Myocardial cell death in reperfused and nonreperfused myocardial infarctions. MR imaging with dysprosioum-DTPA-BMA in the pig.

PURPOSE: To investigate whether Dy-DTPA-BMA-enhanced MR imagining would permit identification of myocardial cell death, myocardial infarction was induced in 12 domestic pigs. MATERIAL AND METHODS: In 6 pigs with irreversible cell damage, Dy-DTPA-BMA (1.0 mmol/kg b.w.) was administered i.v. 70 min after coronary occlusion. In 6 other pigs, the infarctions were reperfused 80 min after the occlusion, followed by injection of Dy-DTPA-BMA after 30 min of reperfusion. In 4 additional pigs, the hearts were reperfused after 2 min of occlusion. All 16 pigs were sacrificed 10 min after the injection of Dy-DTPA-BMA. The hearts were excised and imaged with MR. RESULTS: Reversibly injured myocardium could not be distinguished from adjacent nonischaemic myocardium after the administration of Dy-DTPA-BMA. Reperfused, infarcted myocardium demonstrated a high signal intensity in the proton-density- and T2-weighted sequences, despite a 5-fold higher Dy concentration compared with both nonreperfused infarcted and nonischaemic myocardium. CONCLUSION: This lack of susceptibility effect in infarcted myocardium, due to a homogeneous distribution of Dy, indicates the usefulness of Dy as a marker of tissue viability.

Double-contrast MR imaging of reperfused porcine myocardial infarction. An experimental study using Gd-DTAA and Dy-DTPA-BMA.

PURPOSE: Myocardial infarctions were induced in 12 pigs to investigate whether a double-contrast method, combining a positive and a negative MR contrast agent, could improve the visualization of reperfused myocardial infarctions. MATERIAL AND METHODS: All 12 pigs were subjected to 80 min of occlusion followed by reperfusion. In the double-contrast group (6 pigs), Gd-DTPA-BMA (0.3 mmol/kg b.w.) and Dy-DTPA-BMA (1.0 mmol/kg b.w.) were administered i.v. after 30 min of reperfusion. In the remaining 6 pigs, a single injection of Gd-DTPA-BMA (0.3 mmol/kg b.w.) was given after 30 min of reperfusion. All pigs were sacrificed 10 min post-contrast injection, corresponding to a reperfusion time of 40 min. The hearts were excised and imaged with MR. The concentrations of GD and Dy were measured in infarcted and nonischaemic myocardium using ICP-AES. RESULTS AND CONCLUSION: Contrast media concentrations were more than 4-fold higher in infarcted compared with nonischaemic myocardium. The infarctions were best shown on T1-weighted images, and there were no differences between the double and single contrast groups. In the T2-weighted images, the infarctions were significantly better visualized in the double-contrast group, due to a Dy-induced signal intensity loss in nonischaemic myocardium.

Dy-DTPA-BMA as an indicator of tissue viability in MR imaging. An experimental study in the pig.

The aim of this study was to investigate whether dysprosium (Dy) induced signal intensity (SI) loss in infarcted tissue in MR imaging. Myocardial infarction was induced in 12 pigs and Dy-DTPA-BMA (1.0 mmol/kg b.w.) was administered i.v. to 6 pigs 4 hours after occlusion and allowed to accumulate in the infarctions for 2 hours. Dy was analysed by inductively coupled plasma atomic emission spectrometry in infarcted and non-ischaemic tissue samples. The remaining 6 pigs, not administered contrast medium, served as controls. The infarctions demonstrated a high SI in the proton density- and T2-weighted sequences in both groups (ex vivo), although the Dy-DTPA-BMA group demonstrated a 3-fold greater concentration of Dy in infarcted compared with non-ischaemic myocardium. The lack of SI loss after Dy accumulation indicates that susceptibility effects are minor or absent in infarcted myocardium.

Sodium-calcium relationships and cardiac function during coronary bolus perfusion.

The present review deals with the side-effects of contrast media (CM) on cardiac function during coronary angiography. A physiological approach is used to redefine existing concepts of CM osmotoxicity and chemotoxicity in terms of osmolal, ionic and molecular effects. The main idea conveyed is that purely ionic effects are of central importance during and immediately following the transit of a brief coronary bolus. Ionic effects result largely from rapid transient washout of normal extracellular ions, but are also influenced by ions present in the CM. In particular, the calcium (Ca) and sodium (Na) ions controlling cardiac function are easily affected. The myocardial Na-Ca exchange, which is mainly a physiological mechanism for cellular Ca efflux during cardiac relaxation, is therefore highlighted in detail. The importance of avoiding a potential Na-Ca mismatch is shown by examples from basic physiology, cardiac surgery and coronary angiography and by results of experiments with Visipaque. In the isomolal and isotonic CM Visipaque, which is based on the dimer isodixanol (320 mg I/ml), an available osmolal space is filled with an appropriately balanced supplement consisting of NaCl (19mM) and CaCl2 (0.3 mM).

Complementary use of T2-weighted and postcontrast T1- and T2*-weighted imaging to distinguish sites of reversible and irreversible brain damage in focal ischemic lesions in the rat brain.

The evolution of a photochemically induced cortical infarct was monitored using T2-, postcontrast (GdDOTA) T1-, and postcontrast (DyDTPA-BMA) T2*-weighted NMR imaging techniques. Data acquired with these different NMR imaging types were compared, both qualitatively and quantitatively. The T2*-weighted NMR images after spordiamide injection (DyDTPA-BMA) were perfusion-weighted images that allowed the differentiation between several infarct-related areas in terms of different degrees of perfusion deficiency. No quantitative information on cerebral blood flow (CBF) was obtained. A clear distinction was made between areas with a complete lack of CBF located in the core of the lesion and temporary CBF insufficiencies in the rim surrounding this core. Concomitant observations on T2-weighted and postcontrast T1-weighted images revealed the same temporary rim characterized by an increased water content, and an intact blood-brain barrier (BBB), as well as by reduced perfusion. This rim appeared within the first hours after infarct induction, reached a maximum 24 h later, and lasted between 3-5 days, when its size gradually decreased until complete disappearance. These observations suggest the existence of an area at risk. Only on postcontrast T1-weighted images, the core of the lesion remained visible during the whole experimental period (10 days) and reflected in all likelihood the irreversibly damaged ischemic central core. The combined application of different NMR imaging techniques when studying focal cerebral infarctions in the rat brain allowed us to distinguish, in terms of NMR characteristics, zones of reversible from irreversible brain damage and to estimate the severity of the damage. This might offer an appropriate experimental setup for the screening of cerebroprotective compounds.

Tissue protection by allopurinol in the myocardial calcium paradox.

The aim of the present study was to evaluate the protective properties of the xanthine oxidase inhibitor allopurinol in the myocardial calcium paradox. Two injury levels, minimal and total calcium paradox, caused by different volumes (5 ml and 45 ml) of calcium-free perfusion (5 min) prior to calcium repletion (15 min) were examined +/- allopurinol (0.15 mmol/l) in the normothermic isolated rat heart model. Allopurinol supplementation (5 min prior to, during and 5 min following Ca2+-free perfusion) had no effect upon tissue injury in the total calcium paradox, but afforded considerable protection as assessed by enzymatic, physiologic, and metabolic parameters in the minimal calcium paradox. When allopurinol was omitted during calcium repletion, tissue protection was less apparent. The presence of verapamil (2 mumol/l) in addition to allopurinol (5 min prior to, during, and 5 min following calcium depletion) afforded only a marginal further protection in the minimal calcium paradox. It is concluded from the present study that tissue protection by allopurinol in the calcium paradox is limited to minimal or less severe calcium paradox models and that the protective action of allopurinol may indicate an inhibition of the xanthine oxidase reaction and the generation of free oxygen radicals.

Protection by verapamil in the calcium paradox: dependence on micromolar calcium.

Myocardial protection by verapamil in the calcium paradox has been the subject of considerable controversy. In order to reassess the protective properties of verapamil in the normothermic isolated rat heart three injury levels (minimal, subtotal, total calcium paradox) caused by increasing flow rates (1, 2, 9 ml . min-1) or volumes (5, 10, 45 ml) of calcium free perfusion (5 min) before calcium repletion (15 min) were determined in the presence and absence of verapamil (2 mumol . litre-1) using enzymatic, metabolic, and physiological indices. Verapamil supplementation had minimal effect on tissue injury in the 45 ml and 10 ml volume group of hearts but afforded considerable protection in the 5 ml volume group. The addition of EDTA (0.1 mmol . litre-1) to the calcium free perfusate in the 5 ml volume group produced a subtotal calcium paradox on which verapamil had no effect. Conversely, when 20 mumol . litre-1 calcium was added to the otherwise calcium free perfusate in the 45 ml volume group a minimal calcium paradox was created on which verapamil had a substantial protective effect. It is concluded that tissue protection by verapamil in the calcium paradox requires the presence in the myocardium of both verapamil and trace amounts of calcium before the onset of calcium repletion. Tissue protection by verapamil is therefore limited to minimal injury types.