Potential of Spread Field Imaging Collimation Technology in SPECT to Differentiate Sub-endocardial and Sub-epicardial Regions: A Phantom Study

The purpose of the present study was to evaluate the acoustic properties of myocytes in normal, pressure-overload hypertrophic, and amyloid myocardium. Myocardial tissue specimens at autopsy were obtained from 10 subjects without cardiovascular disease, six patients with left ventricular (LV) hypertrophy, and six patients with cardiac amyloidosis. Sound speed of myocytes was measured at subendocardial and subepicardial regions in myocardium by use of a high-frequency (450 MHz) acoustic microscope. In normal myocardium, the sound speed of myocytes was significantly higher in subendocardial region (1,728+/-19 m/sec) than in subepicardial region (1,645+/-22 m/sec) (p<0.0001). A significantly higher sound speed of myocytes was observed in the subendocardial region in LV hypertrophic myocardium (1,779+/-19 m/sec) than that in normal myocardium (p<0.001). In amyloid myocardium, a significantly lower sound speed of myocytes was observed in subendocardial (1,560+/-8 m/sec) and subepicardial (1,594+/-48 m/sec) regions than that in respective regions of the normal myocardium (p<0.0001 and p<0.05, respectively). Transmural variation in sound speed of myocytes measured by high-frequency acoustic microscopy existed in normal left ventricle. The differential myocyte sound speed and its transmural variation was observed in LV hypertrophic and amyloid myocardium as compared with normal myocardium. High-frequency acoustic microscopy can be a promising technique for myocardial tissue characterization at the myocyte level.

Microstructure-based finite element model of left ventricle passive inflation

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction. This study aimed to analyze whether early HFpEF is already associated with ultrastructural alterations and whether they differ quantitatively among the layers of the left ventricular wall. HFpEF was induced in pigs by deoxy‐corticosterone acetate (DOCA) treatment along with a high‐salt/high lipid diet over 3 months and compared with weight‐matched normal pigs (n = 5 each). Samples of the left ventricle were taken and processed for light and electron microscopy. Interstitial fibrosis, subcellular composition of cardiomyocytes and mean cardiomyocyte diameter were evaluated by stereology in subendocardial, midmyocardial and subepicardial regions. DOCA enhanced the mean cardiomyocyte diameter in all locations of the ventricle wall to the same degree. The subcellular composition did not differ between the locations and was not altered by DOCA. The volume fraction of interstitium was smaller in the subendocardium of DOCA group than of control group. Within the interstitium, the volume fraction of collagen fibrils (between cardiomyocytes) was increased in the subendocardial and midmyocardial wall layers of the DOCA group but not in the subepicardial layer. Although the capillary length density and average supply area were not altered in response to DOCA in any of the wall layers, the volume fraction of blood vessels related to the interstitial space was enhanced in the subendocardium of the DOCA group but not in the other wall layers. In conclusion, cardiomyocyte changes due to DOCA were similar in subepicardial, midmyocardial and subendocardial regions but DOCA‐induced changes in the interstitium appeared to be more pronounced in the subendocardial ventricular wall layers. This suggests a pivotal role of the subendocardial interstitium in the pathogenesis of HFpEF.

Transmural heterogeneity of norepinephrine uptake in failing human hearts

Inhibition of the angiotensin converting enzyme (ACE) is known to enhance coronary blood flow via partial suppression of angiotensin II and potentiation of bradykinin. The purpose of these experiments was to evaluate the contribution of each of these mechanisms to the ACE inhibition induced changes in blood flow in myocardial regions perfused by intact or stenotic coronary arteries. Seven domestic swine were submitted to an 82% stenosis of the left anterior descending artery with the circumflex artery left intact to serve as control area. Regional coronary blood flows were measured by the radioactive microsphere technique in the total area perfused by each coronary artery and in the subepicardial and subendocardial regions of each area separately, at rest and after treatments with captopril, losartan and a bradykinin antagonist given consecutively. We found a significant increase of total flow in both the stenotic and intact areas after captopril. Losartan caused a significant fall in systemic blood pressure with no further changes in overall coronary blood flow and the bradykinin antagonist produced a small but nonsignificant decline in total coronary flow. However, further separate analysis of subregions showed that subendocardial regions had a sharper increase in flow after captopril, and a significantly greater decline after bradykinin inhibition than subepicardial regions, whereas losartan tended to shunt blood from the subendocardial to the subepicardial regions. The results indicate that augmentation of coronary blood flow after ACE inhibition is not further enhanced by angiotensin II blockade and is in part mediated via potentiation of endogenous bradykinin, which exerts a preferential vasodilatory effect on the subendocardial regions of the myocardium.

We have recently shown that the cardiac cycle-dependent variation in myocardial ultrasonic integrated backscatter is blunted with regional ischemia in dogs. To determine if global and intramural regional myocardial contractile performance can be quantified by integrated backscatter, we analyzed ultrasonic responses after induction of increased and decreased contractility in five dogs. A recently developed analog data-acquisition system for measuring integrated backscatter in real time was used to sample radiofrequency signals gated from subepicardial or subendocardial regions. Base-line recordings of integrated backscatter, left ventricular pressure, left ventricular dP/dt, and wall thickness were made at 12 left ventricular sites for both intramural regions. Contractility was modified subsequently by either paired pacing or propranolol to produce significantly elevated or depressed values for maximum left ventricular dP/dt compared with baseline (1083 +/- 289 to 3001 +/- 570 mm Hg/sec; p less than .01 for all). The amplitude of the cyclic variation of integrated backscatter was 50% greater (arithmetically) in subendocardial than in subepicardial regions for all treatments (7.6 +/- 0.3 vs 6.0 +/- 0.5 dB, p less than .001). The maximum rate of change in integrated backscatter waveforms during isovolumetric contraction was faster with paired pacing and slower with propranolol than at baseline for all regions (56 +/- 6 to 74 +/- 6 to 82 +/- 5 dB/sec, p less than .005). The maximum rate of change in integrated backscatter also was greater in subendocardial than subepicardial regions (p less than .001). Thus, both regional and global differences in myocardial contractile performance are manifest quantitatively in integrated backscatter waveforms. We propose that the physiologic determinants of these differences may depend on regional and global variations in myofibril elastic characteristics.

Adenosine and AICA-riboside fail to enhance microvascular endothelial preservation

In order to evaluate the role of carnitine on fatty acid metabolism in subepicardial (Epi) and subendocardial (Endo) regions in ischemic heart, tissue levels of carnitine, free fatty acids (FFA), and adenosine triphosphate (ATP) were determined in ischemic, non-ischemic and border areas in dog hearts with acute regional ischemia. Acute regional ischemia was induced by ligation of the left anterior descending coronary artery for 15 min. In normal hearts, tissue carnitine levels were lower in Endo than in Epi. On the other hand, FFA levels were higher in Endo than in Epi. In ATP levels, no significant differences were observed between Endo and Epi. In acute regional ischemia, tissue carnitine levels decreased not only in ischemic and border areas but also in nonischemic area. And the levels were lower in Endo than in Epi in all areas. Tissue ATP levels were also lower in endo than in Epi in all areas. From nonischemic area toward the center of ischemic area, the difference in ATP levels between Endo and Epi became more prominent. Tissue FFA levels increased in ischemic and border areas, while no significant differences were observed between Endo and Epi. These results confirmed that Endo as metabolically more anaerobic than Epi even in normal heart and it became more prominent in the heart with acute regional ischemia.

BackgroundAfter a transient ischemic episode, the subendocardial region is more severely injured than outer subepicardial layers and may regain a proportionately greater degree of mechanical function in the longitudinal direction. We sought to explore left ventricular (LV) transmural mechanics in patients with ST-segment elevation myocardial infarction (STEMI) for determining the mechanism underlying recovery of global LV function after primary percutaneous coronary intervention (PCI).MethodsA total of 42 patients (62 ± 11 years old, 71% male) with a first STEMI underwent serial assessments of LV longitudinal, circumferential and radial strains (LS, CS and RS) by selective tracking of subendocardial and subepicardial regions within 48 hours and a median of 5 months after PCI. LV mechanical parameters were compared with sixteen age and gender matched normal controls.ResultsIn comparison with controls, endocardial and epicardial LS were markedly attenuated at 48 hours following PCI (P < 0.001). An improvement in LV ejection fraction (EF > 5%) following PCI was seen in 24 (57%) patients and was associated with improvement in endocardial and epicardial LS (P < 0.001 and P = 0.003, respectively) and endocardial CS (P = 0.01). Radial strain and wall motion score index, however, remained persistently abnormal. The change in endocardial LS (OR 1.2, 95% CI 1.03 to 1.42, P = 0.01) and the change in epicardial LS (OR 1.2, 95% 1.03 to 1.46, P = 0.02) were significantly associated with the improvement in LVEF, independent of the location of STEMI and the presence of underlying multivessel disease.ConclusionsIn patients with STEMI treated by PCI, the recovery of LV subendocardial shortening strain seen in the longitudinal direction underlies the improvement in LV global function despite persistent abnormalities in radial mechanics and wall motion score index.

We have previously demonstrated that chemotactic factors released from the ischemic canine myocardium peak early during reperfusion and that they elicit neutrophil adherence reactions in vitro that are dependent on the CD18 glycoprotein family. In this study we investigated the hypothesis that neutrophil localization in ischemic canine myocardium in vivo occurs over a similar time course during early reperfusion and involves a CD18-dependent mechanism. We occluded the circumflex coronary artery for 1 hour in acute, open-chest dogs, followed by reperfusion for 1, 2, 3, or 4 hours. Regional myocardial blood flow was determined using radiolabeled microspheres, and localization was traced using technetium-99m-labeled autologous neutrophils. In the first hour of reperfusion, neutrophil localization occurred preferentially within the subendocardial region and was inversely related to flow. Neutrophil localization diminished across the ischemic myocardium from endocardium to epicardium but remained negatively related to flow in the midmyocardial region. Regardless of flow, little neutrophil localization occurred in the subepicardial region. Neutrophil localization was greatest in the first hour of reperfusion and diminished thereafter. By 4 hours of reperfusion, the rate of localization was markedly attenuated relative to 1 hour. Dogs given anti-CD18 monoclonal antibody R15.7 (1 mg/kg i.v.) before occlusion underwent 1 hour of occlusion followed by 1 hour of reperfusion. When compared with 1-hour reperfusion controls, the R15.7-treated dogs demonstrated significant attenuation of neutrophil localization in the subendocardial region. These data support the concepts that rapid neutrophil localization during reperfusion occurs within regions of previous myocardial ischemia and that neutrophils preferentially localize within the subendocardial region. The rate of neutrophil localization is greatest within the first hour after the initiation of reperfusion, and localization is, at least in part, CD18 dependent. Therapies directed against neutrophil-mediated reperfusion injury should be initiated with these considerations in mind.

Effect of Head-Up Tilt-Table Testing on Left Ventricular Longitudinal Strain in Patients With Neurocardiogenic Syncope

AimsMicrovascular dysfunction in hypertrophic cardiomyopathy (HCM) is predictive of clinical decline, however underlying mechanisms remain unclear. Cardiac diffusion tensor imaging (cDTI) allows in vivo characterization of myocardial microstructure by quantifying mean diffusivity (MD), fractional anisotropy (FA) of diffusion, and secondary eigenvector angle (E2A). In this cardiac magnetic resonance (CMR) study, we examine associations between perfusion and cDTI parameters to understand the sequence of pathophysiology and the interrelation between vascular function and underlying microstructure.Methods and resultsTwenty HCM patients underwent 3.0T CMR which included: spin-echo cDTI, adenosine stress and rest perfusion mapping, cine-imaging, and late gadolinium enhancement (LGE). Ten controls underwent cDTI. Myocardial perfusion reserve (MPR), MD, FA, E2A, and wall thickness were calculated per segment and further divided into subendocardial (inner 50%) and subepicardial (outer 50%) regions. Segments with wall thickness ≤11 mm, MPR ≥2.2, and no visual LGE were classified as ‘normal’. Compared to controls, ‘normal’ HCM segments had increased MD (1.61 ± 0.09 vs. 1.46 ± 0.07 × 10−3 mm2/s, P = 0.02), increased E2A (60 ± 9° vs. 38 ± 12°, P < 0.001), and decreased FA (0.29 ± 0.04 vs. 0.35 ± 0.02, P = 0.002). Across all HCM segments, subendocardial regions had higher MD and lower MPR than subepicardial (MDendo 1.61 ± 0.08 × 10−3 mm2/s vs. MDepi 1.56 ± 0.18 × 10−3 mm2/s, P = 0.003, MPRendo 1.85 ± 0.83, MPRepi 2.28 ± 0.87, P < 0.0001).ConclusionIn HCM patients, even in segments with normal wall thickness, normal perfusion, and no scar, diffusion is more isotropic than in controls, suggesting the presence of underlying cardiomyocyte disarray. Increased E2A suggests the myocardial sheetlets adopt hypercontracted angulation in systole. Increased MD, most notably in the subendocardium, is suggestive of regional remodelling which may explain the reduced subendocardial blood flow.

Pathobiology of acute myocardial ischemia: Metabolic, functional and ultrastructural studies

Effect of beta-adrenergic receptor stimulation on regional myocardial metabolism: Importance of coronary vessel patency

Early impairment of left ventricular function in patients with systemic hypertension: New insights with 2-dimensional speckle tracking echocardiography