Frequent Premature Atrial Contractions Lead to Adverse Atrial Remodeling and Atrial Fibrillation in a Swine Model.

BACKGROUND: Frequent premature atrial complexes (PACs) are associated with future incident atrial fibrillation (AF), but whether PACs contribute to development of AF through adverse atrial remodeling has not been studied. This study aimed to explore the effect of frequent PACs from different sites on atrial remodeling in a swine model. METHODS: Forty swine underwent baseline electrophysiologic studies and echocardiography followed by pacemaker implantations and paced PACs (50% burden) at 250-ms coupling intervals for 16 weeks in 4 groups: (1) lateral left atrium (LA) PACs by the coronary sinus (Lat-PAC; n=10), (2) interatrial septal PACs (Sep-PAC; n=10), (3) regular LA pacing at 130 beats/min (Reg-130; n=10), and (4) controls without PACs (n=10). At the final study, repeat studies were performed, followed by tissue histology and molecular analyses focusing on fibrotic pathways. RESULTS: Lat-PACs were associated with a longer P-wave duration (93.0±9.0 versus 74.2±8.2 and 58.8±7.6 ms; P<0.001) and greater echocardiographic mechanical dyssynchrony (57.5±11.6 versus 35.7±13.0 and 24.4±11.1 ms; P<0.001) compared with Sep-PACs and controls, respectively. After 16 weeks, Lat-PACs led to slower LA conduction velocity (1.1±0.2 versus 1.3±0.2 [Sep-PAC] versus 1.3±0.1 [Reg-130] versus 1.5±0.2 [controls] m/s; P<0.001) without significant change in atrial ERP. The Lat-PAC group had a significantly increased percentage of LA fibrosis and upregulated levels of extracellular matrix proteins (lysyl oxidase and collagen 1 and 8), as well as TGF-ß1 (transforming growth factor-ß1) signaling proteins (latent and monomer TGF-ß1 and phosphorylation/total ratio of SMAD2/3; P<0.05). The Lat-PAC group had the longest inducible AF duration (terminal to baseline: 131 [interquartile range 30, 192] seconds versus 16 [6, 26] seconds [Sep-PAC] versus 22 [11, 64] seconds [Reg-130] versus -1 [-16, 7] seconds [controls]; P<0.001). CONCLUSIONS: In this swine model, frequent PACs resulted in adverse atrial structural remodeling with a heightened propensity to AF. PACs originating from the lateral LA produced greater atrial remodeling and longer induced AF duration than the septal-origin PACs. These data provide evidence that frequent PACs can cause adverse atrial remodeling as well as AF, and that the location of ectopic PACs may be clinically meaningful.

Pulsed Field Ablation of Left Ventricular Myocardium in a Swine Infarct Model.

BACKGROUND: Pulsed field ablation (PFA) leads to cell death by irreversible electroporation. There are limited data about PFA lesion characteristics in the ventricle, particularly in the presence of myocardial scar. OBJECTIVES: This study sought to evaluate the lesion characteristics of PFA and radiofrequency energy (RFA) in healthy and infarcted left ventricular (LV) myocardium in swine. METHODS: Swine (n = 10) underwent either: 1) 120-minute left anterior descending coronary artery balloon occlusion myocardial infarction and survived for 6 to 8 weeks (n = 8); or 2) served as healthy control subjects (n = 2). PFA or RFA was delivered to the LV endocardium in regions of healthy myocardium or scar identified with electroanatomical mapping. Bipolar, biphasic PFA was delivered for 2.5 seconds × 4 applications/site using 2 different catheters: linear quadripolar (FOCAL) or multispline 8-pole catheter (BASKET). Gross and histologic measurements of lesion size were performed. RESULTS: In the PFA group, 21 lesions were delivered to healthy LV and 20 to areas of scar. Overall, there was no significant difference in lesion depth between catheter groups (FOCAL linear vs BASKET; P = 0.740), whereas lesion width was greater for BASKET (10.6 ± 2.4 mm vs 13.3 ± 3.3 mm; P = 0.007). In myocardial scar, lesion depth was not significantly different between PFA catheters (P = 0.235). However, lesion depth for PFA was greater than for RFA (PFA vs RFA; 6.1 ± 1.7 mm vs 3.8 ± 1.7 mm; P = 0.005). CONCLUSIONS: PFA allows rapid, safe, and effective ablation of surviving islands of myocardium within and around infarcted LV substrate. This technology holds promise for treating infarct-related ventricular tachycardia in humans.

Evaluating Radioactive Analogs of Doxorubicin to Quantify ChemoFilter Binding and Whole-Body Positron Emission Tomography/Magnetic Resonance Imaging for Drug Biodistribution.

PURPOSE: To evaluate radiolabeled doxorubicin (Dox) analogs as tracers of baseline Dox biodistribution in vivo during hepatic intra-arterial chemotherapy and to assess the efficacy of ChemoFilter devices to bind Dox in vitro. MATERIALS AND METHODS: In an in vitro static experiment, [fluorine-18]N-succinimidyl 4-fluorobenzoate ([18F]SFB) and [fluorine-18]fluorobenzoyl-doxorubicin ([18F]FB-Dox) were added to a beaker containing a filter material (Dowex cation exchange resin, single-stranded DNA (ssDNA) resin, or sulfonated polymer coated mesh). In an in vitro flow model, [18F]FB-Dox was added into a Dox solution in phosphate-buffered saline, and the solution flowed via a syringe column containing the filter materials. In an in vitro flow experiment, using micro-positron emission tomography (PET), images were taken as [18F]SFB and [18F]FB-Dox moved through a phantom. For in vivo biodistribution testing, a catheter was placed into the common hepatic artery of a swine, and [18F]FB-Dox was infused over 30 seconds. A 10-minute dynamic image and three 20-minute static images were acquired using 3T PET/MR imaging. RESULTS: In the in vitro static experiment, [18F]FB-Dox demonstrated 76.7%, 88.0%, and 52.4% binding to the Dowex resin, ssDNA resin, and coated mesh, respectively. In the in vitro flow model, the first-pass binding of [18F]FB-Dox to the Dowex resin, ssDNA resin, and coated mesh was 76.7%, 74.2%, and 76.2%, respectively, and the total bound fraction was 80.9%, 84.6%, and 79.9%, respectively. In the in vitro flow experiment using micro-PET, the phantom demonstrated a greater amount of [18F]FB-Dox bound to both filter cartridges than of the control [18F]SFB. In in vivo biodistribution testing, the first 10 minutes depicted [18F]FB-Dox moving through the right upper quadrant of the abdomen. A region-of-interest analysis showed that the relative amount increased by 2.97 times in the gallbladder and 1.08 times in the kidney. The amount decreased by 0.74 times in the brain and 0.57 times in the heart. CONCLUSIONS: [18F]FB-Dox can be used to assess Dox binding to ChemoFilters as well as in vivo biodistribution. This sets the stage for the evaluation of ChemoFilter effectiveness in reducing systemic toxicity from intra-arterial chemotherapy.

Effect of Epicardial Pulsed Field Ablation Directly on Coronary Arteries.

BACKGROUND: The unique tissue selectivity of pulsed field ablation (PFA) allows for minimizing collateral damage to the nerves/esophagus. However, the safety profile of epicardial PFA on coronary arteries (CAs) has not been well defined. OBJECTIVES: This study sought to evaluate the effect of epicardial PFA directly on CAs in a swine model. METHODS: In 4 swine, an 8-F linear quadripolar PFA catheter (FARAPULSE Inc) was introduced into the pericardial space via a subxiphoid puncture. After coronary angiography (Angio), QRS synchronized, biphasic, bipolar PFA was delivered directly on the left anterior descending artery, left circumflex artery, or normal myocardium (control) (2.0 kV × 4 applications per site). Angio was repeated immediately after ablation and repeated every 5 minutes to quantify the degree of CA narrowing. After 4- or 8-week survival, repeat Angio was performed followed by gross and histologic lesion analyses. RESULTS: A total of 15 lesions were delivered (8 left anterior descending arteries, 3 left circumflexes, and 4 controls). Target site Angio revealed median of 47% (IQR: 38%-69%) acute luminal narrowing immediately after PFA, which gradually resolved over 30 minutes. Epicardial PFA lesions extended into the myocardium with a median depth of 4.1 mm (IQR: 3.6-5.6 mm) passing across the CAs and adipose tissue. However, 87.5% of the CAs demonstrated minimal to mild CA stenosis associated with neointimal hyperplasia and tunica media fibrosis. CONCLUSIONS: In a swine model, epicardial PFA directly on CAs allowed the creation of myocardial lesions but led to a CA response characterized by acute moderate spasm and chronic mild stenosis via neointimal hyperplasia.

Effect of Low-Frequency Therapeutic Ultrasound on Induction of Nitric Oxide in CKD: Potential to Prevent Acute Kidney Injury.

INTRODUCTION: Post-contrast acute kidney injury (PC-AKI) develops in a significant proportion of patients with CKD after invasive cardiology procedures and is strongly associated with adverse outcomes. OBJECTIVE: We sought to determine whether increased intrarenal nitric oxide (NO) would prevent PC-AKI. METHODS: To create a large animal model of CKD, we infused 250 micron particles into the renal arteries in 56 ± 8 kg pigs. We used a low-frequency therapeutic ultrasound device (LOTUS - 29 kHz, 0.4 W/cm2) to induce NO release. NO and laser Doppler probes were used to assess changes in NO content and blood flow. Glomerular filtration rate (GFR) was measured by technetium-diethylene-triamine-pentaacetic acid (Tc-99m-DTPA) radionuclide imaging. PC-AKI was induced by intravenous infusion of 7 cm3/kg diatrizoate. In patients with CKD, we measured GFR at baseline and during LOTUS using Tc-99m-DTPA radionuclide imaging. RESULTS: In the pig model, CKD developed over 4 weeks (serum creatinine [Cr], mg/dL, 1.0 ± 0.2-2.6 ± 0.9, p < 0.01, n = 12). NO and renal blood flow (RBF) increased in cortex and medulla during LOTUS. GFR increased 75 ± 24% (p = 0.016, n = 3). PC-AKI developed following diatrizoate i.v. infusion (Cr 2.6 ± 0.7 baseline to 3.4 ± 0.6 at 24 h, p < 0.01, n = 3). LOTUS (starting 15 min prior to contrast and lasting for 90 min) prevented PC-AKI in the same animals 1 week later (Cr 2.5 ± 0.4 baseline to 2.6 ± 0.7 at 24 h, p = ns, n = 3). In patients with CKD (n = 10), there was an overall 25% increase in GFR in response to LOTUS (p < 0.01). CONCLUSIONS: LOTUS increased intrarenal NO, RBF, and GFR and prevented PC-AKI in a large animal model of CKD, and significantly increased GFR in patients with CKD. This novel approach may provide a noninvasive nonpharmacological means to prevent PC-AKI in high-risk patients.

Wireless Resonant Circuits Printed Using Aerosol Jet Deposition for MRI Catheter Tracking.

Interventional magnetic resonance imaging (MRI) could allow for diagnosis and immediate treatment of ischemic stroke; however, such endovascular catheter-based procedures under MRI guidance are inherently difficult. One major challenge is tracking the tip of the catheter, as standard fabrication methods for building inductively coupled coil markers are rigid and bulky. Here, we report a new approach that uses aerosol jet deposition to three-dimensional (3-D) print an inductively coupled RF coil marker on a polymer catheter. Our approach enables lightweight conforming markers on polymer catheters and these low-profile markers allow the catheter to be more safely navigated in small caliber vessels. Prototype markers with an inductor with the geometry of a double helix are incorporated on catheters for in vitro studies, and we show that these markers exhibit good signal amplification. We report temperature measurements and, finally, demonstrate feasibility in a preliminary in vivo experiment. We provide material properties and electromagnetic simulation performance analysis. This paper presents fully aerosol jet-deposited and functional wireless resonant markers on polymer catheters for use in 3T clinical scanners.

Endovascular Ion Exchange Chemofiltration Device Reduces Off-Target Doxorubicin Exposure in a Hepatic Intra-arterial Chemotherapy Model.

Purpose: To determine if endovascular chemofiltration with an ionic device (ChemoFilter [CF]) can be used to reduce systemic exposure and off-target biodistribution of doxorubicin (DOX) during hepatic intra-arterial chemotherapy (IAC) in a preclinical model. Materials and Methods: Hepatic IAC infusions were performed in six pigs with normal livers. Animals underwent two 10-minute intra-arterial infusions of DOX (200 mg) into the common hepatic artery. Both the treatment group and the control group received initial IAC at 0 minutes and a second dose at 200 minutes. Prior to the second dose, CF devices were deployed in and adjacent to the hepatic venous outflow tract of treatment animals. Systemic exposure to DOX was monitored via blood samples taken during IAC procedures. After euthanasia, organ tissue DOX concentrations were analyzed. Alterations in systemic DOX exposure and biodistribution were compared by using one-tailed t tests. Results: CF devices were well tolerated, and no hemodynamic, thrombotic, or immunologic complications were observed. Animals treated with a CF device had a significant reduction in systemic exposure when compared with systemic exposure in the control group (P <.009). Treatment with a CF device caused a significant decrease in peak DOX concentration (31%, P <.01) and increased the time to maximum concentration (P <.03). Tissue analysis was used to confirm significant reduction in DOX accumulation in the heart and kidneys (P <.001 and P <.022, respectively). Mean tissue concentrations in the heart, kidneys, and liver of animals treated with CF compared with those in control animals were 14.2 µg/g ± 1.9 (standard deviation) versus 26.0 µg/g ± 1.8, 46.4 µg/g ± 4.6 versus 172.6 µg/g ± 40.2, and 217.0 µg/g ± 5.1 versus 236.8 µg/g ± 9.0, respectively. Fluorescence imaging was used to confirm in vivo DOX binding to CF devices. Conclusion: Reduced systemic exposure and heart bioaccumulation of DOX during local-regional chemotherapy to the liver can be achieved through in situ adsorption by minimally invasive image-guided CF devices.© RSNA, 2019.

An Intravascular Tantalum Oxide-based CT Contrast Agent: Preclinical Evaluation Emulating Overweight and Obese Patient Size.

Purpose To compare the CT imaging performance of a carboxybetaine zwitterionic-coated tantalum oxide (TaCZ) nanoparticle CT contrast agent with that of a conventional iodinated contrast agent in a swine model meant to simulate overweight and obese patients. Materials and Methods Four swine were evaluated inside three different-sized adipose-equivalent encasements emulating abdominal girths of 102, 119, and 137 cm. Imaging was performed with a 64-detector row CT scanner at six scan delays after intravenous injection of 240 mg element (Ta or I) per kilogram of body weight of TaCZ or iopromide. For each time point, contrast enhancement of the aorta and liver were measured by using regions of interest. Two readers independently recorded the clarity of vasculature using a five-point Likert scale. Findings were compared by using paired t tests and Wilcoxon signed-rank tests. Results Mean peak enhancement was higher for TaCZ than for iopromide in the aorta (270 HU [σ = 24.5] vs 199 HU [σ = 10.2], P < .001) and liver (61.3 HU [σ = 11.7] vs 45.2 HU [σ = 8], P < .001). Vascular clarity was higher for TaCZ than for iopromide in 63% (132 of 208), 82% (170 of 208), and 86% (178 of 208) of the individual vessels at the 102-, 119-, and 137-cm girths, respectively (P < .01). Arterial clarity scores were higher for TaCZ than for iopromide in 62% (208 of 336) of vessels. Venous clarity scores were higher for TaCZ than for iopromide in 89% (128 of 144) of the veins in the venous phase and in 100% (144 of 144) of veins in the delayed phase (P < .01). No vessel showed higher clarity score with iopromide than with TaCZ. Conclusion An experimental tantalum nanoparticle-based contrast agent showed greater contrast enhancement compared with iopromide in swine models meant to simulate overweight and obese patients. © RSNA, 2018.

Interventional magnetic resonance imaging guided carotid embolectomy using a novel resonant marker catheter: demonstration of preclinical feasibility.

To assess the visualization and efficacy of a wireless resonant circuit (wRC) catheter system for carotid artery occlusion and embolectomy under real-time MRI guidance in vivo, and to compare MR imaging modality with x-ray for analysis of qualitative physiological measures of blood flow at baseline and after embolectomy. The wRC catheter system was constructed using a MR compatible PEEK fiber braided catheter (Penumbra, Inc, Alameda, CA) with a single insulated longitudinal copper loop soldered to a printed circuit board embedded within the catheter wall. In concordance with IACUC protocol (AN103047), in vivo carotid artery navigation and embolectomy were performed in four farm pigs (40-45 kg) under real-time MRI at 1.5T. Industry standard clots were introduced in incremental amounts until adequate arterial occlusion was noted in a total of n=13 arteries. Baseline vasculature and restoration of blood flow were confirmed via MR and x-ray imaging, and graded by the Thrombolysis in Cerebral Infarction (TICI) scale. Wilcoxon signed-rank tests were used to analyze differences in recanalization status between DSA and MRA imaging. Successful recanalizations (TICI 2b/3) were compared to clinical rates reported in literature via binomial tests. The wRC catheter system was visible both on 5° sagittal bSSFP and coronal GRE sequence. Successful recanalization was demonstrated in 11 of 13 occluded arteries by DSA analysis and 8 of 13 by MRA. Recanalization rates based on DSA (0.85) and MRA (0.62) were not significantly different from the clinical rate of mechanical aspiration thrombectomy reported in literature. Lastly, a Wilcoxon signed rank test indicated no significant difference between TICI scores analyzed by DSA and MRA. With demonstrated compatibility and visualization under MRI, the wRC catheter system is effective for in vivo endovascular embolectomy, suggesting progress towards clinical endovascular interventional MRI.

Endovascular MR-guided Renal Embolization by Using a Magnetically Assisted Remote-controlled Catheter System.

Purpose To assess the feasibility of a magnetically assisted remote-controlled (MARC) catheter system under magnetic resonance (MR) imaging guidance for performing a simple endovascular procedure (ie, renal artery embolization) in vivo and to compare with x-ray guidance to determine the value of MR imaging guidance and the specific areas where the MARC system can be improved. Materials and Methods In concordance with the Institutional Animal Care and Use Committee protocol, in vivo renal artery navigation and embolization were tested in three farm pigs (mean weight 43 kg ± 2 [standard deviation]) under real-time MR imaging at 1.5 T. The MARC catheter device was constructed by using an intramural copper-braided catheter connected to a laser-lithographed saddle coil at the distal tip. Interventionalists controlled an in-room cart that delivered electrical current to deflect the catheter in the MR imager. Contralateral kidneys were similarly embolized under x-ray guidance by using standard clinical catheters and guidewires. Changes in renal artery flow and perfusion were measured before and after embolization by using velocity-encoded and perfusion MR imaging. Catheter navigation times, renal parenchymal perfusion, and renal artery flow rates were measured for MR-guided and x-ray-guided embolization procedures and are presented as means ± standard deviation in this pilot study. Results Embolization was successful in all six kidneys under both x-ray and MR imaging guidance. Mean catheterization time with MR guidance was 93 seconds ± 56, compared with 60 seconds ± 22 for x-ray guidance. Mean changes in perfusion rates were 4.9 au/sec ± 0.8 versus 4.6 au/sec ± 0.6, and mean changes in renal flow rate were 2.1 mL/min/g ± 0.2 versus 1.9 mL/min/g ± 0.2 with MR imaging and x-ray guidance, respectively. Conclusion The MARC catheter system is feasible for renal artery catheterization and embolization under real-time MR imaging in vivo, and quantitative physiologic measures under MR imaging guidance were similar to those measured under x-ray guidance, suggesting that the MARC catheter system could be used for endovascular procedures with interventional MR imaging. (©) RSNA, 2016.

Endovascular biopsy: Technical feasibility of novel endothelial cell harvesting devices assessed in a rabbit aneurysm model.

The lack of safe and reliable methods to sample vascular tissue in situ limits discovery of the underlying genetic and pathophysiological mechanisms of many vascular disorders, including aneurysms. We investigated the feasibility and comparable efficacy of in vivo vascular endothelial cell sampling using a spectrum of endovascular devices. Using the rabbit elastase carotid aneurysm model we evaluated the performance of existing aneurysmal coils, intracranial stents, and stent-like devices to collect vascular endothelial cells. Additionally, we modified a subset of devices to assess the effects of alterations to coil pitch, coil wire contour, and stent surface finishing. Device performance was evaluated by (1) the number of viable endothelial cells harvested, (2) the degree of vascular wall damage analyzed using digital subtraction angiography and histopathological analysis, and (3) the ease of device navigability and retrieval. Isolated cells underwent immunohistochemical analysis to confirm cell type and viability. Coil and stent specifications, technique, and endothelial cell counts were tabulated and statistical analysis performed. Using conventional detachable-type and modified aneurysm coils 11 of 14 (78.6%) harvested endothelial cells with a mean of 7.93 (±8.33) cells/coil, while 15 of 15 (100%) conventional stents, stent-like devices and modified stents harvested endothelial cells with a mean of 831.33 (±887.73) cells/device. Coil stiffness was significantly associated with endothelial cell count in univariate analysis (p = 0.044). For stents and stent-like devices univariate analysis demonstrated stent-to-aorta diameter ratios (p = 0.001), stent length (p = 0.049), and the use of a pulling retrieval technique (p = 0.019) significantly predictive of endothelial cell counts, though a multivariate model using these variables demonstrated only the stent-to-aorta diameter ratio (p = 0.029) predictive of endothelial cell counts. Modified devices did not significantly impact harvesting. The efficacy and safety of existing aneurysm coils, intracranial stents and stent-like devices in collecting viable endothelial cells was confirmed. The technique is reproducible and the quantity and quality of collected endothelial cells is adequate for targeted genetic analysis.

The effect of a peptide-modified thermo-reversible methylcellulose on wound healing and LV function in a chronic myocardial infarction rodent model.

Myocardial infarction is the main contributor to heart failure. In this study we examined whether modification of a thermo-reversible cellulose-based polymer with extracellular-matrix derived functional groups could promote wound healing and improve cardiac function in a chronic rodent model of ischemic cardiomyopathy. To beneficially influence the microenvironment of the injured myocardium, we conjugated either the RGD peptide or the HepIII peptide to the polymer. In vitro cell adhesion studies showed that the peptide-modified polymer promoted cell attachment to the polymer surface. Injection of the thermo-reversible polymer into the aneurismal infarct region of the left ventricle showed that the peptide-modified polymer exhibited significantly improved left ventricular function, increased angiogenesis, decreased infarct size, and an increase in cardiomyocytes within the infarct region at 5 weeks post-treatment (P < 0.05). The results of this study demonstrate that a peptide-modified thermo-reversible polymer has the capability to alter left ventricular (LV) geometry, increase LV function, and promote myocardial regeneration in a chronic model of ischemic cardiomyopathy.

The variable functional effects of the pacing site in normal and scarred ventricles.

BACKGROUND: The pacing site has been shown to influence functional improvement with cardiac resynchronization therapy. We evaluated the effects of the pacing site on left ventricular (LV) function in an animal model. METHODS AND RESULTS: Equilibrium radionuclide angiography was acquired in sinus rhythm (NSR) and with ventricular pacing, from three pacing sites in seven normal and eight infarcted dogs. QRS duration, electrical activation pattern, wall motion, LV ejection fraction (EF), synchrony of ventricular contraction, and mean arterial pressure (MAP), were related to the pacing site and infarct size, during each of 120 episodes. Little changed during pacing in normals. In infarcted dogs, LV wall motion, and synchrony worsened, LVEF and MAP often fell. These changes related to altered activation patterns which were influenced by the pacing site but were not related to infarct size. CONCLUSIONS: Hemodynamic and functional LV changes after infarction were found to vary with the pacing site and associated conduction and synchrony.

Safety and efficacy of endovascular cooling and rewarming for induction and reversal of hypothermia in human-sized pigs.

BACKGROUND AND PURPOSE: Numerous studies indicate that mild hypothermia provides substantial neuroprotection. However, current systems transfer insufficient heat to rapidly vary core temperature. We thus evaluated the safety and efficacy of endovascular cooling and rewarming for the induction and reversal of hypothermia. METHODS: In 10 anesthetized pigs (weight, 66+/-2 kg), a heat-exchange balloon catheter was inserted into the inferior vena cava and used to cool to a core temperature of 32 degrees C and then rewarm to normothermia. Control animals had 38 degrees C saline infused. Venous blood was sampled before, during, and after cooling. Three animals in each group were killed 1 week later, and the lungs and inferior vena cava were removed for gross and microscopic examination. In 5 additional animals, cardiac output was measured during cooling to 32 degrees C. RESULTS: Body temperature in the hypothermic animals decreased at a rate of 4.5+/-0.4 degrees C/h. Animals were subsequently rewarmed to 36.0+/-0.04 degrees C at 2.5+/-0.2 degrees C/h. There was no difference in heart rate between hypothermic and control animals, whereas systolic pressure decreased during cooling. Cardiac output was well maintained during cooling. There were no thermal effects on blood elements or blood vessels. CONCLUSIONS: The endovascular heat-exchange system effectively cooled and rewarmed pigs with large thermal mass without producing any adverse effects on blood elements, blood vessel integrity, or cardiovascular function.

Effect of endovascular cooling on myocardial temperature, infarct size, and cardiac output in human-sized pigs.

Mild hypothermia reduces myocardial infarct size in small animals; however, the extent of myocardial protection in large animals with greater thermal mass remains unknown. We evaluated the effects of mild endovascular cooling on myocardial temperature, infarct size, and cardiac output in 60- to 80-kg isoflurane-anesthetized pigs. We occluded the left anterior descending coronary artery for 60 min, followed by reperfusion for 3 h. An endovascular heat-exchange catheter was used to either lower core body temperature to 34 degrees C (n = 11) or maintain temperature at 38 degrees C (n = 11). Additional studies assessed myocardial viability and microvascular perfusion with (99m)Tc-sestamibi autoradiography. Endovascular cooling reduced infarct size compared with normothermia (9 +/- 6% vs. 45 +/- 8% of the area at risk; P < 0.001), whereas the area at risk was comparable (19 +/- 3% vs. 20 +/- 7%; P = 0.65). Salvaged myocardium showed normal sestamibi uptake, confirming intact microvascular flow and myocyte viability. Cardiac output was maintained in hypothermic hearts because of an increase in stroke volume, despite a decrease in heart rate. Mild endovascular cooling to 34 degrees C lowers myocardial temperature sufficiently in human-sized hearts to cause a substantial cardioprotective effect, preserve microvascular flow, and maintain cardiac output.