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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although previous studies have shown that preconditioning cannot be explained by concurrent myocardial stunning alone, it remains unclear whether reduction of contractile function by preconditioning ischemia is required for its cardioprotective effect. The present study examined whether preconditioning occurs in the absence of regional contractile dysfunction. In the first series of experiments, rabbits received two cycles of 2-min coronary occlusion separated by 5-min reperfusion, with or without dobutamine infusion (10 micrograms/kg/min, i.v.) commencing before the onset of ischemia. Regional thickening fraction measured by epicardial Doppler sensor was 72.8 +/- 4.7% of baseline (mean +/- SEM) in the untreated group and 102.9 +/- 3.1% in the dobutamine group at the end of the second cycle of ischemia/reperfusion. In the second series of the study, four groups of rabbits underwent 30-min coronary occlusion and reperfusion. The control group was untreated, and the PC group was preconditioned with two cycles of 2-min ischemia/5-min reperfusion before the 30-min ischemia. The PC-DOB group received both preconditioning and dobutamine infusion (10 micrograms/kg/min, i.v.), which was started 5 min before the preconditioning and continued for 19 min. The DOB group was given dobutamine infusion like the PC-DOB group, but was not preconditioned. After 72-h reperfusion, infarct size and area at risk were determined by histology and fluorescent particles, respectively. Infarct sizes in the PC and PC-DOB groups (25.0 +/- 3.4% and 22.7 +/- 3.3% of area at risk, respectively) were significantly smaller than that in the control group (48.2 +/- 2.6%). In the DOB groups, infarct size (43.5 +/- 4.0%) was similar to the control value. Infusion of dobutamine at a dose sufficient to abolish the contractile dysfunction which would have been induced by ischemic preconditioning did not attenuate the infarct size-limiting effect of preconditioning. Thus, it is unlikely that reduction of contractile function plays a permissive role in the appearance of the cardioprotective effect of preconditioning.
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PMID:Reduction of regional contractile function by preconditioning ischemia does not play a permissive role in the infarct size-limitation by the preconditioning. 814 24

The present study tested the hypothesis that nitric oxide production in coronary resistance vessels is an important mechanism affecting the regulation of myocardial perfusion in unanesthetized dogs. We inhibited nitric oxide synthesis with the arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) and maintained the compressive determinants of myocardial blood flow constant by ventricular pacing. L-NAME did not affect resting coronary blood flow and reduced the receptor-mediated increase in flow to intracoronary acetylcholine (100 micrograms/min IC) from 143 +/- 20% (mean +/- SEM) under control conditions to 31 +/- 10% after L-NAME (P < .001). Coronary autoregulatory relations were determined as steady-state coronary pressure was reduced by inflating a hydraulic occluder. Initial resistance adjustments over the autoregulatory plateau were not affected by L-NAME. Closed-loop autoregulatory gain was 0.84 +/- 0.09 under control conditions versus 0.78 +/- 0.07 after L-NAME (P = NS). As coronary pressure was reduced further, however, the critical pressure at which myocardial ischemia began (lower autoregulatory break point) increased from 45 +/- 3 mm Hg under control conditions to 61 +/- 2 mm Hg (P < .001) after L-NAME. In addition, the slope of the coronary pressure-flow relation below the autoregulatory break point was reduced (1.0 +/- 0.2 versus 0.58 +/- 0.09 mL.min-1.mm Hg-1 after L-NAME, P < .05), reflecting a reduction in the maximal conductance recruitable during ischemia. In concert with the effects of L-NAME on autoregulatory responses during ischemia, peak reactive hyperemic flow to a 30-second coronary occlusion was also reduced (from 200 +/- 22 to 166 +/- 24 mL/min after L-NAME, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of coronary autoregulatory responses by nitric oxide. Evidence for flow-dependent resistance adjustments in conscious dogs. 833 Mar 72

The aim of the study was to examine the effects of intravenous magnesium sulphate (MS) administration on myocardial contractile function and infarct size after occlusion of the left circumflex artery of the heart for 60 minutes. Under sodium pentobarbital anaesthesia (30 mg/kg. intravenously) the hearts of mongrel dogs (n = 13) were instrumented to measure left ventricular pressure (LVP), regional contractile function of the territories perfused by the left circumflex and anterior descending coronary arteries (%SS), mean arterial pressure (MAP), and coronary blood flow velocity (CFV). Immediately upon release of the coronary occlusion, either intravenous magnesium sulphate (100 mg/kg) or a dextrose vehicle (D5W) was infused. Animals were killed, their hearts excised and cut in 1 cm slices from apex to base and incubated in triphenyl tetrazolium chloride (TTC) for 20 minutes to measure infarcted areas. In the control group (n = 7), myocardial contractile function was severely depressed during the occlusion and displayed the same pattern of dysfunction during 3 h of reperfusion. The %SS of the area perfused by the circumflex artery at the end of the reperfusion period was 0.02 +/- 3 (mean + SEM) P < 0.05 vs MS; P < 0.05 vs pre-occlusion) and percentage of necrosis of the area at risk was 17.42 +/- 6 (P < 0.05 vs MS). In the magnesium sulphate group (n = 6), %SS was depressed during the occlusion as in the control group, but was preserved during reperfusion time, 9.8 +/- 1.0 (P < 0.05 vs D5W; P < 0.05 vs pre-occlusion) and showed significantly less percentage of necrotic tissue, 4.53 +/- 1 (P < 0.05 vs D5W). These results suggest that intravenous magnesium sulphate preserves myocardial contractile function and reduces infarct size significantly following a period of complete coronary occlusion.
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PMID:Intravenous magnesium sulphate and reperfused myocardium: preservation of function and reduction of infarct size. 887 6

In order to clarify the time course of superoxide generation in situ during ischemia and reperfusion in the rabbit heart, we used a method of enhanced chemiluminescence (CL) with 2-methyl-6-[p-methoxyphenyl]-3, 7-dihydroimidazo [1, 2-alpha]pyrazin-3-one (MCLA) as a specific probe for detecting superoxide radicals. The surface of the rabbit heart was exposed to a photomultiplier tube in a light-proof box. We introduced a reversible snare occluder into the box to continuously observe the light emission. An ischemia-reperfusion group (I/R, n = 7) was subjected to 30 mins of coronary occlusion, followed by 90 mins of reperfusion. We performed the same procedure (except for coronary occlusion) in the sham-operated group (n = 4). Another group of rabbits (n = 4) subjected to I/R received superoxide dismutase (SOD: 20 mg/kg, i.v.) during reperfusion to observe the CL response. In the I/R-group, the increase in CL began at 13 +/- 2 (mean +/- SEM) mins and peaked at 52 +/- 12 mins of reperfusion. CL in the I/R-group gradually increased from 818 +/- 350 counts/10 secs in the preischemic period to 1077 +/- 401 counts/10 secs during reperfusion (p < 0.01). In contrast, there was no increase in CL in the sham-operated group. The administration of SOD briefly attenuated CL by 24.1 +/- 6.8% for a period of 24.3 +/- 6.8 mins. The superoxide generation in situ in the ischemic rabbit heart appears to increase gradually and persists for a period following reperfusion.
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PMID:Continuous detection of superoxide in situ during ischemia and reperfusion in the rabbit heart. 918 85

In addition to having anti-ischaemic effects, halothane can protect isolated rat hearts and isolated cardiomyocytes against reperfusion injury of the "oxygen paradox" type. The aim of this study was to investigate if halothane can also protect against myocardial reperfusion injury in vivo. Twenty-two rabbits anaesthetized with alpha-chloralose underwent 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Seven animals received 1 MAC of halothane for the first 15 min of reperfusion (halothane group), and eight animals served as untreated controls (controls group). In seven additional animals, the haemodynamic effects of halothane were antagonized by an i.v. infusion of noradrenaline (halothane-noradrenaline group). We measured cardiac output (CO) by an ultrasonic flow probe around the ascending aorta, left ventricular pressure (LVP) by a tip manometer and infarct size by triphenyltetrazolium staining. Baseline LVP was mean 92 (SEM 4) mm Hg and CO was 289 (16) ml min-1. During coronary occlusion, LVP was reduced to 86 (4)% of baseline and CO to 84 (4)% (similar in all groups). During halothane administration at reperfusion, LVP declined further to 55 (6)% of baseline and CO to 66 (9)% (P < 0.05 halothane group vs control group). Noradrenaline prevented the reduction in LVP (halothane-noradrenaline group 87 (5)% of baseline, control group 84 (6)% and reduction in CO (halothane-noradrenaline group 89 (5)%, control group 83 (6)%. Infarct size was 49 (6)% of the area at risk in controls and was reduced markedly by administration of halothane to 32 (3)% in the halothane group (P < 0.05) and to 30 (3)% in the halothane-noradrenaline group (P < 0.05). Treatment with halothane during the early reperfusion period after myocardial ischaemia protected the myocardium against infarction in vivo, independent of the haemodynamic effect of halothane.
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PMID:Halothane reduces reperfusion injury after regional ischaemia in the rabbit heart in vivo. 930 95

It is known that volatile anaesthetics protect myocardial tissue against ischaemic and reperfusion injury in vitro. In this investigation, we have determined the effects of the inhalation anaesthetics, enflurane, isoflurane, sevoflurane and desflurane, administered only during early reperfusion, on myocardial reperfusion injury in vivo. Fifty chloralose-anaesthetized rabbits were subjected to 30 min of occlusion of a major coronary artery followed by 120 min of reperfusion. Left ventricular pressure (LVP, tip-manometer), cardiac output (CO, ultrasonic flow probe) and infarct size (triphenyltetrazolium staining) were determined. During the first 15 min of reperfusion, five groups of 10 rabbits each received 1 MAC of enflurane (enflurane group), isoflurane (isoflurane group), sevoflurane (sevoflurane group) or desflurane (desflurane group), and 10 rabbits served as untreated controls (control group). Haemodynamic baseline values were similar between groups (mean LVP 106 (SEM 2) mm Hg; CO 281(7) ml min-1). During coronary occlusion, LVP and CO were reduced to the same extent in all groups (LVP 89% of baseline; CO 89%). Administration of inhalation anaesthetics during early reperfusion further reduced both variables, but they recovered after discontinuation of the anaesthetics to values not different from control animals. Infarct size was reduced from 49 (5)% of the area at risk in the control group to 32 (3)% in the desflurane group (P = 0.021), and to 36 (2)% in the sevoflurane group (P = 0.097). In the enflurane group, infarct size was 39 (5)% (P = 0.272). Isoflurane had no effect on infarct size (48 (5)%, P = 1.000). The results show that desflurane and sevoflurane markedly reduced infarct size and therefore can protect myocardium against reperfusion injury in vivo. Enflurane had only a marginal effect and isoflurane offered no protection against reperfusion injury in vivo. These different effects suggest different protective mechanisms at the cellular level.
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PMID:Effects of enflurane, isoflurane, sevoflurane and desflurane on reperfusion injury after regional myocardial ischaemia in the rabbit heart in vivo. 1021 Oct 18

Reperfusion injury after coronary occlusion is in part mediated by leukocyte activation and adhesion. Platelets may interact with polymorphonuclear granulocytes (PMNs), causing aggravated reperfusion injury. We studied whether c7E3Fab, a chimeric Fab fragment blocking platelet glycoprotein (GP) IIb/IIIa, decreases PMN-platelet-dependent myocardial dysfunction after ischemia. Isolated guinea pig hearts (n=5 per group) perfused at a constant flow of 5 mL/min were subjected to ischemia (15 minutes, 37 degrees C) and reperfusion. Human PMNs (10x10(6) cells, 3 mL), platelets (400x10(6), 3 mL), and fibrinogen (1 mg/mL) were infused for 3 minutes after 2 minutes of reperfusion, with or without c7E3Fab. Flow cytometry detected GPIIb/IIIa (platelets) and MAC-1 (aMbeta2, PMNs) as well as coaggregates of both in the effluent, whereas double-fluorescence microscopy visualized intracoronary PMN-platelet coaggregates. Postischemic recovery of pressure-volume work (12-cm H(2)O preload and 60-mm Hg afterload) was defined as the ratio of postischemic to preischemic external heart work (mean+/-SEM). c7E3Fab reduced platelet GPIIb/IIIa detection to 10% of controls, blocked a transcoronary MAC-1 increase (+25% without versus -23% with c7E3Fab), and inhibited PMN-platelet coaggregation in the effluent (49+/-12% without versus 17+/-2% with c7E3Fab) as well as in the hearts themselves (5.0+/-0.7/cm(2) without versus 1.2+/-0.3/cm(2) surface area with c7E3Fab). Postischemic recovery of external heart work (83+/-5% in cell-free hearts) declined to 46+/-4% after postischemic PMN-platelet infusion, but not in the presence of c7E3Fab (74+/-11%) or LPM19c (71+/-6%). We conclude that c7E3Fab inhibits formation of PMN-platelet aggregates during myocardial reperfusion, an effect that protects against PMN-platelet-dependent stunning.
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PMID:c7E3Fab reduces postischemic leukocyte-thrombocyte interaction mediated by fibrinogen. Implications for myocardial reperfusion injury. 1103 Dec 8


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