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Biomedical subjects

G D Buckberg

Publications and source records attributed to G D Buckberg.

At least 73 records · Page 4Linked to original sources
PubMed1995

Studies of hypoxemic/reoxygenation injury: with aortic clamping. XIII. Interaction between oxygen tension and cardioplegic composition in limiting nitric oxide production and oxidant damage.

This study tests the interaction between oxygen tension and cardioplegic composition on nitric oxide production and oxidant damage during reoxygenation of previously cyanotic hearts. Of 35 Duroc-Yorkshire piglets (2 to 3 weeks, 3 to 5 kg), six underwent 30 minutes of blood cardioplegic arrest with hyperoxemic (oxygen tension about 400 mm Hg), hypocalcemic, alkalotic, glutamate/aspartate blood cardioplegic solution during 1 hour of cardiopulmonary bypass without hypoxemia (control). Twenty-nine others were subjected to up to 120 minutes of ventilator hypoxemia (oxygen tension about 25 mm Hg) before reoxygenation on CPB. To simulate routine clinical management, nine piglets underwent uncontrolled cardiac reoxygenation, whereby cardiopulmonary bypass was started at oxygen tension of about 400 mm Hg followed by the aforementioned blood cardioplegic protocol 5 minutes later. All 20 other piglets underwent controlled cardiac reoxygenation, whereby cardiopulmonary bypass was started at the ambient oxygen tension (about 25 mm Hg), and reoxygenation was delayed until blood cardioplegia was given. The blood cardioplegia solution was kept normoxemic (oxygen tension about 100 mm Hg) in 10 piglets and made hyperoxemic (oxygen tension about 400 mm Hg) in 10 others. The cardioplegic composition was also varied so that the cardioplegic solution in each subgroup contained either KCl only (30 mEq/L) or components that theoretically inhibit nitric oxide synthase by including hypocalcemia, alkalosis, and glutamate/aspartate. Function (end-systolic elastance) and myocardial nitric oxide production, conjugated diene production, and antioxidant reserve capacity were measured. Blood cardioplegic arrest without hypoxemia did not cause myocardial nitric oxide or conjugated diene production, reduce antioxidant reserve capacity, or change left ventricular functional recovery. In contrast, uncontrolled cardiac reoxygenation raised nitric oxide and conjugated diene production 19- and 13-fold, respectively (p < 0.05 vs control), reduced antioxidant reserve capacity 40%, and contractility recovered only 21% of control levels. After controlled cardiac reoxygenation at oxygen tension about 400 mm Hg with cardioplegic solution containing KCl only, nitric oxide and conjugated diene production rose 16- and 12-fold, respectively (p < 0.05 vs control), and contractility recovered only 43% +/- 5%. Normoxemic (oxygen tension of about 100 mm Hg) controlled cardiac reoxygenation with the same solution reduced nitric oxide and conjugated diene production 85% and 71%, and contractile recovery rose to 55% +/- 7% (p < 0.05 vs uncontrolled reoxygenation). In comparison, controlled cardiac reoxygenation with an oxygen tension of about 400 mm Hg hypocalcemic, alkalotic, glutamate/aspartate blood cardioplegic solution reduced nitric oxide and conjugated diene production 85% and 62%, respectively, and contractility recovered 63% +/- 4% (p < 0.05 vs KCl only).(ABSTRACT TRUNCATED AT 400 WORDS)

Alkadienes↗
PubMed1995

Reduction of reoxygenation injury and nitric oxide production in the cyanotic immature heart by controlling pO2.

Reintroduction of high levels of molecular oxygen after a hypoxic period is followed by a burst of nitric oxide (NO), peroxynitrite, and oxygen free radicals, which are highly cytotoxic. This study tests the hypotheses that a) controlled reoxygenation of cyanotic immature hearts when starting cardiopulmonary bypass (CPB) with high pO2 pressure of oxygen produces a reoxygenation injury, and b) this oxygen-related damage is avoidable by controlling the circumstances of the reoxygenation period (controlled reoxygenation). Of 40 immature piglets (2-3 weeks), 5 normoxic instrumented piglets served as control, and 6 underwent 1 h of CPB including 30 min of aortic clamping with blood cardioplegic (BCP) arrest without preceding hypoxia (BCP control). Twenty-nine others were made hypoxic (arterial pO2 20-30 mmHg) for up to 2 h by lowering the forced inspiratory oxygen (FiO2) on a ventilator. They were then reoxygenated on CPB as follows, 1) abrupt reoxygenation at pO2 400 mmHg in 5, (Reox), 2) gradual increase in pO2 from 30 to 400 mmHg in 5 (Graded Reox), both without BCP arrest, 3) starting CPB at different pO2 levels (hyperoxic, normoxic or hypoxic) for 5 min, followed by BCP arrest (Reox+BCP: pO2 > 400, 100 or 20-30 mmHg), in 19 others. Reoxygenation on CPB at pO2 more than 400 mmHg depressed contractility (endsystolic elastance [Ees] to 25 +/- 5% of control; P < 0.05), accompanied by reduced antioxidant reserve capacity [AORC] (P < 0.05 vs control), which was only slightly improved by Graded Reox (Ees 34 +/- 4%, P < 0.05 vs control).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Integrated myocardial management: background and initial application.

This report describes the technique of integrated myocardial management, which combines the advantages of various cardioprotective strategies to compensate for their individual shortcomings. This approach coordinates the myocardial protective techniques with the continuity of the operation so that the surgical procedure is never interrupted. This method (1) provides unimpaired vision, (2) avoids unnecessary ischemia and cardioplegic overdose, (3) allows aortic clamping as soon as cardiopulmonary bypass is started, (4) permits aortic unclamping and discontinuation of bypass shortly after the technical procedure is completed, (5) minimizes the duration of ischemia and cardiopulmonary bypass, and (6) maximizes the positive attributes of the strategies available currently. The background for this myocardial management method, which combines antegrade/retrograde delivery, warm/cold blood cardioplegia, intermittent/continuous perfusion, blood/blood cardioplegia, and avoidance of cardioplegic overdose, hemodilution, and tangential aortic clamping, is discussed. The preliminary results in 1474 patients from four centers where surgeons participated in the infrastructure of this method are presented. This has led to our adoption of this approach in all adult cardiac operations.

Cardiac Surgical Procedures↗
PubMed1995

Integrated myocardial management in valvular heart disease.

This report describes the technique of Integrated Myocardial Management that combines the advantages of various cardioprotective strategies to compensate for their individual shortcomings. This approach co-ordinates the myocardial protective techniques with the continuity of the operation so that the surgical continuity of the procedure is never interrupted, and there is simultaneously (a) unimpaired vision, (b) avoidance of unnecessary ischemia and cardioplegic overdose, (c) aortic clamping as soon as cardiopulmonary bypass is started, (d) aortic unclamping and discontinuation of bypass very shortly after the technical procedure is completed, while (e) minimizing the duration of ischemia and cardiopulmonary bypass and (f) maximizing the positive attributes of the strategies available currently. The background for this myocardial management method that combines antegrade/retrograde delivery, warm/cold blood cardioplegia, intermittent/continuous perfusion, blood/blood cardioplegia, and avoidance of cardioplegic overdose, hemodilution, and tangential aortic clamping is discussed. The preliminary results in 394 consecutive patients from three centers where surgeons who participated in the infra-structure of this method is presented. This has led to our adoption of this approach in all adult cardiac operations.

Aortic Valve↗
PubMed1994

Inaccuracies and variability of indirect pressure measurements during cardioplegia administration.

This study shows cardioplegic delivery requires direct measurement of intravascular pressure, rather than its estimation by calibration of individual delivery systems or by aortic palpation. The effects of temperature, hematocrit, flow rate, and cannula type were tested in vitro after recording intravascular pressure during routine cardiac operations. Inaccuracies were introduced by estimating intravascular pressure, as changes in blood viscosity are affected by hematocrit and temperature, and delivery system pressure varied in relation with the type of cannula, direction of perfusion, and flow rate. Additionally, clinical delivery introduces the variable of intravascular resistance. The variability of direct intravascular pressure versus predicted pressure increased as flow rate was raised. These inaccuracies were overcome completely by directly monitoring intravascular pressure from the side ports of antegrade and retrograde cannulas. We conclude that (1) monitoring cardioplegic delivery device pressure is useful primarily to detect potential obstruction in the delivery system that must be corrected intraoperatively and (2) predicted pressure (by either palpation or in vitro calibration) is an unreliable method of determining intravascular pressure during cardioplegic delivery.

Blood Pressure↗
PubMed1994

Simultaneous arterial and coronary sinus cardioplegic perfusion: an experimental and clinical study.

UNLABELLED: The existence of inhomogeneous distribution of coronary flow with antegrade or retrograde perfusion alone has led to alternating between these delivery routes to maximize their individual benefits. Concern over myocardial damage prevented the simultaneous application of antegrade and retrograde cardioplegic blood delivery. Based upon the predominance of retrograde drainage via Thebesian veins, and evidence that pressure-controlled intermittent coronary sinus occlusion during antegrade cardioplegic delivery enhances its distribution and protective properties, this study tests (a) the hypothesis that simultaneous aortic and coronary sinus perfusion is safe during aortic clamping, and (b) reports initial clinical application of this combined strategy in 174 patients. Five minipigs (25-30 kg) underwent 1 hr of aortic clamping with simultaneous aortic (antegrade) and coronary sinus (retrograde) perfusion at 200 ml/min with normal blood (37 degrees C) before and after 30 minutes of perfusion with either warm (37 degrees C) or cold (4 degrees C) blood cardioplegia (BCP). Furthermore, the combined strategy was used in 174 high-risk patients (NYHA class III-IV) at 3 university hospitals to perform myocardial protection during CABG or valve replacement, or a combination of both. Included were 16 patients in cardiogenic shock and 24 undergoing reoperation. In both the clinical and the experimental studies the coronary sinus pressure was always < 40 mmHg in beating or arrested hearts. EXPERIMENTAL: Compared to control values (81.4 +/- 0.4% tissue water content), no right-ventricular (80.8 +/- 0.8%) or left-ventricular (79.5 +/- 0.3%) edema developed, no lactate was produced (control: -1.0 +/- 0.5 mg/100 g/min, empty beating: -0.64 +/- 5, and BCP arrest: -8.6 +/- 6.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The safety of simultaneous arterial and coronary sinus perfusion: experimental background and initial clinical results.

UNLABELLED: Concern over myocardial damage from simultaneous arterial (antegrade) and coronary sinus (retrograde) perfusion has led to alternating between these delivery routes to maximize their individual benefits. Based upon predominant retrograde drainage via Thebesian veins, this study: (1) confirms experimentally the safety of simultaneous arterial and coronary sinus perfusion; and (2) reports initial clinical application of this combined strategy in 155 consecutive patients. EXPERIMENTAL: Five mini-pigs (25 to 30 kg) underwent 1 hour of aortic clamping with simultaneous aortic and coronary sinus perfusion at 200 mL/min with normal blood (37 degrees C) before and after 30 minutes of perfusion with either warm (37 degrees C) or cold (4 degrees C) blood cardioplegia. Coronary sinus pressure was always less than 30 mmHg. There was no right or left ventricular edema, lactate production, or lipid peroxidation as transmyocardial and myocardial conjugated dienes were unaltered, and postbypass recovered left ventricular end-systolic elastance (conductance catheter) and preload recruitable stroke work index 101% +/- 3% and 109% +/- 90%, respectively. CLINICAL: Simultaneous arterial/coronary sinus perfusion was used in 155 consecutive high risk patients (New York Heart Association Class III to IV) undergoing isolated coronary artery bypass grafting (CABG) (n = 109) and CABG+valve replacement/repair or aneurysm (n = 46). Included were 16 patients in cardiogenic shock and 24 undergoing reoperation. Mean aortic clamping time averaged 90 +/- 4 minutes (range 30 to 207), with 3.5 +/- 0.1 grafts per patient; all anastomoses were performed with the aorta clamped. Cold intermittent blood cardioplegia was used for distal anastomoses and valve implantation/repair in 123 patients, and warm continuous blood cardioplegia was used in 32 patients. Following a warm cardioplegic reperfusate, all patients received warm noncardioplegic blood perfusion simultaneously via grafts and coronary sinus. Coronary sinus pressure was always less than 40 mmHg. Of 18 patients requiring postoperative mechanical circulatory support (IABP), 16 had IABP placed preoperatively for cardiogenic shock. There were three postoperative myocardial infarctions (2%), and six patients died (3.9% mortality). CONCLUSION: These experimental and clinical findings overcome perceived concerns about myocardial damage from simultaneous arterial and coronary sinus perfusion, and suggest this approach may add to the armamentarium of cardioprotective strategies.

Anastomosis, Surgical↗
PubMed1994

New approaches to blood cardioplegic delivery to reduce hemodilution and cardioplegic overdose.

These studies present modifications of the cardioplegic components of a standard cardioplegic formulation, delivered previously at 4:1, to allow an 8:1 blood:cardioplegic mixture, thereby limiting hemodilution. Data are included to show that the hyperkalemic (20 mEq/L) glutamate/aspartate enriched solution used previously for warm induction can be used also for warm reperfusion (instead of the 10 mEq/L KCl solution), thereby avoiding the need to formulate two different solutions that vary only in potassium concentration. Studies of cold (4 degrees C) retrograde noncardioplegic blood infusion after arrest with hyperkalemic blood cardioplegia document the safety of maintaining arrest with continuous retrograde infusion of cold normokalemic blood, thereby indicating that ischemia and cardioplegia are unnecessary during aspects of cardiac operations where perfusion does not impair visualization (i.e., construction of proximal anastomoses). A new cardioplegic delivery system containing a shunt line is presented to expedite conversion from blood cardioplegia to blood infusion when continuous infusion is used.

Animals↗
PubMed1994

Role of controlled cardiac reoxygenation in reducing nitric oxide production and cardiac oxidant damage in cyanotic infantile hearts.

Cardiopulmonary bypass (CPB) is used increasingly to correct cyanotic heart defects during early infancy, but myocardial dysfunction is often seen after surgical repair. This study evaluates whether starting CPB at a conventional, hyperoxic pO2 causes an "unintentional" reoxygenation (ReO2) injury. We subjected 2-wk-old piglets to ventilator hypoxemia (FIO2 approximately 0.06, pO2 approximately 25 mmHg) followed by 5 min of ReO2 on CPB before instituting cardioplegia. CPB was begun in hypoxemic piglets by either abrupt ReO2 at a pO2 of 400 mmHg (standard clinical practice) or by maintaining pO2 approximately 25 mmHg on CPB until controlling ReO2 with blood cardioplegic arrest. The effects of abrupt vs. gradual ReO2 without surgical ischemia (blood cardioplegia) were also compared. Myocardial nitric oxide (NO) production (chemiluminescence measurements of NO2- + NO3-) and conjugated diene (CD) generation (spectrophotometric A233 measurements of lipid extracts) using aortic and coronary sinus blood samples were assessed during cardioplegic induction. 30 min after CPB, left ventricular end-systolic elastance (Ees, catheter conductance method) was used to determine cardiac function. CPB and blood cardioplegic arrest caused no functional or biochemical change in normoxic (control) hearts. Abrupt ReO2 caused a depression of myocardial function (Ees = 25 +/- 5% of control). Functional depression was relatively unaffected by gradual ReO2 without blood cardioplegia (34% recovery of Ees), and abrupt ReO2 immediately before blood cardioplegia caused a 10-fold rise in cardiac NO and CD production, with subsequent depression of myocardial function (Ees 21 +/- 2% of control). In contrast, controlled cardiac ReO2 reduced NO production 94%, CD did not rise, and Ees was 83 +/- 8% of normal. We conclude ReO2 injury is related to increased NO production during abrupt ReO2, nullifies the cardioprotective effects of blood cardioplegia, and that controlled cardiac ReO2 when starting CPB to correct cyanotic heart defects may reduce NO production and improve myocardial status postoperatively.

Animals↗
PubMed1994

Normothermic blood cardioplegia. Alternative or adjunct?

Normothermic blood cardioplegia was developed originally to be used during cardioplegic induction and reperfusion as an adjunct for enhancing metabolic reversal of biochemical alterations occurring before, during, and after total myocardial ischemia. This adjunct was introduced clinically after extensive experimental testing. By contrast, continuous normothermic blood cardioplegia without hypothermia was introduced clinically without a scientific infrastructure and has generated great interest because of its simplicity and encouraging early results, but has caused substantial confusion. This report is written to (1) clarify the role of normothermic blood cardioplegia as an adjunct to available hypothermic and antegrade and retrograde methods of myocardial protection, rather than as an alternative to them, (2) call attention to the misconception that continuous coronary perfusion avoids ischemia inasmuch as "unintentional ischemia" may occur despite continuous coronary perfusion, (3) identify theoretic and practical limitations of warm continuous retrograde blood cardioplegia exposed by testing after its clinical introduction, (4) enumerate the unanswered questions posed after clinical use of this method, and (5) focus on the self-imposed inflexibility created by adoption of adversarial positions in regard to cardioprotective strategies that impedes our ability to combine, rationally, the spectrum of approaches to myocardial protection that have evolved from the recognized limitations of individual methods.

Blood↗
PubMed1993

Protean causes of myocardial stunning in infants and adults.

Myocardial stunning can follow regional or global ischemia in the adult or immature heart. This report reviews some of our studies of the protean causes of stunning including energy and substrate depletion, inefficient oxygen utilization, calcium loading, acidosis, oxyradical damage, and summarizes studies and strategies to limit its occurrence. Data showing that reintroduction of molecular oxygen during reoxygenation of immature cyanotic hearts can cause stunning via a newly described biochemical pathway involving superoxide anion and nitric oxide are also included.

Adult↗
PubMed1993

Cardiopulmonary dysfunction produced by reoxygenation of immature hypoxemic animals supported by cardiopulmonary bypass. Prevention by intravenous metabolic pretreatment.

This study tests the hypothesis that reoxygenation injury is produced when cardiopulmonary bypass is initiated in immature hypoxemic piglets and that it causes cardiopulmonary dysfunction that can be avoided by intravenous metabolic treatment before and during cardiopulmonary bypass. Of 18 immature Yorkshire-Duroc piglets (aged < 3 weeks), six were anesthetized, instrumented, and observed for 5 hours (control animals). Twelve piglets underwent up to 2 hours of hypoxemia (arterial oxygen tension = 20 to 30 mm Hg) before initiation of reoxygenation on cardiopulmonary bypass. Six received an intravenous metabolic infusion solution (mercaptopropionyl glycine, catalase, aspartate, glutamate, glucose/insulin), which was started before and continued during cardiopulmonary bypass. Hypoxia produced an initial hyperdynamic response (39% increase in cardiac index; p < 0.05) followed by progressive hemodynamic deterioration, necessitating premature initiation of bypass in 8 of 12 hypoxemic piglets (67%). Reoxygenation-induced injury (assessed 30 minutes after cardiopulmonary bypass) was characterized by 39% reduction of stroke work index (p < 0.05), increased myocardial lipid peroxidation (79% increase of conjugated dienes; p < 0.05), 254% increase in pulmonary vascular resistance index (p < 0.05), 22% decrease in static lung compliance (p < 0.05), and 50% decrease in arterial/alveolar oxygen tension ratio (p < 0.05). These reoxygenation changes were avoided by intravenous metabolic treatment. We conclude that the reoxygenation of immature hypoxemic piglets by initiating cardiopulmonary bypass results in cardiopulmonary dysfunction that may increase vulnerability to subsequent ischemia (i.e., aortic crossclamping). The cardiopulmonary reoxygenation changes are preventable by intravenous metabolic treatment before and during cardiopulmonary bypass needed for cardiac repair.

Animals↗