Jussi Rimpiläinen

Anti-inflammatory effect of high-dose insulin treatment after urgent coronary revascularization surgery.

Background:  The administration of insulin has been shown to exert cardioprotective and immunomodulatory properties. Ischemia and inflammation are typical features of acute coronary syndrome, thus it was hypothesized that high‐dose glucose–insulin–potassium (GIK) treatment could suppress the systemic inflammatory reaction and attenuate myocardial ischemia–reperfusion injury in patients with unstable angina pectoris after urgent coronary artery bypass surgery.

Strategies for Spinal Cord Protection during Descending Thoracic and Thoracoabdominal Aortic Surgery: Up-to-date Experimental and Clinical Results - A review

Surgery of the descending thoracic and thoracoabdominal aorta, apart from postoperative mortality, is threatened by spinal cord ischemic complications resulting in paraplegia or paraparesis. These, in turn, are associated with an increased risk of postoperative and late mortality. Signie cant advances in understanding the pathogenesis of spinal cord ischemic injury occurring after descending thoracic and thoracoabdominal aortic aneurysm repair hasled tothedevelopment of different strategies,whichinseveral seriesdecreasedthe rate of postoperative paraplegia to below 5%. However, since none of these methods alone seems to reduce to nil the riskof postoperative paraplegia, each ofthemshould be wisely supplemented by other neuroprotective maneuvers or drugs. This review article summarizes the current knowledge originating from experimental and clinical studies and the most signie cant advancements achieved in this e eld during the last decade. Furthermore, some of the mostusedsurgical approaches are presented in their fundamental steps.

The Role of Cerebral Microdialysis in Predicting the Outcome after Experimental Hypothermic Circulatory Arrest

Objective –To evaluate whether and which of the cerebral microdialysis parameters are predictive of postoperative outcome after an experimental 75-min period of hypothermic circulatory arrest (HCA) in a chronic porcine model. Design –Seventy-four juvenile female pigs underwent a 75-min period of HCA at 20°C. A microdialysis catheter was placed into the cortex gray matter and brain extracellular concentrations of glucose, lactate, glycerol and glutamate were measured throughout the experiment by enzymatic methods using a microdialysis analyzer. Surviving animals were sacrificed on the 7th postoperative day and histopathological examination of the brain was performed. Results –Brain glucose concentrations were higher in animals that survived ( p = 0.017), especially from the 90-min until the 7-h interval after the start of rewarming. The blood venous concentrations of glucose were also higher among survivors, and correlated significantly with the brain glucose levels at 2-h and 4-h intervals after the start of rewarming. Higher concentrations of brain lactate, glycerol and glutamate were observed throughout the study among animals that died postoperatively. Brain glutamate and glycerol concentrations were significantly, negatively correlated with brain glucose concentrations. The lactate/glucose ratio was significantly lower among survivors during the postoperative period ( p = 0.014). Furthermore, brain glucose concentrations were higher and brain glycerol concentrations lower among the animals that did not develop brain infarction, but such differences did not reach statistical significance. Conclusion –Cerebral microdialysis is a useful tool for cerebral monitoring during experimental HCA. Low brain glucose concentrations and high brain lactate/glucose ratios after HCA are strong predictors of postoperative death. Brain glucose concentrations are negatively correlated with brain glycerol and glutamate concentrations.

Leukocyte depleting filter attenuates myocardial injury during elective coronary artery bypass surgery

Background. Ischemia-reperfusion injury secondary to leukocyte activation has been widely recognized as one of the most relevant mechanism leading to postoperative organ dysfunction occurring after a period of ischemia. The aim of the present study was to evaluate in a prospective, randomized study, the value of leukocyte depleting filter in patients undergoing elective coronary artery bypass surgery. Methods. Twenty patients scheduled for elective on-pump coronary artery bypass surgery were randomized to undergo cardiopulmonary bypass either with a leukocyte depleting filter incorporated in the extracorporeal circulation arterial line or without a filter. Results. The main finding of this study was the significantly lower postoperative concentrations of cardiac troponin I in the leukocyte filter group (Tests of between-subjects effects: p = 0.024). There were also slightly better cardiac indices in the leukocyte filter group. A larger amount of blood units was infused intra- and postoperatively in patients undergoing cardiopulmonary bypass with leukocyte filtration (median, 600 [IQR, 0–1200] vs. 0 [IQR, 0–600], p = 0.08). Two patients in the leukocyte filter group underwent reoperation for bleeding but none in the control group (p = 0.48). Intra-and postoperative platelet count was lower in the leukocyte filter group (Tests of between-subjects effects: p = 0.08). Despite a significant increased concentration of C-reactive protein on the first postoperative day in the control group (p = 0.029), repeated-measures analysis failed to show any significant increase during the study period (p = 0.33). Conclusions. The results of this study suggest a myocardial protective effect of leukocyte filter in the setting of elective coronary artery bypass surgery.

Topical head cooling during rewarming after experimental hypothermic circulatory arrest

BACKGROUND The aim of this study was to evaluate the potential neuroprotective effect of topical head cooling during the first 2 postoperative hours after experimental hypothermic circulatory arrest. METHODS Twenty pigs underwent a 75-minute period of hypothermic circulatory arrest and were randomly assigned to rewarming to 37 degrees C or to undergo topical cooling of the head for 2 hours from the start of rewarming followed by a period of external rewarming to 37 degrees C. RESULTS The 7-day survival rate was 70% in the control group and 60% in the topical head cooling group. Despite brain tissue oxygenation, intracranial pressures, mixed oxygen venous saturation, oxygen consumption, and extraction tended to be favorable in the topical head cooling group as a clear effect of mild hypothermia. The latter group had significantly higher postoperative brain lactate and pyruvate ratios, and lactate and glucose ratios. Furthermore, the topical head cooling group had worse fluid balance throughout the postoperative period. Brain histopathologic scores were comparable with the study groups, but among 7-days survivors these scores tended to be worse in the topical head cooling group. CONCLUSIONS Topical cooling of the head during the first 2 postoperative hours after experimental hypothermic circulatory arrest does not appear to provide any neuroprotective effect.

Outcome after coronary artery bypass surgery with miniaturized versus conventional cardiopulmonary bypass

We have reviewed the results of our experience with the use of miniaturized (Mini-CPB) versus conventional (C-CPB) cardiopulmonary bypass in coronary artery bypass surgery (CABG). This study included 365 patients who underwent CABG with C-CPB and 101 patients with Mini-CPB. In-hospital mortality was lower in the C-CPB group (1.4% vs. 3.0%, P = 0.38). A better, but not statistically significant, immediate outcome was observed in the C-CPB group as indicated by a shorter length of stay in the intensive care unit as well as a lower incidence of combined adverse end-point. However, this was probably due to significantly higher operative risk in the Mini-CPB group (logistic EuroSCORE: 8.5 ± 10.0 vs. 4.6 ± 7.1, P < 0.0001). Seventy-seven propensity score-matched pairs had similar immediate postoperative results after Mini-CPB and C-CPB (30-day mortality: 1.3% vs. 1.3%; stroke: 0% vs. 0%; intensive care unit stay ≥5 days: 6.5% vs. 9.1%; combined adverse events: 14.3% vs. 11.7%). Mini-CPB achieves similar results to C-CPB in patients undergoing isolated CABG. The potential efficacy of Mini-CPB is expected to be more evident in high-risk patients or in complex cardiac surgery requiring much longer cardiopulmonary perfusion.

Cold retrograde cerebral perfusion improves cerebral protection during moderate hypothermic circulatory arrest: A long-term study in a porcine model

BACKGROUND Deep hypothermic circulatory arrest is an effective method of cerebral protection, but it is associated with long cardiopulmonary bypass times and coagulation disturbances. Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcomes after prolonged hypothermic circulatory arrest. We tested the hypothesis that deep hypothermic retrograde cerebral perfusion could improve cerebral outcome during moderate hypothermic circulatory arrest. METHODS Twelve pigs (23-29 kg) were randomly assigned to undergo either retrograde cerebral perfusion (15 degrees C) at 25 degrees C or hypothermic circulatory arrest with the head packed in ice at 25 degrees C for 45 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg throughout retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were carried out until 4 hours after the start of rewarming. Daily behavioral assessment was performed until elective death on day 7. A postmortem histologic analysis of the brain was carried out on all animals. RESULTS In the retrograde cerebral perfusion group, 5 (83%) of 6 animals survived 7 days compared with 2 (33%) of 6 in the hypothermic circulatory arrest group. Complete behavioral recovery was seen in 4 (67%) animals after retrograde cerebral perfusion but only in 1 (17%) animal after hypothermic circulatory arrest. Postoperative levels of serum lactate were higher, and blood pH was lower in the hypothermic circulatory arrest group. There were no significant hemodynamic differences between the study groups. CONCLUSIONS Cold hypothermic retrograde cerebral perfusion during moderate hypothermic circulatory arrest seems to improve neurologic outcome compared with moderate hypothermic circulatory arrest with the head packed in ice.

Lamotrigine plus leukocyte filtration as a neuroprotective strategy in experimental hypothermic circulatory arrest

BACKGROUND Lamotrigine and leukocyte filtration seem to improve cerebral protection during experimental hypothermic circulatory arrest (HCA). This study was performed to evaluate whether their combined use may further improve cerebral protection. METHODS Twenty-four pigs undergoing 75-minute period of HCA at 20 degrees C were randomly assigned to receive saline; lamotrigine (20 mg/kg) before HCA (L); or lamotrigine (20 mg/kg) before HCA plus leukocyte filtration before and after HCA (L + LF). RESULTS Seven animals (87%) in the L + LF group, 4 (50%) in the L group, and 3 (37%) in the control group were alive on the seventh postoperative day. The median electroencephalogram burst recovery was 94% in the L + LF group (p = 0.024 versus control group), 81% in the L group, and 64% in the control group. Among the surviving animals, the median behavioral scores were 9, 9, and 6 at the seventh day, respectively (p = 0.005 between the L + LF group and the control group). The median histopathologic score was 14 in the L + LF group (p = 0.046 versus control group), 14.5 in the L group (p = 0.062 versus control group), and 21 in the control group. CONCLUSIONS Lamotrigine has neuroprotective effect during HCA. The combined use of lamotrigine and LF may further improve the survival outcome.

Determinants of mortality after hypothermic circulatory arrest in a chronic porcine model.

OBJECTIVE Beside neurological morbidity, mortality is a relevant end-point of experimental porcine model of hypothermic circulatory arrest (HCA) and this study was conducted to identify the determinants for postoperative death. METHODS One hundred and thirty-five pigs underwent a 75-min period of HCA at 20 degrees C to evaluate the efficacy of different methods of cerebral protection. RESULTS Survival rate at 7-day follow-up was 52%. Lower oxygen extraction, oxygen consumption/kg, and venous lactate at the end of cooling and higher oxygen delivery rates were significantly associated with better outcome. Logistic regression showed that the oxygen consumption/kg at the end of cooling was the only predictor of mortality (P=0.046). Animals with an oxygen consumption/kg rate less than 1.43 ml/min per kg at the end of cooling had a mortality rate of 28%, whereas it was 50% among animals with an oxygen consumption/kg rate higher or equal to 1.43 ml/min per kg (P=0.020). The latter had even an increased 1-day mortality rate (40% vs. 26%) (P not significant). The mortality rate after anesthesia induction with ketamine plus 100% of oxygen was 38%, 45% after anesthesia induction with ketamine plus 35% oxygen, and 53% after anesthesia with medetomidine plus 35% oxygen (P not significant). CONCLUSIONS Parameters of oxyhemodynamics should be monitored especially from the induction of anesthesia to the end of cooling before a 75-min period of HCA. The use of medetomidine and/or 35% of oxygen at induction of anesthesia should be avoided in favor of ketamine plus 100% of oxygen.

Increase of Intracranial Pressure after Hypothermic Circulatory Arrest in a Chronic Porcine Model

Objective: An increase in intracranial pressure has been shown to threaten the outcome of patients with ischemic or traumatic brain injury. Its impact on the outcome of pigs undergoing hypothermic circulatory arrest has been evaluated in this study. Design: Fifty-six pigs underwent a 75-min period of hypothermic circulatory arrest at 20°C. Intracranial pressure, cerebral microdialysis, hemodynamic and metabolic parameters were monitored throughout the experiment. The animals were allowed to survive until the 7th postoperative day and, then, electively killed. Results: The 7-day survival rate was 60.7%, and among survivors, 20 of them (58.8%) developed brain infarction. A significant increase in intracranial pressure as compared with the baseline level was observed since the end of cooling ( p = 0.047) and the difference became larger during all the postoperative intervals ( p < 0.0001). Animals that died postoperatively tended to have higher intracranial pressure levels during all the postoperative intervals, but such a difference reached significance only at the 4-h postoperative interval ( p = 0.040). The same tendency was observed among animals that survived until the 7th postoperative day and that developed brain infarction or not, but the difference between these two groups did not reach statistical significance. The animals that died or developed postoperatively brain infarction had higher intracranial pressure values postoperatively as compared with those that survived without developing brain infarction and such a difference reached significance at the 2-h ( p = 0.015) and 4-h postoperative intervals ( p = 0.035). The peak intracranial pressure was 17.2 mmHg (IQR, 13.7-20.8) in animals that died or developed brain infarction and 14.1 mmHg (IQR, 11.8-16.4) in those that survived 7 days without developing brain infarction ( p = NS). Conclusion: Intracranial pressure increases significantly after 75 min of experimental hypothermic circulatory arrest and such an increase is associated with a high risk of postoperative death and brain infarction.