Guido A. K. Heidendal

Visualisation of cell death in vivo in patients with acute myocardial infarction

BACKGROUND In-vivo visualisation and quantification of the extent and time-frame of cell death after acute myocardial infarction would be of great interest. We studied in-vivo cell death in the hearts of patients with an acute myocardial infarction using imaging with technetium-99m-labelled annexin-V-a protein that binds to cells undergoing apoptosis. METHODS Seven patients with an acute myocardial infarction and one control were studied. All patients were treated by percutaneous transluminal coronary angioplasty (six primary and one rescue), resulting in thrombolysis in myocardial infarction (TIMI) III flow of the infarct-related artery. 2 h after reperfusion, 1 mg annexin-V labelled with 584 MBq Tc-99m was injected intravenously. Early (mean 3.4 h) and late (mean 20.5 h) single-photon-emission computed tomographic (SPECT) images of the heart were obtained. Routine myocardial resting-perfusion imaging was also done to verify infarct localisation. FINDINGS In six of the seven patients, increased uptake of Tc-99m-labelled annexin-V was seen in the infarct area of the heart on early and late SPECT images. No increased uptake was seen in the heart outside the infarct area. All patients with increased Tc-99m-labelled annexin-V uptake in the infarct area showed a matching perfusion defect. In a control individual, no increased uptake in the heart was seen. INTERPRETATION Increased uptake of Tc-99m-labelled annexin-V is present in the infarct area of patients with an acute myocardial infarction, suggesting that programmed cell death occurs in that area. The annexin-V imaging protocol might allow us to study the dynamics of reperfusion-induced cell death in the area at risk and may help to assess interventions that inhibit cell death in patients with an acute myocardial infarction.

Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis.

To the Editor: Although progressive stenosis of the arterial lumen constitutes the basis for ischemic symptoms in atherosclerotic vascular disease, acute vascular events are for the most part assoc...

Noninvasive Detection of Programmed Cell Loss with 99mTc-Labeled Annexin A5 in Heart Failure

Apoptosis, or programmed cell death (PCD), contributes to the decline in ventricular function in heart failure. Because apoptosis comprises a programmed cascade of events, it is potentially reversible, and timely intervention should delay the development of cardiomyopathy. 99mTc-Labeled annexin A5 has successfully been used for the noninvasive detection of PCD in myocardial infarction and heart transplant rejection. The present study evaluated the role of annexin A5 imaging for detection of PCD in heart failure patients. Methods: Annexin A5 imaging was performed on 9 consecutive heart failure patients with advanced nonischemic cardiomyopathy (dilated, n = 8; hypertrophic, n = 1) and in 2 relatives having the same genetic background as the hypertrophic cardiomyopathy patient but no heart failure. Results: Four of the patients with dilated cardiomyopathy and the 1 with hypertrophic cardiomyopathy and heart failure showed focal, multifocal, or global left ventricular uptake of annexin A5. No uptake was visualized in the remaining 4 patients or in the 2 controls. All cases showing annexin A5 uptake within the left ventricle experienced significant reduction in left ventricular function or functional class. In cases with no annexin A5 uptake, left ventricular function and clinical status remained stable. Conclusion: These data indicate the feasibility of noninvasive PCD detection with annexin imaging in heart failure patients. Annexin A5 uptake is associated with deterioration in left ventricular function, and this association may lend itself to the development of novel management strategies.

Macroporous calcium phosphate ceramics for bone substitution: a tracer study on biodegradation with 45Ca tracer

The value of artificial materials in bone replacement depends highly on their biocompatibility and biostability. Porous calcium phosphate ceramics have a good compatibility with natural bone. To study the biodegradation process of calcium phosphate bioceramics, labelled [45Ca]-beta-whitlockite and [45Ca]-hydroxyapatite were implanted in the femurs of dogs. The effects accompanying the ingrowth of new bone into the pores of these bioceramics and its replacement by natural bone were investigated. In vivo degradation of the implant material by biochemical dissolution processes was observed. The beta-whitlockite implants showed a conspicuous decrease in radioactive calcium, in contrast to the hydroxyapatite implants. 45Ca was absent in adjacent bones and locally newly formed bone in both beta-whitlockite and hydroxyapatite suggesting a restricted availability of the 45Ca liberated in these processes. Indications of minor mechanical degradation of the materials were also found; in the lymph nodes a very small amount of 45Ca with a high specific activity was detectable. Urine, blood or faeces contained no detectable amounts of 45Ca activity.

Value of indium-111 monoclonal antimyosin antibody for imaging in acute myocardial infarction

Abstract In most patients with chest pain, clinical history and observed electrocardiographic and enzymatic changes are sufficient to prove or rule out an acute myocardial infarction (AMI). However, in some patients these methods fail to rule out or do not allow to localize the site of an AMI. In patients admitted several days after the acute attack of chest pain, enzyme levels may have returned to normal and the electrocardiogram may not differentiate old from recent infarction. In addition, the enzyme changes after coronary artery bypass grafting may be comparable to those seen during an AMI, but confirmation of the diagnosis and localization of the AMI on the electrocardiogram may be difficult. Localization of myocardial infarction may also be difficult in patients with a left bundle branch block or Wolff-Parkinson-White syndrome. Finally, although infarct size has been estimated by measuring enzyme levels, these values may be less reliable as a marker of infarct size after thrombolytic therapy. To overcome these problems nuclear imaging techniques have been used, particularly technetium-99m stannous pyrophosphate imaging. 1,2 However, technetium stannous pyrophosphate has disadvantages. Persistent blood pool activity and low-grade uptake in the region of the heart may be confused. In addition, uptake by overlying ribs and sternum may make interpretation of the technetium pyrophosphate scan difficult. Also, one must wait at least 24 hours, and preferably 48 to 72 hours, after the onset of chest pain. These problems may be resolved if single photon emission computed tomography and blood pool overlay techniques are used. 3 Since monoclonal antimyosin antibody labeled to indium-111 was available in our laboratory a study was undertaken to assess the value of this antibody to localize an AMI. To study the value of this technique patients were selected in whom electrocardiographic changes allowed localization of the AMI.

A modified scintigrafic technique for amputation level selection in diabetics

A modified 123I-antipyrine cutaneous washout technique for the selection of amputation levels is described. The modifications imply a reduction of time needed for the examination by simultaneous recordings on different levels, and a better patient acceptance by reducing inconvenience. Furthermore, both skin perfusion pressure (SPP) and skin blood flow (SBF) are determined from each clearance curve. In a prospective study among 26 diabetic patients presenting with ulcers or gangrene of the foot, both SPP and SBF were determined preoperatively on the selected level of surgery and on adjacent amputation sites. These 26 patients underwent 12 minor foot amputations and 17 major lower limb amputations. Two of these amputations failed to heal. SBF values appeared indicative for the degree of peripheral vascular disease, as low SBF values were found with low SPP values. SPP determinations revealed good predictive values: all surgical procedures healed when SPP>20mmmHg, but 2 out of 3 failed when SPP < 20 mmHg. If SPP values would have been decisive, the amputation would have been converted to a lower level in 6 out of 17 cases. This modified scintigrafic technique provides accurate objective information for amputation level selection.

Bringing cell death alive.

The role of apoptosis in ischemia and reperfusion of the heart has been widely debated. This controversy has been continued because of the lack of an apoptosis detection method that allowed obtaining detailed kinetic and quantitative information on apoptosis. Here we focus on recent findings that look into the detection of apoptosis following ischemia and reperfusion in the heart in animal models and in patients using Annexin-A5 based image technology. Following cardiac cell damage, one major characteristic finding is that apoptotic cells express phosphatidylserines (PS) on the outer leaflet of their cell membrane, serving as a “remove me” signal for the immune system. Annexin-A5, a native plasma protein with a high affinity for PS, can be used to measure this mode of cell death. Several Annexin-A5 based imaging systems have been developed to measure apoptosis from cell culture up to patients. In this review, implications, limitations, and clinical relevance of cell death imaging will be discussed.

Radionuclide angiography in the diagnosis of congenital intrapericardial aneurysm of the left atrial appendage.

A healthy looking 34-year-old man was admitted to the coronary care unit with a three-month history of palpitations and dizziness. Physical examination did not reveal any abnormalities except a tachycardia of 190/min which on electrocardiography was shown to be atrial fibrillation. The patient had had similar attacks in the recent past. In the absence of any obvious cause for the arrhythmia, a single synchronised DC shock was applied with successful restoration of sinus activity. Auscultation at the lower heart rate was completely normal. The electrocardiogram in sinus rhythm showed broad, biphasic P waves in lead VI. A postero-anterior chest radiograph showed an abnormal left heart contour compatible with a pathological process in the region of the left atrial appendage. On fluoroscopy the mass did not pulsate.

Evaluation of cold areas on the thyroid scan with 99mTc solcocitran.

Cold areas on a 99mTc pertechnetate thyroid scan were reevaluated using 99mTc Solcocitran in 31 patients. In 27 patients surgical specimens were obtained for histologic studies. Of 20 benign lesions, five showed a relatively increased uptake of 99mTc Solcocitran. Two of seven malignant lesions were interpreted as positive on the 99mTc Solcocitran scan. This study indicates that 99mTc Solcocitran is not a valuable radiopharmaceutical for differentiating cold areas.

Evaluation of cold areas on the thyroid scan with 99mTc-bleomycin

The value of 99mTc-bleomycin scintigraphy in the evaluation of cold areas on a 99mTc-pertechnetate scan was investigated in 35 patients. A histological diagnosis was obtained in 31 patients. Only one of the six malignant lesions was considered as positive and two as doubtful. Of the remaining 25 patients with non-toxic colloid goitre, one was clearly positive and four were doubtful. These results indicate that 99mTc-bleomycin scintigraphy is not a valuable procedure in the further evaluation of patients with cold lesions.