Closed-chest Pigs Research Articles

ST-segment deviation behavior during acute myocardial ischemia in opposite ventricular regions: observations in the intact and perfused heart.

Acute myocardial ischemia in opposite regions may attenuate ST-segment changes, but whether this effect is expressed differently in extracardiac compared to direct intramyocardial recordings is not well known. The purpose of this study was to characterize ST-segment changes induced by opposite ischemic regions in intact and isolated perfused pig hearts. Left anterior descending (LAD) and right coronary arteries (RCA) were occluded in 7 closed chest pigs and in 5 isolated pig hearts. ST-segment changes were analyzed in 12-lead ECG and in local extracellular electrograms. Isolated LAD or RCA occlusion induced maximal ST-segment elevation in leads V4 (0.84 ± 0.30 mV, P = .003) and III (0.16 ± 0.11 mV, P = .04), respectively. RCA occlusion also induced reciprocal ST-segment depression maximal in lead V4 (-0.40 ± 0.16 mV, P = .005). Simultaneous LAD and RCA occlusion reduced ST-segment elevation by about 60% and blunted reciprocal ST-segment changes. Reperfusion of 1 of the 2 occluded arteries induced immediate regional reversion of ST-segment elevation with concurrent beat-to-beat re-elevation in the opposite ischemic region and reappearance of reciprocal ST-segment changes. In the isolated heart, single LAD or RCA ligature induced regional transmural ST-segment elevation that was maximal in endocardial electrograms with no appreciable reciprocal ST-segment depression. Simultaneous LAD and RCA ligature reduced ST-segment elevation by about 30% with no appreciable re-elevation after 1-vessel selective reperfusion. Acute myocardial ischemia in opposite ventricular regions attenuated ST-segment elevation and blunted reciprocal depression in conventional ECG leads but not in direct local myocardial electrograms.

Negative tracheal pressure during obstructive respiratory events promotes atrial fibrillation by vagal activation

Obstructive sleep apnea (OSA) causes negative tracheal pressure (NTP) and is associated with atrial fibrillation (AF). This study aimed to determine the mechanism of atrial electrophysiological changes during tracheal occlusion with or without applied NTP and to evaluate the role of vagal activation, Na(+)/H(+)exchanger (NHE), and ATP-dependent potassium channels (K(ATP)). Seventeen closed-chest pigs were anesthetized with urethane, and an endotracheal tube was placed to apply NTP (up to -100 mbar), comparable to clinically observed OSA in patients by a negative pressure device for a time period of 2 minutes. Right atrial refractory periods (AERP) and AF inducibility were measured transvenously by a monophasic action potential recording and stimulation catheter. All tracheal occlusions with and without applied NTP resulted in comparable increases in blood pressure and hypoxemia. NTP shortened AERP (157.0 ± 2.8 to 102.1 ± 6.2 ms; P <.0001) and enhanced AF inducibility during AERP measurements from 0% at baseline to 90% (P <.00001) during NTP. Release of NTP resulted in a prompt restoration of sinus rhythm, and AERP returned to normal. NTP-induced AERP shortening and AF inducibility were prevented by atropine or vagotomy. Neither the NHE blocker cariporide nor the K(ATP) channel blocker glibenclamide abolished NTP-induced AERP shortening. By contrast, tracheal occlusion without applied NTP caused comparable changes in blood gases but did not induce AERP shortening or AF inducibility. NTP during obstructive events is a strong trigger for AF compared with changes in blood gases alone. NTP caused AERP shortening and increased susceptibility to AF mainly by enhanced vagal activation. AERP shortening was not prevented by K(ATP) channel blockade or NHE blockade.

Ischemic Postconditioning Inhibits Apoptosis aft er Acute Myocardial Infarction in Pigs

Recent studies have shown that ischemic postconditioning reduces myocardial ischemia-reperfusion (I/R) injury; however, the effects of inhibiting apoptosis on cardioprotection induced by ischemic postconditioning remain to be determined. The objective of this study was to investigate whether ischemic postconditioning attenuates myocardial I/R injury by reduced apoptosis in a closed-chest pig model of acute myocardial infarction. Diannan small-ear pigs were randomly divided into 3 groups (5/group): (1) The sham group underwent a sham operation without ischemia; (2) the I/R group received 60 minutes of ischemia and 72 hours of reperfusion; and (3) the ischemic postconditioning (Postcond) group was treated the same as the I/R group except that the pigs received 8 cycles of 30 seconds of reperfusion and 30 seconds of ischemia at the onset of reperfusion. After 72 hours of reperfusion, infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining. Apoptotic cells in the peri-infarct myocardium were evaluated with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, and apoptosis-related molecules were studied with western blotting analysis. After 72 hours of reperfusion, mean (±SEM) infarct size was significantly smaller in the Postcond group than in the I/R group (23.26% ± 3.13% versus 10.89% ± 2.02%, P < .05). Apoptotic myocytes in the peri-infarct region were lower in the Postcond group than in the I/R group (15.31% ± 4.58% versus 33.83% ± 4.44%, P < .05). This decrease in the extent of apoptosis was accompanied by a significant decrease in Bax expression (0.306 ± 0.075 versus 0.433 ± 0.102 for the I/R group; P < .05) and a significant increase in Bcl-2 expression (1.801 ± 0.227 versus 1.267 ± 0.308 for the I/R group; P < .05). In a clinically relevant closed-chest pig model of myocardial infarction, these data suggest the following: (1) Ischemic postconditioning reduces infarct size following prolonged reperfusion, and (2) this cardioprotective effect is likely achieved via antiapoptotic mechanisms.

Transcatheter percutaneous aortic valve implantation: The dream has become a reality

Transcatheter percutaneous aortic valve implantation: The dream has become a reality

Post-hypothermic cardiac left ventricular systolic dysfunction after rewarming in an intact pig model

IntroductionWe developed a minimally invasive, closed chest pig model with the main aim to describe hemodynamic function during surface cooling, steady state severe hypothermia (one hour at 25°C) and surface rewarming.MethodsTwelve anesthetized juvenile pigs were acutely catheterized for measurement of left ventricular (LV) pressure-volume loops (conductance catheter), cardiac output (Swan-Ganz), and for vena cava inferior occlusion. Eight animals were surface cooled to 25°C, while four animals were kept as normothermic time-matched controls.ResultsDuring progressive cooling and steady state severe hypothermia (25°C) cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), maximal deceleration of pressure in the cardiac cycle (dP/dtmin), indexes of LV contractility (preload recruitable stroke work, PRSW, and maximal acceleration of pressure in the cardiac cycle, dP/dtmax) and LV end diastolic and systolic volumes (EDV and ESV) were significantly reduced. Systemic vascular resistance (SVR), isovolumetric relaxation time (Tau), and oxygen content in arterial and mixed venous blood increased significantly. LV end diastolic pressure (EDP) remained constant. After rewarming all the above mentioned hemodynamic variables that were depressed during 25°C remained reduced, except for CO that returned to pre-hypothermic values due to an increase in heart rate. Likewise, SVR and EDP were significantly reduced after rewarming, while Tau, EDV, ESV and blood oxygen content normalized. Serum levels of cardiac troponin T (TnT) and tumor necrosis factor-alpha (TNF-α) were significantly increased.ConclusionsProgressive cooling to 25°C followed by rewarming resulted in a reduced systolic, but not diastolic left ventricular function. The post-hypothermic increase in heart rate and the reduced systemic vascular resistance are interpreted as adaptive measures by the organism to compensate for a hypothermia-induced mild left ventricular cardiac failure. A post-hypothermic increase in TnT indicates that hypothermia/rewarming may cause degradation of cardiac tissue. There were no signs of inadequate global oxygenation throughout the experiments.

Clobutinol Delays Ventricular Repolarization in the Guinea Pig Heart: Comparison With Cardiac Effects of hERG K+ Channel Inhibitor E-4031

Clobutinol has been clinically reported to induce long QT syndrome. To clarify its cardiac electrophysiological properties, we compared effects of clobutinol on the isolated myocardium and anesthetized guinea pig heart with those of a hERG K channel blocker, E-4031. In isolated guinea pig ventricular tissues, clobutinol (3 microM) as well as E-4031 (10-100 nM) prolonged the action potential duration without affecting maximum upstroke velocity, but no further prolongation was observed after application of 30 microM clobutinol. In anesthetized closed-chest guinea pigs, clobutinol (1 and 10 mg/kg, intravenously) and E-4031 (0.01 and 1 mg/kg, intravenously) prolonged the QT interval and duration of the monophasic action potential (MAP) in a dose-dependent manner and at the same time increased the beat-to-beat variability of the MAP duration and reversed use-dependent prolongation of the MAP duration and triangulation of the MAP configuration. These results suggest that clobutinol delayed the ventricular repolarization and increased the proarrhythmic parameters linked to the hERG K channel inhibitor-induced torsade de pointes arrhythmias.

Nonanticoagulant heparin reduces myocyte Na+and Ca2+loading during simulated ischemia and decreases reperfusion injury

Heparin desulfated at the 2-O and 3-O positions (ODSH) decreases canine myocardial reperfusion injury. We hypothesized that this occurs from effects on ion channels rather than solely from anti-inflammatory activities, as previously proposed. We studied closed-chest pigs with balloon left anterior descending coronary artery occlusion (75-min) and reperfusion (3-h). ODSH effects on [Na(+)](i) (Na Green) and [Ca(2+)](i) (Fluo-3) were measured by flow cytometry in rabbit ventricular myocytes after 45-min of simulated ischemia [metabolic inhibition with 2 mM cyanide, 0 glucose, 37 degrees C, pacing at 0.5 Hz; i.e., pacing-metabolic inhibition (PMI)]. Na(+)/Ca(2+) exchange (NCX) activity and Na(+) channel function were assessed by voltage clamping. ODSH (15 mg/kg) 5 min before reperfusion significantly decreased myocardial necrosis, but neutrophil influx into reperfused myocardium was not consistently reduced. ODSH (100 microg/ml) reduced [Na(+)](i) and [Ca(2+)](i) during PMI. The NCX inhibitor KB-R7943 (10 microM) or the late Na(+) current (I(Na-L)) inhibitor ranolazine (10 microM) reduced [Ca(2+)](i) during PMI and prevented effects of ODSH on Ca(2+) loading. ODSH also reduced the increase in Na(+) loading in paced myocytes caused by 10 nM sea anemone toxin II, a selective activator of I(Na-L). ODSH directly stimulated NCX and reduced I(Na-L). These results suggest that in the intact heart ODSH reduces Na(+) influx during early reperfusion, when I(Na-L) is activated by a burst of reactive oxygen production. This reduces Na(+) overload and thus Ca(2+) influx via NCX. Stimulation of Ca(2+) extrusion via NCX later after reperfusion may also reduce myocyte Ca(2+) loading and decrease infarct size.

Cryoablation time-dependent dose-response effect at minimal temperatures (-80 C): an experimental study

AimsTo establish a temporal safety window for cryoablation at minimal temperatures and to assess the electrophysiological and histological changes as a function of the application duration.Methods and resultsTwenty mini-pigs underwent AV nodal cryoablation at −80°C without prior cryomapping. The duration of the cryoapplication following atrioventricular block (AVB) was randomized to 0, 10, 20, 40, or 60 s. Atrioventricular block was obtained in all animals after a median of 3 (1–8 interquartile range) applications. One week later, AV nodal conduction fully recovered in animals with application duration <10 s, whereas persistent AVB incidence increased as a function of time in animals with longer applications duration. Cryoablation application duration following AVB was the only independent predictor of persistent AVB (OR, 1.116; 95% CI, 1.013–1.229; P = 0.026). There was no difference in lesion location or size between animals with vs. those without persistent AVB at 1 week. However, animals randomized to longer application duration demonstrated higher degree of cell destruction and fibrotic content.ConclusionIn this closed-chest pig model, there was a relation between cryoapplication duration following AVB at −80°C and recovery of conduction. A safety window of at least 10 s was observed in all cases.

The role of ACE inhibitors in the treatment of arrhythmias

Several experimental models have been studied to determine the role of angiotensin-converting enzyme (ACE) inhibitors in reducing ischemic and reperfusion arrhythmias. Studies of left main coronary artery occlusion in isolated perfused rat hearts have shown that the ACE inhibitor captopril reduced reperfusion ventricular fibrillation from 100% to 0% and was associated with a reduction in purine overflow and in norepinephrine release. These effects were abolished in the presence of indomethacin. In an anesthetized rat model of acute myocardial infarction (MI), ACE inhibition reduced mean duration of ventricular fibrillation from 1,133 to 135. ACE inhibition at programmed electrical stimulation of the heart in a closed-chest pig model of acute MI reduced the inducibility of sustained, reproducible ventricular tachycardia from a mean of 42 to 8%. In this model, ventricular tachycardia could not be provoked in animals treated with captopril from the time of acute ischemia. Studies on the rate of ventricular ectopy in patients with poor left ventricular function have demonstrated a significant reduction with ACE inhibition. However, while a protective effect has been shown, the mechanism of action is still speculative.

Abstract 4708: Rapid Resolution of ST Segment Elevation and Recovery of Function in Acute Myocardial Infarction Treated with Low Dose Intravenous Thrombolytics, Transthoracic Ultrasound, and Intravenous Microbubbles

Rapid non-invasive methods of recanalizing acutely thrombosed coronary arteries and restoring microcirculatory flow are needed. Failure of ST segment elevation to resolve on the 12 lead electrocardiogram is a marker of microvascular no reflow, and occurs in over 30% of acute myocardial infarctions treated with primary percutaneous interventions. Transthoracic ultrasound (TTU) and intravenous (IV) microbubbles (MB) have the potential to increase epicardial recanalization (RC) when used with low dose thrombolytic therapy (TT). We hypothesized that this therapy may also dissolve microvascular thrombi, and thus improve microvascular recovery during treatment of an acute coronary thrombosis. In 45 closed chest pigs, acute left anterior descending (LAD) thromotic occlusions were created, followed by randomized treatment to either a) IV low dose TT alone (50,000 u/kg recombinant urokinase; n=15), or b) IV low dose TT combined with IV lipid encapsulated MB (ImaRx Therapeutics, Inc) and TTU (1.5 MHz diagnostic transducer using 1.9 MI therapeutic impulses applied only when low MI imaging detected MB within the affected risk area; n=30). Resolution of ST segment elevation as well as wall thickening (WT) within the central portion of the risk area were analyzed in pigs that had epicardial RC versus those that did not exhibit RC in the IV MB treated groups. Epicardial RC occurred within 60 minutes in 15 pigs (50%) treated with IV MB and TTU (p&lt; 0.01 compared to IV TT alone;Table ). Significant &gt;50% ST segment resolution occurred in over 90% of pigs with epicardial RC treated with TT and MB, but also in six of 15 pigs that did not have RC. In these six pigs, WT within the risk area increased similar to the pigs which had epicardial RC (Table ). Diagnostic TTU and IV microbubbles improve microvascular perfusion even if epicardial RC is not achieved, leading to rapid recovery of function. Both epicardial and microvascular reflow can be achieved with this technique. ST segment and WT Changes Before and Following Treatment

Abstract P123: Vasopressin, but not Norepinephrine, causes Ventriculoarterial Mismatch in Experimental Post Ischemic Cardiogenic Shock

Introduction In agreement with existing guidelines, inotropic and vasopressor support is given routinely in cardiogenic shock (CS). However, there is a lack of scientific evidence supporting the efficacy and safety of such treatment. Hypothesis Vasoconstrictors given in cardiogenic shock will increase the ventriculoarterial mismatch and thus lead to reduced cardiac output Methods In a closed chest pig model we tested the inodilator (dobutamine, Dobut) alone and combined with either an inoconstrictor (norepinephrine, NE) or a pure vasopressor (arginine vasopressin, AVP). In anesthetized animals, CS was induced by coronary microembolization under fluoroscopic guidance. Hemodynamic indices were obtained by Swan-Ganz catheters, left ventricular pressure-volume catheters and echocardiography, and the ventriculoarterial coupling calculated. Results In the normal heart, Dobut (2ug/kg/min) enhanced ventriculoarterial energy transfer, shown as a decreased Ea/Ees (ratio of arterial and ventricular elastance), 1.0 ± 0.1 to 0.8 ± 0.1, and an increased preload recruitable stroke work (PRSW), 53 ± 5 to 63 ± 2. This was further enhanced by NE (100 ng/kg/min) to 0.7 ± 0.1 and 79 ± 6. In contrast, adding AVP (0.001 u/kg/min) resulted in an increased Ea/Ees (1.0 ± 0.1) and decreased PRSW (56 ± 8) compared to Dobut alone (a two fold increase in systemic vascular resistance (SVR), concomitant with no elevation in contractility). In post ischemic CS, energy transfer from the ventricle to the arterial system (Ea/Ees 1.8 ± 0.2, PRSW 26 ± 2 and Ejection fraction 42 ± 6 %) was partly restored by Dobut (1.4 ± 0.2, 46 ± 2 and 47 ± 6%) unaffected by further adding NE (1.5 ± 0.2, 53 ± 2 and 45 ± 5%), but impaired after adding AVP (2.0 ± 0.1, 43 ± 1 and 34 ± 4%). Consequently, Dobut improved the shock by increasing cardiac output (CO) and SVO2 from 74 ± 3 ml/kg and 37 ± 2% to 103 ± 8 ml/kg and 49 ± 3%. Adding NE resulted in a further improvement of CO (125 ± 9 ml/kg) and SVO2 (59 ± 4%). In contrast AVP further worsened the shock state by decreasing CO (70 ± 6 ml/kg) and SVO2 (45 ± 5%) compared to Dobut alone. Conclusion A pure afterload increasing substance in acute ischemic hearts with cardiogenic shock aggravate the shock state by causing a ventriculoarterial mismatch.

Effect of intravenous administration of antioxidants alone and in combination on myocardial reperfusion injury in an experimental pig model

Background: Several antioxidants have been found to have conflicting results in attenuating myocardial reperfusion injury. These studies were done primarily in experimental protocols that did not approximate clinical situations. Objective: The aim of this study was to test the efficacy of 3 different antioxidants (ascorbic acid [AA], desferrioxamine, and N-acetylcysteine [NAC]) administered IV alone and in combination in a closed-chest pig model. Methods: Farm-raised domestic male pigs (aged 3–5 months, weight of 30–35 kg) were assigned to 1 of 5 groups to receive treatment as follows: group A, AA 100 mg/kg; group B, desferrioxamine 60 mg/kg; group C, a loading dose of NAC 100 mg/kg for 20 minutes and a 20-mg/kg maintenance dose; group D, all 3 drugs in combination; and group E, normal saline (control group). The infusion of all drugs was started 15 minutes before and completed 5 minutes after reperfusion, except for the administration of NAC, which was terminated 60 minutes postreperfusion. Myocardial ischemia (45 minutes) and reperfusion (210 minutes) were achieved percutaneously by circumflex artery balloon occlusion. Ejection fraction, left ventricular end-diastolic pressure (LVEDP), flow in the infarcted artery, and all ventricular arrhythmias were recorded. Oxidative stress was estimated by serial measurements of thiobarbituric acid reactive substance (TBARS) concentration in coronary sinus blood. Infarct size was assessed as a percentage of the area at risk (I/R ratio) using the tetrazolium red staining method. Results: The 25 pigs were divided into 5 groups of 5 pigs each. No significant between-group differences were found in I/R ratio or in oxidative stress (as measured by TBARS concentration). Group C developed significantly more ventricular atrhythmias than the control group (80% vs 0%, P = 0.02). No other differences among groups were found. LVEDP was significantly elevated in all treatment groups (mean LVEDP difference [SD] for group A, 6.0 [1.6] mm Hg; group B, 17.6 [1.9] mm Hg; group C, 3.6 [1.7] mm Hg; group D, 6.8 [3.2] and group E, 5.4 [3.4] mm Hg). LVEDP elevation was found to be significantly higher in group B compared with all the other groups (all, P < 0.001). No significant between-group differences were found in the other parameters measured. Conclusion: In this experimental pig model, the antioxidants AA, desferrioxamine, and NAC administered alone or in combination did not reduce the deleterious effects of reperfusion injury and specifically the extent of myocardial necrosis.

Intravenous infusion of mesenchymal stem cells enhances regional perfusion and improves ventricular function in a porcine model of myocardial infarction

Transplantation of stem cells may improve regional perfusion and post-infarct ventricular function, but the optimal dose and efficacy of cell delivery via the intravenous route has not been determined. This study tested the hypothesis that intravenous infusion of bone marrow-derived mesenchymal stem cells (MSCs) enhances regional perfusion and improves ventricular function after myocardial infarction. In a closed-chest pig model, the LAD coronary artery was occluded for 75 min by angioplasty balloon inflation followed by 12 weeks of reperfusion. After 15 min of reperfusion, pigs randomly received 1 of 4 treatments: (1) Vehicle (Control, n = 10); (2) 1 x 10(6) MSCs/kg (1 mill, n = 7); (3) 3 x 10(6) MSCs/kg (3 mill, n = 8) and (4) 10 x 10(6) MSCs/kg (10 mill, n = 8). Angiogenesis was demonstrated by immunohistochemical staining, myocardial blood flow (steady state and vasodilator reserve) was measured using 15 microm neutron-activated microspheres, and cardiac function was determined by contrast left ventriculography (ejection fraction) and pressure-volume relationships. After 12 week of reperfusion, von Willebrand Factor-positive vessels and tissue vascular endothelial growth factor (VEGF) expression in the scar zone was significantly greater in all MSCs-treated animals relative to Control. Steady state myocardial blood flow in the scar tissue was comparable among groups. However, adenosine recruited vasodilator reserve in the scar zone induced by intracoronary adenosine was significantly higher in the MSC-treated animals compared to Control. Furthermore, preload-recruitable stroke work and systolic performance were significantly greater compared to Control. In conclusion, these data demonstrate that intravenous delivery of MSCs during early reperfusion augments vasculogenesis, enhances regional perfusion, and improves post-infarct ventricular function. The results suggest that intravenous infusion of MSCs is an effective modality for the treatment of ischemia/reperfusion induced myocardial injury.

Rapid short-duration hypothermia with cold saline and endovascular cooling before reperfusion reduces microvascular obstruction and myocardial infarct size

BackgroundThe aim of this study was to evaluate the combination of a rapid intravenous infusion of cold saline and endovascular hypothermia in a closed chest pig infarct model.MethodsPigs were randomized to pre-reperfusion hypothermia (n = 7), post-reperfusion hypothermia (n = 7) or normothermia (n = 5). A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min. Hypothermia was started after 25 min of ischemia or immediately after reperfusion by infusion of 1000 ml of 4°C saline and endovascular hypothermia. Area at risk was evaluated by in vivo SPECT. Infarct size was evaluated by ex vivo MRI.ResultsPre-reperfusion hypothermia reduced infarct size/area at risk by 43% (46 ± 8%) compared to post-reperfusion hypothermia (80 ± 6%, p < 0.05) and by 39% compared to normothermia (75 ± 5%, p < 0.05). Pre-reperfusion hypothermia infarctions were patchier in appearance with scattered islands of viable myocardium. Pre-reperfusion hypothermia abolished (0%, p < 0.001), and post-reperfusion hypothermia significantly reduced microvascular obstruction (10.3 ± 5%; p < 0.05), compared to normothermia: (30.2 ± 5%).ConclusionRapid hypothermia with cold saline and endovascular cooling before reperfusion reduces myocardial infarct size and microvascular obstruction. A novel finding is that hypothermia at the onset of reperfusion reduces microvascular obstruction without reducing myocardial infarct size. Intravenous administration of cold saline combined with endovascular hypothermia provides a method for a rapid induction of hypothermia suggesting a potential clinical application.

Development of an Electrophysiology (EP)-Enabled Intracardiac Ultrasound Catheter Integrated With NavX 3-Dimensional Electrofield Mapping for Guiding Cardiac EP Interventions

We have developed an integrated high-resolution intracardiac echocardiography (ICE) catheter for electrophysiology (EP) testing, which can be coregistered in 3-dimensional space with EP testing and ablation catheters using electrofield sensing. Twelve open-chest pigs (34-55 kg) and 3 closed-chest pigs were studied. After introduction from the jugular or femoral venous locations, the 9F side-looking, highly steerable (0 degrees -180 degrees), 64-element array catheters could be manipulated easily throughout the right side of the heart. Multisite cardiac pacing was performed for assessing left ventricular (LV) synchrony using tissue Doppler methods. Also, in the open-chest pigs, right atrial (RA) and right ventricular (RV) ablations were performed with a separate radio frequency catheter under fluoroscopic guidance and visualized with ICE to characterize the changes. In the 3 closed-chest pigs, electrofield NavX 3-dimensional coregistration (St Jude Medical Corp, Minneapolis, MN) allowed us to test whether this additional feature could shorten the time necessary to perform 4 targeted ablations in each animal while imaging the ablation catheter and the adjacent region by ICE. Intracardiac anatomy, tricuspid, aortic, pulmonary, and mitral valve function, and pulmonary vein flow were all imaged reproducibly from scanning locations in the RA or RV in all animals, along with assessment of cardiac motion and the effects of multisite pacing. Three-dimensional electrofield displays detailed the spatial relationship between the ICE catheter and ablation catheters such that the time to visualize and ablate 4 sites in each of the 3 closed-chest animals was reduced. This new technology is a first step in the integration of ICE with EP procedures.

Abstract 2242: Very High Resolution Near Field Imaging of Ablation with a Newly-Developed Forward-Looking Catheter Mounted Microlinear Intracardiac Imaging Array

Background: We have developed the first forward-looking highly steerable intracardiac echo probe developed for ultrasound visualization of ablation. It is a 24-element forward-looking microlinear array on a 9 Fr catheter that has additional electrodes so it can be localized compared to separate ablation catheters through electrofield navigation by NavX. Methods: In 4 studies of closed-chest pigs, we have imaged ablation locations in the right atrium and the isthmus and on the right side of the septum and at the right ventricular apex, and also imaged across the septum at ablations in the left ventricle along the septum with this device. Results: Images at 150–170 frames/sec at 12–15 MHz give very high detail of the changes occurring during ablation, including liquefaction, heating changes, brightening and thickening of tissue, and thrombus formation in the adjacent region in unheparinized pigs. The devices are well enough shielded from RF energy that there is little interference, and yet an ablation is being performed. A catheter tip artifact makes it easy to see the actual location of the ablation catheter tip with the microlinear array. Tissue Doppler/strain rate imaging also yields the possibility of determining mechanical changes occurring in ablation where brightening of tissue associated with stiffening diminished mechanical strain deformations in ablated lesions, especially in the ventricles. Conclusions: This new technology provides a new method for guidance and, more importantly, a method for understanding the changes that occur with RF ablations in experimental animals and, eventually, in patients.

Full or pressure limited reperfusion of an acute myocardial infarct results in a different wall thickness and deformation of the distal myocardium – Implications for clinical reperfusion strategies

The study aim was to determine the sequence of changes in both wall thickness and function in 'at risk' myocardium (using M-mode and radial strain/strain-rate imaging) induced by reperfusion of an acute transmural infarction, and to relate these changes to the presence or absence of a pressure-limiting stenosis in the infarct related epicardial vessel. Eighteen closed-chest pigs were randomized into two groups (each with nine animals). In Group I, 4 weeks prior to induction of an acute transmural infarct, a copper coated stent was implanted in the proximal circumflex artery (Cx) to create a coronary artery stenosis of between 30 and 95% lumen diameter. At 4 weeks, the stenotic Cx vessel was occluded for 90 min by inflation of a PTCA balloon placed proximal to the stenosis to produce an acute transmural infarction. In Group II (the control group), 90 min Cx occlusion was performed in a normal vessel. In both groups the resulting acute transmural infarction was reperfused after 90 min by removing the PTCA balloon. For both groups, cardiac ultrasound data, including strain/strain-rate imaging, were collected at all stages of the investigation for subsequent offline analysis. In both groups, acute reperfusion (TIMI flow 3 or 2), immediately increased infarct zone end-diastolic wall thickness due to the development of oedema. The acute increase in wall thickness was significantly higher in the non-stenotic animals as compared to the ones with a residual stenosis. Neither of the groups showed any tendency to normalize deformation (strain) during the reperfusion period. In this experimental study, the measurement of end-diastolic wall thickness was a simple and non-invasive tool to monitor acute infarct reperfusion. It also provided information on the presence of a flow limiting stenosis in the infarct related artery after restoration of the flow. The deformation of the myocardium remained impaired during early reperfusion, whether reflow was at full pressure or low pressure due to a residual stenosis in the infarct related artery.

Attenuation of myocardial reperfusion injury in pigs by Mirococept, a membrane-targeted complement inhibitor derived from human CR1

Membrane-targeted application of complement inhibitors may ameliorate ischemia/reperfusion (I/R) injury by directly targeting damaged cells. We investigated whether Mirococept, a membrane-targeted, myristoylated peptidyl construct derived from complement receptor 1 (CR1) could attenuate I/R injury following acute myocardial infarction in pigs. In a closed-chest pig model of acute myocardial infarction, Mirococept, the non-tailed derivative APT154, or vehicle was administered intracoronarily into the area at risk 5 min pre-reperfusion. Infarct size, cardiac function and inflammatory status were evaluated. Mirococept targeted damaged vasculature and myocardium, significantly decreasing infarct size compared to vehicle, whereas APT154 had no effect. Cardioprotection correlated with reduced serum troponin I and was paralleled by attenuated local myocardial complement deposition and tissue factor expression. Myocardial apoptosis (TUNEL-positivity) was also reduced with the use of Mirococept. Local modulation of the pro-inflammatory and pro-coagulant phenotype translated to improved left ventricular end-diastolic pressure, ejection fraction and regional wall motion post-reperfusion. Local modification of a pro-inflammatory and pro-coagulant environment after regional I/R injury by site-specific application of a membrane-targeted complement regulatory protein may offer novel possibilities and insights into potential treatment strategies of reperfusion-induced injury.

Post-ischaemic myocardial dysfunction (stunning) results from myofibrillar oedema

Objective:To test the hypothesis that myocardial stunning is due to myofibrillar oedema.Methods:Experiments were performed in anaesthetised closed-chest pigs. In 15 pigs (group 1), myocardial stunning was produced by repetitive ischaemia...

854 Different recovery (rate) of longitudinal and radial function after an episode of acute ischemia

Background: Previous studies have shown that the cyclic variation of integrated backscatter returns prior to wall thickening (i.e. radial strain) after acute ischemia. This might be due to a different rate in recovery of radial (R) and longitudinal (L) deformation. In our laboratory, a new ultrasound methodology for the estimation of all in-plane myocardial strain components has been developed. The aim of this study was to measure the amount and the rate of recovery of both R and L deformation after acute ischemia. Material and methods: In 9 closed-chest pigs, a 5 min PTCA circumflex occlusion was used to induce myocardial ischemia. This was followed by 130 min of reperfusion. Radio-frequency (RF) ultrasound data with high spatial and temporal resolution (>160 fps) were acquired in a parasternal longaxis view (Toshiba Aplio) at baseline (BL), after occlusion and at selected points during the following reperfusion. Data were transferred to a personal computer for off-line analysis using dedicated software (SPEQLE-2D). Endsystolic R and L strain were extracted from the „at risk” posterior wall segment and the remote non-ischemic septal segment. For each animal, strain data were normalized to its BL value and a logarithmic fit was made. Finally, an average fit over all animals was determined. Results: During reperfusion of the ischemic segment, L strain showed faster recovery than R strain. However, after 130 min of reperfusion R strain had almost completely recovered while L strain remained reduced. No changes were found in the septal segment during the reperfusion period. Conclusions: The amount of rate of recovery after an episode of acute ischemia is different for radial and longitudinal function. This might be related to a epito endocardial recovery of function in combination with fiber orientation.