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Background. Tricuspid valve regurgitation (TR) after orthotopic heart transplantation (OHT) is common. The aims of this study were to determine the prevalence of TR after OHT, to examine the correlation between its development and various variables, and to determine its outcomes. Methods. All 163 OHT patients who were followed up between 1988 and 2009 for a minimal period of 12 months were divided into those with no TR/mild TR and those with at least mild-moderate TR, as assessed by doppler echocardiography. These groups were compared regarding preoperative hemodynamic variables, surgical technique employed, number of endomyocardial biopsies, number of acute cellular rejections, incidence of graft vasculopathy, and clinical outcomes. Results. At the end of the followup (average 8.2 years) significant TR was evident in 14.1% of the patients. The development of late TR was found by univariate, but not multivariate, analysis to be significantly correlated with the biatrial surgical technique (P < 0.01) and the presence of graft vasculopathy (P < 0.001). TR development was found to be correlated with the need for tricuspid valve surgery but not with an increased mortality. Conclusions. The development of TR after OHT may be related to the biatrial anastomosis technique and to graft vasculopathy.

Electroporation, is known to induce cell membrane permeabilization in the reversible (RE) mode and cell death in the irreversible (IRE) mode. Using an experimental system designed to produce a continuum of IRE followed by RE around a single electrode we used MRI to study the effects of electroporation on the brain. Fifty-four rats were injected with Gd-DOTA and treated with a G25 electrode implanted 5.5 mm deep into the striata. MRI was acquired immediately after treatment, 10 min, 20 min, 30 min, and up to three weeks following the treatment using: T1W, T2W, Gradient echo (GE), serial SPGR (DCE-MRI) with flip angles ranging over 5-25°, and diffusion-weighted MRI (DWMRI). Blood brain barrier (BBB) disruption was depicted as clear enhancement on T1W images. The average signal intensity in the regions of T1-enhancement, representing BBB disruption, increased from 1887±83 (arbitrary units) immediately post treatment to 2246±94 20 min post treatment, then reached a plateau towards the 30 min scan where it reached 2289±87. DWMRI at 30 min showed no significant effects. Early treatment effects and late irreversible damage were clearly depicted on T2W. The enhancing volume on T2W has increased by an average of 2.27±0.27 in the first 24-48 hours post treatment, suggesting an inflammatory tissue response. The permanent tissue damage, depicted as an enhancing region on T2W, 3 weeks post treatment, decreased to an average of 50±10% of the T2W enhancing volumes on the day of the treatment which was 33±5% of the BBB disruption volume. Permanent tissue damage was significantly smaller than the volume of BBB disruption, suggesting, that BBB disruption is associated with RE while tissue damage with IRE. These results demonstrate the feasibility of applying reversible and irreversible electroporation for transient BBB disruption or permanent damage, respectively, and applying MRI for planning/monitoring disruption volume/shape by optimizing electrode positions and treatment parameters.

Myxoedema coma is the most lethal manifestation of hypothyroidism. It represents a true medical emergency, especially in the case of cardiovascular instability. Extracorporeal circulation is usually used for rewarming and for providing cardiac support in patients with severe hypothermia and, in addition, cardiovascular instability. We report the case of an 84-year-old woman who presented to the ED with accidental hypothermia associated with myxoedema that was successfully managed by veno-arterial extracorporeal blood rewarming. This case suggests that veno-arterial extracorporeal rewarming appears to achieve a rapid and consistent rewarming rate and is less invasive and more readily available than cardiopulmonary bypass., (© 2011 The Authors. EMA © 2011 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.)

Background: The involvement of mitochondria in pathological states, such as neurodegenerative diseases, sepsis, stroke, and cancer, are well documented. Monitoring of nicotinamide adenine dinucleotide (NADH) fluorescence in vivo as an intracellular oxygen indicator was established in 1950 to 1970 by Britton Chance and collaborators. We use a multiparametric monitoring system enabling assessment of tissue vitality. In order to use this technology in clinical practice, the commercial developed device, the CritiView (CRV), is tested in animal models as well as in patients., Methods and Results: The new CRV enables the optical monitoring of four different parameters, representing the energy balance of various tissues in vivo. Mitochondrial NADH is measured by surface fluorometry/reflectometry. In addition, tissue microcirculatory blood flow, tissue reflectance and oxygenation are measured as well. The device is tested both in vitro and in vivo in a small animal model and in preliminary clinical trials in patients undergoing vascular or open heart surgery. In patients, the monitoring is started immediately after the insertion of a three-way Foley catheter (urine collection) to the patient and is stopped when the patient is discharged from the operating room. The results show that monitoring the urethral wall vitality provides information in correlation to the surgical procedure performed.

Internationally accepted ethical standards are unequivocal in their prohibition of the use of organs recovered from executed prisoners: yet this practice continues in China despite indications that Ministry of Health officials intend to end this abhorrent practice. Recently published articles on this topic emphasize the medical complications that result from liver transplantation from executed 'donors' but scant attention is given to the source of the organs, raising concern that the transplant community may be becoming inured to unacceptable practice. Strategies to influence positive change in organ donation practice in China by the international transplant community are discussed. They include an absolutist policy whereby no clinical data from China is deemed acceptable until unacceptable donation practices end, and an incremental policy whereby clinical data is carefully evaluated for acceptability. The relative advantages and drawbacks of these strategies are discussed together with some practical suggestions for response available to individuals and the transplant community., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: Associations between cardiovascular diseases and serum enzymes or coagulation activities have been sufficiently documented in patients with myocardial infarction. However, the alterations of these biomarkers in patients with postinfarction myocardial rupture have rarely been reported. The aim of this study is to present the profiles of the markers in patients with postinfarction myocardial rupture., Methods: From 2004 to 2008, 19 consecutive patients were referred to this hospital for surgical repair of postinfarction myocardial rupture. Eight (42.1%) patients had free wall rupture, 5 (26.3%) had papillary muscle rupture, 5 (26.3%) had ventricular septal rupture, and 1 (5.3%) had double structure (ventricular septum + free wall) rupture. Thirteen patients survived the operation, and 6 died. Laboratory findings including serum enzymes and coagulation activities were collected and analyzed., Results: The coagulation markers and serum enzymes except for fibrinogen increased significantly after the development of myocardial rupture. Statistical differences in D-dimer, partial thromboplastin time, peak lactate dehydrogenase, peak creatine kinase and creatine kinase fraction MB were found between non-survivors and survivors. Troponin I values were elevated significantly during the early days after the onset or surgical repair of myocardial rupture. Multivariant regression analysis did not show any significant relationship between creatine phosphokinase fraction MB (Y) and D-dimer (X1) or fibrinogen (X2)., Conclusion: Myocardial rupture leads to extremely high serum enzyme and coagulation activities except for fibrinogen after the onset. The evaluation of these biomarkers may help in making diagnostic and treatment decisions and in judging the clinical prognosis of such patients.

Antifreeze proteins (AFP) are associated with protection from freezing. We measured the effect of type I antifreeze protein on spontaneous bursting of mixed neuronal/glial cultures using a multi-electrode array culture system. Antifreeze protein (10mg/ml) reversibly depressed bursting activity without inhibiting mitochondrial oxidative capacity. The effect of antifreeze protein on cold/re-warming injury was investigated in rat hippocampal slice cultures. Compared to bovine serum albumin at a similar concentration, antifreeze protein protected hippocampal neurons from 8h of profound hypothermia at (4 degrees C) followed by re-warming. The protection observed is believed to be associated with the inhibitory effect of antifreeze protein., (Copyright 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Background: A bicuspid aortic valve (BAV) is a common congenital heart disease, which affects 1-2% of the population. However, the relationship between BAVs and aortic dilation has not been sufficiently elucidated., Methods: A total of 241 BAV patients who were referred to this hospital for cardiac surgery over a 4.75-year period were included in this study. In addition to the clinical characteristics of the included patients, the morphological features of the aortic valve and aorta, the length of the left main coronary artery, and the laboratory findings (the coagulation and hematological parameters as well as the total cholesterol concentration) were determined and compared with those of the tricuspid aortic valve (TAV) patients., Results: The BAV patients were younger than the TAV patients for a valve surgery in the last 3 months of the study period. The BAV patients were predominantly male. Most of the BAVs that were surgically treated were stenotic, regurgitant, or combined, and only 19 (7.88%) were normally functioning valves. According to echocardiography or operative records, 148 (78.31%) were type A, 31 (16.40%) were type B, and 10 (5.29%) were type C. The left main coronary artery was much shorter in the BAV patients than it was in the TAV patients. There was no significant difference between BAV and TAV patients in the total cholesterol concentrations; whereas differences were noted between patients receiving lipid-lowering therapy and those not receiving lipid-lowering therapy. The dimensions of the aortic root, sinotubular junction, and ascending aorta were beyond normal limits, while they were significantly smaller in the BAV patients than in the TAV patients. They were also much smaller in patients receiving statin therapy than those not receiving statin therapy in both groups. Moreover, the aortic dilation in the BAV group was found to be significantly associated with patient age., Conclusions: The BAV patients developed aortic wall and aortic valve disorders at a younger age than the TAV patients and were predominantly male. Aortic dilation was observed in the aortic root, sinotubular junction, and ascending aortic segments in both the BAV and TAV patients undergoing surgical aortic valve replacement, although the BAV patients had a smaller degree of dilation than the TAV patients, and dilation was also significantly age-related in this group. The shorter left main coronary artery that the BAV patients possess may contribute to the progressive course of aortic dilation that these patients experience. Statin therapy did not affect the aortic annulus in either group, but did decrease the dimensions of the aortic root, sinotubular junction and ascending aorta. In general, statin therapy had a better effect on the aortas of the TAV patients than it did on those of the BAV patients.

The unicuspid aortic valve is a very rare congenital anomaly, which usually presents as aortic stenosis, incompetence, or a combination of both. Other congenital disorders may accompany this phenomenon and aortic dilatation and left ventricular hypertrophy are frequent complications. We present a case report of a young, symptomatic patient with a unicuspid aortic valve, complicated by dilatation of the aortic root and ascending aorta, with left ventricular hypertrophy. The patient recovered fully after a Bentall procedure.

Valvular tumors and tumor-like lesions may have similar morphological and clinical characteristics, and may place the patients at a high risk of stroke in different ways. From January 2004 to June 2008, 11 patients underwent surgery for a suspected valvular tumor. Valvular tumor and tumor-like lesions accounted for 0.32% of adult cardiac operations. Five (45.5%) valvular lesions were papillary fibroelastomas, one (9.1%) was myxoma, 2 (18.2%) were organized thrombi, and 3 (27.3%) were calcification lesions. There was a total of 5 (45.5%) atrioventricular valve lesions, 4 arising from the atrial side of the leaflets, and one from the ventricular side. All 5 (45.5%) semilunar valvular lesions were from the aortic valve. One (9.1%) lesion originated from the chorda tendinea of the mitral valve. All leaflet lesions were resected by a simple shave technique, and all the patients recovered favorably. Valvular tumor and tumor-like lesions are rare. Pre-operative differential diagnoses among these valvular lesions pose important clinical implications for appropriate treatment for the underlying diseases. Prompt therapeutic measures in view of the underlying diseases of the valvular lesions are essential to prevent potential embolic events.

Background: The identification and isolation of human cardiac progenitor cells (hCPCs) offer new approaches for myocardial regeneration and repair. Still, the optimal source of human cardiac progenitor cells and the influence of patient characteristics on their number remain unclear. Using a novel method to isolate human cardiac progenitor cells, we aimed to define the optimal source and association between their number and patient characteristics., Methods and Results: We developed a novel isolation method that produced viable cells (7 x 10(6)+/-6.53 x 10(5)/g) from various tissue samples obtained during heart surgery or endomyocardial biopsies (113 samples from 94 patients 23 to 80 years of age). The isolated cardiac cells were grown in culture with a stem cell expansion medium. According to fluorescence-activated cell sorting analysis, cultured cells derived from the right atrium generated higher amounts of c-kit(+) (24+/-2.5%) and Islet-1(+) cells (7%) in culture (mean of passages 1, 2, and 3) than did cultured cells from the left atrium (7.3+/-3.5%), right ventricle (4.1+/-1.6%), and left ventricle (9.7+/-3%; P=0.001). According to multivariable analysis, the right atrium as the cell source and female sex were associated with a higher number of c-kit(+) cells. There was no overlap between c-kit(+) and Islet-1 expression. In vitro assays of differentiation into osteoblasts, adipocytes, and myogenic lineage showed that the isolated human cardiac progenitor cells were multipotent. Finally, the cells were transplanted into infarcted myocardium of rats and generated myocardial grafts., Conclusions: Our results show that the right atrium is the best source for c-kit(+) and Islet-1 progenitors, with higher percentages of c-kit(+) cells being produced by women.

Pseudoaneurysm of the native sinus of Valsalva is exceedingly rare. We present a case of a 32-year-old male who was referred to the hospital after he had been symptomatic for 1.5 years. Transoesophageal echocardiography and computed tomography illustrated a pseudoaneurysm arising from the non-coronary sinus of Valsalva. A prompt operation was performed upon admission, and the patient recovered.

Background: Cardiac tumours are very uncommon and are the topic of little investigation. Imaging features offer reliable diagnostic evidence for cardiac tumours, but diagnostic confusion may arise when tumours with similar features are present., Methods: Between January 2003 and July 2008, 34 patients were operated on for cardiac tumours in this institute. The patients' ages ranged from 31 to 81 years with an average of 54.8 +/- 14.2 years. Thirty (88.2%) tumours were primary [19 (55.9%) myxomas, 8 (23.5%) papillary fibroelastomas, and 1 (2.9%) cavernous hemangioma were benign, 1 (2.9%) recurrent fibrous histiocytoma (undifferentiated sarcoma) and 1 (2.9%) leiomyosarcoma were malignant], and 4 (11.8%) were secondary [1 (2.9%) metastatic cardiac leiomyoma, and 3 (8.8%) were renal cell carcinomas]., Results: Cardiac myxomas represented more than half of the cardiac tumours of this patient series, necessitating surgical resection. More than half of these cardiac myxomas originated from the intraatrial septum with a stalk. Most of them appeared as a round or ovoid soft mass on echo, as a hypoattenuated lesion on computed tomography or magnetic resonance imaging, and with a soft gelatinous appearance on gross appearance. Cardiac papillary fibroelastomas were valvular or subvalvular, mostly pedicled by a short stalk, and all of them were pound 1 cm in size. The cavernous hemangioma was isointense on magnetic resonance imaging and tensile and slithy in gross specimen. Recurrent fibrous histiocytoma, leiomyosarcoma, intravenous leiomyoma and renal cell carcinoma resembled a myxoma on echocardiography due to their soft, friable, and mobile features. There were no misdiagnoses based on preoperative imaging features comparable to surgical and histopathologic findings in this surgical series., Conclusions: Imaging morphology plays a key role in the preoperative differential diagnosis of cardiac tumours. Imaging features could reliably predict primary versus secondary, and benign versus malignant among cardiac tumours. The accurate preoperative imaging assessment of cardiac tumours necessitating surgical resection has become increasingly important in the decision-making of a surgical approach, method, and resection extent.

Surgical procedures using hypothermic temperatures have been linked to complications such as seizures, impaired mental development and impaired memory. Although there is some evidence that the profound hypothermia (<12 ( composite function)C) used in these procedures may be contributing to these neurological impairments, skepticism remains because of lack of evidence from experimental studies isolating the effects of hypothermia on neuronal networks. In order to attain a better understanding of profound hypothermia effects on neurons during surgical procedures, we applied cold to a cultured in-vitro neuronal network. The typical pattern of activity of such cultures is in the form of synchronized bursts, in which most of the recorded neurons fire action potentials in a short time period. In most cases, the bursting activity shows one or more repeating precise spatio-temporal patterns (motifs) that are sustained over long periods of time. In this experimental study, neuronal networks grown on microelectrode arrays (MEA) are subjected to profound hypothermia for an hour and the collective dynamics of the network as a whole are assessed. We show, by using a similarity analysis that compares changes in the time delays between neuronal activation at different burst motifs, that neuronal networks survive total inhibition by profound hypothermia and retain their intrinsic synchronized burst motifs even with substantial generalized neuronal degeneration. By applying multiple sessions of cold, we also show a marked monotonic reduction in the rate of burst firing and in the number of spikes of each neuron after each session.

Objective: "Fast-track" pathways have been successfully used in low-risk, relatively young patients after all types of surgical procedures including cardiac surgery. An increase in the number of referrals of older patients for cardiac surgery prompted the present study on the use of a "fast-track" pathway in septuagenarians and octogenarians. Risk factors for the unsuccessful application of the "fast-track" pathway in these elderly patients were determined., Design: A retrospective observational study., Setting: A single tertiary-care, university-affiliated center., Participants: All 70-year-old or older patients undergoing cardiac surgery between January 1, 2004 and June 30, 2007 were included. Septuagenarians were compared with octogenarians., Measurements and Main Results: During the 42-month period, 860 cardiac operations were performed on 576 septuagenarians and 284 octogenarians. The "fast-track" pathway was successful in 54.5% and 37.3%, respectively. On multiple logistic regression analyses, stroke, renal failure, and procedures other than primary isolated coronary artery bypass graft surgery were independently associated with failed early extubation, delayed intensive care unit discharge, and delayed hospital discharge in both groups. Infections and atrial fibrillation were independent risk factors for delayed hospital discharge in both groups and delayed intensive care unit discharge in the octogenarians. In the octogenarians only, congestive heart failure was an independent risk factor for failed early extubation, delayed intensive care unit discharge, and delayed hospital discharge., Conclusions: A "fast-track" pathway may be applied in selected septuagenarians and octogenarians. Age alone should not exclude consideration for "fast-track" management.

Background: Patients in cardiogenic shock (CS) or with terminal heart failure (THF) are at imminent risk of death while waiting for heart transplantation (HTx). Implantation of left or bi-ventricular assist device (LVAD/BiVAD) as a bridge to HTx may save many of these doomed patients' lives., Patients and Methods: Between March 1994 and December 2006, 29 terminally ill patients (age 2.5-65 years, mean 48 years) underwent VADs implantation as bridge to HTx. The HeartMate VE LVAD was used in 18 patients, Thoratec pneumatic BiVAD in 7, Berlin Heart Excor BiVAD in one, and HeartMate II axial flow, Thoratec pneumatic and Biomedicus centrifugal LVADs in one each. Indications for VADs implantation were CS in 16 patients (55%) and intractable THF in 13 pts (45%). Etiologies were ischemic in 20 patients, idiopathic dilated, myocarditis and congenital in 2 patients each, and valvular, post partum and HTx graft vasculopathy in one patient each., Results: Seventeen patients (59%) survived VADs implantation and underwent HTx or are ongoing. Mean survival on VADs was 72 days (range 1-353 days, total 5.2 patient years). Seven patients (24%) were discharged home while on LVAD support for a mean of 146 days. Nine of the transplanted patients (64%) were discharged home. In 4 LVAD patients the cause of death was RV failure necessitating later implantation of RVAD., Conclusions: VADs implantation as bridge to HTx in CS or THF saves many of these doomed patients, sometimes providing quality out-of-hospital life while waiting for HTx. Early recognition of RV failure and liberal use of BiVAD is important.

The shortage of available donor hearts limits the number of cardiac transplantations worldwide and in Israel as well. This organ shortage results in 15%-20% annual mortality of heart transplant candidates. For the sub-group of hospitalized decompensated heart failure patients depending on continuous inotropic support (Status I), the annual mortality is over 50%. Suboptimal utilization of donor hearts has been one of the reasons for the organ shortage. In 2004, only 42% of the potential donor hearts in Israel were eventually transplanted. The objective of this report is to define guidelines regarding the suitability of potential cardiac donors allowing more liberal criteria for accepting borderline donor hearts. Implementing the new guidelines will permit the utilization of organs that otherwise would have been discarded.

Efficient and safe use of hypothermia during various neuro-medical procedures requires sound understanding of low temperature effects on the neuronal network's activity. In this report, we introduce the use of cultivated dissociated neuronal networks on temperature controlled multi-electrode arrays (MEAs) as a simple methodology for studying the long-term effects of hypothermia. The networks exhibit spontaneous activity in the form of synchronized bursting events (SBEs), followed by long intervals of sporadic firing. Through the use of our correlation method, these SBEs can be clustered into sub-groups of similar spatio-temporal patterns. Application of hypothermia to the network resulted in a reduction in the SBE rate, the spike intensity and an increase in inter-neuronal correlations. Within 2h following the cessation of hypothermia, the cultured network returned to its initial spatio-temporal SBE structure. These results suggest that the network survived cold exposure and demonstrate the feasibility of long-term continuous neural network recording during hypothermic conditions.

Background: All currently used energy sources in surgical ablation for atrial fibrillation create lesions via thermal injury. We report for the first time the in vivo results of a new nonthermal modality of epicardial atrial ablation called irreversible electroporation (IRE). IRE utilizes a sequence of electrical pulses that produce permanent nonthermal damage to tissue in a few seconds with sharp borders between affected and unaffected regions., Methods: Five pigs underwent beating heart surgical epicardial ablations of their right and/or left atrial appendages, utilizing a sequence of 8, 16, or 32 direct current pulses of 1500 to 2000 V, 100 micros each, at a frequency of 5 per second, applied between two 4-cm long parallel electrodes with an IRE pulse generator. Local temperature measurements were performed during ablations followed by electrical isolation testing by pacing. Animal hearts were excised 24 hours after surgery and processed histologically to evaluate the degree of myocardial tissue necrosis and transmurality., Results: A clear demarcation line between ablated and normal tissue, with no tissue disruption or charring, was observed on gross inspection of all lesions. Staining results showed complete transmural destruction of atrial tissue at the site of the electrode application in all 10 atrial lesions, measuring a mean of 0.9 cm in depth. Each 3- to 3.5-cm long lesion was created in 1 to 4 seconds with no local temperature change and with demonstration of electrical isolation., Conclusions: We propose a new modality to perform atrial ablations, which holds the potential of providing very swift, precise, and complete transmurality with no local heating effects.

Organ transplantation using organs taken from prisoners convicted to death is being practiced in China for the last two decades. These transplantations, which harshly violate medical ethics and international conventions, have become a prosperous market in China. This review presents details of the testimonies of a former prisoner and a Chinese physician who fled to the U.S.A., portraying the horrifying process of organ harvesting from executed prisoners, sometimes even before they are even dead. For years the Chinese authorities have denied the existence of this process, but following massive international diplomatic pressure they have recently publicly admitted to it for the first time. Many Israeli transplant candidates, who are desperate due to the organ shortage in Israel, seek their way to China in attempts to try and save their lives. The fact that they are currently being funded by all medical insurance companies constitutes a sort of formal approval to this atrocity. We, as a society, should stop this funding immediately, and divert all our human and financial resources to increase organ donation from brain-dead donors in Israel.

Background: Freeze-tolerant fish survive sub-zero temperatures by non-colligatively lowering the freezing temperature of their body fluids using anti-freeze proteins (AFPs). We sought to evaluate and compare the effects of prolonged sub-zero cryopreservation of transplanted rat hearts using AFP I or AFP III., Methods: Two heterotopic rat heart transplantation protocols were used. In Protocol 1 (n = 104), hearts (n = 8/group) were preserved for 12, 18 and 24 hours in University of Wisconsin solution (UW) at 4 degrees C, UW at -1.3 degrees C, UW/AFP I at -1.3 degrees C and UW/AFP III at -1.3 degrees C, with and without nucleation. Post-operative evaluation consisted of visual viability scoring of the hearts after 60 minutes. Protocol 2 (n = 58) involved evaluation of 24-hour post-transplant viability, echocardiography (fractional shortening [FS], left ventricular end-systolic and -diastolic diameter [ESD, EDD] and anterior and posterior wall systolic and diastolic thickness [AWT-S, AWT-D, PWT-S, PWT-D]), TUNEL staining and electron microscopy (EM) findings for hearts preserved for 18, 21 and 24 hours in UW at 4 degrees C or UW/AFP III at -1.3 degrees C., Results: Hearts preserved in UW at -1.3 degrees C with nucleation froze and died. Three of 8 hearts preserved in UW at 4 degrees C for 24 hours died, whereas all hearts preserved at -1.3 degrees C survived. Hearts preserved in UW/AFP for 18 and 24 hours at -1.3 degrees C had superior viability scores compared with those in UW at 4 degrees C. Hearts in AFP III at -1.3 degrees C displayed greater AWT-S and AWT-D (3.5 +/- 0.2 vs 2.4 +/- 0.2, p < 0.05, and 3.5 +/- 0.2 vs 2.2 +/- 0.2, p < 0.05, respectively) after 18-hour preservation. In the 21-hour preservation group, AFP-treated hearts displayed improved echocardiographic systolic contraction indices, including: improved FS (27 +/- 3.7 vs 15 +/- 4, p = 0.04); diminished ESD (0.28 +/- 0.57 vs 0.47 +/- 0.6, p < 0.05); greater AWT-S (3.4 +/- 0.18 vs 2.8 +/- 0.2, p < 0.05); and fewer positively TUNEL-stained nuclei per specimen (35 +/- 14 vs 5.3 +/- 2.7, p = 0.04). Also, improved EM scores were noted compared with UW at 4 degrees C., Conclusions: In prolonged sub-zero cryopreservation, AFPs protect the heart from freezing, improve survival and hemodynamics, and reduce apoptotic cell death.

The purpose of the present study was to evaluate whether AFPs protect the heart from freezing and improve survival and viability in subzero cryopreservation. Hearts were subject to 5 preservation protocols; University of Wisconsin solution (UW) at 4 degrees C, UW at -1.3 degrees C without nucleation, UW at -1.3 degrees C with nucleation, UW AFP I (15 mg/cm(3)) at -1.3 degrees C with nucleation, and in UW AFP III (15 mg/cm(3)) at -1.3 degrees C with nucleation. Hearts were preserved for 24, 28, and 32 h, rewarmed and connected to the working isolated perfusion system. Data [heart rate (HR), coronary flow (CF), and developed pressure (dP)] was collected 30 and 60 min after reperfusion. Hearts preserved at -1.3 degrees C without AFPs froze, while hearts preserved with AFP did not freeze when nucleation was initiated and survived. Survival and dP of hearts preserved for 24h at -1.3 degrees C using AFP III was better than those preserved at 4 degrees C, (dP; 1.4 vs. 0.8, p<0.05). Four of six hearts and six of six hearts died when preserved at 4 degrees C for 28 and 32 h, respectively, all of the hearts that were preserved at -1.3 degrees C with or without AFPs survived after 28 h (n=18) and 32 h (n=18). CF was higher in UW -1.3 degrees C group without attempted nucleation than in AFP I and AFP III groups after 28 and 32 h (3.4 vs. 1.7, p<0.05, and 3.4 vs. 1.7, p<0.05, respectively). In conclusion, AFPs were found to protect the heart from freezing and improve survival and dP (AFP III) in prolonged subzero preservation.

Background: Arctic fish survive subzero temperatures by producing a family of antifreeze proteins (AFPs) that noncolligatively lower the freezing temperature of their body fluids. We report 24-hour storage of mammalian hearts for transplantation at subzero temperatures using AFPs derived from arctic fish., Methods: Forty-two heterotopic transplantations were performed in isoimmune Sprague-Dawley rats. Harvested hearts were retrogradely infused with cold 4 degrees C University of Wisconsin (UW) solution and were preserved in a specialized cooling bath at two target temperatures, 4 degrees C and -1.3 degrees C for 12,18, and 24 hours (6 experiments/group). Preservation solutions were UW alone for the 4 degrees C group, and UW with 15 mg/mL AFP III for the -1.3 degrees C group. After hypothermic storage the hearts were heterotopically transplanted into isoimmune rats. Viability was assessed and graded on a scale of 0 to 6 (0 = no contractions to 6 = excellent contractions). Transplanted hearts were then fixed in vivo and were subject to electron microscopy and histopathologic examination., Results: None of the hearts preserved at -1.3 degrees C in UW/AFP III solution froze. All control hearts preserved at -1.3 degrees C without AFP protection froze and died at reperfusion. Viability of hearts preserved at -1.3 degrees C in UW/AFP III solution was significantly better after 18 hours of preservation, 30 and 60 minutes after reperfusion (median, 5 versus 3 and 6 versus 3, respectively; p < 0.05) and after 24 hours of preservation 30 and 60 minutes after reperfusion (median, 4.5 versus 1.5 and 5 versus 2, respectively; p < 0.05). Histologic and electron microscopy studies demonstrated better myocyte structure and mitochondrial integrity preservation with UW/AFP III solution., Conclusions: Antifreeze proteins prevent freezing in subzero cryopreservation of mammalian hearts for transplantation. Subzero preservation prolongs ischemic times and improves posttransplant viability.

Background: The use of the radial artery (RA) in coronary bypass operations has become increasingly popular in recent years, but there is almost no documentation regarding the midterm and long-term arm complications., Methods: Between January 1 and December 31, 1998, 109 patients underwent operations for myocardial revascularization employing a pedicled RA as 1 of the coronary grafts. The patients were surveyed for subjective arm morbidities at 2 times during their follow-up: short term (mean, 7 months postoperatively; range, 0.3-14 months) and long term (mean, 49 months postoperatively; range, 46-57 months)., Results: At the short-term follow-up, 33 (33.3%) of the patients had some complaints regarding the arm that was operated on, with 4 (4%) of the patients reporting arm disability with complaints that focused on pain (11, 11%), numbness (15, 15%), and parasthesias (12, 12%). At the longterm follow-up, only 9 patients (10.5%) still experienced some sort of inconvenience with the arm that was operated on, with 1 case of functional disability, 4 complaints (4.6%) of residual parasthesias, and 1 report (2.3%) each of pain or numbness. All but 2 of the patients with complaints at the short-term follow-up reported amelioration of symptoms at the long-term follow-up., Conclusion: It appears that severe arm disability early after RA harvesting is likely to dissolve with time. Our favorable late follow-up results support the continuation of the employment of the RA as a conduit for coronary artery bypass grafting operations.

Objective: Freeze tolerant fish and insects in nature are able to survive subzero temperatures by noncolligatively lowering the freezing temperature of their body fluids using a family of thermal hysteresis proteins (antifreeze proteins, AFPs) specific for each species. Past efforts to cryopreserve mammalian hearts using these proteins were unsuccessful. We report the first successful subzero cryopreservation of rat hearts using fish derived antifreeze proteins with preservation of myocyte structure., Methods: Heterotopic heart transplantations were performed in isoimmunic Sprague Dawley rats. Donors' hearts were arrested using University of Wisconsin (UW) solution and preserved in UW solution containing AFP I (six experiments) or AFP III (six experiments) at concentrations of 15-20 mg/cc for 2-6 h at subzero temperatures ranging from -1.1 to -1.3 degrees C. Four control experiments were performed by preserving harvested hearts in UW solution alone at -1.3 degrees C for 6 h. In all experiments ice was added in the solution for crystallization. Heterotopic transplantations were performed in the abdomen of the recipient rats. Viability was visually assessed and graded on a scale of 1 (poor contraction) to 6 (excellent contraction). The hearts were then fixed in vivo and processed for electron microscopy study., Results: All hearts preserved at subzero temperatures using AFP I or AFP III survived displaying viability scores of 4-6 1 h after transplantation. Three of the four control hearts that were preserved at -1.3 degrees C without the protective effect of AFP froze and died upon reperfusion. Electron microscopy study of hearts preserved with AFP demonstrated preservation of myocyte structure and mitochondrial integrity., Conclusion: Subzero cryopreservation of mammalian hearts for transplantation using AFP I or AFP III is feasible with preservation of myocyte structure and mitochondrial integrity.

The currently available intracorporeal assist systems and total artificial heart provide long-term support for patients terminally ill with congestive heart failure, often in an out-of-hospital environment. While they are currently widely used mainly as a long-term bridge to heart transplantation, their inherent risks of infection or stroke are prompting interest in future devices that will be smaller, fully implantable and hopefully stroke-free. These devices will be described in the last part of this review.

The currently available paracorporeal assist systems provide reliable short or long-term mechanical assistance to the failing heart, albeit necessitating continuous hospitalization. The intracorporeal assist systems, which provide out of hospital assistance, will be described in the next part of this review.

The high prevalence of end-stage heart failure and its influence on the quality of life, force the medical community to seek effective therapeutic modalities. Heart transplantation is the accepted therapy for such patients, nevertheless, a significant percentage of patients do not reach transplantation due to the shortage of donors. Therefore, the establishment of surgical alternatives is very important. Dynamic cardiomyoplasty is accepted as an alternative to heart transplantation. In this technique skeletal muscle is wrapped around the heart and stimulated synchronously with the heart itself. We describe the present status of this procedure.

Pulmonary embolism is a common event in hospitalized patients. In some cases it presents with hemodynamic collapse, indicating massive obliteration of the pulmonary vasculature and has a very grim prognosis; 2/3 of such patients die within 2 hours of onset of symptoms. We describe our experience in 13 patients with massive pulmonary embolism. An aggressive diagnostic and therapeutic approach, utilizing sophisticated imaging techniques, thrombolytic therapy and surgery, led to the survival of 8 of the patients. Our experience supports an aggressive approach in these seriously ill patients.

A major problem in cardiac transplantation is the death of candidates due to the increasing shortage of donors and the consequent longer waiting periods. To determine whether clinical markers for death could be identified in these patients, 168 adult candidates with heart failure (NYHA class III and IV) listed between August 1987 and December 1989 were analyzed. There were 104 patients with ischemic cardiomyopathy (ISCM) and 64 with idiopathic dilated cardiomyopathy (IDCM). Transplantation was performed in 93 patients (55%). Actuarial 1 year survival was 61% in the ISCM group and 78% in the IDCM group (P = NS). Freedom from sudden death at one year was significantly lower in the ISCM group (73%) than in the IDCM group (96%) (P < 0.01). The rate of patients who did not die from terminal myocardial failure was 83% in the ISCM group and 81% in the IDCM group (P = NS). There were no significant differences between the two groups in right atrial, pulmonary artery, and pulmonary wedge pressures, transpulmonic pressure gradient, pulmonary vascular resistance, cardiac index, and ejection fraction. We conclude that candidates for cardiac transplantation with ISCM are at higher risk for sudden death during the first year on the waiting list than patients with IDCM. These results warrant consideration of aggressive arrhythmia control measures, including an automatic implantable defibrillator, to "bridge" these high risk patients to transplantation.

Platelet transfusion and aprotinin administration improve platelet function and clinical hemostasis after extracorporeal circulation. To compare two methods of improving postoperative hemostasis, we preoperatively randomized 40 patients undergoing various open heart procedures into two groups. Group A included 20 patients who, immediately after bypass, received single-donor plateletpheresis concentrates collected from ABO-compatible donors (Baxter Autopheresis-C System). They were compared with 20 patients who received high-dose aprotinin (6 x 10(6) KIU) before and during cardiopulmonary bypass (group B). Group A patients showed significantly higher platelet count after single-donor plateletpheresis concentrate transfusion (157 +/- 36 x 10(9)/L compared with 118 +/- 42 x 10(9)/L (p < 0.05). However, platelet aggregation on extracellular matrix was better in group B (3.4 +/- 0.7 versus 2.8 +/- 0.9; p < 0.05). Total 24-hour blood loss and exposure to homologous blood products were significantly less in group B (396 +/- 125 mL and 1.1 +/- 1.6 units compared with 617 +/- 233 mL and 5.4 +/- 3.4 units; p < 0.01). Despite higher platelet count in patients after single-donor plateletpheresis concentrates transfusion, hemostasis in patients receiving aprotinin is better due to improved platelet function.

Percutaneous balloon pericardiostomy was performed in eight severely ill patients with malignancy (seven patients) and chronic renal failure (one patient). To investigate the feasibility of balloon pericardiostomy as a bedside procedure, echocardiography was used in addition to fluoroscopy in monitoring the procedure. The pericardium was entered from the standard subxiphoid site. An 18 to 25 mm, 3 or 4 cm long, balloon catheter, introduced over a stiff guidewire was inflated across the parietal pericardium. Creation of a pericardial opening was obtained in each of the eight patients. Bleeding from the needle entry site was the only complication observed in one patient. The balloon catheter could be localized by echocardiography only in 2/8 cases. Two patients died, 3 and 14 days after the procedure, from the primary disease; six patients were still alive at follow-up ranging from 32 to 342 days. No recurrence of cardiac tamponade was observed in any patient. Percutaneous balloon pericardiostomy is efficacious and safe in relieving pericardial tamponade and preventing its recurrence in severely ill patients. Fluoroscopy is needed to monitor the procedure. The value of echocardiography is limited for follow-up controls of pericardial effusion.

Rupture of the myocardium in the setting of acute myocardial infarction has a universally grim prognosis. The time that elapses between diagnosis and definitive therapy is the most critical determinant of the patient's outcome when death is not instantaneous. Survivors of this catastrophic event have not been frequently reported. We present a case of free wall left ventricular rupture in a patient with an acute myocardial infarction hospitalized in the Cardiac Care Unit of a small community hospital. The patient was successfully transferred to the referral institution for surgery. Rapid diagnosis, primary bedside therapy, and utilization of new surgical techniques helped obtain a good outcome.

To evaluate the effect of low-dose aprotinin during cardiopulmonary bypass on platelet function and clinical hemostasis, 30 patients undergoing various cardiopulmonary bypass procedures employing bubble oxygenators were randomized to receive either low-dose aprotinin (2 x 10(6) KIU in the cardiopulmonary bypass priming solution, 15 patients [group A]) or placebo (15 patients [group B]). Blood samples were collected before and after cardiopulmonary bypass to assess platelet count and aggregation on extracellular matrix, which was studied by a scanning electron microscope. On a scale of 1 to 4 preoperative mean platelet aggregation grades were similar in both groups (3.8 +/- 0.5 and 3.5 +/- 0.5 for groups A and B, respectively). Postoperatively, platelet aggregation on extracellular matrix decreased slightly in group A (2.8 +/- 1.3; p < 0.01) and significantly in group B (1.3 +/- 0.5; p < 0.001). Eleven of the 15 patients in group A remained in aggregation grade 3 or 4 compared with none of the group B patients. Platelet count was similar in both groups preoperatively and postoperatively. Total 24-hour postoperative bleeding and blood requirement were lower in the aprotinin group (487 +/- 121 mL and 2.3 +/- 1.0 units) than in the placebo group (752 +/- 404 mL and 6.8 +/- 5.1 units; p < 0.01). These results show that the use of low-dose aprotinin during cardiopulmonary bypass provides improved postoperative hemostasis, which might be related to the protection of the platelet aggregating capacity.

Background: Administration of aprotinin during extracorporeal circulation reduces blood loss and improves platelet function., Methods and Results: To evaluate the protective effect of aprotinin on platelets, 50 patients undergoing cardiopulmonary bypass were randomized before surgery to one of three groups. Seventeen patients (group A) received continuous high-dose aprotinin (7 x 10(6) KIU) during cardiopulmonary bypass, 17 (group B) received a single bolus of aprotinin in the pump prime (2 x 10(6) KIU), and 16 (group C) received placebo. Scanning electron microscopy was used to evaluate platelet aggregation on extracellular matrix. The platelet function was graded from 1 to 4, with grade 4 being normal aggregation. Immediately after cardiopulmonary bypass, 16 patients in group A (94%) reached preoperative aggregation grade (mean grade, 3.4 +/- 0.7) compared with nine of 17 in group B (52%) (mean grade, 2.9 +/- 1.2), and none in group C (0%) (mean grade, 1.4 +/- 0.5; p < 0.001). Postoperative platelet count did not differ significantly among the three groups. After surgery, group A bled less than groups B and C (395 +/- 120 versus 488 +/- 135 and 780 +/- 408 ml, respectively; p < 0.01). Patients in the aprotinin groups received fewer red blood cell units (0.9 +/- 1.2 and 1.9 +/- 1.2 versus 3.4 +/- 1.9, respectively; p < 0.01) and were exposed to less homologous blood products (1.3 +/- 1.7 and 2.1 +/- 1.1 versus 6.1 +/- 5, respectively; p < 0.001)., Conclusions: By preserving platelet function, aprotinin improves postoperative hemostasis in all patients who receive high dose and in most who receive low dose.

To evaluate the functional integrity of platelets in patients administered the proteinase inhibitor aprotinin during cardiopulmonary bypass, 20 patients undergoing a complicated and prolonged open heart operation were studied. They were randomized to receive either a high dose of aprotinin (total dose, 6 to 7 x 10(6) KIU) before and during cardiopulmonary bypass (10 patients) or a placebo (10 patients). Blood samples were collected preoperatively, at the termination of bypass, and 90 minutes thereafter to assess platelet count and aggregation on extracellular matrix, which was studied by scanning electron microscopy. On a scale of 1 to 4, mean preoperative platelet aggregation grades were similar in both groups (3.5 +/- 0.5). Postoperatively, at the termination of cardiopulmonary bypass and 90 minutes thereafter, all 10 patients treated with aprotinin revealed normal, unchanged platelet aggregation (grade, 3.5 +/- 0.5), whereas all placebo-treated patients showed severely disturbed aggregation (grade, 1.4 +/- 0.5) (p less than 0.001). The platelet count was similar in both groups before and after operation (preoperatively, 182 +/- 75 x 10(9)/L and 146 +/- 30 x 10(9)/L, and postoperatively, 87 +/- 13 x 10(9)/L and 80 +/- 27 x 10(9)/L for the aprotinin and placebo groups, respectively). Total 24-hour postoperative bleeding and blood requirement were significantly lower in the aprotinin group (371 +/- 84 mL and 2 +/- 0.7 units, respectively) compared with the placebo group (608 +/- 28 mL and 3.4 +/- 1.3 units, respectively) (p less than 0.01). These results demonstrate that improved postoperative hemostasis is directly related to the complete preservation of platelet function achieved by the protective properties of aprotinin.

Review of 463 heart transplants was undertaken to examine the relationship between level of panel-reactive antibody (PRA) and a standard donor-specific lymphocytotoxic crossmatch (LXM) on the incidence of death from hyperacute, acute, and chronic rejection. Death from chronic rejection was defined as being caused by graft atherosclerosis. Hyperacute rejection was diagnosed in 18 allografts, and only two recipients had PRA greater than 10% and another two a positive LXM. Five-year actuarial freedom from death caused by all forms of rejection correlated with PRA values as follows: PRA 0% to 10% (415 patients), 85%; PRA 11% to 25% (29 patients), 68%; PRA greater than 25% (19 patients), 57% (p less than 0.005). Additionally, there was a positive linear relationship between PRA and duration of acute rejection episodes in the first 3 months after transplantation. A positive retrospective donor-specific LXM was present in 42 of 401 patients; most of them (32 patients) were low positive (10% to 50% cell death), and none could be correlated with antibody specificity toward donor HLA antigens. Five-year actuarial freedom from death caused by rejection was 83% in those with a negative LXM, 74% in those with low-positive, and 79% in those with high-positive LXM (p = NS). Negative LXM result did not reduce the risk of death caused by rejection in any of the PRA subgroups. While PRA greater than 10% is a risk factor for rejection-related events, a negative LXM in patients with an elevated PRA does not reduce the risk of death resulting from acute or chronic rejection.

Increased mean arterial pressure during the aortic crossclamp period while on cardiopulmonary bypass was usually treated by us with hypotensive drugs. We noticed, however, that aspirating shed excess pulmonary venous blood from the open pleural cavities causes an immediate reduction in mean arterial pressure, obviating the need for any further pharmaceutical intervention. In this study we investigated the relationship between the reduction in mean arterial pressure and the levels of prostacyclin and prostaglandin E2 in the peripheral and pulmonary venous blood. Ten men undergoing coronary bypass operations had 21 episodes of increased mean arterial pressure (106.9 +/- 11.4 mm Hg) during aortic crossclamping, which was reduced to 67.4 +/- 11.4 mm Hg (p less than 0.001) only by aspirating a mean of 490 ml (range 150 to 1100 ml) of pulmonary venous blood from the pleurae back into the circulation. Mean peripheral prostacyclin level, measured as 6-keto-prostaglandin F1 alpha, and prostaglandin E2 level, both measured by radioimmunoassay technique, were significantly lower at peak mean arterial pressure (419 +/- 180 and 59.5 +/- 21.2 pg/ml) than at lowest mean arterial pressure (632 +/- 271 and 96.7 +/- 52.4 pg/ml for 6-keto-prostaglandin F1 alpha and prostaglandin E2, respectively; p less than 0.001). Prostaglandin F1 alpha and prostaglandin E2 levels in the aspirated pulmonary venous blood were 2309 +/- 3098 pg/ml and 749 +/- 909 pg/ml, respectively. The hypotensive effect of shed pulmonary venous blood that is aspirated back from the pleurae into the circulation seems to be mediated by the high levels of prostacyclin and prostaglandin E2, both powerful vasodilators.

Prevention of disturbed flow (e.g., flow stasis) and consequent thrombosis in heart pumps is based upon design characteristics determined during laboratory bench tests. These tests employ optimal filling and emptying characteristics, such as the full-fill to complete empty mode in the Novacor left ventricular assist system. Filling characteristics of the Novacor LVAS were examined during the first 48 hours after implantation in 14 patients. Fill volume of the pump was reduced in pathologic states, such as cardiac tamponade, and following the initiation of right ventricular mechanical circulatory support. In addition, multiple regression analysis revealed that right ventricular function measured by the amount of inotropic support required, the right ventricular ejection fraction, and the total pulmonary resistance, significantly predicted left ventricular assist pump fill volume during the first 48 hours of support. Flow visualization simulating these clinical conditions of incomplete filling suggest inadequate valve washing, particularly around the inlet valve and its conduit, which may predispose to thrombus formation.

Cardiac tamponade can be a major complication after implantation of the Novacor left ventricular assist system (LVAS). Between 1987 and 1989, 14 patients received an LVAS as a bridge to cardiac transplantation: 3 developed early tamponade (33 +/- 12 hr postoperatively) and 5 were diagnosed with a late tamponade (9.4 +/- 3.2 days postoperatively). One patient had both early and late tamponade. Early tamponade was more common in those with increased perioperative blood loss (5,270 +/- 1,942 ml vs. 1,420 +/- 1,160 ml in other patients, p less than 0.05). Early tamponade was suggested by reduction in mean arterial pressure (74 +/- 1 to 64 +/- 3 mmHg), LVAS output (5 +/- 0.5 to 2.7 +/- 0.7 L/min), LVAS stroke volume (55 +/- 4 to 23 +/- 5 ml), and an increase in central venous pressure (13 +/- 1 to 21 +/- 1 mmHg, p less than 0.05 for all values). Late tamponade was associated with a marked rise in central venous pressure (14 +/- 1 to 22 +/- 2 mmHg, p less than 0.05), with only a mild decrease in LVAS output (4.9 +/- 1 to 3.8 +/- 0.9 L/min) and stroke volume (49 +/- 8 to 36 +/- 3 ml), without a significant change in mean arterial pressure. Two of these five late episodes occurred in patients who were anticoagulated with heparin (PTT 52 and 100 sec), and in one other with warfarin (PT 27 sec, PTT 55 sec); two patients were not on any anticoagulants. Surgical drainage of pericardial effusions, and especially of clotted blood found frequently posterior to the left ventricle in the space created by the LVAS decompressed left ventricle, resulted in an immediate return of all hemodynamic measurements to normal in both early and late tamponade.

It has recently been shown that the hemostatic effect of 1 unit of fresh whole blood is equivalent to the effect of 8 to 10 platelet units. This study was designed to evaluate the effect of short periods of cold (4 degrees C) storage on the hemostatic effect of fresh whole blood transfusion in 36 patients immediately after cardiopulmonary bypass. Twelve patients (group A) received unrefrigerated fresh whole blood, 12 (group B) received fresh whole blood after 5 hours' storage at 4 degrees C, and 12 (group C) after 24 hours' storage at 4 degrees C. For evaluation of platelet function, a method with an extracellular matrix and an electron microscope was used. The platelet function was graded from 1 to 4, with grade 4 being normal aggregation. Postoperatively, group A patients bled less than groups B and C (267 +/- 42 versus 397 +/- 72 and 601 +/- 172 ml/24 hr, respectively, p less than 0.001) and therefore received fewer blood units (1.4 +/- 0.5 versus 2 +/- 0.9 and 3 +/- 1.4, respectively, p less than 0.01). Five patients of group A (42%) reached grade A aggregation after transfusion of unstored fresh whole blood, compared with two (17%) of group B and none (0%) of group C (p less than 0.01). Posttransfusion platelet count and mean platelet volume were not significantly different in the three groups. We conclude that storage at 4 degrees C, even for a short period of 5 hours, diminishes the hemostatic effect of fresh whole blood by decreasing platelet aggregability.