PubMed Health⌕ Search

Biomedical subjects

W Schlack

Publications and source records attributed to W Schlack.

At least 19 recordsLinked to original sources
PubMed2002

Xenon produces minimal haemodynamic effects in rabbits with chronically compromised left ventricular function.

BACKGROUND: Xenon has only minimal haemodynamic side-effects on normal myocardium and might be a preferable anaesthetic agent for patients with heart failure. We studied the haemodynamic changes caused by 70% xenon in rabbits with chronically compromised left ventricular (LV) function. METHODS: Anaesthetized rabbits were thoracotomized and a major coronary artery was ligated to induce ischaemic heart disease. Nine weeks later, rabbits were again anaesthetized (ketamine/propofol), and haemodynamics were measured during inhalation of 70% xenon using echocardiography [LV end-diastolic dimension (LVedD), fractional shortening (FS), velocity of circumferential fibre shortening (VcF), ejection fraction (EF)] in closed-chest animals. Subsequently, rabbits were thoracotomized and instrumented for measurement of LV pressure (tip manometer), LV dP/dtmax and cardiac output (ultrasonic flow probe). Haemodynamics were recorded again during inhalation of 70% xenon. RESULTS: All rabbits had compromised LV function 9 weeks after coronary artery ligation. Mean LVedD increased from 12.9 (SD 0.9) mm to 17.1 (0.4) mm; EF decreased from 73 (9) to 64 (8)%; FS decreased from 36 (7) to 29 (5)%; VcF decreased from 28.9 (6.8) to 17.6 (4.7) mm s(-1); all P<0.05. Inhalation of 70% xenon had no effect on haemodynamics in closed-chest rabbits, as measured by echocardiography. After invasive instrumentation, small decreases in LV pressure from 78 (20) to 72 (19) mm Hg, LV dP/dtmax from 3081 (592) to 2633 (503) mm Hg s(-1) and cardiac output from 239 (69) to 225 (71) ml min(-1) were observed during xenon inhalation (all P<0.05). CONCLUSION: These data show that xenon has only minimal negative inotropic effects in rabbits with LV dysfunction after coronary artery ligation.

Anesthetics, Inhalation↗
PubMed2002

Xenon increases total body oxygen consumption during isoflurane anaesthesia in dogs.

BACKGROUND: This study was designed to examine whether the coupling between oxygen consumption (VO2) and cardiac output (CO) is maintained during xenon anaesthesia. METHODS: We studied the relationship between VO2 (indirect calorimetry) and CO (ultrasound flowmetry) by adding xenon to isoflurane anaesthesia in five chronically instrumented dogs. Different mixtures of xenon (70% and 50%) and isoflurane (0-1.4%) were compared with isoflurane alone (1.4% and 2.8%). In addition, the autonomic nervous system was blocked (using hexamethonium) to study its influence on VO2 and CO during xenon anaesthesia. RESULTS: Mean (SEM) VO2 increased from 3.4 (0.1) ml kg(-1) min(-1) during 1.4% isoflurane to 3.7 (0.2) and 4.0 (0.1) ml kg(-1) min(-1) after addition of 70% and 50% xenon, respectively (P<0.05), whereas CO and arterial pressure remained essentially unchanged. In contrast, 2.8% isoflurane reduced both, VO2 [from 3.4 (0.1) to 3.1 (0.1) ml kg(-1) min(-1)] and CO [from 96 (5) to 70 (3) ml kg(-1) min(-1)] (P<0.05). VO2 and CO correlated closely during isoflurane anaesthesia alone and also in the presence of xenon (r2=0.94 and 0.97, respectively), but the regression lines relating CO to VO2 differed significantly between conditions, with the line in the presence of xenon showing a 0.3-0.6 ml kg(-1) min(-1) greater VO2 for any given CO. Following ganglionic blockade, 50% and 70% xenon elicited a similar increase in VO2, while CO and blood pressure were unchanged. CONCLUSIONS: Metabolic regulation of blood flow is maintained during xenon anaesthesia, but cardiovascular stability is accompanied by increased VO2. The increase in VO2 is independent of the autonomic nervous system and is probably caused by direct stimulation of the cellular metabolic rate.

Anesthetics, Combined↗
PubMed2002

Cardioprotection by sevoflurane against reperfusion injury after cardioplegic arrest in the rat is independent of three types of cardioplegia.

BACKGROUND: Sevoflurane protects the heart against reperfusion injury even after cardioplegic arrest. This protection may depend on the cardioplegic solution. Therefore, we investigated the effect of sevoflurane on myocardial reperfusion injury after cardioplegic arrest with University of Wisconsin solution (UW), Bretschneider's cardioplegia (HTK), and St Thomas' Hospital solution (STH). METHODS: We used an isolated rat heart model where heart rate, ventricular volume, and perfusion pressure were constant. The hearts underwent 30 min of normothermic ischaemia followed by 60 min of reperfusion. Seven groups were studied (n = 9 each). Three groups received 7 degrees C cold cardioplegic solutions (UW, HTK, STH) during the first 2 min of ischaemia at a flow of 2 ml min-1. In three groups (UW + Sevo, HTK + Sevo, STH + Sevo), sevoflurane was additionally added to the perfusion medium (membrane oxygenator) at 3.8% (1.5 MAC) during the first 15 min of reperfusion after cardioplegic arrest. Nine hearts served as untreated control group (control). We measured left ventricular developed pressure (LVDP) and infarct size. RESULTS: LVDP was similar in all groups during baseline (130 (SEM 2) mm Hg). HTK and STH improved recovery of LVDP during reperfusion from 5 (1) (control) to 67 (7) (HTK) and 52 (8) mm Hg (STH, both P < 0.05), while UW had no effect on myocardial function (7 (2) mm Hg). In the sevoflurane-treated groups, LVDP at the end of the experiments was not significantly different from the respective group without anaesthetic treatment (UW + Sevo 11 (2); HTK + Sevo 83 (8); STH + Sevo 64 (8) mm Hg; P = ns). Infarct size was reduced in the HTK and STH groups (HTK 20 (4); STH 17 (3)%; P < 0.05) compared with controls (39 (5)%; P < 0.05), but not in the UW group (52 (4)%). Compared with cardioplegia alone, sevoflurane treatment during reperfusion reduced infarct size (UW + Sevo 31 (4); HTK + Sevo 8 (1); STH + Sevo 4 (1)%; P < 0.05). CONCLUSION: We conclude, that the protection against reperfusion injury offered by sevoflurane is independent of the three cardioplegic solutions used.

Adenosine↗
PubMed2002

[Myocardial protection by volatile anesthetics].

Myocardial ischaemia/reperfusion situations may occur during the perioperative period. The cardioprotective effects of anaesthetics have been known for a long time: volatile anaesthetics reduce the ischaemic cell damage and infarct development. Besides ischaemia, reperfusion itself can also lead to cellular damage, thereby further increasing the ischaemic injury (reperfusion injury). Inhalational anaesthetics offer specific protective effects against reperfusion injury in isolated hearts as well as in rabbit hearts in vivo. This protection does not depend on haemodynamic side-effects of the substances and is even present after protecting the heart against ischaemic damage using a cardioplegic solution. Short periods of ischaemia render the myocardium resistant to subsequent longer periods of ischaemia. This strongest endogenous protective mechanism against the consequences of an ischaemia is known as ischaemic preconditioning. The protective effect can also be produced by stimulation of different types of receptors: the respective agonists produce pharmacological (chemical) preconditioning. The common pathway of the signal transduction cascade of both ischaemic and chemical preconditioning includes the sarcolemnal and/or mitochondrial ATP-sensitive potassium channel. Volatile anaesthetics can imitate the protective effects of a short ischaemia, thereby producing chemical preconditioning. This effect depends, at least in part, on anaesthetic-induced opening of ATP-sensitive potassium channels.

Adenosine Triphosphate↗
PubMed2001

Thiopentone does not block ischemic preconditioning in the isolated rat heart.

PURPOSE: Ischemic preconditioning protects the heart against subsequent prolonged ischemia by opening of adenosine triphosphate-sensitive potassium (K(ATP)) channels. Thiopentone blocks K(ATP) channels in isolated cells. Therefore, we investigated the effects of thiopentone on ischemic preconditioning. METHODS: Isolated rat hearts (n=56) were subjected to 30 min of global no-flow ischemia, followed by 60 min of reperfusion. Thirteen hearts underwent the protocol without intervention (control, CON) and in 11 hearts (preconditioning, PC), ischemic preconditioning was elicited by two five-minute periods of ischemia. In three additional groups, hearts received 1 (Thio 1, n=11), 10 (Thio 10, n=11) or 100 microg x mL(-1) (Thio 100, n=10) thiopentone for five minutes before preconditioning. Left ventricular (LV) developed pressure and creatine kinase (CK) release were measured as variables of myocardial performance and cellular injury, respectively. RESULTS: Recovery of LV developed pressure was improved by ischemic preconditioning (after 60 min of reperfusion, mean +/- SD: PC, 40 +/- 19% of baseline) compared with the control group (5 +/- 6%, P <0.01) and this improvement of myocardial function was not altered by administration of thiopentone (Thio 1, 37 +/- 15%; Thio 10, 36 +/- 16%; Thio 100, 38 +/- 16%, P=0.87-0.99 vs PC). Total CK release over 60 min of reperfusion was reduced by preconditioning (PC, 202 +/- 82 U x g(-1) dry weight) compared with controls (CON, 383 +/- 147 U x g(-1), P <0.01) and this reduction was not affected by thiopentone (Thio 1, 213 +/- 69 U x g(-1); Thio 10, 211 +/- 98 U x g(-1); Thio 100, 258 +/- 128 U x g(-1), P=0.62-1.0 vs PC). CONCLUSION: These results indicate that thiopentone does not block the cardioprotective effects of ischemic preconditioning in an isolated rat heart preparation.

Animals↗
PubMed2001

Additive protective effects of late and early ischaemic preconditioning are mediated by the opening of KATP channels in vivo.

We investigated whether a combination of ischaemic late preconditioning (LPC) and ischaemic early preconditioning (EPC) induces additive myocardial protection in vivo, and the role of ATP-sensitive K (KATP) channels in ischaemic LPC and in LPC + EPC. Sixty rabbits were divided into seven groups. Anaesthetized animals were subjected to 30 min of coronary artery occlusion and 120 min of reperfusion (I/R). Controls (CON, n = 9) were not preconditioned. LPC (n = 10) was induced in conscious rabbits by a 5-min period of myocardial ischaemia 24 h before I/R. The KATP channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg) was given 10 min before I/R with (LPC + 5-HD, n = 9) or without LPC (5-HD, n = 8). EPC (n = 8) was induced by a 5-min period of myocardial ischaemia 10 min before I/R. Animals received LPC and EPC without (LPC + EPC, n = 8) or with 5-HD (LPC + EPC + 5-HD, n = 8). LPC reduced infarct size (IS, triphenyltetrazolium staining) from 57 +/- 11% (MW +/- SD, CON) of the area at risk to 31 +/- 19% (LPC, P = 0.004). 5-HD did not affect IS (5-HD: 60 +/- 12%, P = 0.002 versus LPC), but abolished the cardioprotective effects of LPC (LPC + 5-HD: 62 +/- 18%, P = 0.001 versus LPC). EPC reduced IS to 18 +/- 8%. Additional LPC led to a further reduction to 8 +/- 4% (LPC + EPC, n = 8; P = 0.005 versus EPC; P = 0.004 versus LPC). 5-HD abolished this additional cardioprotective effect of LPC + EPC (LPC + EPC + 5-HD, n = 8; 46 +/- 11%, P < or = 0.001 versus LPC + EPC). We conclude that the combination of ischaemic LPC and EPC induces additive cardioprotection. KATP channel opening mediates the cardioprotective effects of ischaemic LPC and LPC + EPC.

Adenosine Triphosphate↗
PubMed2001

[Acceptance of preoxygenation in clinical routine by patients and by anaesthesiologists].

Preoxygenation is a simple technique to expand the time under planned apnea till the patient is endangered by hypoxia. In this study, we analysed how preoxygenation is used by anaesthesiologists in clinical routine and how this method is tolerated by the patients. One hundred and twenty-one anaesthesiologists of 4 hospitals were interviewed anonymously about training level, rank, indication for preoxygenation and techniques of preoxygenation, as well as their estimation of the patients' discomfort during preoxygenation. Data on 100 patients about oxygen-mask-tolerance were acquired by an anonymous questionnaire from a standard quality control inquiry. We received back 76 of the 121 questionnaires of anaesthesiologists (63 %). Fifty-nine percent of the anaesthesiologists (45/76) preoxygenated in clinical routine. With increasing training time and higher ranks, less anaesthesiologists preoxygenated routinely: junior residents: 80 %; senior residents: 68 %; consultants: 60 %; assistant medical directors: 48 %.80 % of the anaesthesiologists (61/76) used imperfect techniques for preoxygenation (e. g. oxygen-flow < 8 l/min). At the time of preoperative evaluation, the patients estimated the discomfort during preoxygenation on a continuous scale (1 to 10) as 2 (median; 1 - 7: 95 % confidence interval). Postoperatively, the patients mentioned no discomfort: 1 (1 - 1). The anaesthesiologists overestimated their patients' discomfort significantly with 5 (3 - 7) (p < 0.001).In conclusion, preoxygenation, a simple safety procedure, is not routinely used by many anaesthesiologists and imperfect methods are often employed. A possible reason for the anaesthesiologists' reluctance to preoxygenate is an overestimation of the patients' discomfort, though the patients tolerate preoxygenation very well.

Anesthesiology↗
PubMed2001

Can isoflurane mimic ischaemic preconditioning in isolated rat heart?

Ischaemic preconditioning can protect the myocardium against ischaemic injury by opening of the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel. Isoflurane is also thought to open this channel. The present investigation tested the hypothesis that pre-ischaemic treatment with isoflurane mimics ischaemic preconditioning (producing chemical preconditioning) and thereby protects the myocardium against ischaemic injury in an isolated rat heart model. Control hearts underwent 30 min of global no-flow ischaemia followed by 60 min of reperfusion. The hearts of the preconditioning group underwent two 5 min periods of no-flow ischaemia interspersed with 5 min of reperfusion before the sustained ischaemia. In three additional groups, hearts were subjected to 15 min of 1.5 minimal alveolar concentration (MAC) of isoflurane (ISO-1), 15 min 3 MAC (ISO-2) or 25 min 1.5 MAC (ISO-3) of isoflurane followed by 5 min washout before the global ischaemia. Left ventricular (LV) developed pressure and creatine kinase release were measured as variables of myocardial performance and cellular injury, respectively. Recovery of LV developed pressure was improved after ischaemic preconditioning [after 60 min reperfusion, mean 63 (SEM 6)% of baseline] compared with the control group [18 (4)% P<0.01] but not by isoflurane, independently of concentration or duration of administration [ISO-1, 17 (2)%, P=0.99 vs control; ISO-2, 12 (3)%, P=0.64; ISO-3, 4 (1)%, P=0.06]. Total creatine kinase release over 1 h of reperfusion was not significantly different between control [251 (36) U g(-1) dry weight] and all isoflurane groups [ISO-1, 346 (24) U g(-1), P=0.30; ISO-2, 313 (33) U g(-1), P=0.73; ISO-3, 407 (40) U g(-1), P=0.03]. These results indicate that pre-ischaemic administration of isoflurane does not cause anaesthetic-induced preconditioning in the isolated rat heart.

Anesthetics, Inhalation↗
PubMed2001

Lidocaine reduces ischaemic but not reperfusion injury in isolated rat heart.

The local anaesthetic lidocaine protects the myocardium in ischaemia-reperfusion situations. It is not known if this is the consequence of an anti-ischaemic effect or an effect on reperfusion injury. Therefore, we investigated the effect of two concentrations of lidocaine on myocardial ischaemia-reperfusion injury and on reperfusion injury alone. We used an isolated rat heart model where heart rate, ventricular volume and coronary flow were kept constant. Hearts underwent 45 min of low-flow ischaemia followed by 90 min reperfusion. Two groups received lidocaine 1.7 or 17 microg ml(-1) starting 5 min before the onset of reperfusion. In two additional groups, lidocaine infusion started 5 min before low-flow ischaemia. In all groups, lidocaine administration was stopped after 15 min of reperfusion. One group served as an untreated control (n=11 in each group). Left ventricular developed pressure (LVDP) and total creatine kinase release (CKR) were measured. Lidocaine administration during ischaemia and reperfusion led to an improved recovery of LVDP during reperfusion (1.7 microg ml(-1), 54 (SEM 10) mm Hg; 17 microg ml(-1), 71 (9) mm Hg at 30 min of reperfusion; both significantly different from control (21 (4) mm Hg) (P<0.05)) and a reduced CKR (1.7 microg ml(-1), 79 (13) IU; 17 microg ml(-1), 52 (8) IU at 30 min of reperfusion; both significantly different from control (130 (8) IU (P<0.05)). Lidocaine given during early reperfusion only, affected neither LVDP during reperfusion (1.7 microg ml(-1), 19 (6) mm Hg (P=1.0); 17 microg ml(-1), 36 (8) mm Hg (P=0.46)) nor CKR (156 (21) IU (P=0.50) and 106 (14) IU (P=0.57)). We conclude that lidocaine protects the myocardium against ischaemic but not against reperfusion injury in the isolated rat heart.

Analysis of Variance↗
PubMed2001

One MAC of sevoflurane provides protection against reperfusion injury in the rat heart in vivo.

Volatile anaesthetics protect the heart against reperfusion injury. We investigated whether the cardioprotection induced by sevoflurane against myocardial reperfusion injury was concentration-dependent. Fifty-eight alpha-chloralose anaesthetized rats were subjected to 25 min of coronary artery occlusion followed by 90 min of reperfusion. Sevoflurane was administered for the first 15 min of reperfusion at concentrations corresponding to 0.75 (n=11), 1.0 (n=11), 1.5 (n=13), or 2.0 MAC (n=12). Eleven rats served as untreated controls. Left ventricular peak systolic pressure (LVPSP, tipmanometer) and cardiac output (CO, flowprobe) was measured. Infarct size (IS, triphenyltetrazolium staining) was determined as percentage of the area at risk. Baseline LVPSP was 131 (126-135) mm Hg (mean (95% confidence interval)) and CO 33 (31-36) ml min(-1), similar in all groups. During early reperfusion, sevoflurane reduced LVPSP in a concentration-dependent manner to 78 (67-89)% of baseline at 0.75 MAC (not significant vs controls 99 (86-112)%), 71 (62-80)% at 1 MAC (P<0.05), 66 (49-83)% at 1.5 MAC (P<0.05) and 56 (47-65)% at 2 MAC (P<0.05). CO remained constant. While 0.75 MAC of sevoflurane had no effect on IS (34 (27-41)% of the area at risk) compared with controls (38 (31-45)%, P=0.83), 1.0 MAC reduced IS markedly to 23 (17-30)% (P<0.05). Increasing the concentration to 1.5 MAC (23 (17-30)%) and 2 MAC (23 (13-32)%, both P<0.05 vs controls) had no additional protective effect. One MAC sevoflurane protected against myocardial reperfusion injury. Increasing the sevoflurane concentration above 1 MAC resulted in no further protection.

Anesthetics, Inhalation↗
PubMed2001

Late preconditioning is blocked by racemic ketamine, but not by S(+)-ketamine.

UNLABELLED: Racemic ketamine blocks K(ATP) channels in isolated cells and abolishes short-term cardioprotection against prolonged ischemia. We investigated the effects of racemic ketamine and S(+)-ketamine on ischemic late preconditioning (LPC) in the rabbit heart in vivo. A coronary occluder was chronically implanted in 36 rabbits. After recovery, the rabbits divided into four groups (each n = 9). LPC was induced in conscious rabbits by a 5-min coronary occlusion. Twenty-four hours later, the animals were instrumented for measurement of left ventricular systolic pressure (LVSP, tip manometer), cardiac output (CO, ultrasonic flowprobe) and myocardial infarct size (triphenyltetrazolium staining). All rabbits were then subjected to 30-min coronary occlusion and 2 h reperfusion. Controls underwent the ischemia-reperfusion program without LPC. To test whether racemic ketamine or S(+)-ketamine blocks the cardioprotection induced by LPC, the drugs (10 mg/kg) were given 10 min before the 30-min ischemia. Hemodynamic values were not significantly different between groups during the experiments (baseline: LVSP, 94 +/- 3 mm Hg [mean +/- SEM] and CO, 243 +/- 9 mL/min; coronary occlusion: LVSP, 93% +/- 4% of baseline and CO, 84% +/- 4%; after 2 h of reperfusion: LVSP, 85% +/- 4% and CO, 83% +/- 4%). LPC reduced infarct size from 44% +/- 3% of the area at risk in controls to 22% +/- 3% (P = 0.002). Administration of racemic ketamine abolished the cardioprotective effects of LPC (44 +/- 4%, P = 0.002). S(+)-ketamine did not affect the infarct size reduction induced by LPC (26 +/- 6%, P = 0.88). IMPLICATIONS: Racemic ketamine, but not S(+)-ketamine, blocks the cardioprotection induced by ischemic late preconditioning in rabbit hearts in vivo. Thus, the influence of ketamine on ischemic late preconditioning is most likely enantiomer specific, and the use of S(+)-ketamine may be preferable in patients with coronary artery disease.

Animals↗
PubMed2001

Effects of ketamine and its isomers on ischemic preconditioning in the isolated rat heart.

BACKGROUND: Ischemic preconditioning protects the heart against subsequent ischemia. Opening of the adenosine triphosphate-sensitive potassium (KATP) channel is a key mechanism of preconditioning. Ketamine blocks KATP channels of isolated cardiomyocytes. The authors investigated the effects of ketamine and its stereoisomers on preconditioning. METHODS: Isolated rat hearts (n = 80) underwent 30 min of no-flow ischemia and 60 min of reperfusion. Two groups with eight hearts each underwent the protocol without intervention (control-1 and control-2), and, in eight hearts, preconditioning was elicited by two 5-min periods of ischemia before the 30 min ischemia. In the six treatment groups (each n = 8), ketamine, R(-)- or S(+)-ketamine were administered at concentrations of 2 or 20 microg/ml before preconditioning. Eight hearts received 20 microg/ml R(-)-ketamine before ischemia. Left ventricular (LV) developed pressure and creatine kinase (CK) release during reperfusion were determined as variables of ventricular function and cellular injury. RESULTS: Baseline LV developed pressure was similar in all groups: 104 +/- 28 mmHg (mean +/- SD). Controls showed a poor recovery of LV developed pressure (17 +/- 8% of baseline) and a high CK release (70 +/- 17 IU/g). Ischemic preconditioning improved recovery of LV developed pressure (46 +/- 14%) and reduced CK release (47 +/- 17 IU/g, both P < 0.05 vs. control-1). Ketamine (2 microg/ml) and 2 or 20 microg/ml S(+)-ketamine had no influence on recovery of LV developed pressure compared with preconditioning (47 +/- 18, 43 +/- 8, 49 +/- 36%) and CK release (39 +/- 8, 30 +/- 14, 41 +/- 25 IU/g). After administration of 20 microg/ml ketamine and 2 or 20 microg/ml R(-)-ketamine, the protective effects of preconditioning were abolished (LV developed pressure-recovery, 16 +/- 14, 22 +/- 21, 18 +/- 11%; CK release, 67 +/- 11, 80 +/- 21, 82 +/- 41 IU/g; each P < 0.05 vs. preconditioning). Preischemic treatment with R(-)-ketamine had no effect on CK release (74 +/- 8 vs. 69 +/- 9 IU/g in control-2, P = 0.6) and functional recovery (LV developed pressure 12 +/- 4 vs. 9 +/- 2 mmHg in control-2, P = 0.5). CONCLUSION: Ketamine can block the cardioprotective effects of ischemic preconditioning. This effect is caused by the R(-)-isomer.

Animals↗
PubMed2001

Ketamine, but not S(+)-ketamine, blocks ischemic preconditioning in rabbit hearts in vivo.

BACKGROUND: Ketamine blocks KATP channels in isolated cells and abolishes the cardioprotective effect of ischemic preconditioning in vitro. The authors investigated the effects of ketamine and S(+)-ketamine on ischemic preconditioning in the rabbit heart in vivo. METHODS: In 46 alpha-chloralose-anesthetized rabbits, left ventricular pressure (tip manometer), cardiac output (ultrasonic flow probe), and myocardial infarct size (triphenyltetrazolium staining) at the end of the experiment were measured. All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. The control group underwent the ischemia-reperfusion program without preconditioning. Ischemic preconditioning was elicited by 5-min coronary artery occlusion followed by 10 min of reperfusion before the 30 min period of myocardial ischemia (preconditioning group). To test whether ketamine or S(+)-ketamine blocks the preconditioning-induced cardioprotection, each (10 mg kg(-1)) was administered 5 min before the preconditioning ischemia. To test any effect of ketamine itself, ketamine was also administered without preconditioning at the corresponding time point. RESULTS: Hemodynamic baseline values were not significantly different between groups [left ventricular pressure, 107 +/- 13 mmHg (mean +/- SD); cardiac output, 183 +/- 28 ml/min]. During coronary artery occlusion, left ventricular pressure was reduced to 83 +/- 14% of baseline and cardiac output to 84 +/- 19%. After 2 h of reperfusion, functional recovery was not significantly different among groups (left ventricular pressure, 77 +/- 19%; cardiac output, 86 +/- 18%). Infarct size was reduced from 45 +/- 16% of the area at risk in controls to 24 +/- 17% in the preconditioning group (P = 0.03). The administration of ketamine had no effect on infarct size in animals without preconditioning (48 +/- 18%), but abolished the cardioprotective effects of ischemic preconditioning (45 +/- 19%, P = 0.03). S(+)-ketamine did not affect ischemic preconditioning (25 +/- 11%, P = 1.0). CONCLUSIONS: Ketamine, but not S(+)-ketamine blocks the cardioprotective effect of ischemic preconditioning in vivo.

Anesthesia↗
PubMed2000

Influence of the angiotensin II AT1 receptor antagonist irbesartan on ischemia/reperfusion injury in the dog heart.

The aim of the present study was to investigate whether the non-peptide angiotensin II type 1 (AT1) receptor antagonist irbesartan (SR 47436, BMS 186295, 2-n-butyl-3 [2'-(1H-tetrazol-5-yl)-biphenyl-4-yl)methyl]-1,3-diaza-spiro [4,4]non-1-en-4-one) has myocardial protective effects during regional myocardial ischemia/reperfusion in vivo. Eighteen anesthetized open-chest dogs were instrumented for measurement of left ventricular and aortic pressure (tip manometer and pressure transducer, respectively), and coronary flow (ultrasonic flowprobes). Regional myocardial function was assessed by Doppler displacement transducers as systolic wall thickening (sWT) in the antero-apical and the postero-basal wall. The animals underwent 1 h of left anterior descending coronary artery (LAD) occlusion and subsequent reperfusion for 3 hours. Irbesartan (10 mg kg(-1), n = 9) or the vehicle (KOH, control, n = 9) was injected intravenously 30 min before LAD occlusion. Regional myocardial blood flow (RMBF) was measured after irbesartan injection and at 30 min LAD occlusion using colored microspheres. Infarct size was determined by triphenyltetrazolium chloride staining after 3 h of reperfusion. There was no recovery of sWT in the LAD perfused area in both groups at the end of the experiments (systolic bulging, -15.1+/-6.1% of baseline (irbesartan) vs. -12.3+/-3.0% (control), mean+/-SEM). Irbesartan led to an increase in RMBF in normal myocardium (2.47+/-0.40 vs. 1.35+/-0.28 ml min(-1) g(-1), p<0.05), and also to an increase in collateral blood flow to the ischemic area (0.27+/-0.04 vs. 0.17+/-0.02 ml min(-1) g(-1), P = <0.05). Infarct size (percent of area at risk) was 24.8+/-3.2 % in the treatment group compared with 26.9+/-4.8% in the control group (P = 0.72). These results indicate that a blockade of angiotensin II AT1 receptors with irbesartan before coronary artery occlusion led to an increase in RMBF, but did not result in a significant reduction of myocardial infarct size.

Angiotensin II↗
PubMed2000

Effect of dantrolene in an in vivo and in vitro model of myocardial reperfusion injury.

BACKGROUND: In skeletal muscle, dantrolene reduces free cytosolic calcium by inhibiting calcium release from the sarcoplasmic reticulum. A similar effect in ischemic-reperfused heart cells would protect myocardial tissue against reperfusion injury. We tested the hypothesis that dantrolene infusion during reperfusion protects the heart against reperfusion injury. METHODS: Isovolumetric beating rat hearts were subjected to 30 min of ischemia followed by 60 min of reperfusion. Left ventricular (LV) developed pressure (LVDP) and creatine kinase release (CKR) were determined as indices of myocardial performance and cellular injury, respectively. In the treatment groups, dantrolene (25 (DAN25) or 100 (DAN100) micromol l(-1)) was infused during the first 15 min of reperfusion; control hearts received the respective concentration of the vehicle (mannitol (CON25, CON100), each group n=7). To investigate the effects of dantrolene on reperfusion injury in vivo, 18 chloralose-anesthetized rabbits were subjected to 30 min occlusion and 180 min reperfusion of a major coronary artery. LV pressure (LVP), cardiac output (CO), and infarct size were determined. During the last 5 min of ischemia, nine rabbits received 10 mg kg(-1) dantrolene intravenously (DAN). Another nine rabbits received the vehicle (dimethylsulfoxide) and served as controls (CON). RESULTS: In isolated rat hearts, there was no recovery of LVDP in any group. Total CKR during 1 h of reperfusion was 845+/-76 (CON100) and 550+/-81 U g(-1) dry mass (DAN100, P<0.05). In rabbits in vivo, hemodynamic baseline values were similar between groups (CON vs. DAN: LVP, 99+/-6 (mean+/-SEM) vs. 91+/-6mm Hg, P=0.29; CO, 252+/-26 vs. 275+/-23 ml min(-1), P= 0.53). During coronary artery occlusion, LVP and CO were reduced in both groups (CON: LVP, 89+/-3%; CO, 90+/-5% of baseline values) and LVP did not recover to baseline values during reperfusion (51+/-5% (CON) vs. 67+/-7% (DAN) of baseline, P=0.10). Infarct size was 41+/-4% of the area at risk in controls and 37+/-6% in dantrolene treated hearts (P=0.59). CONCLUSIONS: Dantrolene reduced CKR, indicating an attenuation of lethal cellular reperfusion injury in isolated rat hearts. However, in the rabbit in vivo, there was no effect on the extent of reperfusion injury after regional myocardial ischemia.

Animals↗
PubMed2000

Haemodynamic effects of a left stellate ganglion block in ASA I patients. An echocardiographic study.

In anaesthetized dogs, stellate ganglion blockade led to a moderate disturbance in left ventricular diastolic function. We investigated the effect of a left-sided block, following injection of 10 mL bupivacaine 0.5%, on echocardiographic variables of ventricular function in eight otherwise healthy patients with sympathetically mediated pain syndromes. After the blockade, heart rate (control: 66+/-3 (mean+/- SEM), block: 64+/-3 min-1) and mean arterial blood pressure (88.5+/-6.0 vs. 84.0+/-8.1 mmHg) were unchanged, but afterload decreased (end-systolic meridional wall stress; 69.6+/-9.9 vs. 59.8+/-7.1, P < 0.05). Stroke volume increased from 71.2+/-8.1 to 79.6+/-7.4 mL, P < 0.05. Variables of systolic function were unchanged, but relaxation was prolonged (isovolumic relaxation time; 71+/-5 vs. 81+/-4 ms, P < 0.05). In patients who were ASA I, there was a small impairment in echocardiographic variables during ventricular relaxation after a left stellate ganglion blockade. This small effect did not compromise ventricular function, and the heart responded with a small stroke volume increase to the simultaneous afterload reduction.

Adult↗