Patrick R. Treanor

Atherosclerosis is associated with delirium after coronary artery bypass graft surgery.

Objectives: To investigate whether atherosclerosis of the ascending aorta, internal carotid arteries, and coronary arteries is predictive of postoperative delirium in subjects undergoing coronary artery bypass graft (CABG) surgery.

Development and Evaluation of a Novel Solution, Somah, for the Procurement and Preservation of Beating and Nonbeating Donor Hearts for Transplantation

Background— Injury to myocytes, endocardium, and the coronary endothelium during harvesting and storage can compromise outcomes after heart transplantation. Safeguarding of structure and function of cardiomyocytes and endothelium in donor hearts may lead to improved patient survival after transplantation. Information gained from porcine hearts stored in standard transplant solution was used to design a superior preservation solution that would optimally protect and maintain organs from beating heart and/or nonbeating heart donors during long-term storage. Methods and Results— Multiphoton microscopy was used to image deep within cardiac biopsies and coronary artery tissue harvested from porcine hearts obtained from beating heart and nonbeating heart donors for analysis of myocyte and endothelial cell structure and function. Cell structural integrity and viability, calcium mobilization, and nitric oxide generation were determined with fluorescence viability markers, immunofluorescence, and Western blots. During hypothermic storage in standard preservation solution, Celsior, myocyte, and endothelial viability was markedly attenuated in hearts obtained from beating heart donors. In contrast, hearts from beating and nonbeating heart donors stored in the newly formulated Somah solution demonstrated an increase in high-energy phosphate levels, protection of cardiac myocyte viability, mitochondrial membrane polarization, and structural proteins. Similarly, coronary artery endothelial organization and function, calcium mobilization, and nitric oxide generation were well maintained during temporal storage in Somah. Conclusions— The Celsior preservation solution in clinical use today has led to a profound decline in cardiomyocyte and endothelial cell viability, whereas the newly designed Somah solution has safeguarded myocyte and endothelial integrity and function during organ storage. Use of Somah as a storage medium may lead to optimized graft function and long-term patient survival after transplantation.

Microemboli are not associated with delirium after coronary artery bypass graft surgery

Delirium is an acute change in cognition which occurs frequently after coronary artery bypass graft (CABG) surgery. Cerebral microemboli, from plaque, air, or thrombus, have been hypothesized to contribute to delirium and cognitive decline after CABG. The purpose of this study was to determine if there was an association between cerebral microemboli and delirium after cardiac surgery. Non-delirious patients (n=68) were prospectively enrolled and underwent intraoperative monitoring of the middle cerebral arteries with transcranial Doppler (TCD). TCD signals were saved and analyzed postoperatively for microemboli manually, according to established criteria. Postoperatively, patients were assessed for delirium with a standardized battery. Thirty-three patients (48.5%) developed delirium after surgery. Microemboli counts (mean ± SD) were not significantly different in those with and without delirium (303 ± 449 vs. 299 ± 350; p=0.97). While intraoperative microemboli were not associated with delirium after CABG, further investigation into the source and composition of microemboli can further elucidate the long-term clinical impact of microemboli.

A combined approach for improving cardiopulmonary bypass in coronary artery surgery: a pilot study.

Background: This is a pilot study carried out to assess the feasibility and the clinical impact of a combined approach of cardiopulmonary bypass (CPB) with reduced anti-coagulation. Methods: We used a retrospective, non-randomized analysis of 45 consecutive patients undergoing coronary artery bypass using standard CPB with full anticoagulation (activated clotting time, ACT, > 450 s) (Group 1; n = 23) or closed, heparin-coated CPB with low anticoagulation (ACT> 250 s), precise heparin and protamine titration, controlled suction, and retrograde autologous prime (Group 2; n = 22). Results: Patients were similar except for a higher incidence of three-vessel disease in Group 2 (77.3% versus 47.8%; p < 0.03). Heparin was reduced by 41% in Group 2 and protamine by 56% ( p < 0.0001). Total postoperative blood loss was similar between Groups 1 and 2 (429 ± 149 versus 435 ± 168 ml, respectively). However, the operative hematocrit decrease was lower in Group 2 (-1.6± 7.5% versus -6.9± 4.8%; p = 0.007), although hemodilution was similar, as reflected by the blood protein level. The need for postoperative inotropic support was less frequent in Group 2 (36.4% versus 65.2%; p = 0.05). Within the subgroup of patients weaned from CPB without requiring inotropic support ( n = 35), the cardiac index dropped significantly in Group 1 ( p = 0.003) 6 h after the start of CPB, whereas it remained stable in Group 2 ( p = 0.92). Using multivariate analyses, Group 2 was found to be more protected than Group 1 against myocardial cellular injury ( p = 0.046) and need for postoperative inotropic support ( p = 0.014). Conclusion: The pejorative postoperative outcome in coronary artery surgery was attenuated through a combined approach aimed at improving CPB.

Cerebral Hemodynamics during Coronary Artery Bypass Graft Surgery: The Effect of Carotid Stenosis

Carotid stenosis is a frequent coexisting condition in patients undergoing coronary artery bypass graft (CABG) surgery. The impact of carotid stenosis on cerebral perfusion is not fully understood. The purpose of this study was to determine the impact of carotid stenosis on cerebral blood flow velocity in patients undergoing CABG. Seventy-three patients undergoing CABG were prospectively recruited and underwent preoperative Duplex carotid ultrasound to evaluate the degree of carotid stenosis. Intraoperatively, transcranial Doppler ultrasound was used to record the mean flow velocity (MFV) within the bilateral middle cerebral arteries. In addition, during the period of cardiopulmonary bypass, regulators of cerebral hemodynamics such as hematocrit, partial pressure of carbon dioxide and temperature were recorded. The ipsilateral middle cerebral artery mean flow velocity was compared in arteries with and without carotid stenosis using a repeated measures analysis. Seventy-three patients underwent intraoperative monitoring during CABG and 30% (n=22) had carotid stenosis. Overall, MFV rose throughout the duration of CABG including when the patient was on cardiopulmonary bypass. However, there was no significant MFV difference between those arteries with and without stenosis (F=1.2, p=.21). Further analysis during cardiopulmonary bypass, demonstrated that hemodilution and partial pressure of carbon dioxide may play a role in cerebral autoregulation during CABG. Carotid stenosis did not impact mean cerebral blood flow velocity during CABG. The cerebrovascular regulatory process appears to be largely intact during CABG.

Evaluation of blood components exposed to coated arterial filters in extracorporeal circuits

Background: Biocompatible surfaces play an important role in the inflammatory response during cardiopulmonary bypass (CBP), with the arterial filter contributing a large surface area of the circuit. Different filter-coating materials designed to improve blood-filter biocompatibility are currently used in CPB circuits. This study evaluates eight biocompatible coatings used for arterial filters and their effects on blood components during circulation. Methods: Arterial filters were randomly assigned in eight independent heparin-bonded tubing loops and perfused by a single swine (n=8). Arterial blood was routed simultaneously, but separately, into each circuit and circulated for 30 minutes at 37°C. Blood samples were drawn for CBC, ACT, and TAT III measurements at baseline, post-heparinization and post-circulation. At study completion, filters were imaged using multiphoton microscopy. Results: RBC, platelet, and WBC counts, and TAT III complex were all decreased after 30 minutes of circulation; however, WBC count was the only parameter that showed statistically significant differences between the filters. Circulating WBC reduction ranged from 6% (Carmeda and Trillium) to 41% (Terumo-X-coating) with corresponding microscopic confirmation of increased WBC entrapment. Conclusion: All eight filter coatings altered the blood components to varying degrees. Selection of the most effective filter, in conjunction with a heparin-bonded circuit for CPB, may decrease the intraoperative foreign-surface activation of blood cells.

Heparin-bonded circuits without a cardiotomy: a description of a minimally invasive technique of cardiopulmonary bypass.

The deleterious effects of cardiotomy suction have been well recognized and well documented for some time. The use of cardiotomy suction results in the exposure of blood to the defoaming sock, aspiration of stagnant pericardial blood into the systemic circulation, and the entrainment of both fatty and gaseous microemboli. The purpose of this paper is to describe a technique using heparin-bonded cardiopulmonary circuits (HBCs) without the use of a cardiotomy reservoir or cardiotomy suction. Our group has previously demonstrated improved clinical outcomes using HBCs and a low-dose anti-coagulation protocol. It is our goal to further improve clinical outcomes and further attenuate the deleterious effects of cardiopulmonary bypass by eliminating the potential complications attributed to the use of cardiotomy suction.

Subnormothermic Preservation in Somah: A Novel Approach for Enhanced Functional Resuscitation of Donor Hearts for Transplant

Organ preservation at 4°C results in temporally irreversible injury to cellular structure and function. This study was designed to evaluate the possibility of storing hearts at ambient temperatures in novel organ preservation solution Somah to prevent damage and preserve optimum function by maintaining cellular energy over the temperature range of storage. Porcine hearts were stored in Celsior at 4°C and Somah at 4°C, 13°C and 21°C for 5u2009h thereafter reperfused and reanimated in vitro for 3u2009h. Heart weights, histopathology, ultrastructure and 2‐dimensional echocardiography (2D‐Echo) assessments showed preservation of structure in Somah groups. Tissue high‐energy phosphate levels in Somah groups after storage were significantly greater than the Celsior hearts (pu2009<u20090.05) and highest in the 21°C Somah hearts. Upon reperfusion, myocardial O2 consumption and lactate levels quickly achieved steady state in 21°C hearts, but were delayed in Somah 4/13°C groups and severely depressed in the Celsior group. Inotrope and electroconversion requirements were inversely related to storage temperature. In vitro 2D Echo demonstrated a discordantly attenuated function in the Celsior group, moderate functionality in 4°C Somah group and superior reestablishment of performance in the Somah higher temperature groups. Hearts stored in Somah at 21°C were metabolically and functionally superior to any other groups.

Sub-normothermic preservation of donor hearts for transplantation using a novel solution, Somah: A comparative pre-clinical study

BACKGROUNDnHearts preserved ex vivo at extreme hypothermia (4°C) undergo time-dependent irreversible injury. Our studies using a novel solution, Somah, suggest that hearts are viably preserved at 21°C. In this study we evaluate the relative efficacy of Somah for preservation of hearts at 21°C when compared with the clinically used Celsior and University of Wisconsin (UWS) solutions.nnnMETHODSnPorcine hearts arrested by cardioplegia at 21°C using Somah, Celsior or UWS solution were stored in the respective solutions at 21°C (n = 5) for 5 hours and then reperfused ex vivo for functional assessment. We assessed development of edema, cardiac tissue high-energy phosphate (HEP; ATP + creatine phosphate) levels and release of cardiac enzymes. Alterations in left ventricular wall thicknesses and functional parameters were examined by 2-dimensional (2D) echocardiography. Changes in myocardial oxygen consumption (MVO2) and lactate utilization were assessed at reperfusion.nnnRESULTSnHeart weights were unaltered during 5-hour storage in all groups. After storage, HEP levels were 28.33 ± 5.51, 10.20 ± 2.78 and 5.92 ± 1.46 nmol/liter per milligram protein (p < 0.001) in the Somah, Celsior and UWS group hearts, respectively. Upon reanimation, 2D echocardiography showed edema in the Celsior and UWS hearts; prompt attainment of physiologic function was associated with rapid establishment of aerobic metabolism not requiring stimulatory interventions in the Somah hearts, but not in the Celsior/UWS hearts. Percent fractional area change, ejection fraction and stroke volume were significantly higher (p < 0.001) in Somah hearts than in Celsior and UWS group hearts.nnnCONCLUSIONSnIncreased synthesis of HEP, rapid metabolic switch and optimal function together provide evidence that hearts procured for transplantation are preserved in a superior viable condition at 21°C with Somah, but not with other commonly used clinical preservation solutions.

Use of a large bore syringe creates significantly fewer high intensity transient signals (HITS) into a cardiopulmonary bypass system than a small bore syringe

Introduction: High intensity transient signals (HITS) have been reported to occur following perfusionist intervention during cardiac surgery. This study investigates the relationship of the syringe bore, injection rate, and HITS created. Methods: Syringes (10 mL) with a male luer-lock connection (Large Bore) and Abboject ‘jet syringes’ with a 20 GA needle and male luer-lock connector (Small Bore) were filled with 10 mL of 0.9 N saline. A perfusionist was randomly assigned a set of four similar syringes followed by the other syringe bore. Each of the four syringes was injected into an in vitro saline-primed cardiopulmonary bypass (CPB) system over 5, 10, 15, or 20 sec. Sixteen randomizations of small and large bore syringes were completed at the four injection times (128 injections). HITS in the CPB arterial line were detected with transcranial Doppler (TCD) probes, were recorded for the 2 min following the injection, and were counted independently off-line by two reviewers. Results: The use of a large bore syringe compared to a small bore syringe created significantly fewer HITS (29±6 versus 145±17 [mean±SEM], p <0.001) introduced into the CPB arterial line. Injection over a longer time produced significantly fewer HITS than shorter injection times (p <0.001). Conclusion: Significantly fewer HITS are introduced into the CPB system by using standard syringes and slower injection time.