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Biomedical subjects

M Ovize

Publications and source records attributed to M Ovize.

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

[Postconditioning: lethal reperfusion injury as a therapeutic target].

Acute myocardial infarction is the leading cause of morbidity and mortality in western countries. Ischemic postconditioning, that consists of repeated brief episodes of ischemia-reperfusion performed just after reflow following a prolonged ischemic insult, dramatically reduces infarct size. Recent data indicate that it might involve the activation of the PI3-kinase-Akt-eNOS signalling pathway and inhibition of the opening of the permeability transition pore. A recent clinical study demonstrated that postconditioning protects the human heart. Further research is needed to find new pharmacological agents that would mimick postconditioning in order to treat all patients with ongoing acute myocardial infarction.

Humans↗
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↗
PubMed2006

Link between immune cell infiltration and mitochondria-induced cardiomyocyte death during acute cardiac graft rejection.

Acute cardiac graft rejection (ACGR) is associated with cardiomyocyte apoptosis. We investigated the respective role of the Fas/FasL and mitochondrial permeability transition pore (mPTP) pathways in cardiomyocyte apoptosis accompanying ACGR. Heterotopic cardiac transplantations were performed in 7-9-week old C57BL6 or C3H mice. Wild type or Fas-deficient (lpr) mice underwent syngeneic (GS) or allogeneic (GA) transplantation, and received either saline or NIM811, a specific inhibitor of the mPTP. At day 5, we assessed ACGR by histology, cardiomyocyte apoptosis by caspase-3 activity and cytochrome c release, Ca(2+)-induced mPTP opening by a potentiometric approach, and expression of Fas, FasL, TNFalpha, perforin, granzyme using RT-PCR. Myocardial infiltration of CD8(+) T lymphocytes was performed by immunohistochemistry. Allogenic transplantation increased infiltration of inflammatory cells, upregulated FasL, perforin, granzyme, and TNFalpha, favored Ca(2+)-induced mPTP opening and increased caspase-3 activity and cytochrome c release in WT grafts. NIM811, but not Fas-deficiency, significantly reduced all these effects. NIM811 also limited infiltration of CD8(+) into WT and lpr transplants. These data suggest that the mPTP pathway plays a major role in cardiomyocyte apoptosis associated with ACGR. Inhibition of mPTP opening may attenuate cardiomyocyte apoptosis either directly or indirectly via a limitation of CD8(+) T-cell activation.

Acute Disease↗
PubMed2005

Fas-independent mitochondrial damage triggers cardiomyocyte death after ischemia-reperfusion.

The Fas/Fas ligand and mitochondria pathways have been involved in cell death in several cell types. We combined the genetic inactivation of the Fas receptor (lpr mice), on the one hand, to the pharmacological inhibition of the mitochondrial permeability transition pore (mPTP), on the other hand, to investigate which of these pathways is predominantly activated during prolonged ischemia-reperfusion. Anesthetized C57BL/6JICO (control) and C57BL/6-lpr mice were pretreated with either saline or cyclosporin A (CsA; 40 mg/kg, 3 times a day), an inhibitor of the mPTP, and underwent 25 min of ischemia and 24 h of reperfusion. After 24 h of reperfusion, hearts were harvested: infarct size was assessed by 2,3,5-triphenyltetrazolium chloride staining, myocardial apoptosis by caspase 3 activity, and mitochondrial permeability transition by Ca2+-induced mPTP opening using a potentiometric approach. Infarct size was comparable in untreated control and lpr mice, ranging from 77 +/- 5% to 83 +/- 3% of the area at risk. CsA significantly reduced infarct size in control and lpr hearts. Control and lpr hearts exhibited comparable increase in caspase 3 activity that averaged 57 +/- 18 and 49 +/- 5 pmol x min(-1) x mg(-1), respectively. CsA treatment significantly reduced caspase 3 activity in control and lpr hearts. The Ca2+ overload required to open the mPTP was decreased to a similar extent in lpr and controls. CsA significantly attenuated Ca2+-induced mPTP opening in both groups. Our results suggest that the Fas pathway likely plays a minor role, whereas mitochondria are preferentially involved in mice cardiomyocyte death after a lethal ischemia-reperfusion injury.

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↗
PubMed2004

Preconditioning during coronary angioplasty: no influence of collateral perfusion or the size of the area at risk.

AIMS: It is unclear whether the protection observed in human heart following repetition of brief episodes of ischaemia is due to opening of coronary collaterals or to ischaemic preconditioning. We investigated whether the improvement in ST segment change following repeated episodes of brief ischaemia during coronary angioplasty is due to preconditioning when the size of the area at risk and the collateral flow are taken into account. METHODS AND RESULTS: Thirty-six patients underwent percutaneous transluminal coronary angioplasty. Intracoronary ST segment changes were measured throughout the procedure and used as an endpoint. The size of the area at risk and the collateral perfusion within the ischaemic bed were measured using single photon emission computerized tomography (SPECT). Mean ST segment shift observed in all patients significantly decreased from 11.0+/-2.6 mm during the first balloon inflation to 8.5+/-2.3 mm during the second inflation. This protective effect occurred in the absence of any change in the size of the area at risk (mean: 46+/-5% of LV) and of the collateral perfusion to the ischaemic zone (mean: 23+/-4% of flow in the non-ischaemic zone). CONCLUSION: These results suggest that ischaemic preconditioning does occur during repeated brief coronary artery occlusion in the human heart.

Adolescent↗
PubMed2004

Mitochondrial permeability transition in cardiomyocyte apoptosis during acute graft rejection.

Evidence indicates that acute cardiac graft rejection is associated with cardiomyocyte apoptosis. Mitochondrial permeability transition (MPT) induces apoptotic cell death. We sought to determine whether MPT might play a role in cardiomyocyte apoptosis in the rat model of heterotopic cardiac transplantation. Syngenic and allogenic transplantations were performed, and both native and grafted hearts were harvested 3 or 5 d after transplantation for detection of acute rejection, assessment of Ca(2+)-induced MPT, and myocardial apoptosis by TUNEL staining and caspase 3 activity. Allogenic grafts developed severe acute rejection at day 5 with concomitant cardiomyocyte apoptosis (apoptotic index: 7.1 +/- 1.0% vs. 1.0 +/- 0.2% in syngenic hearts, and caspase 3 activity: 38 +/- 25 vs. 5 +/- 9 nmol/mg, in allogenic vs. syngenic grafts, respectively). At day 5, Ca(2+)-induced MPT was dramatically altered in allogenic when compared with syngenic grafts (mean Ca(2+) overload averaged 0 +/- 20 vs. 280 +/- 30 microM in allogenic and syngenic grafts, respectively). NIM811, a nonimmunosuppressive derivative of cyclosporin A (CsA), that specifically inhibits the MPT pore, did not alter acute rejection, but significantly delayed Ca(2+)-induced MPT pore opening, attenuated caspase 3 activity and cardiomyocyte apoptosis in allogenic grafts. This suggests that mitochondrial permeability transition pore opening may play an important role in cardiomyocyte apoptosis associated with acute cardiac graft rejection.

Animals↗
PubMed2003

Alteration of the left ventricular contractile reserve in heart transplant patients: a dobutamine stress strain rate imaging study.

BACKGROUND: Strain rate imaging (SRI), a recently developed Doppler-derived process, allows quantification of myocardial systolic function. We investigate whether SRI quantifies the contractile reserve during dobutamine stress tests in heart transplant patients (HT), when compared with normal individuals. METHODS: An incremental dobutamine test (5 to 40 microg/kg per minute) was performed in 10 HT and 15 control subjects, all of whom displayed normal coronary angiography. Gray-scale and color myocardial Doppler data were acquired in standard B-mode views at baseline, low-dose, peak, and recovery. Longitudinal SR was processed from the myocardial velocities for each segment. The changes in maximal systolic SR were used to quantify myocardial contractile reserve. RESULTS: Dobutamine infusion failed to induce clinical symptoms or electrocardiographic (ECG) changes in either group. Visually determined wall motion score was considered normal in all segments for each stage of the dobutamine stress. Heart rate was augmented similarly in both groups during dobutamine infusion. In controls, systolic SR increased gradually with incremental dobutamine dose and returned to baseline values upon recovery. Conversely, in HT patients, the increase in systolic SR was blunted at peak dobutamine, at which point it was significantly different vs controls. CONCLUSIONS: Quantitative assessment of myocardial function using SRI during dobutamine stress revealed an impaired contractile reserve in HT patients with normal coronary angiography. These subtle changes in regional myocardial function could not be identified using visual wall motion scoring. Additional studies are necessary to evaluate whether SR imaging detection of contractile reserve impairment will improve clinical efficiency or event prediction in this population.

Adrenergic beta-Agonists↗
PubMed2002

Pharmacological preconditioning: comparison of desflurane, sevoflurane, isoflurane and halothane in rabbit myocardium.

BACKGROUND: Recent investigations showed that isoflurane can induce pharmacological preconditioning. The present study aimed to compare the potency of four different halogenated anaesthetics to induce preconditioning. METHODS: Anaesthetized open-chest rabbits underwent 30 min of coronary artery occlusion followed by 3 h of reperfusion. Before this, rabbits were randomized into one of five groups and underwent a treatment period consisting of either no intervention for 45 min (control; n = 10), or 30 min of 1 MAC halogenated anaesthetic inhalation followed by 15 min of washout. End-tidal concentrations of halogenated agents were 3.7% for sevoflurane (n = 11), 1.4% for halothane (n = 9), 2.0% for isoflurane (n = 11), and 8.9% for desflurane (n = 11). Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. RESULTS: Mean (SD) infarct size was 54 (18)% of the risk area in untreated controls and 40 (18)% in the sevoflurane group (P > 0.05, ns). In contrast, mean infarct size was significantly smaller in the halothane, isoflurane, and desflurane groups: 26 (18)%, 32 (18)% and 16 (17)%, respectively (P < 0.05 vs control). CONCLUSIONS: Halothane, isoflurane and desflurane induced pharmacological preconditioning, whereas sevoflurane had no significant effect. In this preparation, desflurane was the most effective agent at preconditioning the myocardium against ischaemia.

Anesthetics, Inhalation↗
PubMed2002

[Changes in left ventricular torsion during ischemia-reperfusion].

We aimed to characterise the alterations of left ventricular twist during ischaemia-reperfusion and to study their relationship to global left ventricular function. Systolic left ventricular twist was measured at the mid-papillary muscle level by colour tissue Doppler echocardiography in 7 anaesthetised open-chest dogs at baseline, 90 min-occlusion of the left anterior descending, and 180 min after reflow. Tissue Doppler was also performed in 34 patients after anterior infarct and in 20 controls. In controls, rotation occurred counterclockwise when viewed from the base. In a random subset of subjects, the assessment of ventricular twist by tissue Doppler was validated against magnetic resonance myocardial tagging. Myocardial ischaemia led to a decrease in ventricular twist in dogs and infarct patients (p < 0.01). This decrease was correlated with the extent of the asynergic area and global left ventricular function (p < 0.001). In dogs, cardiac twist was higher after reflow relative to ischaemia (p < 0.01). Thus, acute myocardial ischaemia is responsible for a decrease in left ventricular twist that is related to global ventricular function. Colour tissue Doppler echocardiography provides straightforward assessment of left ventricular twist in humans.

Aged↗
PubMed2001

Tissue Doppler imaging differentiates transmural from nontransmural acute myocardial infarction after reperfusion therapy.

BACKGROUND: The evaluation of transmural extent of necrosis after acute myocardial infarction remains a major problem in clinical practice. We sought to determine whether color M-mode tissue Doppler imaging (TDI) could differentiate transmural from nontransmural myocardial infarction. METHODS AND RESULTS: Twenty-one anesthetized open-chest dogs underwent 90 or 120 minutes of left anterior descending coronary artery occlusion followed by 180 minutes of reperfusion. The transmural extension of infarct was measured by triphenyltetrazolium chloride (TTC) staining. Segment shortening in the endocardium and epicardium of the anterior and posterior walls was assessed by sonomicrometry. Regional myocardial blood flow was measured by radioactive microspheres. TDI was obtained from an epicardial short-axis view. We calculated systolic and diastolic velocities within the endocardium and epicardium of myocardial walls and the subsequent myocardial velocity gradient (MVG). TTC staining could identify 2 groups according to the transmural extent of necrosis: 15 dogs had a nontransmural (NT) necrosis (42+/-3% of wall thickness), and 6 dogs developed a transmural (T) infarct (81+/-4% of wall thickness). In both groups, ischemia resulted in a significant and similar reduction in endocardial and epicardial velocities, with a resulting low systolic MVG in the anterior wall (0.10+/-0.07 in NT and 0.10+/-0.08 s(-1) in T). At 60 minutes of reperfusion, systolic MVG failed to change significantly in the transmural group (-0.20+/-0.09 s(-1)). In contrast, it increased significantly after reflow in the NT group compared with ischemic values (-0.99+/-0.20 versus 0.10+/-0.07 s(-1), P:<0.05). CONCLUSIONS: TDI can differentiate transmural from nontransmural myocardial infarction early after reperfusion.

Animals↗
PubMed2001

Beta-adrenergic receptors and intracellular signalling pathway in stunned and non-ischemic regions of pig myocardium.

The beta-adrenergic pathway may have a role in the pathophysiology of ischemic syndromes characterised by reversible left ventricular dysfunction, such as myocardial stunning and other clinical conditions of unstable angina or coronary spasms, or chronic reversible left ventricular dysfunction, which might be a consequence of repeated events of short-term ischemia ("repetitive stunning"). A partial-to-total occlusion of the left anterior descending coronary artery in pigs was used to induce short periods of ischemia (total ischemic time 12 +/- 2 min). Hypokinesis and dyskinesis of the myocardium were considered signs of myocardial dysfunction. We found a maintained function of the beta-adrenergic signalling system. Density and affinity of beta-adrenergic receptors were not different in stunned and non-ischemic regions, nor were cyclic AMP and cyclic GMP intracellular contents and ratio, nor well as the ratio of stimulatory/inhibitory G protein a subunits. Our findings are in agreement with a maintained beta-adrenergic signalling system in the pathophysiology of chronic reversible left ventricular dysfunction.

Animals↗
PubMed2001

Safety of oral nicorandil before coronary artery bypass graft surgery.

Nicorandil is a K(ATP) channel opener used to treat angina. It is cardioprotective and a vasodilator. We conducted a prospective, randomized, double-blind, placebo-controlled study to assess oral nicorandil in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Twenty-two patients received nicorandil (10 mg twice a day) and 23 patients received placebo. Haemodynamic data were recorded before induction of anaesthesia (T0), 5 and 20 min after starting mechanical ventilation (T1, T2), before aortic cannulation (T3), after 30 min of CPB (T4), 10 min after CPB (T5) and after 3, 8 and 18 h in the intensive care unit (T6, T7, T8). Serum proteins (creatine kinase metabolite and cardiac troponin I) were measured before and 8 and 18 h after surgery. Haemodynamic values did not differ between the two groups. There was no tachycardia during the study, no significant difference in hypotensive episodes, ST segment changes and no changes in cardiac enzymes. Myocardial infarction after surgery was similar in the two groups. Vasoactive therapy was similar in the two groups. Nicorandil can be continued safely up to premedication without deleterious haemodynamic consequences, but a myocardial protective effect of nicorandil in CABG surgery was not found.

Administration, Oral↗
PubMed2000

Assessment of nonuniformity of transmural myocardial velocities by color-coded tissue Doppler imaging: characterization of normal, ischemic, and stunned myocardium.

BACKGROUND: Transmural myocardial contractile performance is nonuniform across the different layers of the left ventricular wall. We evaluated the accuracy of color M-mode tissue Doppler imaging (TDI) to assess the transmural distribution of myocardial velocities and to quantify the severity of dysfunction induced by acute ischemia and reperfusion in the inner and outer myocardial layers. METHODS AND RESULTS: Thirteen open-chest dogs underwent 15 minutes of left anterior descending coronary artery occlusion followed by 120 minutes of reperfusion. M-mode TDI was obtained from an epicardial short-axis view. Systolic velocities were calculated within endocardium and epicardium of the anterior and posterior walls. Regional myocardial blood flow was assessed by radioactive microspheres. Segment shortening was measured by sonomicrometry in endocardium and epicardium of both the anterior and posterior walls. At baseline, endocardial velocities were higher than epicardial velocities, resulting in an inner/outer myocardial velocity gradient. Ischemia caused a significant and comparable reduction in endocardial and epicardial systolic velocities in the anterior wall with the disappearance of the velocity gradient. Systolic velocities significantly correlated with segment shortening in both endocardium and epicardium during ischemia and reperfusion. In the first minutes after reflow, endocardial velocities showed a greater improvement than epicardial velocities, and the velocity gradient resumed although to a limited extent, indicative of stunning. CONCLUSIONS: TDI is an accurate method to assess the nonuniformity of transmural velocities and may be a promising new tool for quantifying ischemia-induced regional myocardial dysfunction.

Animals↗