Effect of atherosclerosis on thermo-mechanical properties of arterial wall and its repercussion on plaque instability.

Data from the literature report febrile reactions prior to myocardial infarction in patients with normal coronary arteries and that coronary syndromes seem to be triggered by bacterial and viral infections, being fever the common symptom. The thermo-mechanical behavior of thoracic aortas of New Zealand White rabbits with different degrees of atherosclerosis was measured by means of pressure-diameter tests at different temperatures. Specific measurements of the thermal dilatation coefficient of atheroma plaques were performed by means of tensile tests. Results show a different thermo-mechanical behavior, the dilatation coefficient of atheroma plaque being at least twice that of the arterial wall. Temperature-induced mechanical stress at the plaque-vessel interface could be enough to promote plaque rupture. Therefore, increases of corporal temperature, either local or systemic, can play a role in increasing the risk of acute coronary syndromes and deserve a more comprehensive study.

Effects of bosentan on neointimal response following coronary angioplasty.

BACKGROUND: Endothelins are important vasoconstrictors and cellular-growth promoters. ETA-specific antagonists have been shown to reduce neointimal response to injury in some experimental angioplasty models. However, there is little information on the effects of dual ETA/ETB receptor blockers, such as bosentan, on neointimal proliferation following experimental coronary angioplasty. MATERIALS AND METHODS: Coronary injury was achieved by directional atherectomy in the left anterior descending artery of 20 pigs. Animals were randomly assigned to receive a daily dose of oral bosentan (30 mg kg-1) (group I, n = 10) or no treatment (group II, n = 10). At 4 weeks, arteries were processed for histomorphometry and endothelin characterization. RESULTS: Vessel injury score was similar among the two groups. Overall, a linear correlation was found between injury and neointimal development (r = 0.57, P = 0.01). This correlation had a lower slope in group I compared with group II (P < 0.001), indicating a smaller amount of neointimal development for a similar degree of injury in bosentan-treated animals. Multivariate regression showed that neointimal response was reduced by oral treatment with bosentan (beta: -0.59 mm2, 95% CI: -1.11/-0.06 mm2). In addition, immunostaining revealed fewer positive endothelin areas in group I arteries. CONCLUSIONS: Oral treatment with bosentan reduces neointimal development following coronary angioplasty in this experimental model.

Morning cortisol production in coronary heart disease patients.

BACKGROUND: The circadian cycle of the endogenous anti-inflammatory system (EAIS) is characterized by a morning increase in cortisol production. Circulating interleukin-6 (IL-6) activates the EAIS. A circadian variation in the onset of myocardial infarction, sudden death, stable angina (SA) and unstable angina (UA) has been reported. The aim of this study was to determine morning cortisol production in coronary heart disease (CHD) patients. MATERIALS AND METHODS: Serum cortisol and IL-6 were measured in 129 patients with either SA (n = 65) or UA (n = 64) and 40 healthy volunteers. Blood samples were taken between 9 : 00 h and 12 : 00 h. The upper normal range of cortisol (25 microg dL-1) was used as a reference to classify patients. RESULTS: Forty-eight patients had elevated cortisol levels (ECL) (32.5 +/- 5.4 microg dL-1), while 81 patients had normal cortisol levels (NCL) (15.7 +/- 5.9 microg dL-1). In NCL patients, IL-6 levels (26.6 pg mL-1, ranged from 0.2 to 183.7) were significantly higher (P < 0.004) than in ECL patients (9.70 pg mL-1, range 0.07-56.5). Forty-eight patients with UA belonged to the NCL group of patients, while only 16 UA patients belonged to the ECL group (chi(2) = 0.000). Thirty-two patients with SA belonged to the ECL group, and 33 to the NCL group (chi(2) = 0.08). CONCLUSIONS: Patients with 'inappropriately' normal morning cortisol production had high IL-6 levels. 'Inappropriately' normal cortisol, detected in 75% of UA and 50% of SA patients, may be insufficient for limiting inflammation. These findings have novel clinical implications and suggest new therapeutic approaches in the treatment of these patients.

[Effect of cAMP on the function of endothelial cells and fibromuscular proliferation after the injury of the carotid and coronary arteries in a porcine model]. / Efecto del AMPc sobre la función de las células endoteliales y la proliferación fibromuscular tras la lesión de las arterias carótida y coronaria en un modelo porcino.

INTRODUCTION AND OBJECTIVE: Reendothelization of damaged blood vessels protects against the vascular injury response. We evaluated in vivo whether a systemic increase in cAMP accelerates reendothelization and attenuates intimal hyperplasia in injured swine carotid and coronary arteries. METHODS: Both carotid arteries of 10 swines were subjected to balloon injury. Five animals had been treated with 2 ml (10 mg) of Forskolin, an activator of the adenylate cyclase, and another 5 with 2 ml of saline solution. These animals were sacrificed at day 8, and carotid artery reendothelization was evaluated. The descendent coronary (DC) artery of another 19 pigs was injured by atherotome. Nine animals had been treated with 2 ml of Forskolin, and another 10 with 2 ml of saline solution. These animals were sacrificed at day 28, with myointimal proliferation and arterial geometric remodelation being evaluated. Likewise, in these animals intracellular cAMP levels were measured at baseline and 28 and 60 minutes after saline solution or Forskolin administration and 90 min after arterial injury. RESULTS: Eight days after balloon injury, carotid artery reendothelization was greater in the Forskolin-treated group compared with the control group (p = 0.02), and the number of CD31 positive cells was statistically increased in the treated group (38 +/- 11 cells) versus controls (11 +/- 9 cells). Although the degree of vascular injury caused by atherotome was similar in all of the arteries in the control group, restenosis was only observed in 40% of these animals. Correlation analysis demonstrated that intracellular cAMP may condition arterial geometric remodeling and the diameter of the lumen after vascular injury. CONCLUSION: Our results suggest that cAMP may promote reendothelization and attenuate fibromuscular proliferation.

Endogenous anti-inflammatory response after coronary injury in a porcine model.

BACKGROUND: Corticotropin-releasing hormone (CRH)/adrenocorticotropic hormone (ACTH)/cortisol is the major anti-inflammatory system. After percutaneous translumenal angioplasty, an inflammatory process is triggered. We investigate whether CRH/ACTH/cortisol axis is activated after deep vessel wall injury (DVWI). MATERIALS AND METHODS: Plasma and leukocyte CRH and ACTH, serum cortisol and IL-1beta, and leukocyte cAMP were measured (ELISA) in 16 pigs after anaesthesia (baseline), 60 min into anaesthesia without causing vascular injury and 90 min after DVWI of the left anterior descending (LAD) coronary artery induced by percutaneous directional atherectomy (Atherocath GTO 7F; DVI, Inc., Temecula, USA). Biochemical variables were also measured at baseline, 60 and 180 min into anaesthesia in six additional pigs without coronary intervention. RESULTS: MANOVA showed that CRH/ACTH/Cortisol, cAMP and IL-1beta production was not modified during anaesthesia. Post-DVWI plasma CRH (0.077 +/- 0.046 ng mL-1), and cellular cAMP (0.14 +/- 0.067 pmol 10(-6) cells) increased significantly (P = 0.001) with respect to their baseline values (CRH = 0.036 +/- 0.013 ng mL-1; cAMP = 0.081 +/- 0.034 pmol 10-6). There was also a statistically significant increase (P = 0.02) in post-DVWI IL-1beta (from 46.6 +/- 12.8 to 64.05 +/- 13.5 pg mL-1), and in serum cortisol (P = 0.05) compared to its baseline values (8.98 +/- 3.2 microgr dL-1 vs. 6.57 +/- 2.3 microgr dL-1, respectively). CONCLUSION: In our experimental model, coronary vessel wall injury-activated CRH/ACTH/cortisol axis caused a significant increase in plasma CRH, cortisol and cellular cAMP levels, which may influence the response of coronary arteries to injury.

Does focal destruction of the thoracic aorta wall by Staphylococcus aureus lead to the development of infected aneurysms? An experimental study.

OBJECTIVE: The infrequency of infected aneurysms suggests that either infection of segments of the aortic wall is uncommon, or that infections do not always lead top infected aneurysm formation. The purpose of the study was to determine whether focal Staphylococcus aureus infection of aortic wall segments leads consistently to the development of infected aneurysms and to evaluate the segments in which infection did not lead to the infected aneurysm formation. METHODS: Twenty pigs were inoculated with 0.1 ml of a Staphylococcus aureus inoculum in three segments of the thoracic aorta wall (study group). In another 10 pigs, 0.1 ml of saline solution was injected in three segments of the thoracic aorta wall (control group). STUDY GROUP: histological abnormalities and bacterial culture of the inoculation sites were evaluated at 10 days (n = 5 pigs), 30 days (n = 5 pigs), and 90 days (n = 10 pigs). CONTROL GROUP: histological abnormalities were evaluated at 10 days (n = 5 pigs) and 90 days (n = 5 pigs). STUDY GROUP: infected aneurysms developed in only two animals killed at 30 days. At 90 days, destruction of the elastic tissue, scar tissue and neointima formation were found in all the aortic segments studied. CONTROL GROUP: no significant changes were found in any of the segments evaluated. CONCLUSION: In our experimental model, acute local infection by S. aureus caused the development of infected aortic aneurysm in only 10% of the animals. In the remaining 90%, healing of the site of infection followed resolution of the infection.

A new experimental model of isolated myocardial ischemic injury: ECG findings of acute isolated right ventricular ischemic injury.

A new experimental porcine model for creating selective ischemia of a specific part of the myocardium while the rest of the myocardium remains free of ischemia has been used to study the electrocardiographic (ECG) changes deriving from selective ischemia of the right ventricular (RV) free wall. A patch was stitched to the ventricle to produce selective myocardial ischemic injury. In a preliminary study of nine pigs, selective ischemia of the left ventricular free wall in five and of the RV free wall in four animals was induced, and a postmortem dye injection was performed to evaluate blood flow in the area of ischemia. In an ECG study of 20 pigs, the baseline ECG was recorded with use of the standard leads I-III, aVR, aVL, and aVF, left precordial leads (V1-V6), and leads V4R, V3H, and V4H and 1 hour after inducing ischemia, the ECG study was repeated. Our experimental model produced ischemic injury in which the location and surface area were known antemortem. In the 20 pigs, ST-segment changes were recorded in leads V1-V3, V3H, and V4H. In only four pigs (20%) was ST-segment elevation recorded in lead V4R. The results show that the ECG signs of selective ischemia of the RV free wall may imitate the signs of anterior or anterolateral infarction of the left ventricle. In this study, elevation of the ST-segment in lead V4R was not pathognomonic of for RV ischemia. This model is a new tool for studying hemodynamic and ECG changes of selective univentricular or biventricular ischemic injury.

Effect of magnesium sulfate administration on subendocardial and subepicardial perfusion.

The objective of this study was to determine the effect of systemic MgSO4 infusion on subendocardial and subepicardial perfusion. Seventeen spontaneously breathing piglets were examined. Myocardial perfusion was measured using radiolabeled microspheres at baseline, 30 and 60 min after either MgSO4 (80 mg/kg) or saline infusion. Blood pressure, heart rate, and cardiac output were also measured at these time intervals. Comparison of the magnesium-induced changes in systemic blood pressure and on subendocardial and subepicardial perfusion at 30 and 60 min with values obtained with saline solution at 30 and 60 min, yielded no statistically significant difference (Tables 1-3). The ratio of subendocardial/subepicardial blood flow and subendocardial and subepicardial coronary vascular resistance at 30 and 60 min revealed no statistically significant differences between the magnesium and the control group (Table 3). There were no statistically significant difference in cardiac output and heart rate during any of the measured periods (Table 2). Our results suggest that the administration of MgSO4 does not alter the ratio of subendocardial/subepicardial blood flow and the ratio of subendocardial/subepicardial coronary vascular resistance.

Ethanol intake, plasma catecholamine levels, and ST-segment changes without myocardial injury in rats with short-term ethanol consumption.

The authors studied the effect of short-term ethanol consumption on the ST-segment and the association between ST-segment changes and the amount of daily ethanol intake and levels of plasma catecholamines. The study used 63 rats (control group n = 20, study group n = 43). The rats in the study group were exposed for 6 days to progressively larger doses of ethanol followed by 15 days of continuous exposure to ethanol. At baseline an electrocardiogram (ECG) was recorded, and on day 25 the ECG was repeated and plasma catecholamine levels were measured. The animals' hearts were removed and processed for histologic study. Repolarization abnormalities were observed in 68% of the ethanol-consuming rats. Two factors differentiated the subgroup of ethanol-consuming rats with ST-segment changes from the subgroup without ST-segment changes: amount of daily ethanol intake (0.0077 +/- 0.02 mL/g/d vs 0.0058 +/- 0.019 mL/g/d) and plasma epinephrine levels (3,881 +/- 733 pg/mL vs 1,478 +/- 406 pg/mL). No myocardial damage was detected. Our results suggest that in ethanol-consuming rats, high-volume daily ethanol intake and increased plasma catecholamines may mediate changes in the ST-segment.

Intracellular (polymorphonuclear) magnesium content in patients with bronchial asthma between attacks.

Previous studies have demonstrated the role of polymorphonuclears in asthma, the importance of increases in intracellular concentrations of ionized calcium in the release of chemical mediators, the role of magnesium as natural calcium channel blocker, and the importance of magnesium deficiency in plasma histamine concentration and in tissue prostanoid concentration. The objective of our study was to measure the polymorphonuclear magnesium content in patients with asthma in the interval between attacks. We measured the polymorphonuclear magnesium content, and serum and erythrocyte sodium, calcium, and magnesium concentrations in 21 healthy volunteers and 50 patients with different types of asthma. In our patients, the polymorphonuclear magnesium content was lower than in the control group (P < 0.001), while magnesium levels in erythrocytes and serum and the levels of other ions in erythrocytes and serum were normal. This is the first report to document low polymorphonuclear magnesium content in patients with bronchial asthma. The reduction of polymorphonuclear magnesium content may have an important role in the pathogenesis of asthma.

Direct atrioventricular versus atriopulmonary connection: a comparative experimental study.

A study of 31 dogs, divided into two groups, was conducted to compare direct atrioventricular with atriopulmonary connection using a valved conduit to treat tricuspid atresia. The first group (n = 9) acted as controls. In the second group (n = 22), an experimental model was established for direct atrioventricular connection that could be converted to atriopulmonary connection. In subgroup A (n = 11), the blood from the right atrium (RA) was conducted to a haemodynamically effective residual right ventricle (RV), whereas in subgroup B (n = 11) the blood was conducted from the RA to an ineffective residual RV. There were haemodynamic advantages of atrioventricular connection in subgroup A. No such differences were found between the two surgical techniques in subgroup B. In both subgroups, light external compression of the pulmonary artery produced a profound deterioration in the haemodynamic state. The technique of direct atrioventricular connection does not appear to offer any advantages as a method of atriopulmonary bypass.

Does a critical hemodynamic situation develop from right ventriculotomy and free wall infarct or from small changes in dysfunctional right ventricle afterload?

An experimental model for right ventricle free wall infarct associated with double ventriculotomy and tricuspid insufficiency was created to evaluate whether right ventricle failure can cause profound refractory heart failure or whether modifications in right ventricular afterload are more influential in this regard. In our model, the left ventricle, interventricular septum and right atrial wall were maintained intact and pulmonary banding made it possible to modify right ventricular afterload during the experiment. The results of our study showed that pure right ventricular failure does affect the hemodynamic state negatively, but it is not itself, a cause of death in dogs. A slight increase in the dysfunctional right ventricular afterload produced a profound deterioration in the hemodynamic state that required pulmonary artery debanding within no more than 10 minutes.

[Experimental evaluation of the role of the coronary sinus pressure in the regulation of coronary return volume via the coronary sinus. Surgical considerations in atrio-pulmonary diversion procedures]. / Valoración experimental del papel de la presión en seno coronario en la regulación del volumen de retorno vía seno coronario. Consideraciones quirúrgicas en las técnicas de derivación atriopulmonar.

In order to find out the validity of the vascular waterfall mechanism in coronary venous circulation, the role of coronary sinus pressure in the regulation of coronary return volume via the coronary sinus is studied in healthy animals. An experimental model of pressure regulation in the coronary sinus was prepared, and aortic pressure, EKG and the cardiac output (measured by thermodilution) were recorded. The return volume via the coronary sinus was measured at coronary sinus pressure of 10 or less, 15, 20, and 25 mmHg or more, for a total of 36 determinations. Increased coronary sinus pressure did not produce significant changes in aortic pressure, heart rate, cardiac index or coronary return volume via coronary sinus. When coronary sinus pressure was 25 mmHg or more, there was a significant decline in the average of coronary return volume via coronary sinus. Nevertheless, stepwise variant regression showed that the coronary sinus pressure per se does not condition the volume of coronary return via the coronary sinus. Our results suggest that in the healthy animals, the vascular waterfall mechanism in coronary venous circulation is not valid. Our results suggest that in the correction of congenital cardiac malformations using atriopulmonary anastomosis procedures, employing techniques that ensure coronary sinus drainage into the left atrium, in order to avoid the hemodynamic repercussions attributable to the vascular waterfall mechanism, is not justified.

A new physiologic correction technique for re-establishment of pulmonary circulation. Experimental surgical development.

A new physiologic technique is presented for surgical correction of truncus arteriosus, pseudotruncus, transposition of the great arteries, double right ventricular outflow tract with subpulmonary ventricular septal defect and certain cases of Fallot's tetralogy. The basis of the technique are creation of a neo-right atrium, neo-pulmonary trunk, neo-right atrioventricular valve and a neo-pulmonary valve by right angular atriotomy and insertion of a homologous pericardial patch with a monocuspid valve. The pulmonary circulation is re-established by anastomosis of the neo-pulmonary trunk to the pulmonary tree. The technique was used on 26 mongrel dogs. In 14 the experiments were preliminary, to evaluate the technique's validity, and in the other 12 it was performed with extracorporeal circulation and the hemodynamic status was studied at 30 and 180 min postoperatively. The technique and its results and potential advantages are described. Clinical application is considered to be feasible.

Experimental evaluation of atriopulmonary anastomosis in the presence of high pulmonary resistance.

We studied pulmonary resistance as a surgical criterion for atriopulmonary shunt. We created a model of experimental pulmonary hypertension by establishing a systemic-pulmonary shunt in 11 dogs. Two to 3 months after the shunt operation, total pulmonary resistance was calculated before (7.24 +/- 1.54 U . m2) and after (3.50 +/- 1.54 U . m2) ligation of the shunt. An atriopulmonary anastomosis technique was then performed and the hemodynamic status of the dogs during the first 2 postoperative hours was evaluated. Pathologic study of the lungs disclosed no arterial lesions. From our experimental work, we conclude that the surgical criterion for establishing the indication for this operation should be pulmonary resistance, which is conditioned by the state of the intrapulmonary vessels. We propose a procedure for determining real pulmonary resistance in the course of preoperative catheterization.