Assessment of microcirculatory remodeling with intracoronary flow velocity and pressure measurements: validation with endomyocardial sampling in cardiac allografts.

BACKGROUND: Intracoronary physiology techniques have been validated extensively for the assessment of epicardial stenoses but not for the lone study of coronary microcirculation. We performed a comparison between 4 intracoronary physiological indices with the actual structural microcirculatory changes documented in transplanted hearts. METHODS AND RESULTS: In 17 cardiac allograft patients without coronary stenoses, ECG, intracoronary Doppler flow velocity, and aortic pressure were digitally recorded before and during maximal hyperemia with a dedicated system. Postprocessing of data yielded 4 indices of microcirculatory status: coronary flow velocity reserve (2.13+/-0.59), instantaneous hyperemic diastolic velocity pressure slope (2.33+/-1.25 cm x s x (-1)mm Hg(-1)), coronary resistance index (1.65+/-0.88 mm Hg x cm(-1) x s(-1)), and coronary resistance reserve (2.36+/-0.65). Quantitative morphometry was performed in endomyocardial biopsies during the same hospital intake; arteriolar obliteration (76.57+/-6.95%) and density (2.00+/-1.22 arterioles per 1 mm(2)) and capillary density (645+/-179 capillaries per 1 mm(2)) were measured. Univariate regression analysis between intracoronary measurements and histological findings revealed that instantaneous hyperemic diastolic velocity-pressure slope correlated with arteriolar obliteration (r=0.58, P=0.014) and capillary density (r=0.60, P=0.012). Statistical adjustment revealed an independent contribution of arteriolar obliteration (beta=0.61, P=0.0009) and capillary density (beta=-0.60, P=0.0008) to instantaneous hyperemic diastolic velocity-pressure slope values, resulting in an excellent predictive model (r=0.84, P=0.0002). Coronary resistance index correlated only with capillary density (r=0.70, P=0.019). Relative indices (coronary flow velocity reserve and coronary resistance reserve) did not correlate significantly with arteriolar obliteration, capillary density, or arteriolar density. CONCLUSIONS: Intracoronary indices derived from pressure and flow, particularly instantaneous hyperemic diastolic velocity-pressure slope, appear to be superior to coronary flow velocity reserve in detecting structural microcirculatory changes. Both arteriolar obliteration and capillary rarefaction seem to influence microcirculatory hemodynamics independently.

Skeletal myoblast implants induce minor propagation delays, but do not promote arrhythmias in the normal swine heart.

AIMS: Whether skeletal myoblast (SM) implants are proarrhythmic is still controversial due to conflicting pre-clinical and clinical data. We hypothesized that if SM implants are arrhythmogenic, they will facilitate the induction of ventricular tachyarrhythmias by promoting heterogeneous propagation of activation wavefronts. METHODS: Skeletal myoblast cells were harvested from 10 pigs. A month later, 125 ± 37 × 10(6) cells were subepicardially injected in an area of ∼2 cm(2) at the anterolateral aspect of the left ventricle. Four weeks later, a ventricular stimulation protocol was conducted. Once explanted, epicardial wavefronts over SM and adjacent control areas were optically mapped. Eight saline-injected animals were used as controls. To compare with clear arrhythmogenic substrates, propagation patterns were also evaluated in infarcted hearts and on a SM-implanted heart following amiodarone infusion. RESULTS: In SM hearts, fibrosis and differentiated SM cells were consistently found and no tachyarrhythmias were induced. Wavefronts propagated homogeneously over SM and adjacent areas, with no late activation zones, as opposed to the infarcted hearts. The time required for the wavefronts to depolarize both areas were similar, becoming only slightly longer at SM areas after an extra-stimulus (P = 0.025). Conduction velocities and APD(90) were also similar. Saline hearts showed similar results. The extent of the conduction delay was not related to the number of injected SM cells. CONCLUSION: In normal swine hearts, myoblast implants promote localized fibrosis and slightly retard epicardial wavefront propagation only after extra-stimuli. However, SM implants are not associated with local re-entry and do not facilitate ventricular tachyarrhythmias in the whole normal heart.

Interactions between aldosterone and connective tissue growth factor in vascular and renal damage in spontaneously hypertensive rats.

OBJECTIVE: The aim of the present study was to investigate possible inter-relationships between connective tissue growth factor (CTGF) and aldosterone in vascular and renal damage associated with hypertension. METHOD: Spontaneously hypertensive rats (SHR) were treated with two doses (100 and 30 mg/kg per day) of the mineralocorticoid receptor antagonist eplerenone, or with antihypertensive therapy (HHR) (20 mg/kg per day hydralazine + 7 mg/kg per day hydrochlorothiazide + 0.15 mg/kg per day reserpine). RESULTS: CTGF mRNA expression and protein levels in the aorta of SHR were upregulated (P < 0.05) compared with Wistar-Kyoto rats. Both doses of eplerenone similarly and significantly diminished CTGF upregulation, correlated with amelioration of aortic remodelling and endothelium-dependent relaxations. Only high-dose eplerenone and HHR significantly reduced arterial blood pressure. HHR treatment also diminished CTGF overexpression, suggesting a blood-pressure-mediated effect in CTGF regulation. This reduction, however, was lower (P < 0.05) than that produced by eplerenone (100 mg/kg per day). The direct effect of aldosterone on vascular smooth muscle cells was also studied. Incubation of cultured vascular smooth muscle cells with aldosterone increased CTGF production in a dose-related manner, but was reduced (P < 0.05) by the mineralocorticoid receptor antagonist spironolactone. Renal CTGF mRNA and protein levels were higher in SHR than in Wistar-Kyoto rats (P < 0.05), and were similarly diminished by all treatments (P < 0.05). CONCLUSIONS: These data show that aldosterone and haemodynamic stress from elevated blood pressure levels regulate vascular and renal CTGF in SHR. The results suggest that aldosterone, through CTGF stimulation, could participate in vascular and renal structural alterations associated with hypertension, describing a novel mechanism of aldosterone in hypertensive target organ damage.

Activation of peroxisome proliferator-activated receptor-alpha and -gamma in auricular tissue from heart failure patients.

OBJECTIVE: Peroxisome proliferator-activated receptors (PPARs), key transcriptional regulators of lipid and energy metabolism in cardiomyocytes, have recently been proposed to modulate cardiovascular pathophysiological responses in experimental models. However, there is little information about the functional activity of PPARs in human heart failure. AIMS: To investigate PPAR-alpha and -gamma expression and activity, and the association with ET-1 production and fibrosis, in cardiac biopsies from patients with end-stage heart failure due to ischemic cardiomyopathy (ICM) in comparison and from non-failing donor hearts. All samples were obtained during cardiac transplantation. METHODS AND RESULTS: Morphological analysis (by Masson trichrome and image analysis) did not detect fibrosis in the left atrium from non-failing donors (NFLA) or from ICM patients (FLA). However, left ventricles from failing hearts (FLV) contained a greater number of fibrotic areas (NFLA: 3.21+/-1.15, FLA: 1.63+/-0.83, FLV: 14.5+/-3.45%; n = 9, P<0.05). By RT-PCR, preproET-1 expression was similar in the non-failing and failing atrium but was significantly higher in the ventricles from failing hearts (NFLA: 1.00+/-0.06, FLA: 1.08+/-0.11, FLV: 1.74+/-0.19; n = 9, P<0.05). PPAR-alpha and PPAP-gamma mRNA (by RT-PCR) and protein (by Western blot) levels were higher in the ventricles from failing hearts compared with the atrium from failing and non-failing hearts. Electrophoretic mobility shift assays showed that PPAR-alpha and PPAP-gamma were not activated in the ventricles (NFLA: 1.00+/-0.11, FLA: 1.89+/-0.24, FLV: 0.95+/-0.07; n = 9, P<0.05). CONCLUSIONS: These data suggest that PPAR-alpha and PPAP-gamma are selectively activated in the atria from ICM patients and might be functionally important in the maintenance of atrial morphology.

Role of connective tissue growth factor in vascular and renal damage associated with hypertension in rats. Interactions with angiotensin II.

We have evaluated the role of connective tissue growth factor (CTGF) in vascular and renal damage associated with hypertension and possible interactions with angiotensin II (Ang II). Spontaneously hypertensive rats (SHR) were treated with either the Ang II receptor antagonist candesartan (C;2 mg/Kg(-1)/day(-1)) or antihypertensive triple therapy (TT; in mg/Kg(-1)/day(-1);20 hydralazine +7 hydrochlorothiazide +0.15 reserpine) for 10 weeks. Wistar Kyoto rats were used as a normotensive control group. Hypertension was associated with an increase in aortic media area, media-to-lumen ratio and collagen density. Kidneys from SHR showed minimum renal alterations. Aorta and renal gene expression and immunostaining of CTGF were higher in SHR. Candesartan decreased arterial pressure, aortic media area, media-to-lumen ratio and collagen density. However, although arterial pressure decrease was comparable for both treatments, TT partially reduced these parameters. Candesartan-treated rats showed lower levels of vascular CTGF expression, aortic media area, media-to-lumen ratio and collagen density than TT-treated animals. Treatments improve renal damage and reduce renal gene expression and CTGF immunostaining in SHR in a similar manner. The results show that vascular and renal damage is associated with stimulation of CTGF gene and protein content. These results also might suggest that CTGF could be one downstream mediator of Ang II in hypertension-associated organ damage in SHR.

Eplerenone reduces oxidative stress and enhances eNOS in SHR: vascular functional and structural consequences.

The aim of the present study was to evaluate the effect of the aldosterone receptor antagonist eplerenone on endothelial function, oxidative stress, and structural alterations present in spontaneously hypertensive rats (SHR). To carry out the study, male SHR (18 weeks old) were treated with two doses of eplerenone (30 and 100 mg/kg/day) for 10 weeks. A group of n = 8 untreated SHR was used as a control-vehicle group, and a group of Wistar Kyoto rats (n = 8) was used as a reference of normotensive conditions. Systolic arterial pressure (SAP) was measured by the tail-cuff method. Endothelium-dependent and -independent relaxations, as well as endothelial nitric oxide synthase (eNOS) and the subunit p22phox of NAD(P)H oxidase mRNA expressions, were studied in aorta from SHR untreated or treated with eplerenone. Media/lumen ratio was also calculated in aortic preparations. In addition, levels of reduced glutathione (GSH), oxidized glutathione (GSSG), and malonyl dialdehyde (MDA) were evaluated in liver homogenates. Treatment with eplerenone reduced (p < 0.05) SAP and normalized aortic media/lumen ratio and acetylcholine relaxations. Both doses of the drug enhanced (p < 0.05) eNOS and reduced p22phox mRNA expressions. Similarly, eplerenone increased (p < 0.05) hepatic GSH/GSSG ratio, and reduced (p < 0.05) hepatic MDA levels in a comparable manner. Consequently, it could be concluded that aldosterone participates in the functional and structural vascular alterations of SHR through the diminution of nitric oxide availability and an enhancement of vascular and systemic oxidative stress.

Ultrasonographic autopsy (echopsy): a new autopsy technique.

Autopsy has been one of the most important techniques for the development of modern medicine, mainly during the nineteenth century and the first half of last century. However, in the last few years, the number of autopsies performed in hospitals has dramatically decreased all over the world. This loss of interest can be attributed both to important advances in other diagnostic and therapeutic techniques and to the fear of malpractice suits. Several groups have tried to overcome this problem, developing different autopsy techniques, one of which is needle autopsy. Most authors using this technique have acknowledged that it is difficult to obtain material from certain organs and lesions, which makes its diagnostic reliability worse than that of conventional autopsy. To overcome this drawback, our team has recently developed a modification of needle autopsy, called ultrasonographic autopsy or echopsy, in which samples are obtained under ultrasonographic control. We report the results of the first 100 cases of echopsy performed in our hospital, comparing this technique with conventional autopsy performed on all the corpses. The concordance rate for the cause of death and the main pathological diagnosis between echopsy and classical autopsy was 83% in our series, which makes echopsy a feasible and reliable alternative to conventional autopsy in cases in which families refuse to give their consent for classical autopsy or in cases of infectious diseases.

Eplerenone enhances cardioprotective effects of standard heart failure therapy through matricellular proteins in hypertensive heart failure.

AIMS: The addition of an aldosterone receptor antagonist on top of current optimal therapy (based on angiotensin II inhibition) has demonstrated an important clinical benefit in heart failure patients with systolic dysfunction. Whether this finding also applies to heart failure patients with preserved systolic function is unknown. Therefore, we have studied the effect of adding eplerenone to standard pharmacological heart failure therapy (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and diuretic and ß-blocker) in the progression of heart failure in spontaneously hypertensive heart failure (SHHF) rats. METHODS AND RESULTS: Two-month-old SHHF rats were randomized to receive no treatment (SHHF group), a standard heart failure therapy (quinapril-torasemide-carvedilol; ST-SHHF group), or the combination of eplerenone and standard heart failure therapy (Eple+ST-SHHF group) for 20 months. Untreated SHHF was characterized by progressive left ventricular hypertrophy, fibrosis, and myocardial contractile and relaxation abnormalities, leading to pulmonary congestion. Despite similar blood pressure control, the addition of eplerenone to standard heart failure therapy further prevented left ventricular hypertrophy, contractile and relaxation alterations, and pulmonary congestion than standard heart failure therapy alone. ST-SHHF and Eple + ST-SHHF rats showed similar inhibition of structural extracellular matrix proteins collagen I, collagen III and fibronectin and metalloproteinase (MMP)-2, MMP-7, MMP-12, and MMP-13. However, only the coadministration of eplerenone with standard heart failure therapy normalized the expression of matricellular proteins thrombospondin 1, tenascin C, periostin, and secreted protein acidic rich in cysteine/osteonectin to values comparable to normotensive rats. CONCLUSION: In a hypertensive heart failure rat model, the addition of eplerenone to conventional heart failure therapy further improves cardiac structural and functional parameters, delaying the progression of heart failure. These beneficial effects of eplerenone were associated with normalization of matricellular protein expression.

The role of postmortem study in the diagnosis of the cause of death in a young man: a rare case of Ehlers-Danlos syndrome type IV.

Diagnosis of the cause of death in young people is a challenge to both the clinician and the pathologist. Ehlers-Danlos syndrome (EDS) type IV is an inherited connective tissue disorder. It is characterised by thin translucent skin, abnormal fragility of blood vessels, and a typical facial appearance. The cause of death is usually due to large arterial rupture. We describe an unusual case of a 23-year-old man clinically diagnosed with myocarditis, who suffered from recurrent pulmonary haemorrhage and died of massive myocardial haemorrhage and ischaemia without coronary artery disease. Diagnosis of EDS type IV was made by autopsy. To our knowledge, this is the first such report in the literature. Delay in diagnosing this syndrome is common even when clinical features are typical, and the condition often goes unrecognised until necropsy. The diagnosis of EDS should be considered in young people who seek medical attention because of arterial rupture.

Rosuvastatin added to standard heart failure therapy improves cardiac remodelling in heart failure rats with preserved ejection fraction.

AIMS: Although statins may provide potential therapeutic pathways for patients with heart failure with preserved ejection fraction (HFpEF), no studies have evaluated statins in combination with standard HF therapy, which would reflect clinical practice more closely. To address this question, we evaluated whether rosuvastatin added to a standard HF therapy provides additional improvement in cardiac structure and function in rats with hypertensive heart failure (SHHF). METHODS AND RESULTS: Two-month-old SHHF rats were randomly assigned to four groups: (i) non-treated SHHF rats; (ii) rosuvastatin-treated SHHF rats; (iii) SHHF rats treated with quinapril plus torasemide plus carvedilol (considered as standard HF therapy); and (iv) SHHF rats treated with the combination of standard HF therapy and rosuvastatin. The administration of a standard anti-hypertensive HF therapy to SHHF rats for 17 months attenuated left ventricular (LV) chamber dilatation, cardiac hypertrophy, fibrosis, and inflammation compared with non-treated SHHF rats. Rosuvastatin alone prevented LV dilatation and cardiac inflammation similar to standard HF therapy-treated SHHF, despite being unable to normalize blood pressure (BP) or influence cardiac hypertrophy. However, and importantly, the addition of rosuvastatin to the standard HF therapy further prevented LV dilatation, preserved cardiac function, and normalized inflammation. CONCLUSION: These data show that the use of rosuvastatin plus a standard HF therapy results in a significant additional improvement in HF and cardiac remodelling in a rat model of HFpEF. These beneficial effects were independent of BP and plasma lipid changes, and seem to be due, at least in part, to decreased myocardial inflammation.

[Thrombosis of an apparently normal thoracic aorta and arterial embolism]. / Trombosis en aorta torácica aparentemente normal y embolias arteriales.

With the advent of new imaging techniques, the aorta has been increasingly identified as a source of arterial embolism. The majority of thrombi occur in aneurysms or are adherent to atherosclerotic lesions in the abdominal aorta. Thrombi in the thoracic aorta are much less common, particularly in apparently normal aortas. Consequently, the natural history and optimal treatment of these lesions are not well-defined. The aim of this article was to describe the clinical characteristics, treatment, and outcome in three patients with thoracic aorta thrombosis and arterial embolism. Currently available literature on this pathology is reviewed and the differential diagnosis of these lesions is discussed.

Lipid cartography of atherosclerotic plaque by cluster-TOF-SIMS imaging.

Several frozen vessels bearing atherosclerotic lesion were analysed by cluster TOF-SIMS (time-of-flight secondary ion mass spectrometry) to map their lipid (fatty acids, cholesterol, vitamin E, phosphatidic acids, phosphatidylinositols and triglycerides) content at a micrometric resolution.

[The influence of pressure and temperature on the behavior of the human aorta and carotid arteries]. / Influencia de la presión y la temperatura en el comportamiento de la aorta y las carótidas humanas.

INTRODUCTION AND OBJECTIVES: The thermomechanical behavior of human arteries is still not well characterized despite its importance for understanding arterial physiology, and for evaluating and improving surgical procedures. The aim of this study was to provide, for the first time, experimental data illustrating how the mechanical responses of two types of human artery -the carotid artery and the aorta- are affected by changes in temperature. METHODS: The mechanical properties of the arteries were derived in vitro from internal pressure-external diameter curves measured at four different temperatures (i.e., 17, 27, 37 and 42 degree C). Coefficients of expansion and stiffness were obtained by thermomechanical analysis. The condition of the arterial wall was determined histologically. RESULTS: The aorta and the carotid artery became slightly more compliant as the temperature increased. In both vessels, the coefficient of expansion depended critically on internal pressure. At low pressures, the coefficient of expansion was negative (i.e., the vessel contracted when heated), whereas close to a specific threshold pressure, which is different for each type of artery, the coefficient became positive. CONCLUSIONS: The mechanical behavior of arteries is affected by the combination of internal pressure and temperature. Consequently, the effect of this combination should be taken into account in clinical situations involving a change in temperature. Moreover, the strength of the effect depends on the type of artery under study. As a result, more detailed experimental data focusing on vessels of clinical interest are required.

[Acute coronary syndrome in infective endocarditis]. / Síndrome coronario agudo en la endocarditis infecciosa.

INTRODUCTION AND OBJECTIVES: To describe the clinical, microbiologic, echocardiographic characteristics, and disease progression in patients who experience an acute coronary syndrome during an episode of endocarditis. METHODS: The study included 586 consecutive patients who were diagnosed of infective endocarditis (481 left-sided) at one of five hospitals between 1995 and 2005. RESULTS: Overall, 14 patients (2.9%) had an acute coronary syndrome. Their mean age was 50 (17) years, and 50% had a prosthetic valve. For 11 episodes of endocarditis, laboratory cultures tested positive, with Staphylococcus aureus being the most frequently isolated microorganism. Vegetations were detected by transesophageal echography in 12 cases. The infection was located in the aortic valve in 12 cases. In the 14 patients, periannular complications were found more frequently (11 [78.6%] vs 172 [36.8%]; P=.03), and their size was greater than in other patients. Thirteen had moderate-to-severe valvular regurgitation. In most patients, acute coronary syndrome was an early complication of endocarditis. Myocardial ischemia was due to an embolism in three cases and to coronary artery compression in eight. During follow-up, patients with acute coronary syndrome had higher incidences of heart failure (6 [42.85%] vs 77 [16.48%]; P=.021), cardiogenic shock (5 [35.7%] vs 71 [15.2%]; P=.038), complete atrioventricular block (4 [28.57%] vs 43 [9.2%]; P=.039), and mortality (9 [64.29%] vs 151 [32.33%]; P=.019). CONCLUSIONS: Acute coronary syndrome is usually an early complication of infective endocarditis. It is associated with virulent microorganisms, aortic valve infection, severe valvular regurgitation, extensive periannular complications, and increased mortality. The most frequent cause of myocardial ischemia was coronary artery compression secondary to periannular complications.

Pathological effects of pulmonary vein beta-radiation in a swine model.

INTRODUCTION: Atrial fibrillation (AF) may be triggered by ectopic beats originating in sleeves of atrial myocardium entering the pulmonary veins (PVs). PV isolation by means of circumferential ostial or atrial radiofrequency ablation is an effective but also a difficult and long procedure, requiring extensive applications that can have serious potential complications. Our objective was to examine pathological effects of PV beta-radiation, particularly the ability to destroy PV myocardial sleeves without inducing PV stenosis and other unwanted effects, in order to establish its potential feasibility for the treatment of AF. METHODS AND RESULTS: Ten minipigs were studied. A phosphorus-32 source wire centered within a 2.5-mm diameter balloon catheter (Galileo III Intravascular Radiotherapy System, Guidant, Santa Clara, CA, USA) was used to deliver beta-radiation to the superior wall of the right PV trunk. Pathological analysis was performed either immediately after ablation (2 pigs) or 81 +/- 27 days later (8 pigs). Acute effects of PV beta-radiation consisted of endothelial denudation covered by white thrombus, elastic lamina disruption, and PV sleeve necrosis. Late effects consisted of mild focal neointimal hyperplasia that reduced the PV luminal area by only 1.3 +/- 1.8%, elastic lamina thickening, and PV sleeve fibrosis. Four of these 8 PVs were completely re-endothelized. Lesions were transmural in 6 of 10 radiated PVs and segmental, involving 28 +/- 7% of the right PV perimeter. CONCLUSION: Intravascular beta-radiation can induce transmural necrosis and fibrosis of PV myocardial sleeves without PV stenosis and other unwanted effects, which supports a potential usefulness of this energy source in the treatment of AF.

Comparison between the effects of mixed dyslipidaemia and hypercholesterolaemia on endothelial function, atherosclerotic lesions and fibrinolysis in rabbits.

We compared the impact of hypercholesterolaemia and mixed dyslipidaemia on vascular function, vascular structure and fibrinolytic balance in rabbits. To this end, vascular reactivity was studied in aortic rings from rabbits fed a control diet, a diet containing 0.5% cholesterol+14% coconut oil (mixed dyslipidaemia) or a diet containing 1% cholesterol (hypercholesterolaemia) for 12-14 weeks. Morphometric analysis of aorta was also performed and plasminogen activator inhibitor-1 (PAI-1) as well as tissue-type plasminogen activator (t-PA) plasma activities were measured. Both diets induced a similar increase in cholesterol plasma levels, although triacylglycerols (triglycerides) were increased in animals with mixed dyslipidaemia. Hypercholesterolaemia was associated with intimal thickening, reduction in acetylcholine-induced relaxation ( P <0.05) and increased vasoconstriction induced by acetylcholine+ N (G)-nitro-L-arginine methyl ester (L-NAME) when compared with controls ( P <0.05). These effects were more marked ( P <0.05) in animals with mixed dyslipidaemia. Incubation with ifetroban, a thromboxane A(2)/prostaglandin H(2) receptor antagonist, increased acetylcholine-induced relaxation ( P <0.05) and reduced acetylcholine+L-NAME contraction ( P <0.05) in both diet groups. In contrast, the presence of PD 145, an endothelin (ET)(A)/ET(B) receptor antagonist, exerted these effects only in rabbits with mixed dyslipidaemia. Both hypercholesterolaemia and mixed dyslipidaemia induced a similar increase in PAI-1 and a similar decrease in t-PA plasma activities. These data suggest that hypertriglyceridaemia can increase the deleterious effects of hypercholesterolaemia on endothelial function and vascular structure. This additional harmful effect exerted by triacylglycerols on endothelial function could, in part, be mediated by ET.

Synergistic effect of angiotensin-converting enzyme (ACE) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibition on inflammatory markers in atherosclerotic rabbits.

In the present study, we compared the effect of atorvastatin (1 mg.kg(-1).day(-1)) and quinapril (0.5 mg.kg(-1).day(-1)) alone or in combination on inflammatory markers, endothelial function, intimal thickening and fibrinolytic balance in rabbits fed with either a control diet or a diet containing 1% (v/v) cholesterol for 12 weeks. Atorvastatin alone or in combination partially prevented the increase in cholesterol plasma levels observed in rabbits fed with the cholesterol-rich diet, but did not modify blood pressure levels. Quinapril administration did not alter any of these parameters in any group. Hypercholesterolaemia increased plasma levels of interleukin-1beta, interleukin-6, interferon-gamma and C-reactive protein, reduced acetylcholine-induced relaxation and produced intimal thickening. Likewise, atherosclerotic rabbits had reduced plasma tissue-type plasminogen activator activity and D-dimer levels and an increase in plasminogen-activator inhibitor-1 activity. Both drugs enhanced acetylcholine-induced relaxation, reduced intimal thickening and improved fibrinolytic balance in atherosclerotic rabbits in a similar manner. Their combination did not induce additive effects on these parameters. However, only the combination of both drugs was able to prevent the increase in inflammatory markers induced by hypercholesterolaemia. In summary, these data suggest that quinapril and atorvastatin had comparable beneficial effects on the alterations of vascular function and structure as well as fibrinolytic balance in atherosclerotic rabbits. In addition, the combination of atorvastatin and quinapril exerts a synergistic effect on inflammatory markers, which individual treatment, at the doses used, was not able to modify.