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1.
Transplant Proc ; 46(5): 1601-5, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24935334

ABSTRACT

INTRODUCTION: Most studies investigating machine perfusion preservation for heart transplantation perfuse through the aortic root (antegrade), but the coronary sinus (retrograde) is a potential option. We hypothesized that retrograde machine perfusion provides better functional protection than static storage, while avoiding the potential irregular perfusion seen when aortic insufficiency occurs with antegrade perfusion. MATERIALS AND METHODS: Eighteen canine donor hearts were arrested, procured, and stored in modified Celsior solution for 4 hours by using either static storage at 0°C to 4°C (n = 6) or machine perfusion preservation at 5°C via the aortic root (antegrade, n = 6) or coronary sinus (retrograde, n = 6). Lactate and myocardial oxygen consumption were measured in perfused hearts. Hearts were reimplanted and reperfused for 6 hours with hourly function calculated by using the preload recruitable stroke work (PRSW) relation. Myocardial water content was determined at the end of the experiment. RESULTS: Storage lactate levels and myocardial oxygen consumption were comparable in both perfused groups. The PRSW was increased immediately after bypass in the antegrade group (120.6 ± 19.1 mm Hg) compared with the retrograde (75.0 ± 11.3 mm Hg) and static (78.1 ± 10.5 mm Hg) storage groups (P < .05). At the end of reperfusion, PRSW was higher in the retrograde group (69.8 ± 7.4 mm Hg) compared with the antegrade (40.1 ± 6.8 mm Hg) and static (39.9 ± 10.9 mm Hg) storage groups (P < .05). Myocardial water content was similar among groups. CONCLUSIONS: Both antegrade and retrograde perfusion demonstrated excellent functional preservation, at least equivalent to static storage. Initial function was superior in the antegrade group, but the retrograde hearts displayed better function late after reperfusion. Neither perfused group developed significant edema. Machine perfusion preservation is a promising technique for improving results of cardiac transplantation.


Subject(s)
Heart Transplantation/veterinary , Animals , Dogs , Organ Preservation Solutions , Oxygen Consumption , Perfusion
2.
Transplant Proc ; 42(7): 2771-6, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20832585

ABSTRACT

BACKGROUND: We have previously demonstrated that adding pyruvate to Perfadex increased graft metabolism during 24-hour storage and improved reperfusion lung function. This increased metabolism was associated with progressively lower pH of the storage solution during the preservation interval. OBJECTIVE: To determine whether more effective pH regulation would result in further improvements in lung survival after hypothermic storage. MATERIALS AND METHODS: Rat lungs were stored for 24 hours in Perfadex, Perfadex with HEPES (N-2-hydroxyethylpiperazine-propanesulfonic acid) buffer, pyruvate-modified Perfadex, and pyruvate-modified Perfadex with HEPES. Change in pH in the storage solution was measured. Structural lung injury was evaluated using hematoxylin-eosin stained tissue sections. Cell death was quantified by measuring necrotic cells using trypan blue exclusion and apoptotic cells via the TUNEL (terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling) assay. RESULTS: Lungs stored in Perfadex demonstrated the greatest degree of cell death. Lungs in the Pyruvate group exhibited decreased cell death despite greater acidosis. The addition of HEPES reduced cell death and preservation solution acidosis in both Perfadex and pyruvate-modified Perfadex (P < .05). Almost all cell death resulted from necrosis. Adding pyruvate to the preservation solution increases acid formation during storage, but decreases cell death. HEPES ameliorates this acidosis and decreases allograft cell destruction. CONCLUSION: Increasing the preservation solution buffering capacity may be a simple strategy for improving lung preservation for transplantation.


Subject(s)
Acidosis/prevention & control , Lung Transplantation/pathology , Organ Preservation/methods , Animals , Cell Death/drug effects , Cell Survival/drug effects , Citrates , Hypothermia , In Situ Nick-End Labeling , Male , Necrosis , Organ Preservation Solutions/pharmacology , Rats , Rats, Sprague-Dawley , Tissue and Organ Harvesting/methods , Transplantation, Homologous/physiology
3.
Transplant Proc ; 42(5): 1591-4, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20620480

ABSTRACT

OBJECTIVE: Machine perfusion preservation has been used experimentally to extend the storage interval of donor hearts. We previously demonstrated that machine perfusion with glucose-supplemented Celsior preservation solution led to superior reperfusion function but resulted in increased myocardial edema compared with conventional static preservation. We hypothesized that other solutions that contain an oncotic agent, such as University of Wisconsin Machine Perfusion Solution (UWMPS), might reduce graft edema development while maintaining myocardial oxidative metabolism during long-term storage. METHODS: Canine hearts were stored and perfused in a perfusion preservation device (LifeCradle; Organ Transport Systems) after cardioplegic arrest and donor cardiectomy. Hearts were perfused either with glucose-supplemented Celsior (which lacks an oncotic agent) or UWMPS (which contains hydroxyethyl starch) at 5 degrees C in the perfusion device over 10 hours. Oxygen consumption (MVO(2)), lactate accumulation, regional flow distribution, and myocardial water content were measured. RESULTS: Hearts in both groups continued to extract oxygen over the entire perfusion interval. Lactate accumulation was minimal in both groups. Both solutions delivered perfusate evenly to all regions of myocardium. Heart weight increase (Celsior 31.3 +/- 4.3%, UWMPS -3.3 +/- 1.9%) and final myocardial water content (Celsior 80.2 +/- 1.3%, UWMPS 75.9 +/- 0.3%) were higher in the Celsior group (P < .005). CONCLUSIONS: Donor hearts can be supported by a perfusion device over relatively extended storage intervals. These organs continue to undergo oxidative metabolism with little lactate accumulation. An oncotic agent appears to be important in limiting increases in myocardial water content. UWMPS appears to be superior for perfusion preservation of myocardium by reducing edema development during storage.


Subject(s)
Edema, Cardiac/prevention & control , Heart Transplantation/physiology , Organ Preservation Solutions/chemistry , Organ Preservation Solutions/pharmacology , Perfusion/methods , Adenosine/pharmacology , Allopurinol/pharmacology , Animals , Body Water/metabolism , Disaccharides/pharmacology , Dogs , Electrolytes/pharmacology , Glutamates/pharmacology , Glutathione/pharmacology , Heart/anatomy & histology , Heart/physiology , Heart Transplantation/methods , Histidine/pharmacology , Insulin/pharmacology , Mannitol/pharmacology , Organ Size , Oxygen Consumption/drug effects , Raffinose/pharmacology
4.
Circulation ; 104(12 Suppl 1): I265-9, 2001 Sep 18.
Article in English | MEDLINE | ID: mdl-11568067

ABSTRACT

BACKGROUND: Extracorporeal circulation induces a systemic inflammatory response, which may adversely affect organ function. One manifestation of this response is increased fibrinolysis. Antifibrinolytic drugs such as aprotinin and epsilon-aminocaproic acid have been effective in reducing fibrinolysis and blood loss after extracorporeal circulation; however, the effects of antifibrinolytic drugs on proinflammatory and anti-inflammatory mediators are not known. This study examined the effects of aprotinin and epsilon-aminocaproic acid on plasma levels of proinflammatory [interleukin-6 (IL-6)] and anti-inflammatory [interleukin-10 (IL-10)] cytokines during and after extracorporeal circulation. METHODS AND RESULTS: Seventy-two patients undergoing coronary artery bypass grafting with extracorporeal circulation were randomly assigned in a double-blind study to receive high-dose aprotinin, epsilon-aminocaproic acid, or saline placebo. Plasma levels of IL-6 and IL-10 were measured at 5 time points before, during, and after extracorporeal circulation. In all 3 groups, both IL-6 and IL-10 rose significantly after institution of extracorporeal circulation and remained elevated through the first postoperative day. Compared with saline, aprotinin significantly reduced IL-10 (P=0.02) and peak IL-6 (P=0.02) after extracorporeal circulation. In contrast, none of the reductions in IL-6 and IL-10 by epsilon-aminocaproic acid achieved statistical significance. Both aprotinin and epsilon-aminocaproic acid decreased blood loss compared with saline, but there was no significant difference in the number of patients receiving blood products among the treatment groups. CONCLUSIONS: These data suggest that aprotinin and epsilon-aminocaproic acid differ in their effects on the inflammatory response to extracorporeal circulation. Aprotinin but not epsilon-aminocaproic acid appears to attenuate the rise in the proinflammatory and anti-inflammatory cytokines IL-6 and IL-10. Further studies will be required to determine if these cytokine alterations translate to changes in clinical outcomes.


Subject(s)
Aminocaproic Acid/administration & dosage , Antifibrinolytic Agents/administration & dosage , Aprotinin/administration & dosage , Interleukin-10/blood , Serine Proteinase Inhibitors/administration & dosage , Systemic Inflammatory Response Syndrome/prevention & control , Coronary Artery Bypass , Double-Blind Method , Extracorporeal Circulation/adverse effects , Fibrinolysis/drug effects , Humans , Interleukin-6/blood , Middle Aged , Postoperative Period , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/etiology , Treatment Outcome
5.
Ann Thorac Surg ; 72(2): 342-7, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11515863

ABSTRACT

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been shown to be an accurate method for identifying diaphragmatic injuries (DIs). The purpose of this investigation was to establish specific indications for the use of VATS after penetrating chest trauma. METHODS: A retrospective review of all patients undergoing VATS after penetrating chest trauma at a level 1 trauma center over an 8-year period was performed. Logistic regression was used in an attempt to identify independent predictors of DI. RESULTS: One hundred seventy-one patients underwent VATS assessment of a hemidiaphragm, and 60 patients (35%) were found to have a DI. Five independent risk factors for DI were identified from analyzing the patient records: abnormal chest radiograph, associated intraabdominal injuries, high-velocity mechanism of injury, entrance wound inferior to the nipple line or scapula, and right-sided entrance wound. CONCLUSIONS: In the largest published series of patients undergoing VATS to exclude a DI, this review identifies five independent predictors of DI after penetrating chest trauma. A diagnostic algorithm incorporating these five factors was designed with the goal of reducing the number of unrecognized DIs after penetrating chest trauma by using VATS for patients at greatest risk for such injuries.


Subject(s)
Diaphragm/injuries , Thoracic Injuries/diagnosis , Thoracic Surgery, Video-Assisted , Wounds, Penetrating/diagnosis , Adult , Diaphragm/surgery , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Risk Factors , Thoracic Injuries/surgery , Wounds, Gunshot/diagnosis , Wounds, Gunshot/surgery , Wounds, Penetrating/surgery , Wounds, Stab/diagnosis , Wounds, Stab/surgery
6.
J Am Coll Cardiol ; 37(5): 1450-5, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11300460

ABSTRACT

OBJECTIVES: This study was performed to validate the accuracy of color flow vena contracta (VC) measurements of aortic regurgitation (AR) severity by comparing them to simultaneous intraoperative flow probe measurements of regurgitant fraction (RgF) and regurgitant volume (RgV). BACKGROUND: Color Doppler imaging of the vena contracta has emerged as a simple and reliable measure of the severity of valvular regurgitation. This study evaluated the accuracy of VC imaging of AR by transesophageal echocardiography (TEE). METHODS: A transit-time flow probe was placed on the ascending aorta during cardiac surgery in 24 patients with AR. The flow probe was used to measure RgF and RgV simultaneously during VC imaging by TEE. Flow probe and VC imaging were interpreted separately and in blinded fashion. RESULTS: A good correlation was found between VC width and RgF (r = 0.85) and RgV (r = 0.79). All six patients with VC width >6 mm had a RgF >0.50. All 18 patients with VC width <5 mm had a RgF <0.50. Vena contracta area also correlated well with both RgF (r = 0.81) and RgV (r = 0.84). All six patients with VC area >7.5 mm2 had a RgF >0.50, and all 18 patients with a VC area <7.5 mm2 had a RgF <0.50. In a subset of nine patients who underwent afterload manipulation to increase diastolic blood pressure, RgV increased significantly (34 +/- 26 ml to 41 +/- 27 ml, p = 0.042) while VC width remained unchanged (5.4 +/- 2.8 mm to 5.4 +/- 2.8 mm, p = 0.41). CONCLUSIONS: Vena contracta imaging by TEE color flow mapping is an accurate marker of AR severity. Vena contracta width and VC area correlate well with RgF and RgV obtained by intraoperative flow probe. Vena contracta width appears to be less afterload-dependent than RgV.


Subject(s)
Aortic Valve Insufficiency/diagnostic imaging , Aortic Valve/diagnostic imaging , Blood Volume/physiology , Echocardiography, Transesophageal , Ultrasonography, Doppler, Color , Adult , Aged , Aortic Valve/surgery , Aortic Valve Insufficiency/surgery , Blood Flow Velocity/physiology , Female , Humans , Male , Middle Aged , Sensitivity and Specificity
7.
Ann Thorac Surg ; 70(2): 487-91, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10969668

ABSTRACT

BACKGROUND: Endoscopic methods of saphenous vein procurement have recently been introduced. These techniques have been successful in limiting pain and wound complications, but less information on assessing potential trauma to the harvested vein segment is available. METHODS: Fourteen male patients undergoing coronary artery bypass grafting were included in the study. Nine patients underwent endoscopic procurement of saphenous vein whereas 5 patients underwent procurement using standard open techniques. Histologic appearance and immunohistochemical studies (factor VIII:vWF [von Willebrand factor protein] and CD34) of the vein segments were reviewed in a blinded fashion. RESULTS: On histologic analysis, no differences in the intima, media, or adventitia were found between endoscopically and conventionally obtained vein segments. Immunohistochemical staining for factor VIII:vWF and CD34 showed no differences between veins harvested by the two techniques. CONCLUSIONS: Endoscopic saphenous vein harvesting does not appear to traumatize the vessel wall any more than open techniques. Longitudinal assessment is necessary to evaluate long-term patency in vein grafts procured using this method.


Subject(s)
Coronary Artery Bypass , Endoscopy , Saphenous Vein/transplantation , Tissue and Organ Harvesting/methods , Vascular Surgical Procedures/methods , Aged , Coronary Disease/surgery , Humans , Male , Middle Aged , Saphenous Vein/pathology , Vascular Surgical Procedures/instrumentation
8.
Ann Thorac Surg ; 70(1): 264-9, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10921720

ABSTRACT

BACKGROUND: Lung transplantation requires a period of storage and ischemia; we examined the largely unknown effects of that period on intermediary metabolism. METHODS: Two groups of isolated rat lung blocks (n = 16 each) were flushed with Euro-Collins solution and harvested. The lung blocks were immediately ventilated and either perfused for 30 minutes with an erythrocyte-based solution containing carbon 13 labeled substrates (group 1) or stored for 6 hours at 1 degree C and then reperfused (group 2). Half of each group was reperfused at a physiologic Po2 the other half at high Po2. Analysis of carbon 13 isotopomers was performed to determine substrate utilization through aerobic pathways in lung tissue. RESULTS: Lungs from both groups oxidized all major substrates. The contribution of fatty acids to acetylcoenzyme acid oxidized in the citric acid cycle was significantly higher in group 2 than in group 1 (31.3% +/- 2.2% versus 22.0% +/- 2.1%, p < 0.05). Perfusate Po2 did not affect substrate preference. Gas exchange was worse in stored lungs. CONCLUSIONS: After a period of hypothermic ischemia and storage, substrate preference in lung tissue exhibits a switch towards fatty acids. As fatty acid oxidation occurring after ischemia is deleterious in other organs, strategies to inhibit this process in stored lungs may warrant further investigation.


Subject(s)
Ischemic Preconditioning , Lung Transplantation , Lung/metabolism , Organ Preservation , Oxygen/administration & dosage , Reperfusion , Animals , In Vitro Techniques , Male , Rats , Rats, Sprague-Dawley
9.
Ann Thorac Surg ; 69(6): 1782-6, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10892923

ABSTRACT

BACKGROUND: Perioperative management of cardiac surgical patients frequently mandates measurements of cardiac output and left ventricular filling. This study compared cardiac output and left ventricular filling measured by pulmonary artery (PA) catheter and esophageal Doppler monitor (EDM). METHODS: Thirty-four patients undergoing coronary artery bypass grafting were prepared by implanting a PA catheter, an EDM, and a transit-time ultrasonic flow probe around the ascending aorta. In 20 patients, left ventricular end-diastolic short-axis area (EDA) was measured by transesophageal echocardiography. At five time points, cardiac output was measured from the flow probe, the EDM, and the PA catheter (by thermodilution), and left ventricular filling was assessed from the PA catheter (as PA diastolic pressure), the EDM (corrected flow time), and the EDA. For cardiac output, concordance correlations relating EDM to flow probe and PA catheter to flow probe were calculated, transformed (Fisher's z transformation), and compared by Student's t test. For left ventricular filling, regression coefficients were created between corrected flow time and EDA and between PA diastolic pressure and EDA. Spearman correlations were compared by Wilcoxon rank sum test. RESULTS: The EDM and the PA catheter exhibited similar relationships to the flow probe (concordance correlations, 0.55 +/- 0.35 [mean +/- standard deviation] and 0.49 +/- 0.34, respectively; p = 0.088). The correlation between corrected flow time and EDA was better than the correlation between PA diastolic pressure and EDA (concordance correlations, 0.49 +/- 0.55 versus 0.10 +/- 0.43, respectively; p < 0.01). CONCLUSIONS: These data suggest that the EDM may offer a less invasive technique for evaluating cardiac output and a more accurate estimate for preload compared with the PA catheter.


Subject(s)
Blood Pressure/physiology , Cardiac Catheterization , Coronary Artery Bypass , Intraoperative Complications/physiopathology , Laser-Doppler Flowmetry , Monitoring, Intraoperative , Stroke Volume/physiology , Ventricular Function, Left/physiology , Aged , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Thermodilution
11.
J Biomater Sci Polym Ed ; 10(2): 235-46, 1999.
Article in English | MEDLINE | ID: mdl-10091933

ABSTRACT

We employed gamma scintigraphy to quantify the transient accumulations of platelets in pump-oxygenator systems employed in cardiopulmonary bypass (CPB). A flat sheet microporous polypropylene membrane oxygenator (Cobe Duo) was employed, with and without siloxane/caprolactone oligomer coating (SMA) (n = 8 each). The effect of nitric oxide gas infusion on platelet deposition was also evaluated for the uncoated Cobe Duo system (n = 10 each). Scintigraphic images of radiolabelled cells were obtained and converted to numbers of all platelets, labeled and unlabeled, adhering to the pump and oxygenator surfaces. These numbers were compared, by study group, for a 90-min period of normothermic CPB in the adult pig, employing standard prime and anticoagulation regimens. Platelets adhered in large numbers to control oxygenators, reaching maxima (> 20% of the circulating platelet mass) 30 min following institution of CPB, and decreasing for the duration of CPB. SMA treatment significantly decreased platelet adhesion following a 5-10-min transient accumulation period. Nitric oxide infusion significantly reduced platelet adhesion throughout the CPB period. Platelet accumulations on the high fluid shear centrifugal pump surfaces increased monotonically to maxima at about the same time as for the oxygenators, but did not decrease thereafter. Higher platelet surface densities were observed on the centrifugal pump surfaces than on the oxygenator surfaces. CPB with the untreated circuit tended to reduce circulating platelet counts vs theoretical values based on hemodilution alone. In contrast, SMA significantly increased the circulating platelet count versus the untreated control group. These results indicate that platelet adherence to the foreign surfaces of CPB equipment are influenced in characteristic ways by time and fluid shear. SMA treatment and nitric oxide infusion both reduce platelet adhesion to oxygenator surfaces. SMA treatment spares these cells for the circulation.


Subject(s)
Blood Platelets/metabolism , Cell Adhesion , Oxygenators/adverse effects , Polymers/metabolism , Animals , Hematocrit , Male , Nitric Oxide/metabolism , Nitric Oxide/therapeutic use , Polypropylenes/metabolism , Siloxanes/metabolism , Siloxanes/therapeutic use , Swine , Time Factors
12.
Am J Cardiol ; 83(2): 270-2, A6, 1999 Jan 15.
Article in English | MEDLINE | ID: mdl-10073835

ABSTRACT

Multiple endocardial countershocks applied during intraoperative endocardial implantable cardioverter-defibrillator testing for the purpose of defibrillation threshold determination resulted in detectable myocardial injury in 5 of 12 patients, as indicated by elevations in cardiac troponin I levels. This injury was not associated with acute changes on the surface electrocardiogram.


Subject(s)
Defibrillators, Implantable/adverse effects , Electric Countershock/adverse effects , Heart Injuries/etiology , Troponin I/blood , Adult , Aged , Female , Humans , Intraoperative Period , Male , Middle Aged
13.
J Extra Corpor Technol ; 31(4): 211-5, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10915479

ABSTRACT

The most common anticoagulant used for cardiopulmonary bypass is heparin. An alternate form of anticoagulant therapy is needed for patients who have immune-mediated heparin-associated thrombocytopenia (HIT). Thrombocytopenia causes bleeding and may lead to serious arterial and venous thrombosis. HIT or heparin-induced thrombocytopenia with thrombosis type II (HITT) are both described as adverse reactions to heparin. They are diagnosed with a platelet count less than a 100,000/mcl for 2 consecutive days. HITT, the severe form, is characterized with the thrombocytopenia in combination with thromboembolic complications, such as strokes, myocardial infarctions, and limb ischemia. Two cases are presented in which r-hirudin was used for anticoagulation for aortocoronary bypass surgery and mitral valve replacement. The activated partial prothrombin time (aPTT) was used to monitor coagulation. In the first case, the aPTT was maintained greater than 100 seconds, and at the termination of cardiopulmonary bypass, some clot was noted in the cardiopulmonary bypass circuit. In the second case, a longer cardiopulmonary bypass run was anticipated, the hirudin bolus and infusion rate were increased, and the aPTT was maintained at greater than 200 sec. Adequate coagulation resulted, and, at the end of bypass, no clot was noted. These case studies seem to suggest a higher dosage of r-hirudin may be required for the use of cardiopulmonary bypass and a need to maintain aPTT values greater than 200 sec to help monitor anticoagulation.


Subject(s)
Anticoagulants/therapeutic use , Cardiopulmonary Bypass , Hirudin Therapy , Recombinant Proteins/therapeutic use , Thrombocytopenia/prevention & control , Cardiopulmonary Bypass/adverse effects , Drug Administration Schedule , Humans , Male , Middle Aged , Thrombocytopenia/blood
14.
Mol Cell Biochem ; 180(1-2): 145-51, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9546641

ABSTRACT

Previously, we have demonstrated the role of nucleoside transport and purine release in post-ischemic reperfusion injury (myocardial stunning) in several canine models of ischemia. Since rabbits are deficient of xanthine oxidase, it is not known whether selective blockade of purine release is beneficial in a rabbit model of coronary artery occlusion and reperfusion (stunning). Therefore, we determined the hemodynamic and metabolic correlates in response to myocardial stunning in the presence or absence of selective nucleoside transport blocker (p-nitrobenzylthioinosine, NBMPR) and adenosine deaminase inhibitor (erythro-9-(2-hydroxy-3-nonyl)adenine, EHNA). Sixty adult anaesthetized rabbits were surgically prepared for hemodynamic measurements. After stabilization period, the left anterior descending coronary artery was occluded for 15 min and reperfused for 30 min. Transmural myocardial biopsies were obtained from the ischemic LAD area and from the non-ischemic posterior (circumflex, CFX) segment of the myocardium. Rabbits (n = 60) were randomly assigned to either the control or the EHNA/NBMPR-treated group (n = 30 each). Each group was further divided to either functional or metabolic groups (n = 15 each subgroup). Each animal received intravenously 30 ml of either a vehicle solution or 100 M EHNA and 25 M NBMPR 10 min before ischemia. Although administration of EHNA/NBMPR did not affect the heart rate, it did cause mild hypotension (about 20-30%). Fifteen minutes of LAD occlusion resulted in significant ATP depletion and concomitant accumulation of nucleosides in both groups (p < 0.05 vs. baseline and non-ischemic CFX segment). AMP was higher in the LAD compared to the CFX segment. Significant accumulation of adenosine was observed in the treated group compared to the control group. It is concluded that EHNA/NBMPR induced site specific entrapment of adenosine of nucleoside transport in the rabbit heart, in vivo.


Subject(s)
Carrier Proteins/physiology , Heart/physiopathology , Membrane Proteins/physiology , Myocardial Stunning/physiopathology , Purines/metabolism , Adenine/analogs & derivatives , Adenine/pharmacology , Adenine Nucleotides/metabolism , Adenosine Deaminase Inhibitors , Animals , Carrier Proteins/antagonists & inhibitors , Dogs , Enzyme Inhibitors/pharmacology , Female , Hemodynamics , Male , Membrane Proteins/antagonists & inhibitors , Myocardial Ischemia/enzymology , Myocardial Ischemia/physiopathology , Myocardial Reperfusion , Myocardium/metabolism , Nucleoside Transport Proteins , Rabbits , Thioinosine/analogs & derivatives , Thioinosine/pharmacology
15.
Mol Cell Biochem ; 180(1-2): 179-91, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9546645

ABSTRACT

In a previous report, we have demonstrated that simultaneous inhibition of nucleoside transport and adenosine deaminase accumulates endogenous adenosine and protects the myocardium against stunning. The differential cardioprotective effects of erythro-9(2-hydroxy-3-nonyl)-adenine (EHNA), a potent inhibitor of adenosine deamination but not transport, and p-nitrobenzylthioinosine (NBMPR), a selective blocker of adenosine and inosine transport, are not known. Thirty-seven anaesthetized adult dogs were instrumented to monitor left ventricular performance using sonomicrometery. Dogs were randomly assigned into four groups. The control group (n = 8) received only the vehicle solution. Treated groups received saline containing 100 microM EHNA (EHNA-group, n = 7), 25 microM NBMPR (NBMPR-group, n = 7), or a combination of 100 microM EHNA and 25 microM NBMPR (EHNA/NBMPR-group, n = 10). Hearts were subjected to 30 min of normothermic global ischaemia and 60 min of reperfusion while on bypass. Adenine nucleotides, nucleosides, oxypurines and NAD+ were determined in extracts of transmural myocardial biopsies using HPLC. TTC staining revealed the absence of necrosis in this model. Drug administration did not affect myocardial ATP metabolism and cardiac function in the normal myocardium. Ischemia caused about 50% ATP depletion and accumulation of nucleosides. The ratio between adenosine/inosine at the end of ischemia was 1:10, 1:1, 1:1 and 10:1 in the control, EHNA-, NBMPR- and EHNA/NBMPR-group, respectively. Upon reperfusion, both nucleosides washed out from the myocardium in the control and EHNA-group while retained in the myocardium in the NBMPR and EHNA/NBMPR groups. Ventricular dysfunction 'stunning' persisted in the control group (52%) and in the EHNA-treated group (32%) after 30 min of reperfusion. Significant improvement of function was observed in the EHNA group only after 60 min of reperfusion. LV function recovered in the NBMPR- and EHNA/NBMPR-treated groups during reperfusion. ATP recovery occurred only when animals were pretreated with the combination of EHNA/NBMPR and remained depressed in the control group and EHNA and NBMPR-treated groups. At post mortem, TTC staining revealed the absence of myocardial necrosis. Superior myocardial protection was observed with inhibition of nucleoside transport by NBMPR alone or in combination with inhibition of adenosine deaminase by EHNA. Selective blockade of nucleoside transport by NBMPR is more cardioprotective than inhibition of adenosine deaminase alone in attenuating myocardial stunning. It is not known why EHNA partially inhibit adenosine deaminase, in vivo.


Subject(s)
Adenosine/metabolism , Myocardial Ischemia/metabolism , Myocardial Reperfusion Injury/metabolism , Purines/metabolism , Adenine/analogs & derivatives , Adenine/pharmacology , Adenosine Deaminase Inhibitors , Animals , Biological Transport/drug effects , Carrier Proteins/antagonists & inhibitors , Carrier Proteins/drug effects , Dogs , Enzyme Inhibitors/pharmacology , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/drug effects , Models, Cardiovascular , Nucleoside Transport Proteins , Thioinosine/analogs & derivatives , Thioinosine/pharmacology
16.
J Cardiovasc Pharmacol ; 31(3): 336-44, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9514176

ABSTRACT

The effects of dichloroacetate (DCA) on fatty acid oxidation and flux through pyruvate dehydrogenase (PDH) were studied in ischemic, reperfused myocardium supplied with glucose, long-chain fatty acids, lactate, pyruvate, and acetoacetate. The oxidation rates of all substrates were determined by combined 13C nuclear magnetic resonance (NMR) spectroscopy and oxygen-consumption measurements, and PDH flux was assessed by lactate plus pyruvate oxidation. In nonischemic control hearts, DCA increased PDH flux more than eightfold (from 0.68 +/- 0.28 to 5.81 +/- 1.16 micromol/min/g dry weight; n = 8 each group; p < 0.05) and significantly inhibited the oxidation of acetoacetate and fatty acids. DCA also improved mechanical recovery after 30 min of ischemia plus 30 min of reperfusion but did not significantly increase PDH flux measured at the end of the reperfusion period (1.35 +/- 0.42 micromol/min/g dry weight) compared with untreated ischemic hearts (0.87 +/- 0.28 micromol/min/g dry weight; n = 8 each group; p = NS). Although DCA had a modest effect on functional recovery in the reperfused myocardium, this beneficial effect was not associated with either marked stimulation of PDH flux or inhibition of fatty acid oxidation.


Subject(s)
Dichloroacetic Acid/pharmacology , Heart/drug effects , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/physiopathology , Acetoacetates/metabolism , Animals , Fatty Acids/metabolism , Glucose/metabolism , Heart/physiopathology , In Vitro Techniques , Lactates/metabolism , Magnetic Resonance Spectroscopy , Male , Myocardial Ischemia/metabolism , Myocardial Reperfusion Injury/metabolism , Oxidation-Reduction , Oxygen/metabolism , Pyruvic Acid/metabolism , Rats , Rats, Sprague-Dawley
17.
Ann Thorac Surg ; 64(5): 1396-400; discussion 1400-1, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9386710

ABSTRACT

BACKGROUND: Failure to adequately evacuate blood from the pleural space after trauma may result in extended hospitalization and complications such as empyema. METHODS: Patients with retained hemothoraces were prospectively randomized to either a second tube thoracostomy (group 1, n = 24) or video-assisted thoracoscopy (VATS) (group 2, n = 15). Group 1 patients in whom additional tube drainage failed were subsequently randomized to either VATS or thoracotomy. Study end points included duration and costs of hospitalization. RESULTS: During a 4-year period, 39 patients were entered into the study. Patients in group 2 had shorter duration of tube drainage (2.53 +/- 1.36 versus 4.50 +/- 2.83 days, mean +/- standard deviation; p < 0.02), shorter hospital stay after the procedure (3.60 +/- 1.64 versus 7.21 +/- 5.30 days; p < 0.02), and shorter total hospital stay (5.40 +/- 2.16 versus 8.13 +/- 4.62 days; p < 0.02). Hospital costs were also less in this group ($7,689 +/- 3,278 versus $13,273 +/- 8,158; p < 0.02). There was no mortality in either group. No group 2 patient required conversion to thoracotomy. In 10 group 1 patients additional tube placement failed, and this subset was randomized to VATS (n = 5) or thoracotomy (n = 5). No significant difference in clinical outcome was found between these subgroups. CONCLUSIONS: In many patients treated only with additional tube drainage (group 1), this therapy fails, necessitating further intervention. Intent to treat with early VATS for retained hemothoraces decreases the duration of tube drainage, the length of hospital stay, and hospital cost. Early intervention with VATS may be a more efficient and economical strategy for managing retained hemothoraces after trauma.


Subject(s)
Hemothorax/therapy , Thoracic Injuries/complications , Thoracoscopy , Adolescent , Adult , Chest Tubes , Female , Hemothorax/economics , Hemothorax/etiology , Hospital Costs , Humans , Length of Stay , Male , Middle Aged , Prospective Studies , Thoracotomy , Time Factors , Treatment Outcome
18.
ASAIO J ; 43(5): M710-4, 1997.
Article in English | MEDLINE | ID: mdl-9360139

ABSTRACT

Membrane oxygenator designs were examined with particular attention to the influence of radial and axial flow around windings of microporous polypropylene hollow fibers. Oxygen transfer performance was calculated, employing the Mockros-Leonard modified heat transfer analysis and Curtis-Eberhart normalization methods. Flow through an Avecor Affinity oxygenator was imaged by gamma scintigraphy using a bolus injection of 99mTc-DTPA. Experimental mass transfer correlations were developed for this oxygenator using saline. The oxygen exchange of the Avecor Affinity was slightly less than that for the Medtronic Maxima or COBE Optima models, which are based on similar designs.


Subject(s)
Oxygenators, Membrane , Biomedical Engineering , Equipment Design , Evaluation Studies as Topic , Humans , In Vitro Techniques , Membranes, Artificial , Models, Theoretical , Oxygen/blood , Polypropylenes
19.
ASAIO J ; 43(5): M739-44, 1997.
Article in English | MEDLINE | ID: mdl-9360144

ABSTRACT

The authors employed gamma scintigraphy to quantify the post bypass accumulations of platelets and neutrophils in the lung, liver, and heart of adult pigs subjected to a standard 90 min regimen of normothermic cardiopulmonary bypass (CPB). Coated and uncoated microporous polypropylene oxygenator circuits were studied for Cobe Duo (Arvada, CO) oxygenators (amphophilic silicone-caprolactone oligomer [SMA] coating, n = 8 each) and Medtronic Maxima (Irvine, CA) oxygenators (Carmeda heparin coating, n = 5 each). Images of cells in the organs (deposited + blood pool) were corrected for tissue absorption and other factors and compared for a 2 hr period post CPB, using repeat measures ANOVA and rank tests. Platelet accumulations in internal organs correlated positively with whole blood platelet counts and negatively with platelet deposits in oxygenators during CPB. In general, uncoated CPB circuits significantly reduced platelet and neutrophil accumulations in lung, liver, and heart versus preCPB controls for the post CPB interval, for both systems. The SMA treatment significantly increased platelet accumulations versus uncoated controls in lung, liver, and heart for the 2 hr period, including the majority of the post CPB sampling intervals; platelet densities did not reach preCPB levels. Neutrophil accumulations were unaffected by the SMA coating. Carmeda heparin treatment significantly increased platelet accumulations in the liver, but not lung or heart. Despite preservation of circulating neutrophils observed with the Carmeda heparin treatment, neutrophil accumulations in internal organs were not elevated post CPB.


Subject(s)
Blood Platelets/physiology , Cardiopulmonary Bypass/adverse effects , Neutrophils/pathology , Animals , Blood Platelets/diagnostic imaging , Blood Platelets/pathology , Cardiopulmonary Bypass/instrumentation , Cell Adhesion , Cell Movement , Evaluation Studies as Topic , Gamma Cameras , Heart/diagnostic imaging , Hemodilution/adverse effects , Indium Radioisotopes , Liver/diagnostic imaging , Liver/pathology , Lung/diagnostic imaging , Lung/pathology , Male , Myocardium/pathology , Neutrophils/diagnostic imaging , Organ Specificity , Platelet Adhesiveness , Polypropylenes , Radionuclide Imaging , Swine
20.
J Cardiovasc Electrophysiol ; 8(4): 432-5, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9106428

ABSTRACT

INTRODUCTION: Ventricular tachycardia is commonly seen in patients following surgical repair for tetralogy of Fallot. The technique of ablation for this arrhythmia is not well defined. METHODS AND RESULTS: In two patients with ventricular tachycardia following surgical repair of tetralogy of Fallot, the traditional indicators for a site for ventricular tachycardia ablation did not yield cure. Based on careful mapping, the circuit was found to involve the isthmus between the outflow tract patch and the tricuspid annulus; linear radiofrequency lesions across this isthmus resulted in cure of ventricular tachycardia. Not only was the tachycardia no longer inducible, but bidirectional block at the line of ablation confirmed interruption of the reentrant circuit. CONCLUSION: A linear radiofrequency lesion was effective in eliminating ventricular tachycardia in both patients. The demonstration of bidirectional block confirms a cure independent of inducibility of ventricular tachycardia.


Subject(s)
Catheter Ablation , Tachycardia, Ventricular/surgery , Tetralogy of Fallot/surgery , Adult , Electrocardiography , Humans , Male , Tachycardia, Ventricular/complications , Tachycardia, Ventricular/physiopathology , Tetralogy of Fallot/complications , Tetralogy of Fallot/physiopathology
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