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It is well known that brain death is responsible for major problems encountered in the clinical setting that may alter heart graft viability before transplantation. To investigate these myocardial dysfunctions, a model of brain death was... more
It is well known that brain death is responsible for major problems encountered in the clinical setting that may alter heart graft viability before transplantation. To investigate these myocardial dysfunctions, a model of brain death was prepared in pigs. Anaesthetised pigs were ventilated with FiO2 of 50% through an endotracheal tube. Animals were monitored by measuring systemic arterial pressure, pulmonary artery pressure, cardiac output, left ventricular developed pressure and dP/dT (Millar probe), cardiac contractility (sonomicrometers crystals), ECG, myocardial tissue oedema (impedance spectroscopy) and heart rate. Blood samples were drawn to assess arterial blood gases, serum electrolytes, plasma catecholamine levels, LDH isoenzymes and ascorbil free radicals production. Myocardial high energy contents (adenosine triphosphate, creatine phosphate) were measured by spectroscopy MRI. After 30 minutes stabilisation, brain death was induced by ligation of the supra-aortic vessels. ...
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Research Interests: Diet, Medicine, Prospective studies, Humans, Internal Medicine, and 15 morePlatelet aggregation, Antioxidant, Male, Immunosuppression, Cyclosporine, Nephrotoxicity, Lymphocytes, Graft Rejection, Heart Transplantation, Creatinine, Blood platelets, Platelet Aggregation Inhibitors, Lymphocyte, Medical and Health Sciences, and leukocyte Count
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Background The objective of this study was to evaluate different tests of heart viability in a pig model of warm ischemia. Methods and Results Pig hearts (n=30) were submitted to 0 (= group I), 10 (group II), 20 (group III), 30 (group... more
Background The objective of this study was to evaluate different tests of heart viability in a pig model of warm ischemia. Methods and Results Pig hearts (n=30) were submitted to 0 (= group I), 10 (group II), 20 (group III), 30 (group IV), and 60 (group V) minutes of in situ warm ischemia (animal exsanguination). Hearts were removed, then flushed with cardioplegic solution for 3 minutes at a fixed pressure of 60 cm H 2 O, and edema formation, initial coronary flow, and ionic composition (Na + , K + , and Ca ++ ) of coronary sinus effluent were evaluated. Hearts were then stored for 2 hours in a cold (4°C) preservation solution. Myocardial biopsies (and evaluation of energetic index) were performed, then the hearts were reperfused for 30 minutes with whole blood with an in vitro functional testing system. No edema occurred during cardioplegic flush in the hearts in groups I through IV, but a 37±11% weight increase ( P
Research Interests: Cardiology, Calcium, Medicine, Soft Tissue Preservation, Internal Medicine, and 14 moreIschemia, Female, Animals, Male, Potassium, Clinical Sciences, Sodium, Myocardium, Public health systems and services research, Swine, Circulation, Coronary Circulation, Heart Transplantation, and Cardiovascular medicine and haematology
There is not general agreement concerning the optimal time of reperfusion necessary to assess myocardial function and necrosis on isolated perfused heart model. Nevertheless, the study of cardioprotection (especially, pre- and... more
There is not general agreement concerning the optimal time of reperfusion necessary to assess myocardial function and necrosis on isolated perfused heart model. Nevertheless, the study of cardioprotection (especially, pre- and postconditioning) requires a reliable and standardized assessment of myocardial necrosis. The objective of this study was thus to evaluate whether 1 h of reperfusion was sufficient to assess rat heart viability on Langendorff preparation. Isolated rat hearts (n = 30) underwent 40 min of global normothermic ischemia followed by 60 or 120 min Langendorff reperfusion. In each group, hearts were also randomly assigned into the 2 following sub-groups: postconditioning (PostC, consisting in 2 episodes of 30 s ischemia and 30 s reperfusion at the onset of reperfusion), and control (no intervention). Coronary flow, heart rate, dP/dt and rate-pressure-product were measured. Myocardial necrosis was assessed by TTC staining and LDH, CK release analysis. Our results indicated that heart function tended to slightly decrease between 60 min and 120 min reperfusion. Infarct size was identical at 60 min and 120 min reperfusion, averaging 33-34% of total LV area in controls versus 17% in PostC (p < 0.001 between control and PostC groups). Similarly, the maximum of enzymatic releases (CK and LDH) measured in coronary effluents was at 60 min of reperfusion, followed by a progressive decrease at 90 min and 120 min. As expected, postconditioning limited enzymatic releases whatever the studied time of reperfusion. In conclusion, we showed that prolonged reperfusion beyond 60 min was not useful for function assessment and did not change infarct size measurement, on Langendorff rat model of ischemia-reperfusion.
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The aim of this study was to evaluate the viability of arrested pig hearts harvested after animal death. Hearts (n = 25) were preserved for 2 hours by cold storage (4 degrees C) with St. Thomas' cardioplegic solution no warm ischemia... more
The aim of this study was to evaluate the viability of arrested pig hearts harvested after animal death. Hearts (n = 25) were preserved for 2 hours by cold storage (4 degrees C) with St. Thomas' cardioplegic solution no warm ischemia (0 minutes; control) or 10, 20, 30, or 60 minutes of in situ warm ischemia (animal exsanguination). Hearts were then reperfused for 1 hour with whole blood with an in vitro functional testing system. Left ventricular developed pressure and coronary flow were measured during reperfusion. Energetic compound measurements and histologic analysis were performed on tissue biopsy specimens. After 10- and 20-minute warm ischemia, hearts showed a significant decrease in energetic compounds, a 51% and 73% decreases of left ventricular developed pressure, and 38% and 65% decreases in coronary flow, respectively. After 30 minutes hearts showed irreversible ischemic injury with ultrastructural tissue damage, a large decrease in energetic adenine nucleotide compo...
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The myocardial infarction represents a major cause of mortality. The deleterious phenomena arising during the ischaemia and the reperfusion of the myocardium are studied for more than 40 years. We thought for a long time that the... more
The myocardial infarction represents a major cause of mortality. The deleterious phenomena arising during the ischaemia and the reperfusion of the myocardium are studied for more than 40 years. We thought for a long time that the ischaemia was the harmful stage, at the origin of the decrease of the energy stores, the dysregulation of the ionic homeostasis and the metabolic deregulation. We know now that the reperfusion itself is also a source of noxious effects (calcium overload, free radicals production, mitochondrion alteration). To combat these deleterious processes, two maneuvers demonstrated their efficiency by protecting the ischemic myocardium : it is the preconditioning and the postconditionning.
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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... more
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. Male Wistar rats (n = 60) were anesthetized by i.m. injection of ...
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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... more
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 ...
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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... more
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 die...
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In order to improve the assessment of the viability of donor's heart before transplantation, the feasibility of measuring electrical bio-impedance of myocard during long term preservations has been tested. The protocol, which was... more
In order to improve the assessment of the viability of donor's heart before transplantation, the feasibility of measuring electrical bio-impedance of myocard during long term preservations has been tested. The protocol, which was applied on pig hearts, simulated the conditions of real human organ preservations. The myocardial impedance was recorded in a wide frequency range against time. The whole set of impedance parameters of the cardiac muscle was recorded under various experimental parameters. This study has confid the feasibility of monitoring heart impedance during long term preservation. Furthermore, it appears that, in most cases, major changes in tissue impedance occur in the first hours of preservation.
The myocardial impedance between 25 kHz and 1 MHz was monitored in 29 porcine hearts during experimental preservations using a 4-electrode sensor placed in the left ventricle. Ischemia and edema were induced using three protocols. The... more
The myocardial impedance between 25 kHz and 1 MHz was monitored in 29 porcine hearts during experimental preservations using a 4-electrode sensor placed in the left ventricle. Ischemia and edema were induced using three protocols. The changes observed in the elements of the equivalent circuit model of the myocardium were (i) compared between the different protocols and (ii) correlated with the measured weight increase (attributed to the presence of edema). The largest changes were observed in the magnitude of the pseudo-capacitance and the characteristic frequency. The strongest correlation was observed during long term preservations between the final weight increase and the initial change in the characteristic frequency. Apart from this prognostic ability, the characteristic frequency has also the advantage to be directly calculable from the experimental data, independently of any equivalent circuit model
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ABSTRACT In order to increase heart graft preservation time, a simple portable and reliable mlcroperfuslon system has been realized experimentally. This system satisfied : (i) continuous heart microperfusion at 4ºC, (ii) good viability of... more
ABSTRACT In order to increase heart graft preservation time, a simple portable and reliable mlcroperfuslon system has been realized experimentally. This system satisfied : (i) continuous heart microperfusion at 4ºC, (ii) good viability of the keeping cardiac grafts. Faisability tests were studied on isolated pig heart, safely preserved 24 H with the microperfusion apparatus. Hypothermic heart preservation by this microperfusion method could be assessed by 4 different ways as followed : (i) by NM R spectroscopy. NMR antenna was specially realized to performed measurements without graft extraction of its sterilized transport jar, (ii) by electronic microscopy imaging, from cardiac biopsies, (iii) biochemically. Biopsies were analyzed by HPLC for high energy phosphate, (iv) by reanimation, on exvivo functional testing system at the end of the mlcroperfusion preservation period. All studies demonstrated a good viability and functionality of the hearts preserved 24 H with this hypothermic microperfusion apparatus.
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Recent work has demonstrated the benefit of low pressure (LP) reperfusion to protect the heart undergoing an ischemic insult. The goal of the present study was to determine the optimal pressure for the application of LP reperfusion.... more
Recent work has demonstrated the benefit of low pressure (LP) reperfusion to protect the heart undergoing an ischemic insult. The goal of the present study was to determine the optimal pressure for the application of LP reperfusion. Isolated rats hearts (n = 30) were exposed to 40 minutes of global warm ischemia followed by 70 minutes of reperfusion with a pressure fixed at 100 cm H(2)O (normal pressure [NP] = control group), 85 cm (group LP [low pressure]-85), 70 cm (group LP-70), or 55 cm (group LP-55). Cardiac function was assessed during reperfusion using the Langendorff model. Myocardial necrosis was assessed by measuring lactate dehydrogenase (LDH) and creatine kinase (CK) leakage in the coronary effluents. Functional recovery was progressively and significantly improved with decreased perfusion pressure. Rate-pressure product (RPP) averaged 3765 +/- 408, 6824 +/- 439, and 12,036 +/- 664 mm Hg/min, respectively, among the control, LP-85, and LP-70 groups (P &lt; .001, LP-70 vs other groups). However, RPP collapsed in the LP-55 group. Similarly, necrosis as measured by LDH and CK leakage progressively reduced between LP-100 and LP-70 hearts (P &lt; .01), with a drastic increase in enzyme in the LP-55 group. In conclusion, this study demonstrated that 70 cm H(2)O is an optimal LP to improve postischemic contractile dysfunction and attenuate necrosis during reperfusion.
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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... more
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 (&gt;50-fold, P &lt; .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.
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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... more
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 &lt; .05 and P &lt; .01 versus group I). The ICF strongly correlated with the energetic index (r = 0.76, P &lt; .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.
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Previous studies have shown the capacity of low-pressure (LP) reperfusion to protect the ischemic heart. The present study sought to determine the optimal time for the application of LP reperfusion. Isolated rat hearts (n = 30) were... more
Previous studies have shown the capacity of low-pressure (LP) reperfusion to protect the ischemic heart. The present study sought to determine the optimal time for the application of LP reperfusion. Isolated rat hearts (n = 30) were exposed to 40 minutes of global warm ischemia followed by 70 minutes of reperfusion. Reperfusion was performed under LP (LP = 70 cm H(2)O) for 0 (control group), 5 (group LP-5), 10 (group LP-10), 30 (group LP-30), or 60 (group LP-60) minutes. Following the LP period the hearts were reperfused with normal pressure (100 cm H(2)O) until the end of reperfusion. Cardiac function was assessed during reperfusion using the Langendorff model. Myocardial necrosis was assessed by measuring LDH leakage in the coronary effluents. Functional recovery was reduced among the control and LP-5 groups with rate-pressure products (RPP) averaging 3788 +/- 499 and 5333 +/- 892 mm Hg/min, respectively. RPP was significantly improved in other groups with RPP averaging 7363 +/- 1159, 7441 +/- 863, and 7269 +/- 692 mm Hg/min in LP-10, LP-30, and LP-60 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01). Similarly, necrosis measured by LDH leakage was significantly reduced in LP-10, LP-30, and LP-60 hearts (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01). This study demonstrated that LP reperfusion improves postischemic contractile dysfunction and attenuates necrosis when applied for at least 10 minutes.
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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... more
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 &lt; 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 &lt; 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.
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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. In the first phase, the hearts and lungs of 5... more
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. 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. 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. 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.
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HL-1, the first cell line with a cardiac phenotype for biological experiments, displays spontaneous electrophysiological and mechanical regular activity, and cyclic calcium movements. We isolated a derived line, devoid of transient... more
HL-1, the first cell line with a cardiac phenotype for biological experiments, displays spontaneous electrophysiological and mechanical regular activity, and cyclic calcium movements. We isolated a derived line, devoid of transient movements, for confocal microscopy experiments. These cells do express cardiac proteins: connexin 43, the cardiac isoform of dihydropyridine receptors, desmin, and developmental myosin but have no sarcomeric arrangement. They still possess the electrophysiological characteristics and ionic currents of cardiac cells, among them the cardiac potassium current IKr. We also found diazoxide and glibenclamide sensitive potassium channels with properties similar to IK(ATP) in adult cardiac myocytes. The pacemaker current I(f) was not observed, in agreement with the cells showing excitability but lacking in pacemaker activity. The absence of movement is an advantage for studies which include changes of media in order to follow morphological changes under continuous perfusion. We observed however a basal spontaneous movement of mitochondria and we developed a method to quantify its amplitude using confocal microscopy. No mitochondrial depolarization could be detected when the membrane potential was measured by using very low light photomultiplier and confocal fluorescence imaging under the K(ATP) channel opener diazoxide. Thus cardiac pharmacological preconditioning by K(ATP) channel openers might involve other routes than mitochondrial K channels targeting.
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The aim of this study is to evaluate the use of tetrazolium reductase (TR) activity as an indicator of myocardial viability in an isolated arrested pig heart biopsy model. Methyl Tetrazolium (MTT) is cleaved by an enzyme in the presence... more
The aim of this study is to evaluate the use of tetrazolium reductase (TR) activity as an indicator of myocardial viability in an isolated arrested pig heart biopsy model. Methyl Tetrazolium (MTT) is cleaved by an enzyme in the presence of coenzymes NAD, NADP. Cleavage yields a highly colored formazan product which is DMSO soluble. Efficient bioreduction of MTT has been investigated with heart biopsies. The relationship between MTT reduction and (1) oxygen consumption (r = 0.96, P &lt; 0.001), (2) the sum of the adenine nucleotide levels (r = 0.87, P &lt; 0.001) and (3) localization of coloration, has been established. The use of MTT in colorimetric assays offers high sensitivity. MTT reduction is a valid method. It is rapid and reproducible, and can be used as an indicator of myocardial viability. The MTT test has been used to rapidly compare the effect of different cardioplegic solutions (St Thomas and improved St Thomas) on hypothermic cardiac preservation. Significant differences have been established between the two solutions (P &lt; 0.01).
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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... more
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&lt;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&lt;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&lt;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.
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The aim of this study was to compare several methods of hypothermic heart preservation. We preserved isolated pig hearts for 24 hours in cold cardioplegia (4 degrees C), using either continuous microperfusion (Group I) or simple storage... more
The aim of this study was to compare several methods of hypothermic heart preservation. 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&amp;amp;#39; 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. 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 &amp;amp;gt; IB (p &amp;amp;lt; 0.001) and IIA &amp;amp;gt; IIB (p &amp;amp;lt; 0.01); the rate pressure products were higher in NPS groups compared with St. Thomas groups (IA &amp;amp;gt; IB, p &amp;amp;lt; 0.01); IIA &amp;amp;gt; IIB, p &amp;amp;lt; 0.05). The microperfusion method associated with the NPS provides excellent protection in long-term hypothermic heart preservation.
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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. After anesthesia and monitoring, 16 pigs were randomized... more
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. 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. 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 &amp;amp;lt; 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. In this model, biphasic plasmatic catecholamine release appears to primarily explain the physiopathology of the hemodynamic response to brain death induction.
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ABSTRACT Recent clinical and experimental studies have suggested that antioxidant supplements might actually have harmful as well as beneficial effects in the setting of cardiovascular disease. The mechanisms underlying the beneficial... more
ABSTRACT Recent clinical and experimental studies have suggested that antioxidant supplements might actually have harmful as well as beneficial effects in the setting of cardiovascular disease. The mechanisms underlying the beneficial effects of the various antioxidants are poorly understood in humans. Reperfusion-associated myocardial injury, and particularly the phenomenon of stunning, is important because it occurs in clinical settings and may condition the prognosis after short ischemic insult. We studied the effects of chronic (3 months) alpha-tocopherol supplementation with a large oral dose (500 mg daily) on myocardial contractility (stunning) and ventricular arrhythmias in a dog model of short ischemia followed by reperfusion. Twenty dogs were randomized to either an alpha-tocopherol supplemented or a control group. After 3 months, dogs were anesthetized and underwent a 20-min coronary artery occlusion followed by reperfusion. Myocardial regional blood flow was measured by the radioactive microsphere technique and myocardial contractility by sonomicrometry. Plasma alpha-tocopherol was measured by high-performance liquid chromatography in all dogs. Twelve dogs (seven supplemented and five controls) developed ventricular fibrillation at reperfusion, showing no difference between groups. Hemodynamic parameters, blood flow in the ischemic area (collateral flow), and area at risk were similar in the two groups. Regional systolic segment shortening in the ischemic area was similar during ischemia and reperfusion in both groups, representing 41 +/- 15% (mean +/- SEM) of baseline contractility in controls and 51 +/- 8% in supplemented dogs after 150 min of reperfusion. Plasma alpha-tocopherol level was higher in supplemented than in controls (19.1 +/- 1.6 and 6.9 +/- 0.6 mg/L; p &lt; 0.001). Thus a long-term large dose of alpha-tocopherol had no significant effect on postischaemic ventricular arrhythmias and dysfunction (myocardial stunning) in this canine model. These data suggest that if alpha-tocopherol supplementation might be useful to improve the prognosis of coronary patients, it is likely not by interfering with the stunning phenomenon.
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Myocardial injury after ischemia/reperfusion has been attributed in part to the effects of neutrophils. We examined whether colchicine, a potent and rapid inhibitor of neutrophils, may reduce inflammatory leukocytosis, prevent... more
Myocardial injury after ischemia/reperfusion has been attributed in part to the effects of neutrophils. We examined whether colchicine, a potent and rapid inhibitor of neutrophils, may reduce inflammatory leukocytosis, prevent postischemic myocardial neutrophil accumulation, and reduce infarct size (IS). Twenty-four dogs were randomized to either a control (saline administration) or a colchicine (1 mg/kg intravenously, i.v.) group. Anesthetized open-chest dogs underwent 120-min coronary artery occlusion followed by 6-h reperfusion. Determinants of IS [area-at-risk (AAR) and collateral flow] and IS were measured in 22 dogs (11 in each group). We evaluated neutrophil toxicity by measuring ex vivo production of reactive oxygen species by chemiluminescence. Myocardial localization and accumulation of neutrophils were histologically evaluated by independent observers. The number of circulating neutrophils (p &lt; 0.01), neutrophil cytotoxicity (p &lt; 0.05), and neutrophil myocardial accumulation after 6-h reperfusion (p = 0.006) were reduced in treated dogs. Left ventricular (LV) peak rate of pressure increase was similar in both groups during ischemia /reperfusion. However, whereas collateral blood flow and AAR, the main determinants of IS, were similar in control and treated dogs, there was no reduction in IS: 37.1 +/- 7% of AAR in controls and 37.4 +/- 8% in treated dogs. Despite marked reduction of neutrophil toxicity and postischemic myocardial neutrophil accumulation, no myocardial protection could be detected in this dog model.