Detection of impaired coronary flow reserve in coronary artery disease using transthoracic echocardiographic assessment of coronary sinus blood flow.

In order to establish whether coronary flow reserve (CFR) can be measured by transthoracic echocardiography (TTE) with pulse wave Doppler echocardiography, 14 patients with coronary artery disease (CAD) and 12 normal subjects were studied. Coronary sinus blood flow was measured at rest and 2 minutes after intravenous injection of 0.56 mg/kg dipyridamole (DP). CFR was calculated as the DP to rest flow ratio. Patients with CAD were found to have significantly decreased CFR when compared to normal subjects. These findings suggest that TTE may be useful in diagnosing CAD.

Collagen fiber morphology determines echogenicity of myocardial scar: implications for image interpretation.

Fibrous tissue appears as echo dense areas on conventional ultrasound images; however, the determinants of such echo brightness have not been assessed. We demonstrated previously, using 600-MHz ultrasound images, that collagen fiber morphology determines echo brightness. In the current study, we tested the hypothesis that collagen fiber morphology also determines echogenicity of myocardial scar at the lower transducer frequencies used in conventional ultrasound. We examined both the infarcted and noninfarcted regions of rat hearts 1 and 3 weeks after permanent coronary artery occlusion. Ultrasound images obtained from excised hearts were digitized to quantify echocardiographic brightness. The hearts were then sectioned, stained with picrosirius red, and examined with polarized light microscopy. We found that myocardial scar tissue appeared either hyperechoic or normoechoic depending on collagen fiber morphology. Specifically, the hyperechoic areas corresponded to the 3-week-old infarcted regions containing thick collagen fibers that appeared predominantly orange when viewed with polarized light. In contrast, normoechoic areas corresponded to the 1-week-old infarcted regions containing thin collagen fibers that appeared predominantly green and also to noninfarcted myocardium. We conclude that the echogenicity of tissue early after infarction is similar to that found in normal, noninfarcted myocardium, thus compromising the ability of echocardiography to distinguish between these two states based on echotexture.

Hypoechoic areas on ultrasound images of atheroma are not always diagnostic of fatty plaque.

Atherosclerotic plaques in ultrasound (US) images may have bright areas suggestive of fibrous plaque and hypoechoic areas that are often interpreted as fatty plaque. The current study was designed to test the hypothesis that fibrous tissue in atherosclerotic plaques will be hyperechoic or hypoechoic, depending on collagen fiber morphology. Twelve segments of aortic arch containing atherosclerotic plaques obtained from cadavers were imaged with an 8-MHz US transducer, then sectioned, stained with picrosirius red and examined with polarized light microscopy. There were 12 bright areas that contained predominantly thick collagen fibers. Two areas were anechoic, with predominantly thin collagen fibers. There were 11 hypoechoic areas; six of these contained thin fibers and five contained no collagen on polarized light microscopy, suggesting fat or thrombus. We conclude that fibrous aortic plaques consisting of predominantly thin fibers appear hypoechoic or anechoic on US images and, therefore, may be indistinguishable from fatty plaques.

Helicobacter pylori infection inhibits healing of the wounded duodenal epithelium in vitro.

Helicobacter pylori (Hp) infection causes duodenal ulcers, delays the healing of such ulcers, and is associated with ulcer recurrence. The pathogenic mechanisms involved in Hp-induced duodenal mucosal injury and delay in ulcer healing remain unclear. In this study we sought to investigate the possible pathogenic actions of Hp infection and vacuolating cytotoxin (Vac A) on duodenal epithelial wound healing, using an in vitro wound model consisting of excisionally scraped or eroded IEC-6 duodenal monolayers. Two isogenic strains of Hp were used: wild-type strain 60190, producing Vac A; and an isogenic mutant strain, 60190-v1, that lacks the gene to produce the cytotoxin. The addition of Vac A-positive or Vac A-negative Hp (50:1 ratio of bacterial to epithelial cells) to the eroded or "wounded" IEC-6 monolayers resulted in significant inhibition of wound reepithelialization. The Vac A-positive Hp produced significantly greater inhibition than did the Vac A-negative Hp (70% and 35% inhibition, respectively; P <.001). Additionally, the bacterial supernatant containing Vac A (but not the supernatant lacking the cytotoxin) caused significant inhibition of IEC-6 wound reepithelialization in the absence of Hp infection, indicating that Vac A has an independent inhibitory action on wound reepithelialization. The Vac A inhibition of IEC-6 reepithelialization correlated with down-regulation of actin stress fibers in the migrating cells. Epidermal growth factor (EGF) stimulated IEC-6 wound reepithelialization with a corresponding increase in the formation of actin stress fiber. Vac A-positive bacterial supernatant (but not Vac A-negative supernatant) prevented the EGF-stimulated increase in IEC-6 actin stress fiber formation and wound reepithelialization. These findings demonstrate that Hp infection inhibits the process of duodenal epithelial wound healing. Hp inhibition of duodenal wound healing may therefore be an important pathogenic factor contributing to duodenal mucosal injury and delay in ulcer healing in vivo.