The challenge to detect heart transplant rejection and transplant vasculopathy non-invasively - a pilot study

<p>Abstract</p> <p>Background</p> <p>Cardiac allograft rejection and vasculopathy are the main factors limiting long-term survival after heart transplantation.</p> <p>In this pilot study we investigated whether non-invasive methods are beneficial to detect cardiac allograft rejection (Grade 03 R) and cardiac allograft vasculopathy. Thus we compared multi-slice computed tomography and magnetic resonance imaging with invasive methods like coronary angiography and left endomyocardial biopsy.</p> <p>Methods</p> <p>10 asymptomatic long-term survivors after heart transplantation (8 male, 2 female, mean age 52.1 ± 12 years, 73 ± 11 months after transplantation) were included. In a blinded fashion, coronary angiography and multi-slice computed tomography and ventricular endomyocardial biopsy and magnetic resonance imaging were compared against each other.</p> <p>Results</p> <p>Cardiac allograft vasculopathy and atherosclerosis were correctly detected by multi-slice computed tomography and coronary angiography with positive correlation (r = 1). Late contrast enchancement found by magnetic resonance imaging correlated positively (r = 0.92, r²= 0.85, p < 0.05) with the histological diagnosis of transplant rejection revealed by myocardial biopsy. None of the examined endomyocardial specimen revealed cardiac allograft rejection greater than Grade 1 R.</p> <p>Conclusion</p> <p>A combined non-invasive approach using multi-slice computed tomography and magnetic resonance imaging may help to assess cardiac allograft vasculopathy and cardiac allograft rejection after heart transplantation before applying more invasive methods.</p

Delayed development of pneumothorax after pulmonary radiofrequency ablation

Acute pneumothorax is a frequent complication after percutaneous pulmonary radiofrequency (RF) ablation. In this study we present three cases showing delayed development of pneumothorax after pulmonary RF ablation in 34 patients. Our purpose is to draw attention to this delayed complication and to propose a possible approach to avoid this major complication. These three cases occurred subsequent to 44 CT-guided pulmonary RF ablation procedures (6.8%) using either internally cooled or multitined expandable RF electrodes. In two patients, the pneumothorax, being initially absent at the end of the intervention, developed without symptoms. One of these patients required chest drain placement 32 h after RF ablation, and in the second patient therapy remained conservative. In the third patient, a slight pneumothorax at the end of the intervention gradually increased and led into tension pneumothorax 5 days after ablation procedure. Underlying bronchopleural fistula along the coagulated former electrode track was diagnosed in two patients. In conclusion, delayed development of pneumothorax after pulmonary RF ablation can occur and is probably due to underlying bronchopleural fistula, potentially leading to tension pneumothorax. Patients and interventionalists should be prepared for delayed onset of this complication, and extensive track ablation following pulmonary RF ablation should be avoided

Human cardiac tissue in a microperfusion chamber simulating extracorporeal circulation - ischemia and apoptosis studies

<p>Abstract</p> <p>Background</p> <p>After coronary artery bypass grafting ischemia/reperfusion injury inducing cardiomyocyte apoptosis may occur. This surgery-related inflammatory reaction appears to be of extreme complexity with regard to its molecular, cellular and tissue mechanisms and many studies have been performed on animal models. However, finding retrieved from animal studies were only partially confirmed in humans. To investigate this phenomenon and to evaluate possible therapies in vitro, adequate human cardiomyocyte models are required. We established a tissue model of human cardiomyocytes preserving the complex tissue environment. To our knowledge human cardiac tissue has not been investigated in an experimental setup mimicking extracorporeal circulation just in accordance to clinical routine, yet.</p> <p>Methods</p> <p>Cardiac biopsies were retrieved from the right auricle of patients undergoing elective coronary artery bypass grafting before cardiopulmonary bypass. The extracorporeal circulation was simulated by submitting the biopsies to varied conditions simulating cardioplegia (cp) and reperfusion (rep) in a microperfusion chamber. Cp/rep time sets were 20/7, 40/13 and 60/20 min. For analyses of the calcium homoeostasis the fluorescent calcium ion indicator FURA-2 and for apoptosis detection PARP-1 cleavage immunostaining were employed. Further the anti-apoptotic effect of carvedilol [10 μM] was investigated by adding into the perfusate.</p> <p>Results</p> <p>Viable cardiomyocytes presented an intact calcium homoeostasis under physiologic conditions. Following cardioplegia and reperfusion a time-dependent elevation of cytosolic calcium as a sign of disarrangement of the calcium homoeostasis occurred. PARP-1 cleavage also showed a time-dependence whereas reperfusion had the highest impact on apoptosis. Cardioplegia and carvedilol could reduce apoptosis significantly, lowering it between 60-70% (p < 0.05).</p> <p>Conclusions</p> <p>Our human cardiac preparation served as a reliable cellular model tool to study apoptosis in vitro. Decisively cardiac tissue from the right auricle can be easily obtained at nearly every cardiac operation avoiding biopsying of the myocardium or even experiments on animals.</p> <p>The apoptotic damage induced by the ischemia/reperfusion stimulus could be significantly reduced by the cold crystalloid cardioplegia. The additional treatment of cardiomyocytes with a non-selective β-blocker, carvedilol had even a significantly higher reduction of apoptotis.</p

The challenge to verify ceramide's role of apoptosis induction in human cardiomyocytes - a pilot study

<p>Abstract</p> <p>Background</p> <p>Cardioplegia and reperfusion of the myocardium may be associated with cardiomyocyte apoptosis and subsequent myocardial injury. In order to establish a pharmacological strategy for the prevention of these events, this study aimed to verify the reliability of our human cardiac model and to evaluate the pro-apoptotic properties of the sphingolipid second messenger ceramide and the anti-apoptotic properties of the acid sphingomyelinase inhibitor amitryptiline during simulated cardioplegia and reperfusion ex vivo.</p> <p>Methods</p> <p>Cardiac biopsies were retrieved from the right auricle of patients undergoing elective CABG before induction of cardiopulmonary bypass. Biopsies were exposed to <it>ex vivo </it>conditions of varying periods of cp/rep (30/10, 60/20, 120/40 min). Groups: I (untreated control, n = 10), II (treated control cp/rep, n = 10), III (cp/rep + ceramide, n = 10), IV (cp/rep + amitryptiline, n = 10) and V (cp/rep + ceramide + amitryptiline, n = 10). For detection of apoptosis anti-activated-caspase-3 and PARP-1 cleavage immunostaining were employed.</p> <p>Results</p> <p>In group I the percentage of apoptotic cardiomyocytes was significantly (p < 0.05) low if compared to group II revealing a time-dependent increase. In group III ceramid increased and in group IV amitryptiline inhibited apoptosis significantly (p < 0.05). In contrast in group V, under the influence of ceramide and amitryptiline the induction of apoptosis was partially suppressed.</p> <p>Conclusion</p> <p>Ceramid induces and amitryptiline suppresses apoptosis significantly in our ex vivo setting. This finding warrants further studies aiming to evaluate potential beneficial effects of selective inhibition of apoptosis inducing mediators on the suppression of ischemia/reperfusion injury in clinical settings.</p

Tuberculous pseudoaneurysms of the aortic arch

AbstractJ Thorac Cardiovasc Surg 2003;125:411-

Cerebral Protection During Surgery for Acute Aortic Dissection Type A

Background— Cerebral protection during surgery for acute aortic dissection type A relies on hypothermic circulatory arrest, either alone or in conjunction with cerebral perfusion. Methods and Results— The perioperative and intraoperative conditions of 1558 patients submitted from 44 cardiac surgery centers in German-speaking countries were analyzed. Among patients with acute aortic dissection type A, 355 (22.8%) underwent surgery with hypothermic circulatory arrest alone. In 1115 patients (71.6%), cerebral perfusion was used: Unilateral antegrade cerebral perfusion (ACP) in 628 (40.3%), bilateral ACP in 453 (29.1%), and retrograde perfusion in 34 patients (2.2%). For 88 patients with acute aortic dissection type A (5.6%), no circulatory arrest and arch intervention were reported (cardiopulmonary bypass–only group). End points of the study were 30-day mortality (15.9% overall) and mortality-corrected permanent neurological dysfunction (10.5% overall). The respective values for the cardiopulmonary bypass–only group were 11.4% and 9.1%. Hypothermic circulatory arrest alone resulted in a 30-day mortality rate of 19.4% and a mortality-corrected permanent neurological dysfunction rate of 11.5%, whereas the rates were 13.9% and 10.0%, respectively, for unilateral ACP and 15.9% and 11.0%, respectively, for bilateral ACP. In contrast with the ACP groups, there was a profound increase in mortality when systemic circulatory arrest times exceeded 30 minutes in the hypothermic circulatory arrest group ( P &lt;0.001). Mortality-corrected permanent neurological dysfunction correlated significantly with perfusion pressure in the ACP groups. Conclusions— This study reflects current surgical practice for acute aortic dissection type A in Central Europe. For arrest times less than 30 minutes, hypothermic circulatory arrest and ACP lead to similar results. For longer arrest periods, ACP with sufficient pressure is advisable. Outcomes with unilateral and bilateral ACP were equivalent. </jats:sec