NCT01718561.

Experimental myocardial infarction was induced in rats. The myocardial accumulation of hyaluronan (HA) and water during the development of infarction was measured. The extractable HA content of the infarcted area increased progressively from day 1 and on day 3 reached a threefold increase compared with the HA amounts in myocardium of sham operated controls. The relative water content of infarcted areas also increased progressively reaching a maximum value by day 3 and was strongly correlated with the HA accumulation. Affinity histochemistry visualized a thin rim of HA in the endoperimysium in healthy myocardium. By day 2 an interstitial edema with inflammatory cells was apparent. The widened endoperimysium stained extensively for HA. By its water-binding ability, interstitial accumulation of HA will contribute to the interstitial edema in infarcted myocardial tissue. An interstitial edema is likely to influence the electromechanical characteristics of the myocardium and facilitate reentry phenomena due to a loss of contact between muscle cells. The edema also induces an increased extracellular pressure and an altered myocardial wall compliance that might impair myocardial microcirculation. The findings are relevant to an understanding of the beneficial effect of hyaluronidase treatment in limiting cellular damage during myocardial ischemia. (J. Clin. Invest. 1991. 88:1622-1628

Six pigs with coronary artery occlusion were investigated with MR imaging before and subsequently for about 2.5 hours at repeated intervals after the intravenous administration of Gd-DTPA (0.4 mmol/kg). The animals were sacrificed after a total occlusion time of 6 hours and the hearts were excised. The excised hearts were then reexamined in the MR equipment and stained with TTC (triphenyl tetrazolium) in order to define areas of infarction. Four control hearts with 6-hour-old infarctions were only imaged ex vivo without any previous administration of contrast media. In vivo, there was no clear demarcation of infarction with or without Gd-DTPA. Ex vivo, without any contrast media, the infarctions were poorly discriminated with a discretely increased signal intensity relative to normal myocardium in the T2 weighted images. Gd-DTPA was found to accumulate in the infarctions, which caused an elevated signal intensity most pronounced in the T1 weighted images. This considerably improved the delineation of the infarcted area.

Myocardial infarction was induced by ligating a diagonal branch of the left anterior descending artery in 18 pigs. All pigs were sacrificed 6 h after the occlusion. Dysprosium diethylenetriaminepentaacetic acid bismethylamide (Dy-DTPA-BMA, 1 .O mmol/kg) was administered i.v. to 6 pigs, starting 3 min before sacrifice (injection time approximately 1 min). In a second group of 6 pigs, a double-contrast technique was used, consisting of an i.v. injection of gadolinium-DTPA-BMA (0.4 mmol/kg) 2 h before sacrifice, followed by an i.v. injection of Dy-DTPA-BMA (1.0 mmol/kg) 3 min before sacrifice. Six additional pigs, subjected to 6 h of coronary artery occlusion without administration of contrast medium, served as controls. The hearts were excised and imaged with MR. In the control animals. the infarctions demonstrated an increased signal intensity in the proton density-and T2-weighted images. Administration of Dy-DTPA-BMA primarily improved infarct visualization in the proton density-and T2-weighted images, due to reduction of signal intensity in nonischemic myocardium. The double-contrast technique further improved infarct visualization in all sequences.

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