PubMed Health⌕ Search

Biomedical subjects

R Ferrera

Publications and source records attributed to R Ferrera.

At least 19 recordsLinked to original sources
PubMed2006

Controlled reperfusion after hypothermic heart preservation inhibits mitochondrial permeability transition-pore opening and enhances functional recovery.

We investigated whether low-pressure reperfusion may attenuate postischemic contractile dysfunction, limits necrosis and apoptosis after a prolonged hypothermic ischemia, and inhibits mitochondrial permeability transition-pore (MPTP) opening. Isolated rats hearts (n = 72) were exposed to 8 h of cold ischemia and assigned to the following groups: 1) reperfusion with low pressure (LP = 70 cmH(2)O) and 2) reperfusion with normal pressure (NP = 100 cmH(2)O). Cardiac function was assessed during reperfusion using the Langendorff model. Mitochondria were isolated, and the Ca(2+) resistance capacity (CRC) of the MPTP was determined. Malondialdehyde (MDA) production, caspase-3 activity, and cytochrome c were also assessed. We found that functional recovery was significantly improved in LP hearts with rate-pressure product averaging 30,380 +/- 1,757 vs. 18,000 +/- 1,599 mmHg/min in NP hearts (P < 0.01). Necrosis, measured by triphenyltetrazolium chloride staining and creatine kinase leakage, was significantly reduced in LP hearts (P < 0.01). The CRC was increased in LP heart mitochondria (P < 0.01). Caspase-3 activity, cytochrome c release, and MDA production were reduced in LP hearts (P < 0.001 and P < 0.01). This study demonstrated that low-pressure reperfusion after hypothermic heart ischemia improves postischemic contractile dysfunction and attenuates necrosis and apoptosis. This protection could be related to an inhibition of mitochondrial permeability transition.

Animals↗
PubMed2006

High energy compound stability during experimental brain death.

The aim of this study was to examine the effect of sudden brain death (BD) on myocardial function and high energy phosphate (HEP) stores. BD was induced by cerebral vessel ligation in six swine (BD group) that were compared to six control swine. At the end of the BD period (3 hours), harvested hearts were stored at 4 degrees C. Myocardial tissue HEP were assessed by: (i) (31)P-NMR spectroscopy of left ventricle for phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi) and intracellular pH (pHi), and by (ii) HPLC for ATP, ADP, and AMP levels in left ventricle biopsies. Brain death resulted in a instantaneous major increase in catecholamines (>50-fold, P < .001) and paradoxically a significant progressive decrease in the regional contractility of the left ventricle. After cardioplegia, no significant differences on HEP compounds (ATP/Pi, PCr/Pi, ATP, energetic index) or in pHi were observed between BD and control groups. These data suggest that early heart injury occurring during BD does not seem to be an ischemic phenomenon.

Animals↗
PubMed2006

A simple and reliable method to assess heart viability after hypothermic procurement.

Hearts from brain dead pigs (n = 18) were submitted to 0 (group I), 10 (group II), or 20 (group III) minutes of in situ warm ischemia (animal exsanguination). After harvesting, cold cardioplegia solution was perfused in retrograde fashion and initial coronary flow (ICF) measured. After left ventricular energetic indices were measured using NMR spectroscopy, the hearts were transplanted orthotopically. Follow-up was performed over 120 minutes after cardiopulmonary bypass. We observed a progressive decrease in ICF with increased warm ischemia times: 50 +/- 3.4 mL/min per 100 g of tissue in the group I, 36 +/- 7 and 30 +/- 3.5 in groups II and III, respectively (P < .05 and P < .01 versus group I). The ICF strongly correlated with the energetic index (r = 0.76, P < .001) and with posttransplant function of the transplanted heart. These data showed that measurement of initial coronary flow after cardioplegia was a reliable test to evaluate cardiac graft viability before transplantation.

Animals↗
PubMed2005

Low-pressure reperfusion alters mitochondrial permeability transition.

We hypothesized that low-pressure reperfusion may limit myocardial necrosis and attenuate postischemic contractile dysfunction by inhibiting mitochondrial permeability transition pore (mPTP) opening. Male Wistar rat hearts (n = 36) were perfused according to the Langendorff technique, exposed to 40 min of ischemia, and assigned to one of the following groups: 1) reperfusion with normal pressure (NP = 100 cmH(2)O) or 2) reperfusion with low pressure (LP = 70 cmH(2)O). Creatine kinase release and tetraphenyltetrazolium chloride staining were used to evaluate infarct size. Modifications of cardiac function were assessed by changes in coronary flow, heart rate (HR), left ventricular developed pressure (LVDP), the first derivate of the pressure curve (dP/dt), and the rate-pressure product (RPP = LVDP x HR). Mitochondria were isolated from the reperfused myocardium, and the Ca(2+)-induced mPTP opening was measured using a potentiometric approach. Lipid peroxidation was assessed by measuring malondialdehyde production. Infarct size was significantly reduced in the LP group, averaging 17 +/- 3 vs. 33 +/- 3% of the left ventricular weight in NP hearts. At the end of reperfusion, functional recovery was significantly improved in LP hearts, with RPP averaging 10,392 +/- 876 vs. 3,969 +/- 534 mmHg/min in NP hearts (P < 0.001). The Ca(2+) load required to induce mPTP opening averaged 232 +/- 10 and 128 +/- 16 microM in LP and NP hearts, respectively (P < 0.001). Myocardial malondialdehyde was significantly lower in LP than in NP hearts (P < 0.05). These results suggest that the protection afforded by low-pressure reperfusion involves an inhibition of the opening of the mPTP, possibly via reduction of reactive oxygen species production.

Animals↗
PubMed2002

[Adaptation of perfusion flow during reperfusion to protect ischemic myocardium from calcium loading].

The aim of this study was (i) to evaluate calcium exchanges occurring during the first stage of reperfusion, and (ii) to investigate the effect of reperfusion flow applied on safe and ischemic hearts. Pig hearts (n = 20) were arrested with cardioplegia and randomly assigned into 2 groups: an ischemic group (1 hour in vitro ischemia at 38 degrees C) versus control group, before being subjected to aortic reperfusion (using 1 and 0.1 ml min-1 g-1 perfusion flow). Both oedema and arterio-venous differences in calcium were analysed during reperfusion. The data showed myocardial Ca++ loading in control hearts reperfused at low flow (p < 0.01) and in ischemic hearts reperfused at high flow (p < 0.01), whereas a low flow reperfusion appeared to protect ischemic hearts. In all groups, reperfusion oedema was greater than 20%. In conclusion, the data suggest that reperfusion flow of arrested hearts should be adapted to the state of the heart: a high flow, necessary for a safe heart, can be deleterious for ischemic heart, whereas a low flow, protective for ischemic hearts, can be deleterious for safe heart.

Animals↗
PubMed2002

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.

Animals↗
PubMed2002

Lung transplantation by continuous perfusion in an experimental auto-transplant animal model.

OBJECTIVE: The aim of this study was to evaluate the preservation of the lung using the cold flushing technique in association with continuous perfusion of the organ during static hypothermic storage. METHODS: In the first phase, the hearts and lungs of 5 New Zealand rabbits were removed three hours after establishing brain death. The left lungs were each conserved in 200 ml of low-potassium UW solution at 10 degrees C for 3 hours of cold ischemia (control group I). The right lungs were also placed in cold storage but were perfused continuously for three hours with low-potassium UW solution at 10 degrees C (group II). In the second phase, ten rabbits underwent a right lung auto-transplant. Lungs were conserved using two techniques. Histoenzymatic and pathological tests were performed: lung function was evaluated. RESULTS: In the first phase the histopathological examination carried out at the end of storage revealed fewer ischemic alterations in the second group compared to the first. In the second phase a significant hypoxia was observed in group I when both lungs and the right lung only were perfused. The histopathological examination revealed ischaemia/reperfusion lesions in both groups though mainly in group I and a good level of ATPase activity in group II though these results were not significant. CONCLUSIONS: Cold flushing of the pulmonary artery and continuous perfusion during static hypothermic storage appears to guarantee a better partial arterial pressure of oxygen in this model of auto-transplant compared to the classical cold storage method.

Adenosine↗
PubMed2000

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.

Animals↗
PubMed2000

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.

Animals↗
PubMed2000

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.

Animals↗
PubMed2000

[Evaluation of a new preservation solution for hypothermic heart transplant].

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.

Animals↗
PubMed1999

[Chest wall tumors. Report of 17 cases].

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.

Adolescent↗
PubMed1998

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.

Animals↗
PubMed1998

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.

Animals↗