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M Ovize

Publications and source records attributed to M Ovize.

54 records · Page 3Linked to original sources
PubMed1995

Preconditioning reduces infarct size but accelerates time to ventricular fibrillation in ischemic pig heart.

Preconditioning protects the rat heart from ventricular arrhythmias. However, the mechanism of this beneficial effect and its existence in large animal models remain unknown. We submitted 49 pigs to 40 min of left anterior descending coronary occlusion and 2 h of reperfusion and assessed the incidence of ventricular fibrillation (VF) and time to VF. Monophasic action potential duration (MAPD) and ventricular fibrillation threshold (VFT) were measured throughout the experiment. Preconditioning significantly reduced infarct size but failed to reduce the incidence of VF either during the 40-min ischemic insult or the following reperfusion. Moreover, preconditioning accelerated the onset of VF during the prolonged ischemia; time to VF averaged 8 +/- 2 min in the preconditioned group vs. 18 +/- 2 min in the control group (P < 0.05). This premature peak of VF in preconditioned hearts was associated with a significant decrease of VFT and shortening of MAPD. This suggests that preconditioning does not limit the incidence of VF in the pig model. Rather, preconditioning decreases the time to VF in this species, likely through lowering of the VFT and shortening of the action potential duration.

Action Potentials↗
PubMed1995

[Ischemic preconditioning: concept of endogenous myocardial protection].

Preconditioning is a temporary tolerance to ischaemia acquired by the myocardium after a short period of ischaemia. It results in the limitation of the infarct size induced by prolonged coronary occlusion. The mechanism of this cytoprotection remains poorly understood. The A1 adenosine receptors, the ATP-sensitive potassium channels and protein-kinase C seem to play prominent roles. The effects of preconditioning on the complications of ischaemia/reperfusion such as myocardial stunning, ventricular arrhythmias or decreased coronary reserve are not well known. Several studies suggest that the cytoprotection resulting from preconditioning could be applied to human myocardium and constitute a preventive anti-ischaemic therapy during coronary angioplasty, cardiac surgery or the conservation of transplant grafts.

Adaptation, Physiological↗
PubMed1994

Stretch preconditions canine myocardium.

Preconditioning is believed to be directly triggered by brief ischemia-reperfusion. However, brief ischemia results in transient dilation (or stretching) of the heart. We therefore sought to determine whether stretch per se, induced by rapid volume overload instead of brief coronary occlusion, could precondition the heart via stretch-activated ion channels. Forty-two anesthetized dogs underwent 1 h of coronary artery occlusion followed by 4.5 h of reperfusion. Before this, each dog underwent either no intervention (control) or acute volume overload. In three additional groups, Gd3+, a potent blocker of stretch-activated channels was injected as a bolus into the left atrium of each dog at the onset of the treatment period. Then the dogs underwent either acute volume overload, a 5-min episode of coronary occlusion followed by 10 min of reperfusion, or no intervention. Myocardial stretch significantly reduced infarct size after a subsequent 60-min ischemic insult. Protection afforded by stretch was completely prevented by Gd3+. Reduction in infarct size afforded by ischemic preconditioning was partially reversed by Gd3+. Gd3+ per se did not, however, alter the extent of necrosis. The present study suggests that myocardial stretch per se can precondition the canine heart, probably by activation of stretch-activated ion channels.

Animals↗
PubMed1994

Pulsatility improves hemodynamics during fetal bypass. Experimental comparative study of pulsatile versus steady flow.

BACKGROUND: The main advantage of pulsatile flow compared with steady flow during cardiopulmonary bypass is to prevent a rise in systemic vascular resistances. We hypothesized that pulsatile flow could overcome the progressive rise in peripheral and placental vascular resistances observed during fetal bypass and leading to progressive irreversible hypoxemia. METHODS AND RESULTS: A study was undertaken in 17 fetal lambs (110 to 140 days of gestation). Fetal bypass was established for a 30-minute period through right atrial and main pulmonary artery cannulation. The circuit had no oxygenator. Flow was delivered by a standard roller pump for the continuous study (group 1, n = 9) or by a centrifugal pulsatile pump for the pulsatile study (group 2, n = 8). Oxymetric and hemodynamic parameters, along with organ blood flow determined by radiolabeled microspheres counting, were recorded before (T1) and after 10 minutes (T2) and 30 minutes (T3) of bypass. SaO2 and PaO2 were significantly higher in group 2 than in group 1 at T2 but thereafter deteriorated similarly in both groups, whereas PCO2 remained unchanged. Pump flow in group 2 was significantly higher than in group 1 at T2 and T3 (957.6 +/- 49 and 1104 +/- 152 versus 437.6 +/- 23 and 467.8 +/- 43 mL/min, respectively). Systemic vascular resistances during pulsatile bypass were also significantly lower than in group 1 at T2 (402 +/- 12 versus 930 +/- 79 dynes/sec/cm-5) and T3 (374 +/- 60 versus 1017 +/- 192 dynes/sec/cm-5). At T2 and T3, all individual blood flows except the brain but including the placenta were statistically higher in group 2 than in group 1. Placental vascular resistances gradually increased during bypass in group 1 to reach 2.9 +/- 0.2 mm Hg.mL-1.min-1.kg-1 at T3 and remained approximately stable in group 2 during 30 minutes of pulsatile bypass, varying from 0.35 +/- 0.02 to 1.26 +/- 0.14 from T2 to T3 (P < .01). CONCLUSIONS: The data suggest that pulsatile flow for 30 minutes of bypass in a fetal lamb preparation temporarily prevents the progressive hypoxemia observed under steady-flow bypass. Pulsatile flow allows higher pump flow through a significant decrease in systemic vascular resistances. Individual organ blood flow, including placenta, was significantly higher under pulsatile bypass. With technical improvements in the design of pulsatile devices adapted to more physiological beat rates, pulsatility may become a valuable adjunct to overcome placental dysfunction observed during experimental fetal cardiac surgery.

Animals↗
PubMed1993

Ischemic preconditioning and long-chain acyl carnitine in the canine heart.

BACKGROUND: This study investigated the effects of ischemic preconditioning on myocardial carnitine-linked metabolism and high-energy phosphates in the canine model of ischemia and reperfusion. METHODS: Anesthetized dogs underwent 1 hour of coronary artery occlusion and 4.5 hours of reperfusion. The dogs were randomly assigned to a control group (no intervention for 30 minutes), a preconditioned group (four repeated episodes of 3 minutes of mechanical coronary occlusion, each followed by 5 minutes of reperfusion), and a coronary cyclic flow variation (CFV) group (coronary artery stenosis and endothelial injury, resulting in an average of four episodes of platelet thrombosis and dislodgment). After completion of the protocol, ATP, creatine phosphate, and long-chain acyl carnitine concentrations were studied in both nonischemic and previously ischemic myocardium. RESULTS: In Part I of this study (Ovize et al., Circulation 1992, 85:779-789), it was reported that both mechanical occlusion and CFV before sustained occlusion resulted in a decrease in infarct size. In the present paper, we report changes in high-energy phosphates and long-chain acyl carnitine in these groups. Control, preconditioned, and CFV groups showed similar depletion in ATP content and "overshoot" in creatine phosphate stores. Control dogs exhibited a significant accumulation of long-chain acyl carnitine in the previously ischemic tissue (219 +/- 61 vs 131 +/- 38 nmoles/g wet weight in the nonischemic tissue; P < 0.05). No significant increase in long-chain acyl carnitine occurred in the mechanically preconditioned and CFV groups. CONCLUSIONS: These results indicate that brief episodes of transient ischemia before sustained coronary occlusion prevent long-chain acyl carnitine accumulation in the ischemic and reperfused canine myocardium.

Acetylcarnitine↗
PubMed1993

Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion.

BACKGROUND: One or more brief episodes of coronary artery occlusion protect or "precondition" the myocardium perfused by that artery from a subsequent episode of sustained ischemia. We sought to determine whether ischemic preconditioning protects only those myocytes subjected to brief coronary occlusion or whether brief occlusions in one vascular bed also limit infarct size and/or attenuate contractile dysfunction in remote virgin myocardium subjected to subsequent sustained coronary occlusion. METHODS AND RESULTS: In the preliminary limb of the study, six anesthetized dogs underwent four episodes of 5-minute circumflex branch occlusion plus 5-minute reperfusion, followed by 1 hour of sustained left anterior descending coronary artery occlusion and 4.5 hours of reflow. Subendocardial blood flow during left anterior descending coronary artery occlusion (measured by injection of radiolabeled microspheres) was 0.07 +/- 0.03 mL.min-1 x g tissue-1, similar to the value of 0.07 +/- 0.02 mL.min-1 x g-1 observed in a group of eight concurrent control dogs. However, infarct size (assessed by triphenyltetrazolium staining) in the circumflex preconditioned group averaged 4 +/- 1% of the myocardium at risk, significantly less (p < 0.05) than the value of 13 +/- 4% observed in the concurrent controls. An additional 18 dogs were then randomized to undergo either four episodes of circumflex branch occlusion (n = 8) or no intervention (n = 10) before 1 hour of left anterior descending coronary artery occlusion and 4.5 hours of reflow. Subendocardial blood flow averaged 0.08 +/- 0.02 versus 0.08 +/- 0.03 mL.min-1 x g-1 in the control versus circumflex preconditioned groups, yet infarct size was significantly smaller in circumflex preconditioned dogs than in the controls (6 +/- 2% versus 16 +/- 5% of the risk region; p < 0.05). At 4.5 hours following reperfusion, segment shortening in the left anterior descending coronary artery bed (assessed by sonomicrometry) averaged -21 +/- 19% of baseline in control animals versus 13 +/- 12% of baseline in the preconditioned group (p = NS). Circumflex preconditioning did not, however, have an independent beneficial effect on contractile function: Regression analysis revealed that the trend toward improved function in circumflex preconditioned dogs reflected the smaller infarct sizes in this group. CONCLUSIONS: Brief episodes of ischemia in one vascular bed protect remote, virgin myocardium from subsequent sustained coronary artery occlusion in this canine model. These data imply that preconditioning may be mediated by factor(s) activated, produced, or transported throughout the heart during brief ischemia/reperfusion.

Animals↗
PubMed1993

[Myoglobin and CPK-MM isoforms during the acute phase of myocardial infarction].

The biological diagnosis is usually late with respect to clinical and electrocardiographic signs of acute myocardial infarction. Recent laboratory methods have stimulated renewed interest in very early marker of infarction: myoglobin and CPK isoforms. The authors undertook a prospective study of the diagnostic sensitivity of myoglobin (MG), CPK and CPK-MM isoforms in 30 consecutive patients undergoing intravenous thrombolytic therapy in the acute phase of myocardial infarction. Blood samples were obtained on admission and every 30 minutes for 1 h 30. The Mb contributed to diagnosis of infarction on admission in 89% of patients. This percentage fell to 44% for the ratio MM3/MM1 > 0.5 to 27% for the CPK and to 24% for the ratio MM3/MM1 > 1. The sensitivity of all tests increased in the later blood samples but it remained low in the CPK and MM3/MM1 > 1 criteria. The diagnostic sensitivity of the first sample was also better in patients admitted after the 3rd hour (Mb = 100%; MM3/MM1 > 0.5: 58%; CPK: 41%) compared with those admitted before the 3rd hour (Mb = 82%; MM3/MM1 > 0.5: 35%; CPK: 17%). These results show that the diagnostic sensitivity of biological markers of myocardial infarction is very different. The serum myoglobin is an earlier and more sensitive marker than the CPK or CPK-MM isoforms.

Aged↗
PubMed1992

Importance of the flow perfusion deficit in the response to captopril in experimental myocardial infarction.

Previous results on the effects of angiotensin-converting enzyme (ACE) inhibition in myocardial ischemia are conflicting. To determine whether acute ACE inhibition may influence myocardial perfusion deficit during ischemia and reduce ischemia-reperfusion injury, anesthetized open-chest dogs underwent 2-h left anterior descending coronary artery (LAD) occlusion followed by 6-h reperfusion. After 1-h coronary occlusion, each dog was randomized to receive either captopril [5 mg/kg intravenous (i.v.) bolus and 0.25/kg/h infusion for 7 h] or saline. Whereas arterial pressure was reduced (p = 0.001), captopril did not influence myocardial perfusion deficit: Blood flow in the central ischemic zone represented 17.1 +/- 2.8% of the flow in the nonischemic zone versus 20.5 +/- 3.8% before treatment (NS). The values of the control group were 17.8 +/- 2.5 and 16.7 +/- 2.4%, respectively. In addition, there was no difference in infarct size: 35.9 +/- 3.3% of the area at risk in captopril-treated dogs versus 40.0 +/- 3.6% in controls. Analysis of subgroups based on the level of the collateral flow indicated, however, that ACE inhibition had an adverse effect on infarct size in dogs with high collateral flow: 31.9 +/- 4.6% in captopril dogs versus 17.6 +/- 4.7 (p = 0.048). This effect was related to a decrease in collateral flow because animals exhibiting the highest increase in perfusion deficit presented the greatest increase in infarct size (r = -0.92, p = 0.003). Although in dogs with low collateral flow, ACE inhibition appeared to exert a slight beneficial effect on infarct size, we conclude that at least in this dog model, acute ACE inhibition could exacerbate myocardial injury.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Coronary cyclic flow variations "precondition" ischemic myocardium.

BACKGROUND: Repeated brief episodes of myocardial ischemia performed by mechanical clamping of a coronary artery "precondition" the heart and reduce infarct size after a subsequent sustained ischemia. It is not known, however, whether spontaneous episodes of transient ischemia caused by formation of platelet thrombi, which may occur in unstable angina, have a similar cardioprotective effect. METHODS AND RESULTS: Therefore, our objective was to determine whether brief spontaneous thrombotic episodes of ischemia/reperfusion could limit infarct size and preserve contractile function following 60 minutes (protocol 1) or 90 minutes (protocol 2) of sustained ischemia and 4-4.5 hours of reperfusion in the canine model. Before the sustained coronary occlusion, dogs underwent a 30-minute "treatment" period consisting of: no intervention (control group), four repeated episodes of 3-minute mechanical occlusion plus 5-minute reperfusion (preconditioned group), or coronary artery stenosis and endothelial injury, resulting in a mean of four spontaneous episodes of cyclic flow variations (CFV group) caused by formation and dislodgment of platelet thrombi. In protocol 1 (60-minute sustained ischemia plus 4.5-hour reperfusion), infarct size was significantly smaller in both the preconditioned and CFV groups compared with controls (3.5 +/- 1.4%,* 3.4 +/- 2.1%,* and 9.9 +/- 2.7% of the myocardium at risk, respectively; *p less than 0.05 versus control). In contrast, neither preconditioning nor CFV preserved contractile function: Segment shortening during sustained occlusion was equally depressed at -15% to -20% of baseline values among the three groups and equally stunned at +12% to +18% of baseline during the 4.5 hours of reflow. In protocol 2 (90-minute sustained ischemia plus 4-hour reperfusion), only CFV continued to exert a cardioprotective effect: Infarct size averaged 15.0 +/- 4.1%, 7.4 +/- 2.5%,* and 16.5 +/- 4.4% of the region at risk in the preconditioned, CFV, and control groups, respectively (*p less than 0.05 versus control). Contractile function, however, was similar among all three groups both during 90 minutes of sustained occlusion and throughout 4 hours of reperfusion. CONCLUSIONS: We therefore conclude that repeated coronary thrombus formation preconditions the ischemic myocardium: In fact, in contrast to mechanical preconditioning, cardioprotection provided by CFV persisted following 90 minutes of sustained coronary occlusion. However, preconditioning by thrombotic or mechanical occlusion neither preserved myocardial contractile function during sustained coronary occlusion nor prevented stunning after reperfusion. These data raise the possibility that clinical episodes of unstable angina prior to acute myocardial infarction may precondition the ischemic myocardium.

Animals↗
PubMed1992

Preconditioning does not attenuate myocardial stunning.

BACKGROUND: Despite numerous reports that one or more episodes of brief coronary artery occlusion preconditions the myocardium and dramatically reduces myocardial infarct size produced by a subsequent prolonged ischemia, we recently demonstrated that preconditioning does not attenuate contractile dysfunction in the peri-infarct tissue. However, the specific effects of preconditioning on myocardium in which wall motion has not been compromised by the preconditioning regimen per se and is further submitted to a short ischemic insult (that is, not confounded by necrosis) remain unknown. METHODS AND RESULTS: We addressed these issues in the canine model of myocardial stunning. Eighteen anesthetized dogs underwent 15 minutes of coronary occlusion followed by 3 hours of reperfusion. Before the 15-minute coronary occlusion, each dog received one of three treatments: no intervention (control group, n = 6), one episode of 5-minute coronary occlusion/5-minute reperfusion (PC5 group, n = 6), or one episode of 2.5-minute coronary occlusion/5-minute reperfusion (PC2.5 group, n = 6). Segment shortening (SS) in the ischemic/reperfused midmyocardium was monitored by sonomicrometry, and myocardial blood flow was assessed by injection of radiolabeled microspheres. All three groups were equally ischemic during the 15-minute coronary occlusion: Midmyocardial blood flow averaged 0.05 +/- 0.02, 0.07 +/- 0.04, and 0.08 +/- 0.03 ml/min/g in control, PC2.5, and PC5 groups, respectively. Before the 15-minute coronary occlusion, PC5 dogs exhibited significant stunning (SS = 55% baseline; p less than 0.01 versus control), whereas PC2.5 dogs did not (SS = 91% baseline; p = NS versus control). However, segment shortening during the subsequent 15-minute coronary occlusion was equally depressed at -25% to -42% of baseline values among the three groups. Furthermore, all three groups demonstrated a similar degree of stunning after reperfusion: SS at 3 hours after reflow averaged 24 +/- 12%, 34 +/- 16%, and 48 +/- 12% of baseline in control, PC2.5, and PC5 groups, respectively (p = NS). The degree of recovery of function after reperfusion correlated with the amount of midmyocardial blood flow during coronary artery occlusion. However, this relation was not different among the three groups: Specifically, for any given collateral flow during ischemia, preconditioning did not reduce the degree of stunning. CONCLUSIONS: Preconditioning neither preserves contractile function during a reversible ischemic insult nor prevents myocardial stunning during the initial hours of reflow.

Adenosine Triphosphate↗
PubMed1992

Partial coronary stenosis is sufficient and complete reperfusion is mandatory for preconditioning the canine heart.

Repeated brief episodes of total coronary artery occlusion (i.e., severe ischemia), each separated by brief periods of reperfusion, reduce infarct size after a subsequent sustained ischemia. The importance of the intensity of ischemia during these coronary artery occlusions and the role of the following transient reflow are poorly understood. Therefore, our objective was to determine whether moderate preconditioning ischemia induced by partial coronary artery stenosis (reducing coronary flow to approximately 50% of its baseline values), with or without a brief period of total reperfusion, could precondition the canine myocardium. Dogs were randomized to receive one of three preconditioning "treatments": the R(-) group underwent 15 minutes of partial coronary stenosis without subsequent brief reperfusion (n = 8); the R(+) group underwent 15 minutes of partial coronary stenosis followed by 10 minutes of full reflow (n = 8); and the control group underwent no intervention (n = 8). All dogs then underwent 1 hour of total coronary artery occlusion and 4.5 hours of reperfusion. Both treated groups were equally and moderately ischemic during partial stenosis: myocardial blood flow in the inner two thirds of the left ventricular wall averaged 0.25 +/- 0.05 and 0.31 +/- 0.07 ml/min per gram in the R(-) and R(+) groups, respectively (p = NS). Furthermore, all three groups were equally and severely ischemic during sustained total occlusion: myocardial blood flow in the inner two thirds of the left ventricular wall averaged 0.06 +/- 0.05, 0.05 +/- 0.03, and 0.07 +/- 0.03 ml/min/g in control, R(-), and R(+) groups, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1992

[Myocardial infarction beyond the 48 first hours: treatment with calcium channel antagonists].

Calcium channel blocking agents prevent calcium entering cardiac and smooth muscle cells. With reduction of the blood pressure, heart rate and myocardial contractility, they reduce myocardial oxygen demand. By relieving spasm and coronary constriction, and dilating the collateral coronary vessels, they improve perfusion of the ischemic zones. The results in experimental infarction are contradictory: the reduction in the infarct size and ischaemia is not constant. In the Myocardial Infarction Study, a trial of lidoflazine in 1792 subjects followed up for an average of 5 years, there was no significant difference between the mortality rates of the two groups. In the Danish Verapamil Infarction Trial I, which included 436 subjects receiving 360 mg/day of verapamil or placebo, the 6 months mortality was less (NS) in the verapamil group (12.8%) than in the placebo group (13.9%) as was the reinfarction rate (7.8% versus 9.2%; NS). In the DAVIT II trial of 1775 subjects, treatment was introduced 9 +/- 2.7 days after admission. Mortality was lower (NS) in the verapamil group (11.1%) than in the placebo group (13.8%) and the recurrences were less common (p = 0.04) in the treatment group (11.0%) than with placebo (13.2%). The Secondary Prevention Reinfarction Israeli Nifedipine Trial is a comparison of Nifedipine 30 mg/day and placebo introduced 7-21 days after infarction in 2276 subjects. After 10 months, the mortality and reinfarction rate were similar in both groups, as in the SPRINT II trial (60 mg/day of nifedipine or placebo) at 6 months. In the Multicenter Diltiazem Postinfarction Trial of 2466 patients, Diltiazem 240 mg/day or placebo was administered 3 to 15 days after infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

U74006F, a novel 21-aminosteroid, inhibits in vivo lipid peroxidation but fails to limit infarct size in a canine model of myocardial ischemia reperfusion.

Peroxidation of membrane lipids has been suggested to play a role in the pathogenesis of myocardial ischemia/reperfusion injury. We therefore assessed the efficacy of U74006F, a potent in vitro vitamin E-like inhibitor of lipid peroxidation, in limiting infarct size in a canine model of transient coronary artery occlusion. Twenty dogs underwent 2 hours of occlusion of the left anterior descending coronary artery and 6 hours of reperfusion. U74006F or saline solution was administered continuously from 1 hour of occlusion to the end of the experiment. U74006F blunted any increase in production of conjugated dienes (an index of lipid peroxidation) at both 30 minutes (1.73 +/- 0.16 mol/L x 10(-4) vs 2.62 +/- 0.22 in control dogs, p less than 0.05) and 6 hours (1.39 +/- 0.22 vs 2.06 +/- 0.18 in control dogs, p less than 0.05) after reperfusion. Furthermore, 6 hours after reflow vitamin E levels tended to be lower than baseline values in control dogs and higher than baseline values in dogs treated with U74006F. However, analysis of infarct size indicated no statistically significant difference between the two groups when expressed either as a percentage of the left ventricle (10.4 +/- 1.8% in U74006F vs 15.2 +/- 2.4% in control dogs) or as a percentage of the area at risk (33.0 +/- 5.5% in U74006F vs 37.8 +/- 4.5% in control dogs). Although U74006F appeared to be a potent in vivo inhibitor of lipid peroxidation, it failed to limit infarct size after 2 hours of occlusion and 6 hours of reperfusion in this canine model.

Animals↗
PubMed1991

Quantitation of reperfused myocardial infarction by Gd-DOTA-enhanced magnetic resonance imaging. An experimental study.

Because there is evidence that myocardial infarct size is modified by coronary artery reperfusion, an ex vivo experimental model of myocardial infarction was developed to determine the influence of the timing of gadolinium-tetraazacyclododecane tetraacetic acid (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) on the accuracy of infarct size quantitation. Eighteen dogs underwent a 2-hour coronary occlusion followed by 1 (n = 6), 6 (n = 6), or 48 (n = 6) hours of reperfusion. Gd-DOTA was injected 10 minutes before the dogs were killed. T1 (SE 250/26) and T2 (SE 1500/78) weighted images were performed on excised hearts. Gd-DOTA concentration was measured in myocardium by atomic emission spectrometry, and correlated with myocardial blood flow evaluated by radioactive microspheres. All dogs presented with myocardial infarction (mean size 20.4% +/- 3.1% of the left ventricle), and a corresponding area of increased signal intensity on T1-weighted MR images. In none of the three groups did the area of high signal intensity correlate with the ischemic area. By contrast, after 6 and 48 hours of reperfusion, the high signal intensity area (17.9% +/- 2.4%) closely matched the area of nonreversible jeopardized tissue (16.4% +/- 2.5%), as determined on tetrazolium-stained heart slices. Although a noreflow phenomenon was observed in the jeopardized tissue, Gd-DOTA concentration was higher in the subendocardial central ischemic zone than in normally perfused myocardium. Gd-DOTA imaging enhancement seems to be the consequence of a delayed clearance of the agent from the injured tissue. Gd-DOTA-enhanced MRI accurately quantitates the size of reperfused myocardial infarction on the ex vivo heart for more than 6 hours after the beginning of reperfusion. It remains to be determined whether the in vitro results obtained here can be applied to assess the myocardial infarct size in vivo.

Animals↗
PubMed1990

Inhibition of coronary artery thrombosis by SIN-1, a donor of nitric oxide.

Molsidomine and its metabolite, SIN-1, a donor of nitric oxide, are potent coronary vasodilator and anti-ischemic agents. Recently, SIN-1 and nitric oxide have also been shown to inhibit platelet adhesion and aggregation in vitro. The present study in dogs was designed to evaluate the in vivo antithrombotic properties of SIN-1. Coronary intimal damage and stenosis are known to induce coronary cyclic flow variations that reflect platelet thrombus formation followed by disaggregation and embolization (Folts preparation). This model of coronary artery thrombosis appears to simulate the combination of some of the factors contributing to unstable angina and myocardial infarction in human. SIN-1 infusion (10 micrograms/kg/min) significantly reduced the frequency of cyclic flow variations: 4.9 +/- 6.2/h vs. 14 +/- 4.6/h (before treatment, p less than 0.03, n = 6). Results were similar to those obtained with aspirin (5 mg/kg, bolus i.v.: 1.5 +/- 0.6/h vs. 11.7 +/- 3/h, p less than 0.03, n = 5) whereas saline had no effect (17.8 +/- 2.2/h vs. 19.3 +/- 2.4/h, n = 5). As expected, blood pressure was decreased only in the SIN-1 group: 56.2 +/- 7.8 vs. 87.3 +/- 9.3 mm Hg (p less than 0.02) (mean arterial blood pressure). The present results suggest that the well-documented anti-ischemic properties of SIN-1 could be partly due to its antithrombotic activity, clearly demonstrated with the model of coronary thrombosis used here in the dog.

Animals↗
PubMed1990

[The natural history of coronary disease. The role of cholesterol].

The natural history of the complications of coronary heart disease has been defined by anatomicopathological and epidemiological studies, particularly the Framingham study. At the same time, research is being carried out on risk factors which play a role in the progressive development of atheromatous plaque (atherogenic factors: hypertension: hypercholesterolaemia) and those factors which lead to complications in the atheromatous plaque (aggravating or precipitating factors: smoking, thrombosis, etc.). This schematic perspective may lead to the redefinition of the strategy to adopt in fighting atherosclerotic arterial disease; a better aim will thus the taken in the fight against hypercholesterolaemia.

Cholesterol↗
PubMedDate not supplied

Increased platelet aggregation after heart transplantation: influence of aspirin.

Accelerated graft coronary artery disease remains the most dramatic complication in long-term survivors of heart transplantation. The main purpose of this study was to evaluate ex vivo platelet function of heart transplant recipients as compared with that of healthy subjects and nontransplant coronary patients. The influence of aspirin, the chief antiplatelet agent, was also evaluated. The heart transplant recipients exhibited a marked platelet hyperaggregation to adenosine diphosphate as compared with the two control groups. In addition, platelets of the heart transplant recipients appeared to be resistant to the inhibitory effect of aspirin. These results could, at least partly, explain the failure of antiplatelet agents to prevent myocardial infarction in these patients.

Adenosine Diphosphate↗