Insular infarct size but not levosimendan influenced myocardial injury triggered by cerebral ischemia in rats.

Cerebral injuries can trigger stress-related cardiomyopathy. The extent of cerebral injury and the involvement of the insular cortex influence the incidence and extent of myocardial injury (MI), and drugs with proven neuroprotective and cardioprotective properties such as levosimendan might be beneficial. This hypothesis was addressed in a rat model of transient middle cerebral artery occlusion. Transient brain ischemia was induced for 60 min by intraluminal occlusion of the middle cerebral artery in 40 male Wistar rats. Treatment with levosimendan (24 µg/kg) was started briefly before reperfusion. Hemodynamic parameters were recorded and cerebral and MI quantified after 24 h. Levosimendan treatment significantly reduced cerebral infarct size in the cortex, but not in the striatal and insular regions. However, its effects on survival (28 vs. 45%), incidence of MI (8 vs. 33%) as indicated by a troponin I (sTnI) threshold of 4.8 µg/L and large insular infarcts of ≥10 mm(3) (23 vs. 50%) failed to reach statistical significance. Blood pressure demonstrated significant differences related to insular infarct size during reperfusion. Levosimendan demonstrated no relevant effects on markers of MI (sTnI = 1.5 ± 2.8 vs. 5.3 ± 7.2 µg/L, P = 0.121). Insular infarct size could be identified as the only predictor of MI (odds ratio = 1.86, P = 0.037). In conclusion, the current investigation confirmed insular infarct size as a predictor of MI and source of hemodynamic compromise, but failed to demonstrate an effect of levosimendan on MI trigged by brain ischemia. A hardly protectable insular region might explain this.

Effect of anesthesia and cerebral blood flow on neuronal injury in a rat middle cerebral artery occlusion (MCAO) model.

Middle cerebral artery occlusion (MCAO) models have become well established as the most suitable way to simulate stroke in experimental studies. The high variability in the size of the resulting infarct due to filament composition, rodent strain and vessel anatomy makes the setup of such models very complex. Beside controllable variables of homeostasis, the choice of anesthetics and the grade of ischemia and reperfusion played a major role for extent of neurological injury. Transient MCAO was induced during either isoflurane or ketamine/xylazine (ket/xyl) anesthesia with simultaneously measurement of cerebral blood flow (CBF) in 60 male Wistar rats (380-420 g). Neurological injury was quantified after 24 h. Isoflurane compared with ket/xyl improved mortality 24 h after MCAO (10 vs. 50 %, p = 0.037) and predominantly led to striatal infarcts (78 vs. 18 %, p = 0.009) without involvement of the neocortex and medial caudoputamen. Independent of anesthesia type, cortical infarcts could be predicted with a sensitivity of 67 % and a specificity of 100 % if CBF did not exceed 35 % of the baseline value during ischemia. In all other cases, cortical infarcts developed if the reperfusion values remained below 50 %. Hyperemia during reperfusion significantly increased infarct and edema volumes. The cause of frequent striatal infarcts after isoflurane anesthesia might be attributed to an improved CBF during ischemia (46 ± 15 % vs. 35 ± 19 %, p = 0.04). S-100ß release, edema volume and upregulation of IL-6 and IL-1ß expression were impeded by isoflurane. Thus, anesthetic management as well as the grade of ischemia and reperfusion after transient MCAO demonstrated important effects on neurological injury.

Xenon is not superior to isoflurane on cardiovascular function during experimental acute pulmonary hypertension.

BACKGROUND: Acute right ventricular afterload increase is a known perioperative challenge for the anaesthetic regime especially for patients with a compromised right ventricle. The accused negative inotropic action of volatile anaesthetics, with the exception of xenon, might be crucial for the adaptation of the right ventricle. METHODS: Reversible pulmonary hypertension (mean pressure 40 mmHg) was induced by an infusion of the stable thromboxane A(2) analog U46619 in a porcine model (n = 35). The effects of 70 vol% xenon and 0.9 vol% isoflurane on biventricular function were studied by conductance catheter technique. Inflammation and myocardial injury was quantified using serum probes [tumour necrosis factor α (TNFα), interleukin 6 (IL-6), troponin] and myocardial tissue [B natriuretic peptide (BNP), TNFα, activated caspase 3] by enzyme-linked immunosorbance assays and reverse-transcription polymerase chain reaction. RESULTS: After wash in of xenon global haemodynamic parameters remained stable whereas isoflurane caused a systemic vasodilation. This led to a significant decrease in mean arterial pressure in the isoflurane group whereas cardiac output remained stable. Both substances did not alter the biventricular contractility nor did they induce changes in preload for both ventricles. Xenon led to an additional increase in right ventricular afterload, whereas isoflurane reduced pulmonary vascular resistance. No effects on systemic inflammatory response and myocardial injury were found, whereas higher apoptosis rate and expression of BNP and IL-6 was determined in the right ventricle. CONCLUSIONS: These results do not support the idea that xenon is more beneficial than isoflurane in right ventricular failure during pulmonary hypertension. Isoflurane did not compromise systolic ventricular function during acute PHT it only led to vasodilation in contrast to xenon.

Xenon and isoflurane improved biventricular function during right ventricular ischemia and reperfusion.

BACKGROUND: Although anesthetics have some cardioprotective properties, these benefits are often counterbalanced by their negative inotropic effects. Xenon, on the other hand, does not influence myocardial contractility. Thus, xenon may be a superior treatment for the maintenance of global hemodynamics, especially during right ventricular ischemia, which is generally characterized by a high acute complication rate. METHODS: The effects of 70 vol% xenon and 0.9 vol% isoflurane on biventricular function were assessed in a porcine model (n=36) using the conductance catheter technique, and the expression of the type B natriuretic peptide (BNP) gene was measured. The animals underwent 90 min of right ventricular ischemia followed by 120 min of reperfusion. A barbiturate-anesthetized group was included as a control. RESULTS: Cardiac output was compromised in unprotected animals during ischemia by 33+/-18% and during reperfusion by 53+/-17%. This was mainly due to impaired contractility in the left ventricle (LV) and increased stiffness. Isoflurane attenuated the increase in stiffness and resulted in a higher preload. In contrast, xenon increased the right ventricular afterload, which was compensated by an increase in contractility. Its effects on diastolic function were less pronounced. Upregulation of BNP mRNA expression was impeded in the remote area of the LV by both isoflurane and xenon. CONCLUSIONS: Xenon and isoflurane demonstrated equipotent effects in preventing the hemodynamic compromise that is induced by right ventricular ischemia and reperfusion, although they acted through somewhat differential inotropic and vasodilatory effects.

Establishment of a porcine right ventricular infarction model for cardioprotective actions of xenon and isoflurane.

BACKGROUND: Right ventricular (RV) function is an important determinant of post-operative outcome. Consequences of RV infarction might be limited by pre-conditioning with volatile anesthetic drugs. Therefore, we used a porcine model of RV ischemia and reperfusion (IR) injury to study the influence of isoflurane and xenon on the extent and degree of myocardial injury. METHODS: IR injury was induced by a 90-min ligation of the distal right coronary artery and 120-min reperfusion in thiopental anesthetized pigs. A control group (n=12) was compared with two groups, which received either 0.55 minimum alveolar concentration (MAC) isoflurane (n=10) or xenon (n=12) starting 60 min before ischemia. Myocardial injury was described by three criteria: the infarct size related to area at risk (IS/AAR), the infiltration of neutrophils as determined by myeloperoxidase (MPO) activity, and the plasma levels of tumor necrosis factor alpha (TNFalpha), interleukin 6 (IL-6), myoglobin and troponin-T (TnT). RESULTS: IS/AAR was reduced from 58.3+/-6.2% in the control group to 41.8+/-7.8% after isoflurane and 42.7+/-8.5% after xenon pre-treatment, which equals an absolute reduction of 16.5% [95% confidence interval (CI): 10.9-22.1] and 15.5% (95% CI: 10.1-20.9). The maximum increase of TnT could be observed within the xenon group. Both treatment groups were characterized by lower MPO activity, in the infarct and periinfarct region and lower plasma concentrations of TNFalpha and IL-6. CONCLUSIONS: It could be demonstrated for the first time in a model of RV infarction that the continuous application of isoflurane or xenon before, during and after ischemia reduced the extent (size) and severity (inflammation) of myocardial injury.