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Biomedical subjects

W Schlack

Publications and source records attributed to W Schlack.

At least 55 records · Page 3Linked to original sources
PubMed1998

The impact of vasoactive substances on intraosseous pressure and blood flow alterations in the femoral head: a study based on magnetic resonance imaging.

In beagle dogs, the alterations of intraosseous pressure and blood supply in the femoral head that result from the administration of vasoactive substances were examined, and the changes were documented by magnetic resonance imaging (MRI). Vasoactive substance were infused into the medial and lateral circumflex femoral arteries of 12 beagle dogs. All infusions were done under standardised conditions with simultaneous measurements of venous blood flow and intraosseous pressure distribution in the proximal femur. The drugs were infused in three cycles of 30 min each separated by 30 min recovery periods, followed by MRI examination at the end of each experiment. At an intraosseous pressure of 14.3 (+/- 4.2) mmHg in the femoral head epiphysis (I), 11.6 (+/- 2.7) mmHg in the greater trochanter (II) and 9.3 (+/- 3.2) mmHg in the femoral shaft (III), a baseline flow of 96.2 (+/- 18.8, n = 12) ml/min was measured in the femoral vein. After infusing bradykinin at a concentration of 10(-6) moles, which is commonly known to lead to cerebral and subcutaneous oedema formation by vessel dilatation, the intraosseous pressure increased to (I): 49.1 (+/- 6.2) mmHg, (II): 42.5 (+/- 5.8) mmHg and (III): 38.3 (+/- 7.1) mmHg in the three measured femoral areas (n = 3). After the bradykinin injection, femoral vein flow increased to a peak value of 238.4 (+/- 43.4) ml/min and then dropped to 62.3 (+/- 14.2) ml/min after discontinuation of the bradykinin infusion. In a second and third series of tests, hyperosmolar (20% NaCl) and hypo-osmolar (distilled water) solutions were applied, also resulting in increased but lower mean intraosseous pressure values (17.3 +/- 4.1 and 25.7 +/- 5.1 ml/min, respectively) in all regions. When administering bradykinin, MRI scans taken immediately after completion of the experiment showed substantial oedema in the femoral muscular system, but without any changes of osseous signals in T1- or short time inversion recovery (STIR)-weighted images, nor did any changes occur when solutions of 20% NaCl or distilled H2O were injected. The results of our experiments demonstrate that acute increases of intraosseous pressure do not cause MRI signal alterations. We therefore conclude that in addition to the described pressure increase, other intraosseous alterations must occur to lead to the detectable signal changes found among patients with diagnosed femoral head necrosis. Finally, the short time period between the rise in intraosseous pressure and performing a conventional MRI may be one reason for missing the development of an intraosseous oedema. On the other hand, conventional MRI might have additional disadvantages for detecting intraosseous fluid compared with a dynamic imaging modality.

Animals↗
PubMed1998

Effects of enflurane, isoflurane, sevoflurane and desflurane on reperfusion injury after regional myocardial ischaemia in the rabbit heart in vivo.

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.

Anesthetics, Inhalation↗
PubMed1998

Effects of halothane, enflurane, isoflurane, sevoflurane and desflurane on myocardial reperfusion injury in the isolated rat heart.

A specific action against myocardial reperfusion injury of the oxygen paradox type was recently characterized for halothane after anoxic perfusion in isolated rat hearts and isolated cardiomyocytes. In this study, we have characterized the protective effects of the clinically available inhalation anaesthetics during reperfusion after ischaemia. In isolated, isovolumically beating rat hearts perfused at a constant flow (10 ml min-1, PO2 80 kPa) and paced at 350 beat min-1, we determined left ventricular developed pressure (LVDP) and release of creatine kinase (CKR) as indices of myocardial performance and cellular injury, respectively. Seven control hearts underwent 30 min of no-flow ischaemia and 1 h of reperfusion. In the treatment groups, halothane, enflurane, isoflurane, sevoflurane or desflurane (each group n = 6) was added to the perfusion medium for the first 30 min of reperfusion at a concentration corresponding to 1.5 MAC in the rat. In the control group, cellular injury occurred at early reperfusion (peak CKR 283 (SEM 57) iu litre-1 at 10 min of reperfusion). Peak CKR to the coronary venous effluent was attenuated by all anaesthetics (halothane group 156 (45), enflurane group 134 (20), sevoflurane group 132 (20), desflurane group 159 (25) iu litre-1; each P < 0.05). Isoflurane did not differ from controls (303 (53) iu litre-1; P = 0.5). In the sevoflurane group, there was a delayed peak CKR after discontinuation of the anaesthetic at 30 min of reperfusion (260 (34) iu litre-1). Functional recovery was improved by all anaesthetics, but was seen much earlier with desflurane (LVDP 28 (3)% of baseline at 5 min reperfusion compared with halothane (6 (1)%), enflurane (11 (3)%), isoflurane (9 (6)%), sevoflurane (10 (2)%) and controls (3 (1)% of baseline)). At 30 min of reperfusion, recovery of LVDP was improved to a similar extent by all anaesthetics (halothane 30 (9)%, enflurane 36 (9)%, isoflurane 33 (5)%, sevoflurane 30 (5)%, desflurane 36 (4)% of baseline values) compared with controls (13 (5)%; each P < 0.05). All inhalation anaesthetics protected against myocardial reperfusion injury, but showed differences in attenuation of cellular injury and functional recovery. These differences may suggest different protective mechanisms.

Anesthetics, Inhalation↗
PubMed1998

Enflurane and isoflurane, but not halothane, protect against myocardial reperfusion injury after cardioplegic arrest with HTK solution in the isolated rat heart.

UNLABELLED: To investigate the effects of halothane, enflurane, and isoflurane on myocardial reperfusion injury after ischemic protection by cardioplegic arrest, isolated perfused rat hearts were arrested by infusion of cold HTK cardioplegic solution containing 0.015 mmol/L Ca2+ and underwent 30 min of ischemia and a subsequent 60 min of reperfusion. Left ventricular (LV) developed pressure and creatine kinase (CK) release were measured as variables of myocardial function and cellular injury, respectively. In the treatment groups (each n = 9), anesthetics were given during the first 30 min of reperfusion in a concentration equivalent to 1.5 minimum alveolar anesthetic concentration of the rat. Nine hearts underwent the protocol without anesthetics (controls). Seven hearts underwent ischemia and reperfusion without cardioplegia and anesthetics. In a second series of experiments, halothane was tested after cardioplegic arrest with a modified HTK solution containing 0.15 mmol/L Ca2+ to investigate the influence of calcium content on protective actions against reperfusion injury by halothane. LV developed pressure recovered to 59%+/-5% of baseline in controls. In the experiments with HTK solution, isoflurane and enflurane further improved functional recovery to 84% of baseline (P < 0.05), whereas halothane-treated hearts showed a functional recovery similar to that of controls. CK release was significantly reduced during early reperfusion by isoflurane and enflurane, but not by halothane. After cardioplegic arrest with the Ca2+-adjusted HTK solution, halothane significantly reduced CK release but did not further improve myocardial function. Isoflurane and enflurane given during the early reperfusion period after ischemic protection by cardioplegia offer additional protection against myocardial reperfusion injury. The protective actions of halothane depended on the calcium content of the cardioplegic solution. IMPLICATIONS: Enflurane and isoflurane administered in concentrations equivalent to 1.5 minimum alveolar anesthetic concentration in rats during early reperfusion offer additional protection against myocardial reperfusion injury even after prior cardioplegic protection. Protective effects of halothane solely against cellular injury were observed only when cardioplegia contained a higher calcium concentration.

Anesthetics, Inhalation↗
PubMed1998

Effect of acidotic blood reperfusion on reperfusion injury after coronary artery occlusion in the dog heart.

A prolongation of the intracellular acidosis after myocardial ischemia can protect the myocardium against reperfusion injury. In isolated hearts, this was achieved by prolongation of the extracellular acidosis. The aim of this study was to investigate whether regional reperfusion with acidotic blood after coronary artery occlusion can reduce infarct size and improve myocardial function in vivo. Anesthetized open-chest dogs were instrumented for measurement of regional myocardial function, assessed by sonomicrometry as systolic wall thickening (sWT). Infarct size was determined by triphenyltetrazolium staining after 3 h of reperfusion. The left anterior descending coronary artery (LAD) was perfused through a bypass from the left carotid artery. The animals underwent 1 h of LAD occlusion and subsequent bypass-reperfusion with normal blood (control, n = 6) or blood equilibrated to pH = 6.8 by using 0.1 mM HCl during the first 30 min of reperfusion (HCl, n = 5). Regional collateral blood flow (RCBF) at 30-min occlusion was measured by using colored microspheres. There was no difference in recovery of sWT in the LAD-perfused area between the two groups at the end of the experiments [-2.8+/-1.2% (HCl) vs. -4.4+/-2.5% (control); mean +/- SEM; p = NS]. RCBF was comparable in both groups. Infarct size (percentage of area at risk) was reduced in the treatment group (12.8+/-2.8%) compared with the control group (26.2+/-4.8%; p < 0.05). These results indicate that reperfusion injury after coronary artery occlusion can be reduced by a prolonged local extracellular acidosis in vivo.

Acidosis↗
PubMed1998

Effect of heart rate reduction by 4-(N-ethyl-N-phenyl-amino)-1,2-dimethyl-6-(methylamino)pyrimidinium chloride on infarct size in dog.

Heart rate (HR) reduction may reduce the severity of myocardial ischemia. ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium++ + chloride) is a novel bradycardic agent with a specific effect on the sinoatrial node without having any other direct effects on the heart. In the present study, the effect of ZD7288 on infarct size and regional myocardial function during regional myocardial ischemia and reperfusion was investigated. Seventeen anesthetized open chest dogs (control, n = 8, and ZD7288, n = 9) underwent 1 h of left anterior descendent artery (LAD) occlusion followed by 6 h of reperfusion. In one group, ZD7288 was given intravenously (0.7 mg/kg body weight) 45 min before LAD occlusion. Regional myocardial function was assessed by sonomicrometry as systolic wall thickening fraction (sWTF) in the anteroapical (interest region, IR) and the posterobasal wall (control region, CR). Ischemic regional myocardial blood flow (RMBF) was determined by colored microspheres and infarct size (IS) by triphenyltetrazolium staining. ZD7288 injection decreased HR from 104 +/- 5 to 74 +/- 3 bpm (mean +/- SEM, p < 0.001 vs control, vs baseline), but did not change sWTF. During reperfusion, sWTF of the IR was significantly greater in the ZD7288 group (26 +/- 12 vs -14 +/- 13%, 1 h reperfusion, p < 0.05), while sWTF of CR stayed equal (120 +/- 13 vs 111 +/- 16%, p = ns). IS was markedly reduced in the ZD7288 group (4.7 +/- 1.8 vs 18.0 +/- 5.2% of IR, p < 0.05). There was no difference in ischemic endocardial RMBF (ZD7288 11.0 +/- 4.3 vs control 12.3 +/- 6.5 ml/min/100 g, p = ns). ZD7288 reduces HR without having direct effects on regional myocardial function. This HR reduction leads to a smaller IS and to a better regional functional recovery.

Animals↗
PubMed1997

Halothane protects cardiomyocytes against reoxygenation-induced hypercontracture.

BACKGROUND: Resupply of oxygen to the myocardium after extended periods of ischemia or hypoxia can rapidly aggravate the already existing injury by provoking hypercontracture of cardiomyocytes (acute reperfusion injury). Previous studies indicated that halothane can protect ischemic-reperfused myocardium. The aim of the present study was to analyze on the cellular level the mechanism by which halothane may protect against reoxygenation-induced hypercontracture. METHODS AND RESULTS: To simulate ischemia-reperfusion, isolated adult rat cardiomyocytes were incubated at pH 6.4 under anoxia and reoxygenated at pH 7.4 in the presence or absence of 0.4 mmol/L halothane. Reoxygenation was started when intracellular Ca2+ (measured with fura 2) had increased to > or = 10(-5) mol/L and pHi (BCECF) had decreased to 6.5. Development of hypercontracture was determined microscopically. In the control group, reoxygenation provoked oscillations of cytosolic Ca2+ (72+/-9 per minute at fourth minute of reoxygenation) accompanied by development of hypercontracture (to 65+/-3% of end-ischemic cell length). When halothane was added on reoxygenation, Ca2+ oscillations were markedly reduced (4+/-2 per minute, P<.001) and hypercontracture was virtually abolished (90+/-4% of end-ischemic cell length, P<.001). Halothane did not influence the recovery of pHi during reoxygenation. Similar effects on Ca2+ oscillations and hypercontracture were observed when ryanodine (3 micromol/L), an inhibitor of the sarcoplasmic reticulum Ca2+ release, or cyclopiazonic acid (10 micromol/L), an inhibitor of the sarcoplasmic reticulum Ca2+ pump, were applied instead of halothane. CONCLUSIONS: Halothane protects cardiomyocytes against reoxygenation-induced hypercontracture by preventing oscillations of intracellular Ca2+ during the early phase of reoxygenation.

Anesthetics, Inhalation↗
PubMed1997

Inotropic effects of glyceryl trinitrate and spontaneous NO donors in the dog heart.

BACKGROUND: In vitro, NO has a biphasic effect on myocardial inotropy. To determine the inotropic effect of NO in vivo, we investigated the activity of glyceryl trinitrate (GTN) and the NO donors S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and sodium-(2)-1-(N,N-diethyl-amino)-diazen-1-ium-1,2-diolat+ ++ (DEA/NO) in dogs. METHODS AND RESULTS: Eight anesthetized open-chest dogs were instrumented for measurement of left ventricular and aortic pressures (tip manometers) and coronary flow (ultrasonic flow probes). Regional myocardial function was assessed by sonomicrometry as systolic wall thickening (sWT), mean systolic thickening velocity (Vs), and regional myocardial stroke work index (RSW). GTN, SNAP, and DEA/NO were infused into the left anterior descending coronary artery (LAD) to achieve defined coronary plasma concentrations of GTN, SNAP (both 10 to 100 micromol/L), and DEA/NO (2 to 20 micromol/L). All drugs increased LAD flow and myocardial contractile function in the LAD-dependent myocardium within the first 120 seconds. The greatest inotropic effect was noted after infusion of DEA/NO (20 micromol/L), which increased sWT by 9.7+/-3.1% from 28.5+/-2.2%, Vs by 10.3+/-3.4% from 9.1+/-1.1 mm/s, and RSW by 7.1+/-2.1% from 200.0+/-22.1 mm Hg x mm (P<.05). At the same time, systemic hemodynamics remained unchanged. Prevention of the flow response to GTN by external narrowing of the LAD did not influence the inotropic effect of GTN. CONCLUSIONS: Organic nitrates and NO donors evoke a small but constant positive inotropic effect in vivo that is not caused by coronary vasodilation.

Animals↗
PubMed1997

[Effect of magnesium on infarct size after coronary occlusion. Animal experiment studies].

In addition to its antiarrhythmic and antithrombotic effects magnesium is said to have a beneficial effect in patients with acute myocardial infarction. Magnesium can protect myocardial tissue after coronary occlusion and reduces infarct size in experimental models of ischaemia and reperfusion, though the given doses of magnesium are relatively high and differ from clinically reachable serum concentrations. We tested 2 hypotheses in a dog model of ischaemia-reperfusion: 1. The protective effect may be due to a direct, local influence of magnesium on myocardial reperfusion injury. 2. Systemic magnesium treatment with low doses comparable to clinical study regiments may reduce myocardial infarct size. Anaesthetized open chest dogs underwent 1 h of left anterior descending artery occlusion followed by 6 h of reperfusion. 1. Ten animals received intracoronary magnesium aspartate (Mg i.c.) or vehicle infusion (control i.c.) for the first hour of reperfusion to increase regional Mg-concentration by 2 mmol/l. 2. Fourteen animals received intravenous infusion with magnesium potassium aspartate (Mg-K i.v.) or vehicle infusion (control i.v.), beginning 1 h before occlusion until the end of the 6 h reperfusion period. Regional magnesium concentration in the Mg i.c.-group increased to 2.7 +/- 1.00 mmol/l at 45 min of reperfusion. Intravenous infusion raised serum magnesium from 0.71 +/- 0.03 mmol/l to 1.29 +/- 0.14 mmol/l in the Mg-K i.v. group (5 min of reperfusion, p < 0.01 vs. baseline). Infarct size after 6 h reperfusion (TTC staining) was similar in both groups of intracoronary treatment (Mg i.c., 20.6 +/- 5.0; control, 24.4 +/- 8.7% of area at risk; p = n.s.) and intravenous treatment (Mg-K i.v. 18.1 +/- 14.8; control 14.1 +/- 12.2% of area at risk; p = n.s.). Neither regional nor systemic magnesium leads to a clinically relevant reduction of infarct size in the regional ischaemic-reperfused dog heart when it is given in clinically usable doses. The beneficial action of systemic Mg is probably not due to an early direct protective effect on ischaemic-reperfused myocardium but to its antiarrhythmic and antithrombotic effects. Possibly only to high doses of Mg applied under experimental conditions can reduce infarct size.

Animals↗
PubMed1997

Halothane reduces reperfusion injury after regional ischaemia in the rabbit heart in vivo.

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.

Anesthetics, Inhalation↗
PubMed1996

Characterisation of left ventricular relaxation in the isolated guinea pig heart.

The time constant of left ventricular pressure fall, tau, has frequently been used as a measure of myocardial relaxation in the blood-perfused, ejecting heart. The aim of the present study was to characterise tau in relation to beta-adrenergic activation, coronary perfusion pressure and flow as well as cardiac oxygen supply and demand in the isolated, isovolumically beating heart. Therefore, tau was analysed from digitised left ventricular pressure data in a total of 23 guinea pig hearts perfused with saline at constant pressure (60 cmH2O). The coronary venous adenosine concentration ([ADO]) served as an index of myocardial oxygenation. Isoprenaline (0.4-3.2 nmol l-1) decreased and propranolol (3-9 mumol l-1) increased tau dose-dependently (linear regression tau vs lg([isoprenaline]), r = 0.74; tau vs. lg([propranolol]), r = 0.66, both P < 0.05). During graded reductions in cardiac oxygen supply from 96.1 +/- 12.6 (SEM) to 44.4 +/- 4.4 microliters min-1 g-1, tau was prolonged from 61.5 +/- 12.7 to 109.9 +/- 22.6 ms while left ventricular developed pressure (LVDP) decreased from 90.7 +/- 7.2 to 40.7 +/- 5.1 mmHg. In parallel, [ADO] increased from 23.7 +/- 9.1 to 58.0 +/- 19.1 pmol ml-1 (P < 0.05). Increasing oxygen supply to 165.4 +/- 32.4 microliters min-1 g-1 augmented LVDP to 102.7 +/- 7.3 mmHg but did not change tau or [ADO]. There was a dual response of tau to changes in cardiac oxygen supply or demand. As long as oxygen supply and demand matched, tau remained constant. However, when the oxygen supply was less than 100 microliters min-1 g-1, left ventricular relaxation was prolonged in parallel to the reduction in oxygen supply. In addition, a close relationship was observed between [ADO] as an indicator of myocardial oxygenation and tau (Spearman correlation, r = 0.99, P < 0.005). We conclude that the time constant of left ventricular pressure fall, tau, sensitively reflects myocardial relaxation in the isolated, isovolumically beating guinea pig heart. Moreover, in this model left ventricular relaxation is not influenced by alterations in coronary perfusion pressure or flow as long as cardiac oxygen demand is matched by an adequate supply. Rather relaxation is strictly coupled to myocardial oxygenation as reflected by coronary venous adenosine concentrations.

Animals↗
PubMed1996

Effect of halothane on myocardial reoxygenation injury in the isolated rat heart.

Several studies have reported a protective effect of halothane on myocardial injury in an ischaemia-reperfusion situation. It is unclear if the protection is a result of the haemodynamic effects of halothane or if halothane has a specific action on ischaemia or reperfusion pathomechanisms. To examine this question, we have used an isolated rat heart model where heart rate (300 beat min-1), ventricular volume and coronary flow are constant. Left ventricular developed pressure (LVDP) and release of creatine kinase (CK) were measured as variables of myocardial performance and cellular injury, respectively. Five control hearts were subjected to 35 min of low-flow (2 ml min-1) anoxic and substrate-free perfusion and were then perfused for 1 h with the oxygenated buffer. In the treatment groups, halothane 0.4 mmol litre-1 was added during the first 30 min of anoxic perfusion (n = 5) or during the first 30 min of reoxygenation (n = 5). In five additional hearts, the effect of halothane 0.4 mmol litre-1 was tested under normoxic conditions. Mean basal CK release was 0.29 (SEM 0.13) iu g-1 min-1 and LVDP was 105.5 (4.0) mm Hg. Under normoxic conditions, halothane reduced LVDP to 52.0 (2.6) mm Hg. In control hearts, the major cell injury occurred at the onset of reoxygenation (CK release increased to 149.1 (9.1) iu g-1 min-1) and functional recovery after 1 h of reoxygenation was poor (control LVDP, 14.2(2.)% of baseline). Halothane during anoxia attenuated myocardial injury only moderately (CK release 50.2(5.7) iu g-1 min-1) and LVDP recovered to 30.8(3.0)% (each P < 0.05 vs control). When halothane was administered at reoxygenation, CK release was reduced to 10.1 (0.9) iu g-1 min-1 and LVDP recovered to 69.4(4.9)% (each P < .05 vs control). We conclude that halothane not only attenuated ischaemic injury but had a specific protective action against reoxygenation injury.

Anesthetics, Inhalation↗
PubMed1996

Unilateral changes of sympathetic tone to the heart impair left ventricular function.

BACKGROUND: Different regions within the left ventricle are preferentially supplied by the left or right sympathetic system. In order to characterize different influences of left vs right sympathetic lateralization on LV function, haemodynamic effects of right and left stellate ganglion stimulations (RSGS and LSGS) as well as a right sympathetic block (RSB) were compared. METHODS: Seven alpha-chloralose anaesthetized open chest dogs were instrumented for measurement of LV pressure (tip manometers) and regional LV wall thickness (WT, sonomicrometry) in the antero-apical wall (AW, innervated by right stellate ganglion) and postero-basal wall (PW, left stellate ganglion). Timing of regional myocadial wall motion was evaluated by the phase of the first Fourier transform of the WT signals, LV asynchrony by the phase difference (phi) between both regions, and LV diastolic function by the time constant of isovolumic relaxation (tau). Measurements were performed before and after RSB (5 ml of lidocaine 1%); in 6 dogs of this group, RSGS and LSGS (4 V, 0.2 ms, 20 Hz) were performed before RSB. In order to investigate a regional inotropic stimulation without systemic effect, 6 additional dogs received intracoronary noradrenaline injections (NIC, 0.25 microgram) into the left circumflex artery perfused myocardium. RESULTS: LSGS and NIC led to an earlier PW-motion within the cardiac cycle (phase reduction by 40.0 +/- 15.0 degree (SEM) and 55.5 +/- 11.2 degrees) and RSGS induced an earlier AW-motion (by 33.7 +/- 15.2 degrees). After RSB, AW-motion was delayed (38.1 +/- 9.2 degrees). The consequence was an asynchronous wall motion pattern after all interventions (change in phi: LSGS-64.7 +/- 18.7 degrees, RSGS 41.1 +/- 15.7 degrees, NIC -74.5 +/- 17.4 degrees, RSB -52.6 +/- 14.6 degrees), and a prolonged relaxation (tau increase: RSGS 9.4 +/- 1.9, NIC 8.3 +/- 1.5, RSB 3.7 +/- 0.8 ms). CONCLUSION: Unilateral increases as well as decreases of sympathetic tone to the heart result in an asynchronous wall motion pattern and an impaired LV relaxation.

Animals↗
PubMed1996

Effect of inotropic stimulation on the synchrony of left ventricular wall motion in a dog model of myocardial stunning.

BACKGROUND: Reperfusion after short coronary occlusion induces regional myocardial dysfunction ("stunning"), including asynchrony of left ventricular (LV) wall motion. Contractile function of stunned myocardium can be increased by inotropic stimulation, but whether this has an influence on wall motion asynchrony is unknown. METHODS: In six anaesthetized dogs, the effect of inotropic stimulation on regional myocardial function, and LV asynchrony was tested after the induction of regional stunning (by 15 min of left circumflex artery side branch occlusion). Regional myocardial function was assessed as mean systolic wall thickening velocity (Vswt) by sonomicrometry in the stunned (posterobasal wall) and normal myocardium (anteroapical wall), and LV asynchrony by the phase difference (phi) of the first Fourier transform of the wall thickness signals. RESULTS: In the stunned myocardium, Vswt decreased from 8.6 +/- 1.0 to 1.7 +/- 1.4 mm s-1 (mean +/- SEM), P < 0.01, and simultaneously phi increased from 10.8 +/- 3.6 to 85.7 +/- 14.3 degrees, P < 0.01. Intracoronary noradrenaline (NADR, 0.25 microgram) improved Vswt (8.3 +/- 1.4 mm s-1, P < 0.01) in the stunned region and changed phi to -38.1 +/- 18.0 degrees, P < 0.05. Systemic NADR (5 micrograms) also increased Vswt of the stunned region (to 3.8 +/- 2.1 mm s-1, P < 0.05), but left phi unchanged (82.9 +/- 19.8 degrees). CONCLUSION: Regional function of stunned myocardium can be augmented by inotropic stimulation with noradrenaline, but this does not result in an improvement of LV wall motion asynchrony during systemic inotropic stimulation.

Animals↗
PubMed1995

Intracoronary SIN-1C during reperfusion reduces infarct size in dog.

Reperfusion of ischemic myocardium may aggravate the ischemic state of injury and thus augment infarct size (reperfusion injury). The aim of this study was to reduce infarct size by an intervention at the time of reperfusion that acts only on a reperfusion-specific pathomechanism. It was investigated whether SIN-1C, a metabolite of molsidomine, can protect against reperfusion injury in canine hearts in vivo. Ten anesthetized open chest dogs underwent 1 h of left anterior descendent artery (LAD) occlusion and were randomly assigned to receive either intracoronary SIN-1C or vehicle infusion as a placebo during the first hour of reperfusion. The infusion was adjusted to LAD flow to achieve a regional blood concentration of 5 x 10(-3) M. Infarct size was assessed by triphenyltetrazolium staining after 6 h of reperfusion. Left ventricular pressure (LVP) was similar in both groups (SIN-1C: 101 +/- 6, placebo: 89 +/- 6 mm Hg, mean +/- SEM, n = 5) at the beginning of the experiment and did not change significantly thereafter from baseline values in both groups. During SIN-1C infusion, the LAD flow was increased (SIN-1C: 195 +/- 38, control: 86 +/- 17 ml/min/100 g at 30 min of reperfusion, p < 0.05), while systemic hemodynamics remained unaltered. A reduction in infarct size (percent of area at risk) was seen in the SIN-1C group (11.4 +/- 2.8%) compared with the placebo group (24.4 +/- 3.9%, p < 0.05). Infusion of papaverin (5 x 10(-5) M) following an identical protocol caused a similar vasodilation as SIN-IC, but did not reduce infarct size in five additional dox experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetonitriles↗
PubMed1995

Intracoronary magnesium is not protective against acute reperfusion injury in the regional ischaemic-reperfused dog heart.

Intravenous magnesium lowers mortality in patients with suspected myocardial infarction. We tested the hypothesis that the protective effect may be due to a direct, local influence of magnesium on myocardial reperfusion injury in a dog model of ischaemia/reperfusion. Ten anaesthetized open chest dogs underwent 1 h of left anterior descending artery (LAD) occlusion and 6 h of reperfusion. The animals received intracoronary (i.c.) magnesium aspartate (Mg, n = 5) or vehicle infusion (n = 5) for the first hour of reperfusion. Mg infusion was adapted to actual LAD flow (ultrasonic flow probe) to increase regional plasma concentration by 4 mmol L-1. Regional myocardial function was measured as percent systolic wall thickening (sWTh, sonomicrometry). Intracoronary Mg increased LAD flow during application (at 15 min reperfusion; Mg, 194 +/- 44 (mean +/- SD); control, 116 +/- 41 mL min-1 100 g-1, P < 0.01). sWTh decreased during coronary occlusion from 14.3 +/- 7.1% to -4.7 +/- 2.7% in the control group and from 14.8 +/- 2.5% to -4.1 +/- 3.1% in the Mg group. Throughout the reperfusion period wall function remained depressed in both groups to a similar degree (control, -3.5 +/- 1.8%; Mg, -3.0 +/- 1.9% at 6 h reperfusion). Global haemodynamics were not different. Infarct size after 6 h reperfusion (TTC staining) was similar in both groups (Mg, 20.6 +/- 5.0; control, 24.4 +/- 8.7% of area at risk). Regional magnesium application (i.c.) to post-ischaemic reperfused myocardium had no influence on infarct size or post-ischaemic regional wall function in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Regional contractile blockade at the onset of reperfusion reduces infarct size in the dog heart.

An important mechanism of lethal myocardial reperfusion injury is the development of cellular hypercontracture at the onset of reperfusion. Hypercontracture can lead to cytolysis by mutual mechanical disruption of myocardial cells. 2,3-Butanedione monoxime (BDM) inhibits myofibrillar cross-bridge cycling and may therefore reduce infarct size in ischaemic reperfused myocardium. This study investigated whether a temporary presence of BDM protects against myocardial reperfusion injury in an intact-animal preparation. Anaesthetized open-chest dogs (n = 10) underwent 1 h of left anterior descendent artery (LAD) occlusion and received intracoronary BDM (25 mM, n = 5) or vehicle (n = 5) for 65 min starting with an anoxic local infusion 5 min before reperfusion. Infarct size was assessed by triphenyltetrazolium staining after 6 h reperfusion. The infusion of BDM was accompanied by a transient reduction of left ventricular systolic pressure from 84.3 +/- 11.2 mm Hg during occlusion to 66.4 +/- 9.9 mm Hg at 30 min reperfusion (mean +/- SD, P < 0.01 vs. control). LAD-flow and regional wall motion in the area at risk showed no difference between groups. Infarct size (% of area at risk) was reduced from 24.4 +/- 8.7 (control) to 6.6 +/- 2.0% (BDM) (P < 0.01). The results demonstrate that development of necrosis in reperfused myocardium can be greatly reduced by temporary presence of the contractile inhibitor BDM at the onset of reperfusion.

Animals↗