Dynamic contrast-enhanced MR lymphangiography: feasibility study in swine.

PURPOSE: To demonstrate the feasibility of dynamic four-dimensional ( 4D four-dimensional ) intranodal contrast material-enhanced magnetic resonance (MR) lymphangiography with inguinal lymph node injection of gadopentetate dimeglumine. MATERIALS AND METHODS: All procedures were performed in accordance with the guidelines on the use of animals in research and were approved by the animal care and use committee. Five swine underwent nonenhanced MR lymphangiography with a heavily T2-weighted MR sequence, bilateral inguinal lymph node injection of 2 mL of undiluted gadopentetate at a rate of 1 mL/min, and 60 minutes of MR imaging with T1-weighted high-spatial- and high-temporal-resolution MR angiography. Images were reviewed by a radiologist with expertise in lymphatic imaging and a pediatric cardiac MR imaging specialist for visualization of the thoracic duct ( TD thoracic duct ). Categorical variables were compared by using the exact conditional McNemar test. A difference with a P value less than .05 was considered significant. RESULTS: The TD thoracic duct was visualized in three of the five animals (60%) on T2-weighted images. In contrast, the TD thoracic duct was visualized in all five of the animals (100%) after contrast agent injection (P = .25). The median time for flow of the contrast agent through the lymphatic system to the TD thoracic duct outlet was 244 seconds (range, 201-387 seconds). Enhancement was seen in the TD thoracic duct up to 1 hour after injection. All animals survived without any complications. CONCLUSION: Dynamic 4D four-dimensional contrast-enhanced MR lymphangiography with intranodal injection of gadopentetate dimeglumine is feasible, produces good images of the central lymphatic system, and demonstrates the time course of flow of contrast agent up the central lymphatic ducts. On the basis of the results of this initial animal experiment, it appears that dynamic 4D four-dimensional contrast-enhanced MR lymphangiography is potentially feasible and safe with commercially available contrast agents.

Hypercholesterolemia exacerbates in-stent restenosis in rabbits: Studies of the mitigating effect of stent surface modification with a CD47-derived peptide.

BACKGROUND AND AIMS: Hypercholesterolemia (HC) has previously been shown to augment the restenotic response in animal models and humans. However, the mechanistic aspects of in-stent restenosis (ISR) on a hypercholesterolemic background, including potential augmentation of systemic and local inflammation precipitated by HC, are not completely understood. CD47 is a transmembrane protein known to abort crucial inflammatory pathways. Our studies have examined the interrelation between HC, inflammation, and ISR and investigated the therapeutic potential of stents coated with a CD47-derived peptide (pepCD47) in the hypercholesterolemic rabbit model. METHODS: PepCD47 was immobilized on metal foils and stents using polybisphosphonate coordination chemistry and pyridyldithio/thiol conjugation. Cytokine expression in buffy coat-derived cells cultured over bare metal (BM) and pepCD47-derivatized foils demonstrated an M2/M1 macrophage shift with pepCD47 coating. HC and normocholesterolemic (NC) rabbit cohorts underwent bilateral implantation of BM and pepCD47 stents (HC) or BM stents only (NC) in the iliac location. RESULTS: A 40 % inhibition of cell attachment to pepCD47-modified compared to BM surfaces was observed. HC increased neointimal growth at 4 weeks post BM stenting. These untoward outcomes were mitigated in hypercholesterolemic rabbits treated with pepCD47-derivatized stents. Compared to NC animals, inflammatory cytokine immunopositivity and macrophage infiltration of peri-strut areas increased in HC animals and were attenuated in HC rabbits treated with pepCD47 stents. CONCLUSIONS: Augmented inflammatory responses underlie severe ISR morphology in hypercholesterolemic rabbits. Blockage of initial platelet and leukocyte attachment to stent struts through CD47 functionalization of stents mitigates the pro-restenotic effects of hypercholesterolemia.

Impact of scar, viable myocardium, and epicardial fat on substrate identification of ventricular tachycardia in a case with nonischemic cardiomyopathy.

A 56-year-old man with nonischemic cardiomyopathy underwent orthotopic cardiac transplantation after endocardial and epicardial radiofrequency catheter ablation for pleomorphic ventricular tachycardia. The myocardial substrate and epicardial fat were comprehensively analyzed with three-dimensional electroanatomic maps, late gadolinium enhanced ex-vivo cardiac magnetic resonance, and histological examination. The association of scar, viable myocardium, and epicardial fat with endocardial and epicardial electrogram voltage and duration was quantitatively defined. This case provides a unique opportunity to explore the reliability of electrical surrogates of scar in nonischemic cardiomyopathy.

A prospective evaluation of a protocol for magnetic resonance imaging of patients with implanted cardiac devices.

BACKGROUND: Magnetic resonance imaging (MRI) is avoided in most patients with implanted cardiac devices because of safety concerns. OBJECTIVE: To define the safety of a protocol for MRI at the commonly used magnetic strength of 1.5 T in patients with implanted cardiac devices. DESIGN: Prospective nonrandomized trial. (ClinicalTrials.gov registration number: NCT01130896) SETTING: One center in the United States (94% of examinations) and one in Israel. PATIENTS: 438 patients with devices (54% with pacemakers and 46% with defibrillators) who underwent 555 MRI studies. INTERVENTION: Pacing mode was changed to asynchronous for pacemaker-dependent patients and to demand for others. Tachyarrhythmia functions were disabled. Blood pressure, electrocardiography, oximetry, and symptoms were monitored by a nurse with experience in cardiac life support and device programming who had immediate backup from an electrophysiologist. MEASUREMENTS: Activation or inhibition of pacing, symptoms, and device variables. RESULTS: In 3 patients (0.7% [95% CI, 0% to 1.5%]), the device reverted to a transient back-up programming mode without long-term effects. Right ventricular (RV) sensing (median change, 0 mV [interquartile range {IQR}, -0.7 to 0 V]) and atrial and right and left ventricular lead impedances (median change, -2 Ω [IQR, -13 to 0 Ω], -4 Ω [IQR, -16 to 0 Ω], and -11 Ω [IQR, -40 to 0 Ω], respectively) were reduced immediately after MRI. At long-term follow-up (61% of patients), decreased RV sensing (median, 0 mV, [IQR, -1.1 to 0.3 mV]), decreased RV lead impedance (median, -3 Ω, [IQR, -29 to 15 Ω]), increased RV capture threshold (median, 0 V, IQR, [0 to 0.2 Ω]), and decreased battery voltage (median, -0.01 V, IQR, -0.04 to 0 V) were noted. The observed changes did not require device revision or reprogramming. LIMITATIONS: Not all available cardiac devices have been tested. Long-term in-person or telephone follow-up was unavailable in 43 patients (10%), and some data were missing. Those with missing long-term capture threshold data had higher baseline right atrial and right ventricular capture thresholds and were more likely to have undergone thoracic imaging. Defibrillation threshold testing and random assignment to a control group were not performed. CONCLUSION: With appropriate precautions, MRI can be done safely in patients with selected cardiac devices. Because changes in device variables and programming may occur, electrophysiologic monitoring during MRI is essential.

Establishing a multicenter, preclinical consortium in resuscitation: A pilot experimental trial evaluating epinephrine in cardiac arrest.

BACKGROUND: Large animal studies are an important step in the translation pathway, but single laboratory experiments do not replicate the variability in patient populations. Our objective was to demonstrate the feasibility of performing a multicenter, preclinical, randomized, double-blinded, placebo-controlled cardiac arrest trial. We evaluated the effect of epinephrine on coronary perfusion pressure (CPP) as previous single laboratory studies have reported mixed results. METHODS: Forty-five swine from 5 different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous cardiopulmonary resuscitation (CPR). After 2 min of CPR, 9 animals from each lab were randomized to 1 of 3 interventions given over 12 minutes: (1) Continuous IV epinephrine infusion (0.00375 mg/kg/min) with placebo IV normal saline (NS) boluses every 4 min, (2) Continuous placebo IV NS infusion with IV epinephrine boluses (0.015 mg/kg) every 4 min or (3) Placebo IV NS for both infusion and boluses. The primary outcome was mean CPP during the 12 mins of drug therapy. RESULTS: There were no significant differences in mean CPP between the three groups: 14.4 ± 6.8 mmHg (epinephrine Infusion), 16.9 ± 5.9 mmHg (epinephrine bolus), and 14.4 ± 5.5 mmHg (placebo) (p = NS). Sensitivity analysis demonstrated inter-laboratory variability in the magnitude of the treatment effect (p = 0.004). CONCLUSION: This study demonstrated the feasibility of performing a multicenter, preclinical, randomized, double-blinded cardiac arrest trials. Standard dose epinephrine by bolus or continuous infusion did not increase coronary perfusion pressure during CPR when compared to placebo.

Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models.

OBJECTIVE: Sodium nitroprusside-enhanced cardiopulmonary resuscitation consists of active compression-decompression, an impedance threshold device, abdominal binding, and large intravenous doses of sodium nitroprusside. We hypothesize that sodium nitroprusside-enhanced cardiopulmonary resuscitation will significantly increase carotid blood flow and return of spontaneous circulation compared to standard cardiopulmonary resuscitation after prolonged ventricular fibrillation and pulseless electrical activity cardiac arrest. DESIGN: Prospective randomized animal study. SETTING: Hennepin County Medical Center Animal Laboratory. SUBJECTS: Forty Yorkshire female farm-bred pigs weighing 32 ± 2 kg. INTERVENTIONS: In protocol A, 24 isoflurane-anesthetized pigs underwent 15 mins of untreated ventricular fibrillation and were subsequently randomized to receive standard cardiopulmonary resuscitation (n = 6), active compression-decompression cardiopulmonary resuscitation + impedance threshold device (n = 6), or sodium nitroprusside-enhanced cardiopulmonary resuscitation (n = 12) for up to 15 mins. First defibrillation was attempted at minute 6 of cardiopulmonary resuscitation. In protocol B, a separate group of 16 pigs underwent 10 mins of untreated ventricular fibrillation followed by 3 mins of chest compression only cardiopulmonary resuscitation followed by countershock-induced pulseless electrical activity, after which animals were randomized to standard cardiopulmonary resuscitation (n = 8) or sodium nitroprusside-enhanced cardiopulmonary resuscitation (n = 8). MEASUREMENTS AND MAIN RESULTS: The primary end point was carotid blood flow during cardiopulmonary resuscitation and return of spontaneous circulation. Secondary end points included end-tidal CO2 as well as coronary and cerebral perfusion pressure. After prolonged untreated ventricular fibrillation, sodium nitroprusside-enhanced cardiopulmonary resuscitation demonstrated superior rates of return of spontaneous circulation when compared to standard cardiopulmonary resuscitation and active compression-decompression cardiopulmonary resuscitation + impedance threshold device (12 of 12, 0 of 6, and 0 of 6 respectively, p < .01). In animals with pulseless electrical activity, sodium nitroprusside-enhanced cardiopulmonary resuscitation increased return of spontaneous circulation rates when compared to standard cardiopulmonary resuscitation. In both groups, carotid blood flow, coronary perfusion pressure, cerebral perfusion pressure, and end-tidal CO2 were increased with sodium nitroprusside-enhanced cardiopulmonary resuscitation. CONCLUSIONS: In pigs, sodium nitroprusside-enhanced cardiopulmonary resuscitation significantly increased return of spontaneous circulation rates, as well as carotid blood flow and end-tidal CO2, when compared to standard cardiopulmonary resuscitation or active compression-decompression cardiopulmonary resuscitation + impedance threshold device.

Intra-cardiopulmonary resuscitation hypothermia with and without volume loading in an ischemic model of cardiac arrest.

BACKGROUND: We investigated the effects of intra-cardiopulmonary resuscitation (CPR) hypothermia with and without volume loading on return to spontaneous circulation and infarction size in an ischemic model of cardiac arrest. METHODS AND RESULTS: Using a distal left anterior descending artery occlusion model of cardiac arrest followed by resuscitation with a total of 120 minutes of occlusion and 90 minutes of reperfusion, we randomized 46 pigs into 5 groups and used myocardial staining to define area at risk and myocardial necrosis. Group A had no intervention. Immediately after return of spontaneous circulation, group B received surface cooling with cooling blankets and ice. Group C received intra-CPR 680+/-23 mL of 28 degrees C 0.9% normal saline via a central venous catheter. Group D received intra-CPR 673+/-26 mL of 4 degrees C normal saline followed by surface cooling after return of spontaneous circulation. Group E received intra-CPR and hypothermia after return of spontaneous circulation with an endovascular therapeutic hypothermia system placed in the right atrium and set at a target of 32 degrees C. Intra-CPR volume loading with room temperature (group C) or iced saline (group D) significantly (P<0.05) decreased coronary perfusion pressure (group C, 12.8+/-4.78 mm Hg; group D, 14.6+/-9.9 mm Hg) compared with groups A, B, and E (20.6+/-8.2, 20.1+/-7.8, and 21.3+/-12.4 mm Hg). Return of spontaneous circulation was significantly improved in group E (9 of 9) compared with groups A plus B and C (10 of 18 and 1 of 8). The percent infarction to the area at risk was significantly reduced with intra-CPR hypothermia in groups D (24.3+/-4.2%) and E (4+/-3.4%) compared with groups A (72+/-5.1%) and B (67.3+/-4.2%). CONCLUSIONS: Intra-CPR hypothermia significantly reduces myocardial infarction size. Elimination of volume loading further improves outcomes.

QRS prolongation in myotonic muscular dystrophy and diffuse fibrosis on cardiac magnetic resonance.

Current noninvasive surrogates of cardiac involvement in myotonic muscular dystrophy have low positive predictive value for sudden death. We hypothesized that the cardiac MR signal-to-noise ratio variance (SNRV) is a surrogate of the spatial heterogeneity of myocardial fibrosis and correlates with electrocardiography changes in myotonic muscular dystrophy. The SNRV for contrast enhanced cardiac MR images was calculated over the entire left ventricle in 43 patients with myotonic muscular dystrophy. All patients underwent standard electrocardiography, and a subset of 23 patients underwent signal averaged electrocardiography. After correcting for body mass index, age, and ejection fraction, SNRV was predictive of QRS duration on standard electrocardiography (1.35-msec increased QRS duration/unit increase in SNRV, P < 0.001). SNRV was also predictive of the low-amplitude late-potential duration (1.49-msec increased low-amplitude late-potential duration/unit increase in SNRV, P < 0.001). Ten-fold cross-validation yielded an area under the receiver operating characteristic curve of 0.87 for the predictive value of SNRV for QRS duration greater than 120 msec. The SNRV of the left ventricle is associated with QRS prolongation, likely due to late depolarization of tissue within islands of patchy fibrosis. The association of SNRV with future clinical events warrants further study.

Outcomes from low versus high-flow cardiopulmonary resuscitation in a swine model of cardiac arrest.

BACKGROUND: Return of spontaneous circulation (ROSC) is improved by greater vital organ blood flow during cardiopulmonary resuscitation (CPR). We tested the hypothesis that myocardial flow above the threshold needed for ROSC may be associated with greater vital organ injury and worse outcome. METHODS: Aortic and right atrial pressures were measured with micromanometers in 27 swine. After 10 minutes of untreated ventricular fibrillation, chest compression was performed with an automatic, load-distributing band. Animals were randomly assigned to receive flows just sufficient for ROSC (low flow: target coronary perfusion pressure = 12 mm Hg) or well above the minimally effective level (high flow: coronary perfusion pressure = 30 mm Hg). Myocardial flow was measured with microspheres, defibrillation was performed after 3.5 minutes of CPR, and ejection fraction was measured with echocardiography. RESULTS: Return of spontaneous circulation was achieved by 9 of 9 animals in the high-flow group and 15 of 18 in the low-flow group. All animals in the high-flow group defibrillated initially into a perfusing rhythm, whereas 12 of 15 animals achieving ROSC in the low-flow group defibrillated initially into pulseless electrical activity (P < .05, Fisher exact test). Compared with animals in the low-flow group, animals in the high-flow group had shorter resuscitation times, higher mean aortic pressures at ROSC, and higher ejection fractions at 2 hours post-ROSC (all P < .05). CONCLUSION: High-flow CPR significantly improved arrest hemodynamics, rates of ROSC, and post-ROSC indicators of myocardial status, all indicating less injury with higher flows. No evidence of organ injury from vital organ blood flow substantially above the threshold for ROSC was found.

Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy.

AIMS: The ability of mesenchymal stem cells (MSCs) to heal the chronically injured heart remains controversial. Here we tested the hypothesis that autologous MSCs can be safely injected into a chronic myocardial infarct scar, reduce its size, and improve ventricular function. METHODS AND RESULTS: Female adult Göttingen swine (n = 15) underwent left anterior descending coronary artery balloon occlusion to create reproducible ischaemia-reperfusion infarctions. Bone-marrow-derived MSCs were isolated and expanded from each animal. Twelve weeks post-myocardial infarction (MI), animals were randomized to receive surgical injection of either phosphate buffered saline (placebo, n = 6), 20 million (low dose, n = 3), or 200 million (high dose, n = 6) autologous MSCs in the infarct and border zone. Injections were administered to the beating heart via left anterior thoracotomy. Serial cardiac magnetic resonance imaging was performed to evaluate infarct size, myocardial blood flow (MBF), and left ventricular (LV) function. There was no difference in mortality, post-injection arrhythmias, cardiac enzyme release, or systemic inflammatory markers between groups. Whereas MI size remained constant in placebo and exhibited a trend towards reduction in low dose, high-dose MSC therapy reduced infarct size from 18.2 +/- 0.9 to 14.4 +/- 1.0% (P = 0.02) of LV mass. In addition, both low and high-dose treatments increased regional contractility and MBF in both infarct and border zones. Ectopic tissue formation was not observed with MSCs. CONCLUSION: Together these data demonstrate that autologous MSCs can be safely delivered in an adult heart failure model, producing substantial structural and functional reverse remodelling. These findings demonstrate the safety and efficacy of autologous MSC therapy and support clinical trials of MSC therapy in patients with chronic ischaemic cardiomyopathy.

Feasibility of real-time magnetic resonance imaging for catheter guidance in electrophysiology studies.

BACKGROUND: Compared with fluoroscopy, the current imaging standard of care for guidance of electrophysiology procedures, magnetic resonance imaging (MRI) provides improved soft-tissue resolution and eliminates radiation exposure. However, because of inherent magnetic forces and electromagnetic interference, the MRI environment poses challenges for electrophysiology procedures. In this study, we sought to test the feasibility of performing electrophysiology studies with real-time MRI guidance. METHODS AND RESULTS: An MRI-compatible electrophysiology system was developed. Catheters were targeted to the right atrium, His bundle, and right ventricle of 10 mongrel dogs (23 to 32 kg) via a 1.5-T MRI system using rapidly acquired fast gradient-echo images (approximately 5 frames per second). Catheters were successfully positioned at the right atrial, His bundle, and right ventricular target sites of all animals. Comprehensive electrophysiology studies with recording of intracardiac electrograms and atrial and ventricular pacing were performed. Postprocedural pathological evaluation revealed no evidence of thermal injury to the myocardium. After proof of safety in animal studies, limited real-time MRI-guided catheter mapping studies were performed in 2 patients. Adequate target catheter localization was confirmed via recording of intracardiac electrograms in both patients. CONCLUSIONS: To the best of our knowledge, this is the first study to report the feasibility of real-time MRI-guided electrophysiology procedures. This technique may eliminate patient and staff radiation exposure and improve real-time soft tissue resolution for procedural guidance.

Effect of high flow transnasal dry air on core body temperature in intubated human subjects.

PURPOSE: Early initiation of hypothermia is recommended in the setting of cardiac arrest. Current hypothermia methods are invasive and expensive and not applicable in ambulatory settings. We investigated the evaporative cooling effect of high flow transnasal dry air on core esophageal temperature in human volunteers. METHODS & RESULTS: A total of 32 subjects (mean age 53.2 ± 9.3 yrs., mean weight 90 ± 17 kg) presenting for elective electrophysiological procedures were enrolled for the study. Half of the subjects were men. Following general anesthesia induction, high flow (30 LPM) medical grade ambient dry air with a relative humidity ∼20% was administered through a nasal mask for 60 min. Core temperature was monitored at the distal esophagus. Half of the subjects (16/32) were subject to high flow air and the remainder served as controls. Over a 1-h period, mean esophageal temperature decreased from 36.1 ± 0.3 °C to 35.5 ± 0.1 °C in the test subjects (p < 0.05). No significant change in temperature was observed in the control subjects (36.3 ± 0.3 °C to 36.2 ± 0.2 °C, p = NS). No adverse events occurred. CONCLUSION: Transnasal high flow dry air through the nasopharynx reduces core body temperature. This mechanism can be harnessed to induce hypothermia in patients where clinically indicated without any deleteriouseffects in a short time exposure.

The Application of Virtual Reality for Preoperative Planning of Lymphovenous Anastomosis in a Patient with a Complex Lymphatic Malformation.

The management of lymphatic malformations (LMs) is challenging, particularly for large and complex lesions involving anatomical structures in the adjacent tissue. While lymphovenous anastomosis (LVA) has been reported as an effective treatment for lymphedema, it has hardly been described as a treatment for LM. Virtual reality has the ability to visualize human structures in three dimensions and can be used for the preoperative planning of complex cases. Here, we describe the first case of the management of an LM by LVA preoperatively planned with virtual reality. A young woman presented with an LM previously treated by gross excision. Following persistent complaints of swelling, a minimally invasive microsurgical intervention was planned. The results of the single photon emission tomography with computed tomography (SPECT-CT) and lymphoscintigraphy were analyzed using a virtual reality program, and a 3D patient-specific model was constructed. Based on the combined findings of this 3D model and lymphography with a fluorescent marker, a precise skin incision could be determined and one lymph vessel was anastomosed to a nearby vein. The swelling of the thigh reduced and the discomfort disappeared. Although more reports are needed to confirm its efficacy, LVA planned with virtual reality constructed images appears to be a valuable treatment option for complex lesions, including LMs.

Determinants of gradient field-induced current in a pacemaker lead system in a magnetic resonance imaging environment.

BACKGROUND: The determinants of low-frequency-induced current by magnetic resonance imaging (MRI) gradient fields in a pacemaker lead system are largely unknown. OBJECTIVE: The purpose of this study was to determine the magnitude of MRI low-frequency-induced current in an implanted pacemaker lead system and to investigate in vivo determinants of low-frequency-induced current in an animal model. METHODS: Six mongrel dogs underwent conventional single-chamber pacemaker implantation with a current recorder connected in series. Pulse generator (PG) was programmed to VOO 120 bpm with subthreshold output. MRI was performed in a 1.5-T scanner. Low-frequency-induced current was recorded during unipolar pacing, bipolar pacing, and bipolar pacing with the PG case electrically isolated from the pocket. In each mode, low-frequency-induced current was recorded with and without a large loop of additional lead connected in series. RESULTS: With a conventional implant, low-frequency-induced current was < or =0.5 mA in all three pacing modes. With five external loops, the magnitude of low-frequency-induced current increased to >30 mA, with consistent myocardial capture in unipolar and bipolar pacing. However, in bipolar pacing with the PG electrically isolated from the pocket, low-frequency-induced current decreased to <0.5 mA with no myocardial capture even with additional looped leads. CONCLUSION: Under conventional implant conditions, the magnitude of low-frequency-induced current is <0.5 mA and is unlikely to cause myocardial capture; however, arrhythmia induction cannot be excluded. With sufficient increase in effective loop area (additional looped leads), direct myocardial capture by the low-frequency-induced current is possible. In this study, breaking the return pathway by electrically isolating the PG case from the circuit abolished low-frequency-induced current.

Clinical utility and safety of a protocol for noncardiac and cardiac magnetic resonance imaging of patients with permanent pacemakers and implantable-cardioverter defibrillators at 1.5 tesla.

BACKGROUND: Magnetic resonance imaging (MRI) is an important diagnostic modality currently unavailable for millions of patients because of the presence of implantable cardiac devices. We sought to evaluate the diagnostic utility and safety of noncardiac and cardiac MRI at 1.5T using a protocol that incorporates device selection and programming and limits the estimated specific absorption rate of MRI sequences. METHODS AND RESULTS: Patients with no imaging alternative and with devices shown to be MRI safe by in vitro phantom and in vivo animal testing were enrolled. Of 55 patients who underwent 68 MRI studies, 31 had a pacemaker, and 24 had an implantable defibrillator. Pacing mode was changed to "asynchronous" for pacemaker-dependent patients and to "demand" for others. Magnet response and tachyarrhythmia functions were disabled. Blood pressure, ECG, oximetry, and symptoms were monitored. Efforts were made to limit the system-estimated whole-body average specific absorption rate to 2.0 W/kg (successful in >99% of sequences) while maintaining the diagnostic capability of MRI. No episodes of inappropriate inhibition or activation of pacing were observed. There were no significant differences between baseline and immediate or long-term (median 99 days after MRI) sensing amplitudes, lead impedances, or pacing thresholds. Diagnostic questions were answered in 100% of nonthoracic and 93% of thoracic studies. Clinical findings included diagnosis of vascular abnormalities (9 patients), diagnosis or staging of malignancy (9 patients), and assessment of cardiac viability (13 patients). CONCLUSIONS: Given appropriate precautions, noncardiac and cardiac MRI can potentially be safely performed in patients with selected implantable pacemaker and defibrillator systems.

Contrast-enhanced multidetector computed tomography viability imaging after myocardial infarction: characterization of myocyte death, microvascular obstruction, and chronic scar.

BACKGROUND: The ability to distinguish dysfunctional but viable myocardium from nonviable tissue has important prognostic implications after myocardial infarction. The purpose of this study was to validate the accuracy of contrast-enhanced multidetector computed tomography (MDCT) for quantifying myocardial necrosis, microvascular obstruction, and chronic scar after occlusion/reperfusion myocardial infarction. METHODS AND RESULTS: Ten dogs and 7 pigs underwent balloon occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. Contrast-enhanced (Visipaque, 150 mL, 325 mg/mL) MDCT (0.5 mm x 32 slice) was performed before occlusion and 90 minutes (canine) or 8 weeks (porcine) after reperfusion. MDCT images were analyzed to define infarct size/extent and microvascular obstruction and compared with postmortem myocardial staining (triphenyltetrazolium chloride) and microsphere blood flow measurements. Acute and chronic infarcts by MDCT were characterized by hyperenhancement, whereas regions of microvascular obstruction were characterized by hypoenhancement. MDCT infarct volume compared well with triphenyltetrazolium chloride staining (acute infarcts 21.1+/-7.2% versus 20.4+/-7.4%, mean difference 0.7%; chronic infarcts 4.15+/-1.93% versus 4.92+/-2.06%, mean difference -0.76%) and accurately reflected morphology and the transmural extent of injury in all animals. Peak hyperenhancement of infarcted regions occurred approximately 5 minutes after contrast injection. MDCT-derived regions of microvascular obstruction were also identified accurately in acute studies and correlated with reduced flow regions as measured by microsphere blood flow. CONCLUSIONS: The spatial extent of acute and healed myocardial infarction can be determined and quantified accurately with contrast-enhanced MDCT. This feature, combined with existing high-resolution MDCT coronary angiography, may have important implications for the comprehensive assessment of cardiovascular disease.

Novel electrode design for potentially painless internal defibrillation also allows for successful external defibrillation.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) save lives, but the defibrillation shocks delivered by these devices produce substantial pain, presumably due to skeletal muscle activation. In this study, we tested an electrode system composed of epicardial panels designed to shield skeletal muscles from internal defibrillation, but allow penetration of an external electric field to enable external defibrillation when required. METHODS AND RESULTS: Eleven adult mongrel dogs were studied under general anesthesia. Internal defibrillation threshold (DFT) and shock-induced skeletal muscle force at various biphasic shock strengths were compared between two electrode configurations: (1) a transvenous coil placed in the right ventricle (RV) as cathode and a dummy can placed subcutaneously in the left infraclavicular fossa as anode (control configuration) and (2) RV coil as cathode and the multielectrode epicardial sock with the panels connected together as anode (sock-connected). External DFT was also tested with these electrode configurations, as well as with the epicardial sock present, but with panels disconnected from each other (sock-disconnected). Internal DFT was higher with sock-connected than control (24 +/- 7 J vs. 16 +/- 6 J, P < 0.02), but muscle contraction force at DFT was greatly reduced (1.3 +/- 1.3 kg vs. 10.6 +/- 2.2 kg, P < 0.0001). External defibrillation was never successful, even at 360 J, with sock-connected, while always possible with sock-disconnected. CONCLUSION: Internal defibrillation with greatly reduced skeletal muscle stimulation can be achieved using a novel electrode system that also preserves the ability to externally defibrillate when required. This system may provide a means for painless ICD therapy.

Rapid Induction of Therapeutic Hypothermia Using Transnasal High Flow Dry Air.

Early induction of therapeutic hypothermia (TH) is recommended in out-of-hospital cardiac arrest (CA); however, currently no reliable methods exist to initiate cooling. We investigated the effect of high flow transnasal dry air on brain and body temperatures in adult porcine animals. Adult porcine animals (n = 23) under general anesthesia were subject to high flow of transnasal dry air. Mouth was kept open to create a unidirectional airflow, in through the nostrils and out through the mouth. Brain, internal jugular, and aortic temperatures were recorded. The effect of varying airflow rate and the air humidity (0% or 100%) on the temperature profiles were recorded. The degree of brain cooling was measured as the differential temperature from baseline. A 10-minute exposure of high flow dry air caused rapid cooling of brain and gradual cooling of the jugular and the aortic temperatures in all animals. The degree of brain cooling was flow dependent and significantly higher at higher airflow rates (0.8°C ± 0.3°C, 1.03°C ± 0.6°C, and 1.3°C ± 0.7°C for 20, 40, and 80 L, respectively, p < 0.05 for all comparisons). Air temperature had minimal effect on the brain cooling over 10 minutes with similar decrease in temperature at 4°C and 30°C. At a constant flow rate (40 LPM) and temperature, the degree of cooling over 10 minutes during dry air exposure was significantly higher compared to humid air (100% saturation) (1.22°C ± 0.35°C vs. 0.21°C ± 0.12°C, p < 0.001). High flow transnasal dry air causes flow dependent cooling of the brain and the core temperatures in intubated porcine animals. The mechanism of cooling appears to be evaporation of nasal mucus as cooling is mitigated by humidifying the air. This mechanism may be exploited to initiate TH in CA.

Magnetic resonance assessment of the substrate for inducible ventricular tachycardia in nonischemic cardiomyopathy.

BACKGROUND: Patients with left ventricular dysfunction have an elevated risk of sudden cardiac death. However, the substrate for ventricular arrhythmia in patients with nonischemic cardiomyopathy remains poorly understood. We hypothesized that the distribution of scar identified by MRI is predictive of inducible ventricular tachycardia. METHODS AND RESULTS: Short-axis cine steady-state free-precession and postcontrast inversion-recovery gradient-echo MRI sequences were obtained before electrophysiological study in 26 patients with nonischemic cardiomyopathy. Left ventricular ejection fraction was measured from end-diastolic and end-systolic cine images. The transmural extent of scar as a percentage of wall thickness (percent scar transmurality) in each of 12 radial sectors per slice was calculated in all myocardial slices. The percentages of sectors with 1% to 25%, 26% to 50%, 51% to 75%, and 76% to 100% scar transmurality were determined for each patient. Predominance of scar distribution involving 26% to 75% of wall thickness was significantly predictive of inducible ventricular tachycardia and remained independently predictive in the multivariable model after adjustment for left ventricular ejection fraction (odds ratio, 9.125; P=0.020). CONCLUSIONS: MR assessment of scar distribution can identify the substrate for inducible ventricular tachycardia and may identify high-risk patients with nonischemic cardiomyopathy currently missed by ejection fraction criteria.

A Magnetic Resonance Imaging-Conditional External Cardiac Defibrillator for Resuscitation Within the Magnetic Resonance Imaging Scanner Bore.

BACKGROUND: Subjects undergoing cardiac arrest within a magnetic resonance imaging (MRI) scanner are currently removed from the bore and then from the MRI suite, before the delivery of cardiopulmonary resuscitation and defibrillation, potentially increasing the risk of mortality. This precludes many higher-risk (acute ischemic and acute stroke) patients from undergoing MRI and MRI-guided intervention. An MRI-conditional cardiac defibrillator should enable scanning with defibrillation pads attached and the generator ON, enabling application of defibrillation within the seconds of MRI after a cardiac event. An MRI-conditional external defibrillator may improve patient acceptance for MRI procedures. METHODS AND RESULTS: A commercial external defibrillator was rendered 1.5 Tesla MRI-conditional by the addition of novel radiofrequency filters between the generator and commercial disposable surface pads. The radiofrequency filters reduced emission into the MRI scanner and prevented cable/surface pad heating during imaging, while preserving all the defibrillator monitoring and delivery functions. Human volunteers were imaged using high specific absorption rate sequences to validate MRI image quality and lack of heating. Swine were electrically fibrillated (n=4) and thereafter defibrillated both outside and inside the MRI bore. MRI image quality was reduced by 0.8 or 1.6 dB, with the generator in monitoring mode and operating on battery or AC power, respectively. Commercial surface pads did not create artifacts deeper than 6 mm below the skin surface. Radiofrequency heating was within US Food and Drug Administration guidelines. Defibrillation was completely successful inside and outside the MRI bore. CONCLUSIONS: A prototype MRI-conditional defibrillation system successfully defibrillated in the MRI without degrading the image quality or increasing the time needed for defibrillation. It can increase patient acceptance for MRI procedures.