Fredrik Lennmyr

Activation of mitogen-activated protein kinases in experimental cerebral ischemia

Lennmyr F, Karlsson S, Gerwins P, Ata KA, Terént A. Activation of mitogen‐activated protein kinases in experimental cerebral ischemia. Acta Neurol Scand 2002: 106: 333–340.

Minimal Safe Arterial Blood Flow During Selective Antegrade Cerebral Perfusion at 20° Centigrade

BACKGROUNDnSelective antegrade cerebral perfusion (SACP) enables surgery on the aortic arch, where cerebral ischemia may cause neurologic sequels. This study aims to identify the minimum arterial flow level to maintain adequate cerebral perfusion during SACP in deep hypothermia in the pig.nnnMETHODSnTwo groups of pigs were subjected to SACP at 20(°)C α-stat. In group 1 (n = 6), flow was stepwise adjusted from 8-6-4-2-8 mL · kg(-1) · min(-1) and in group 2 (n = 5), flow was kept constant at 6 mL · kg(-1) · min(-1). Magnetic resonance imaging and spectroscopy were performed at each flow level together with hemodynamic monitoring and blood gas analysis. The biochemical marker of cerebral damage protein S100β was measured in peripheral blood.nnnRESULTSnDecreased mixed venous oxygen saturation and increased lactate in magnetic resonance spectroscopy was seen as a sign of anaerobic metabolism below 6 mL · kg(-1) · min(-1). No ischemic damage was seen on diffusion-weighted imaging, but the concentrations of S100β were significantly elevated in group 1 compared with group 2 at the end of the experiment (p < 0.05). Perfusion-weighted imaging showed coherence between flow setting and cerebral perfusion, increase of blood volume across time, and regional differences in perfusion during SACP.nnnCONCLUSIONSnThe findings suggest an ischemic threshold close to 6 mL · kg(-1) · min(-1) in the present model. Regional differences in perfusion during SACP may be of pathogenic importance to focal cerebral ischemia.

Venous obstruction and cerebral perfusion during experimental cardiopulmonary bypass

To investigate the effects on cerebral perfusion by experimental venous congestion of the superior vena cava (SVC) during bicaval cardiopulmonary bypass (CPB) at 34 °C, pigs were subjected to SVC obstruction at levels of 75%, 50%, 25% and 0% of baseline SVC flow at two arterial flow levels (low, LQ, high, HQ). The cerebral perfusion was examined with near-infrared spectroscopy (NIRS), cerebral microdialysis and blood gas analysis. SVC obstruction caused significant decreases in the NIRS tissue oxygenation index (TOI) and in SVC oxygen saturations (P<0.05, both groups), while the mixed venous saturation was decreased only in the LQ group. Sagittal sinus venous saturations were measured in the HQ group and found significantly reduced in response to venous congestion (P<0.05). No microdialysis changes were seen at the group level, however, individual ischemic patterns in terms of concomitant venous desaturation, decreased TOI and increased lactate/pyruvate occurred in both groups. The total venous drainage remained stabile throughout the experiment, indicating increased flow in the inferior vena cava cannula. The results indicate that SVC congestion may impair cerebral perfusion especially in the case of compromised arterial flow during CPB. Reduced SVC cannula flow may pass undetected during bicaval CPB, if SVC flow is not specifically monitored.

MEK-inhibitor U0126 in hyperglycaemic focal ischaemic brain injury in the rat

Backgroundu2002 Hyperglycaemia aggravates ischaemic brain injury, possibly due to activation of signalling pathways involving mitogen‐activated protein kinases (MAPK). In this study, the activation of MAPK/ERK was inhibited using the upstream inhibitor of MAPK‐ERK‐kinase (MEK) U0126, and the effects on focal brain ischaemia were evaluated during normo‐ and hyperglycaemia.

Experimental treatment for focal hyperglycemic ischemic brain injury in the rat

Hyperglycemia aggravates ischemic brain injury, possibly due to the activation of signaling pathways involving reactive oxygen species, Src and mitogen-activated protein kinases. The aim of this study was to investigate the effects of the spin trap agent α-phenyl-N-tert-butyl nitrone (PBN), the Src family kinase inhibitor PP2 and the MEK1-inhibitor U0126 on focal hyperglycemic ischemic brain injury. Temporary middle cerebral artery occlusion (90xa0min) was induced in four groups of rats (PBN, PP2, and U0126 vs. control). Neurological testing and tetrazolium red staining were performed after 1xa0day. PBN decreased the infarct volume by 70% compared with the control (P<0.05) and a tendency towards reduced infarcts was seen in the PP2 or U0126 groups. Furthermore, neurological testing was consistent with the volumetric analysis. In conclusion, PBN appears to be a potential neuroprotective agent in hyperglycemic, focal ischemic brain injury, while the efficacy of PP2 and U0126 could not be confirmed by the present data.

Efficacy and Safety of Continuous Local Infusion of Ropivacaine after Retroperitoneoscopic Live Donor Nephrectomy

Morphine‐based analgesia is effective but can compromise donor safety. We investigated whether continuous infusion of local anesthetics (CILA) can provide sufficient pain control and reduce morbidity related to opiate analgesics after hand‐assisted retroperitoneoscopic (HARS) live donor nephrectomy. Forty consecutive live kidney donors underwent HARS and were treated with the ON‐Q system providing CILA with 0.5% ropivacaine through two SilvaGard® catheters placed in the retroperitoneal cavity and the rectus sheath, respectively. The case control group consisted of 40 donors matched with regard to sex, age, BMI and surgical technique. All donors were maintained on standardized multimodal analgesia combining nurse‐controlled oxycodone treatment and acetaminophen. CILA donors had lower median cumulative consumption of morphine equivalents (CCME) (7 mg [0–56] vs. 42 mg [15–127]; p < 0.0000001), lower incidence of nausea (18 [45%] vs. 35 [87.5%] donors; p < 0.001), shorter time in postoperative care unit (160 vs. 242.5 min; p < 0.001) and shorter hospital stay (4 [4–7] vs. 6 [4–11] days; p < 0.001). In 32.5% of CILA donors the CCME was 0 mg (0% in matched control group, p < 0.001). CILA with 0.5% ropivacaine provides effective postoperative pain relief, reduces the need for opioid treatment and promotes postoperative recovery.

Hyperglycaemia increases S100β after short experimental cardiac arrest.

Hyperglycaemia is associated with aggravated ischaemic brain injury. The main objective of this study was to investigate the effects on cerebral perfusion of 5u2009min of cardiac arrest during hyperglycaemia and normoglycaemia.

Neuroprotection by S-PBN in hyperglycemic ischemic brain injury in rats

Abstract Background. Hyperglycemia exacerbates focal ischemic brain damage supposedly through various mechanisms. One such mechanism is oxidative stress involving reactive oxygen and nitrogen species (RONS) production. Nitrones attenuate oxidative stress in various models of brain injury. Sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) can be administered experimentally and has been shown to be neuroprotective in experimental brain trauma. Aims of the study. We hypothesized that S-PBN might be neuroprotective in hyperglycemic focal cerebral ischemia. Material and methods. Rats were made hyperglycemic by an intraperitoneal bolus injection of glucose (2 g/kg) and then subjected to 90 min transient middle cerebral artery occlusion (MCAO). They were randomized to a therapeutic regime of S-PBN (156 mg/kg) or saline given intravenously. Neurological testing according to Bederson and tetrazolium red staining were performed after 1 day. Results. S-PBN improved the neurological performance at day 1 both in Bederson score (1.3 ± 0.8 versus 2.7 ± 0.48) and on the inclined plane (74.5% ± 4.6 (S-PBN) versus 66% ± 8.3 (control), P < 0.05) but did not reduce the infarct size. Physiological data did not differ between groups. Conclusion. S-PBN may improve neurological performance at short-term survival (1 day) in the present model of hyperglycemic-ischemic brain injury in rats. This effect appeared not to be primarily related to reduced infarct size.

Milrinone and esmolol decrease cardiac damage after resuscitation from prolonged cardiac arrest.

Long‐term survival after cardiac arrest (CA) due to shock‐refractory ventricular fibrillation (VF) is low. Clearly, there is a need for new pharmacological interventions in the setting of cardiopulmonary resuscitation (CPR) to improve outcome. Here, hemodynamic parameters and cardiac damage are compared between the treatment group (milrinone, esmolol and vasopressin) and controls (vasopressin only) during resuscitation from prolonged CA in piglets.

Experimental treatment of superior venous congestion during cardiopulmonary bypass

OBJECTIVESnSuperior venous outflow obstruction affects cerebral perfusion negatively by reducing cerebral perfusion pressure (CPP). We present a randomized study designed to compare two alternative strategies to preserve the CPP during superior vena cava (SVC) congestion and cardiopulmonary bypass (CPB).nnnMETHODSnFourteen pigs on bi-caval CPB were subjected to 75% occlusion of the SVC flow. CPP was restored either by vasopressor treatment (VP, n = 7) or by partial relief (PR) of the congestion (n = 7). The cerebral effects of the interventions were studied for 60 min with intracranial pressure (ICP) monitoring, cerebral blood flow measurement, the near-infrared light spectroscopy tissue oxygen saturation index (StO2), arterial and venous blood gas analyses and serial measurements of the glial cell damage marker protein S100β.nnnRESULTSnBoth strategies restored the CPP to baseline levels and no signs of severe ischaemia were observed. In the PR group, the venous and ICPs were normalized in response to the intervention, while in the VP group those parameters remained elevated throughout the experiment. The haemoglobin oxygen saturation in the sagittal sinus (SsagO2) was increased by both VP and PR, while significant improvement in the StO2 was observed only in the PR group. The S100β concentrations were similar in the two groups.nnnCONCLUSIONSnExperimental SVC obstruction during CPB may reduce the CPP, resulting in impaired cerebral perfusion. Both vasopressor treatment and improved venous drainage can, in the short term, individually restore the CPP during these circumstances.