iliac crest. BMMNCs (mean 1.6, standard error [SE] 0.3 × 10⁹) including CD34-positive cells (mean 6.8, SE 1.1 × 10⁶) and AC133-positive cells (mean 3.1, SE 1.7 × 10⁶) were injected into the nongraftable ischemic myocardium. Heart function was evaluated with the use of echocardiography, and myocardial perfusion was examined with single photon emission computed tomography technetium-99mTc sestamibi scans.

Results

Two months after cell transplantation, the mean ejection fraction had increased by 7.4%, SE 1.9% (p = 0.016) compared with that before cell transplantation and off-pump coronary artery bypass grafting. The increase in ejection fraction was not correlated with the number of transplanted total mononuclear cells, CD34-positive cells and AC133-positive cells. Myocardial perfusion at the cell-transplanted area increased after cell transplantation and off-pump coronary artery bypass grafting. No arrhythmia was observed.

Conclusion

The present clinical study suggests that intramyocardial transplantation of autologous BMMNCs into the ischemic area during off-pump coronary artery bypass grafting is both feasible and safe and has beneficial effects on cardiac function.     

11C-choline positron emission tomography/computerized tomography for tumor localization of primary prostate cancer in comparison with 12-core biopsy

PURPOSE: (11)C-choline positron emission tomography is an innovative imaging technique for prostate cancer. We assessed the sensitivity of positron emission tomography used together with computerized tomography for intraprostatic localization of primary prostate cancer on a nodule-by-nodule basis, and compared its performance with 12-core transrectal biopsy. MATERIALS AND METHODS: In 43 patients with known prostate cancer who had received positron emission tomography/computerized tomography before initial biopsy, we assessed sensitivity of positron emission tomography/computerized tomography for localization of nodules 5 mm or greater (those theoretically large enough for visualization) using radical prostatectomy histopathology as the reference standard. Comparison with transrectal ultrasound guided biopsy was based on sextant assessment of all cancer foci following sextant-by-sextant matching and reconstruction. Sensitivity/specificity of positron emission tomography/computerized tomography and magnetic resonance imaging for prediction of extraprostatic extension was also assessed. RESULTS: Positron emission tomography/computerized tomography showed 83% sensitivity for localization of nodules 5 mm or greater. At logistic regression analysis only nodule size appeared to influence sensitivity. At sextant assessment positron emission tomography/computerized tomography had slightly better sensitivity than transrectal ultrasound guided biopsy (66% vs 61%, p = 0.434) but was less specific (84% vs 97%, p = 0.008). For assessment of extraprostatic extension, sensitivity of PET/CT was low in comparison with magnetic resonance imaging (22% vs 63%, p <0.001). CONCLUSIONS: Positron emission tomography/computerized tomography has good sensitivity for intraprostatic localization of primary prostate cancer nodules 5 mm or greater. Positron emission tomography/computerized tomography and transrectal ultrasound guided biopsy show similar sensitivity for localization of any cancer focus. Positron emission tomography/computerized tomography does not seem to have any role in extraprostatic extension detection. Studies of diagnostic accuracy (as opposed to tumor localization) are needed in patients with suspected prostate cancer to see whether positron emission tomography/computerized tomography could have a role in not selected patients.