Endovascular therapeutic hypothermia adjunctive to percutaneous coronary intervention in acute myocardial infarction: realistic simulation as a game changer.

BACKGROUND: Endovascular therapeutic hypothermia (ETH) reduces the damage by ischemia/reperfusion cell syndrome in cardiac arrest and has been studied as an adjuvant therapy to percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). New available advanced technology allows cooling much faster, but there is paucity of resources for training to avoid delays in door-to-balloon time (DTB) due to ETH and subsequently coronary reperfusion, which would derail the procedure. The aim of the study was to describe the process for the development of a simulation, training & educational protocol for the multidisciplinary team to perform optimized ETH as an adjunctive therapy for STEMI. METHODS AND RESULTS: We developed an optimized simulation protocol using modern mannequins in different realistic scenarios for the treatment of patients undergoing ETH adjunctive to PCI for STEMIs starting from the emergency room, through the CathLab, and to the intensive care unit (ICU) using the Proteus® Endovascular System (Zoll Circulation Inc™, San Jose, CA, USA). The primary endpoint was door-to-balloon (DTB) time. We successfully trained 361 multidisciplinary professionals in realistic simulation using modern mannequins and sham situations in divisions of the hospital where real patients would be treated. The focus of simulation and training was logistical optimization and educational debriefing with strategies to reduce waste of time in patient's transportation from different departments, and avoiding excessive rewarming during transfer. Afterwards, the EHT protocol was successfully validated in a trial randomizing 50 patients for 18 minutes cooling before coronary recanalization at the target temperature of 32 ± 1.0 ∘C or PCI-only. A total of 35 patients underwent ETH (85.7% [30/35] in 90 ± 15 minutes), without delays in the mean door-to-balloon time for primary PCI when compared to 15 control group patients (92.1 minutes versus 87 minutes, respectively; p = 0.509). CONCLUSIONS: Realistic simulation, intensive training and educational debriefing for the multidisciplinary team propitiated feasible endovascular therapeutic hypothermia as an adjuvant therapy to primary PCI in STEMI. CLINICALTRIALS: gov: NCT02664194.

Effects of endovascular cooling on infarct size in ST-segment elevation myocardial infarction: A patient-level pooled analysis from randomized trials.

OBJECTIVES: This study sought to examine the relationship between temperature at reperfusion and infarct size. BACKGROUND: Hypothermia consistently reduces infarct size when administered prior to reperfusion in animal studies, however, clinical results have been inconsistent. METHODS: We performed a patient-level pooled analysis from six randomized control trials of endovascular cooling during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in 629 patients in which infarct size was assessed within 1 month after randomization by either single-photon emission computed tomography (SPECT) or cardiac magnetic resonance imaging (cMR). RESULTS: In anterior infarct patients, after controlling for variability between studies, mean infarct size in controls was 21.3 (95%CI 17.4-25.3) and in patients with hypothermia <35°C it was 14.8 (95%CI 10.1-19.6), which was a statistically significant absolute reduction of 6.5%, or a 30% relative reduction in infarct size (P = 0.03). There was no significant difference in infarct size in anterior ≥35°C, or inferior infarct patients. There was no difference in the incidence of death, ventricular arrhythmias, or re-infarction due to stent thrombosis between hypothermia and control patients. CONCLUSIONS: The present study, drawn from a patient-level pooled analysis of six randomized trials of endovascular cooling during primary PCI in STEMI, showed a significant reduction in infarct size in patients with anterior STEMI who were cooled to <35°C at the time of reperfusion. The results support the need for trials in patients with anterior STEMI using more powerful cooling devices to optimize the delivery of hypothermia prior to reperfusion.

Cooling as an Adjunctive Therapy to Percutaneous Intervention in Acute Myocardial Infarction: COOL-MI InCor Trial.

Endovascular Therapeutic hypothermia (ETH) reduces the damage caused by postischemia reperfusion injury syndrome in cardiopulmonary arrest and has already established its role in patients with sudden death; however, its role in ST-segment elevation myocardial infarction (STEMI) remains controversial. The objectives of this study were to investigate the safety, feasibility, and 30-day efficacy of rapid induction of therapeutic hypothermia as adjunctive therapy to percutaneous coronary intervention (PCI) in patients with anterior and inferior STEMIs. This was a prospective, controlled, randomized, two-arm, prospective, interventional study of patients admitted to the emergency department within 6 hours of angina onset, with anterior or inferior STEMI eligible for PCI. Subjects were randomized to the hypothermia group (primary PCI+ETH) or to the control group (primary PCI) at a 4:1 ratio. The ETH was induced by 1 L cold saline (1-4°C) associated with the Proteus™ System, by cooling for at least 18 minutes before coronary reperfusion with a target temperature of 32°C ± 1°C. Maintenance of ETH was conducted for 1-3 hours, and active reheating was done at a rate of 1°C/h for 4 hours. Primary safety outcomes were the feasibility of ETH in the absence of (1) door-to-balloon (DTB) delay; (2) major adverse cardiac events (MACE) within 30 days after randomization. The primary outcomes of effectiveness were infarct size (IS) and left ventricular ejection fraction (LVEF) at 30 days. An as-treated statistical analysis was performed. Fifty patients were included: 35 (70%) randomized to the hypothermia group and 15 (30%) to the control group. The mean age was 58 ± 12 years; 78% were men; and associated diseases were 60% hypertension, 42% diabetes, and 72% dyslipidemia. The compromised myocardial wall was anterior in 38% and inferior in 62%, and the culprit vessels were left anterior descending artery (LAD) (40%), right coronary artery (38%), and left circumflex (18%). All 35 patients who attempted ETH (100%) had successful cooling, with a mean endovascular coronary reperfusion temperature of 33.1°C ± 0.9°C. The mean ischemic time was 375 ± 89.4 minutes in the hypothermia group and 359.5 ± 99.4 minutes in the control group. The mean DTB was 92.1 ± 20.5 minutes in the hypothermia group and 87 ± 24.4 minutes in the control group. The absolute difference of 5.1 minutes was not statistically significant (p = 0.509). The MACE rates were similar between both groups (21.7% vs. 20% respectively, p = 0.237). In the comparison between the hypothermia and control groups, no statistically significant differences were observed at 30 days between mean IS (13.9% ± 8% vs. 13.8% ± 10.8%, respectively, p = 0.801) and mean final LVEF (43.3% ± 11.2% vs. 48.3 ± 10.9%, respectively; p = 0.194). Hypothermia as an adjunctive therapy to primary PCI in STEMI is feasible and can be implemented without delay in coronary reperfusion. Hypothermia was safe regarding the incidence of MACE at 30 days. However, there was a higher incidence of arrhythmia and in-hospital infection in the hypothermia group, with no increase in mortality. Regarding efficacy, there was no difference in IS or LVEF at 30 days that would suggest additional myocardial protection with ETH. ClinicalTrials.gov: NCT02664194.

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.

Percutaneous implantation of an intraventricular device for the treatment of heart failure: experimental results and proof of concept.

BACKGROUND: A percutaneous system to implant a ventricular partitioning device (VPD) has been developed to partition the left ventricular (LV) cavity for treating regional wall motion abnormalities associated with post-left anterior descending (LAD) infarction, dilated left ventricle, and systolic dysfunction. The hemodynamic effects of this novel approach were evaluated in an ovine model with an anteroapical infarction created by a coil placed in the LAD. METHODS AND RESULTS: LV anteroapical infarction (MI) was induced in 10 animals. The VPD device was implanted at 6 weeks after MI in 5 animals. The hemodynamic status of each animal was evaluated at 30 weeks post-MI in treated ("VPD+MI" group, n=5) and nontreated ("MI" group, n=5). The comparison of end-point hemodynamic variables shows a significantly smaller end-systolic LV volume in the animals receiving the implant (70.1+/-9.0 mL in "VPD+MI" group vs. 102.9+/-10.3 mL in "MI" group, P < .02), improved ejection fraction (46.9+/-5.2% in "VPD+MI" group vs. 34.7+/-6.8% in "MI" group, P < .04) and preserved cardiac output (5.2+/-0.7 L/min in "VPD+MI" group vs. 5.0+/-1.8 L/min in "MI" group, P=NS), suggesting more efficient mechanical performance of the LV with the implanted VPD. CONCLUSIONS: A significant reduction in LV volumes and corresponding improvement in LV function occurred after device implantation indicating a potential beneficial effect of this new device in treatment of post MI LV dilation.

Pediatric nuclear cardiology.

Echocardiography, magnetic resonance imaging and, more recently, multidetector computed tomography, have led to major advances in noninvasive image assessment of anatomy in pediatric cardiology. The radionuclide methods often lack sufficient resolution to precisely characterize complex morphology in congenital heart lesions. However, these methods provide an accurate and reproduceable quantitative assessment of the physiological consequences of structural heart disease. These unique capabilities will continue to assure ongoing clinical relevance of radionuclide methodology, as is the case in the assessment of heart disease in adult cardiology.

Rodent brain imaging with SPECT/CT.

We evaluated methods of imaging rat models of stroke in vivo using a single photon emission computed tomography (SPECT) system dedicated to small animal imaging (X-SPECT, Gamma Medica-Ideas, Northridge, CA). An animal model of ischemic stroke was developed for in vivo SPECT/CT imaging using the middle cerebral artery occlusion (MCAO) technique. The presence of cerebral ischemia was verified in ex vivo studies using triphenyltetrazolium chloride (TTC) staining. In vivo radionuclide imaging of cerebral blood flow was performed in rats following MCAO using dynamic planar imaging of 99mTc-exametazime with parallel hole collimation. This was followed immediately by in vivo radionuclide imaging of cerebral blood flow with 99mTc-exametazime in the same animals using 1-mm pinhole SPECT. Correlated computed tomography imaging was performed to localize radiopharmaceutical uptake. The animals were allowed to recover and ex vivo autoradiography was performed with separate administration of 99mTc-exametazime. Time activity curve of 99mTc-exametazime showed that the radiopharmaceutical uptake could be maintained for over 9 min. The activity would be expected to be relatively stable for a much longer period, although the data were only obtained for 9 min. TTC staining revealed sizable infarcts by visual observation of inexistence of TTC stain in infracted tissues of MCAO rat brains. In vivo SPECT imaging showed cerebral blood flow deficit in the MCAO model, and the in vivo imaging result was confirmed with ex vivo autoradiography. We have demonstrated a capability of imaging regions of cerebral blood flow deficit in MCAO rat brains in vivo using a pinhole SPECT dedicated to small animal imaging.

Acute neurocardiogenic injury after subarachnoid hemorrhage.

BACKGROUND: Left ventricular (LV) systolic dysfunction has been reported in humans with subarachnoid hemorrhage (SAH), and its underlying pathophysiology remains controversial. Possible mechanisms include myocardial ischemia versus excessive catecholamine release from sympathetic nerve terminals. METHODS AND RESULTS: For 38 months, echocardiography and myocardial scintigraphy with technetium sestamibi (MIBI) and meta-[(123)I]iodobenzylguanidine (MIBG) were performed on 42 patients admitted with SAH to assess myocardial perfusion and sympathetic innervation, respectively. A blinded observer interpreted the scintigraphic images. Cardiac troponin I (cTI) was measured to quantify the degree of myocyte necrosis. Blinded observers calculated the LV ejection fraction and graded each LV segment as normal (score=1), hypokinetic (score=2), or akinetic (score=3). A wall-motion score was calculated by averaging the sum of the 16 segments. All subjects with interpretable scans (N=41) had normal MIBI uptake. Twelve subjects had either global (n=9) or regional (n=3) absence of MIBG uptake. In comparison with patients with normal MIBG uptake, those with evidence of functional denervation were more likely to have LV regional wall-motion abnormalities (92% versus 52%, P=0.030) and cTI levels >1 microg/L (58% versus 21%, P=0.029). CONCLUSIONS: LV systolic dysfunction in humans with SAH is associated with normal myocardial perfusion and abnormal sympathetic innervation. These findings may be explained by excessive release of norepinephrine from myocardial sympathetic nerves, which could damage both myocytes and nerve terminals.

Prospective analysis of prevalence, distribution, and rate of recovery of left ventricular systolic dysfunction in patients with subarachnoid hemorrhage.

OBJECT: Subarachnoid hemorrhage (SAH) has been associated with cardiac injury and left ventricular (LV) dysfunction. The incidence and natural history of neurocardiogenic injury after SAH remains poorly understood. The objective of this study was to describe the incidence, time course, recovery rate, and segmental patterns of LV dysfunction after SAH. METHODS: Echocardiography was performed three times over a 7-day period in 173 patients with SAH. The incidence of global (ejection fraction [EF] < 50%) and segmental (any regional wall-motion abnormality [RWMA]) LV dysfunction was measured. The time course of LV dysfunction was determined by comparing the prevalence of LVEF less than 50% and RWMA at 0 to 2, 3 to 5, and 6 to 8 days after SAH. The recovery rate was defined as the proportion of patients with partial or complete normalization of function. The distribution of RWMAs among 16 LV segments was also determined. An LVEF less than 50% was found in 15% of patients, and 13% had an RWMA with a normal LVEF. There was a trend toward increased dysfunction at 0 to 2 days after SAH, compared with 3 to 8 days after SAH. Recovery of LV function was observed in 66% of patients. The most frequently abnormal LV segments were the basal and middle ventricular portions of the anteroseptal and anterior walls. The apex was rarely affected. CONCLUSIONS: Left ventricular systolic dysfunction occurs frequently after SAH and usually improves over time. The observed segmental patterns of LV dysfunction often do not correlate with coronary artery distributions.

Pinhole single-photon emission computed tomography for myocardial perfusion imaging of mice.

OBJECTIVES: Although transgenic mice have emerged as powerful experimental models of cardiovascular disease, methods for in vivo phenotypic assessment and characterization remain limited, motivating the development of new instruments for biologic measurement. BACKGROUND: We have developed a single-photon emission computed tomography system with a pinhole collimator (pinhole SPECT) for high-resolution cardiovascular imaging of mice. In this study, we describe a protocol for myocardial perfusion imaging of mice using technetium-99m ((99m)Tc)-sestamibi and demonstrate the feasibility for measurement of perfusion defect size from pinhole SPECT images. METHODS: Mice were anesthetized and injected with 370 MBq (10 mCi) of (99m)Tc-sestamibi. Tomographic projection images were acquired by rotating each mouse in a vertical axis in front of a stationary clinical scintillation camera equipped with a pinhole collimator. BALB/c mice (n = 15) were imaged after the permanent ligation of the left anterior descending coronary artery. The resulting defect size was measured from circumferential profiles of short-axis images. After imaging, the hearts were excised and sectioned to obtain ultra-high resolution digital autoradiographs of (99m)Tc-sestamibi, from which the actual infarct size was determined. RESULTS: Reconstructed image quality was equivalent to that obtained for clinical myocardial perfusion imaging. Linear regression analysis produced a correlation coefficient of 0.83 (p < 0.001) between the measured and actual values of the defect size. CONCLUSIONS: These results demonstrate that myocardial perfusion can be characterized qualitatively and quantitatively in mice using pinhole SPECT.

Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the safety and feasibility of endovascular cooling during primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: In experimental models of AMI, mild systemic hypothermia has been shown to reduce metabolic demand and limit infarct size. METHODS: In a multi-center study, 42 patients with AMI (<6 h from symptom onset) were randomized to primary PCI with or without endovascular cooling (target core temperature 33 degrees C). Cooling was maintained for 3 h after reperfusion. Skin warming, oral buspirone, and intravenous meperidine were used to reduce the shivering threshold. The primary end point was major adverse cardiac events at 30 days. Infarct size at 30 days was measured using (99m)Tc-sestamibi SPECT imaging. RESULTS: Endovascular cooling was performed successfully in 20 patients (95%). All achieved a core temperature below 34 degrees C (mean target temperature 33.2 +/- 0.9 degrees C). The mean temperature at reperfusion was 34.7 +/- 0.9 degrees C. Cooling was well tolerated, with no hemodynamic instability or increase in arrhythmia. Nine patients experienced mild episodic shivering. Major adverse cardiac events occurred in 0% vs. 10% (p = NS) of treated versus control patients. The median infarct size was non-significantly smaller in patients who received cooling compared with the control group (2% vs. 8% of the left ventricle, p = 0.80). CONCLUSIONS: Endovascular cooling can be performed safely as an adjunct to primary PCI for AMI. Further clinical trials are required to determine whether induction of mild systemic hypothermia with endovascular cooling will limit infarct size in patients undergoing reperfusion therapy.

Age and aneurysm position predict patterns of left ventricular dysfunction after subarachnoid hemorrhage.

Cardiac injury, including left ventricular dysfunction, frequently occurs in patients with subarachnoid hemorrhage. Patterns of left ventricular dysfunction often do not follow coronary artery distributions, and may correlate with myocardial sympathetic innervation. Left ventricular dysfunction of the anterior and anteroseptal walls that spares the apex is unusual for patients with myocardial infarction and may represent a neurally mediated pattern of injury. We performed serial echocardiography on 225 patients with subarachnoid hemorrhage and classified those with regional wall-motion abnormalities as following either an apex-sparing (AS) or apex-affected (AA) pattern. Wall-motion abnormalities were found in 61 of 225 patients studied (27%). The AS pattern was found in 49% of these patients. Younger age and anterior aneurysm position were independent predictors of this AS pattern. Both patterns of wall-motion abnormalities appear to be transient, reversible phenomena. The AS pattern may represent a unique form of neurally mediated cardiac injury.

Hypothermia during reperfusion limits 'no-reflow' injury in a rabbit model of acute myocardial infarction.

OBJECTIVE: Reflow following coronary artery occlusion is an important predictor of clinical outcome. This study tests the effects of regional hypothermia, initiated late during ischemia and maintained for 2 h of reperfusion, on the no-reflow phenomenon. METHODS: Anesthetized, open-chest New Zealand White rabbits received 30 min of coronary artery occlusion and 3 h reperfusion. Regional myocardial hypothermia (H, n=14), starting 10 min before reperfusion and continuing for 2 h of reperfusion, was compared with normothermia (N, n=14). Regional myocardial blood flow (microspheres) was measured during occlusion and at the end of reperfusion. The anatomic zone of no-reflow (thioflavin S in vivo injection) and infarct size were measured in the ischemic risk region at the end of the study. RESULTS: Myocardial temperature in H rabbits was decreased by 5.0+/-0.4 degrees C from baseline (37.1+/-0.2 degrees C) and remained about 32 degrees C during the cooling phase, returning to 36.0+/-0.3 degrees C at 3 h. N hearts remained within 0.2 degrees C of baseline (37.3+/-0.1 degrees C) throughout. Both groups were equally ischemic during occlusion, but at the end of reperfusion reflow to the previously ischemic zone was significantly higher in H, 77+/-5% of normal blood flow versus 36+/-4% in N (P=0.0001). The zone of anatomic no-reflow was significantly smaller in H, 11+/-3% of the ischemic risk zone versus 37+/-3% in N (P=0.0001), and was proportionally smaller when represented as a percent of the necrotic zone 36+/-6% compared with 75+/-5% in N. Infarct size, expressed as a percent of the ischemic risk zone was significantly smaller in H vs. N hearts (27+/-4 and 51+/-5%, P=0.0000). CONCLUSION: This study shows that hypothermic therapy initiated late during ischemia and continuing for several hours of reperfusion significantly improves reflow and reduces macroscopic zones of no-reflow and necrosis in this model. The improvement in reflow was greater than would be expected in the H group compared with N, based on the extent of necrosis. As reflow is a predictor of outcome, this intervention may have clinical implications.

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 endomyocardial laser channels on regional innervation shown with (125)I-MIBG and autoradiography.

UNLABELLED: The aim of this study was to map regional innervation against regional flow early after laser channel placement using autoradiography in a porcine model. METHODS: Four juvenile male swine underwent left ventricular mapping using a catheter-based mapping system and laser treatment with 20-30 channels to the mid and distal anterior wall of the left ventricle. Three days later animals were injected with 37 MBq (125)I-metaiodobenzylguanidine (MIBG) followed in 3 h with 1,110 MBq (99m)Tc-sestamibi; 1 h later the animals were killed. Hearts were removed, perfusion fixed, and sliced into 1-cm slices. The slices best showing laser holes were selected, and circumferential sections were taken for autoradiography and hematoxylin-eosin staining. Phosphor screens were exposed for (99m)Tc and (125)I, and images were processed. The MIBG image was subtracted from the methoxyisobutylisonitrile (MIBI) image and vice versa, and color tables were applied to the difference images and overlaid on the perfusion images. Quantitative analysis of the light image data was also performed. RESULTS: Thirty-three sections from the last 3 experiments were analyzed. Acoustic damage from 30 laser channels was identified from the hematoxylin-eosin sections. Reduced MIBG relative to regional flow was seen in surrounding tissue corresponding to only 1 channel. There was no statistically significant difference in light units expressed as (MIBG - MIBI)/maximal MIBG value between laser channels and unmarked myocardial map regions. The regions identified from the color table on the map as low MIBG relative to MIBI were significantly lower than remaining laser channels and remaining myocardium. Mean light units for the regions with high MIBG relative to MIBI were significantly higher than the remaining laser channels and remaining myocardium. CONCLUSION: Using a high-resolution technique correlated with microscopic pathology in an animal model, there is negligible regional denervation 3 d after placement of endomyocardial laser channels.

Combined effects of mild hypothermia and glycoprotein IIb/IIIa antagonists on platelet-platelet and leukocyte-platelet aggregation.

Endovascular cooling was assessed as a potential treatment for percutaneous coronary intervention in patients with acute myocardial infarction. Here we show that mild hypothermia: (1) inhibits platelet aggregation; (2) augments eptifibatide- and tirofiban- but not abciximab-induced inhibition of platelet aggregation; (3) increases the formation of adenosine diphosphate-induced leukocyte-platelet aggregates; and (4) diminishes the glycoprotein IIb/IIIa antagonist-induced decrease in leukocyte-platelet aggregates.

Performance evaluation of a pinhole SPECT system for myocardial perfusion imaging of mice.

The increasing use of transgenic mice as models of human physiology and disease has motivated the development of dedicated in vivo imaging systems for anatomic and functional characterization of mice as an adjunct to or a replacement for established ex vivo techniques. We have developed a pinhole single photon emission computed tomography (SPECT) system for high resolution imaging of mice with cardiovascular imaging as the primary application. In this work, we characterize the system performance through phantom studies. The spatial resolution and sensitivity were measured from images of a line source and point source, respectively, and were reported for a range of object-to-pinhole distances and pinhole diameters. Tomographic images of a uniform cylindrical phantom, Defrise phantom, and grid phantom were used to characterize the image uniformity and spatial linearity. The uniform phantom image did not contain any ring or reconstruction artifacts, but blurring in the axial direction was evident in the Defrise phantom images. The grid phantom images demonstrated excellent spatial linearity. A novel phantom modeling perfusion of the left ventricle of a mouse was designed and built with perfusion defects of varying sizes to evaluate the system performance for myocardial perfusion imaging of mice. The defect volumes were measured from the pinhole SPECT images and correlated to the actual defect volumes calculated according to geometric formulas. Linear regression analysis produced a correlation coefficient of r = 0.995 (p < 0.001), demonstrating the feasibility for measurement of perfusion defect size in mice using pinhole SPECT. We have performed phantom studies to characterize the spatial resolution, sensitivity, image uniformity, and spatial linearity of the pinhole SPECT system. Measurement of the perfusion defect size is a valuable phenotypic assessment and will be useful for hypothesis testing in murine models of cardiovascular disease.

Automatic TAC extraction from dynamic cardiac PET imaging using iterative correlation from a population template.

This work describes a new iterative method for extracting time-activity curves (TAC) from dynamic imaging studies using a priori information from generic models obtained from TAC templates. Analytical expressions of the TAC templates were derived from TACs obtained by manual segmentation of three (13)NH3 pig studies (gold standard). An iterative method for extracting both ventricular and myocardial TACs using models of the curves obtained as an initial template was then implemented and tested. These TACs were extracted from masked and unmasked images; masking was applied to remove the lungs and surrounding non-relevant structures. The resulting TACs were then compared with TACs obtained manually; the results of kinetic analysis were also compared. Extraction of TACs for each region was sensitive to the presence of other organs (e.g., lungs) in the image. Masking the volume of interest noticeably reduces error. The proposed method yields good results in terms of TAC definition and kinetic parameter estimation, even when the initial TAC templates do not accurately match specific tracer kinetics.

Combining dynamic and ECG-gated 8²Rb-PET for practical implementation in the clinic.

OBJECTIVES: For many cardiac clinics, list-mode PET is impractical. Therefore, separate dynamic and ECG-gated acquisitions are needed to detect harmful stenoses, indicate affected coronary arteries, and estimate stenosis severity. However, physicians usually order gated studies only because of dose, time, and cost limitations. These gated studies are limited to detection. In an effort to remove these limitations, we developed a novel curve-fitting algorithm [incomplete data (ICD)] to accurately calculate coronary flow reserve (CFR) from a combined dynamic-ECG protocol of a length equal to a typical gated scan. METHODS: We selected several retrospective dynamic studies to simulate shortened dynamic acquisitions of the combined protocol and compared (a) the accuracy of ICD and a nominal method in extrapolating the complete functional form of arterial input functions (AIFs); and (b) the accuracy of ICD and ICD-AP (ICD with a-posteriori knowledge of complete-data AIFs) in predicting CFRs. RESULTS: According to the Akaike information criterion, AIFs predicted by ICD were more accurate than those predicted by the nominal method in 11 out of 12 studies. CFRs predicted by ICD and ICD-AP were similar to complete-data predictions (PICD=0.94 and PICD-AP=0.91) and had similar average errors (eICD=2.82% and eICD-AP=2.79%). CONCLUSION: According to a nuclear cardiologist and an expert analyst of PET data, both ICD and ICD-AP predicted CFR values with sufficient accuracy for the clinic. Therefore, by using our method, physicians in cardiac clinics would have access to the necessary amount of information to differentiate between single-vessel and triple-vessel disease for treatment decision making.