Early Gastrointestinal Complications From Ventricular Assist Devices is Increased by Non-Pulsatile Flow.

BACKGROUND: Measurements of organ flow and perfusion during cardiopulmonary bypass suggest that perfusion of the splanchnic bed can be impaired by non-pulsatile flow. We postulated that non-pulsatile flow from centrifugal ventricular assist devices might also compromise splanchnic blood flow and cause bowel ischaemia especially in the period of circulatory instability early post-implant. The aim of the present studies was to compare the incidence of gastrointestinal (GI) complications in patients having a non-pulsatile device with the incidence in those having a pulsatile device. METHODS: In a pilot study, the initial 12 patients who received the Ventrassist (Ventracor, Sydney, NSW, Australia) centrifugal, non-pulsatile device during the period from June 2003 to September 2005 at the Alfred Hospital, Melbourne were compared with 11 patients who received a Thoratec (Thoratec, Pleasanton, CA, USA), pulsatile, positive displacement device and the incidence was recorded of GI complications requiring an intervention either surgical, endoscopic or by interventional radiology. This was followed by a larger (full) study of a second cohort of similar ventricular assist device (VAD) patients from January 1992 until December 2012 comparing 53 patients having non-pulsatile devices and 110 having pulsatile devices. RESULTS: In the pilot study, the overall incidence of complications in the non-pulsatile group (67%) was almost double that in the pulsatile group (36%) but the difference was not statistically significant (p = 0.15) because of the small number (n = 23) of participants. In the full study, all GI complications with either device occurred within the first 3 weeks post-implant. In the non-pulsatile patients, there was a higher incidence of GI bleeding, 23% vs 4% (p = 0.002), endoscopies, 24% vs 12% (p = 0.049). More patients with a non-pulsatile flow device had delayed absorption of nasogastric feeds than their pulsatile counterparts, 35% vs 7% (p < 0.0001). Patients with a non-pulsatile flow device had a higher overall rate of gastrointestinal complications than patients had with a pulsatile flow device, 56% vs 20% (p < 0.0001). After correcting for the other predictors, the odds of developing a gastrointestinal complication in the pulsatile group was significantly lower (odds ratio 0.07) than in the non-pulsatile device group (p < 0.0001). CONCLUSIONS: We conclude that the use of non-pulsatile centrifugal VADs compared with pulsatile positive displacement VADs is associated with a higher incidence of both haemorrhagic and ischaemic complications in the gastro-intestinal system especially in the very early post-implant period. Whether these complications could be reduced in centrifugal devices by increasing their pulsatility is not clear and merits further research.

On-Pump Beating Heart Versus Conventional Coronary Artery Bypass Grafting Early After Myocardial Infarction: A Propensity-Score Matched Analysis From the ANZSCTS Database.

BACKGROUND: Coronary artery bypass grafting (CABG) performed early after acute myocardial infarction (AMI) carries a high risk of mortality. By avoiding cardioplegic arrest and aortic cross-clamping, on-pump beating heart CABG (ONBEAT) may benefit patients requiring urgent or emergency revascularisation in the setting of AMI. We evaluated the early and long-term outcomes of ONBEAT versus conventional CABG (ONSTOP) utilising the ANZSCTS National Cardiac Surgery Database. METHODS: Between 2001 and 2015, 5,851 patients underwent non-elective on-pump CABG within 7 days of AMI. Of these, 77 patients (1.3%) underwent ONBEAT and 5774 (98.7%) underwent ONSTOP surgery. Propensity-score matching (with a 1:2 matching ratio) was performed for risk adjustment. Survival data were obtained from the National Death Index. RESULTS: Before matching, the unadjusted 30-day mortality was ONBEAT: 9/77 (11.7%) vs. ONSTOP: 256/5,774 (4.4%), p<0.001. Preoperative factors independently associated with the ONBEAT were: septuagenarian age, peripheral vascular disease, redo surgery, cardiogenic shock, emergency surgery and single-vessel disease. After propensity-score matching, 30-day mortality was similar (ONBEAT: 9/77 (11.7%) vs. ONSTOP: 16/154 (10.4%), p=0.85), as was the rate of major adverse cardiac and cerebrovascular events (ONBEAT: 17/77 (22.1%) vs. ONSTOP: 38/154 (24.7%), p=0.84). ONBEAT patients received fewer distal anastomoses and were more likely to have incomplete revascularisation (ONBEAT: 15/77 (19.5%) vs. ONSTOP: 15/154, (9.7%), p=0.03). Despite this, 12-year survival was comparable (ONBEAT: 64.8% (95% CI 39.4-82.4%) vs. ONSTOP: 63.6% (95% CI 50.5, 74.3%), p=0.89). CONCLUSIONS: ONBEAT can be performed safely in high-risk patients requiring CABG early after AMI with similar short and long-term survival compared to ONSTOP.

Relationships Among Cognitive Function and Cerebral Blood Flow, Oxidative Stress, and Inflammation in Older Heart Failure Patients.

BACKGROUND: The mechanisms for cognitive impairment in heart failure (HF) are unclear. We investigated the relative contributions of cerebral blood flow velocity (BFV), oxidative stress, and inflammation to HF-associated cognitive impairment. METHODS AND RESULTS: Thirty-six HF patients (≥60 years) and 40 healthy controls (68 ± 7 vs 67 ± 5 years, P > .05; 69% vs 50% male, P > .05) completed the Cognitive Drug Research computerized assessment battery and Stroop tasks. Common carotid (CCA) and middle cerebral arterial BFV were obtained by transcranial Doppler. Blood samples were collected for oxidant (diacron-reactive oxygen metabolites; F2-isoprostanes), antioxidant (coenzyme Q10; CoQ10), and inflammatory markers (high-sensitivity C-reactive protein). Compared with controls, patients exhibited impaired attention (Cognitive Drug Research's Power of Attention domain, congruent Stroop) and executive function (incongruent Stroop). Multiple regression modeling showed that CCA-BFV and CoQ10 but not group predicted performance on attention and executive function. Additionally, in HF patients, CCA-BFV and CoQ10 (ß = -0.34 vs ß = -0.35) were significant predictors of attention, and CCA-BFV (ß = -0.34) was a predictor of executive function. CONCLUSIONS: Power of Attention and executive function is impaired in older HF patients, and reduced CCA-BFV and CoQ10 are associated with worse cognition. Interventions addressing these mechanisms may improve cognition in older HF patients.

Cold Crystalloid Perfusion Provides Cardiac Preservation Superior to Cold Storage for Donation After Circulatory Death.

BACKGROUND: We previously showed that donation after circulatory death (DCD) canine hearts can be resuscitated if perfused with warm blood. However, clinical application of this technique is complex and difficult. We have developed a simplified system of cold crystalloid perfusion and compared it with standard cold storage for DCD heart preservation. METHODS: Anesthetized greyhounds underwent 30 minutes DCD by withdrawal of ventilation followed by assignment to either 4 hours of perfusion (n = 6) or cold storage (n = 7). Nonpreserved hearts (n = 5) served as a normal reference group. Perfusion hearts were reperfused with a protective solution then perfused for 4 hours with a novel oxygenated, nutrient-containing solution at 20 mL/min at 4°C to 10°C. Cold storage hearts were flushed with St Thomas' cardioplegic solution and stored in ice. After preservation, the recovery of the hearts was assessed on a blood-perfused working heart rig. RESULTS: During preservation, perfusion hearts consumed oxygen (0.09 ± 0.01 mL/100 g per minute) and showed decreasing lactate production in the perfusate (initial: 0.031 ± 0.004 vs final: 0.007 ± 0.002 mmol/min; P = 0.001). After preservation, compared to cold storage hearts, perfusion hearts had higher cardiac output (P = 0.004), LV dP/dt max (P = 0.003) and myocardial oxygen efficiency (P = 0.01), with lower blood perfusate lactate (P = 0.007). Hemodynamic values of perfused hearts reached 60% or more those in the normal reference group. CONCLUSIONS: Continuous cold crystalloid perfusion in a canine model of DCD: (1) facilitates aerobic metabolism and resuscitates the DCD heart, (2) provides functional and metabolic recovery superior to cold storage, (3) shows promise for improved clinical preservation of DCD and marginal donor hearts.

Anatomy and Physiology of Left Ventricular Suction Induced by Rotary Blood Pumps.

This study in five large greyhound dogs implanted with a VentrAssist left ventricular assist device focused on identification of the precise site and physiological changes induced by or underlying the complication of left ventricular suction. Pressure sensors were placed in left and right atria, proximal and distal left ventricle, and proximal aorta while dual perivascular and tubing ultrasonic flow meters measured blood flow in the aortic root and pump outlet cannula. When suction occurred, end-systolic pressure gradients between proximal and distal regions of the left ventricle on the order of 40-160 mm Hg indicated an occlusive process of variable intensity in the distal ventricle. A variable negative flow difference between end systole and end diastole (0.5-3.4 L/min) was observed. This was presumably mediated by variable apposition of the free and septal walls of the ventricle at the pump inlet cannula orifice which lasted approximately 100 ms. This apposition, by inducing an end-systolic flow deficit, terminated the suction process by relieving the imbalance between pump requirement and delivery from the right ventricle. Immediately preceding this event, however, unnaturally low end-systolic pressures occurred in the left atrium and proximal left ventricle which in four dogs lasted for 80-120 ms. In one dog, however, this collapse progressed to a new level and remained at approximately -5 mm Hg across four heart beats at which point suction was relieved by manual reduction in pump speed. Because these pressures were associated with a pulmonary capillary wedge pressure of -5 mm Hg as well, they indicate total collapse of the entire pulmonary venous system, left atrium, and left ventricle which persisted until pump flow requirement was relieved by reducing pump speed. We suggest that this collapse caused the whole vascular region from pulmonary capillaries to distal left ventricle to behave as a Starling resistance which further reduced right ventricular output thus contributing to a major reduction in pump flow. We contend that similar complications of manual speed control also occur in the human subject and remain a major unsolved problem in the clinical management of patients implanted with rotary blood pumps.

Increased myocardial methionine-enkephalin with reduced arterial oxygenation in congenital heart disease.

BACKGROUND: Cardiac opioid peptides have been identified to exert important adaptive metabolic signalling for cardioprotection against ischaemia or hypoxia-related injury. AIMS: To determine myocardial methionine-enkephalin content in children with hypoxemic congenital heart defects and to correlate myocardial content of methionine-enkephalin with the extent of arterial oxygen desaturation. METHODS: Children (n= 20, median age of 16 months), undergoing cardiac surgical repair (tetralogy of Fallot, 17/20), were included in this study. Arterial oxygen saturation was measured on admission. Myocardial samples obtained during surgery were assayed via radioimmunochemistry for methionine-enkephalin content. RESULTS: Greater methionine-enkephalin content was measured in the right ventricles of the patients suffering from recent cyanotic spells compared with those with no recent spells (cyanotic spells: 2418 ± 844 pg/g wet weight tissue, n= 6; no spells: 1175 ± 189 pg/g wet weight tissue, n= 14, P= 0.04). An inverse correlation was evident between the arterial oxygen saturation and myocardial methionine-enkephalin content. CONCLUSION: Myocardial methionine-enkephalin levels increase with the severity of hypoxic stress in congenital cardiac disease and may play an important adaptive role in countering adrenergic over-activity and related excess demand on myocardial metabolic capacity.

Bacteraemia in ventricular assist devices: a common complication that need not affect clinical outcomes.

BACKGROUND: Ventricular assist device (VAD) implantation has become an effective option for patients with severe heart failure. However, device-related infections remain a significant problem. The aim of this study was to describe the incidence and microbiological aetiology of bacteraemia in patients with VADs, and to assess the impact of bacteraemia on clinical outcomes. METHODS: A retrospective study was conducted of patients having VAD implantation at the Alfred Hospital (Melbourne, Australia) from October 1990 to July 2009. Medical records and microbiology databases were reviewed. Patients who were supported with a VAD for 72h or more were evaluated for demographic data, VAD type, the occurrence of bacteraemia and clinical outcomes. RESULTS: During the 19-year period, 135 VAD patients (89 Thoratec PVAD, 10 Novacor, and 36 Ventrassist) supported for a total duration of 17,304 (median 74) support days were included. Sixty-one patients (45%) developed VAD-associated bacteraemia, an incidence of 5.6 episodes per 1000 support days. The incidence of bacteraemia per 1000 days of support was similar for the three devices used: Thoratec PVAD, Novacor and Ventrassist VADs (7.8±0.8, 5.2±1.5 and 3.4±0.5, respectively, p=0.74). Staphylococcus aureus was the most common pathogen (25%). The rates of death on device, survival to transplant, recovery with explant and outcomes after transplantation, including 30-day mortality, median survival time and incidence of cerebrovascular accidents were not significantly impacted upon by bacteraemia. CONCLUSIONS: Bacteraemia is common in VAD patients. However, the incidence of VAD-associated bacteraemia is independent of device type and with aggressive antimicrobial therapy; clinical outcomes need not be affected by the bacteraemia.

Prophylaxis against atrial fibrillation after cardiac surgery: beneficial effect of perioperative metoprolol.

INTRODUCTION: Multiple agents have been investigated to prevent atrial fibrillation (AF) after cardiac surgery. Several studies have investigated the use of ß-blockers such as metoprolol or amiodarone with promising results. We aimed to investigate perioperative pharmacologic prophylaxis against AF using metoprolol, and amiodarone in combination with metoprolol. METHODS: We conducted a prospective, randomised, single-blind, controlled pilot study in patients undergoing elective cardiac surgery. Subjects were randomised pre-operatively to one of three treatment groups: standard therapy (control) or metoprolol (5 mg IV over 5 min on commencement of bypass then 5 mg IV qid for 24h then 25-50 mg tds orally until discharge) or amiodarone (300 mg over 1h starting shortly after the commencement of bypass, then 900 mg over 24h then 400 mg orally tds until discharge) plus metoprolol as above. Patients had ECG monitoring for the occurrence of AF for six days or until discharge. RESULTS: Two hundred and fifteen patients were enrolled. Between-group differences in AF in an intention-to-treat analysis were not significant: control 34% (23-45%), metoprolol 35% (24-46%), combined 22% (12-33%) (p = 0.21). However 87 patients (40%) did not receive the assigned treatment mainly due to side effects, especially bradycardia. The remaining 128 patients were analysed on a per-protocol basis with the overall difference between the three groups bordering on significance: control 34% (23-45%), metoprolol 26% (9-43%), combined 11% (0-23%) (p = 0.06). Logistic regression analysis, correcting for age and gender, was used to separate the individual effects of metoprolol and amiodarone in the presence of metoprolol which showed that compared to control there was a significant effect of metroprolol on AF incidence (O.R. 0.31 (0.10-0.99), p = 0.048) but not of amiodarone (O.R. 0.97 (0.19-5.02), p = 0.97). CONCLUSIONS: (1) Perioperative metoprolol but not amiodarone itself in combination with metoprolol is associated with a significant reduction in postoperative AF. (2) Perioperative administration of metoprolol and combination of metoprolol with amiodarone is associated with a high incidence of side effects, especially bradycardia. (3) Further studies are indicated to confirm these preliminary findings but in the meantime it would not be unreasonable to implement the use of perioperative metoprolol for routine prophylaxis of AF.

Carbon dioxide insufflation in open-chamber cardiac surgery: a double-blind, randomized clinical trial of neurocognitive effects.

OBJECTIVE: The aims of this study were first to analyze neurocognitive outcomes of patients after open-chamber cardiac surgery to determine whether carbon dioxide pericardial insufflation reduces incidence of neurocognitive decline (primary end point) as measured 6 weeks postoperatively and second to assess the utility of carbon dioxide insufflation in cardiac chamber deairing as assessed by transesophageal echocardiography. METHODS: A multicenter, prospective, double-blind, randomized, controlled trial compared neurocognitive outcomes in patients undergoing open-chamber (left-sided) cardiac surgery who were assigned carbon dioxide insufflation or placebo (control group) in addition to standardized mechanical deairing maneuvers. RESULTS: One hundred twenty-five patients underwent surgery and were randomly allocated. Neurocognitive testing showed no clinically significant differences in z scores between preoperative and postoperative testing. Linear regression was used to identify factors associated with neurocognitive decline. Factors most strongly associated with neurocognitive decline were hypercholesterolemia, aortic atheroma grade, and coronary artery disease. There was significantly more intracardiac gas noted on intraoperative transesophageal echocardiography in all cardiac chambers (left atrium, left ventricle, and aorta) at all measured times (after crossclamp removal, during weaning from cardiopulmonary bypass, and at declaration of adequate deairing by the anesthetist) in the control group than in the carbon dioxide group (P < .04). Deairing time was also significantly longer in the control group (12 minutes [interquartile range, 9-18] versus 9 minutes [interquartile range, 7-14 minutes]; P = .002). CONCLUSIONS: Carbon dioxide pericardial insufflation in open-chamber cardiac surgery does not affect postoperative neurocognitive decline. The most important factor is atheromatous vascular disease.

Effect of parameter variations on the hemodynamic response under rotary blood pump assistance.

Numerical models, able to simulate the response of the human cardiovascular system (CVS) in the presence of an implantable rotary blood pump (IRBP), have been widely used as a predictive tool to investigate the interaction between the CVS and the IRBP under various operating conditions. The present study investigates the effect of alterations in the model parameter values, that is, cardiac contractility, systemic vascular resistance, and total blood volume on the efficiency of rotary pump assistance, using an optimized dynamic heart-pump interaction model previously developed in our laboratory based on animal experimental measurements obtained from five canines. The effect of mean pump speed and the circulatory perturbations on left and right ventricular pressure volume loops, mean aortic pressure, mean cardiac output, pump assistance ratio, and pump flow pulsatility from both the greyhound experiments and model simulations are demonstrated. Furthermore, the applicability of some of the previously proposed control parameters, that is, pulsatility index (PI), gradient of PI with respect to pump speed, pump differential pressure, and aortic pressure are discussed based on our observations from experimental and simulation results. It was found that previously proposed control strategies were not able to perform well under highly varying circulatory conditions. Among these, control algorithms which rely on the left ventricular filling pressure appear to be the most robust as they emulate the Frank-Starling mechanism of the heart.

Numerical optimization studies of cardiovascular-rotary blood pump interaction.

A heart-pump interaction model has been developed based on animal experimental measurements obtained with a rotary blood pump in situ. Five canine experiments were performed to investigate the interaction between the cardiovascular system and the implantable rotary blood pump over a wide range of operating conditions, including variations in cardiac contractility and heart rate, systemic vascular resistance (SVR), and total blood volume (V(total) ). It was observed in our experiments that SVR decreased with increasing mean pump speed under the healthy condition, but was relatively constant during the speed ramp study under reduced cardiac contractility conditions. Furthermore, we also found a significant increase in pulmonary vascular resistance with increasing mean pump speed and decreasing total blood volume, despite a relatively constant SVR. Least squares parameter estimation methods were utilized to fit a subset of model parameters in order to achieve better agreement with the experimental data and to evaluate the robustness and validity of the model under various operating conditions. The fitted model produced reasonable agreement with the experimental measurements, both in terms of mean values and steady-state waveforms. In addition, all the optimized parameters were within physiological limits.

Negative pressure wound therapy reduces deep infection rate in open tibial fractures.

OBJECTIVES: To evaluate the effect of negative pressure wound therapy (NPWT) on deep infection rate in open tibial fractures. DESIGN: Retrospective cohort study. Data was collected from medical records and radiographs. SETTING: Two level-1 trauma centers. PATIENTS/PARTICIPANTS: Patients who sustained an open tibial fracture which underwent delayed soft tissue coverage between January 2002 and December 2007 were included. Exclusion criteria included open fractures receiving a combination of NPWT and conventional dressings, fractures which were treated with a primary amputation, and fractures associated with mortality. INTERVENTION: : NPWT with reticulated open cell foam or conventional dressings at surgeon's discretion. MAIN OUTCOME MEASUREMENT: Deep infection rate. RESULTS: A total of 229 open tibial fractures in 220 patients met the inclusion criteria and received either NPWT (166/229-72%) or conventional dressings (63/229-28%). There was a decreased rate of deep infection in the NPWT group compared with the conventional dressing group [8.4% (14/166) vs. 20.6% (13/63); P = 0.01]. Univariate predictors of deep infection included Gustilo type {odds ratio (OR): 3.13 [95% confidence interval (CI): 1.74-5.64]; P < 0.001} and use of NPWT [OR: 0.35 (95% CI: 0.16-0.80); P = 0.01]. When adjustment was performed for Gustilo type with multivariate analysis, use of NPWT was found to reduce the risk of deep infection by almost 80% [OR: 0.22 (95% CI: 0.09-0.55); P = 0.001]. CONCLUSIONS: These results suggest that NPWT reduces the rate of deep infection when used for the dressing of traumatic wounds in open tibial fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Coronary artery bypass surgery provides long-term results superior to percutaneous coronary intervention.

Traditionally, patients presenting with symptoms of coronary artery disease (CAD) were managed medically. If medical treatment proved unsuccessful, patients were referred for coronary artery bypass surgery (CABG). However, in recent years, increasing numbers of patients have received percutaneous coronary intervention (PCI), usually a coronary stent, for primary treatment. PCI is attractive because it is minimally invasive, has proven success in the immediate treatment of acute myocardial infarction and is well-accepted for poor surgical candidates in selected cases. However, evidence from emerging and ongoing clinical trials and registries suggests that compared to PCI, CABG offers superior long-term prognostic benefits in many, if not most, patients with significant CAD. We present an analysis of recent evidence showing that patients with complex atherosclerotic lesions, multivessel disease, left main stem disease, left ventricular dysfunction and diabetes mellitus derive more benefit from surgical revascularisation than from PCI. We conclude that PCI should be restricted to patient groups where superiority or equivalence to CABG has been demonstrated and that the decision-making process in allocating treatment should be made by a multidisciplinary team to ensure that every patient receives balanced advice and therapy that is most effective in the long term.

Protective role of coenzyme Q10 in two models of rat lung injury.

BACKGROUND: Ischaemia-reperfusion injury is a life-threatening complication of lung transplantation. Attempts to ameliorate this injury have included optimization of donor management and improving techniques of lung preservation. However, few investigators have sought to pretreat potential recipients. Coenzyme Q(10) (CoQ(10)) is a potent antioxidant and cellular energizer that has been shown to protect the heart against injury. However, its protective effect in the lung is unknown. We therefore set out to study the impact of Coenzyme Q(10) pretreatment in a model of mild and severe lung injury. METHODS: We evaluated the impact of CoQ(10) in a two-stage laboratory study. In the first stage, in order to measure the magnitude of increase in tissue and plasma CoQ(10) following oral therapy we administered high-dose oral CoQ(10) to rats (n = 6). In the second stage we evaluated the impact of CoQ(10) in the rat lung (n = 10) that was subjected to 230 min of normoxic lung injury or 90 min of warm ischaemia and 120 min of reperfusion in a model of lung transplantation. RESULTS: High-dose oral CoQ(10) for 7 days produced a 15-fold increase in plasma and a 3-fold increase in lung CoQ(10). In the normoxic lung, the injury-induced rise in peak airway pressure was reduced by CoQ(10) treatment at 90 min (P = 0.037) and at 120 min (P = 0.005) without any change in arterial oxygen. In the lung subjected to severe ischaemia-reperfusion injury, CoQ(10) did not reduce the injury-induced increase in peak airway pressure (P = 0.599) nor the decrease in arterial oxygen (P = 0.844). However, CoQ(10) markedly reduced the increase in tumour necrosis factor-alpha in ischaemic compared with normoxic lung (P = 0.027). CONCLUSIONS: The effect of CoQ(10) pretreatment is insufficient to protect the lung against severe ischaemia-reperfusion as may occur in lung transplantation. However, in the setting of less severe pulmonary injury as in anaesthesia and non-transplant surgery, CoQ(10) may have a protective role.

Cardiac reanimation for donor heart transplantation after cardiocirculatory death.

BACKGROUND: This study was conducted in donor hearts obtained after cardiocirculatory death (DCD) to determine whether pre-reperfusion cardioplegia, followed by warm blood perfusion, is superior to cold storage in preserving function sufficient for transplantation. METHODS: Greyhound dogs (n = 15) were anesthetized and cardiocirculatory death and circulatory failure was induced by cessation of mechanical ventilation. After 30-minutes, the hearts were preserved by perfusion or were infused with modified St. Thomas' cardioplegia, explanted, and stored for 4 hour at 4 degrees C. Perfusion hearts were briefly reperfused with an acidic, mitochondrial protective cardioplegic solution and then continuously perfused for 4 hours with normothermic blood. Hearts from a normal reference group (no cardiocirculatory arrest) were preserved by St. Thomas' cardioplegia and cold storage. In all groups, 40 minutes of room temperature ischemia was used to simulate the conditions of transplantation. Final functional and metabolic assessments were made on a working heart apparatus. RESULTS: Perfusion hearts (n = 6), when compared with cold storage hearts (n = 6), produced a greater rate of change in left ventricular pressure (1121 +/- 273 vs 336 +/- 193 mm Hg/sec, p = 0.04), greater echocardiographic fractional area reduction (71.3% +/- 10.0% vs 25.4% +/- 2.9% of baseline, p = 0.004) and lower perfusate lactate levels (1.5 +/- 1.4 vs 9.7 +/- 1.4 mmol/liter; p = 0.002). Functional recovery in perfusion hearts was comparable to the normal hearts (n = 3). CONCLUSION: For DCD hearts, a strategy of pre-reperfusion cardioplegia, followed by continuous warm blood perfusion, is superior to cold storage. These results suggest DCD hearts may be more suitable for transplantation after continuous warm blood perfusion than after cold storage.

Skeletonized internal thoracic artery harvesting reduces chest wall dysesthesia after coronary bypass surgery.

OBJECTIVE: A pain syndrome related to intercostal nerve injury during internal thoracic artery harvesting causes significant morbidity after coronary bypass surgery. We hypothesized that its incidence and severity might be reduced by using skeletonized internal thoracic artery harvesting rather than pedicled harvesting. METHODS: In a prospective double-blind clinical trial, 41 patients undergoing coronary bypass were randomized to receive either unilateral pedicled or skeletonized internal thoracic artery harvesting. Patients were assessed 7 (early) and 21 (late) weeks postoperatively with reproducible sensory stimuli used to detect chest wall sensory deficits (dysesthesia) and with a pain questionnaire used to assess neuropathic pain. RESULTS: At 7 weeks postoperatively, the area of harvest dysesthesia (percentage of the chest) in the skeletonized group (n = 21) was less (median, 0%; interquartile range, 0-0) than in the pedicled group (n = 20) (2.8% [0-13], P = .005). The incidence of harvest dysesthesia at 7 weeks was 14% in the skeletonized group versus 50% in the pedicled group (P = .02). These differences were not sustained at 21 weeks, as the median area of harvest dysesthesia in both groups was 0% (P = .89) and the incidence was 24% and 25% in the skeletonized and pedicled groups, respectively (P = 1.0). The incidence of neuropathic pain in the skeletonized group compared with the pedicled group was 5% versus 10% (P = .6) at 7 weeks and 0% versus 0% (P = 1.0) at 21 weeks. CONCLUSIONS: Compared with pedicled harvesting, skeletonized harvesting of the internal thoracic artery provides a short-term reduction in the extent and incidence of chest wall dysesthesia after coronary bypass, consistent with reduced intercostal nerve injury and therefore the reduced potential for neuropathic chest pain.

Quantifying recirculation in extracorporeal membrane oxygenation: a new technique validated.

RATIONALE: The efficacy of veno-venous extracorporeal membrane oxygenation is limited by the phenomenon of recirculation, which is difficult to quantify. Existing measurement techniques using readily available equipment are unsatisfactory. OBJECTIVES: 1) To compare the accuracy of measurements of recirculation made using equations comparing blood oxygen content or saturation alone at different points in an ex vivo circuit; 2) to validate a new step-change technique for quantifying recirculation in vivo. METHODS: anesthetized greyhound dogs cannulated for veno-arterial support were connected to a circuit that allowed the creation of a known level of recirculation ex vivo and blood oxygen content/saturation monitoring. In two dogs, the accuracy of measurements derived from oxygen content and oxygen saturation were compared. The potential of a new technique for measuring recirculation in vivo by comparing the oxygen content of blood sampled during oxygenator bypass to that following a step-change in circuit oxygenation was demonstrated in a veno-venous pilot study and validated in a three-dog veno-arterial study. RESULTS: Measurements made using oxygen content versus oxygen saturation showed superior correlation with true recirculation (r(2)=0.87 vs. 0.64, p<0.0001) and less proportional measurement bias (10.3% vs. 49.8%, p=0.0045). Measurements of recirculation made using a step-change in circuit oxygenation and comparing oxygen content as is required for measuring in vivo recirculation overestimated by only 18.6% (95% Cl: 3.9-33.2%) and had excellent correlation with true values (r(2)=0.89). CONCLUSIONS: 1) Measurement of recirculation using oxygen content is superior to that using oxygen saturation alone, which demonstrates significant measurement bias; 2) the novel step-change technique is a sufficiently accurate technique for the measurement of recirculation in animal models.

p38 Mitogen-activated protein kinase inhibition reduces inflammatory cytokines in a brain-dead transplant donor animal model.

UNLABELLED: The aim of this study was to determine the degree of p38 mitogen-activated protein kinase (p38 MAPK) activation in rat heart and lungs after experimentally induced brain death and to test whether SD-282, a synthetic and selective small molecule inhibitor of p38 MAPK, abrogates p38 MAPK activation invoked by this brain death model. METHODS: Adult male Sprague Dawley rats were treated with vehicle (control, n=7) or SD-282 (40mg/kg, n=6), for 15min prior to the induction of brain death and maintained with ventilatory support for 3h. IL-6 and TNFalpha were measured in plasma, heart and lungs using ELISA, and p38 MAPK via Western blot assay. RESULTS: p38 MAPK inhibition was demonstrated by lower p38 MAPK activity in lungs from SD-282-treated donors compared to control (Median [inter-quartile range]: 13.6[4.0-19.0]% vs 20.2[14.7-31.5]% activity, p=0.06). Although levels varied, significant inhibition of p38 MAPK by SD-282 was not observed in the heart. SD-282 significantly lowered IL-6 and TNFalpha values compared to control in plasma (64[51-81]pg/ml vs 352[200-755]pg/ml, p=0.003 and 4.3[1.5-9.0]pg/ml vs 21.1[10.5-31.5]pg/ml, p=0.015, respectively) and lungs (0.14[0.12-0.62] vs 5.8[3.6-6.0]pg/mg protein, p=0.03 and 0.41[0.33-0.45] vs 2.1[1.4-2.7]pg/mg protein, p=0.0027, respectively), however SD-282 did not significantly affect cardiac cytokine levels. CONCLUSIONS: p38 MAPK inhibition with SD-282 decreases the pro-inflammatory response as represented by lower IL-6 and TNFalpha in plasma and lungs following brain death. However, although in heart this response was variable, no significant effect could be demonstrated under the present conditions.