Identifying risk factors for perioperative decline in right ventricular performance in cardiac surgery patients: a prospective observational study in a tertiary care hospital.

OBJECTIVES: Impaired right ventricular (RV) function after cardiac surgery is associated with morbidity and long-term mortality. The purpose of this study was to identify factors that play a role in the development of RV dysfunction in the perioperative cardiac surgery setting. DESIGN: We performed a prospective, observational, single centre study. Over a 2-year period, baseline and perioperative characteristics were recorded. For analysis, subjects were divided into three groups: patients with a ≥3% absolute increase in postoperative RV ejection fraction (RVEF) in comparison to baseline (RVEF+), patients with a ≥3% absolute decrease in RVEF (RVEF-) and patients with a <3% absolute change in RVEF (RVEF=). SETTING: Tertiary care hospital in the Netherlands. PARTICIPANTS: We included all cardiac surgery patients ≥18 years of age equipped with a pulmonary artery catheter and admitted to the ICU in 2015-2016. There were no exclusion criteria. A total number of 267 patients were included (65.5% men). OUTCOME MEASURES: Risk factors for a perioperative decline in RV function. RESULTS: A reduction in RVEF was observed in 40% of patients. In multivariate analysis, patients with RVEF- were compared with patients with RVEF= (first-mentioned OR) and RVEF+ (second-mentioned OR). Preoperative use of calcium channel blocker (CCB) (OR 3.06, 95% CI 1.24 to 7.54/OR 2.73, 95% CI 1.21 to 6.16 (both p=0.015)), intraoperative fluid balance (FB) (OR 1.45, 95% CI 1.02 to 2.06 (p=0.039)/OR 1.09, 95% CI 0.80 to 1.49 (p=0.575)) and baseline RVEF (OR 1.22; 95% CI 1.14 to 1.30/OR 1.27, 95% CI 1.19 to 1.35 (both p<0.001)) were identified as independent risk factors for a decline in RVEF during surgery. CONCLUSION: Apart from the impact of the perioperative FB, preoperative use of a CCB as a risk factor for perioperative reduction in RVEF is the most prominent new finding of this study.

High Versus Normal Blood Pressure Targets in Relation to Right Ventricular Dysfunction After Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVE: Management of right ventricular (RV) dysfunction is challenging. Current practice predominantly is based on data from experimental and small uncontrolled studies and includes augmentation of blood pressure. However, whether such intervention is effective in the clinical setting of cardiac surgery is unknown. DESIGN: Randomized controlled trial. SETTING: Single-center study in a tertiary teaching hospital. PARTICIPANTS: The study comprised 78 patients equipped with a pulmonary artery catheter (PAC), classified according to PAC-derived RV ejection fraction (RVEF); 44 patients had an RVEF of <20%, and 34 patients had an RVEF between ≥20% and <30%. INTERVENTIONS: Patients randomly were assigned to either a normal target group (mean arterial pressure 65 mmHg) or a high target group [mean arterial pressure 85 mmHg]). The primary end- point was the change in RVEF over a one-hour study period. MEASUREMENTS AND MAIN RESULTS: There was no significant between-group difference in change of RVEF <20% (-1% [-3.3 to 1.8] in the normal-target group v 0.5% [-1 to 4] in the high-target group; p = 0.159). There was no significant between-group difference in change in RVEF 20%-to-30% (-1% [-3 to 0] in the normal-target group v 1% [-1 to 3] in the high-target group; p = 0.074). These results were in line with the simultaneous observation that echocardiographic variables of RV and left ventricular function also remained unaltered over time, irrespective of either baseline RVEF or treatment protocol. CONCLUSION: In a mixed cardiac surgery population with RV dysfunction, norepinephrine-mediated high blood pressure targets did not result in an increase in PAC-derived RVEF compared with normal blood pressure targets.

Hemodynamic Characteristics of Mechanically Ventilated COVID-19 Patients: A Cohort Analysis.

BACKGROUND: Solid data on cardiovascular derangements in critically ill COVID-19 patients remain scarce. The aim of this study is to describe hemodynamic characteristics in a cohort of COVID-19-related critically ill patients. METHODS: A retrospective observational cohort study in twenty-eight consecutive mechanically ventilated COVID-19 patients. Pulse contour analysis-derived data were obtained from all patients, using the PiCCO® system. RESULTS: The mean arterial pressure increased from 77 ± 10 mmHg on day 1 to 84 ± 9 mmHg on day 21 (p=0.04), in combination with the rapid tapering and cessation of norepinephrine and the gradual use of antihypertensive drugs in the vast majority of patients. The cardiac index increased significantly from 2.8 ± 0.7 L/min/m2 on day 1 to 4.0 ± 0.8 L/min/m2 on day 21 (p < 0.001). Dobutamine was administered in only two patients. Mean markers of left ventricular contractility and peripheral perfusion, as well as lactate levels, remained within the normal range. Despite a constant fluid balance, extravascular lung water index decreased significantly from 17 ± 7 mL/kg on day 1 to 11 ± 4 mL/kg on day 21 (p < 0.001). Simultaneously, intrapulmonary right-to-left shunt fraction (Q s/Q t) decreased significantly from 27 ± 10% in week 1 to 15 ± 9% in week 3 (p=0.007). PaO2/FiO2 ratio improved from 159 ± 53 mmHg to 319 ± 53 mmHg (p < 0.001), but static lung compliance remained unchanged. CONCLUSIONS: In general, this cohort of patients with COVID-19 respiratory failure showed a marked rise in blood pressure over time, not accompanied by distinctive markers of circulatory failure. Characteristically, increased extravascular lung water, vascular permeability, and intrapulmonary shunt diminished over time, concomitant with an improvement in gas exchange.

The Reduction in Right Ventricular Longitudinal Contraction Parameters Is Not Accompanied by a Reduction in General Right Ventricular Performance During Aortic Valve Replacement: An Explorative Study.

OBJECTIVE: The aim of the present study was to identify whether the decrease of longitudinal parameters after cardiothoracic surgery (ie, tricuspid annular systolic plane excursion [TAPSE] and systolic excursion velocity [S']) is accompanied by a reduction in global right ventricular (RV) performance. DESIGN: Prospective, observational study. SETTING: Single-center explorative study in a tertiary teaching hospital. PARTICIPANTS: The study comprised 20 patients who underwent aortic valve replacement with or without coronary artery bypass grafting. INTERVENTIONS: During cardiac surgery, simultaneous measurements of RV function were performed with a pulmonary artery catheter and transesophageal echocardiography. MEASUREMENTS AND MAIN RESULTS: TAPSE and S' were reduced significantly directly after surgery compared with the time before surgery (TAPSE from 20.8 [16.6-23.4] mm to 9.1 [5.6-15.5] mm; p < 0.001 and S' from 8.7 [7.9-10.7] cm/s to 7.2 [5.7-8.6] cm/s; p = 0.041). However, the reduction in TAPSE and S' was not accompanied by a reduction in RV performance, as assessed with the TEE-derived myocardial performance index (MPI) and pulmonary artery catheter-derived RV ejection fraction (RVEF). Both remained statistically unaltered before and after the procedure (MPI from 0.52 [0.43-0.58] to 0.50 [0.42-0.88]; p = 0.278 and RVEF from 27% [22%-32%] to 26% [22%-28%]; p = 0.294). CONCLUSIONS: In the direct postoperative phase, the reduction of echocardiographic parameters of longitudinal RV contractility (TAPSE and S') were not accompanied by a reduction in global RV performance, expressed as MPI and RVEF. Solely relying on a single RV parameter as a marker for global RV performance may not be adequate to assess the complex adaptation of the right ventricle to aortic valve replacement.

Right Ventricular Function and Long-Term Outcome in Sepsis: A Retrospective Cohort Study.

BACKGROUND: Sepsis-related myocardial dysfunction is associated with impaired outcome. Traditionally, in this setting the main focus has been on left ventricular performance. Currently, specific knowledge on the prognostic importance of right ventricular dysfunction is scarce. The aim of this study was to determine whether right ventricular ejection fraction (RVEF) is predictive of long-term mortality in sepsis. METHODS: Single-centre retrospective cohort study in adult patients admitted to the ICU with severe sepsis and septic shock, and equipped with a pulmonary artery catheter within the first day after admission. RVEF was recorded as an average over the first 24 h (sample rate of 1 per min). Patients were separated a priori into subgroups according to their RVEF: RVEF less than 20% (A), RVEF 20% to 30% (B), and RVEF more than 30% (C). The primary endpoint was 1-year all-cause mortality. RESULTS: In a 7-year period, 101 patients fulfilled all entry criteria and 98 were included in the study. One-year all-cause mortality was significantly different between groups: 57% in group A (n = 21), 18% in group B (n = 55), and 23% in group C (n = 22); P = 0.003. Kaplan-Meier survival analysis revealed a clear separation between groups A and B/C (X = 14.00, P = 0.001). In a multivariate logistic regression analysis RVEF, both as a categorical variable (RVEF <20%) and as a continuous variable remained independently associated with the primary endpoint (odds ratio [OR] 4.1; 95% confidence interval [CI], 1.3-13.4; P = 0.018 and OR 0.92; 95% CI, 0.85-0.99; P = 0.018, respectively). CONCLUSIONS: RVEF was independently associated with 1-year all-cause mortality in a highly selected group of patients with severe sepsis and septic shock.

Impaired right ventricular ejection fraction after cardiac surgery is associated with a complicated ICU stay.

BACKGROUND: Right ventricular (RV) dysfunction is a known risk factor for increased mortality in cardiac surgery. However, the association between RV performance and ICU morbidity is largely unknown. METHODS: We performed a single-centre, retrospective study including cardiac surgery patients equipped with a pulmonary artery catheter, enabling continuous right ventricular ejection fraction (RVEF) measurements. Primary endpoint of our study was ICU morbidity (as determined by ICU length of stay, duration of mechanical ventilation, usage of inotropic drugs and fluids, and kidney dysfunction) in relation to RVEF. Patients were divided into three groups according to their RVEF; < 20%, 20-30%, and > 30%. RESULTS: We included 1109 patients. Patients with a RVEF < 20% had a significantly longer stay in ICU, a longer duration of mechanical ventilation, higher fluid balance, a higher incidence of inotropic drug usage, and more increase in postoperative creatinine levels in comparison to the other subgroups. In a multivariate analysis, RVEF was independently associated with increased ICU length of stay (OR 0.934 CI 0.908-0.961, p < 0.001), prolonged duration of mechanical ventilation (OR 0.969, CI 0.942-0.998, p = 0.033), usage of inotropic drugs (OR 0.944, CI 0.917-0.971, p < 0.001), and increase in creatinine (OR 0.962, CI 0.934-0.991, p = 0.011). CONCLUSIONS: A decreased RVEF is independently associated with a complicated ICU stay.

Right Ventricular Function After Cardiac Surgery Is a Strong Independent Predictor for Long-Term Mortality.

OBJECTIVE: To establish the all-cause mortality of right ventricular dysfunction after cardiac surgery in a heterogeneous group of cardiac surgery patients. DESIGN: Retrospective analysis of a heterogeneous group of 1,109 cardiac surgery patients in a 4-year period. SETTING: Single-center study in a tertiary teaching hospital. PARTICIPANTS: One thousand one hundred nine cardiac surgery patients. By protocol, patients were monitored with a pulmonary artery catheter, enabling continuous right ventricular ejection fraction (RVEF) measurements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements were performed once per minute for the first 24 postoperative hours and expressed as average over the complete period. Primary outcome was 2-year all-cause mortality. RVEF was categorized into 3 subgroups: <20%, 20-30%, and >30%. Median follow-up time was 739 days. Two-year mortality was significantly different across groups: 4.1% for patients with RVEF >30%, 8.2% in the group with RVEF 20-30%, and 16.7% for patients with RVEF <20%, p < 0.001. Additional risk factors for a poor RVEF were age, body weight, New York Heart Association class, chronic obstructive pulmonary disease, poor left ventricular function, and higher risk scores (Acute Physiology and Chronic Health Evaluation and European System for Cardiac Operative Risk Evaluation). In a multivariate analysis, RVEF as a continuous variable was associated independently with the primary outcome (odds ratio 0.95 confidence interval 0.91-0.99, p = 0.011.) Odds ratios for RVEF <20% were 1.88 (confidence interval 1.18-3.00, p = 0.008). CONCLUSIONS: Right ventricular function is associated independently with 2-year all-cause mortality in a heterogenic cardiac surgery population.

Effect of high or low protamine dosing on postoperative bleeding following heparin anticoagulation in cardiac surgery. A randomised clinical trial.

While experimental data state that protamine exerts intrinsic anticoagulation effects, protamine is still frequently overdosed for heparin neutralisation during cardiac surgery with cardiopulmonary bypass (CPB). Since comparative studies are lacking, we assessed the influence of two protamine-to-heparin dosing ratios on perioperative haemostasis and bleeding, and hypothesised that protamine overdosing impairs the coagulation status following cardiac surgery. In this open-label, multicentre, single-blinded, randomised controlled trial, patients undergoing on-pump coronary artery bypass graft surgery were assigned to a low (0.8; n=49) or high (1.3; n=47) protamine-to-heparin dosing group. The primary outcome was 24-hour blood loss. Patient haemostasis was monitored using rotational thromboelastometry and a thrombin generation assay. The low protamine-to-heparin dosing ratio group received less protamine (329 ± 95 vs 539 ± 117 mg; p<0.001), while post-protamine activated clotting times were similar among groups. The high dosing group revealed increased intrinsic clotting times (236 ± 74 vs 196 ± 64 s; p=0.006) and the maximum post-protamine thrombin generation was less suppressed in the low dosing group (38 ± 40 % vs 6 ± 9 %; p=0.001). Postoperative blood loss was increased in the high dosing ratio group (615 ml; 95 % CI 500-830 ml vs 470 ml; 95 % CI 420-530 ml; p=0.021) when compared to the low dosing group, respectively. More patients in the high dosing group received fresh frozen plasma (11 % vs 0 %; p=0.02) and platelet concentrate (21 % vs 6 %; p=0.04) compared to the low dosing group. Our study confirms in vitro data that abundant protamine dosing is associated with increased postoperative blood loss and higher transfusion rates in cardiac surgery.

Impaired microcirculatory perfusion in a rat model of cardiopulmonary bypass: the role of hemodilution.

Although hemodilution is attributed as the main cause of microcirculatory impairment during cardiopulmonary bypass (CPB), this relationship has never been investigated. We investigated the distinct effects of hemodilution with or without CPB on microvascular perfusion and subsequent renal tissue injury in a rat model. Male Wistar rats (375-425 g) were anesthetized, prepared for cremaster muscle intravital microscopy, and subjected to CPB (n = 9), hemodilution alone (n = 9), or a sham procedure (n = 6). Microcirculatory recordings were performed at multiple time points and analyzed for perfusion characteristics. Kidney and lung tissue were investigated for mRNA expression for genes regulating inflammation and endothelial adhesion molecule expression. Renal injury was assessed with immunohistochemistry. Hematocrit levels dropped to 0.24 ± 0.03 l/l and 0.22 ± 0.02 l/l after onset of hemodilution with or without CPB. Microcirculatory perfusion remained unaltered in sham rats. Hemodilution alone induced a 13% decrease in perfused capillaries, after which recovery was observed. Onset of CPB reduced the perfused capillaries by 40% (9.2 ± 0.9 to 5.5 ± 1.5 perfused capillaries per microscope field; P < 0.001), and this reduction persisted throughout the experiment. Endothelial and inflammatory activation and renal histological injury were increased after CPB compared with hemodilution or sham procedure. Hemodilution leads to minor and transient disturbances in microcirculatory perfusion, which cannot fully explain impaired microcirculation following cardiopulmonary bypass. CPB led to increased renal injury and endothelial adhesion molecule expression in the kidney and lung compared with hemodilution. Our findings suggest that microcirculatory impairment during CPB may play a role in the development of kidney injury.

Intraoperative High-Dose Dexamethasone in Cardiac Surgery and the Risk of Rethoracotomy.

BACKGROUND: Cardiac surgery with the use of cardiopulmonary bypass is associated with a systemic inflammatory response. Intraoperative corticosteroids are administered to attenuate this inflammatory response. The recent Dexamethasone for Cardiac Surgery (DECS) trial could not demonstrate a beneficial effect of dexamethasone on major adverse events in cardiac surgical patients. Previous studies suggest that corticosteroids may affect postoperative coagulation and blood loss, and therefore could influence the risk of surgical reinterventions. We investigated the effects of prophylactic intraoperative dexamethasone treatment on the rate of rethoracotomy after cardiac surgery. METHODS: We performed a post-hoc additional data collection and analysis in the DECS trial. A total of 4,494 adult patients undergoing cardiac surgery with cardiopulmonary bypass were randomly assigned to intravenous dexamethasone (1.0 mg/kg) or placebo. The primary endpoint for the present study was the incidence of any rethoracotomy within the first 30 postoperative days. Secondary endpoints included the reason for rethoracotomy and the incidence of perioperative transfusion of blood products. RESULTS: In the dexamethasone group, 217 patients (9.7%) underwent a rethoracotomy, and in the placebo group, 165 patients did (7.3%; relative risk 1.32, 95% confidence interval: 1.09 to 1.61, p = 0.005). The most common reason for rethoracotomy was tamponade in both groups: 3.9% versus 2.1%, respectively (relative risk 1.84, 95% confidence interval: 1.30 to 2.61, p < 0.001). CONCLUSIONS: Intraoperative high-dose dexamethasone administration in cardiac surgery was associated with an increased rethoracotomy risk.

Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac Surgery.

Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT, as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19 to 0.96). In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m(2). In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD.

'Sepsis-related anemia' is absent at hospital presentation; a retrospective cohort analysis.

BACKGROUND: Anemia is a common feature during sepsis that occurs due to iatrogenic blood loss, depression of serum iron levels and erythropoietin production, and a decreased lifespan of erythrocytes. However, these mechanisms are unlikely to play a role in anemia at the start of sepsis. Moreover, sequestration of fluids, renal failure and increase of intravascular space may additionally influence the change in hemoglobin concentration during intravenous fluid administration in the acute phase of sepsis. METHODS: In this retrospective study, patients who were admitted acutely to the Intensive Care Unit (ICU) were included. Patients who fulfilled the international criteria for severe sepsis or septic shock were included in the sepsis group (S-group). The remaining patients were allocated to the control group (C-group). Laboratory data from blood samples taken at first presentation to the hospital and at admission to the ICU, the amount of intravenous fluid administration and length of stay in the emergency department were collected and tested for significant differences between groups. RESULTS: The difference in hemoglobin concentration between the S-group (n = 296) and C-group (n = 320) at first presentation in hospital was not significant (8.8 ± 1.2 versus 8.9 ± 1.2 mmol/l, respectively, p = 0.07). The reduction in hemoglobin concentration from the first presentation at the emergency department to ICU admission was significantly greater in the S-group compared to the C-group (1 [0.5-1.7] versus 0.5 [0.1-1.1] mmol/l, (p < 0.001)). Spearman rho correlation coefficients between the reduction in hemoglobin concentration and the amount of intravenous fluids administered or the creatinine level in the emergency department were significant (0.3 and 0.4, respectively, p < 0.001). In a multivariate regression analysis, creatinine, the amount of fluid administration and the presence of sepsis remained independently associated. CONCLUSIONS: Prior to in-hospital intravenous fluid administration, there is no significant difference in hemoglobin concentration between acute septic patients and acutely ill controls. Within several hours after hospital admission, there is a significant reduction in hemoglobin concentration, not only associated with the amount of intravenous fluids administered and the creatinine level, but also independently with sepsis itself.

Three-dimensional transesophageal echocardiography for perioperative right ventricular assessment.

BACKGROUND: In high-risk cardiac procedures, dynamic analysis of right ventricular (RV) performance is desirable, but the geometric complexity of the RV limits the applicability of current two-dimensional echocardiographic imaging techniques. This study aimed to evaluate the utility of three-dimensional transesophageal echocardiography (TEE) for the perioperative assessment of RV function and dimensions. METHODS: Patients undergoing cardiac surgical procedures with complete TEE examinations were identified and reviewed according to current guidelines to exclude patients with significant coexisting valvular regurgitation. Full-volume, three-dimensional datasets were analyzed by two independent investigators using stand-alone software, and left ventricular and RV dimensions were recorded. RESULTS: Datasets from 50 patients undergoing cardiac surgical procedures were evaluated for this study. The mean RV volume was 111.7 mL (range, 37.5 to 349.7 mL) at end diastole and 67.6 mL (range, 25.5 to 274.4 mL) at end systole. Intraobserver reliability was 0.93 and 0.90 for end diastolic and 0.77 and 0.87 for end systolic volumes. The interobserver reliability for RV volumes was 0.83 at end diastole and 0.86 at end systole. The mean stroke volume was 43.6 mL (range, 12 to 111.2 mL) for the RV and 49.1 mL (range, 19.9 to 102.8 mL) for the left ventricle; the correlation coefficient between the two was 0.85. CONCLUSIONS: Three-dimensional TEE volumetric measurements were reproducible across a wide range of RV dimensions. As postulated by the continuity principle, stroke volume measurements between both ventricles correlated well, supporting the validity of this approach. Therefore, our work provides preliminary evidence that three-dimensional TEE offers reproducible information about RV function and size in the dynamic and complex perioperative setting of cardiac surgical procedures.

The impact of a pulmonary-artery-catheter-based protocol on fluid and catecholamine administration in early sepsis.

Objective. The pulmonary artery catheter (PAC) remains topic of debate. Despite abundant data, it is of note that many trials did not incorporate a treatment protocol. Methods. We retrospectively evaluated fluid balances and catecholamine doses in septic patients after the introduction of a PAC-based treatment protocol in comparison to historic controls. Results. 2 × 70 patients were included. The first day the PAC group had a significantly higher positive fluid balance in comparison to controls (6.1 ± 2.6 versus 3.8 ± 2.4 litre, P < 0.001). After 7 days the cumulative fluid balance in the PAC group was significantly lower than in controls (9.4 ± 7.4 versus 13 ± 7.6 litre, P = 0.001). Maximum dose of norepinephrine was significantly higher in the PAC group. Compared to controls this was associated with a significant reduction in ventilator and ICU days. Conclusions. Introduction of a PAC-based treatment protocol in sepsis changed the administration of fluid and vasopressors significantly.

Animal models of cardiopulmonary bypass: development, applications, and impact.

Neurologic and neurocognitive complications after cardiac surgery have been reported repeatedly. To better understand its etiology and design protective strategies, small animal models have been developed. This study describes the development of a survival rat cardiopulmonary bypass (CPB) model, along with the introduction of an appropriately sized oxygenator. This model led the way for even more complicated models with CPB, facilitating full cardiac arrest with anterograde cardioplegia administration, air embolization, and deep hypothermic circulatory arrest. In addition, the results of several of those rat CPB studies are summarized and their preclinical relevance is pointed out.

Exacerbation of systemic inflammation and increased cerebral infarct volume with cardiopulmonary bypass after focal cerebral ischemia in the rat.

OBJECTIVE: Stroke remains a significant contributor to morbidity and mortality after cardiac surgery. Cardiopulmonary bypass is known to induce a significant inflammatory response, which could adversely influence outcomes. We hypothesized that cardiopulmonary bypass, through an enhanced systemic inflammatory response, might affect outcomes after focal cerebral ischemia. METHODS: Wistar rats (275-300 g) were anesthetized, surgically prepared for cardiopulmonary bypass and right middle cerebral artery occlusion, and randomly allocated to 2 groups: focal cerebral ischemia alone (n = 9) and focal cerebral ischemia combined with normothermic cardiopulmonary bypass (n = 8). Serum cytokines (tumor necrosis factor alpha and interleukins 1beta, 6, and 10) were measured at baseline, at end of bypass, and at 2, 6, and 24 hours after bypass. On postoperative day 3, animals underwent neurologic testing, after which the brains were prepared for assessment of cerebral infarct volume. Data were compared between groups by Mann-Whitney U test. RESULTS: Compared with the ischemia-alone group, the ischemia plus bypass group had significantly higher levels of circulating tumor necrosis factor alpha and interleukins 1beta and 10 at the end of bypass and 2 hours after bypass. In addition, the ischemia plus bypass animals had larger total cerebral infarct volumes (286 +/- 125 mm(3)) than did those with ischemia alone (144 +/- 85 mm(3), P = .0124). CONCLUSIONS: Cardiopulmonary bypass increased cerebral infarct size after focal cerebral ischemia in rats. This worsening of outcome may in part be related to an augmented inflammatory response that accompanies cardiopulmonary bypass.

Unilateral intracarotid injection of holmium microspheres to induce bilateral MRI-validated cerebral embolization in rats.

BACKGROUND: Cerebral embolization models have been hindered by the fact that delivery is predominantly one-sided and cannot be quantified easily. We have developed a model for bilateral cerebral micro-embolization. By using holmium microspheres, it is possible to quantify intracerebral delivery using MRI. METHODS: To validate the quantification of holmium microspheres a phantom study was performed in which concentration of microspheres in solution was compared with the number of holmium-induced artifacts on MRI. After that identical microspheres were administered by unilateral injection in the carotid artery, while the opposite carotid artery was clamped. On post-injection MRI scans, intracerebral delivery and right/left distribution of the microspheres was determined. RESULTS: In the phantom study it was shown that quantification by MRI is possible and that MRI artifacts represent single microspheres. In the rat brain, about one-third of the injected dose was consistently located on the contralateral side. The administration was reproducible regarding distribution and number of microspheres. CONCLUSIONS: The use of holmium microspheres enables quantification of delivered dose as single microspheres induce artifacts on MRI. By clamping the contralateral carotid artery, one-third of the dose is diverted to the contralateral hemisphere.

A novel survival model of cardioplegic arrest and cardiopulmonary bypass in rats: a methodology paper.

BACKGROUND: Given the growing population of cardiac surgery patients with impaired preoperative cardiac function and rapidly expanding surgical techniques, continued efforts to improve myocardial protection strategies are warranted. Prior research is mostly limited to either large animal models or ex vivo preparations. We developed a new in vivo survival model that combines administration of antegrade cardioplegia with endoaortic crossclamping during cardiopulmonary bypass (CPB) in the rat. METHODS: Sprague-Dawley rats were cannulated for CPB (n = 10). With ultrasound guidance, a 3.5 mm balloon angioplasty catheter was positioned via the right common carotid artery with its tip proximal to the aortic valve. To initiate cardioplegic arrest, the balloon was inflated and cardioplegia solution injected. After 30 min of cardioplegic arrest, the balloon was deflated, ventilation resumed, and rats were weaned from CPB and recovered. To rule out any evidence of cerebral ischemia due to right carotid artery ligation, animals were neurologically tested on postoperative day 14, and their brains histologically assessed. RESULTS: Thirty minutes of cardioplegic arrest was successfully established in all animals. Functional assessment revealed no neurologic deficits, and histology demonstrated no gross neuronal damage. CONCLUSION: This novel small animal CPB model with cardioplegic arrest allows for both the study of myocardial ischemia-reperfusion injury as well as new cardioprotective strategies. Major advantages of this model include its overall feasibility and cost effectiveness. In future experiments long-term echocardiographic outcomes as well as enzymatic, genetic, and histologic characterization of myocardial injury can be assessed. In the field of myocardial protection, rodent models will be an important avenue of research.