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Background: Recent evidence suggests that cancer and cardiovascular diseases are associated. Chemotherapy drugs are known to result in cardiotoxicity, and studies have shown that heart failure and stress correlate with poor cancer prognosis. However, whether cardiac remodeling in the absence of heart failure is sufficient to promote cancer is unknown. Methods: To investigate the effect of early cardiac remodeling on tumor growth and metastasis colonization, we used transverse aortic constriction (TAC), a model for pressure overload–induced cardiac hypertrophy, and followed it by cancer cell implantation. Results: TAC-operated mice developed larger primary tumors with a higher proliferation rate and displayed more metastatic lesions compared with controls. Serum derived from TAC-operated mice potentiated cancer cell proliferation in vitro, suggesting the existence of secreted tumor-promoting factors. Using RNA-sequencing data, we identified elevated mRNA levels of periostin in the hearts of TAC-operated mice. Periostin levels were also found to be high in the serum after TAC. Depletion of periostin from the serum abrogated the proliferation of cancer cells; conversely, the addition of periostin enhanced cancer cell proliferation in vitro. This is the first study to show that early cardiac remodeling nurtures tumor growth and metastasis and therefore promotes cancer progression. Conclusions: Our study highlights the importance of early diagnosis and treatment of cardiac remodeling because it may attenuate cancer progression and improve cancer outcome.

Background Chronic pressure overload and a variety of mediators induce concentric cardiac hypertrophy. When prolonged, cardiac hypertrophy culminates in decreased myocardial function and heart failure. Activation of the extracellular signal-regulated kinase (ERK) is consistently observed in animal models of hypertrophy and in human patients, but its role in the process is controversial. Methods We generated transgenic mouse lines with cardiomyocyte restricted overexpression of intrinsically active ERK1, which similar to the observations in hypertrophy is phosphorylated on both the TEY and the Thr207 motifs and is overexpressed at pathophysiological levels. Results The activated ERK1 transgenic mice developed a modest adaptive hypertrophy with increased contractile function and without fibrosis. Following induction of pressure-overload, where multiple pathways are stimulated, this activation did not further increase the degree of hypertrophy but protected the heart through a decrease in the degree of fibrosis and maintenance of ventricular contractile function. Conclusions The ERK pathway acts to promote a compensated hypertrophic response, with enhanced contractile function and reduced fibrosis. The activation of this pathway may be a therapeutic strategy to preserve contractile function when the pressure overload cannot be easily alleviated. The inhibition of this pathway, which is increasingly being used for cancer therapy on the other hand, should be used with caution in the presence of pressure-overload.

Objective: Despite significant advances in the understanding of vein graft remodeling during the post-implantation, vein graft disease is still a major limitation of surgical revascularization. The study objective was to evaluate the performance of a new cobalt chrome external support device designed to mitigate vein graft remodeling and development of intimal hyperplasia. Methods: Bilateral carotid interposition of reversed saphenous vein graft segments was performed in seven‏ adult sheep. Following completion of the first anastomosis, randomization was performed to allocate the experimental and control grafts in each animal. Post-procedure, Doppler US was used to assess grafts lumen diameter at T0 and then 3-5 and 12-14 weeks after surgery. At 12-14 weeks, all sheep underwent angiography to assess grafts patency and lumen uniformity (coefficient of variance - CV) after which they were sacrificed, and all grafts were harvested for microscopic histological analysis. Results: Baseline (T0) internal diameter was not significantly different between the supported and unsupported grafts. At twelve to fourteen weeks, the internal diameter of supported grafts remained unchanged and was significantly lower compared to the non-supported grafts (6.6mm±0.4mm vs. 12.8mm±4.0mm respectively, p= 0.0001). Percentage coefficient of variance (%CV) was 4.6%±4.3 in the supported grafts as opposed to average CV% of 14.7%±6.5 in the non-stented group (p=0.011). Neointimal area was significantly lower in the stented compared to the non-stented group (1.4 mm2±3.3mm2 versus 9.6mm2±9.7mm2 respectively, p=0.009). Conclusions: External support of vein grafts using a braided cobalt chrome external stent reduces early vein graft remodeling and mitigates the development of neointimal hyperplasia. [Arch Clin Exp Surg 2018; 7(3.000): 108-115]

We have previously reported that the topical application of erythropoietin (EPO) to cutaneous wounds in rats and mice with experimentally induced diabetes accelerates their healing by stimulating angiogenesis, reepithelialization, and collagen deposition, and by suppressing the inflammatory response and apoptosis. Aquaporins (AQPs) are integral membrane proteins whose function is to regulate intracellular fluid hemostasis by enabling the transport of water and glycerol. AQP3 is the AQP that is expressed in the skin where it facilitates cell migration and proliferation and re-epithelialization during wound healing. In this report, we provide the results of an investigation that examined the contribution of AQP3 to the mechanism of EPO action on the healing of burn wounds in the skin of pigs with experimentally induced type 1 diabetes. We found that topical EPO treatment of the burns accelerated their healing through an AQP3-dependent mechanism that activates angiogenesis, triggers collagen and hyaluronic acid synthesis and the formation of the extracellular matrix (ECM), and stimulates reepithelialization by keratinocytes. We also found that incorporating fibronectin, a crucial constituent of the ECM, into the topical EPO-containing gel, can potentiate the accelerating action of EPO on the healing of the burn injury.

Background Myocardial ischemia causes contractile dysfunction in ischemic, stunned, and tethered regions with larger infarcted zones having a negative prognostic impact on patients' outcomes. To distinguish the infarcted myocardium from the other regions, we investigated the diagnostic potential of circumferential strain (CS) and radial strain (RS) during the acute and chronic stages of myocardial infarction. Methods Ten pigs underwent 90-minute occlusion of the left anterior descending artery, followed by reperfusion. Echocardiography was performed at baseline, after 90-minute occlusion, and at 2 hours, 30, and 60 days postreperfusion. CS and RS were measured using speckle tracking echocardiography. Subsequently, the pigs were sacrificed, and histological analysis for infarct size was performed. Results After 90-minute occlusion, reduced strains were detected for all segments (infarcted anterior wall – baseline: CS: −17.6 ± 5.7%, RS: 54.4 ± 16.9%; 90 min: CS: −10.3 ± 3.0%, RS: 23.3 ± 7.0%; tethered posterior wall – baseline: CS: −18.4 ± 3.5%, RS: 68.7 ± 21.1%; 90 min: CS: −10.7 ± 6.4%, RS: 34.5 ± 14.7%, P < 0.001). However, postsystolic shortening was detected only in the infarcted segments, and the time-to-peak CS was 25% longer (P < 0.05). At 30 and 60 days postreperfusion, time-to-peak CS could only detect large scars in the anterior and anterior-septum walls (P < 0.05), while peak CS also detected smaller scars in the lateral wall (P < 0.05). RS failed to distinguish between normal, stunned/tethered, and infarcted myocardium. Conclusions During occlusion and 2 hours postreperfusion, time-to-peak CS could distinguish between infarcted and stunned/tethered myocardial segments, while at 30 and 60 days postreperfusion, peak CS was the best detector of infarction.

BACKGROUND The current cornerstone treatment of myocardial infarction (MI) is restoration of coronary blood flow by means of thrombolytic therapy or primary percutaneous coronary intervention. However, reperfusion of ischemic myocardium can actually provoke tissue damage, defined as "ischemia-reperfusion (I/R) injury." TVP1022 [the S-isomer of rasagiline (Azilect), FDA-approved anti-Parkinson's drug] was found to exert cardioprotective activities against various cardiac insults, such as chronic heart failure and I/R, in rat models. Therefore, we tested the hypothesis that TVP1022 will provide cardioprotection against I/R injury and post-MI remodeling in a pig model. METHODS For inducing MI, we used an I/R model of midleft anterior descending artery occlusion for 90 minutes followed by follow-up for 8 weeks in 18 farm pigs (9 pigs in each group, MI + TVP1022 or MI + Vehicle). Echocardiographic measurements were performed and cardiac scar size was calculated using histopathological methods. For fibrosis evaluation, we measured the interstitial collagen volume fraction in the remote noninfarcted tissue. RESULTS TVP1022 administration significantly decreased cardiac scar size, attenuated left ventricular dilation, and improved cardiac function assessed by segmental circumferential strain analysis. Furthermore, TVP1022 significantly reduced myocardial fibrosis 8 weeks post-MI. CONCLUSIONS Collectively, these findings indicate that TVP1022 provides prominent cardioprotection against I/R injury and post-MI remodeling in this I/R pig model.

Background Narrowing of the coronary sinus (CS) has recently emerged as a new therapeutic option for the treatment of patients with chronic refractory angina pectoris. The results of the preclinical study presented here, evaluate the safety, feasibility, and efficacy of reducer implantation in a swine model with and without myocardial ischemia. Methods and results The study included a safety/feasibility arm, and a safety/efficacy arm. In the safety/feasibility arm, reducers were implanted in 26 mini swine; follow up of up to 6 months included cardiac catheterization with CS angiogram, and histological evaluation of the stented segments of the CS. In the safety/efficacy arm, eight swine with evidence of inducible myocardial ischemia were divided into reducer implantation group (n = 4) and a control group (n = 4). Follow-up in this arm included 6 weeks and 6 months dobutamine stress echo and myocardial contrast echo to evaluate severity and extent of ischemia. In the safety/feasibility arm (n = 26), reducers were implanted with procedural success rate of 100% and with no short or long-term complications. All CS reducers were found to be patent at the time of sacrifice. In the safety/efficacy arm, all four animals with myocardial ischemia that underwent reducer implantation showed improvement in ischemia parameters at 6 weeks and 6 months follow-up, with no mortality. Among the control group, no improvement in ischemia parameters was observed and three out of four animals died. Conclusions Narrowing of the CS using percutaneous implantation of the reducer in swine is feasible, safe, and improves the extent and severity of ischemia.

c-Jun dimerization protein (JDP2) and Activating Transcription Factor 3 (ATF3) are closely related basic leucine zipper proteins. Transgenic mice with cardiac expression of either JDP2 or ATF3 showed maladaptive remodeling and cardiac dysfunction. Surprisingly, JDP2 knockout (KO) did not protect the heart following transverse aortic constriction (TAC). Instead, the JDP2 KO mice performed worse than their wild type (WT) counterparts. To test whether the maladaptive cardiac remodeling observed in the JDP2 KO mice is due to ATF3, ATF3 was removed in the context of JDP2 deficiency, referred as double KO mice (dKO). Mice were challenged by TAC, and followed by detailed physiological, pathological and molecular analyses. dKO mice displayed no apparent differences from WT mice under unstressed condition, except a moderate better performance in dKO male mice. Importantly, following TAC the dKO hearts showed low fibrosis levels, reduced inflammatory and hypertrophic gene expression and a significantly preserved cardiac function as compared with their WT counterparts in both genders. Consistent with these data, removing ATF3 resumed p38 activation in the JDP2 KO mice which correlates with the beneficial cardiac function. Collectively, mice with JDP2 and ATF3 double deficiency had reduced maladaptive cardiac remodeling and lower hypertrophy following TAC. As such, the worsening of the cardiac outcome found in the JDP2 KO mice is due to the elevated ATF3 expression. Simultaneous suppression of both ATF3 and JDP2 activity is highly beneficial for cardiac function in health and disease.

We hypothesized that attachment of elastic coil to the left ventricular (LV) wall, capable of exerting outward forces may allow the transfer of energy from systole to diastole and improve diastolic function.An extra-ventricular-device, composed of a series of elastic elements interposed between spiral screws attached to the epimyocardium of the LV free-wall was developed. The hemodynamic and mechanical effects of the device were tested using a computerized model, an in vitro model utilizing a computerized-controlled fluid pump, eight healthy sheep and 10 mini-pigs induced with diastolic dysfunction by renal wrapping. The computerized and in vitro models predicted a reduction of the LV diastolic pressure curve and partial normalization of the pressure-volume loop. The sheep study demonstrated preservation of animal's wellbeing including maintaining cardiac mechanical function with stable energy transfer from systole to diastole throughout the 6 months follow-up. The mini-pigs study showed an increase in the early diastolic to systolic strain-rate ratio in the mid-endocardial level (23 ± 10%, P = 0.008) and an increase in early apical reverse rotation rate of 50% (P = 0.016 compared to control).This study presents a novel concept of using a mechanical device to transfer energy from systole to diastole, potentially enhancing diastolic function.

Purpose To analyze the stability, visibility, and histology of a novel implantable soft-tissue marker (nonradioactive and radioactive) implanted in dog prostate and rabbit liver. Methods and Materials A total of 34 nonradioactive and 35 radioactive markers were implanted in 1 dog and 16 rabbits. Stability was assessed by measuring intermarker distance (IMD) variation relative to IMDs at implantation. The IMDs were measured weekly for 4 months in the dog and biweekly for 2–4 weeks in the rabbits. Ultrasound and X-ray imaging were performed on all subjects. Computed tomography and MRI were performed on the dog. Histologic analysis was performed on the rabbits after 2 or 4 months. Results A total of 139 measurements had a mean (± SD) absolute IMD variation of 1.1 ± 1.1 mm. These IMD variations are consistent with those reported in the literature as due to random organ deformation. The markers were visible, identifiable, and induced minimal or no image artifacts in all tested imaging modalities. Histologic analysis revealed that all pathologic changes were highly localized and not expected to be clinically significant. Conclusions The markers were stable from the time of implantation. The markers were found to be compatible with all common medical imaging modalities. The markers caused no significant histologic effects. With respect to marker stability, visibility, and histologic analysis these implanted fiducials are appropriate for soft-tissue target positioning in radiotherapy.

Purpose Conventional imaging and navigation during intravascular intervention employ fluoroscopic positioning of intracoronary devices. It may also include intravascular ultrasound (IVUS), allowing two-dimensional slice visualization of blood vessels for enhanced imaging, diagnosis, and stent placement. We report the use of an innovative 3D imaging system (GIVUS™), as well as stent placement (Guided Stent™) using a new non-fluoroscopic, intra-coronary Medical Positioning System (MPS™; MediGuide Ltd., Israel). Methods The GIVUS™ system consists of a miniaturized sensor that might be assembled on tips of various catheters (such as IVUS and stent delivery system) and provides accurate real-time position and orientation, enabling real-time tracking of a catheter tip in 3D space. GIVUS™ is the integration of two technologies, MPS™ and IVUS, thus providing automatic real-time quantitative 3D reconstruction of an inspected vessel. The GIVUS system was used to accurately navigate and deploy 12 stents in six adult pigs. 2D angiogram roadmaps and 3D reconstructed models were used to place stents at pre-defined locations in different coronary arteries close to bifurcations. Results GIVUS™ 3D image reconstruction was completed and displayed within 15 s after finishing pullback. MPS tracked the fluoroscopic image with a mean accuracy of 0.210 ± 0.306 mm. Pathologic measurements proved a high accuracy of stents deployment: 11 of 12 stents were less than 1 mm from selected bifurcation site, 1 was 2 mm into the bifurcation. Conclusions The MPS™ non-fluoroscopic system allows highly accurate computer-assisted stent navigation and deployment. The MPS™ system is a promising new method used to improve ease and accuracy of stent/device placement during intravascular interventions.

Glatiramer acetate (GA, Copaxone, copolymer 1) for injection is an approved drug for relapsing-remitting multiple sclerosis. The clinical and immunological effects of GA were extensively studied in experimental autoimmune encephalomyelitis (EAE), the experimental animal model for MS. The effect of oral administration of GA was tested in both rodents and primates in acute as well as in chronic relapsing (CR) models of EAE. Oral GA was found to suppress acute EAE induced in rats, mice, and rhesus monkeys. The effect of GA was also tested in several models of CR-EAE: proteolipid protein and myelin oligodendrocyte glycoprotein induced CR-EAE in mice, CR-EAE in Biozzi mice, and CR-EAE in cynomolgus monkeys. In all the murine models, oral treatment with GA initiated at the peak of first relapse reduced the severity of disease and suppressed further relapses. Suppression of EAE with oral GA was associated with marked inhibition of spleen cell proliferation and Th1 cytokine (IL-2 and IFN-gamma) response to the respective autoantigens. GA-specific T cell lines of the Th2/3 type that inhibit EAE induction in vivo, similarly to those induced by injection of GA, could be isolated from spleens of GA-fed mice and rats. Furthermore, as demonstrated previously for GA-specific cells induced by the parenteral route, the orally induced GA-specific cells accumulate in the CNS and secrete in situ Th2 cytokines in response to both GA and MBP as well as brain-derived neurotrophic factor (BDNF). Although a clinical trial in MS with two doses of oral GA in enteric-coated tablets did not show a significant effect either at the clinical or immunological level, the results presented here suggest that oral GA may still be developed into a therapeutic modality in MS.

Neovascularization has been suggested as a biological response to vessel injury and associated with restenosis. Self-expanding (SE) stents generate a lasting force on the arterial wall and may lead to an increased arterial response with time.To characterize the process of neovascularization with SE stents, and to correlate it with vascular injury, inflammation and intimal proliferation.Sixty-nine SE stents were im-planted in 37 non-atherosclerotic pigs.Detailed, multisection histological examination was performed at 15 days, 1, 3 and 6 months post-deployment. Neo-vascularization in addition to other histologic parameters where determined and scored.Intravascular-ultrasound-based average vessel diameter was 3.3 +/- 0.04 mm; stent size was 3.75 +/- 0.35 mm leading to an oversizing ratio of 1.14 +/- 0.15. Intimal thickness (IT), inflammatory score (IFS) and vascularization score(VAS) reached peak values at three months (IT = 344 +/- 202 1m, IFS = 0.91 +/- 0.5, and VAS = 1.56 +/- 0.8). In contrast,the injury score (INS) continued to increase at all time-points, with maximum value at six months (INS = 1.6 +/- 0.7). Both vascularization and inflammation indices increased with an increase in the injury score (p0.01). When vessels were divided according to vascularization score (VAS1.5 and1.5) there was a significant difference in IT.Neovascularization in response to SE stents is a time-dependent phenomenon and interacts with injury and inflammation. The remodeling of the vessel wall caused by the sustained force of the SE stent on the arterial wall enhances the formation of neovascularization. Neointimal formation is related to the degree of neovascularization.

This study delineates between infarcts varying in transmurality by using endocardial electrophysiologic information obtained during catheter-based mapping.The degree of infarct transmurality extent has previously been linked to patient prognosis and may have significant impact on therapeutic strategies. Catheter-based endocardial mapping may accurately delineate between infarcts differing in the transmural extent of necrotic tissue.Electromechanical mapping was performed in 13 dogs four weeks after left anterior descending coronary artery ligation, enabling three-dimensional reconstruction of the left ventricular chamber. A concomitant reduction in bipolar electrogram amplitude (BEA) and local shortening indicated the infarcted region. In addition, impedance, unipolar electrogram amplitude (UEA) and slew rate (SR) were quantified. Subsequently, the hearts were excised, stained with 2,3,5-triphenyltetrazolium chloride and sliced transversely. The mean transmurality of the necrotic tissue in each slice was determined, and infarcts were divided into30%, 31% to 60% and 61% to 100% transmurality subtypes to be correlated with the corresponding electrical data.From the three-dimensional reconstructions, a total of 263 endocardial points were entered for correlation with the degree of transmurality (4.6 +/- 2.4 points from each section). All four indices delineated infarcted tissue. However, BEA (1.9 +/- 0.7 mV, 1.4 +/- 0.7 mV, 0.8 +/- 0.4 mV in the three groups respectively, p0.05 between each group) proved superior to SR, which could not differentiate between the second (31% to 60%) and third (61% to 100%) transmurality subgroups, and to UEA and impedance, which could not differentiate between the first (30%) and second transmurality subgroups.The degree of infarct transmurality extent can be derived from the electrical properties of the endocardium obtained via detailed catheter-based mapping in this animal model.

Background —Low-energy laser irradiation (LELI) has been found to attenuate various biological processes in tissue culture and experimental animal models. The aim of the present study was to investigate the effect of LELI on the formation of scar tissue in experimentally induced chronic infarct in rats and dogs. Methods and Results —Myocardial infarction (MI) was induced in 50 dogs and 26 rats by ligation of the left anterior descending coronary artery. After induction of MI, the laser-irradiated (LI) group received laser irradiation (infrared laser, 803-nm wavelength) epicardially. Control MI-induced non–laser irradiated (NLI) dogs were sham-operated, and laser was not applied. All dogs were euthanized at 5 to 6 weeks after MI. Infarct size was determined by TTC staining and histology. The laser treatment ( P P Conclusions —Our observations indicate that epicardial LELI of rat and dog hearts after chronic MI caused a marked reduction in infarct size, probably due to a cardioprotective effect of the LELI.

Intravascular ultrasound (IVUS) has established itself as a useful tool for coronary assessment. The vast amount of data obtained by a single IVUS study renders manual analysis impractical for clinical use. A computerized method is needed to accelerate the process and eliminate user-dependency. In this study, a new algorithm is used to identify the lumen border and the media-adventitia border (the external elastic membrane). Setting an initial surface on the IVUS catheter perimeter and using active contour principles, the surface inflates until virtual force equilibrium defined by the surface geometry and image features is reached. The method extracts these features in three dimensions (3-D). Eight IVUS procedures were performed using an automatic pullback device. Using the ECG signal for synchronization, sets of images covering the entire studied region and corresponding to the same cardiac phase were sampled. Lumen and media-adventitia border contours were traced manually and compared to the automatic results obtained by the suggested method. Linear regression results for vessel area enclosed by the lumen and media-adventitia border indicate high correlation between manual vs. automatic tracings ( y = 1.07 × −0.38; r = 0.98; SD = 0.112 mm 2 ; n = 88). These results indicate that the suggested algorithm may potentially provide a clinical tool for accurate lumen and plaque assessment.

Thermography is suggested as a tool to estimate myocardial and coronary epicardial flow in open-chest heart surgery. To test the feasibility and compare various methods for coronary flow estimation in open-chest surgery, thermographic imaging was applied to eight open-chest dogs which were injected with cold saline into the aortic root. Blood flow in the left arterial descending (LAD) coronary vessel was measured by a transit-time flowmeter. ECG gated images were acquired for 20-30 s, while the cold saline (20 ml) was injected into the aortic root. Several flow levels were achieved during repeated hyperaemic response to transient occlusions of the LAD. A temperature response curve for each flow level was obtained by averaging over an edge-detected arterial segment for each image frame. Several indices were calculated from the temperature curve and correlated with the measured coronary flow. These include: an index based on a corrective heat transfer model ( r = 0.69, p < 0.001), the slope of the descending part of the response curve ( r = 0.76, p < 0.001), the peak temperature difference ( r = 0.66, p < 0.001), and the area above the temperature response curve ( r = 0.61, p < 0.01). As shown, coronary flow can be estimated quantitatively by intraoperative epicardial thermography, and may therefore provide important on-line information regarding blood flow during open-chest surgical procedures. Further studies are required for optimal application of this technique so as to increase its potential as a valid clinical tool. Keywords: thermography, coronary arteries, blood flow

We sought to investigate the acute and long-term patency rates and the histologic response of coronary arteries to a self-expandable nitinol coil stent. Twenty-two stents were implanted. Angiographic patency was demonstrated acutely in all but one dog, in which the stent was released in a small branch (1 mm); mismatch in stent-to-artery diameters resulted in vessel closure. Two dogs died from anesthesia overdose and two from bleeding within 24 hours. All dogs were treated with aspirin (80 mg/day) and warfarin (2.5 mg/day) for up to 1 month. Sixteen dogs were monitored for 1 to 2 weeks, 1 month, 3 months, 6 months, and 1 year and underwent subsequent angiography and histopathologic examination. Angiographic artery dimensions measured immediately after stent implantation (2.72 +/- 0.4 mm) did not differ from those noted at follow-up (2.68 +/- 0.44 mm, p not significant). Histologic examination showed outward stent pressure compressing the internal elastic membrane and media in most cases. Intimal hyperplasia started at 2 weeks and was most apparent at 3 and 6 months. Mean intimal thickness was 30.7 +/- 10.9 mu, 141.8 +/- 105.4 mu, 227.1 +/- 104.1 mu, 211.8 +/- 99.1 mu, and 170.1 +/- 42.7 mu at 1 to 2 weeks and 1, 3, 6 and 12 months, respectively. Therefore the nitinol self-expandable stent provokes a moderate cellular proliferative response that reaches its maximum in 3 to 6 months without further progression.

The initial experimental and clinical experience with the cardiovascular self-expandable Nitinol stent (vascular and coronary versions) is described. The stent is designed as a helical coil with two terminal balls that are used for restraining it on the delivery catheter. Upon release, the stent self-expands immediately. A temporary stent version continues with a long wire that can be removed by pulling it as a straight wire through a small profile catheter. The stent uncoils in its own groove upon removal, a relatively atraumatic procedure. The stents have been studied in dogs and in peripheral arteries in patients. The results show a transient nonocclusive proliferative response to the stent that is maximal at 3-6 mo. The removability of the permanent stent has been proven in dogs. The preliminary results in patients are encouraging and demonstrate its feasibility for permanent and potentially temporary arterial support.

The normal phasic flow wave form in an epicardial coronary artery has a distinct characteristic shape, which reflects the interaction between the coronary tree, myocardial function and hemodynamic conditions. Since clinical measurements of phasic coronary wave forms are becoming available, determination of abnormal coronary flow wave forms is important. The authors suggest here an objective and automatic method to discriminate between normal and abnormal flow wave forms based on the Karhunen-Loeve transform (KLT), and experimentally test it. The normal flow domain was represented by the resting flow waves measured in the left anterior descending arteries in 31 anesthetized dogs. The abnormal flow conditions, imposed and tested experimentally, were varying stenosis severity and severely reduced left ventricular pressure. In addition, the effects of reactive hyperemia on the shape of the flow were examined. The sorting index was based on the mean-square error (MSE) calculated for each flow signal based on a truncated KLT expansion. The results show excellent discrimination between the normal and the abnormal groups. During reactive hyperemia, however, MSE did not change significantly. These results indicate that the shape of abnormal coronary flow wave forms can be identified and discriminated from normal wave forms. >

A 4-year-old, intact male Dogue de Bordeaux dog with congenital valvular pulmonic stenosis, tricuspid valve dysplasia, and chronic atrial fibrillation underwent ultrasound-guided balloon valvuloplasty in addition to pharmacological treatment. Owner compliance to prescribed pharmacotherapy proved very poor, and concerns developed regarding the ability to successfully control heart rate and symptoms using drug therapy alone. These concerns were addressed by the implantation of a novel vagal stimulation system that was programmed to prevent a ventricular rate of >145 bpm. Consequently, post-operative ventricular response rate decreased from up to 250 to 140 bpm. Successful ventricular rate control was maintained for 291 days post-operatively, following which euthanasia was elected by the owner due to persistent right-sided congestive heart failure. To the authors' knowledge, this is the first report of successful continuous rate control using a vagal stimulating system in a closed-chest, client-owned dog with chronic atrial fibrillation secondary to spontaneously occurring organic heart disease.

Background: The new method of three-dimensional (3D) electroanatomic mapping was presented as an important tool for cardiac imaging and intervention. We present herein the first use of this technology for the monitoring, analysis, and development of cardiac surgery at the preclinical stage. Methods: The method is based on utilizing a locatable catheter connected to an endocardial mapping and navigating system, to accurately establish the location and orientation of the tip of the mapping catheter and simultaneously record its local electrogram. The 3D geometry of the beating cardiac chamber is reconstructed in real time. The system was tested on six goats that underwent dynamic cardiomyoplasty. Two maps of each animal were performed: preoperative and postoperative during the stimulation protocol of the skeletal muscle. Results: The electroanatomic mapping system provided detailed maps of the left ventricle during the stimulation protocol, which demonstrated a striking geometric difference between the assisted and the unassisted beats. These geometric changes are best described by referring to left ventricular long-axis movements (22.3 3.8° vs 3.4 1.6°, p < 0.001), center-of-mass movements (10.4 3.0 mm vs 3.9 1.6 mm, p < 0.005), and the changes in upward movement viewed along the base (7.9 1.9 mm vs 3.6 1.7 mm, p < 0.01), middle (13.8 4.0 mm vs 7.3 1.8 mm, p < 0.005), and the apex of the heart (28.1 4.5 vs 5.3 2.3 mm, p < 0.001) [mean SD]. Conclusions: The 3D electroanatomic mapping system allows detailed reconstruction of the left ventricular geometry and a clear view of the difference between the assisted and the unassisted beats. This novel monitoring system may serve as an important tool for the analysis and development of new techniques in cardiac surgery. (CHEST 2004; 125:1830 –1836)

Hypothesis Repeated cycles of freezing improve the necrotizing effect of cryosurgery. We investigated whether multiple, very short periods of freezing and thawing (pulse cryocycling) enlarged the area of cell cryonecrosis within the iceball, compared with the standard method of cryocycling. Design Liver cryonecrosis was produced in 3 groups of rabbits by means of 2 cycles of 5-minute freezing processes, each followed by 5 minutes of spontaneous thawing. In the control group (group 1), the freezing periods were uninterrupted. In the pulse cryocycling groups, the freezing periods consisted of repeated episodes of freezing and active thawing of 15 seconds (group 2) or 30 seconds (group 3) each. The edges of all lesions were visually marked. The correlation between marking and borders of the cryolesion were examined ultrasonographically. All animals were killed on the following day, and the liver was harvested and examined histologically. Setting Animal experimental laboratory. Results Complete liver cell demise was observed up to the edge of the cryolesions in all 3 groups of animals. However, a thin, sharply bounded intermediate zone of incomplete tissue destruction was observed at the border of the cryolesions, which was relatively thicker in group 2. Conclusions In our study, pulse cryocycling had no advantage compared with regular cryocycling, which obtained optimal results in normal liver tissue. However, compared with the 30-second cycles, the 15-second pulse cycling yielded poorer results.

Surgery of the sympathetic system is performed for a variety of indications, hyperhidrosis being a major one. Despite excellent results, sympathectomy for hyperhidrosis bears a number of sequels, some of which may be devastating. Several surgical methods, empirically advocated to alleviate these problems, have only limited success. Chronic in vivo recording of the electrical activity from sympathetic ganglia may assist in understanding and clarifying complex problems of sympathetic surgery; however, no suitable method has been reported. An electrode device developed by our group was implanted on the stellate ganglion, in a chronic animal model (dog). The signals obtained were amplified, filtered, and transmitted via an A/D interface to be acquired and saved on a computer, using special software which we developed. Our method enabled the separate recording of neuroelectrical signals, ECG, and respiration waves. An additional software program, also developed by our group, was used to analyze the data. This chronic animal model allows investigation of surgical and pharmacological manipulations of the sympathetic system.

Background. The CorLink™ Automated Anastomotic Device (AD) was developed to create a sutureless vein-to-aorta anastomosis without the need to clamp the aorta. This study examined the effectiveness and safety of this device in an animal model. Materials and methods. Forty-seven vein-to-aorta anastomoses using the AD and 27 control hand-sutured anastomoses were constructed in 28 sheep. The distal part of these grafts were connected either to the main pulmonary artery (40 AD, 20 control), or to the sheep’s brachiocephalic trunk (7 AD, 7 control). Procedural details focusing on deployment, leakage, and early patency rates were examined. Sheep were sacrificed after periods ranging from 1 to 180 days. Specimens were examined grossly and histologically. Results. All but three attempts to construct an anastomosis were successful (2 AD, 1 control). All anastomoses were patent immediately after their construction. There was no difference between control and AD anastomoses in respect to flow rates at the end of operation and before sacrifice. No metal breaks were detected. Fourteen of the 47 AD anastomoses and 6 of the control anastomoses (29.8% versus 22.2% P = ns) were occluded at autopsy. Histological findings characteristic of the healing process, were evenly distributed between AD and control anastomoses in both models. Intimal thickening was found in a notable number of anastomoses, but without any significant difference between the AD and control sutured (44.7% versus 40.7% P = ns). Conclusions. The AD proved safe and effective for the construction of proximal vein-to-aorta anastomoses as compared to control hand-sutured anastomoses.

Objective: Descending and ascending aortomyoplasty are two surgical procedures intended to induce hemodynamic benefits similar to those of the intra-aortic-balloon-pump (IABP). To date, there have been no studies comparing the two surgical techniques. The objective of this study was to compare coronary blood flow augmentation and afterload reduction as produced by descending and ascending aortomyoplasty counterpulsation Methods: Twenty-two mongrel dogs (18‐35 kg) underwent IABP application (n ¼ 7), descending (n ¼ 8), or ascending (n ¼ 7) aortomyoplasty. Left anterior descending (LAD) coronary artery blood flow was measured using a Transonic Doppler flow probe. Left ventricular pressure as well as aortic pressures proximal and distal to either the aortomyoplasty site or the IABP position were monitored continuously. Results: Descending aortomyoplasty induced higher elevation in the LAD blood flow during assisted beats (27% from 10.8 ^ 4 to 13.8 ^ 6 ml/min, P , 0:001) than that induced by either ascending aortomyoplasty (19% from 11.7 ^ 5t o 14^ 5 ml/ min, P , 0:001) or IABP counterpulsation (18% from 8.6 ^ 3 to 10.2 ^ 4 ml/min, P , 0:001). Conversely, while ascending aortomyoplasty reduced the left ventricular end-diastolic pressure by 16% (from 60 ^ 18 to 50 ^ 22 mmHg, P , 0:001), similar to the 16% after load reduction achieved by the IABP counterpulsation, descending aortomyoplasty failed to induce afterload reduction. Conclusions: Descending aortomyoplasty produces higher coronary blood flow augmentation than either ascending aortomyoplasty or IABP. However, afterload reduction comparable to that achieved by IABP was observed only with ascending aortomyoplasty and not with descending aortomyoplasty. q 2002 Elsevier Science B.V. All rights reserved.

Background . Three-dimensional electromechanical mapping has previously been shown to be a clinically important tool for cardiac imaging and intervention. We hypothesized that this technology may be beneficial as an intraoperative modality for assessing cardiac hemodynamics and viability during cardiac surgery. We report here the use of this technology as an imaging modality for intraoperative cardiac surgery. Methods . The tip of a locatable catheter connected to an endocardial mapping and navigating system is accurately localized while simultaneously recording local electrical and mechanical functions. Thus the three-dimensional geometry of the beating cardiac chamber is reconstructed in real time. The system was tested on 6 goats that underwent acute dynamic cardiomyoplasty and on 5 dogs that underwent left anterior descending (LAD) coronary artery ligation. Results . The electromechanical mapping system provided an accurate three-dimensional reconstruction of the beating left ventricle during cardiomyoplasty. After the wrapping procedure, significant end-diastolic area reduction was noted in the base and mid parts of the heart (948 ± 194 mm 2 vs 1245 ± 33 mm 2 , p=0.021; and 779 ± 200 mm 2 vs 1011 ± 80 mm 2 , p=0.016). The area of the cross-section of the apex did not change during the operation. Acute infarcted tissue was characterized 3 days after LAD ligation by concomitant deterioration in both electrical and mechanical function. Conclusions . By providing both a clear view of the anatomical changes that occur during cardiac surgery, and an accurate assessment of tissue viability, electroanatomic mapping may serve as an important adjunct tool for imaging and analysis of the heart during cardiac surgery

Objective: Aortomyoplasty is a surgical procedure that aims to induce hemodynamic benefits similar to those of the intra-aortic-balloonpump (IABP). The objective of this study was to compare the coronary blood flow augmentation and afterload reduction produced by IABP and descending aortomyoplasty counterpulsation. Methods: From a series of fifteen mongrel dogs (18‐35 kg), eight underwent acute descending aortomyoplasty and seven had IABP application. Left anterior descending (LAD) coronary artery blood flow was measured using a Doppler flow probe. Left ventricular pressure in addition to aortic pressures both proximal and distal to either the aortomyoplasty site or the IABP position were monitored continuously. All experiments were acute and performed in normal hearts. Results: Descending aortomyoplasty induced a 27% increase in the LAD blood flow integral during assisted beats (14:0 ^ 6 ml/min integral compared to 10:8 ^ 4 ml/min integral in unassisted beats [P , 0:001]). This was comparable to an 18% rise in the LAD blood flow integral during IABP counterpulsation (from 8:6 ^ 3 ml/min to 10:2 ^ 4 ml/min [P , 0:001]). Conversely, while IABP counterpulsation reduced the left ventricular afterload by 16% (from 102 ^ 23 mmHg to 86 ^ 26 mmHg [P , 0:001]), descending aortomyoplasty did not result in afterload reduction. Conclusions: Descending aortomyoplasty produces coronary blood flow augmentation comparable to that achieved by the IABP. This may be important for end-stage ischemic patients. However, afterload reduction achieved by the IABP was not reproduced during descending aortomyoplasty counterpulsation. The surgical technique of descending aortomyoplasty should be modified to attain afterload reduction, thus improving treatment for congestive heart failure patients. q 2001 Elsevier Science B.V. All rights reserved.

Wireless capsule endoscopy is a new, painless method of imaging the entire small bowel. It has not been compared with push enteroscopy. We compared the sensitivity, specificity, and safety of capsule and push enteroscopy in detecting small-bowel lesions.Nine to 13 radiopaque, colored beads (3-6 mm diameter) were sewn in random order inside 9 canine small bowels, half within the first meter, and confirmed on x-ray. After recovery, the number, order, and color of beads were assessed in 23 capsule enteroscopies and 9 push enteroscopies in a random order. The surgeons, push enteroscopists, capsule video interpreters, and pathologist were blinded to the others' findings.The capsules identified more beads than push enteroscopy (median, 6 [range, 2-9] vs. 3 [range, 2-6 beads]; P0.001). The sensitivity of the capsule was 64% compared with 37% for push enteroscopy. The specificity was 92% for capsule enteroscopy and 97% for push enteroscopy. The capsules identified significantly more beads beyond the reach of the push enteroscope (median, 4 [range, 2-7] vs. 0; P0.0001). Hair, ingested plastic, ulceration, submucosal swelling, and worms were clearly identified by the capsule. The capsules passed safely through the animals with no significant histologic findings.Wireless capsule endoscopy detected more abnormalities in the small bowel than push enteroscopy.

Aortomyoplasty is a procedure aimed to improve cardiac output in patients suffering from heart failure. Stimulation of the latissimus dorsi muscle around the aorta produces hemodynamic effects similar to those of the intraaortic balloon pump. These may be maintained without the accompanying complications or the need for anticoagulation. The objective of this study was to test the acute effects of aortomyoplasty on coronary artery blood flow.Eight mongrel dogs (18 to 30 kg) underwent acute descending aortomyoplasty. Several stimulation protocols were applied after wrapping of the latissimus dorsi muscle around the aorta in different surgical configurations. The left anterior descending coronary blood flow was measured using a transonic Doppler flow probe. Left ventricular and aortic pressures, proximal and distal to the aortomyoplasty site, were monitored continuously.Significant aortic diastolic pressure augmentation was expressed both as an increase in peak values, from 110 +/- 24 mm Hg to 120 +/- 24 mm Hg (p0.001) and as an increase in the diastolic integral, from 64 +/- 23 mm Hg x s to 84 +/- 37 mm Hg x s (p0.001). Concomitantly, peak left anterior descending coronary blood flow increased from 26 +/- 10 mL/min to 32 +/- 12 mL/min (p0.001). This was associated with an increase in the diastolic flow integral from 11 +/- 4 mL to 14 +/- 6 mL (p0.001).Descending aortomyoplasty induces significant augmentation of coronary blood flow. Optimal timing of muscle stimulation is important in achieving the best assist. This procedure may prove beneficial for end-stage ischemic patients.

Objectives Low patency rates of saphenous vein grafts remain a major predicament in surgical revascularization. We examined a novel expandable external support device designed to mitigate causative factors for early and late graft failure. Methods For this study, fourteen adult sheep underwent cardiac revascularization using two vein grafts for each; one to the LAD and the other to the obtuse marginal artery. One graft was supported with the device while the other served as a control. Target vessel was alternated between consecutive cases. The animals underwent immediate and late angiography and were then sacrificed for histopathologic evaluation. Results Of the fourteen animals studied, three died peri-operatively (unrelated to device implanted), and ten survived the follow-up period. Among surviving animals, three grafts were thrombosed and one was occluded, all in the control group (p = 0.043). Quantitative angiographic evaluation revealed no difference between groups in immediate level of graft uniformity, with a coefficient-of-variance (CV%) of 7.39 in control versus 5.07 in the supported grafts, p = 0.082. At 12 weeks, there was a significant non-uniformity in the control grafts versus the supported grafts (CV = 22.12 versus 3.01, p

Purpose: A novel Platinum/Iridium implantable soft tissue marker is being developed for radiographic and/or radioactive target localization to optimize external beam radiation therapy. In this study, non‐radioactive and radioactive versions of the marker were implanted in the prostate of 1 dog and the liver of 19 rabbits to assess marker stability and visibility.Method and Materials: In the canine prostate and each rabbit liver, 3–4 markers were implanted. A total of 34 non‐radioactive markers and 35 radioactive markers were implanted. Stability was assessed by measuring intermarker distance (IMD) variation relative to IMDs measured at the time of implantation. IMDs were measured on a weekly basis for 3 months in the dog and a biweekly basis for 2–4 weeks in the rabbits. Ultrasound and X‐ray imaging were performed on all subjects. CT and MRI were performed on the dog. Results: No differences in marker migration or visibility were found between non‐radioactive and radioactive versions of the marker. A total of 139 IMD variation measurements made in 1 dog and 16 rabbits had a mean absolute variation (+/− SD) of 1.1 +/− 1.1mm. These IMD variations are consistent with those reported in the literature due to random organ deformation. The markers were visible, identifiable, and induced minimal or no image artifacts in all tested imaging modalities. Conclusion: The observed stability of the markers from the time of implantation suggests that these markers may allow the immediate onset of treatment without the 1–2 week post‐implantation stabilization period required with most implanted fiducials. The markers were found to be compatible with all common medical imaging modalities. With respect to marker stability and visibility these implanted fiducials are appropriate for target positioning in the radiation treatment of cancers of the prostate and other mobile organs. Conflict of Interest: Research sponsored by Navotek Medical Ltd.

When the rib cage and abdomen are compressed during cardiopulmonary resuscitation (CPR), the effect on intrathoracic pressure, and therefore on haemodynamics, cannot be quantitatively predicted without a physiologically based mathematical model of chest wall dynamics. Using such a model, we compared model simulations of pleural Ppl and abdominal Pab pressures with those from dog experiments in which the compression of the rib cage was delayed from 0 to 500 ms after compression of the abdomen. Integrals of Ppl and transdiaphragmatic pressure, Pdi = Pab-ppl, over their positive and negative values during a cycle were chosen as indices of driving pressures for cardiac output. Both from the model output and experimental data, we found that the positive ppl integral PPI tends to increase with a longer delay between rib cage and abdominal compressions. The negative ppl integral NPI, however, tends to decrease according to the model predictions and data. Furthermore, the positive and negative integrals of Pdi also tend to change with delay time in the opposite way, as shown by both the model simulations and the experiments. Our results show that chest wall tissues modify the externally applied pressures, thereby not allowing us to use the externally applied pressure sources directly as the driving pressure of the cardiovascular system under study. The optimal conditions for haemodynamics during CPR require a compromise between the positive and negative integral indices. Prediction of the optimal haemodynamics from externally applied pressures requires the coupling of appropriate physiological models of chest wall dynamics and haemodynamics.

A new approach for delivering cardiopulmonary resuscitation (CPR) in which the airway opening is (occluded during chest-wall compression was studied both theoretically and experimentally with a vest system. Using a mathematical model for lung and chest wall dynamics, we simulated CPR by chest-wall compression with a standard method (S-CPR) and with the addition of expiratory occlusion (OE-CPR). The model quantifies the effect of occluding the expiration during chest-wall compression, which increases intrathoracic pressure and lung volume and decreases tidal volume. The increased intrathoracic pressure from OE-PCR is expected to produce more cardiac output from an arrested heart than can be obtained by S-CPR. Furthermore, the hemodynamic and metabolic indices of OE-CPR may be improved compared with those of S-CPR. To test this hypothesis, we conducted experiments with six mongrel dogs. In comparison with S-CPR, the OE-CPR CPR method produced higher values of intrathoracic pressure and cardiac output. Also, OE-CPR yielded less hypocapnea and more oxygen delivery than the S-CPR.

We studied the effect of CPR rate on the hemodynamic indices of surgically instrumented canine experimental models. Using pneumatic vest CPR, we applied simultaneous rib cage and abdominal compressions at rates of 1 to 12 Hz. CPR with 2-Hz frequency yielded the highest aortic and coronary flows (252 +/- 14 and 6.8 +/- 1.1 ml/min vs. 178 + 12 and 0.96 +/- 0.08 ml/min at 1 Hz, respectively; p less than .005). The validity of the present American Heart Association recommendation for 1-Hz CPR rate would benefit from further studies.