Ischemic preconditioning does not prevent placental dysfunction induced by fetal cardiac bypass.

BACKGROUND: Remote ischemic preconditioning (rIPC) has been applied to attenuate tissue injury. We tested the hypothesis that rIPC applied to fetal lambs undergoing cardiac bypass (CB) reduces fetal systemic inflammation and placental dysfunction. METHODS: Eighteen fetal lambs were divided into three groups: sham, CB control, and CB rIPC. CB rIPC fetuses had a hindlimb tourniquet applied to occlude blood flow for four cycles of a 5-min period, followed by a 2-min reperfusion period. Both study groups underwent 30 min of normothermic CB. Fetal inflammatory markers, gas exchange, and placental and fetal lung morphological changes were assessed. RESULTS: The CB rIPC group achieved higher bypass flow rates (p < .001). After CB start, both study groups developed significant decreases in PaO2 , mixed acidosis, and increased lactate levels (p < .0004). No significant differences in tissular edema were observed on fetal lungs and placenta (p > .391). Expression of Toll-like receptor 4 and intercellular adhesion molecule-1 in the placenta and fetal lungs did not differ among the three groups, as well as with vascular cell adhesion molecule-1 (VCAM-1) of fetal lungs (p > .225). Placental VCAM-1 expression was lower in the rIPC group (p < .05). Fetal interleukin-1 (IL-1) and thromboxane A2 (TXA2) levels were lower at 60 min post-CB in the CB rIPC group (p < .05). There were no significant differences in tumor necrosis factor-α, prostaglandin E2, IL-6, and IL-10 plasma levels of the three groups at 60-min post-bypass (p > .133). CONCLUSION: Although rIPC allowed increased blood flow during fetal CB and decreased IL-1 and TXA2 levels and placental VCAM-1, it did not prevent placental dysfunction in fetal lambs undergoing CB.

Hypertonic saline reduces cell infiltration into the lungs after brain death in rats.

BACKGROUND: Lung transplantation is a treatment method for end stage lung disease, but the availability of donor lungs remains a major constraint. Brain death (BD) induces hemodynamic instability with microcirculatory hypoperfusion and increased inflammation, leading to pulmonary dysfunction. Hypertonic saline solution (HSS) is a volume expander possessing immunomodulatory effects. This study evaluated the influence of HSS on pulmonary dysfunction and inflammation in a rat model of BD. METHODS: BD was induced by inflation of an intracranial balloon catheter. Rats were divided into [1]: Sham, without BD [2]; NS, NaCl treatment (0.9%, 4 mL/kg, i.v.) immediately after BD [3]; HSS1, HSS treatment (NaCl 7.5%, 4 mL/kg, i.v.) immediately after BD; and [4] HSS60, HSS treatment 60 min post BD. All groups were analyzed after 360 min. RESULTS: Animals subjected to BD exhibited increased exhaled O2 and decreased CO2.The number of leukocytes in the lungs was significantly increased in the NS group (p = 0.002) and the HSS treatment was able to reduce it (HSS1, p = 0.018 and HSS60 = 0.030). In parallel, HSS-treated rats showed reduced levels of ICAM-1 expression, which was increased in the NS compared to Sham group. Lung edema was found increased in the NS group animals compared to Sham and no effect of the HSS treatment was observed. There were no differences among the groups in terms of TNF-α, VEGF, and CINC-1 lung concentrations. CONCLUSIONS: HSS is capable of reducing inflammatory cell infiltration into the lung after BD induction, which is associated with the reduction of ICAM-1 expression in organ vessels.

Hypertonic Saline Modulates Heart Function and Myocardial Inflammatory Alterations in Brain-Dead Rats.

BACKGROUND: Brain death (BD) in potential organ donors is responsible for hemodynamic instability and organ hypoperfusion, leading to myocardial dysfunction. Hypertonic saline (HS) is a volume expander with positive effects on hemodynamics and immunomodulation and was tested in this study to prevent left ventricular (LV) dysfunction and myocardial injury. METHODS: BD was induced in anesthetized Wistar rats by inflating a subdural balloon catheter, except in sham-operated animals (n = 6). After BD induction, Control animals received only normal saline solution (NaCl 0.9%, 4 mL/kg; n = 6), and treated animals were divided to receive HS (NaCl, 7.5% 4 mL/kg) at 1 min (HS1, n = 6) or 60 min (HS60, n = 6) thereafter. We continuously assessed cardiac function for 6 h with LV pressure-volume analysis. Inflammatory response, markers of myocardial injury, and cellular apoptosis-related proteins were investigated. RESULTS: BD was associated with decreased LV systolic and diastolic function. In comparison with the Control group, HS treatments improved LV ejection fraction (HS1, 51% [40-66]; HS60, 71% [28-82]; Control, 46% [23-55]; P < 0.05) and other parameters of LV systolic function 6 h after BD induction. However, no ventricular relaxation advantages were observed during the same period. HS treatments increased antiapoptotic protein expression and decreased vascular adhesion molecule and tumor necrosis factor alpha expression. No significant differences in histologic or structural protein changes were observed between groups. CONCLUSIONS: The observed data suggest that HS ameliorates LV systolic dysfunction and seems to reduce myocardial tissue compromise in BD rats, even when the treatment is performed during the process triggered by this event.

Evidence of bone marrow downregulation in brain-dead rats.

Experimental findings support the evidence of a persistent leucopenia triggered by brain death (BD). This study aimed to investigate leucocyte behaviour in bone marrow and blood after BD in rats. BD was induced using intracranial balloon catheter inflation. Sham-operated (SH) rats were trepanned only. Thereafter bone marrow cells were harvested every six hours from the femoral cavity and used for total and differential counts. They were analysed further by flow cytometry to characterize lymphocyte subsets, granulocyte adhesion molecules expression and apoptosis/necrosis [annexin V/propidium iodide (PI) protocol]. BD rats exhibited a reduction in bone marrow cells due to a reduction in lymphocytes (40%) and segmented cells (45%). Bone marrow lymphocyte subsets were similar in BD and SH rats (CD3, P = 0.1; CD4, P = 0.4; CD3/CD4, P = 0.4; CD5, P = 0.4, CD3/CD5, P = 0.2; CD8, P = 0.8). Expression of L-selectin and beta2 -integrins on granulocytes did not differ (CD11a, P = 0.9; CD11b/c, P = 0.7; CD62L, P = 0.1). There were no differences in the percentage of apoptosis and necrosis (Annexin V, P = 0.73; PI, P = 0.21; Annexin V/PI, P = 0.29). In conclusion, data presented suggest that the downregulation of the bone marrow is triggered by brain death itself, and it is not related to changes in lymphocyte subsets, granulocyte adhesion molecules expression or apoptosis and necrosis.

Sex-related differences in lung inflammation after brain death.

BACKGROUND: Donor sex has been suggested to be a factor influencing organ transplantation outcome. Sex hormones possess inflammatory and immune-mediating properties; therefore, immune responses may differ between males and females. Brain death (BD) affects organ function by numerous mechanisms including alterations in hemodynamics, hormonal changes, and increased systemic inflammation. In this study, we investigated sex-dependent differences in the evolution of lung inflammation in a rat model of BD. MATERIALS AND METHODS: BD was induced by a sudden increase in intracranial pressure by rapidly inflating a balloon catheter inserted into the intracranial space. Groups of male, female, and ovariectomized (OVx) female rats were used. Lung vascular permeability, inducible nitric oxide synthase, and intercellular adhesion molecule 1 expression were analyzed 6 h after BD. Serum female sex hormones, vascular endothelial growth factor, and cytokine-induced neutrophil chemoattractant 1 levels were also quantified. Lung sections were analyzed by histology. RESULTS: After 6 h of BD, serum estradiol and progesterone concentrations in female rats were significantly reduced. Lung microvascular permeability was increased in females compared to males. Cytokine-induced neutrophil chemoattractant 1 and vascular endothelial growth factor concentrations were increased in female rats compared to males. Furthermore, female rats showed higher levels of leukocyte infiltration and inducible nitric oxide synthase expression in the lung parenchyma. CONCLUSIONS: Our results indicate that the more severe lung inflammation in female animals after BD might be related to acute estradiol reduction. Based on our findings, we believe that, in a future study, a group of female treated with estradiol after BD could indicate a possible therapy for the control of lung inflammation in the female donor.

Cardiac MicroRNA Expression Profile After Experimental Brain Death Is Associated With Myocardial Dysfunction and Can Be Modulated by Hypertonic Saline.

BACKGROUND: Brain death (BD) is associated with systemic inflammatory compromise, which might affect the quality of the transplanted organs. This study investigated the expression profile of cardiac microRNAs (miRNAs) after BD, and their relationship with the observed decline in myocardial function and with the changes induced by hypertonic saline solution (HSS) treatment. METHODS: Wistar rats were assigned to sham-operation (SHAM) or submitted to BD with and without the administration of HSS. Cardiac function was assessed for 6 h with left ventricular (LV) pressure-volume analysis. We screened 641 rodent miRNAs to identify differentially expressed miRNAs in the heart, and computational and functional analyses were performed to compare the differentially expressed miRNAs and find their putative targets and their related enriched canonical pathways. RESULTS: An enhanced expression in canonical pathways related to inflammation and myocardial apoptosis was observed in BD induced group, with 2 miRNAs, miR-30a-3p, and miR-467f, correlating with the level of LV dysfunction observed after BD. Conversely, HSS treated after BD and SHAM groups showed similar enriched pathways related to the maintenance of heart homeostasis regulation, in agreement with the observation that both groups did not have significant changes in LV function. CONCLUSIONS: These findings highlight the potential of miRNAs as biomarkers for assessing damage in BD donor hearts and to monitor the changes induced by therapeutic measures like HSS, opening a perspective to improve graft quality and to better understand the pathophysiology of BD. The possible relation of BD-induced miRNA's on early and late cardiac allograft function must be investigated.

Self-assembled guanosine-hydrogels for drug-delivery application: Structural and mechanical characterization, methylene blue loading and controlled release.

It is known that guanosine derivatives (G) self-assemble in water forming long, flexible, and interacting aggregates (the so-called G-quadruplexes): by modulating the quadruplex charges, e.g. simply using a mixture of guanosine 5'-monophosphate (GMP) and guanosine (Gua), multi-responsive, self-healing hydrogels can be obtained. In this paper, the potential application of G-hydrogels as drug delivery systems has been assessed. Hydrogels were prepared at different Gua:GMP molar ratios. The photosensitizer Methylene Blue and the pro-apoptotic protein cytochrome C were used as cargo molecules. Small angle x-ray scattering and atomic force microscopy experiments confirmed the presence of G-quadruplexes disposed in swollen matrices with different mesh-sizes. Rheology measurements showed that the Gua:GMP molar ratio leads to specific drug release mechanisms, as the gel strength is finely tuned by electrostatic repulsion and van der Waals attraction between G-quadruplexes. Noteworthy, the gel cohesion and the drug release were pH responsive. Swelling, self-healing and cell viability features were also investigated: the results qualify the Gua:GMP hydrogel as an excellent biomaterial that can entrap and deliver key biomolecules in a sustained and responsive release manner.

Effects of sympathectomy on myocardium remodeling and function.

OBJECTIVES: To evaluate the effects of sympathectomy on the myocardium in an experimental model. METHODS: The study evaluated three groups of male Wistar rats: control (CT; n=15), left unilateral sympathectomy (UNI; n=15), and bilateral sympathectomy (BIL; n=31). Sympathectomy was performed by injection of absolute alcohol into the space of the spinous process of the C7 vertebra. After 6 weeks, we assessed the chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines, and beta-adrenergic receptors in the myocardium. The treadmill test consisted of an escalated protocol with a velocity increment until the maximal velocity tolerated by the animal was reached. RESULTS: The bilateral group had higher levels of peripheral catecholamines, and consequently, a higher heart rate (HR) and blood pressure levels. This suggests that the activation of a compensatory pathway in this group may have deleterious effects. The BIL group had basal tachycardia immediately before the exercise test and increased tachycardia at peak exercise (p<0.01); the blood pressure had the same pattern (p=0.0365). The variables related to autonomic modulation were not significantly different between groups, with the exception of the high frequency (HF) variable, which showed significant differences in CT vs UNI. There was no significant difference in beta receptor expression between groups. There was a higher concentration of peripheral norepinephrine in the BIL group (p=0.0001), and no significant difference in myocardial norepinephrine (p=0.09). CONCLUSION: These findings suggest that an extra cardiac compensatory pathway increases the sympathetic tonus and maintains a higher HR and higher levels of peripheral catecholamines in the procedure groups. The increase in HF activity can be interpreted as an attempt to increase the parasympathetic tonus to balance the greater sympathetic activity.

17ß-Estradiol protects against lung injuries after brain death in male rats.

BACKGROUND: Brain death elicits microvascular dysfunction and inflammation, and thereby compromises lung viability for transplantation. As 17ß-estradiol was shown to be anti-inflammatory and vascular protective, we investigated its effects on lung injury after brain death in male rats. METHODS: Wistar rats were assigned to: sham-operation by trepanation only (SH, n = 7); brain death (BD, n = 7); administration of 17ß-estradiol (280 µg/kg, iv) at 60 minutes after brain death (BD-E2, n = 7). Experiments were performed 180 minutes thereafter. Histopathological changes in the lung were evaluated by histomorphometry. Gene expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and endothelin-1 was measured by real-time polymerase chain reaction. Protein expression of NO synthases, endothelin-1, platelet endothelial cell adhesion molecule-1 (PECAM-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), BCL-2, and caspase 3 was assessed by immunohistochemistry. Cytokines were quantified by enzyme-linked immunosorbent assay. RESULTS: Treatment with 17ß-estradiol after brain death decreased lung edema and hemorrhage (p < 0.0001), and serum levels of cytokine-induced neutrophil chemoattractant-1 (CINC-1; p = 0.0020). iNOS (p < 0.0001) and VCAM-1 (p < 0.0001) also diminished at protein levels, while eNOS accumulated (p = 0.0002). However, gene expression of iNOS, eNOS, and endothelin-1 was comparable among groups, as was protein expression of endothelin-1, ICAM-1, BCL-2, and caspase 3. CONCLUSIONS: 17ß-Estradiol effectively reduces lung injury in brain-dead rats mainly due to its ability to regulate NO synthases. Thus, the drug may improve lung viability for transplantation.

* Ethical Issues in the Use of Animal Models for Tissue Engineering: Reflections on Legal Aspects, Moral Theory, Three Rs Strategies, and Harm-Benefit Analysis.

Animal experimentation requires a solid and rational moral foundation. Objective and emphatic decision-making and protocol evaluation by researchers and ethics committees remain a difficult and sensitive matter. This article presents three perspectives that facilitate a consideration of the minimally acceptable standard for animal experiments, in particular, in tissue engineering (TE) and regenerative medicine. First, we review the boundaries provided by law and public opinion in America and Europe. Second, we review contemporary moral theory to introduce the Neo-Rawlsian contractarian theory to objectively evaluate the ethics of animal experiments. Third, we introduce the importance of available reduction, replacement, and refinement strategies, which should be accounted for in moral decision-making and protocol evaluation of animal experiments. The three perspectives are integrated into an algorithmic and graphic harm-benefit analysis tool based on the most relevant aspects of animal models in TE. We conclude with a consideration of future avenues to improve animal experiments.

Bilateral sympathectomy improves postinfarction left ventricular remodeling and function.

OBJECTIVES: To evaluate the influence of bilateral or left sympathectomy on left ventricular remodeling and function after myocardial infarction in rats. METHODS: Myocardial infarction was induced in rats by ligation of the left anterior descending coronary. Seven days later, rats were divided into 4 groups: the myocardial infarction, myocardial infarction with left sympathectomy, myocardial infarction with bilateral sympathectomy, and sham groups. After 8 weeks, left ventricular function was evaluated with the use of a pressure-volume conductance catheter under steady-state conditions and pharmacological stress. Infarct size and extracellular matrix fibrosis were evaluated, and cardiac matrix metalloproteinases and myocardial inflammatory markers were analyzed. RESULTS: The myocardial infarction and left sympathectomy group had an increased end diastolic volume, whereas the bilateral sympathectomy group had a mean end-diastolic volume similar to that of the sham group (P < .002). Significant reduction in ejection fraction was observed in the myocardial infarction and left sympathectomy group, whereas it was preserved after bilateral sympathectomy (P < .001). In response to dobutamine, left ventricular contractility increased in sham rats, rising stroke work, cardiac output, systolic volume, end-diastolic volume, ejection fraction, and dP/dt max. Only bilateral sympathectomy rats had significant increases in ejection fraction (P < .001) with dobutamine. Fibrotic tissue and matrix metalloproteinase expression decreased in the bilateral sympathectomy group compared to that in the myocardial infarction group (P < .001) and was associated with left ventricular wall thickness maintenance and better apoptotic markers in noninfarcted myocardium. CONCLUSIONS: Bilateral sympathectomy effectively attenuated left ventricular remodeling and preserved systolic function after myocardial infarction induction in rats.

Effects of sympathectomy on myocardium remodeling and function

OBJECTIVES: To evaluate the effects of sympathectomy on the myocardium in an experimental model. METHODS: The study evaluated three groups of male Wistar rats: control (CT; n=15), left unilateral sympathectomy (UNI; n=15), and bilateral sympathectomy (BIL; n=31). Sympathectomy was performed by injection of absolute alcohol into the space of the spinous process of the C7 vertebra. After 6 weeks, we assessed the chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines, and beta-adrenergic receptors in the myocardium. The treadmill test consisted of an escalated protocol with a velocity increment until the maximal velocity tolerated by the animal was reached. RESULTS: The bilateral group had higher levels of peripheral catecholamines, and consequently, a higher heart rate (HR) and blood pressure levels. This suggests that the activation of a compensatory pathway in this group may have deleterious effects. The BIL group had basal tachycardia immediately before the exercise test and increased tachycardia at peak exercise (p<0.01); the blood pressure had the same pattern (p=0.0365). The variables related to autonomic modulation were not significantly different between groups, with the exception of the high frequency (HF) variable, which showed significant differences in CT vs UNI. There was no significant difference in beta receptor expression between groups. There was a higher concentration of peripheral norepinephrine in the BIL group (p=0.0001), and no significant difference in myocardial norepinephrine (p=0.09). CONCLUSION: These findings suggest that an extra cardiac compensatory pathway increases the sympathetic tonus and maintains a higher HR and higher levels of peripheral catecholamines in the procedure groups. The increase in HF activity can be interpreted as an attempt to increase the parasympathetic tonus to balance the greater sympathetic activity.

Immediate ischemic preconditioning based on somatosensory evoked potentials seems to prevent spinal cord injury following descending thoracic aorta cross-clamping.

OBJECTIVE: Delayed ischemic preconditioning has demonstrated neuroprotective effects in spinal cord ischemia. We investigated the effects of immediate ischemic preconditioning based on somatosensory evoked potentials monitoring in a model of spinal cord injury due descending thoracic aorta occlusion in dogs. METHODS: Twenty-one dogs were submitted to spinal cord ischemia induced by descending thoracic aorta cross-clamping for 45 min. Control group underwent only the aortic cross-clamping (n=7), group A underwent one cycle of ischemic preconditioning (n=7) and group B underwent three equal cycles of ischemic preconditioning (n=7), immediately before the aortic cross-clamping. Ischemic preconditioning cycles were determined by somatosensory evoked potentials monitoring. Neurologic evaluation was performed according to the Tarlov score at 72 h of follow-up. The animals were then sacrificed and the spinal cord harvested for histopathology. RESULTS: Aortic pressures before and after the occluded segment were similar in the three groups. Ischemic preconditioning periods corresponded to a mean ischemic time of 3+/-1 min and a mean recovery time of 7+/-2 min. Severe paraplegia was observed in three animals in Control group, in four in group A and in none in group B. Tarlov scores of group B were significantly better in comparison to the Control group (P=0.036). Histopathologic examination showed severe neuronal necrosis in the thoracic and lumbar gray matter in animals who presented paraplegia. CONCLUSIONS: Immediate repetitive ischemic preconditioning based on somatosensory evoked potentials monitoring seems to protect spinal cord during descending aorta cross-clamping, reducing paraplegia incidence.

Reevaluation of long-term outcomes of dynamic cardiomyoplasty.

BACKGROUND: Palliative procedures have been proposed for treatment of dilated cardiomyopathies. This study analyzes long-term outcomes of 43 patients who underwent dynamic cardiomyoplasty. METHODS: Patients were in New York Heart Association class III (n = 35) or IV (n = 8) before the procedure. Hospital mortality was 2.2%, and patients were followed for 44 +/- 33 months. Thirty-nine patients completed the skeletal muscle adaptation period, and the muscle flaps were stimulated to contract in concert with every cardiac beat (n = 27) or with every other beat (n = 12). RESULTS: One-year event-free survival was 81.3% +/- 5.9%; 2-year, 65.1% +/- 7.2%; 5-year, 34.7% +/- 7.2%; and 9-year, 10.8% +/- 5.3%. Causes of late deaths were equally divided between progressive heart failure and arrhythmia-related events. Multivariable Cox proportional hazard regression identified that functional class IV, high pulmonary vascular resistance, and muscle flap stimulation synchronized to every cardiac beat were independent predictors of poor event-free survival. The same factors were associated with the occurrence of progressive heart failure, but none was a predictor of arrhythmia-related deaths. Five-year survival of patients maintained with the muscle flap stimulated at every other cardiac beat was 58.3% +/- 14.2%. Skeletal muscle stimulation protocols also influenced the long-term behavior of left ventricular ejection fraction. CONCLUSIONS: Long-term results of dynamic cardiomyoplasty are limited by the patient's preoperative condition and by a high incidence of sudden cardiac death. These results may be improved using modified skeletal muscle stimulation protocols and cardioverter-defibrillator implantation, while maintaining dynamic cardiomyoplasty as an option for selected patients.

Heart failure surgery in Brazil.

Heart failure is a major cause of morbidity and mortality in Brazil as in other western countries. The authors review the experience with heart transplantation in the country based on 835 patients showing that the most frequent indication was idiopathic dilated cardiomyopathy followed by ischemic and Chagas disease cardiomyopathy. Early mortality was higher than other series and differently from literature, age and gender had no influence in survival. Unexpectedly, Chagas disease had better results. In regard to palliative surgical procedures it is made an analysis of the results literature of cardiomyoplasty in Brazil and South America comparing with data from literature. Following, it is reviewed the experience with ventriculectomy, showing its benefits and limitations and finally, correction of mitral insufficiency in cardiomyopathy, through valvoplasty or replacement, is considered. In summary, it is shown that palliative procedures can lead to improvement of clinical condition and ventricular function but are limited by recurrence of heart failure or sudden death.

Determinants of long-term mortality of current palliative surgical treatment for dilated cardiomyopathy.

OBJECTIVE: Dynamic cardiomyoplasty and partial left ventriculectomy have shown limited and controversial results in the treatment of dilated cardiomyopathies. This study investigates causes and determinants of long-term mortality after these procedures. METHODS: Forty-three patients submitted to dynamic cardiomyoplasty and 43 who underwent partial ventriculectomy were studied. Patients were in New York Heart Association (NYHA) class III or IV before the procedures. In dynamic cardiomyoplasty group, hospital mortality was 2.2% and patients were followed for 48+/-31 months. Nine hospital deaths occurred after partial ventriculectomy and the remaining patients were followed for 38+/-29 months. RESULTS: For patients submitted to dynamic cardiomyoplasty, 1-year event-free survival was 81.3+/-5.9%; 2-year, 65.1+/-7.2%; and 6-year, 23.1+/-6.7%. Partial left ventriculectomy patients presented event-free survival rates of 58.1+/-7.5%, 46.6+/-7.6% and 21.6+/-6.4% at the same periods, respectively. Late deaths were equally related to heart failure progression and arrhythmia events in both groups. Preoperative NYHA class IV, pulmonary hypertension and absence of left ventricular (LV) function improvement at the time of the final event were identified as independent predictors of poor long-term event-free survival and heart failure progression in cardiomyoplasty patients, while NYHA class IV, elevated serum nor-epinephrine and absence of LV function improvement were associated with these events after partial left ventriculectomy. Arrhythmia related deaths were only predicted by previous events of sustained ventricular tachycardia in partial left ventriculectomy group. CONCLUSIONS: Long-term results of dynamic cardiomyoplasty and partial left ventriculectomy are limited by patients' preoperative condition, by the loss of LV function benefits and by high incidence of sudden cardiac death. Palliative surgical treatment of dilated cardiomyopathies needs to be indicated earlier and may achieve better efficiency with the combination of different procedures to provide sustained improvement of LV function, to interrupt the progressive remodeling process and to prevent sudden cardiac death.

Effects of skeletonized versus pedicled radial artery on postoperative graft patency and flow.

BACKGROUND: Radial artery (RA) was the second arterial graft introduced in clinical practice for myocardial revascularization. The skeletonization technique of the left internal thoracic artery (LITA) may actually change the graft's flow capacity with potential advantages. This leads to the assumption that the behavior of the RA, as a coronary graft, is similar to that of the LITA, when skeletonized. OBJECTIVE: This study evaluated 'free' aortic-coronary radial artery (RA) grafts, whether skeletonized or with adjacent tissues. METHODS: A prospective randomized study comparing 40 patients distributed into two groups was conducted. In group I, we used skeletonized radial arteries (20 patients), and in group II, we used radial arteries with adjacent tissues (20 patients). After the surgical procedure, patients underwent flow velocity measurements. RESULTS: The main surgical variables were: RA internal diameter, RA length, and free blood flow in the radial artery. The mean RA graft diameters as calculated using quantitative angiography in the immediate postoperative period were similar, as well as the flow velocity measurement variables. On the other hand, coronary cineangiography showed the presence of occlusion in one RA graft and stenosis in five RA grafts in GII, while GI presented stenosis in only one RA graft (p = 0.045). CONCLUSION: These results show that the morphological and pathological features, as well as the hemodynamic performance of the free radial artery grafts, whether prepared in a skeletonized manner or with adjacent tissues, are similar. However, a larger number of non-obstructive lesions may be observed when RA is prepared with adjacent tissues.

Reversible pulmonary trunk banding VIII: Intermittent overload causes harmless hypertrophy in adult goat.

BACKGROUND: Traditional pulmonary artery banding (PAB) is not always suitable for mature subpulmonary ventricle retraining. We sought to assess in detail the myocardial morphologic adaptations of two different protocols for inducing right ventricular (RV) hypertrophy in an adult animal model. METHODS: Eighteen adult goats were distributed into three groups: sham (no systolic overload), traditional (continuous systolic overload), and intermittent (daily 12-hour systolic overload). Systolic overload was adjusted to achieve a 0.7 RV-to-aortic pressure ratio. All animals underwent weekly echocardiographic studies, and hemodynamic evaluations were performed 3 times a week. After 4 weeks, the animals were humanely killed for morphologic assessment. RESULTS: A 37.2% increase was observed in the RV wall thickness of the intermittent group (p<0.05), but no significant echocardiographic changes were observed in the other two groups. The intermittent and traditional groups had a 55.7% and 36.7% increase in RV mass, respectively, compared with the sham group (p<0.05). No differences were observed in myocardial water content of the three groups (p=0.27). RV myocardial fiber and nuclei diameters were increased in the intermittent group compared with the sham group (p<0.05). The area of collagen deposition in the RV interstitium was increased 98% in traditional group compared with the sham group (p<0.05). No significant cellular proliferation occurred in any group. CONCLUSIONS: This study suggests that a more effective and harmless hypertrophy can be achieved in adult animals using intermittent PAB compared with the traditional approach.

Reversible pulmonary trunk banding: VII. Stress echocardiographic assessment of rapid ventricular hypertrophy in young goats.

BACKGROUND: Ventricle retraining with abrupt systolic overload can cause myocardial edema and necrosis, followed by late ventricular failure. Intermittent systolic overload could minimize the inadequacy of conventional pulmonary artery banding. The present study compared ventricle function under dobutamine stress in 2 protocols of systolic overload in young goats. METHODS: Nineteen young goats were divided into 3 groups: sham (n = 7; no systolic pressure overload), continuous (n = 6; systolic overload maintained for 96 hours), and intermittent (n = 6; 4 periods of 12-hour systolic overload, paired with a 12-hour resting period). Echocardiographic and hemodynamic evaluations were performed daily. The myocardial performance index and ejection fraction were evaluated at rest and during dobutamine stress. The goats were then killed for morphologic evaluation. RESULTS: The intermittent group underwent less systolic overload than the continuous group (P < .05). Nevertheless, both groups had increased right ventricular and septal masses compared with the sham group (P < .0002). Echocardiography revealed a major increase in right ventricular wall thickness in the intermittent group (+64.8% ± 23.37%) compared with the continuous group (+43.9% ± 19.26%; P = .015). Only the continuous group remained with significant right ventricular dilation throughout the protocol (P < .001). The intermittent group had a significantly better myocardial performance index at the end of the protocol, under resting and dobutamine infusion, compared with the continuous group (P < .012). CONCLUSIONS: Both systolic overload protocols have induced rapid right ventricular hypertrophy. However, only the intermittent group had better preservation of right ventricular function at the end of the protocol, both at rest and during dobutamine infusion.