Cold Crystalloid Research Articles

EVAR: is Suprarenal Fixation Really without Consequence on the Renal Function?

Objectives: To determine if renal perfusion with a cold crystalloid solution enriched with histidine-tryptophanketoglurarate (Custodiol, Dr. Franz-Kohler Chemie GmbH, Bensheim, Germany) offers a better protection against renal ischemic lesions compared to cold Ringer lactate in patients treated by open surgery for a pararenal aortic aneurysms (PAA). Materials and Methods: We studied 256 consecutive patients treated by open surgery for PAA between 1993 and 2013. In181cases thedirect perfusionof at least one renal artery was carried out. Among these patients, 87 had renal perfusion with Ringer lactate solution and 94 with a Custodiol solution. A score of propensity, based on clinical variables which would probably have influenced the renal function, was carried out to correct skews which could be associated with the use of Custodiol. Acute postoperative renal failure (ARF)was stratified in five classes according to the postoperative serum creatinine values and the need for dialysis, and wascompared in the twogroups, and the independent predictive factors ofARFwere identifiedwith amultivariate analysis. Results: After the score of propensity we could compare 74 patients perfused with Custodiol with those receiving a Ringer lactate perfusion. Overall mortality at 30 days was 3.4%,with a need for temporary hemodialysis or continuous venovenous hemofiltration in 4.7% of cases, and dialysis at discharge in 2.7% of the cases. Absence of ARF > 2 (> 100% rise in the baseline level of creatinine) and the need for dialysis were significantly better in the Custodiol group (P1⁄4.007; and P1⁄4.04, respectively). With the multivariate analysis the Custodiol perfusion and the duration of clamping were the predictive factors independent of non-IRA> 2. Conclusion: In our series of PAA repair, renal perfusion with 4 C Custodiol offers a better renal protection compared to Ringer lactate at 4 C. More series and/or randomized trials are necessary to confirm this conclusion.

Techniques and Strategies for Renal Protection in the Open Surgery of Pararenal Aneurysms

Objectives: To determine if renal perfusion with a cold crystalloid solution enriched with histidine-tryptophanketoglurarate (Custodiol, Dr. Franz-Kohler Chemie GmbH, Bensheim, Germany) offers a better protection against renal ischemic lesions compared to cold Ringer lactate in patients treated by open surgery for a pararenal aortic aneurysms (PAA). Materials and Methods: We studied 256 consecutive patients treated by open surgery for PAA between 1993 and 2013. In181cases thedirect perfusionof at least one renal artery was carried out. Among these patients, 87 had renal perfusion with Ringer lactate solution and 94 with a Custodiol solution. A score of propensity, based on clinical variables which would probably have influenced the renal function, was carried out to correct skews which could be associated with the use of Custodiol. Acute postoperative renal failure (ARF)was stratified in five classes according to the postoperative serum creatinine values and the need for dialysis, and wascompared in the twogroups, and the independent predictive factors ofARFwere identifiedwith amultivariate analysis. Results: After the score of propensity we could compare 74 patients perfused with Custodiol with those receiving a Ringer lactate perfusion. Overall mortality at 30 days was 3.4%,with a need for temporary hemodialysis or continuous venovenous hemofiltration in 4.7% of cases, and dialysis at discharge in 2.7% of the cases. Absence of ARF > 2 (> 100% rise in the baseline level of creatinine) and the need for dialysis were significantly better in the Custodiol group (P1⁄4.007; and P1⁄4.04, respectively). With the multivariate analysis the Custodiol perfusion and the duration of clamping were the predictive factors independent of non-IRA> 2. Conclusion: In our series of PAA repair, renal perfusion with 4 C Custodiol offers a better renal protection compared to Ringer lactate at 4 C. More series and/or randomized trials are necessary to confirm this conclusion.

Side effect management

Therapeutic hypothermia (TH) induces a paraphysiological state that can determine clinical modifications which do not constitute necessarily adverse effects, thus warranting monitoring rather than over corrective action in most circumstances. Others are known side effects related to hypothermia and can be anticipated. Rapid induction of hypothermia by infusion of cold crystalloids with a pressure bag (2 l at 300 mmHg) is associated with an increase rate of pulmonary edema and rearrests [1]. The Hypothermia Network Registry reports adverse events of 986 patients treated with TH [2]. Bradycardia was the most common arrhythmia (13%), but pacing was very rarely necessary, suggesting that bradycardia should be tolerated rather than treated if hemodynamic stability is preserved. Pneumonia was the most frequent infection (41%). Bleeding requiring transfusion occurred in 4%; the risk was significantly higher if coronary angiography was performed (2.8% vs. 6.2%, P = 0.02). Sustained hyperglycemia (8 mmol >4 hours) was observed in 37% of patients. Electrolyte disorders were also quite common (18%): specifically hypokalemia, hypomagnesemia, and hypophosphatemia. These derangements should be anticipated, tightly monitored and promptly corrected. The incidence of sepsis was only 4% but was higher in patients with: intravascular devices for temperature management (OR 2.6), intraortic balloon pump (OR 3.2) or undergoing coronary angiography (OR 4.4). Yet infection, bleeding, arrhythmia and electrolyte disorders were not associated with increased mortality. The Target Temperature Management Trial – the largest trial on temperature management – reported the rate of adverse events as one of the secondary outcomes [3]. There was no difference in adverse events between the 33°C and 36°C arms (respectively 93% vs. 90%, P= 0.086). Among the over 30 subtypes, bleeding, particularly in critical sites, was extremely rare. Bleeding was most common from the insertion sites (33°C, 9.2% vs. 36°C, 6.1%, P= 0.076). Again pneumonia was the most common infection regardless the level of hypothermia (52% vs. 46%, P = 0.089). The incidence of bradycardia requiring pacing was low and equal in the two groups, suggesting that hypothermia is not responsible for hemodynamically compromising bradycardia (5.2% vs. 6.4%). The only subgroup with a significantly different rate was hypokalemia (19% vs. 13%, P = 0.018). Hypomagnesemia and hypophosphatemia did not differ but were frequent (respectively 20% and 41%), highlighting the need to anticipate electrolyte imbalances. In conclusion, adverse events can be anticipated and managed. The incidence is not related to the level of temperature management and is not associated with worse survival or neurological recovery.

Temperature management after cardiac arrest.

Temperature management for patients comatose after cardiac arrest has been an integral component of postcardiac arrest care for the last decade. In this review, we present recent findings and discuss implications for future trials. The two largest trials on temperature management after cardiac arrest were recently presented. The first investigated prehospital induction of hypothermia using ice-cold intravenous saline in 1364 patients. The intervention gave a significant reduction in time from return of circulation to start of hypothermia and lower body temperature on admission to hospital. There was no difference in survival or neurological function between the study groups, but there were indications of possible harm in the group that received saline. The second trial investigated two actively controlled temperatures provided in intensive care units, randomizing 950 unconscious patients suffering out-of-hospital cardiac arrest of a presumed cardiac cause to targeted temperature management at 33 and 36°C. There was no difference in survival until end of trial or neurological function at 180 days. Prehospital hypothermia induced by cold crystalloid infusion does not benefit cardiac arrest patients. For patients treated in an intensive care unit targeting a temperature of 36°C provides similar results as targeting 33°C.

Improved Contractility with Modified Tepid Full Blood Cardioplegia Compared to Cold Crystalloid Cardioplegia in a Piglet Model

Objectives: Experience regarding warm blood cardioplegia according to Calafiore results from its broad use in adult patients. In this experimental study, tepid (28°C) modified full blood cardioplegia (MBC) was adopted for pediatric use and compared with cold crystalloid cardioplegia (CCC).

Low-Flow Hypothermic Crystalloid Perfusion Is Superior to Cold Storage During Prolonged Heart Preservation

BackgroundPreservation of donor hearts for transplantation has traditionally been performed with the use of static cold storage. We have developed and tested a novel gravity-powered system of cold crystalloid perfusion for prolonged donor heart preservation. MethodsGreyhounds were anesthetized; their hearts were arrested with cold cardioplegic solution and excised. Hearts were allocated to 12 hours of perfusion preservation (n = 6) or cold storage in ice (n = 5). Non-preserved hearts (n = 5) served as a normal reference group. Perfusion hearts were perfused (20 mL/min, 8–12°C) with a novel oxygenated nutrient-containing preservation solution. After preservation, the recovery of the hearts was assessed in a blood-perfused working heart rig over 2 hours in terms of function, blood lactate level, myocardial adenosine triphosphate, and histology. ResultsAfter 2 hours of reperfusion, in comparison with cold storage hearts, perfused heart function curves showed superior recovery of cardiac output (P = .001), power (P = .001), and efficiency (0.046 ± 0.01 vs 0.004 ± 0.003 joules/mL O2, P = .034). Myocardial adenosine triphosphate content (mmol/mg protein) was reduced significantly from the normal level of 26.5 (15.9, 55.8) to 5.08 (0.50, 10.4) (P = .049) in cold storage hearts but not in perfused hearts. Over a period of 2 hours, lactate levels in the blood perfusate were significantly lower in the perfusion group than in the cold storage group (P < .05). ConclusionsContinuous hypothermic crystalloid perfusion provides myocardial preservation superior to cold storage for long-term heart preservation, with potential applicability to marginal and donation after circulatory death hearts.

Improved cardiac protection with Sabax cardioplegia in Langendorff isolated rat hearts

Abstract Objective: Cardioplegia is an important step to facilitate cardiac surgery while limiting intraoperative myocardial injury. Although recent advances in cardioplegic arrest methods have significantly contributed to better postoperative outcomes, there is still controversy regarding the optimal composition and temperature of the cardioplegic solution. Accordingly, we aimed to assess whether cold or lukewarm Sabax cardioplegia offer improved myocardial protection compared with the classical Krebs-Henseleit solution. Methods: The hearts of 40 male Wistar rats were isolated and submitted to constant-flow retrograde perfusion using a Langendorff perfusion apparatus. The hearts were randomly assigned to cold Krebs-Henseleit (K-H), cold Sabax, or lukewarm Sabax cardioplegia. The ECG, heart rates, and left ventricular systolic pressures (LVSP) were recorded pre- and post-cardioplegia. The time needed for cardioplegia induction and post-cardioplegia recovery were also noted. Results: Both cold and lukewarm Sabax cardioplegia insured faster induction and faster recovery following isothermic reperfusion compared to the standard K-H solution (both p&lt; 0.01). With K-H cardioplegia, the hearts presented a 21.7% force loss after reperfusion (p&lt; 0.001), whilst Sabax cardioplegia was associated with a slight increase in ventricular mechanical activity (3% LVSP increase with lukewarm Sabax cardioplegia, p&lt; 0.001 and 2% LVSP increase with cold Sabax cardioplegia, p = 0.02). With Sabax cardioplegia the hearts displayed considerably less major arrhythmic events and presented less significant bradycardia. Conclusions: The present data suggest that Sabax cardioplegia may be superior to the classical cold crystalloid K-H solution in preserving mechanical activity of the heart and may provide superior protection against major arrhythmias.

Enhancing Approaches to Therapeutic Hypothermia in Patients with Sudden Circulatory Arrest

Cardiac arrest is common and causes substantial morbidity and mortality. Despite advances in prevention and resuscitation, most patients remain unconscious and survival remains poor. Therapeutic hypothermia (32-34°C) has emerged as a potent neuroprotective modality following resuscitation. In early clinical trials, application of therapeutic hypothermia improved survival in patients with ventricular fibrillation (VF), which led to the recommended use of therapeutic hypothermia for patients resuscitated from VF. However, two recent clinical trials have challenged some assumptions. First, the use of paramedic-initiated rapid infusion of cold crystalloids as a mean to achieve faster cooling rates after resuscitation in patients with and without VF arrest did not improve survival. Second, once patients were admitted to the hospital, targeting their temperature to 33 versus 36°C for 36h (in addition to active hyperthermia prevention) after out-of-hospital cardiac arrest did not to change clinical outcomes, suggesting that 36°C may represent the target temperature instead of temperatures of less than 34°C.

Оценка эффективности применения различных кардиоплегических растворов на основании изучения лабораторных показателей у хирургических пациентов с инфекционным эндокардитом левых отделов сердца

The study included 238 cases of surgical treatment of patients with infectious endocarditis of left parts of heart. The operations of single or multivalve reconstruction or restoration in conditions of artificial circulation were made to these patients. The patients were divided into groups depending on the type of cardioplegic solution. The influence of methods of cold crystalloid (extracellu-lar and intracellular), and blood cardioplegia on clinical and laboratory indices, which characterize the severity of myocardial damage in intra - and postoperative periods, was studied. The obtained results showed that the use of all types of cardioplegic solutions allows to provide the myocardial protection during the operation and to decrease the risk of life-threatening complications in this category of patients. The increase in the level of laboratory parameters of myocardial damage was registered in the use of all types of cardioplegic solutions in patients with long anoxia. The lowest intensity of changes in the levels of blood lactate marked using a solution for cold crystalloid intracellular cardioplegia. The greatest changes of this indicator were identified in patients receiving blood potassium cardioplegia. The use of cardioplegic solution &amp;#34;Custodial&amp;#34; caused the greatest intensity of acidosis in the intra-operative period.

Closing the pore on reperfusion injury: myocardial protection with cyclosporine.

Closing the pore on reperfusion injury: myocardial protection with cyclosporine.

Hypothermic cardiopulmonary bypass without exchange transfusion in sickle-cell patients: a matched-pair analysis.

Sickle-cell patients undergo cardiopulmonary bypass (CPB) surgery in our institution without perioperative exchange transfusion. We sought to determine whether this protocol increased mortality or important sickle-cell-related complications. We adopted a 1:1 matched-pair case-control methodology to evaluate the safety of our protocol. Sickle-cell patients who underwent CPB between January 1995 and January 2014 were matched with haemoglobin AA (HbAA) controls according to sex, age, weight and type of cardiac procedure. Thirty-three sickle-cell patients (21 HbAS, 7 HbSS and 5 HbSC) underwent CPB surgery using our institutional protocol. Sickle-cell patients and controls were similar according to the matching criteria. Preoperatively, haemoglobin SS (HbSS) and haemoglobin SC (HbSC) patients were anaemic (8.5 ± 1.4 vs 13.5 ± 1.9 g/dl; P <0.01 and 11.0 ± 0.6 vs 12.7 ± 0.9 g/dl; P = 0.01, respectively). Operative procedures included valve repair and replacement (12) as well as repair of congenital cardiac malformations (21). The duration of CPB and lowest CPB temperatures was similar for sickle-cell patients and controls. Systemic hypothermia (23.8-33.5°C), aortic cross-clamping, cold crystalloid antegrade cardioplegia and topical hypothermia were used in sickle-cell patients without complications. There was no acidosis, hypoxia or low cardiac output state. No mortality or important sickle-cell-related complications occurred. Although blood loss was similar between sickle-cell patients and controls, HbSS (unlike HbAS and HbSC) patients required more blood transfusion than controls (30.0 ± 13.3 vs 10.8 ± 14.2 ml/kg; P = 0.02) to counter haemodilution and replace blood loss. In-patient stay was similar for sickle-cell patients and controls. Perioperative exchange transfusion is not essential for a good outcome in sickle-cell patients undergoing CPB. A simple transfusion regimen to replace blood loss is safe in HbSS patients; blood transfusion requirements for HbSC and HbAS patients undergoing CPB are similar to those of matched HbAA controls. The use of systemic hypothermia during CPB does not increase sickle-cell-related complications. Cold crystalloid cardioplegia and topical hypothermia provide safe myocardial protection without the need for more sophisticated measures.

Cold Blood Versus Crystalloid Cardioplegia for Myocardial Protection in Adult Cardiac Surgery: A Meta-analysis of Randomized Controlled Studies

The purpose of this article was to systematically review randomized controlled trials in which cold blood cardioplegia was compared with cold crystalloid cardioplegia for cardiac surgery. Correlation studies were searched independently in the EMBASE, MEDLINE and Cochrane library databases. The primary endpoints of interest were spontaneous sinus rhythm (SSR) after declamping, perioperative myocardial infarction (MI) and mortality (within 30 days). A hospital. Randomized controlled trials. A meta-analysis of 12 studies. The 12 included trials recruited a total of 2866 participants; 1357 patients received cold crystalloid cardioplegia, and 1509 patients received cold blood cardioplegia. The pooled analysis showed no significant difference favoring either cold crystalloid cardioplegia or cold blood cardioplegia in terms of spontaneous sinus rhythm (SSR) after declamping (789/1028 [76.75%] v 773/1025 [75.41%], relative risk (RR) = 0.92 [0.76, 1.13], p = 0.43 with 6 studies included), mortality (within 30 days) (20/1335 [1.50%] v 24/1469 [1.63%], relative risk (RR) = 1.09 [0.62, 1.91], p = 0.77 with 11 studies included), atrial fibrillation (AF) (329/1043 [31.54%] v 365/1040 [35.10%], RR =0.90 [0.80, 1.01], p = 0.08 with 6 studies included) or stroke (45/1114 [4.04%] v 20/1240 [1.61%], RR = 2.18 [0.69, 6.93], p = 0.19 with 4 studies included). The aggregate data showed that the incidence of perioperative myocardial infarction was lower in patients who received cold blood cardioplegia (CB) (32/1310 [2.44%] v 17/1434 [1.19%], RR = 2.30 [1.33, 3.98], p = 0.003 with 11 studies included). Cold blood cardioplegia reduced perioperative myocardial infarction when compared with cold crystalloid cardioplegia. No differences in the overall incidence rates of spontaneous sinus rhythm, mortality (within 30 days), atrial fibrillation or stroke were observed.

Comparison of renal perfusion solutions during thoracoabdominal aortic aneurysm repair

To determine whether renal perfusion with cold crystalloid solution enriched with histidine-tryptophan-ketoglutarate (Custodiol; Dr Franz-Kohler Chemie GmbH, Bensheim, Germany) provides better protection against renal ischemic injury than cold lactated Ringer's solution in patients undergoing thoracoabdominal aortic aneurysm open repair. We analyzed a prospectively compiled database containing all 111 consecutive patients who underwent thoracoabdominal aortic aneurysm open repair at our center from 2008 to 2011. A cohort of 104 consecutive patients was identified of which 50 (48%) had renal perfusion with Custodiol and 54 (52%) with lactated Ringer's solution. Propensity score matching based on baseline clinical variables, which were expected to influence renal outcomes, was performed to correct for any bias that may have been associated with the use of Custodiol. Acute kidney injury (AKI) as defined by Kidney Disease Improving Global Outcomes guidelines and perioperative estimated glomerular filtration rate were compared in the two groups. Independent predictors of AKI were also identified by multivariate analysis. After propensity score matching, we were able to match 42 Custodiol cases one-to-one with those receiving perfusion with lactated Ringer's solution. Overall 30-day mortality was 5.9%; temporary hemodialysis or continuous veno-venous hemofiltration was needed in 4.8% of the patients without any case of dialysis at discharge. Freedom from AKI was significantly increased in the Custodiol group (38.1% vs 9.5%; P = .002) despite longer total renal ischemic time (51.5 ± 16.4 minutes vs 43.6 ± 16.0 minutes; P = .05). By analysis of variance for repeated measures, a significant upward trend of perioperative estimated glomerular filtration rate was observed in the Custodiol group (group × time interaction = F3,66; P < .001), and by multivariate analysis, Custodiol perfusion was the only independent predictor of non-AKI (P = .04). The use of Custodiol was safe and provided improved perioperative renal function compared with lactated Ringer's solution. Randomized trials are needed to confirm these data and to assess their clinical consequences.

Minimised closed circuit coronary artery bypass grafting in the elderly is associated with lower levels of organ-specific biomarkers

Restrictive fluid management may protect organ function and improve postoperative outcome in elderly coronary artery bypass grafting (CABG) patients. We assessed organ-specific biomarker release to study the contribution of a fluid restrictive closed circuit concept to organ protection in elderly CABG patients. Cardiac, respiratory and abdominal organ injury was measured during and following minimal fluid coronary artery bypass grafting (mCABG), off-pump coronary artery bypass (opCAB) surgery and conventional CABG with high volume prime and cold crystalloid cardioplegia (cCABG). The results were related to differences in clinical outcome. Prospective randomised trial. Dutch tertiary single centre study. Sixty patients over 70 years of age (38 men and 22 women) were randomised to one of the three different techniques. Inclusion criteria were as follows: first time CABG, elective surgery, ejection fraction more than 30% and multivessel disease. Acetylsalicylic acid and clopidogrel administration or requiring less than three distal anastomoses were an exclusion. Organ-specific markers of the heart--heart fatty acid binding protein (HFABP), troponin T, pro-brain natriuretic peptide (pro-BNP) and creatinine phosphokinase (CPK), lung clara cell 16 protein, pneumoprotein (CC16), intestinal fatty acid binding protein (IFABP) and liver glutathione S-transferase (α-GST)--were measured perioperatively. Postoperative PaO2 levels, ventilation time, blood product consumption and adverse events were noted. Myocardial organ-specific biomarker troponin T showed significantly lower median levels during mCABG compared with the cCABG and opCAB groups [troponin 0.25 mg l(-1) (interquartile range, IQR 0.18 to 0.40), 0.39 mg l(-1) (IQR 0.23 to 0.49) and 0.36 mg l(-1) (IQR 0.23 to 0.50), respectively (P<0.003)]. HFABP, IFABP and α-GST levels were significantly higher during cCABG compared with opCAB and mCABG [HFABP 38.6 mg l(-1) (IQR 29.6 to 47.1), 23.3 mg l(-1) (IQR 16.5 to 31.0) and 21.1 mg l(-1) (IQR 15.7 to 28.8; P<0.001), IFABP 0.57 mg l(-1) (IQR 0.37 to 1.11), 0.44 mg l(-1) (IQR 0.16 to 0.74) and 0.37 mg l(-1) (IQR 0.13 to 1.05; P<0.02) and α-GST 11.5 mg l(-1) (IQR 7.7 to 15.7), 7.0 mg l(-1) (IQR 4.5 to 13.8) and 7.3 mg l(-1) (IQR 6.2 to 11.2), respectively (P<0.009)]. There was a trend towards higher median CC16 levels in the cCABG group (P<0.07). CPK and pro-BNP were not significantly different. On the first postoperative day, PaO2 levels and duration of mechanical ventilation were significantly improved, and there was lower use of blood products in the mCABG group than in the cCABG and opCAB groups (P<0.05). Following mCABG with low volume myocardial preservation and restrictive fluid management, early respiratory performance was improved and consumption of blood products reduced compared with opCAB and cCABG.

Twelve-hour Reanimation of a Human Heart Following Donation After Circulatory Death

Despite increasing use of donation after cardiac death (DCD) and encouraging results for non-cardiac transplants, DCD cardiac transplantation has not been widely adopted because, (1) the DCD heart sustains warm ischaemic injury during the death process and (2) conventional static cold storage significantly adds to the ischaemic injury. We have developed a simple system for perfusion of the DCD heart with cold crystalloid solution using gravity-feed that can reduce ischaemic injury and potentially render the heart suitable for transplantation. This report describes the first application of this technique to a human DCD heart with good functional metabolic recovery over 12h on an ex vivo rig.

Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial

Remote ischaemic preconditioning has been associated with reduced risk of myocardial injury after coronary artery bypass graft (CABG) surgery. We investigated the safety and efficacy of this procedure. Eligible patients were those scheduled to undergo elective isolated first-time CABG surgery under cold crystalloid cardioplegia and cardiopulmonary bypass at the West-German Heart Centre, Essen, Germany, between April, 2008, and October, 2012. Patients were prospectively randomised to receive remote ischaemic preconditioning (three cycles of 5 min ischaemia and 5 min reperfusion in the left upper arm after induction of anaesthesia) or no ischaemic preconditioning (control). The primary endpoint was myocardial injury, as reflected by the geometric mean area under the curve (AUC) for perioperative concentrations of cardiac troponin I (cTnI) in serum in the first 72 h after CABG. Mortality was the main safety endpoint. Analysis was done in intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT01406678. 329 patients were enrolled. Baseline characteristics and perioperative data did not differ between groups. cTnI AUC was 266 ng/mL over 72 h (95% CI 237-298) in the remote ischaemic preconditioning group and 321 ng/mL (287-360) in the control group. In the intention-to-treat population, the ratio of remote ischaemic preconditioning to control for cTnI AUC was 0·83 (95% CI 0·70-0·97, p=0·022). cTnI release remained lower in the per-protocol analysis (0·79, 0·66-0·94, p=0·001). All-cause mortality was assessed over 1·54 (SD 1·22) years and was lower with remote ischaemic preconditioning than without (ratio 0·27, 95% CI 0·08-0·98, p=0·046). Remote ischaemic preconditioning provided perioperative myocardial protection and improved the prognosis of patients undergoing elective CABG surgery. German Research Foundation.

Abstract 335: Activation of BKCa Channels With Rottlerin Greatly Improves Cardiac Functional Improvement Following Surgical Ischemia Associated With Cardioplegic Arrest.

Introduction: BKCa channels are thought to provide protection during ischemic insults in the heart. Rottlerin, has been implicated as a potent BKCa activator, however this has not been firmly established. The purpose of this study was two fold: 1) assess the specificity of rottlerin for BKCa channels and 2) investigate the efficacy of BKCa channel activation as a cardioprotective agent during cardioplegia/reperfusion (CP/R). Methods: Wild type and BKCa knock-out mice with and without rottlerin (only administered in CP) were subjected to an isolated heart model of CP/R. Hearts were perfused for 30 min at 37C (baseline), followed by intermittent cold crystalloid cardioplegia (intermittent St Thomas II, 10C), and normothermic, normoxic, reperfusion for 30 min. In additional studies, mechanism of rottlerin-induced cardioprotection was investigated using H9c2 cells subjected to in vitro CP/reoxygenation and assessed for mitochondrial membrane potential (TMRE) and ROS (DCFDA) production. Results: CP and 30 min reperfusion decreased LVDP (58.7 +/- 5 % baseline, n=8 ), +/- dP/dt ( 71.1+/- 6.4, 59.2 +/-6.6, % baseline respectively) and coronary flow (CF) (66.8+/-7.4, %baseline) in wild type mice. Rottlerin, (100 (n=3), 500 nM (n=5)) delivered in the CP solution dose dependently increased the recovery of LV function and CF to near baseline levels (500 nM rottlerin, LVDP: 94.1+/- 2.3, +/-dPdt: 99.6 +/- 7.2, 111.0+/- 15.0, % baseline, and CF: 128.9 +/-30.0 %baseline ). BKCa KO hearts treated with (n=4)or without (n=3) 500nM rottlerin, were similar to wt CP hearts, showing no improved cardioprotection (BKCa KO + 500 nM rott: LVDP: 57.7+/- 4.0, +/-dP/dt 69.5 +/-12.0, 59.8+/- 4.9, and CF 73 +/- 6.7). H9c2 cells subjected to in vitro CP/R, displayed reduced mitochondrial membrane potential (39% +/-.09 % decrease relative to control, p&lt;.01) and increased ROS generation (50%+/-.04 increase, p&lt;.01), both of which were dose dependently normalized by rottlerin (100 nM-1 uM) (minimum n=8). Conclusions: Activation of BKCa channels profoundly rescues ischemic damage associated with CP, likely via mitochondrial effects on improved mitochondrial membrane potential and reduced ROS generation.

Impact of Different Surgical Strategies on Perioperative Protein S100β Release in Elderly Patients Undergoing Coronary Artery Bypass Grafting

This study was designed to compare neurological injury-associated protein S100β release during three different treatment modalities, minimized closed circuit coronary artery bypass grafting (CABG) (MCABG), off-pump CABG (OPCAB), and conventional CABG (CCABG), comprising high-volume prime and cold crystalloid cardioplegia. Our working hypothesis was that fluid restriction as provided by MCABG may decrease neurological injury-associated protein S100β release. In this prospective trial, in a tertiary center, 30 surgical patients (aged >70 years, 25 men and 5 women) undergoing first-time elective CABG were enrolled. The inclusion criteria were three-vessel disease and elective surgery. The exclusion criteria were left ventricular ejection fraction of less than 30%, use of clopidogrel, carotid disease, or needing fewer than three distal anastomoses. Protein S100β concentrations, hematocrit (Ht) levels, and PO2 levels were measured after induction of anesthesia, 10 minutes after reperfusion, upon arrival at the intensive care unit, 3 hours postoperatively at the intensive care unit, and the next morning. Statistics consisted of areas under the curve, peak levels, and correlation and variance tests. A significant negative correlation was found indicating higher S100β release at lower Ht levels and at lower PO2 levels in all study groups. The lowest S100β variance was measured during MCABG (Wilks Λ P = 0.052). The perioperative Ht was significantly higher in the MCABG group and in the OPCAB group compared with the CCABG group (P = 0.04 vs P < 0.01). At all time points, the S100β protein concentration showed no significant differences between the different surgical techniques. The mean (95% confidence interval) values of S100 area under the curve were the following: CCABG, 2.3 (1.06-3.5); MCABG, 1.44 (0.6-2.21); and OPCAB, 1.87 (1.5-2.19) [independent nonparametric Kruskal-Wallis test (P = 0.13)]. The mean (95% confidence interval) peak S100 values (calculated as the maximum value seen in a patient during the research period) were the following: CCABG, 1.07 (0.4-1.68); MCABG, 0.59 (0.28-0.90); and OPCAB, 0.83 (0.59-1.06) [independent nonparametric Kruskal-Wallis test (P = 0.22)]. Despite similar perioperative S100β protein release for all techniques studied, higher Ht and PO2 levels correlated with lower S100β release within all study groups. The low S100β variance during the fluid restrictive MCABG technique may be due to more efficient oxygen transport to the brain provided by significantly higher perioperative Ht levels. Further prospective data are required to better understand this complex issue.

Aquaporin 1 plays an important role in myocardial edema caused by cardiopulmonary bypass surgery in goat

Myocardial stunning, which is closely related to myocardial edema, is a severe complication that may occur following cardiac surgery. In this study, we examined the expression of aquaporin1 (AQP1) and Connexin43 (Cx43) following cardiopulmonary bypass (CPB) surgery in goats. We assessed myocardial muscle tissue water content according to changes in dry-wet weight. Our results showed that AQP1 expression and myocardial muscle tissue water content increased significantly 6h after CPB surgery, reaching peak levels 48h after surgery; additionally, the protein expression of Cx43 was inversely correlated with AQP1 expression. Overexpression of AQP1 during CPB surgery enhanced the degree of myocardial edema, whereas the addition of water channel protein inhibitor Hg2+ in cold crystalloid cardioplegia and knockdown of AQP1 during surgery weakened the degree of myocardial edema. These findings revealed that the severity of myocardial edema after CPB surgery is correlated with AQP1 protein expression levels, suggesting the important role played by AQP1 protein in the regulation of Cx43 in the pathological progression of myocardial edema.

Comparison of cold crystalloid and colloid infusions for induction of therapeutic hypothermia in a porcine model of cardiac arrest

IntroductionLarge-volume cold intravenous infusion of crystalloids has been used for induction of therapeutic hypothermia after cardiac arrest. However, the effectiveness of cold colloids has not been evaluated. Therefore, we performed an experimental study to investigate the cooling effect of cold normal saline compared to colloid solution in a porcine model of ventricular fibrillation.MethodsVentricular fibrillation was induced for 15 minutes in 22 anesthetized domestic pigs. After spontaneous circulation was restored, the animals were randomized to receive either 45 ml/kg of 1°C cold normal saline (Group A, 9 animals); or 45 ml/kg of 1°C cold colloid solution (Voluven®, 6% hydroxyethyl starch 130/0.4 in 0.9% NaCl) during 20 minutes (Group B, 9 animals); or to undergo no cooling intervention (Group C, 4 animals). Then, the animals were observed for 90 minutes. Cerebral, rectal, intramuscular, pulmonary artery, and subcutaneous fat body temperatures (BT) were recorded. In the mechanical ex-vivo sub study we added a same amount of cold normal saline or colloid into the bath of normal saline and calculated the area under the curve (AUC) for induced temperature changes.ResultsAnimals treated with cold fluids achieved a significant decrease of BT at all measurement sites, whereas there was a consistent significant spontaneous increase in group C. At the time of completion of infusion, greater decrease in pulmonary artery BT and cerebral BT in group A compared to group B was detected (−2.1 ± 0.3 vs. -1.6 ± 0.2°C, and −1.7 ± 0.4 vs. -1.1 ± 0.3°C, p < 0.05, respectively). AUC analysis of the decrease of cerebral BT revealed a more vigorous cooling effect in group A compared to group B (−91 ± 22 vs. -68 ± 23°C/min, p = 0.046). In the mechanical sub study, AUC analysis of the induced temperature decrease of cooled solution revealed that addition of normal saline led to more intense cooling than colloid solution (−7155 ± 647 vs. -5733 ± 636°C/min, p = 0.008).ConclusionsIntravenous infusion of cold normal saline resulted in more intense decrease of cerebral and pulmonary artery BT than colloid infusion in this porcine model of cardiac arrest. This difference is at least partially related to the various specific heat capacities of the coolants.