Left ventricular weight but not blood pressure is associated with sex chromosomes in Lyon rats.

OBJECTIVE: To investigate, by studying reciprocal back-crosses to Lyon hypertensive (LH) rats, the involvement of sex chromosome loci in high blood pressure and heart weight in LH rats. METHODS: Reciprocal F1 and F'1 generation male rats obtained from male LH x female Lyon normotensive (LN) and male LN x female LH crosses respectively, male back-cross rats obtained from male LH x female F1 or F'1 and from male F1 or F'1 x female LH crosses, and parental LH and LN male rats were studied at 29-31 weeks of age. Systolic, diastolic, mean and pulse pressures were measured beat to beat in unrestrained rats for 1 h. In addition, relative left and right ventricular weights were measured. RESULTS: The average blood pressures did not differ between F1 and F'1 rats or between the four populations of back-cross rats. On the contrary, the relative left ventricular weight was higher in F'1 than in F1 rats. As a role for loci on the Y chromosome could be discarded by comparison of the two populations of back-cross rats, which differ only in the origin of their Y chromosome, this increase in the relative left ventricular weight of F'1 rats was consistent with an effect of a locus on the LH X chromosome. This was supported by findings in the back-cross populations, those populations in which 100% of the rats carried an LH X chromosome having a significantly higher left ventricular weight than those in which only 50% of the rats carried such a chromosome. The estimate of the genetic determination was higher for left ventricular weight (41%) than for mean arterial pressure (19%). Although these two parameters were associated in the back-cross population, the origin of the X chromosome had no influence on this association. CONCLUSIONS: These findings indicate that, against the genetic background provided by the cross studied and at the age studied, the sex chromosomes of LH and LN rats do not contain loci at which alleles differentially influence blood pressure. They do, however, suggest that relative left ventricular weight in this model has a specific genetic determination, partly contributed by a locus on the X chromosome.

Evaluation of a new preservative solution for cardiac graft during hypothermia.

BACKGROUND: Reports conflict on the beneficial effects of several cardioplegic solutions such as University of Wisconsin and St. Thomas' Hospital solutions. Therefore our objective was to assess the efficacy of several cardioplegic solutions for cardiac preservation by comparing University of Wisconsin modified solution (UW-1 and UW-1 + calcium = UW-2), St. Thomas' Hospital solution N degrees 1 (STH-1), Celsior solution, and a solution from our laboratory, Lyon preservation solution (LYPS). METHODS: We randomized male rats (n = 70) to 7 groups: LYPS, Celsior, STH-1, UW-1, UW-2, normal saline solution, and control. All hearts, except control hearts were preserved by cold storage (8 hours, 4 degrees C) in the various solutions. We used isolated non-working-heart preparations (left ventricular function evaluation, n = 5/group) or biopsy specimens (energetic store evaluation, n = 5/group) to assess quality of heart preservation. RESULTS: Hearts stored with the saline solution had a mean left ventricular developed pressure (LVDP) of 3.6 +/- 1.3 mm Hg. In contrast, LYPS and Celsior hearts had mean LVDP close to that of the control hearts (97 +/- 2.6, 92.1 +/- 2.2, and 122 +/- 1.9 mm Hg, respectively), whereas STH-1, UW-1, and UW-2 hearts presented an intermediate functional response (48 +/- 4, 39.9 +/- 4.1, and 69 +/- 1.8 mm Hg, respectively). The STH-1 and saline hearts showed increased release of creatine kinase (541.9 +/- 168 and 1,080.8 +/- 126.2 UI/liter, respectively). The energetic charge (EC = [(0.5 ADP + ATP)/ATP + ADP + AMP]) in Celsior, UW-2, and saline was significantly lower (p < 0.001) than in the other groups. CONCLUSION: The composition of the preservation solutions had a notable effect on myocardial viability. Our results indicated that LYPS and Celsior solutions had comparable efficacy for left ventricular function. However these solutions may offer better preservation than do UW-1, UW-2, or STH-1 solutions.

Microperfusion techniques for long-term hypothermic preservation.

BACKGROUND: The aim of this study was to compare several methods of hypothermic heart preservation. METHODS: We preserved isolated pig hearts for 24 hours in cold cardioplegia (4 degrees C), using either continuous microperfusion (Group I) or simple storage (Group II), and with a new preservative solution (NPS, groups IA and IIA) vs St. Thomas' solution (groups IB and IIB). The main characteristics of the NPS include (1) prevention of cell swelling with polyethelene glycol (PEG), (2) low calcium and magnesium, and (3) presence of metabolic substrates, such as glucose, insulin, pyruvate, aspartate, alanyl-glutamine, and membrane stabilization compounds such as ethanol and chlorpromazine. RESULTS: The 4 above groups were compared with hearts harvested and immediately reperfused (control group). During preservation, only Group IB showed significant edema (40% +/- 8.4% water gain). Adenylate charge was 25% to 50% higher in microperfused Groups IA and IB (0.678 +/- 0.049 and 0.795 +/- 0.071, respectively) as compared with simple-storage groups IIA and IIB (0.605 +/- 0.048 and 0.524 +/- 0.160, respectively). Ultrastructural analysis showed that tissue injury occurred mainly in Group IIB (altered mitochondria, chromatin clumping). Functional data showed better recovery of NPS groups as compared with St. Thomas groups: coronary flow was identical in Group IB and control (57.8 +/- 22 and 56.6 +/- 14 ml/min/100 g, respectively), and in IA > IB (p < 0.001) and IIA > IIB (p < 0.01); the rate pressure products were higher in NPS groups compared with St. Thomas groups (IA > IB, p < 0.01); IIA > IIB, p < 0.05). CONCLUSIONS: The microperfusion method associated with the NPS provides excellent protection in long-term hypothermic heart preservation.

Biphasic response after brain death induction: prominent part of catecholamines release in this phenomenon.

BACKGROUND: The physiopathology of hemodynamic instability that occurs after brain death remains unknown. The aim of this study was to examine the initial response to brain death induction. METHODS: After anesthesia and monitoring, 16 pigs were randomized into a control group (C, n = 8) and a brain death group (BD, n = 8). We inflated a subdural catheter balloon to induce brain death. We analyzed hemodynamic and plasmatic biochemical data for 180 minutes after brain death induction. Energetic compounds were measured. We expressed the results in comparison with the C group. RESULTS: The C group remained stable. One minute after brain death, the Cushing reflex appeared, with a hyperdynamic response to plasma catecholamines levels increasing (norepinephrine and epinephrine, 3.1-fold, p = 0. 02, and 3.8-fold, p = 0.07, respectively). After a return to baseline, we recorded a second hyperdynamic profile 120 minutes later. At this time, a second peak of catecholamines appeared (6. 3-fold, p = 0.04, and 9.1-fold, p = 0.02, concerning norepinephrine and epinephrine). At the same time, we observed brief myocardial lactate production (+175%, p < 0.01), with a rise of troponine I (+64%, p = 0.03). The energetic index was similar in both groups: 0. 85 (+/-0.02) in the C group vs 0.87 (+/-0.02) in the BD group. CONCLUSIONS: In this model, biphasic plasmatic catecholamine release appears to primarily explain the physiopathology of the hemodynamic response to brain death induction.

Magnetic susceptibility of Dy-DTPA-BMA to reperfused myocardial infarction in an excised dog heart model: evidence of viable myocardium.

OBJECTIVE: To assess the effects of Dy-DTPA-BMA (sprodiamide) on ex-vivo MR imaging of reperfused acute myocardial infarction. METHODS: Eighteen dogs were subjected to 2-hour coronary artery occlusion followed by 24-hour reperfusion. Dysprosium-chelate (Dy-DTPA-BMA) was injected into 16 dogs. Twenty minutes before their sacrifice. Two dogs did not receive the contrast medium and were used as controls. Excised hearts were imaged on T2-weighted spin-echo sequence (T2W SE) and T2*-weighted gradient recalled echo sequence (T2*W GRE), then sectioned and double-perfused for planimetric comparison. RESULTS: Dy-DTPA-BMA induced myocardial signal loss was detected on T2W SE and on T2*W GRE images. The signal loss was observed at the subendocardial location of the myocardial wall inducing an apparent enlargement of the left ventricle cavity and a thinning appearance of the anterior myocardial wall. CONCLUSIONS: Myocyte necrosis diminishes the potency of dysprosium to cause MR imaging signal intensity loss in reperfused myocardial infarction. Pre-infarcted myocardium with potentially reversible viability may be responsible for the effect of the contrast medium.

[Evaluation of a new preservation solution for hypothermic heart transplant]. / Evaluation d'une nouvelle solution de préservation du greffon cardiaque en hypothermie.

AIM: One of the major problems encountered in heart transplant is the limited cardiac preservation time. The time limit from the moment the donor heart is removed to the transplant itself is 4-6 hours at maximum. Extending the preservation time would therefore provide access to a larger pool of donors, and also permit long-distance (transfrontier) organ transfer. To attain this aim, a number of different cardiac preservation solutions have been proposed and evaluated either clinically or experimentally; however, no consensus has yet been reached by the various heart transplant teams involved. As finding an optimal solution is of major importance, the aim of the present study was therefore to assess the efficacy of several cardiac preservation solutions: the University of Wisconsin solutions (UW-1 and UW-1 + calcium = UW-2), the Saint-Thomas' Hospital solution (STH-1) and a new solution (NS) developed by our laboratory. METHOD: Male Wistar rats (n = 60) were anesthetized by i.m. injection of pentobarbitol, and randomized into six groups, i.e., NS (group I), STH-1 (group II), UW-1 (group III), UW-2 (group IV), saline solution, NaCl (group V), and controls (group VI). All the hearts except those in the control group were preserved by immersion (8 hours, 4 degrees C) in the different solutions (n = 10/group). The hearts were either a) reperfused in Langendorff mode (functional assessment, n = 5/group); or b) frozen (energetic assessment, n = 5/group). RESULTS: The hearts treated with NaCl displayed arrhythmia and a collapsed mean left ventricular pressure throughout the reperfusion period (3.6 +/- 1.3 mmHg) compared to the NS hearts and the control group (97 +/- 2.6 and 122 +/- 1.9 respectively), while the STH-1, UW-1 and UW-2 hearts showed an intermediate-range ventricular function (48 +/- 4; 39.9 +/- 4.1; and 69 +/- 1.8 respectively). Creatine kinase levels were higher in the STH-1 and NaCl groups (541.9 +/- 168 and 1,080.8 +/- 126.2 IU/L respectively). The energetic charge was significantly lower in the NaCl and UW-2 groups (P = 0.001) compared to the control, NS, STH-1 and UW-1 groups. CONCLUSION: It was found that the composition of the respective solutions had a major effect on the the quality of myocardial preservation. Compared to the other solutions tested in this study, the NS solution was found to be optimal for the preservation of isolated hypothermic rat hearts.

[Chest wall tumors. Report of 17 cases]. / Tumeurs de la paroi thoracique. A propos de 17 observations.

The aim of this work was to evaluate the different approaches to surgical repair of the thoracic wall and to discuss technical indications. From June 1987 to June 1997, we cared for 17 patients, 14 males (82.3%) and 3 females (17.7%) with parietal neoplasia. All patients underwent a preoperative respiratory work-up to identify tumoral extension. In 6 patients, the morphology and location of the tumor led to CT-guided transthoracic needle aspiration. Tumoral excision in 14 patients (82.3%) included wide resection of osteomuscular structures. Reconstruction of the thoracic wall associated myoplasty in all cases. A prosthesis was installed in 5 cases and a rib transposition in 2. Pathology examination of the surgical specimen revealed 13 primary tumors (76.5%) and 4 secondary tumors (23.5%) CT-guided transthoracic needle aspiration confirmed the diagnosis in 82.2% of the cases. Twelve patients (70.5%) were alive and recurrence free at 85.6 +/- 40 months after surgery. Five patients died (29.5%) 12.2 +/- 10.1 months after surgery. There was one case of prosthesis infection (5.8%). The appropriate choice of the surgical technique and repair materials gave satisfactory oncological, esthetic and functional results independently of the extent of the parietal defect.

Effect of chronic oral supplementation with alpha-tocopherol on myocardial stunning in the dog.

Recent clinical and experimental studies have suggested that antioxidant supplements might actually have harmful as well as beneficial effects in the setting of cardiovascular disease. The mechanisms underlying the beneficial effects of the various antioxidants are poorly understood in humans. Reperfusion-associated myocardial injury, and particularly the phenomenon of stunning, is important because it occurs in clinical settings and may condition the prognosis after short ischemic insult. We studied the effects of chronic (3 months) alpha-tocopherol supplementation with a large oral dose (500 mg daily) on myocardial contractility (stunning) and ventricular arrhythmias in a dog model of short ischemia followed by reperfusion. Twenty dogs were randomized to either an alpha-tocopherol supplemented or a control group. After 3 months, dogs were anesthetized and underwent a 20-min coronary artery occlusion followed by reperfusion. Myocardial regional blood flow was measured by the radioactive microsphere technique and myocardial contractility by sonomicrometry. Plasma alpha-tocopherol was measured by high-performance liquid chromatography in all dogs. Twelve dogs (seven supplemented and five controls) developed ventricular fibrillation at reperfusion, showing no difference between groups. Hemodynamic parameters, blood flow in the ischemic area (collateral flow), and area at risk were similar in the two groups. Regional systolic segment shortening in the ischemic area was similar during ischemia and reperfusion in both groups, representing 41 +/- 15% (mean +/- SEM) of baseline contractility in controls and 51 +/- 8% in supplemented dogs after 150 min of reperfusion. Plasma alpha-tocopherol level was higher in supplemented than in controls (19.1 +/- 1.6 and 6.9 +/- 0.6 mg/L; p < 0.001). Thus a long-term large dose of alpha-tocopherol had no significant effect on postischaemic ventricular arrhythmias and dysfunction (myocardial stunning) in this canine model. These data suggest that if alpha-tocopherol supplementation might be useful to improve the prognosis of coronary patients, it is likely not by interfering with the stunning phenomenon.

In vivo colon wall imaging using endoluminal coils: feasibility study on rabbits.

PURPOSE: To assess in vivo distal colon wall magnetic resonance imaging (MRI) feasibility on rabbits using an endoluminal radio frequency (RF) coil on a 1.5-T clinical scanner. MATERIALS AND METHODS: The endoluminal coil signal-to-noise ratio (SNR) was compared to a clinical four-element phased-array body coil. High-resolution (HR) MRI of rabbit colon walls was performed on six rabbits. The imaging protocol combined T1-weighted fast low-angle-shot (FLASH) sequences with and without fat saturation (FS), T2-weighted True-Fast imaging with steady state precession (Fisp), turbo spin-echo (TSE), and T1-weighted FLASH FS after contrast media injection. Images were compared to histological sections. Catheter tracking using an endoluminal coil in addition to external coils was also evaluated on two rabbits. RESULTS: HR images allow visualization and identification of rabbit colon wall layers. Real-time tracking allows a clear visualization and a good positioning of the endoluminal coil within the rabbit. CONCLUSION: Compared to a clinical multielement array coil, a dedicated endoluminal RF coil provides an important SNR increase at the region of interest (ROI). Very HR images of in vivo rabbit colon walls were achieved providing detailed information on the different wall layers. This technique could be considered on humans for accurate tumoral and inflammatory bowel disease diagnosis.

Myocardial "low reflow" assessed by Dy-DTPA-BMA-enhanced first-pass MR imaging in a dog model.

The aim of this study was to determine whether the use of a magnetic resonance (MR) susceptibility contrast medium, dysprosium diethylenetriamine pentaacetic acid-bismethylamide (Dy DTPA-BMA; Sprodiamide), may characterize myocardial perfusion abnormalities in a dog model of 90 minutes of coronary occlusion followed by 24 hours of reperfusion (no-reflow phenomenon installed). First-pass MR imaging after an intravenous bolus administration of the contrast agent was performed at the end of reperfusion. Signal intensity analysis on MR imaging, planimetry of pathological data, and blood flow determination were obtained by reference methods for comparison. Dogs were separated into two groups according to the level of collateral blood flow level (group I, <22.5 % of the flow in the non-ischemic zone; group II, >22.5 % of the flow in the non-ischemic zone). Signal intensity-time curves in the ischemic and non-ischemic left ventricle walls were extracted. Mean collateral blood flow was lower during occlusion in group I (9.8 +/- 5.4%, n = 5) than in group II (38 +/- 12.5%, n = 7, P < 0.05). Mean infarct size (expressed as a percentage of the area at risk) was significantly larger in group I (low collateral blood flow; 25.3 +/- 14.6%) than in group II (high collateral blood flow; 5.8 +/- 1.1%, P < 0.05). After rapid injection, a transient decrease of signal intensity induced by Dy DTPA-BMA was observed in both remote and ischemic myocardium but more markedly in remote normally perfused myocardium. Hence, during the transit of a susceptibility-type contrast agent, ischemic myocardium after ischemia and reperfusion appeared as a relative high signal intensity area. First-pass MR imaging with susceptibility contrast agent demonstrated the no- or low-reflow phenomenon. However, the behavior of the myocardial signal intensity-time-related curves did not allow distinction between the two groups of dogs.

Improved myocardial tolerance to ischaemia in the diabetic rabbit.

Because cardiac complications after myocardial infarction are more frequent in diabetics, we tested whether experimentally-induced diabetes may increase ischaemic myocardial injury in 23 rabbits. Diabetes was induced in randomized rabbits with the alloxan method. After 2 months, diabetic rabbits underwent a 30-min coronary occlusion followed by 3-h reperfusion and were compared with controls. Collateral flow was measured by the radioactive microsphere technique and infarct size by tetrazolium staining. Infarct size represented 28.6+/-4% of area-at-risk in controls and 16.5+/-3% in diabetics (P<0.05). Collateral flow (0.06+/-0.03 ml/min/g in controls and 0.014+/-0.004 ml/min/g in diabetics) and area-at-risk (50.2+/-4.2% of left ventricle in controls and 53.9+/-5. 4% in diabetics) were similar in both groups. There was a significant positive correlation between area-at-risk and infarct size in both groups (r=0.60 and 0.70, respectively) and for a given area-at-risk, diabetic rabbits developed smaller myocardial infarction than controls (covariance analysis, P<0.01). In additional experiments, hyperglycemia induced by intravenous glucose infusion in non-diabetic rabbits did not protect the ischaemic myocardium (infarct size: 37.9+/-12.5%). In conclusion, diabetes in the rabbit induces a chronic and metabolic form of preconditioning. Further studies are needed to explore the mechanism and time course of this protection.

Effect of chronic severe diabetes on myocardial stunning in the dog.

In this study, we examined whether chronic severe diabetes may affect ischaemic and post-ischaemic regional myocardial dysfunction in vivo in the dog. Diabetes was chemically induced in randomized animals and major metabolic alterations were observed confirming the severity and chronicity of the diabetes. After 70 days, halothane-anaesthetized dogs underwent a 20-min coronary occlusion, followed by reperfusion. During ischaemia, global left ventricle function (dP/dtmax) was more altered (P<0.005) in diabetics ( n=10) than in controls (n=10), whereas area-at-risk (29+/-2.5% of the left ventricle in diabetics v 32.4+/-1.9% in controls) and ischaemic subendocardial myocardial blood flow (radioactive microsphere technique, 0.11+/-0.02 v 0.10+/-0.03 ml/min/g) were similar. During reperfusion, both groups developed significant (P<0.05) regional myocardial dysfunction (somomicrometry, 41+/-14% of baseline in controls and 66+/-8% in diabetics), whereas the difference between groups was not significant. No dog of either group developed myocardial cell necrosis on tissue histology. Multivariate analyses, including the severity of prior ischaemia and the occurrence of ventricular fibrillation as covariables, confirmed that myocardial stunning was not increased in diabetics, although ischaemia was clearly less-well-tolerated in diabetic dogs as global (dP/dtmax) as well as regional myocardial function were significantly (P<0.05) more altered in diabetics during ischaemia. Whilst alteration of arachidonate and cholesterol metabolism may partly explain this apparent paradox, further studies are required to resolve this issue.

[Brain death: myocardial consequences, an experimental study on pigs]. / La morte cerebrale: conseguenze miocardiche, studio sperimentale nel maiale.

It is well known that brain death is responsible for major problems encountered in the clinical setting that may alter heart graft viability before transplantation. To investigate these myocardial dysfunctions, a model of brain death was prepared in pigs. Anaesthetised pigs were ventilated with FiO2 of 50% through an endotracheal tube. Animals were monitored by measuring systemic arterial pressure, pulmonary artery pressure, cardiac output, left ventricular developed pressure and dP/dT (Millar probe), cardiac contractility (sonomicrometers crystals), ECG, myocardial tissue oedema (impedance spectroscopy) and heart rate. Blood samples were drawn to assess arterial blood gases, serum electrolytes, plasma catecholamine levels, LDH isoenzymes and ascorbil free radicals production. Myocardial high energy contents (adenosine triphosphate, creatine phosphate) were measured by spectroscopy MRI. After 30 minutes stabilisation, brain death was induced by ligation of the supra-aortic vessels. To assess myocardial impairment all the parameters mentioned were recorded at baseline, 1', 30', 60', 120' and 180' following the brain death. Results showed initial tachycardia and a significant increase (p < 0.05) in cardiac function at 1' and 30', related to the cathecolamine level variations, followed by a significant depression (p < 0.05) of cardiac contractility by the end of the third hour; there was no modification whatsoever of myocardial high energy contents and of ascorbil free radical and LDH isoenzymes productions. In this pig model of brain death the observed myocardial dysfunction was directly related to the induced catecholamine secretion without any myocardial high energy substrate depletion up until 180'. Such results could be taken into account when evaluating a donor heart, allowing to use organs judged nowadays not feasible, and could be of some help in lowering the number of the "défaillances" of the transplanted hearts.

Effect of colchicine on circulating and myocardial neutrophils and on infarct size in a canine model of ischemia and reperfusion.

Myocardial injury after ischemia/reperfusion has been attributed in part to the effects of neutrophils. We examined whether colchicine, a potent and rapid inhibitor of neutrophils, may reduce inflammatory leukocytosis, prevent postischemic myocardial neutrophil accumulation, and reduce infarct size (IS). Twenty-four dogs were randomized to either a control (saline administration) or a colchicine (1 mg/kg intravenously, i.v.) group. Anesthetized open-chest dogs underwent 120-min coronary artery occlusion followed by 6-h reperfusion. Determinants of IS [area-at-risk (AAR) and collateral flow] and IS were measured in 22 dogs (11 in each group). We evaluated neutrophil toxicity by measuring ex vivo production of reactive oxygen species by chemiluminescence. Myocardial localization and accumulation of neutrophils were histologically evaluated by independent observers. The number of circulating neutrophils (p < 0.01), neutrophil cytotoxicity (p < 0.05), and neutrophil myocardial accumulation after 6-h reperfusion (p = 0.006) were reduced in treated dogs. Left ventricular (LV) peak rate of pressure increase was similar in both groups during ischemia /reperfusion. However, whereas collateral blood flow and AAR, the main determinants of IS, were similar in control and treated dogs, there was no reduction in IS: 37.1 +/- 7% of AAR in controls and 37.4 +/- 8% in treated dogs. Despite marked reduction of neutrophil toxicity and postischemic myocardial neutrophil accumulation, no myocardial protection could be detected in this dog model.

Effect of diaspirin cross-linked haemoglobin (DCLHb) on mean arterial pressure during cardiopulmonary bypass in swine.

Diaspirin cross-linked haemoglobin (DCLHb) is a haemoglobin-based oxygen carrier which had been proposed as a resuscitative solution to replace red cell transfusion in many clinical situations. The present study was designed to evaluate the effect of different volumes of DCLHb 10% (1, 5 and 10 mL kg-1) on the cardiovascular system during cardiopulmonary bypass (CPB), and to determine the effect of DCLHb (18 mL kg-1) when added directly to the CPB prime in anaesthetized swine. DCLHb, when used as a priming solution, induced a significant increase (around 20%) in mean arterial pressure (MAP), which persisted during the entire period of CPB (P < 0.05) as compared with controls. Administration of increasing doses of DCLHb during the time course of CPB resulted in a progressive increase in MAP (P < 0.05), suggesting a linear dose-response relationship. Nicardipine, a calcium channel blocker, returned MAP to baseline. Finally, weaning of CPB was easier in animals that received DCLHb, thereby suggesting a potential protective effect of free haemoglobin in this particular clinical situation.

Effect of trimetazidine on postischemic regional myocardial stunning in the halothane-anesthetized dog.

Trimetazidine (TMZ) has been described as a new antiischemic agent. Whereas its precise mechanism of action remains unknown, antioxidant properties and the ability to preserve high-energy phosphate metabolism have been reported. Accordingly, we studied whether TMZ may limit postischemic regional myocardial stunning (known to be caused by reactive oxygen species) and influence recruitment of contractile reserve by inotropic stimulation in a dog model, using halothane to maintain steady anesthesia throughout the experiment. Dogs were submitted to a 15-min coronary artery occlusion followed by reperfusion. The blinded protocol included a 3-day oral pretreatment (1 mg/kg/day), a bolus injection (0.5 mg/kg), followed by intravenous infusion (0.5 mg/h) initiated 15 min before coronary artery occlusion. Despite lower heart rate (HR) and significant reduction of lipid peroxidation in treated dogs, myocardial stunning and recruitment of contractile reserve by dobutamine infusion in the postischemic myocardium were not modified by TMZ. Adenine nucleotide pool in the postischemic myocardium was considerably reduced as compared with the nonischemic myocardium in both groups. Therefore, in halothane-anesthetized dogs, the antioxidant properties of TMZ were not sufficient to protect myocardium in terms of postischemic dysfunction after 15-min ischemia.

Contrast enhancement in atherosclerosis development in a mouse model: in vivo results at 2 Tesla.

To develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE-/- mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T1 spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 microm spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice.